Medicines doi: 10.3390/medicines11030007
Authors: Jeong Man Cho Sojung Sun Eunji Im Hyunwon Yang Tag Keun Yoo
Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.
]]>Medicines doi: 10.3390/medicines11030006
Authors: Subrata Deb Robert Hopefl Anthony Allen Reeves Dena Cvetkovic
Pharmacogenomics (PGx) can facilitate the transition to patient-specific drug regimens and thus improve their efficacy and reduce toxicity. The aim of this study was to evaluate the overlap of PGx classification for drug absorption, distribution, metabolism, and elimination (ADME)-related genes in the U.S. Food and Drug Administration (FDA) PGx labeling and in the Clinical Pharmacogenetics Implementation Consortium (CPIC) database. FDA-approved drugs and PGx labeling for ADME genes were identified in the CPIC database. Drugs were filtered by their association with ADME (pharmacokinetics)-related genes, PGx FDA labeling class, and CPIC evidence level. FDA PGx labeling was classified as either actionable, informative, testing recommended, or testing required, and varying CPIC evidence levels as either A, B, C, or D. From a total of 442 ADME and non-ADME gene–drug pairs in the CPIC database, 273, 55, and 48 pairs were excluded for lack of FDA labeling, mixed CPIC evidence level provisional classification, and non-ADME gene–drug pairs, respectively. The 66 ADME gene–drug pairs were classified into the following categories: 10 (15%) informative, 49 (74%) actionable, 6 (9%) testing recommended, and 1 (2%) testing required. CYP2D6 was the most prevalent gene among the FDA PGx labeling. From the ADME gene–drug pairs with both FDA and CPIC PGx classification, the majority of the drugs were for depression, cancer, and pain medications. The ADME gene–drug pairs with FDA PGx labeling considerably overlap with CPIC classification; however, a large number of ADME gene–drug pairs have only CPIC evidence levels but not FDA classification. PGx actionable labeling was the most common classification, with CYP2D6 as the most prevalent ADME gene in the FDA PGx labeling. Health professionals can impact therapeutic outcomes via pharmacogenetic interventions by analyzing and reconciling the FDA labels and CPIC database.
]]>Medicines doi: 10.3390/medicines11020005
Authors: Ronald B. Brown Philip Bigelow
Background: Cancer therapeutics have a low success rate in clinical trials. An interdisciplinary approach is needed to translate basic, clinical, and remote fields of research knowledge into novel cancer treatments. Recent research has identified high dietary phosphate intake as a risk factor associated with cancer incidence. A model of tumor dynamics predicted that reducing phosphate levels sequestered in the tumor microenvironment could substantially reduce tumor size. Coincidently, a low-phosphate diet is already in use to help patients with chronic kidney disease manage high serum phosphate levels. Methods: A grounded-theory literature-review method was used to synthesize interdisciplinary findings from the basic and clinical sciences, including oncology, nephrology, nutritional epidemiology, and dietetic research on cancer. Results: Findings of tumor remission associated with fasting and a ketogenic diet, which lower intake of dietary phosphate, support the hypothesis that a low-phosphate diet will reduce levels of phosphate sequestered in the tumor microenvironment and reduce tumor size. Additionally, long-term effects of a low-phosphate diet may reverse dysregulated phosphate metabolism associated with tumorigenesis and prevent cancer recurrence. Conclusions: Evidence in this article provides the rationale to test a low-phosphate diet as a dietary intervention to reduce tumor size and lower risk of cancer recurrence.
]]>Medicines doi: 10.3390/medicines11020004
Authors: Stephanie Trofymenko Randa Kutob Amit Algotar
Background: Obesity is linked to chronic diseases in adults and children. Its prevalence continues to grow in the United States, necessitating the need for healthcare provider training and presenting an opportunity for the education of future medical providers. Despite this need, effectively implementing obesity education into medical school curricula has been challenging. Anti-obesity bias amongst healthcare providers and trainees represents a significant obstacle to the care of patients with obesity. Obesity bias may affect up to 1/3 of medical students. Methods: This study describes the development and preliminary testing of a brief, 2.5 h multi-modality teaching intervention consisting of online, interactive, and independent learning modules for first-year medical students and a patient panel focused on obesity, obesity bias, and motivational interviewing. The participants took Crandall’s anti-fat attitude (AFA) questionnaire before and after an online independent learning module on motivational interviewing and obesity bias. The AFA consists of three subscales (“dislike”, “fear of fat”, and “willpower”). Individual responses were measured using a nine-point Likert-type response format (0 = very strongly disagree; 9 = very strongly agree). An average composite score was calculated for each subscale. Results: Data were analyzed from 103 first-year medical students enrolled at a college of medicine in the southwestern United States in 2022. The AFA mean composite scores decreased significantly, indicating a decrease in explicit anti-obesity attitude bias after completing the online module. This decrease was present in all three domains of fear (4.63 vs. 3.72, p < 0.001), dislike (1.25 vs. 0.88, p < 0.001) and willpower (3.23 vs. 2.31, p < 0.001). Conclusions: Relatively brief educational interventions can positively impact students’ anti-obesity attitudes.
]]>Medicines doi: 10.3390/medicines11010003
Authors: Swagatika Das Praveen K. Roayapalley Hiroshi Sakagami Naoki Umemura Dennis K. J. Gorecki Mohammad Hossain Masami Kawase Umashankar Das Jonathan R. Dimmock
Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins.
]]>Medicines doi: 10.3390/medicines11010002
Authors: Hye Lim Bae Kyeonghun Jeong Suna Yang Hyeji Jun Kwangsoo Kim Young Jun Chai
Background: Hypoxia is a well-recognized characteristic of the tumor microenvironment of solid cancers. This study aimed to analyze hypoxia-related genes shared by groups based on tumor location. Methods: A total of 9 hypoxia-related pathways from the Kyoto Encyclopedia of Genes and Genomes database or the Reactome database were selected, and 850 hypoxia-related genes were analyzed. Based on their anatomical locations, 14 tumor types were categorized into 6 groups. The group-specific genetic risk score was classified as high- or low-risk based on mRNA expression, and survival outcomes were evaluated. Results: The risk scores in the Female Reproductive group and the Lung group were internally and externally validated. In the Female Reproductive group, CDKN2A, FN1, and ITGA5 were identified as hub genes associated with poor prognosis, while IL2RB and LEF1 were associated with favorable prognosis. In the Lung group, ITGB1 and LDHA were associated with poor prognosis, and GLS2 was associated with favorable prognosis. Functional enrichment analysis showed that the Female Reproductive group was enriched in relation to cilia and skin, while the Lung group was enriched in relation to cytokines and defense. Conclusions: This analysis may lead to better understanding of the mechanisms of cancer progression and facilitate establishing new biomarkers for prognosis prediction.
]]>Medicines doi: 10.3390/medicines11010001
Authors: Cezara Andreea Soysaler Cătălina Liliana Andrei Octavian Ceban Crina Julieta Sinescu
Heart failure (HF) presents an increasingly significant problem as the population ages. The cause of HF plays a significant role in determining treatment options and outcomes. It is worth noting that several studies have identified gender disparities in both morbidity and mortality, which may suggest differing causes of HF. The purpose of this research is to investigate the influence of various factors, including demographics and comorbidities, on ejection fraction (EF). The objectives of this study involve implementing preventive measures, ensuring timely diagnosis, and implementing interventions that target risk factors and specific comorbidities. These efforts aim to improve the prognosis for individuals affected by heart failure. The main method consists of linear regression. The demographic factors under scrutiny are gender and education, while the comorbidities of interest encompass valvulopathy, ischemia, smoking, obesity, high cholesterol, and diabetes. The main results consist of the fact that high education is associated with a 12.8% better EF on average, while among the factors with a negative role analyzed, ischemia is the most harmful, being 12.8% lower on average. Factors with a smaller impact are smoking, obesity, and high cholesterol. Diabetes does not seem to affect EF.
]]>Medicines doi: 10.3390/medicines10120062
Authors: Hiromitsu Kataoka Sayumi Suzuki Yuichi Suzuki Ryota Sato Makoto Sano Satoshi Mogi Atsushi Sakamoto Kenichiro Suwa Yoshihisa Naruse Hayato Ohtani Masao Saotome Mikihiro Shimizu Keiichi Odagiri Yuichiro Maekawa
Background: Malnutrition in cardiovascular disease is associated with poor prognosis, especially in patients with heart failure and acute coronary syndrome (ACS). High bleeding risk is also linked to coronary artery disease prognosis, including ACS. However, whether the extent of malnutrition and high bleeding risk have a cumulative impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention remains unclear. Methods: We analyzed 275 patients with ACS treated with percutaneous coronary intervention. The Controlling Nutritional Status score and Japanese version of the Academic Research Consortium for High Bleeding Risk criteria (J-HBR) were retrospectively evaluated. The primary and secondary outcomes were adjusted using the inverse probability treatment weighting method. Results: The prevalence of moderate or severe malnutrition in this cohort was 16%. Kaplan–Meier analysis showed a significantly higher incidence of major adverse cardiovascular and cerebrovascular events in patients who were moderately or severely malnourished than in those who were not. Notably, the incidence of these major events was similar between severely malnourished patients with J-HBR and those without. Conclusion: Moderate or severe malnutrition has a significant impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention.
]]>Medicines doi: 10.3390/medicines10110061
Authors: Toshiaki Ara Hiroyuki Kitamura
As an alternative to animal use, computer simulations are useful for predicting pharmacokinetics and cardiovascular activities. For this purpose, we constructed a statistical model to simulate the effects of local anesthetic agents. To train the model, animal experiments were performed on 6-week-old male Hartley guinea pigs. Firstly, the guinea pigs’ backs were shaved, then local anesthetic agents were subcutaneously injected, with subsequent stimulation of the anesthetized site with a needle six times at regular intervals. The number of reactions (score value) was counted. In this statistical model, the probability of reacting to needle stimulation was calculated using the elapsed time, type of local anesthetic agent, and presence or absence of adrenaline. Score values were assumed to follow a binomial distribution at the calculated probability. Parameters were estimated using the Bayesian hierarchical model and Hamiltonian Monte Carlo method. The predicted curves using the estimated parameters fitted well the observed animal values. When score values were predicted using randomly generated parameters, the median of duration was similar between animal experiments and simulations (Procaine: 55 min vs. 50 min, Lidocaine: both 60 min, and Mepivacaine: both 85 min). This approach effectively modeled the effects of local anesthetic agents. It is possible to create the simulator using the parameter values estimated in this study.
]]>Medicines doi: 10.3390/medicines10110060
Authors: Chikage Kato Akira Komatsuzaki Sachie Ono Asami Iguchi Kiyoka Arashi Shiho Motoi Mio Susuga
Background: There is a high prevalence of sleep disorders in Japan, and they are a factor in a decreased quality of life. The main objective of this study was to clarify the background factors of sleep disorders that affect sleep duration, such as subjective symptoms and working hours. Methods: We performed a cross-sectional study on the Japanese national statistics data. Answers from a household questionnaire were used to analyze risk factors for decreases in sleep duration. The subjects were a total of 3972 men and women aged 40–59 years, the age group that forms the core of the working population. For the analysis, a univariate analysis (contingency table) between sleep duration (two groups: sleep duration ≥ 6 h and <6 h) and 42 subjective symptoms was carried out. A multivariate analysis (binomial logistic regression) was conducted using sleep duration and subjective health assessment as objective variables, and odds ratios (ORs) adjusted for sex, working hours, and other factors were obtained. Results: The univariate analysis by subjective symptom showed significant ORs for eight symptoms, including poor sleep quality (OR: 2.24), constipation (OR: 2.24), and dizziness (OR: 1.77). In the multivariate analysis, the model with sleep duration as the objective variable showed significantly adjusted ORs for four variables, including constipation (1.72) and poor sleep quality (1.66). The model with subjective health assessment as the objective variable showed significantly adjusted ORs for eight variables, including dizziness (4.18), while poor sleep quality (1.45) was not significant. Conclusions: The present results suggest the presence of subjective symptoms that may be inferred to be related to decreases in sleep duration.
]]>Medicines doi: 10.3390/medicines10110059
Authors: Mallika Chuansangeam Bunyarat Srithan Pattharawin Pattharanitima Pawit Phadungsaksawasdi
Background: Early detection of elderly patients with COVID-19 who are at high risk of mortality is vital for appropriate clinical decisions. We aimed to evaluate the risk factors associated with all-cause in-hospital mortality among elderly patients with COVID-19. Methods: In this retrospective study, the medical records of elderly patients aged over 60 who were hospitalized with COVID-19 at Thammasat University Hospital from 1 July to 30 September 2021 were reviewed. Multivariate logistic regression was used to identify independent predictors of mortality. The sum of weighted integers was used as a total risk score for each patient. Results: In total, 138 medical records of patients were reviewed. Four identified variables based on the odds ratio (age, respiratory rate, glomerular filtration rate and history of stroke) were assigned a weighted integer and were developed to predict mortality risk in hospitalized elderly patients. The AUROC of the scoring system were 0.9415 (95% confidence interval, 0.9033–0.9716). The optimized scoring system was developed and a risk score over 213 was considered a cut-off point for high mortality risk. Conclusions: A simple predictive risk score provides an initial assessment of mortality risk at the time of admission with a high degree of accuracy among hospitalized elderly patients with COVID-19.
]]>Medicines doi: 10.3390/medicines10100058
Authors: Supawadee Suppadungsuk Charat Thongprayoon Jing Miao Pajaree Krisanapan Fawad Qureshi Kianoush Kashani Wisit Cheungpasitporn
The exponential growth of artificial intelligence (AI) has allowed for its integration into multiple sectors, including, notably, healthcare. Chatbots have emerged as a pivotal resource for improving patient outcomes and assisting healthcare practitioners through various AI-based technologies. In critical care, kidney-related conditions play a significant role in determining patient outcomes. This article examines the potential for integrating chatbots into the workflows of critical care nephrology to optimize patient care. We detail their specific applications in critical care nephrology, such as managing acute kidney injury, alert systems, and continuous renal replacement therapy (CRRT); facilitating discussions around palliative care; and bolstering collaboration within a multidisciplinary team. Chatbots have the potential to augment real-time data availability, evaluate renal health, identify potential risk factors, build predictive models, and monitor patient progress. Moreover, they provide a platform for enhancing communication and education for both patients and healthcare providers, paving the way for enriched knowledge and honed professional skills. However, it is vital to recognize the inherent challenges and limitations when using chatbots in this domain. Here, we provide an in-depth exploration of the concerns tied to chatbots’ accuracy, dependability, data protection and security, transparency, potential algorithmic biases, and ethical implications in critical care nephrology. While human discernment and intervention are indispensable, especially in complex medical scenarios or intricate situations, the sustained advancements in AI signal that the integration of precision-engineered chatbot algorithms within critical care nephrology has considerable potential to elevate patient care and pivotal outcome metrics in the future.
]]>Medicines doi: 10.3390/medicines10100057
Authors: Jonathan Lai Erik Almazan Thomas Le Matthew T. Taylor Jihad Alhariri Shawn G. Kwatra
Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60–6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819–11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.
]]>Medicines doi: 10.3390/medicines10100056
Authors: Jobar Bouzan Peter Willschrei Marcus Horstmann
Background: Cognitive impairment is poorly addressed in G8 screening. The aim of the present study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores. Methods: Seventy-four consecutive urogeriatric patients aged 75 and above were evaluated. All patients underwent G8 and Mini-Cog© screening. Patients with a G8 score above 14 were considered geriatric “healthy or fit”. A Mini-Cog© from four to five points was considered inconspicuous in screening for cognitive impairment. The additional information of a Mini-Cog© screening during G8 screening was evaluated by looking at G8 “fit and healthy” patients who had conspicuous Mini-Cog© tests and vice versa. Additionally, the results of the neuropsychological subitem “E” of the G8 score were compared with the results of the Mini-Cog© screening. Results: The mean age of the patients was 83 y (min. 75–max. 102). Sixty-one of the patients were males, and 13 were females. Twenty-nine of the patients had a normal G8 score and were considered “healthy or fit”, and 45 were not. Forty-three of the patients had an inconspicuous Mini-Cog©, and 31 had a conspicuous Mini-Cog© of less than four points. The majority of G8 “healthy or fit” patients (n = 24/29) had an inconspicuous Mini-Cog© test. However, of them, five patients had a Mini-Cog© of less than four points, which is suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 subscore in item “E” of two points, 6 patients had a conspicuous Mini-Cog© of less than four points. Conclusions: As shown by the present study, the Mini-Cog© might extend the G8 screening with regard to the detection of cognitive functional impairments that are not detected by the G8 screening alone. It can be easily added to G8 screening.
]]>Medicines doi: 10.3390/medicines10100055
Authors: José C. De La Flor Maribel Monroy-Condori Jacqueline Apaza-Chavez Iván Arenas-Moncaleano Francisco Díaz Xavier E. Guerra-Torres Jorge L. Morales-Montoya Ana Lerma-Verdejo Edna Sandoval Daniel Villa Coca-Mihaela Vieru
Background: Monoclonal immunoglobulin deposition disease (MIDD) includes three entities: light chain deposition disease (LCDD), heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LHCDD). The renal presentation can manifest with varying degrees of proteinuria and/or nephrotic syndrome, microhematuria, and often leads to end-stage renal disease. Given the rarity of LHCDD, therapeutic approaches for this condition remain inconclusive, as clinical trials are limited. Case presentation: We report two male patients with underlying monoclonal gammopathy of renal significance (MGRS) associated with LHCDD lesions. Both cases had non-nephrotic proteinuria, moderately impaired renal function, and normal levels of C3 and C4. Light microscopy of the renal biopsies in both patients did not show lesions of nodular glomerulosclerosis. Immunofluorescence showed a staining pattern with interrupted linear IgA-κ in patient #1 and IgA-λ in patient #2 only along the glomerular basement membrane (GBM). Electron microscopy of patient #1 revealed electrodense deposits in the subendothelial and mesangial areas only along the GBM. Discussion: In this case series, we discuss the clinical, analytical, and histopathological findings of two rare cases of LHCDD. Both patients exhibited IgA monoclonality and were diagnosed with monoclonal gammopathy of undetermined significance (MGUS) by the hematology department at the time of renal biopsy. Treatment with steroids and cytotoxic agents targeting the clone cells responsible for the deposition disease resulted in a favorable renal and hematologic response.
]]>Medicines doi: 10.3390/medicines10090054
Authors: Swagatika Das Praveen K. Roayapalley Sarvesh C. Vashishtha Umashankar Das Jonathan R. Dimmock
There is a need for novel antiepileptic agents whose modes of action differ from those of current antiepileptic drugs. The objective of this study was to determine whether 1-diethylamino-3-phenylprop-2-en-1-one (2) could prevent or at least diminish convulsions caused by different mechanisms. This amide afforded protection in the maximal electroshock and subcutaneous pentylenetetrazole screens when given intraperitoneally to both mice and rats. A number of specialized tests in mice were conducted and are explained in the text. They revealed (2) to have efficacy in the 6 Hz psychomotor seizure test, the corneal kindling model, the mouse temporal epilepsy screen and a peripheral neuronal transmission test using formalin. Three screens in rats were undertaken, which revealed that (2) blocked chloride channels, inhibited peripheral neuronal transmission (tested using sciatic ligation and von Frey fibres) and afforded protection in the lamotrigine-resistant kindled rat model. The biodata generated reveal that (2) is an important lead molecule in the quest for novel structures to combat epilepsy.
]]>Medicines doi: 10.3390/medicines10090053
Authors: Hidetaka Hamasaki
Background: Previous research has demonstrated the effectiveness of mindfulness interventions in improving glycemic control. By enhancing attention control, emotion regulation, and self-awareness, mindfulness shows promise in managing the lifestyle factors associated with cardiovascular disease risk. However, the impact of mindfulness on glycemic control in people with diabetes remains unclear. This overview aims to summarize the current evidence of the impact of mindfulness interventions on glycemic control in people with diabetes and propose suggestions for future research. Methods: The author searched electronic databases (PubMed/MEDLINE, Embase, and Cochrane Library) to identify relevant systematic reviews and meta-analyses. The current evidence regarding the effects of mindfulness on glycemic control in people with diabetes was summarized. Results: This review evaluated a total of five systematic reviews and meta-analyses of randomized controlled trials (RCTs). Mindfulness interventions show potential for improving glycemic control as measured by hemoglobin A1c (HbA1c) levels, as well as reducing stress, depression, and anxiety in people with diabetes. Four out of five systematic reviews and meta-analyses reported a significant reduction in HbA1c levels by approximately 0.3%. However, the available studies lacked adequate description of key characteristics of study subjects, such as body mass index, medication, and disease conditions, which are essential for assessing the impact of mindfulness on glycemic control. Moreover, there was significant heterogeneity in the intervention methods employed across the included RCTs. Conclusions: Mindfulness interventions are effective in improving glycemic control in people with type 2 diabetes. However, the overall quality of the reviewed studies raises uncertainty regarding the effectiveness of mindfulness as a treatment for people with diabetes. Further research is necessary to elucidate the biological effects of mindfulness on physiological, neurological, and endocrinological functions in humans.
]]>Medicines doi: 10.3390/medicines10090052
Authors: Jamir Pitton Rissardo Ursula Medeiros Araujo de Matos Ana Letícia Fornari Caprara
Background: Gabapentin (GBP)-induced movement disorders (MDs) are under-recognized adverse drug reactions. They are commonly not discussed with patients, and their sudden occurrence can lead to misdiagnosis. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of GBP-associated MD. Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1990 and 2023. Results: A total of 99 reports of 204 individuals who developed a MD associated with GBP were identified. The MDs encountered were 135 myoclonus, 22 dyskinesias, 7 dystonia, 3 akathisia, 3 stutterings, 1 myokymia, and 1 parkinsonism. The mean and median ages were 54.54 (SD: 17.79) and 57 years (age range: 10–89), respectively. Subjects were predominantly male (53.57%). The mean and median doses of GBP when the MD occurred were 1324.66 (SD: 1117.66) and 1033 mg/daily (GBP dose range: 100–9600), respectively. The mean time from GBP-onset to GBP-associated MD was 4.58 weeks (SD: 8.08). The mean recovery time after MD treatment was 4.17 days (SD: 4.87). The MD management involved GBP discontinuation. A total of 82.5% of the individuals had a full recovery in the follow-up period. Conclusions: Myoclonus (GRADE A) and dyskinesia (GRADE C) were the most common movement disorders associated with GBP.
]]>Medicines doi: 10.3390/medicines10090051
Authors: Eleni Avramidou Antonios Gkantaras Iasonas Dermitzakis Konstantinos Sapalidis Maria Eleni Manthou Paschalis Theotokis
Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions. Methods: Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens. Results: Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected. Conclusions: Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies.
]]>Medicines doi: 10.3390/medicines10090050
Authors: Christina E. Larder Michèle M. Iskandar Stan Kubow
Osteoarthritis (OA) is the most common joint disorder, with a social and financial burden that is expected to increase in the coming years. Currently, there are no effective medications to treat it. Due to limited treatment options, patients often resort to supplements, such as collagen hydrolysates (CHs). CHs are products with low molecular weight (MW) peptides, often between 3 and 6 kDa, and are a result of industrialized processed collagen. Collagen extraction is often a by-product of the meat industry, with the main source for collagen-based products being bovine, although it can also be obtained from porcine and piscine sources. CHs have demonstrated positive results in clinical trials related to joint health, such as decreased joint pain, increased mobility, and structural joint improvements. The bioactivity of CHs is primarily attributed to their bioactive peptide (BAP) content. However, there are significant knowledge gaps regarding the digestion, bioavailability, and bioactivity of CH-derived BAPs, and how different CH products compare in that regard. The present review discusses CHs and their BAP content as potential treatments for OA.
]]>Medicines doi: 10.3390/medicines10080049
Authors: Ana Leticia Fornari Caprara Hossam Tharwat Ali Ahmed Elrefaey Sewar A. Elejla Jamir Pitton Rissardo
An aura is a subjective experience felt in the initial phase of a seizure. Studying auras is relevant as they can be warning signs for people with epilepsy. The incidence of aura tends to be underestimated due to misdiagnosis or underrecognition by patients unless it progresses to motor features. Also, auras are associated with seizure remission after epilepsy surgery and are an important prognostic factor, guiding the resection site and improving surgical outcomes. Somatosensory auras (SSAs) are characterized by abnormal sensations on one or more body parts that may spread to other parts following a somatotopic pattern. The occurrence of SSAs among individuals with epilepsy can range from 1.42% to 80%. The upper extremities are more commonly affected in SSAs, followed by the lower extremities and the face. The most common type of somatosensory aura is paresthetic, followed by painful and thermal auras. In the primary somatosensory auras, sensations occur more commonly contralaterally, while the secondary somatosensory auras can be ipsilateral or bilateral. Despite the high localizing features of somatosensory areas, cortical stimulation studies have shown overlapping sensations originating in the insula and the supplementary sensorimotor area.
]]>Medicines doi: 10.3390/medicines10080048
Authors: Kosuke Karatsu Ryota Tamura Tsubasa Miyauchi Junki Sogano Utaro Hino Takashi Iwama Masahiro Toda
Background: Postoperative trigeminal neuropathy may be seen after surgery for middle and posterior cranial fossa lesions. Although neuropathic pain is a cause of reduced quality of life, global consensus on postoperative pain management is lacking. Mirogabalin besylate is a selective ligand for the α2δ subunit of voltage-gated calcium channels. Although mirogabalin has been used for patients with postherpetic neuralgia and painful diabetic peripheral neuropathy, few reports have assessed the effect on postsurgical neuropathy. In this report, we describe a clinical effectiveness of mirogabalin for trigeminal neuropathy after skull base surgery. Case description: Case 1: A 51-year-old female with right trigeminal schwannoma was operated on via the anterior transpetrosal approach. She had tingling and numb feelings in the right face postoperatively. Mirogabalin was orally administered after the operation. Her continuous facial numbness immediately improved. Case 2: A 55-year-old female with left middle fossa base meningioma extending into the infratemporal fossa was operated on via the infratemporal fossa approach. She had a tingling feeling in the left face postoperatively. Mirogabalin was orally administered for this symptom after the operation, which gradually improved. Conclusions: Mirogabalin may show significant pain relief for patients with trigeminal neuropathy after skull base surgery. Further studies using a larger number of patients are warranted to confirm these findings.
]]>Medicines doi: 10.3390/medicines10080047
Authors: John O. Obasuyi Mathias A. Emokpae
There is an indication of abrupt rise in chronic kidney disease (CKD) in Nigeria and thyroid function involvement has not been sufficiently evaluated. This study determined thyroid gland function among subjects with CKD in Benin City, Nigeria. A total of 184 randomized CKD patients attending specialist clinic and 80 healthy control subjects were recruited for this study. A well-structured questionnaire was used to obtain data on socio-demography. Blood specimens were collected and used for the determination of thyroid function parameters; thyroid stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4), free thyroxine (fT4), thyroid peroxidase antibody (TPO-Abs), thyroid globulin antibody (Tg-Abs) and Deiodinase enzyme Type 1 (D1). SPINA GD and SPINA GT were calculated using Michaelis-Menten model. The CKD was classified into stages using Modification of Drug in Renal Disease (MDRD) formula. Thyroid dysfunctions observed were clinical hyperthyroidism 1 (0.54%), non-thyroidal illness 78 (42.4%), clinical hypothyroidism 11 (6.0%), sub-clinical hyperthyroidism 3 (1.60%), and sub-clinical hypothyroidism 11 (6.0%), while euthyroid were 80 (43.5%). SPINA GD of CKD patients (33.85 ± 10.94) was not significantly different when compared with controls (24.85 ± 1.57), whereas, SPINA GT was significantly higher (p < 0.01) among CKD patients (3.74 ± 0.31) than controls (2.68 ± 0.11). Autoimmune thyroid disease demonstrated by positive Tg-Abs and TPO-Abs were observed among approximately 7.9% of CKD patients. Serum TPO-Abs concentration increased with CKD progression. Thyroid dysfunction is involved in the pathogenesis of CKD patients. The etiologies are multifactorial and immunological mechanisms of autoimmune thyroid disease may be a contributing factor.
]]>Medicines doi: 10.3390/medicines10080046
Authors: Paul W. Davis Pajaree Krisanapan Supawit Tangpanithandee Charat Thongprayoon Jing Miao Mohamed Hassanein Prakrati Acharya Michael A. Mao Iasmina M. Craici Wisit Cheungpasitporn
Background: Contrast-induced encephalopathy (CIE) is an infrequent but serious neurological condition that occurs shortly after the administration of contrast during endovascular and angiography procedures. Patients suffering from chronic kidney disease (CKD) or end-stage kidney disease (ESKD) are considered to be at a higher risk of contrast medium neurotoxicity, due to the delayed elimination of the contrast medium. However, the occurrence and characteristics of CIE in CKD/ESKD patients have not been extensively investigated. Methods: We conducted a comprehensive literature search, utilizing databases such as MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, up to September 2022. The purpose was to identify documented cases of CIE among patients with CKD or ESKD. Employing a random-effects model, we calculated the pooled incidence and odds ratio (OR) of CIE in CKD/ESKD patients. Results: Our search yielded a total of eleven articles, comprising nine case reports and two observational studies. Among these studies, 2 CKD patients and 12 ESKD patients with CIE were identified. The majority of the CKD/ESKD patients with CIE (93%) had undergone intra-arterial contrast media and/or endovascular procedures to diagnose acute cerebrovascular disease, coronary artery disease, and peripheral artery disease. The male-to-female ratio was 64%, and the median age was 63 years (with an interquartile range of 55 to 68 years). In the two observational studies, the incidence of CIE was found to be 6.8% in CKD patients and 37.5% in ESKD patients, resulting in a pooled incidence of 16.4% (95% CI, 2.4%–60.7%) among the CKD/ESKD patients. Notably, CKD and ESKD were significantly associated with an increased risk of CIE, with ORs of 5.77 (95% CI, 1.37–24.3) and 223.5 (95% CI, 30.44–1641.01), respectively. The overall pooled OR for CIE in CKD/ESKD patients was 32.9 (95% CI, 0.89–1226.44). Although dialysis prior to contrast exposure did not prevent CIE, approximately 92% of CIE cases experienced recovery after undergoing dialysis following contrast exposure. However, the effectiveness of dialysis on CIE recovery remained uncertain, as there was no control group for comparison. Conclusions: In summary, our study indicates an association between CIE and CKD/ESKD. While patients with CIE showed signs of recovery after dialysis, further investigations are necessary, especially considering the lack of a control group, which made the effects of dialysis on CIE recovery uncertain.
]]>Medicines doi: 10.3390/medicines10080045
Authors: Mirjam Bonanno Rocco Salvatore Calabrò
Translational neuroscience is intended as a holistic approach in the field of brain disorders, starting from the basic research of cerebral morphology and with the function of implementing it into clinical practice. This concept can be applied to the rehabilitation field to promote promising results that positively influence the patient’s quality of life. The last decades have seen great scientific and technological improvements in the field of neurorehabilitation. In this paper, we discuss the main issues related to translational neurorehabilitation, from basic research to current clinical practice, and we also suggest possible future scenarios.
]]>Medicines doi: 10.3390/medicines10070044
Authors: Yang Lei Jennifer Halasz Kerri L. Novak Stephen E. Congly
Background: High-dose proton pump inhibitor (PPI) therapy, given either intermittently or continuously for non-variceal upper gastrointestinal bleeding (NV-UGIB), is efficacious. Using intermittent PPI for low-risk patients may be cost-saving. Our objective was to estimate the annual cost savings if all low-risk NV-UGIB patients received intermittent PPI therapy. Methods: Patients who presented to hospital in Calgary, Alberta, who received a PPI for NV-UGIB from July 2015 to March 2017 were identified using ICD-10 codes. Patients were stratified into no endoscopy, high-risk, and low-risk lesion groups and further subdivided into no PPI, oral PPI, intermittent intravenous (IV), and continuous IV subgroups. Average length of stay (LOS) in each subgroup and costs were calculated. Results: We identified 4141 patients with NV-UGIBs, (median age 61, 57.4% male). One-thousand two-hundred and thirty-one low-risk patients received continuous IV PPI, with an average LOS of 6.8 days (95% CI 6.2–7.3) versus 4.9 days (95% CI 3.9–5.9) for intermittent IV patients. If continuous IV PPI patients instead received intermittent IV PPI, 3852 patient days and CAD 11,714,390 (2017 CAD)/year could be saved. Conclusions: Using real-world administrative data, we demonstrate that a sizable portion of low-risk patients with NV-UGIB who were given continuous IV PPI if switched to intermittent IV therapy could generate significant potential cost savings.
]]>Medicines doi: 10.3390/medicines10070043
Authors: Tomoyuki Abe Hiroshi Sakagami Shigeru Amano Shin Uota Kenjiro Bandow Yoshihiro Uesawa Shiori U Hiroki Shibata Yuri Takemura Yu Kimura Koichi Takao Yoshiaki Sugita Akira Sato Sei-ichi Tanuma Hiroshi Takeshima
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.
]]>Medicines doi: 10.3390/medicines10070042
Authors: Katsuya Sakai Tsubasa Kawasaki Hiroya Kiminarita Yumi Ikeda
Background and Objectives: This report described two cases with clear longitudinal changes in motor estimation error (difference between the motor imagery and motor execution) and their progression and motor and activities of daily living (ADL) function changes in patients with PD. Materials and Methods: Patient 1 was a 68-year-old man (Hoehn and Yahr [H and Y] stage: IV, diagnosed with PD for 11.8 years) and patient 2 was a 68-year-old woman (H and Y stage: II, diagnosed with PD for 9.6 years). Imagined two-step test (iTST), two-step test (TST), and PD-related assessments (Unified Parkinson’s Disease Rating Scale [UPDRS], and Freezing of Gait Questionnaire [FOGQ]) were assessed at baseline and after 6 months. Motor estimation error was calculated as the iTST distance minus TST distance. Results: In patient 1, motor estimation error was greater after 6 months (baseline: 5.7 [4.8%]/after 6 months: 25.7 cm [26.1%]). Moreover, UPDRS and FOGQ total scores deteriorated after 6 months (UPDRS total: 29/34 point, and FOGQ: 9/16 point). Conversely, in patient 2, motor estimation error did not change notably (−3.6 [7.6%]/−2.5 cm [7.0%]), while UPDRS and FOGQ total scores improved after 6 months (UPDRS total: 17/12 point, and FOGQ: 6/1 point). Conclusions: This report indicated that greater motor estimation error may be associated with declining motor and ADL function and disease progression in patients with PD.
]]>Medicines doi: 10.3390/medicines10070041
Authors: Natapon Rattanamusik Suriyon Uitrakul Atchara Charoenpiriya
Background: The association between Graves’ disease (GD) and serum vitamin D levels has been studied for decades although the results were controversial. Moreover, the difference in vitamin D levels between the different stages of GD is not well studied. Therefore, this study aimed to compare the vitamin D levels between active and remission GD and to investigate the factors affecting vitamin D levels in GD patients. Methods: This cross-sectional study was performed between 1 January to 31 December 2021. The eligible patients were in either the active or remission stage of GD. The demographic and clinical data of the patients willing to participate in the study were collected, as well as their vitamin D levels. Comparisons of continuous parameters between the active and remission groups were performed using the Mann–Whitney U test, while categorical parameters were performed using the Chi-square test. Results: 75 patients were diagnosed with GD, with 54.7% in the active stage. The mean vitamin D level was lower in the active GD group than in the remission GD group (28.23 vs. 31.58 ng/mL, respectively, p-value 0.079). The prevalence of vitamin D deficiency (i.e., serum vitamin D level < 20 ng/mL) in the active GD group was 14.6%, and in the remission GD group was 0% (p-value 0.02). Moreover, there was a significant negative correlation between the serum vitamin D level and serum free T4 level (p-value 0.03). Conclusions: In spite of non-significance, patients with active GD had lower mean vitamin D levels compared to those with remission GD. The prevalence of vitamin D deficiency was significantly higher in the active GD patients. Additionally, a negative correlation between serum vitamin D levels and serum free T4 levels was observed in this study.
]]>Medicines doi: 10.3390/medicines10070040
Authors: E. Scott Sills Samuel H. Wood
Platelet-rich plasma (PRP) is an ‘orthobiologic’ with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, ‘ovarian rejuvenation’. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors. However, if the observed effect of rectifying embryo ploidy error can be proven beyond case reports and small series, activated PRP (or its condensed plasma cytokines) would deliver a welcome therapeutic disruption that is difficult to overstate. Because shortcomings in ovarian function are presently addressed mainly by pharmacological approaches (i.e., via recombinant gonadotropins, GnRH analogs, or luteal support), autologous PRP would represent an unusual departure from these interventions. Given the diversity of platelet cargo proteins, the target response of intraovarian PRP is probably not confined to oocytes or follicles. For example, PRP manipulates signal networks driving improved perfusion, HOX regulation, N-glycan post-translational modification, adjustment of voltage-gated ion channels, telomere stabilization, optimization of SIRT3, and ribosome and mitochondria recovery in older oocytes. While multichannel signals operating on various pathways are not unique to reproductive biology, in intraovarian PRP this feature has received little study and may help explain why its standardization has been difficult. Against this background, our report examines the research themes considered most likely to shape clinical practice.
]]>Medicines doi: 10.3390/medicines10070039
Authors: Dora Palčevski Andrej Belančić Ivan Mikuličić Eduard Oštarijaš Robert Likić Oliver Dyar Vera Vlahović-Palčevski
Background: Antimicrobials are some of the most prescribed drugs by junior doctors, but studies suggest most medical graduates feel unprepared for their future prescribing tasks. The aim of the present study was to compare the self-reported preparedness to prudently prescribe antimicrobials of final-year medical students in Croatia in 2015 and 2019. Methods: The same self-reported web-based survey on the preparedness to prescribe antibiotics was used in both 2015 and 2019. All final-year students at all four medical schools in Croatia (Osijek, Rijeka, Split, and Zagreb) were invited to participate in both 2015 and 2019. Preparedness scores were divided into “topic preparedness scores” and “global preparedness scores”. Topic preparedness scores represented the percentage of students at a medical school who felt sufficiently prepared for each topic. They were first established at a medical school level and then at the national level. Global preparedness scores were determined for each student separately and then calculated at the medical school and national levels. Results: The country’s global preparedness score, representing the average proportion of topics in which students felt sufficiently prepared, was slightly higher in 2015 compared with the 2019 results (62.7% vs. 56.5%; p = 0.191). Croatian students reported higher preparedness in 2015 than in 2019 for 25 out of 27 topics included in the survey. The majority of students reported a need for more education on antibiotic use both in 2015 and 2019 (78.0% vs. 83.0%; p = 0.199). Conclusions: Despite increasing antimicrobial stewardship activities in various healthcare settings, medical students who are about to start prescribing antibiotics on their own do not feel sufficiently prepared to do so. Antimicrobial stewardship programs should be designed to incorporate undergraduate medical student education, for instance, as a specific, mandatory course or integrated into other courses, such as clinical pharmacology.
]]>Medicines doi: 10.3390/medicines10070038
Authors: Victor Abiola Adepoju Olanrewaju Oladimeji Olusola Daniel Sokoya
Background: TB is a major cause of morbidity and mortality, with slum residents being disproportionately affected. This study aimed to assess health-seeking behavior among adult residents of slum communities presenting with coughs in Lagos, Nigeria. Methods: A community-based, cross-sectional study was conducted across six urban slums in Nigeria as part of community outreaches to mark World TB Day. A structured, pretested questionnaire was used to capture relevant sociodemographic details and questions regarding symptoms of coughs and related symptoms as well as care-seeking behavior. Data were explored, analyzed, and presented using descriptive statistics. Results: A total of 632 respondents participated in this study. The majority were 25–34 years old (24.7%), male (65.8%), Christian (55.7%), married (73.7%), with secondary education (37.8%), with 3–4 persons per household (41%) and with 1–2 persons per room (44.5%). In total, 26.6% had had a cough for two weeks or more and were considered as presumptive TB patients. Overall, 37.2% of respondents with a cough visited patent proprietary medicine vendors (PPMVs) as the first port of call. Good health-seeking behavior was exhibited by only 36.2% of respondents. In total, 38.9% delayed seeking care from a health facility (government or private) more than one month after the onset of symptoms. None of the factors included in the multivariate analysis showed a significant association with good health-seeking behavior (i.e., visiting government or private hospitals/clinics). Conclusions: The poor health-seeking behavior, delay in seeking TB care and preference for PPMVs emphasizes the need for National tuberculosis programs (NTPs) to further engage these informal providers in TB prevention, diagnosis and treatment services in urban slum communities.
]]>Medicines doi: 10.3390/medicines10060037
Authors: Nina Werkhäuser Ursula Pieper-Fürst Hacer Sahin Antonia Claas Ralph Mösges
Background: Rhinosinusitis is commonly treated with decongestants, analgesics, and local corticosteroids. Phytotherapeutics are also utilised for symptomatic relief, including cineole, the main component of eucalyptus oil. Methods: The current non-interventional, anonymised survey investigated quality of life in participants with rhinosinusitis (with or without additional symptoms of bronchitis) via the German version of a validated quality of life questionnaire (RhinoQol). Overall, 310 subjects administered a cineole preparation (Sinolpan) and 40 subjects applying nasal decongestant were recruited in German pharmacies. Results: Significant improvements in frequency (64.0%), bothersomeness (52.1%), and impact (53.9%) of rhinosinusitis symptoms were reported upon treatment with cineole over a mean treatment period of seven days (p < 0.001 each). The overall treatment efficacy of cineole was evaluated as good or very good by 90.0% of the participants, and the quality of life during work or leisure time improved upon treatment. Six (non-serious) possibly related side effects were reported in four participants who were administered cineole. The tolerability of the treatment was assessed as good or very good by 93.9% of the participants. Conclusions: Cineole can be considered as a safe and well-tolerated rhinosinusitis treatment conferring a clear improvement in quality of life outcomes.
]]>Medicines doi: 10.3390/medicines10060036
Authors: Leonardo Marques da Fonseca Israel Diniz-Lima Marcos André Rodrigues da Costa Santos Tatiany Nunes Franklim Kelli Monteiro da Costa Ariely Costa dos Santos Alexandre Morrot Debora Decote-Ricardo Raphael do Carmo Valente Celio Geraldo Freire-de-Lima Jhenifer Santos dos Reis Leonardo Freire-de-Lima
Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial–mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis.
]]>Medicines doi: 10.3390/medicines10060035
Authors: Jamir Pitton Rissardo Ana Leticia Fornari Caprara Maritsa Casares Holly J. Skinner Umair Hamid
Background: Adverse effects of antiseizure medications (ASMs) remain one of the major causes of non-adherence. Cosmetic side effects (CSEs) are among the most commonly reported side effects of ASMs. In this context, alopecia is one of the CSEs that has a high intolerance rate leading to poor therapeutical compliance. Methods: We performed a literature review concerning alopecia as a secondary effect of ASMs. Results: There are 1656 individuals reported with ASM-induced alopecia. Valproate (983), lamotrigine (355), and carbamazepine (225) have been extensively reported. Other ASMs associated with alopecia were cenobamate (18), levetiracetam (14), topiramate (13), lacosamide (7), vigabatrin (6), phenobarbital (5), gabapentin (5), phenytoin (4), pregabalin (4), eslicarbazepine (3), brivaracetam (2), clobazam (2), perampanel (2), trimethadione (2), rufinamide (2), zonisamide (2), primidone (1), and tiagabine (1). There were no reports of oxcarbazepine and felbamate with drug-induced alopecia. Hair loss seen with ASMs was diffuse and non-scarring. Telogen effluvium was the most common cause of alopecia. A characteristic feature was the reversibility of alopecia after ASM dose adjustment. Conclusions: Alopecia should be considered one important adverse effect of ASMs. Patients reporting hair loss with ASM therapy should be further investigated, and specialist consultation is recommended.
]]>Medicines doi: 10.3390/medicines10060034
Authors: Lakshmi Reka Chamari Maheshika Godage Jayantha Wijayabandara Aravinda Siriwardhene
Background: The rhizome of Languas galangal is traditionally used in Sri Lanka for the treatment of skin infections caused by fungi. The aim of the present study was to evaluate the antifungal activity of L. galangal rhizome and to develop a topical antifungal formulation from it. Methods: The dried, powdered rhizome of L. galangal was successively extracted with hexane, dichloromethane, ethyl acetate and methanol using Soxhlet extraction. The agar well diffusion method was used to assess the antifungal activity against Candida albicans and Aspergillus nger. The antifungal activities of the extracts were compared with clotrimazole as the positive control and dimethyl sulfoxide (DMSO) as the negative control. The most active hexane extract was used to prepare the cream. The antifungal activity of the formulated cream was tested. Results: The hexane extract of L. galangal rhizome powder was more effective on C. albicans and A. niger. The hexane extract of L. galangal showed the maximum zone of inhibition against C. albicans and A. niger (20.20 mm ± 0.46, 18.20 mm ± 0.46) compared to the other three extracts, while clotrimazole, which was used as a positive control, produced a larger zone of inhibition (36.10 mm ± 0.65) and dimethyl sulfoxide (DMSO), the negative control, did not produce inhibitory zones. Stability testing of the formulated cream showed a stable and good appearance. Conclusions: The cream developed using the hexane extract showed in vitro antifungal activity against C. albicans and A. niger. Further evaluations on shelf life, stability and safety are required.
]]>Medicines doi: 10.3390/medicines10060033
Authors: Jamir Pitton Rissardo Ana Letícia Fornari Caprara
Background: Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs). Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022. Results: A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25–87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1–68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1–56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management. Conclusions: Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies.
]]>Medicines doi: 10.3390/medicines10050032
Authors: Abdelaziz Ghanemi Mayumi Yoshioka Jonny St-Amand
Coronavirus disease-2019 (COVID-19) has had and will have impacts on public health and health system expenses. Indeed, not only it has led to high numbers of confirmed COVID-19 cases and hospitalizations, but its consequences will remain even after the end of the COVID-19 crisis. Therefore, therapeutic options are required to both tackle the COVID-19 crisis and manage its consequences during the post COVID-19 era. Secreted protein acidic and rich in cysteine (SPARC) is a biomolecule that is associated with various properties and functions that situate it as a candidate which may be used to prevent, treat and manage COVID-19 as well as the post-COVID-19-era health problems. This paper highlights how SPARC could be of such therapeutic use.
]]>Medicines doi: 10.3390/medicines10050031
Authors: Dimitrios Symeonidis Ismini Paraskeua Athina A. Samara Effrosyni Bompou Alexandros Valaroutsos Maria P. Ntalouka Dimitrios Zacharoulis
Introduction: Primary sclerosing cholangitis sets the scene for several pathologies of both the intrahepatic and the extrahepatic biliary tree. Surgical treatment, when needed, is almost unanimously summarized in the creation of a Roux-en-Y hepaticojejunostomy, a procedure with a relatively high associated failure rate. Presentation of case: A 70-year-old male, diagnosed with primary sclerosing cholangitis, was submitted to a Roux-en-Y hepaticojejunostomy due to a dominant stricture of the extrahepatic biliary tree. Recurrent episodes of acute cholangitis dictated a workup in the direction of a possible stenosis at the level of the anastomosis. The imaging studies were inconclusive while both the endoscopic and the transhepatic approach failed to assess the status of the anastomosis. A laparotomy, with the intent to revise a high suspicion for stenosis hepaticojejunostomy, was decided. Intraoperatively, a decision to assess the hepaticojejunostomy prior to the scheduled surgical revision, via endoscopy, was made. In this direction, an enterotomy was made on the short jejunal blind loop in order to gain luminal access and an endoscope was propelled through the enterotomy towards the biliary enteric anastomosis. Results: The inspection of the anastomosis under direct endoscopic vision showed no evidences of stenosis and averted an unnecessary, under these circumstances, revision of the anastomosis. Conclusions: The surgical revision of a Roux-en-Y hepaticojejunostomy is a highly demanding operation with an increased associated morbidity, and it should be reserved as the final resort in the treatment algorithm. An approach of utilizing surgery to facilitate the endoscopic assessment prior to proceeding to the surgical revision of the anastomosis appears justified.
]]>Medicines doi: 10.3390/medicines10050030
Authors: Esmael Besufikad Belachew Adey Feleke Desta Dinksira Bekele Deneke Bizunesh Dires Fenta Alemwosen Teklehaymanot Alem Abdo Kedir Abafogi Fekade Yerakly Lukas Mesele Bezabih Dareskedar Tsehay Sewasew Eva J. Kantelhardt Tesfaye Sisay Tessema Rawleigh Howe
Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015–2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ2 = 8.55, p = 0.033) and type of surgery (χ2 = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.
]]>Medicines doi: 10.3390/medicines10050029
Authors: Pierre-Louis Naillon Valentin Flaudias Georges Brousse Catherine Laporte Julien S. Baker Valentin Brusseau Aurélie Comptour Marek Zak Jean-Baptiste Bouillon-Minois Frédéric Dutheil
Background: Cannabis use by physicians can be detrimental for them and their patients. We conducted a systematic review and meta-analysis on the prevalence of cannabis use by medical doctors (MDs)/students. Method: PubMed, Cochrane, Embase, PsycInfo and ScienceDirect were searched for studies reporting cannabis use in MDs/students. For each frequency of use (lifetime/past year/past month/daily), we stratified a random effect meta-analysis depending on specialties, education level, continents, and periods of time, which were further compared using meta-regressions. Results: We included 54 studies with a total of 42,936 MDs/students: 20,267 MDs, 20,063 medical students, and 1976 residents. Overall, 37% had used cannabis at least once over their lifetime, 14% over the past year, 8% over the past month and 1.1 per thousand (‰) had a daily use. Medical students had a greater cannabis use than MDs over their lifetime (38% vs. 35%, p < 0.001), the past year (24% vs. 5%, p < 0.001), and the past month (10% vs. 2%, p < 0.05), without significance for daily use (0.5% vs. 0.05%, NS). Insufficient data precluded comparisons among medical specialties. MDs/students from Asian countries seemed to have the lowest cannabis use: 16% over their lifetime, 10% in the past year, 1% in the past month, and 0.4% daily. Regarding periods of time, cannabis use seems to follow a U-shape, with a high use before 1990, followed by a decrease between 1990 and 2005, and a rebound after 2005. Younger and male MDs/students had the highest cannabis use. Conclusions: If more than a third of MDs tried cannabis at least once in their lifetime, this means its daily use is low but not uncommon (1.1‰). Medical students are the biggest cannabis users. Despite being common worldwide, cannabis use is predominant in the West, with a rebound since 2005 making salient those public health interventions during the early stage of medical studies.
]]>Medicines doi: 10.3390/medicines10040028
Authors: Amane Otaki Atsuko Furuta Kazuhito Asano
Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 105 cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 μL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 μL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 μM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 μM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.
]]>Medicines doi: 10.3390/medicines10040027
Authors: Hiroshi Kusunoki Kazumi Ekawa Masakazu Ekawa Nozomi Kato Keita Yamasaki Masaharu Motone Hideo Shimizu
Background: The rise in antibody titers against the novel coronavirus (SARS-CoV-2) and its duration are considered an important indicator for confirming the effect of a COVID-19 vaccine, and self-paid tests of antibody titer are conducted in many facilities nationwide. Methods: The relationship between the number of days after the second and third dose of vaccines, age, and antibody titer was determined from the medical records of general internal medicine clinics that conducted self-paid testing of the SARS-CoV-2 antibody titer using Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics); the relationship between the number of days after two or more doses of vaccines and antibody titer was also determined. We also examined the antibody titers in cases of spontaneous infection with SARS-CoV-2 after two or more doses of the vaccine. Results: Log-transformed SARS-CoV-2 antibody titers measured within 1 month from the second or third dose of vaccine showed a negative correlation with age (p < 0.05). In addition, the log-transformed antibody titers also showed a negative correlation trend with the number of days after the second dose of vaccine (p = 0.055); however, there were no significant correlations between the log-transformed antibody titers and the number of days after the third dose of vaccine. The median antibody titer after the third vaccination was 18,300 U/mL, more than 10 times the median antibody titer after the second dose of vaccine, of 1185 U/mL. There were also some cases of infection after the third or fourth dose of vaccine, with antibody titers in the tens of thousands of U/ml after infection, but the patients still received further booster vaccinations after the infection. Conclusions: The antibody titers after the third vaccination did not attenuate after a short follow-up period of one month, while they tended to attenuate after the second vaccination. It is considered that many people in Japan received further booster vaccinations after spontaneous infection, even though they already had antibody titers in the tens of thousands of U/mL due to “hybrid immunity” after spontaneous infection following two or more doses of vaccine. The clinical significance of the booster vaccination in this population still needs to be thoroughly investigated and should be prioritized for those with low SARS-CoV-2 antibody titers.
]]>Medicines doi: 10.3390/medicines10040026
Authors: Cezara-Andreea Soysaler Cătălina Liliana Andrei Octavian Ceban Crina-Julieta Sinescu
Hypertension frequently coexists with obesity, diabetes, hyperlipidemia, or metabolic syndrome, anditsassociation with cardiovascular disease is well established. The identification and management of these risk factors is an important part of overall patient management. In this paper, we find the most relevant patterns of hospitalized patients with cardiovascular diseases, consideringaspects of their comorbidities, such as triglycerides, cholesterol, diabetes, hypertension, and obesity. To find the most relevant patterns, several clusterizations were made, playing with the dimensions of comorbidity and the number of clusters. There are three main patient types who require hospitalization: 20% whose comorbidities are not so severe, 44% with quite severe comorbidities, and 36% with fairly good triglycerides, cholesterol, and diabetes but quite severe hypertension and obesity. The comorbidities, such as triglycerides, cholesterol, diabetes, hypertension, and obesity, were observed in different combinations in patients upon hospital admission.
]]>Medicines doi: 10.3390/medicines10040025
Authors: Charat Thongprayoon Pradeep Vaitla Caroline C. Jadlowiec Napat Leeaphorn Shennen A. Mao Michael A. Mao Fahad Qureshi Wisit Kaewput Fawad Qureshi Supawit Tangpanithandee Pajaree Krisanapan Pattharawin Pattharanitima Prakrati C. Acharya Pitchaphon Nissaisorakarn Matthew Cooper Wisit Cheungpasitporn
Background: Better understanding of the different phenotypes/subgroups of non-U.S. citizen kidney transplant recipients may help the transplant community to identify strategies that improve outcomes among non-U.S. citizen kidney transplant recipients. This study aimed to cluster non-U.S. citizen kidney transplant recipients using an unsupervised machine learning approach; Methods: We conducted a consensus cluster analysis based on recipient-, donor-, and transplant- related characteristics in non-U.S. citizen kidney transplant recipients in the United States from 2010 to 2019 in the OPTN/UNOS database using recipient, donor, and transplant-related characteristics. Each cluster’s key characteristics were identified using the standardized mean difference. Post-transplant outcomes were compared among the clusters; Results: Consensus cluster analysis was performed in 11,300 non-U.S. citizen kidney transplant recipients and identified two distinct clusters best representing clinical characteristics. Cluster 1 patients were notable for young age, preemptive kidney transplant or dialysis duration of less than 1 year, working income, private insurance, non-hypertensive donors, and Hispanic living donors with a low number of HLA mismatch. In contrast, cluster 2 patients were characterized by non-ECD deceased donors with KDPI <85%. Consequently, cluster 1 patients had reduced cold ischemia time, lower proportion of machine-perfused kidneys, and lower incidence of delayed graft function after kidney transplant. Cluster 2 had higher 5-year death-censored graft failure (5.2% vs. 9.8%; p < 0.001), patient death (3.4% vs. 11.4%; p < 0.001), but similar one-year acute rejection (4.7% vs. 4.9%; p = 0.63), compared to cluster 1; Conclusions: Machine learning clustering approach successfully identified two clusters among non-U.S. citizen kidney transplant recipients with distinct phenotypes that were associated with different outcomes, including allograft loss and patient survival. These findings underscore the need for individualized care for non-U.S. citizen kidney transplant recipients.
]]>Medicines doi: 10.3390/medicines10030024
Authors: Chan Hum Park Takashi Tanaka Yoshie Akimoto Jin Pyeong Jeon Takako Yokozawa
Background: Hachimijiogan (HJG) and Bakumijiogan (BJG), two derivative prescriptions of Rokumijiogan (RJG), were selected to investigate their renoprotective potential in the 5/6 nephrectomized (5/6Nx) rat model. Methods: Rats were treated with HJG and BJG orally at 150 mg/kg body weight/day once daily for 10 weeks after resection of 5/6 of the renal volume, and their renoprotective effects were compared with 5/6Nx vehicle-treated and sham-operated control rats. Results: Improvements in renal lesions, glomerulosclerosis, tubulointerstitial injury, and arteriosclerotic lesions estimated by histologic scoring indices in the HJG-treated group were compared with those in the BJG-treated group. HJG- and BJG-treated groups ameliorated the renal function parameters. Elevated levels of renal oxidative stress-related biomarkers were reduced, while decreased antioxidant defence systems (superoxide dismutase and the glutathione/oxidized glutathione ratio) were increased in the HJG-treated group rather than the BJG-treated group. In contrast, BJG administration significantly reduced expression of the inflammatory response through oxidative stress. The HJG-treated group showed a decrease in inflammatory mediators through the JNK pathway. To gain a deeper understanding of their therapeutic action, the effects of the main components detected in HJG and BJG were evaluated using the LLC-PK1 renal tubular epithelial cell line, which is the renal tissue most vulnerable to oxidative stress. Corni Fructus and Moutan Cortex-originated compositions afforded important protection against oxidative stress induced by peroxynitrite. Conclusions: From our described and discussed analyses, it can be concluded that RJG-containing prescriptions, HJG and BJG are an excellent medicine for chronic kidney disease. In the future, appropriately designed clinical studies in people with chronic kidney disease are necessary to evaluate the renoprotective activities of HJG and BJG.
]]>Medicines doi: 10.3390/medicines10030023
Authors: Olivier Bruyère Johann Detilleux Jean-Yves Reginster
Objective: The aim of this study was to evaluate the cost-effectiveness of different glucosamine formulations and preparations used for the management of osteoarthritis in Thailand compared with placebo. Methods: We used a validated model to simulate the individual patient Utility score from aggregated data available from 10 different clinical trials. We then used the Utility score to calculate the quality-adjusted life year (QALY) over 3 and 6 months treatment period. We used the public costs of glucosamine products available in Thailand in 2019 to calculate the incremental cost-effectiveness ratio. We separated the analyses for prescription-grade crystalline glucosamine sulfate (pCGS) and other formulations of glucosamine. A cost-effectiveness cut-off of 3.260 USD/QALY was considered. Results: Irrespective of the glucosamine preparation (tablet or powder/capsule), the data show that pCGS is cost-effective compared with placebo over a 3 and 6 months. However, the other glucosamine formulations (e.g., glucosamine hydrochloride) never reached the breakeven point at any time. Conclusions: Our data show that pCGS is cost-effective for the management of osteoarthritis in the Thai context while other glucosamine formulations are not.
]]>Medicines doi: 10.3390/medicines10030022
Authors: Abrar-Ahmad Zulfiqar Ibrahima Amadou Dembele Emmanuel Andres
Introduction: The aim of our study is to evaluate the nutritional status of patients in an acute geriatric unit. Methods: Patients included in the study were hospitalized in an acute geriatric unit over a period of 6 months. The nutritional status of each patient was evaluated with anthropometric measurements (the BMI and MNA scales), and biological measurements (albumin). Frailty was evaluated using three scales: the Fried scale, the CFS and the modified SEGA scale. Results: A total of 359 patients were included, comprising 251 women (70%) with an average age of 85.28 years. The study showed that 102 elderly subjects were considered undernourished according to the BMI scale, 52 subjects were undernourished according to the MNA scale, and 50 subjects were undernourished according to their albumin levels. The relationships between undernutrition and frailty syndrome studied in our work show that elderly subjects who are undernourished according to the BMI and MNA scales are significantly frail according to Fried and Rockwood, whereas those who are undernourished according to their albumin levels are significantly frail according to Fried and the modified SEGA scale. Conclusion: The relationship between undernutrition and the frailty syndrome is close, and their joint screening is necessary, whether on an outpatient or in-hospital basis, in order to prevent negative events related to comorbidities and geriatric syndromes.
]]>Medicines doi: 10.3390/medicines10030021
Authors: Subrata Deb Mohamed Ben-Eltriki Hans Adomat Mei Y. Chin Emma S. Tomlinson Guns
Background: Abiraterone acetate is a cytochrome P450 17A1 (CYP17A1) inhibitor that is indicated for use in both castration-resistant and castration-sensitive prostate cancer patients. To manage the mineralocorticoid effects of CYP17A1 inhibition, a glucocorticoid such as dexamethasone is co-administered with abiraterone. The goal of the present study was to understand the effect of dexamethasone on the disposition of abiraterone. Methods: Adult male CD-1 mice were treated with either dexamethasone (80 mg/kg/day) or vehicle for three consecutive days, followed by the administration of a single dose of abiraterone acetate (180 mg/kg) as an oral gavage. Blood samples were collected by tail bleeding at timepoints between 0 to 24 h. Subsequently, abiraterone was extracted from the mouse serum using a neutral pH condition and serum abiraterone levels were determined using a liquid chromatography–mass spectrometry assay. Results: Our results demonstrated that dexamethasone lowered the maximum plasma concentration and area under the curve parameters by approximately five- and ten-fold, respectively. Similar effects were also observed on the plasma half-life and oral clearance parameters. This is the first report of dexamethasone effect on abiraterone disposition in vivo. Conclusions: We conclude that dexamethasone has the potential to reduce the plasma abiraterone level and thus compromise its CYP17A1 inhibitory ability in the procancerous androgen biosynthesis pathway. Thus, use of a higher abiraterone dose may be warranted when used alongside dexamethasone.
]]>Medicines doi: 10.3390/medicines10030020
Authors: Joao Victor Souza-Peres Kimberly Flores Bethany Umloff Michelle Heinan Paul Herscu Mary Beth Babos
A lack of reliable information hinders the clinician evaluation of suspected herb–drug interactions. This pilot study was a survey-based study conceived as a descriptive analysis of real-life experiences with herb–drug interaction from the perspective of herbalists, licensed health-care providers, and lay persons. Reported dietary supplement–drug interactions were evaluated against the resources most commonly cited for the evaluation of potential supplement–drug interactions. Disproportionality analyses were performed using tools available to most clinicians using data from the U.S. Federal Adverse Event Reporting System (FAERS) and the US Center for Food Safety and Applied Nutrition (CFSAN) Adverse Event Reporting System (CAERS). Secondary aims of the study included exploration of the reasons for respondent use of dietary supplements and qualitative analysis of respondent’s perceptions of dietary supplement–drug interaction. While agreement among reported supplement–drug interactions with commonly cited resources for supplement–drug interaction evaluation and via disproportionality analyses through FAERS was low, agreement using data from CAERS was high.
]]>Medicines doi: 10.3390/medicines10030019
Authors: Athanasios Garavelas Panagiotis Mallis Efstathios Michalopoulos Eros Nikitos
Background: The intraovarian administration of autologous platelet-rich plasma (PRP) acts beneficially for the stimulation of follicle production in women presenting different forms of ovarian dysfunction. This pilot study aimed to evaluate and provide significant data regarding the efficacy of PRP to rejuvenate the ovaries. Methods: A total of 253 women aged 22–56 years, were divided into five groups, based on their status. All participants signed for informed consent for the current study. Blood sampling, preparation of PRP and intraovarian infusion of the latter were performed on all participants. The evaluation of PRP efficacy, a two-month follow-up detecting the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-mullerian hormone (AMH), was performed for all participants. For women with advanced ages (>48 years), the restoration and regularity of the menstrual cycle were additionally evaluated. Results: After the two-month follow-up, the majority of the participants presented improvement in their hormonal profiles. Additionally, 17% of the women in this pilot study successfully conceived. The restoration of the menstrual cycle was detected in 15% of the women with advanced ages. Conclusions: Intraovarian infusion of autologous PRP exhibited remarkable evidence and promising results to restore ovarian insufficiency.
]]>Medicines doi: 10.3390/medicines10020018
Authors: Raed Y. Ageeli Sunita Sharma Melissa Puppa Richard J. Bloomer Randal K. Buddington Marie van der Merwe
Background: The intestinal ecosystem, including epithelium, immune cells, and microbiota, are influenced by diet and timing of food consumption. The purpose of this study was to evaluate various dietary protocols after ad libitum high fat diet (HFD) consumption on intestinal morphology and mucosal immunity. Methods: C57BL/6 male mice were fed a 45% high fat diet (HFD) for 6 weeks and then randomized to the following protocols; (1) chow, (2) a purified high fiber diet known as the Daniel Fast (DF), HFD consumed (3) ad libitum or in a restricted manner; (4) caloric-restricted, (5) time-restricted (six hours of fasting in each 24 h), or (6) alternate-day fasting (24 h fasting every other day). Intestinal morphology and gut-associated immune parameters were investigated after 2 months on respective protocols. Results: Consuming a HFD resulted in shortening of the intestine and reduction in villi and crypt size. Fasting, while consuming the HFD, did not restore these parameters to the extent seen with the chow and DF diet. Goblet cell number and regulatory T cells had improved recovery with high fiber diets, not seen with the HFD irrespective of fasting. Conclusion: Nutritional content is a critical determinant of intestinal parameters associated with gut health.
]]>Medicines doi: 10.3390/medicines10020017
Authors: Veronica Gagliardi Giuseppe Gagliardi Francesco Ceccherelli Antonello Lovato
Background: The regulation of microcirculation depends on the dynamic interaction of different factors: the autonomic nervous system plays a pivotal role in the blood flow and acupuncture can modulate it, obtaining different results depending on the site, the frequency, and the intensity of the stimulation. Methods: 18 healthy subjects have been enrolled and have undergone two sessions of electroacupuncture stimulations: one session using high frequency and one with low frequency. Microcirculation has been monitored continuously during stimulation using the laser Doppler method. Results: The microcirculatory parameters have shown a significant difference between high and low-frequency stimulation, suggesting that low-frequency stimulation is more effective for obtaining a vasodilator effect. Discussion: Our results show that low-frequency stimulation can increase the cutaneous microcirculatory flux, without significantly modifying blood pressure and heart rate. The auricular stimulation causes an increase in the activity of the vagus nerve, increasing the cholinergic activity without acting on post-junctional muscarinic receptors. Conclusion: Auricular acupuncture has a significant impact on the regulation of microcirculation.
]]>Medicines doi: 10.3390/medicines10020016
Authors: Adriana Piccolo Francesco Corallo Davide Cardile Michele Torrisi Chiara Smorto Simona Cammaroto Viviana Lo Buono
Patients affected by global aphasia are no longer able to understand, produce, name objects, write and read. It occurs as a result of functional damage of ischemic or hemorrhagic origin affecting the entire peri-silvan region and frontal operculum. Rehabilitation training aims to promote an early intervention in the acute phase. We described a case of a 57-year-old female patient with left intraparenchymal fronto-temporo-parietal cerebral hemorrhage and right hemiplegia. After admission to clinical rehabilitative center, the patient was not able to perform simple orders and she presented a severe impairment of auditory and written comprehension. Eloquence was characterized by stereotypical emission of monosyllabic sounds and showed compromised praxis-constructive abilities. Rehabilitation included a program of Neurologic Music Therapy (NMT), specifically Symbolic Communication Training Through Music (SYCOM) and Musical Speech Stimulation (MUSTIM). Rehabilitative treatment was measured by improved cognitive and language performance of the patient from T0 to T1. Music rehabilitative interventions and continuous speech therapy improve visual attention and communicative intentionality. In order to confirm the effectiveness of data presented, further extensive studies of the sample would be necessary, to assess the real role of music therapy in post-stroke global aphasia.
]]>Medicines doi: 10.3390/medicines10020015
Authors: Jhenifer Santos dos Reis Israel Diniz-Lima Marcos André Rodrigues da Costa Santos Pedro Marçal Barcelos Kelli Monteiro da Costa Raphael do Carmo Valente Lorrane de Souza Chaves Luma Petel de Campos Ariely Costa dos Santos Rafaela Gomes Correia de Lima Debora Decote-Ricardo Alexandre Morrot Jose Osvaldo Previato Lucia Mendonça-Previato Celio Geraldo Freire-de-Lima Leonardo Marques da Fonseca Leonardo Freire-de-Lima
In this article, we discuss the main aspects regarding the recognition of cell surface glycoconjugates and the immunomodulation of responses against the progression of certain pathologies, such as cancer and infectious diseases. In the first part, we talk about different aspects of glycoconjugates and delve deeper into the importance of N-glycans in cancer immunotherapy. Then, we describe two important lectin families that have been very well studied in the last 20 years. Examples include the sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), and galectins. Finally, we discuss a topic that needs to be better addressed in the field of glycoimmunology: the impact of oncofetal antigens on the cells of the immune system. New findings in this area are of great importance for advancement, especially in the field of oncology, since it is already known that cellular interactions mediated by carbohydrate–carbohydrate and/or carbohydrate proteins are able to modulate the progression of different types of cancer in events that compromise the functionality of the immune responses.
]]>Medicines doi: 10.3390/medicines10020014
Authors: Medicines Editorial Office Medicines Editorial Office
High-quality academic publishing is built on rigorous peer review [...]
]]>Medicines doi: 10.3390/medicines10010013
Authors: Yapeng Wang Li Li Zhanlan Wei Shan Lu Wenxue Liu Janghui Zhang Junbo Feng Dongjin Wang
Background: Edoxaban is a novel oral anticoagulant which may decrease the risk of stroke and systemic embolism in patients suffering from atrial fibrillation (AF). However, the decreased efficacy of edoxaban versus warfarin for the avoidance of stroke and systemic embolism in AF with creatinine clearance (CrCl) > 95 mL/min has been reported. The purpose of this meta-analysis is to further clarify the safety (major bleeding) and efficacy (stroke or systemic embolism) of edoxaban for AF patients with various CrCl. Methods: A systematic search of studies on edoxaban and warfarin in AF patients related to renal function was conducted in PubMed, Medline, Web of Science databases, EBSCO, Embase, and the Cochrane Central Register of Controlled Trials. In this meta-analysis (protocol number: PROSPERO CRD 42021245512), we included studies that provide specific data on three outcomes: ischemic stroke or systemic embolism (S/SE), bleeding, and all-cause mortality. Results: This meta-analysis enrolled two randomized controlled trials (RCTs) studies and two retrospective studies that enrolled 28,065 patients. According to CrCl, subjects are divided into three groups (CrCl 30–50 mL/min, CrCl 50–95 mL/min, CrCl > 95 mL/min). In AF patients with CrCl 30–50 mL/min, edoxaban 30 mg daily is similar to warfarin in the prevention of ischemic S/SE and all-cause mortality, resulting in lower bleeding rate and better net clinical outcome (ischemic S/SE: hazard ratio (HR), 0.85, 95% confidence interval (CI), 0.19–1.87; all-cause mortality: HR, 0.65, 95% CI, 0.35–1.19; bleeding: HR, 0.75, 95% CI, 0.60–0.93; net clinical outcome: HR, 0.75, 95% CI, 0.63–0.90). In the group of CrCl 50–95 mL/min, the net clinical outcome was more favorable with edoxaban 60 mg daily than warfarin (HR, 0.81, 95% CI: 0.68–0.96), and there was no significant difference between edoxaban 60 mg daily and warfarin in terms of prevention of bleeding, ischemic S/SE, and all-cause mortality. For AF patients with CrCl > 95 mL/min, there was a statistically significant difference in lower bleeding rate between edoxaban 60 mg daily and warfarin (bleeding: HR: 0.70, 95% CI: 0.58–0.84). There was no differential safety in ischemic S/SE, all-cause mortality, and net clinical outcome. Conclusion: Overall, edoxaban was superior to warfarin in terms of net clinical outcome in various groups of CrCl with AF patients. Although there was no significant difference in net clinical outcome between edoxaban and warfarin for AF patients with CrCl > 95 mL/min, edoxaban is not inferior to warfarin in safety and effectiveness in the various levels of CrCl. Edoxaban may be a more effective and safe treatment than warfarin for patients with chronic kidney disease (CKD) who require anticoagulation. More high-quality and long-term clinical research are needed to further estimate the effects of edoxaban.
]]>Medicines doi: 10.3390/medicines10010012
Authors: Nor Fariza Ngah Nor Asiah Muhamad Roslin Azni Abdul Aziz Elias Hussein Mohammad Aziz Salowi Zabri Kamarudin Noor Hisham Abdullah Tahir Aris
Introduction. Cataract is the leading cause of blindness. About 90% of cataract blindness occurs in low- and middle-income countries. The prevalence of blindness and low vision in any country depends on the socioeconomic status, the availability of medical and healthcare facilities, and the literacy of the population. Aim: This paper aims to estimate the cataract surgery rate (CSR) at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang (Cataract Operation Centre), and provide descriptive assessments of the patients who received eye treatments in the center. Methods: The data were retrieved from the clinical database from 2013 to 2016. Information on the patient’s sociodemographic and clinical and treatment history was collected. Results: The cataract surgery rate for 2013 was about 27 and increased to 37.3 in 2014. However, it declined to 25 in 2015 before it resumed to 36 in 2016. For female patients who received eye treatments at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang, the rate was higher (53.7%) compared to male patients (46.3%). The mean duration of cataract surgery from 2013 to 2016 was 21.25 ± 11.071 min. Conclusion: The increased cataract surgery rate for MAIWP-HS through smart partnerships for day care cataract surgery proved that better accessibility makes the short- and long-term strategies for the reduction and prevention of blindness in Malaysia possible to achieve.
]]>Medicines doi: 10.3390/medicines10010011
Authors: Noha Soliman Diaa Mamdouh Aisha Elkordi
Choroidal melanoma is a rare malignant tumour, yet it is the most common primary intra-ocular neoplasm and second on the list of top ten most malignant melanoma sites in the body. Clinical presentation can be non-specific and includes photopsia, floaters, progressive visual field loss, and blurry vision. The tumour is quite often diagnosed clinically during fundus examination; however, the most valued diagnostic tests are A- and B-scan ultrasonography (US). Several factors affect prognosis, including the patient’s age, tumour size, histological features, and presence of metastases. Still, with primary treatment and tight surveillance, around 50% of choroidal melanoma patients metastasise.
]]>Medicines doi: 10.3390/medicines10010010
Authors: Joshni Simon Joella Lambert Jose Mosco-Guzman Kaitlyn Dittmer Alison Stern-Harbutte Weston Connelly
Patients with Human Immunodeficiency Virus (HIV), and especially Acquired Immunodeficiency Syndrome (AIDS), can present in a multitude of ways with a variety of possible pathologies. This can prove to be a challenge to a clinician. The patient, in this case, was found to have disseminated Mycobacterium-avium-intracellulare (MAI), despite compliance with antiretroviral therapy (ART), who presented with right upper quadrant pain, isolated elevated alkaline phosphatase, and sepsis. Imaging revealed multiple splenic lesions, bilateral psoas abscesses, abdominal lymphadenopathy, and a large right pleural effusion with a mediastinal shift to the left. Psoas abscesses were drained and the cultures grew acid-fast bacilli. The patient was treated with azithromycin, ethambutol and rifabutin. Classically, MAI infections of patients compliant with ART therapy present with localized disease. This case offers a different presentation of MAI despite compliance with ART therapy.
]]>Medicines doi: 10.3390/medicines10010009
Authors: Takashi I Sawako Noda Seigo Ohba Izumi Asahina Yoshinori Sumita
Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues.
]]>Medicines doi: 10.3390/medicines10010008
Authors: Paul Herscu Gitanjali Talele Shashikant Vaidya Rajesh Shah
Objectives: Regulatory clinical Phase I studies are aimed at establishing the human safety of an active pharmaceutical agent to be later marketed as a drug. Since homeopathic medicines are prepared by a potentizing method using alcohol, past a certain dilution, their toxicity/infectivity is assumed to be unlikely. We aimed to develop a bridge study between homeopathic pathogenetic trials and clinical trials. The primary purpose was to evaluate the safety of a nosode, developed from clinical samples of a COVID-19 patient. The secondary objectives were to explore whether a nosode developed for a specific clinical purpose, such as use during an epidemic, may elicit laboratory signals worthy of further exploration. Methods: An open-label study was designed to evaluate the safety and immune response of the Coronavirus nosode BiosimCovex, given orally on three consecutive days to ten healthy volunteers. Clinical examinations, laboratory safety and immune parameters were established. Interferon–gamma, Interleukin-6, and CD 4 were measured. (CTRI registration number: CTRI/2020/05/025496). Results: No serious/fatal adverse events were reported. Laboratory tests to measure safety were unchanged. Three subjects showed elevated Interleukin-6 (IL-6) on day 17 in comparison to the baseline, and ten subjects showed elevated IL-6 on day 34. A significant difference between IL-6 observations, calculated by repeated measures ANOVA, was found to be highly significant. On day 60, the IL-6 values of nine subjects were found to return to normal. Corresponding CD4 cell elevation was observed on day 60, when compared to day 34. Conclusions: HPT may potentially extend into physiological changes with regards to immune response and should encourage future studies.
]]>Medicines doi: 10.3390/medicines10010007
Authors: Mirjana A. Bogavac Dejan D. Ćelić Tamara M. Perić
Background: The prevention of preterm delivery (PTD) represents one of the major topics in modern obstetrics. The aim was to design a prospective study and investigate if mid-trimester serum and amniotic fluid levels of MCP-1 could predict the occurence of spontaneous PTD. Methods: The study involved 198 women who underwent genetic amniocentesis and blood sampling in the middle of their trimester. After applying the criteria for inclusion in the study, there were 16 respondents in the study group, and 38 respondents in the control group. Level of MCP-1 in amniotic fluid and serum was measured with commercially available enzyme-linked immunosorbent assays (ELISA) and statistical analysis was conducted. Results: There was no statistically significant difference in serum or amniotic fluid MCP1 levels between PTD and the control groups. Conclusion: The results suggest that MCP-1 is probably not the most relevant marker for predicting PTD. This study provides new normative data for MCP-1 levels in amniotic fluid and maternal sera and is a valuable tool for future diagnostic and comparative studies.
]]>Medicines doi: 10.3390/medicines10010006
Authors: Giacomo Drago Giulia Pastorello Paolo Gallinaro Roberto Zanata Jacopo Del Verme Altin Stafa Enrico Giordan
Introduction: The management of osteoporotic fractures is sometimes rather challenging for spinal surgeons, and considering the longer life expectancy induced by improved living conditions, their prevalence is expected to increase. At present, the approaches to osteoporotic fractures differ depending on their severity, location, and the patient’s age. State-of-the-art treatments range from vertebroplasty/kyphoplasty to hardware-based spinal stabilization in which screw augmentation with cement is the gold standard. Case presentation: We describe the case of a 74-year-old man with an L5 osteoporotic fracture. The patient underwent a vertebroplasty (VP) procedure, which was complicated by a symptomatic cement leakage in the right L4–L5 neuroforamen. We urgently decompressed the affected pedicle via hemilaminectomy. At that point, the column required stability. The extravasation of cement had ruled out the use of cement-augmented pedicle screws but leaving the pedicular screws alone was not considered sufficient to achieve stability. We decided to cover the screws with a polyethylene terephthalate sleeve (OGmend®) to avoid additional cement leakage and to reinforce the screw strength required by the poor bone quality. Conclusion: In the evolving technologies used for spinal surgery, screws sleeve implants such as OGmend® are a useful addition to the surgeon’s armamentarium when an increased pull-out strength is required and other options are not available.
]]>Medicines doi: 10.3390/medicines10010005
Authors: Orgilbayar Ganbat Oyuntugs Byambasukh Tserendagva Dalkh Byambasuren Dagvajantsan
(1) Background: There is no specific treatment for concussion in modern medicine, and existing treatment is only limited to resting and restoring cognition. For centuries, Mongolians have used traditional Mongolian medicine (TMM) methods to treat a variety of diseases such as Baria zasal. In this study, we aimed to explore the treatment parents and guardians seek when their children have suffered a concussion. (2) Methods: In this study, we used an online questionnaire. The study participants (n = 400) were randomly selected parents and guardians. The definition of bariachi is an advanced practitioner of baria zasal, which covers most of the massage therapy techniques mentioned in this study. (3) Results: In total, 72% of the parents and guardians went to a bariachi when their children suffered a concussion, while only 10.3% chose western medical hospitals. When asked what they did after the initial treatment was not effective, 47.8% of the participants responded that they went to the bariachi. Based on the days of treatment result, 11.8% reported on the beneficial effects of the treatment appearing in one day, and 60.3% in 1–3 days, which shows that the participants suffered a healing effect of the baria zasal shortly after application to their children. In the regression analysis, visiting a Bariachi was independent of age, gender, or even religion. (4) Conclusions: Although Western medicine is highly developed in Mongolia, the baria zasal of TMM has not lost its appeal in treating concussion. This suggests that baria zasal could be a unique method of concussion treatment even today. This also suggests that the techniques of Baria zasal should be further studied, and as in modern medicine.
]]>Medicines doi: 10.3390/medicines10010004
Authors: Abdelaziz Ghanemi Mayumi Yoshioka Jonny St-Amand
It has been shown that the risk of developing obesity, a serious modern health problem, increases with air pollution. However, the molecular links are yet to be fully elucidated. Herein, we propose a hypothesis via which air pollution-induced DNA damage would be the mechanistic link between air pollution and the enhanced risk of obesity and overweight. Indeed, whereas air pollution leads to DNA damage, DNA damage results in inflammation, oxidative stress and metabolic impairments that could be behind energy balance changes contributing to obesity. Such thoughts, worth exploring, seems an important starting point to better understand the impact of air pollution on obesity development independently from the two main energy balance pillars that are diet and physical activity. This could possibly lead to new applications both for therapies as well as for policies and regulations.
]]>Medicines doi: 10.3390/medicines10010003
Authors: Gunawan Dwi Prayitno Keri Lestari Cynthia Retna Sartika Tono Djuwantono Andi Widjaya R. Muharam Yudi Mulyana Hidayat Dewi Wulandari Rima Haifa Nabilla Farah Naura Kristin Talia Marbun Annisah Zahrah
Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40–80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.
]]>Medicines doi: 10.3390/medicines10010002
Authors: Christian von Rüden Andre Ewers Andreas Brand Sven Hungerer Christoph J. Erichsen Philipp Dahlmann Daniel Werner
Background: Air rescue crew members work equally in aviation and medicine, and thus occupy an important interface between the two work environments of aviation and medicine. The aim of this study was to obtain responses from participants to a validated online-based questionnaire regarding whether hospitals may benefit from the commitment of a medical hospital staff which is also professionally involved in the aviation system as emergency physicians and Helicopter Emergency Medical Services Technical Crew Members (HEMS TC). Furthermore, it focused on the question of whether the skills acquired through Crew Resource Management (CRM) training in the air rescue service might also be used in the ground-based rescue service and, if so, whether they may have a positive effect. Methods: Medical air rescue staff of 37 German air rescue stations was included. Between 27 November 2020 and 03 March 2021, 253 out of 621 employees (response rate: 40.7%) participated voluntarily in a validated anonymized online survey. A quantitative test procedure was performed using the modified questionnaire on teamwork and patient safety (German version). Results: The examination and interpretation of the internal consistency (Cronbach’s alpha) resulted in the following reliabilities: Factor I (Cooperation): α = 0.707 (good); Factor II (Human factors): α = 0.853 (very good); Factor III (Communication): α = 0.657 (acceptable); and Factor IV (Safety): α = 0.620 (acceptable). Factor analysis explained 53.1% of the variance. Conclusions: The medical clinicians participating in this online survey believed that the skills they learned in human factors training such as CRM are helpful in their daily routine work in hospitals or other medical facilities, as well as in their ground-based rescue service activities. These findings may result in the recommendation to make CRM available on a regular to the medical staff in all medical facilities and also to ground-based rescue service staff aiming to increase patient safety and employee satisfaction.
]]>Medicines doi: 10.3390/medicines10010001
Authors: Saranya Prathibha Anders D. Westanmo Jane Yuet Ching Hui Katie Westanmo Amy A. Gravely Todd M. Tuttle Christopher J. LaRocca
Background: The proportion of women Veterans are increasing and, as such, access to high-quality breast cancer care is important. Prior studies have shown that rural location, age, and a mental health diagnosis negatively impact breast cancer screening rates. Methods: We aimed to retrospectively assess the impact of these risk factors on breast cancer screening adherence rates among Veterans at our institution. Women who were eligible for breast cancer screening per the United States Preventative Services Taskforce guidelines were included. Results: Of 2321 women, overall adherence was 78.2%. There were no significant differences in screening rates between races, various age groups, geographical distribution, and having anxiety or post-traumatic stress disorder (PTSD). However, Veterans with a diagnosis of depression were more likely to adhere to screening guidelines. Having multiple mental health diagnoses was also not a negative risk factor. Conclusions: Our Veteran population’s adherence rates are higher than the national average and rural location, race, age, and certain mental health disorders did not negatively affect adherence to screening mammography. Though more research is needed, screening reminders from our women’s health coordinator may have improved adherence rates and lowered disparities.
]]>Medicines doi: 10.3390/medicines9120064
Authors: Jeanne Martin Pietro G. di Summa Wassim Raffoul Nathalie Koch
Background: Considering present concerns about healthcare costs and the lack of evidence and published articles on breast reconstruction costs in Switzerland, we retrospectively investigated charges to the Swiss healthcare system for different breast reconstruction procedures at the Centre Hospitalier Universitaire Vaudois. Methods: We selected all hospitalized patients at the University Hospital who underwent a “total” delayed breast reconstruction from January 2012 to December 2015. Analysis included 72 women who underwent autologous or implant-based reconstructions. Three main breast reconstruction techniques were included: Deep Inferior Epigastric Perforator (n = 46) autologous flap reconstruction, Tissue Expander followed by Implant (n = 12) and pedicled Latissimus Dorsi (n = 12) flap with or without tissue expander and implant (n = 7). For all different groups, the global costs of reconstruction and total number of required operations were statistically compared. Results: Global costs for Deep Inferior Epigastric Perforator reconstruction were 29,728 ± 1892 CHF (avg ± Std. Error of Mean), while Tissue Expander reconstruction showed a significantly higher global cost, reaching an average of 44,313 ± 5553 CHF (avg ± Std. Error of Mean). LD showed a similar cost, compared to the Deep Inferior Epigastric Perforator reconstruction (29,813 ± 3637 CHF), increasing when including an implant (37,688 ± 4840 CHF). No significant differences in the number of interventions were detected. Conclusion: These data show that autologous breast reconstruction (DIEP) delivers the best cost ratio, with lower overall costs. Implant-based reconstructions showed a greater likelihood of complications and re-intervention, globally creating superior costs when compared to autologous reconstructions.
]]>Medicines doi: 10.3390/medicines9120063
Authors: Oana Almășan Raluca Ancuța Roman Mihaela Hedeşiu Simion Bran Sara Roman Bianca Petric Cristian Dinu
Background: This study aimed at identifying errors encountered in orthopantomography (OPG) in post-traumatic patients caused by limitations in performing a correct technique. Methods: A retrospective observational study was performed. Diagnosis, exposure/processing mistakes, positioning-related errors, and bimaxillary immobilization were evaluated. Results: Thirty panoramic radiographs with mandible fractures were examined. Twelve error types were encountered: errors in exposure or processing, air radiolucency in the palatoglossal space, errors in the alignment of the Frankfort horizontal plane: head in flexion, with a joyful expression or head extended, with a somber appearance, errors towards the mid-sagittal plane (lateral head inclination, deviation, or rotation), errors caused by the non-use of the bite-block or inappropriate position on the device, errors caused by positioning outside the focal plane, artifacts/shadow images produced by post-operative metal plates, and bimaxillary immobilization errors. The number of errors per radiograph ranged from two to a maximum of five. The most dominant ones were inappropriate alignment in the focal plane and lateral rotation of the head in over 70% of cases. Lateral deviation and palatoglossal air were present in more than 50% of images. Conclusions: In trauma cases, technical difficulties in obtaining a proper OPG image are common and often insurmountable, limiting the diagnosis.
]]>Medicines doi: 10.3390/medicines9120062
Authors: Mirjana A. Bogavac Tamara M. Perić Jovana Mišković Maja Karaman
Commercial essential oils (EOs) of incense, Boswellia serrata Roxb, and mint, Mentha piperita L., were investigated against vaginal bacterial and Candida albicans isolates for antimicrobial potential and safety use. The antimicrobial activity of EOs was investigated through a double-dilution micro-plate assay. A brine shrimp assay was used for the determination of toxicity, while the determination of the chemical composition of EOs was carried out using GS–MS. Obtained minimal inhibitory (MIC) and minimal bactericidal concentration (MBC) point to the activity of mint essential oil (EO) against the multi-resistant P. aeruginosa isolate (MIC/MBC at 6.25 µL/mL), while MIC and MBC values for other isolates were reached at higher concentrations (25–50 µL/mL). According to the toxicity assay, the incense EO reached the LC50 value at 3.07 µL/mL, while mint EO showed higher toxicity at lower concentrations (0.5 µL/mL) and the LC50 could not be determined. The highest antimicrobial potential was obtained for incense against P. aeruginosa. Although the toxicity assay showed high toxicity of mint EO to the eggs of aquatic crustaceans Artemia salina, further testing of EO toxicity is proposed, for example on healthy cell-lines. According to the GC/MS spectrometry, the most represented components of mint EO were the oxygenated hydrocarbons L-menthone (20.86%) and menthol (31.86%), and they could be proposed for further antimicrobial and toxicity investigation.
]]>Medicines doi: 10.3390/medicines9120061
Authors: Khalid Hasan Sreenivasulu Metikala Madana Mohana R. Vallem
Diabetic Charcot arthropathy of the ankle, due to the presence of multiplanar deformities, and associated medical comorbidities, poses a challenge for treating physicians. The situation becomes more complicated when accompanied by ulceration and osteomyelitis, leaving limited salvage options. We present a case of advanced Charcot ankle arthropathy with osteomyelitis and ulcerated hindfoot. It was managed by talectomy and antibiotic-impregnated cement beads, followed by hindfoot arthrodesis using a retrograde intramedullary nail six weeks later. This two-stage reconstruction approach resulted in an ulcer-free, stable, plantigrade foot at one-year postoperative follow-up.
]]>Medicines doi: 10.3390/medicines9120060
Authors: Amit Algotar Stephanie Trofymenko Myra Muramoto Amy Howerter Randa Kutob
The effect of group medical visits (GMV) compared to individual medical visits (IMV), on weight and blood pressure in a large primary care practice serving a predominantly underserved population, was assessed. The records of 304 patients attending a weight-loss program were analyzed using mixed-effects regression models. Patients in GMV lost an average of 11.63 lbs, whereas patients in IMV lost an average of 3.99 lbs (p < 0.001). A total of 55% of patients lost ≥7% in GMV compared to 11% of patients in IMV (p ≤ 0.001). Individuals who lost >5% of their baseline weight had a higher reduction in overall blood pressure. For systolic and diastolic blood pressure, the differences between baseline and three months for GMV and IMV were −7.4 vs. 4.1 mm of Hg (p = 0.002) and −4.6 vs. 4.2 mm of Hg (p = 0.003), respectively. Results from this study demonstrate that GMV may be a potentially useful modality for addressing weight and blood pressure in an underserved population.
]]>Medicines doi: 10.3390/medicines9120059
Authors: Suriyon Uitrakul Krittika Aksonnam Pimchanok Srivichai Sorawit Wicheannarat Supatcha Incomenoy
Background: The incidence and risk of urinary tract infection (UTI) in patients with type 2 diabetes mellitus (T2DM) who use sodium glucose co-transporter-2 (SGLT2) inhibitors are still controversial. Therefore, this study aimed to investigate the incidence and risk factors of using SGLT2 inhibitors, particularly in Thai patients. Methods: Electronic medication records of all patients, who started the treatment of T2DM between 1 January 2019 and 30 June 2021 at a tertiary hospital in Thailand, were reviewed. The patients were divided into SGLT2 inhibitor and non-SGLT2 inhibitor groups to compare the incidence of UTI. Results: The overall incidence rate of UTI was 33.49% in the SGLT2 inhibitor group and 11.72% in the non-SGLT2 inhibitor group. The incidence rates of UTI were not different between dapagliflozin and empagliflozin treatment (34.00% and 33.03%, respectively). Patients treated with SGLT2 inhibitors had a 3.70 higher risk of UTI compared with those treated with non-SGLT2 inhibitors (95%CI 2.60–5.29). Moreover, the significant risk factors for UTI found in this study were gender, age, and occupation. Conclusions: This study highlighted the high incidence of UTI in patients using dapagliflozin and empagliflozin compared with non-SGLT2 inhibitors. Additionally, patients of female gender and older age had a significantly higher risk of UTI when treated with SGLT2 inhibitors, whereas those with permanent jobs had a lower risk.
]]>Medicines doi: 10.3390/medicines9110058
Authors: Abrar-Ahmad Zulfiqar Léo Martin Perla Habchi Delwende Noaga Damien Massimbo Ibrahima Amadou Dembele Emmanuel Andres
Introduction: We designed a new scale for the rapid detection of frailty for use in primary care, referred to as the Zulfiqar Frailty Scale (ZFS). Objective: To evaluate the performance of the “ZFS” tool to screen for frailty as defined in the Clinical Frailty Scale (CFS) criteria in an ambulatory population of patients at least 75 years old. Method: A prospective study conducted in Alsace, France, for a duration of 6 months that included patients aged 75 and over was judged to be autonomous with an ADL (Activity of Daily Living) > 4/6. Results: In this ambulatory population of 124 patients with an average age of 79 years, the completion time for our scale was less than two minutes, and the staff required no training beforehand. Sensibility was 67%, while specificity was 87%. The positive predictive value was 80%, and the negative predictive value was 77%. The Youden index was 59.8%. In our study, we have a moderate correlation between CFS and ZFS (r = 0.674 with 95%CI = [0.565; 0.760]; p-value < 2.2 × 10−16 < 0.05). The Pearson correlations between these two geriatric scores were all strong and roughly equivalent to each other. The kappa of Cohen (k) = 0.46 (Unweighted), moderate concordance between the ZFS and CFS scales according to Fleiss classification. Conclusion: The “ZFS” tool makes it possible to screen for frailty with a high level of specificity and positive/negative predictive value.
]]>Medicines doi: 10.3390/medicines9110057
Authors: Anastasia Kotzaeroglou Ioannis Tsamesidis
Background: Increasing evidence suggests that the presence of oxidative stress and disorders of the antioxidant defense system are involved in a wide range of neuropsychiatric disorders, such as bipolar disorder, schizophrenia and major depression, but the exact mechanism remains unknown. This review focuses on a better appreciation of the contribution of oxidative stress to depression and bipolar disorder. Methods: This review was conducted by extracting information from other research and review studies, as well as other meta-analyses, using two search engines, PubMed and Google Scholar. Results: As far as depression is concerned, there is agreement among researchers on the association between oxidative stress and antioxidants. In bipolar disorder, however, most of them observe strong lipid peroxidation in patients, while regarding antioxidant levels, opinions are divided. Nevertheless, in recent years, it seems that on depression, there are mainly meta-analyses and reviews, rather than research studies, unlike on bipolar disorder. Conclusions: Undoubtedly, this review shows that there is an association among oxidative stress, free radicals and antioxidants in both mental disorders, but further research should be performed on the exact role of oxidative stress in the pathophysiology of these diseases.
]]>Medicines doi: 10.3390/medicines9110056
Authors: Prawej Ansari J. M. A. Hannan Samara T. Choudhury Sara S. Islam Abdullah Talukder Veronique Seidel Yasser H. A. Abdel-Wahab
Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca2+ chelation. EECS also depolarized the β-cell membrane and elevated intracellular Ca2+, suggesting the involvement of a KATP-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7–36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.
]]>Medicines doi: 10.3390/medicines9110055
Authors: Giuseppe Lippi Fabian Sanchis-Gomar Camilla Mattiuzzi Carl J. Lavie
We provide here updated analysis of the impact of physical inactivity on risk of developing ischemic heart disease (IHD)-related disability along with the latest 10-year progression. We collected data through an electronic search in the 2019 Global Health Data Exchange (GHDx) database using the keywords “low physical activity”, complemented with the additional epidemiologic variables “disability-adjusted life years” (DALYs; number); “ischemic heart disease”; “socio-demographic index” (SDI); “age”; “sex” and “year”, for calculating volume of DALYs lost due to physical activity (PA)-related disability after IHD (LPA-IHD impairment). Based on this search, the overall LPA-IHD impairment was estimated at 7.6 million DALYs in 2019 (3.9 and 3.7 million DALYs in males and females, respectively), thus representing nearly 50% of all PA-related disabilities. The highest impact of LPA-IHD impairment was observed in middle SDI countries, being the lowest in low SDI countries. The LPA-IHD DALYs increased by 17.5% in both sexes during the past 10 years (19.2% in males, and 15.8% in females, respectively), though this trend was dissimilar among different SDI areas, especially during the past two years. In high and high–middle SDI countries, the LPA-IHD grew during the past 2 years, whilst the trend remained stable or declined in other regions. In conclusion, LPA-IHD impairment remains substantial worldwide, leading the way to reinforce current policies aimed at increasing PA volume in the population.
]]>Medicines doi: 10.3390/medicines9110054
Authors: Jung-Lung Hsu Shy-Chyi Chin Ming-Huei Cheng Yih-Ru Wu Aileen Ro Long-Sun Ro
Background: Postpartum spinal cord infarction is a very rare disease. Only two cases have been reported in the English literature. Methods: We reported a 26 year old female who received second doses of the mRNA-1273 vaccine 52 days before delivery. She presented as sudden onset of paraplegia, sensory level, and sphincter incontinence at postpartum period. No history of heparin exposure was noted. Imaging findings confirmed the T10-11 level infarction and her anti–human heparin platelet factor 4 (anti-PF4) antibody was positive. After 7 days of dexamethasone therapy, her paraplegia and urinary incontinence gradually improved. Results: The CT angiography (CTA) of the artery of Adamkiewicz (Aka) showed tandem narrowing, most conspicuous at the T10-11 level, which was presumably due to partial occlusion of the arteriolar lumen. The thoracolumbar spine magnetic resonance imaging with contrast medium showed owl’s eyes sign at the T10 and T11 levels. We compared our case with two other case reports from the literature. Conclusions: Post-partum spinal cord infarction with positive anti-PF4 antibody and relatively thrombocytopenia are the characteristics of our case.
]]>Medicines doi: 10.3390/medicines9110053
Authors: Miki Endo Nami Nakayama Miki Yamada Yosuke Iijima Shunsuke Hino Kiyoko Ariya Norio Horie Takahiro Kaneko
Purpose: Denture loss is still being reported as a problem in geriatric facilities, although losses seem less frequent than in the last decade. However, there have been no reports that have examined recent losses of dentures in detail. The aim of this study was to clarify the actual situation of recent denture loss, together with the denture loss rate in Japan. Materials and methods: This retrospective study investigated the number of cases of denture loss, the denture loss rate for denture wearers, and the details of losses in geriatric facilities during the 1-year period from 1 April 2020 to 31 March 2021. Results: Eleven special elderly nursing homes and four group homes participated in this research. The number of residents from each was 315 and 40 and the number of denture wearers was 165 and 33, respectively (p < 0.001). The loss of dentures was found in one case from a special elderly nursing home and in one case from a group home. The loss rate for denture wearers was 1.01% in total, with 0.61% for special elderly nursing homes and 3.03% for group homes, with no significant differences between the two types of facilities. Conclusion: In geriatric facilities in Japan, the current 1-year denture loss rate for denture wearers was 1.01%. This seems to represent a considerable decrease when compared with the previous report. Further, proper denture management and staff efforts appear to have contributed to a reduction in denture loss against a background of promoting oral healthcare.
]]>Medicines doi: 10.3390/medicines9110052
Authors: Alam Eldin Musa Mustafa Niemat Mohammed Tahir Nur Allah Elnaji Ahmed Mohamed Adil Abdullah Mohammed Sara Ismail Mohammed
This is a case of an eleven-year-old female Sudanese child, a known Sickle Cell Anemia (SCA) patient, who presented with fever, as well as left thigh and leg swelling that was associated with pain and warmness, which was diagnosed as Deep Vein Thrombosis (DVT) of her left lower limb. She had a previous history of admissions to the emergency room, during which she once received blood. The patient was managed by carrying out a basic routine initial laboratory investigation. A Doppler ultrasound scan showed features consistent with DVT. Based on the clinical findings and investigation results, management began by providing the patient with intravenous fluid, analgesia, packed Red Blood Cells (RBCs), intravenous antibiotics, and low-molecular-weight heparin. Further consultations showed that there was no need for vascular surgery or surgical intervention. This case highlights the need for more studies on DVT and Venous Thromboembolism (VTE) complications in children with SCA, so as to develop strategies for diagnosis and management in order to reduce the risk of life-threatening complications of VTE in patients with Sickle Cell Disease SCD.
]]>Medicines doi: 10.3390/medicines9100051
Authors: Abrar-Ahmad Zulfiqar Habib Habchi Perla Habchi Ibrahima Amadou Dembele Emmanuel Andres
Objectives: Physical activity carries numerous therapeutic benefits, and it is more effective when applied before the onset of symptoms. The objective of this study is to compare the correlation of the evaluation of physical activity carried out using the Ricci and Gagnon test and the frailty profile measured by the mSEGA scale in a population of patients consulting in general medicine. Methods: We conducted a retrospective study within a general practitioner clinic in Chaumont and Bologne (Haute-Marne department) during a 3-month period. Patients aged 65 years and up were screened for frailty using the modified SEGA (mSEGA) assessment, and physical activity was measured using the Ricci–Gagnon questionnaire. Results: A total of 44 patients were selected, with a slightly female predominance (59.1%). Of these, 21 patients reported having worked in manual labor. Seven patients were found to be frail using the SEGAm assessment, while 10 (22.73%) patients had an inactive profile according the Ricci–Gagnon score. Malnutrition was detected in six patients (13.64%) using the MNA survey. Frailty as defined by the mSEGA scale had no statistical correlation (p = 0.68) with the Ricci–Gagnon score. A Ricci–Gagnon inactive profile showed statistical correlations with fall indicators (unipedal balance test, p = 0.014) and malnutrition scores using the MNA (p = 0.0057) as well as with the Charlson Comorbidity Index (p = 0.027). Conclusion: A systematic survey of the elderly by a general practitioner implementing a regular and suitable physical activity regimen would allow a better screening of frailty, minimizing its complications.
]]>Medicines doi: 10.3390/medicines9100050
Authors: Nnennaya Opara Emmanuella Osuala Ugochinyere Nwagbara
Salter–Harris fractures may occur due to a single injury or repetitive stress fractures on the extremities. Type I to III fractures are managed medically, while types IV and V, which are rare, are treated surgically. In the pediatric population, Salter–Harris I fractures of the distal tibia are commonly seen, and management of such fractures are well established in the literature. Despite the availability of a wide range of treatment for such fractures, osteonecrosis or avascular necrosis of the proximal femur can subsequently develop. Avascular necrosis is cell death secondary to metabolic disturbances, trauma, adverse effects of certain medications, or sickle cell disease. Avascular necrosis commonly affects the talus, humerus, or tibia in addition to the femoral head. Radiographic images are essential for prompt diagnosis and to minimize negative health outcomes in these patients. However, Salter–Harris I fracture in sickle cell patients can be very challenging due to these patients’ vulnerability to bone infections and sickle cell crisis. In this case report, our patient with a history of sickle cell disease and with a diagnosis of Salter–Harris I fracture was treated with surgical intervention as type V, which is discussed in this article, and responded well to treatment. Thus, this case suggests a new approach to managing Salter–Harris I fractures complicated with osteomyelitis in sickle cell patients.
]]>Medicines doi: 10.3390/medicines9100049
Authors: Hannah Roland Amanda Brown Amy Rousselot Natalie Freeman J. Wieting Stephen Bergman Debasis Mondal
Osteopathic manipulative treatment (OMT) is used in both inpatient and outpatient settings. Evidence suggests that OMT can reduce both patients’ recovery time and the financial cost of their acute medical treatment and rehabilitation. Multiple studies from neonatal intensive care units (NICUs) are presented in this article that demonstrate infants treated with OMT recover faster, are discharged earlier, and have lower healthcare costs than their non-OMT-treated counterparts. Data clearly show that adjunctive OMT facilitates feeding coordination in newborns, such as latching, suckling, swallowing, and breathing, and increases long-term weight gain and maintenance, which reduces hospital length of stay (LOS). Osteopathic techniques, such as soft tissue manipulation, balanced ligamentous tension, myofascial release, and osteopathic cranial manipulation (OCM), can reduce regurgitation, vomiting, milky bilious, or bloody discharge and decrease the need for constipation treatment. OMT can also be effective in reducing the complications of pneumonia in premature babies. Studies show the use of OCM and lymphatic pump technique (LPT) reduces the occurrence of both aspiration and environmentally acquired pneumonia, resulting in significantly lower morbidity and mortality in infants. Based on published findings, it is determined that OMT is clinically effective, cost efficient, a less invasive alternative to surgery, and a less toxic choice to pharmacologic drugs. Therefore, routine incorporation of OMT in the NICU can be of great benefit in infants with multiple disorders. Future OMT research should aim to initiate clinical trial designs that include randomized controlled trials with larger cohorts of infants admitted to the NICU. Furthermore, a streamlined and concerted effort to elucidate the underlying molecular mechanisms associated with the beneficial effects of OMT will aid in understanding the significant value of incorporating OMT into optimal patient care.
]]>Medicines doi: 10.3390/medicines9100048
Authors: Abrar-Ahmad Zulfiqar Perla Habchi Ibrahima Amadou Dembele Emmanuel Andres
Introduction: The objective was to study the association of frailty status in hospitalized elderly patients with risk of fall in an acute geriatric unit and to characterize elderly “fallers” using a comprehensive gerontological assessment. Patients and Methods: A cross-sectional study was conducted in patients over 65 years of age and hospitalized in an acute geriatric unit. This work was carried out in the Acute Geriatric Medicine Unit, Saint-Julien Hospital, Center Hospitalier Universitaire de Rouen from 1 June 2016 to 15 August 2016. Results: 172 patients were included during the collection period, with a female predominance of 115 patients (66.9%). The average age of the sample was 79.37 years old (65–85). The average CHARLSON score was 6.93 (3–16). Patients came from home in 81.4% of cases (i.e., 140 patients), and from a nursing home in 18.6% of cases (i.e., 32 patients). The risk of falling, as assessed by the Monopodal Support Test, returned as abnormal for 127 patients. In our series, there was a statistically strong link between the risk of falling and the presence of a dementia pathology (p = 0.009), the presence of a vitamin D deficiency (p = 0.03), the presence of frailty, as assessed by the three scales (modified SEGA scale, Fried scale and CFS/7 (<0.001), a high comorbidity score (p = 0.04), and a disturbed autonomy assessment according to IADL (p = 1.02 × 10−5) and according to ADL (p = 6.4 × 10−8). There was a statistically strong link between the risk of falling and the occurrence of death (p = 0.01). Conclusion: The consequences of the fall in terms of morbidity and mortality and the frequency of this event with advancing age and its impact on the quality of life as well as on health expenditure justify a systematic identification of the risk of falling in the elderly population. It is therefore important to have sensitive, specific, and reproducible tools available for identifying elderly people at high risk of falling.
]]>Medicines doi: 10.3390/medicines9090047
Authors: Yoshinori Ozeki Takayuki Masaki Akari Kamata Shotaro Miyamoto Yuichi Yoshida Mitsuhiro Okamoto Koro Gotoh Hirotaka Shibata
Background and Objectives: This study aimed to investigate the changes in obesity severity, glucose metabolism, and body composition in patients with obesity and type 2 diabetes mellitus treated with glucagon-like peptide 1 receptor agonist (GLP1-RA) semaglutide. Materials and Methods: Body weight (BW), metabolic parameters, and body composition were examined before and 3 months after semaglutide administration. The mass of body fat (FM), fat weight percentage (%FM), mass of skeletal muscle (MM), skeletal MM percentage (%MM), and limb muscles were measured using the bioelectrical impedance method. Results: Semaglutide dramatically reduced the weight, the body mass index (BMI), and the levels of the glucose metabolic markers, including fasting blood glucose and hemoglobin A1c, and accelerated the loss of excess BW. FM, MM, and %FM after semaglutide treatment also decreased. Conversely, semaglutide had no effect on the %MM after 3 months. In limb muscle analyses, right upper and lower leg muscle percentages, left upper and lower leg muscles, and the ratios of the lower/upper muscles were maintained by semaglutide treatment. Conclusions: These results suggest that the GLP1-RA semaglutide effectively reduces body adiposity while maintaining the MM in obese type 2 diabetic patients.
]]>Medicines doi: 10.3390/medicines9090046
Authors: Olanrewaju Oladimeji Adenike Temitope Adeniji-Sofoluwe Yasir Othman Victor Abiola Adepoju Kelechi Elizabeth Oladimeji Bamidele Paul Atiba Felix Emeka Anyiam Babatunde A. Odugbemi Tolulope Afolaranmi Ayuba Ibrahim Zoakah
Chest X-ray (CXR) characteristics of patients with drug-resistant tuberculosis (DR-TB) depend on a variety of factors, and therefore, identifying the influence of these factors on the appearance of DR-TB in chest X-rays can help physicians improve diagnosis and clinical suspicion. Our aim was to describe the CXR presentation of patients with DR-TB and its association with clinical and demographic factors. A retrospective analysis of the CXRs of DR-TB patients in Nigeria between 2010 and 2016 was performed, reviewing features of chest radiographs, such as cavitation, opacity and effusion, infiltration and lung destruction. The association of these abnormal CXR findings with clinical and demographic characteristics was evaluated using bivariate and multivariate models, and a p-value < 0.05 was considered statistically significant with a 95% confidence interval. A total of 2555 DR-TB patients were studied, the majority (66.9%) were male, aged 29–38 years (36.8%), previously treated (77%), from the South West treatment zone (43.5%), HIV negative (76.7%) and bacteriologically diagnosed (89%). X-ray findings were abnormal in 97% of the participants, with cavitation being the most common (41.5%). Cavitation, effusion, fibrosis, and infiltration were higher in patients presenting in the South West zone and in those previously treated for DR-TB, while lung destruction was significantly higher in patients who are from the South South zone, and in those previously treated for DR-TB. Patients from the South East zone (AOR: 6.667, 95% CI: 1.383–32.138, p = 0.018), the North East zone (AOR: 6.667, 95% CI: 1.179–37.682, p = 0.032) and the North West zone (AOR: 6.30, 95% CI: 1.332–29.787, p = 0.020) had a significantly increased likelihood of abnormal chest X-ray findings, and prior TB treatment predisposed the patient to an increased likelihood of abnormal chest X-ray findings compared to new patients (AOR: 8.256, 95% CI: 3.718–18.330, p = 0.001). The finding of a significantly higher incidence of cavities, effusions and fibrosis in DR-TB patients previously treated could indicate late detection or presentation with advanced DR-TB disease, which may require a more individualized regimen or surgical intervention.
]]>Medicines doi: 10.3390/medicines9090045
Authors: Rosaria De Luca Mirjam Bonanno Alfredo Manuli Rocco Salvatore Calabrò
Post-SSRI sexual dysfunction (PSSD) is a set of heterogeneous sexual problems, which may arise during the administration of selective serotonin reuptake inhibitors (SSRIs) and persist after their discontinuation. PSSD is a rare clinical entity, and it is commonly associated with non-sexual concerns, including emotional and cognitive problems and poor quality of life. To date, however, no effective treatment is available. The aim of this study was to retrospectively evaluate the potential efficacy of the different treatments used in clinical practice in improving male PSSD. Of the 30 patients referred to our neurobehavioral outpatient clinic from January 2020 to December 2021, 13 Caucasian male patients (mean age 29.53 ± 4.57 years), previously treated with SSRIs, were included in the study. Patients with major depressive disorder and/or psychotic symptoms were excluded a priori to avoid overlapping symptomatology, and potentially reduce the misdiagnosis rate. To treat PSSD, we decided to use drugs positively affecting the brain dopamine/serotonin ratio, such as bupropion and vortioxetine, as well as other compounds. This latter drug is known not to cause or reverse iatrogenic SD. Most patients, after treatment with vortioxetine and/or nutraceuticals, reported a significant improvement in all International Index of Erectile Function-(IIEF-5) domains (p < 0.05) from baseline (T0) to 12-month follow-up (T1). Moreover, the only patient treated with pelvic muscle vibration reached very positive results. Although our data come from a retrospective open-label study with a small sample size, drugs positively modulating the central nervous system serotonin/dopamine ratio, such as vortioxetine, could be used to potentially improve PSSD. Large-sample prospective cohort studies and randomized clinical trials are needed to investigate the real prevalence of this clinical entity and confirm such a promising approach to a potentially debilitating illness.
]]>Medicines doi: 10.3390/medicines9080044
Authors: Qiong Schürer Hamdy Shaban Andreas R. Gantenbein Giada Todeschini Saroj K. Pradhan
Background: Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory, demyelinating, and axonal degeneration disease of the central nervous system. Trigeminal neuralgia (TN), a neuropathic facial paroxysmal pain, is prevalent among MS patients. Because of the inadequacy of the comprehension of MS-related TN pathophysiological mechanisms, TN remains arduous in its treatment approaches. Acupuncture as a non-pharmacological therapy could be a promising complementary therapy for the treatment of TN. MS gradual neural damage might affect the muscles’ function. This can lead to acute or paroxysmal pain in the form of spasms that might progress to formation of myofascial trigger points also known in traditional Chinese medicine as Ashi points (AP). Localising these AP through palpation and pain sensation feedback in patients with MS is an indicator of disease progression. Pathologically, these points reveal the disharmony of soft tissue and internal organs. Methods: This case report examined the pain relief outcome with Ashi scalp acupuncture (ASA) in a secondary TN patient who was unsuccessfully treated multiple times with body acupuncture. The main outline measure was to quantify pain intensity using a numerical rating scale (NRS) before and after each acupuncture therapy. The patient was treated on the scalp for a total of eight times, twice a week over four weeks. Results: A reduction in secondary TN pain intensity was observed after each session. On average, the patient expressed severe pain (NRS: 8.0 ± 2.20) before ASA treatment, which significantly decreased after therapy to mild pain (NRS: 2.0 ± 1.64). Conclusions: Significant improvements in pain intensity reduction after each acupuncture treatment without any adverse effects were observed.
]]>Medicines doi: 10.3390/medicines9080043
Authors: Rana I. Oueijan Olivia R. Hill Peter D. Ahiawodzi Pius S. Fasinu Dorothea K. Thompson
Background: Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. Methods: A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Results: Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. Conclusions: As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.
]]>Medicines doi: 10.3390/medicines9080042
Authors: Gary Arendash Haitham Abulaban Susan Steen Ross Andel Yanhong Wang Yun Bai Rob Baranowski Jon McGarity Lyle Scritsmier Xiaoyang Lin Ning Shen Ali Aljassabi Yitong Li Chuanhai Cao
Background: There is currently no therapeutic that can stop or reverse the progressive memory impairment of Alzheimer’s disease (AD). However, we recently published that 2 months of daily, in-home transcranial electromagnetic treatment (TEMT) reversed the cognitive impairment in eight mild/moderate AD subjects. These cognitive enhancements were accompanied by predicted changes in AD markers within both the blood and cerebrospinal fluid (CSF). Methods: In view of these encouraging findings, the initial clinical study was extended twice to encompass a period of 2½ years. The present study reports on the resulting long-term safety, cognitive assessments, and AD marker evaluations from the five subjects who received long-term treatment. Results: TEMT administration was completely safe over the 2½-year period, with no deleterious side effects. In six cognitive/functional tasks (including the ADAS-cog13, Rey AVLT, MMSE, and ADL), no decline in any measure occurred over this 2½-year period. Long-term TEMT induced reductions in the CSF levels of C-reactive protein, p-tau217, Aβ1-40, and Aβ1-42 while modulating CSF oligomeric Aβ levels. In the plasma, long-term TEMT modulated/rebalanced levels of both p-tau217 and total tau. Conclusions: Although only a limited number of AD patients were involved in this study, the results suggest that TEMT can stop the cognitive decline of AD over a period of at least 2½ years and can do so with no safety issues.
]]>Medicines doi: 10.3390/medicines9080041
Authors: Imre Bihari Jean-Jérôme Guex Arkadiusz Jawien Gyozo Szolnoky
Background: Edema is highly prevalent in patients with cardiovascular disease and is associated with various underlying pathologic conditions, making it challenging for physicians to diagnose and manage. Methods: We report on presentations from a virtual symposium at the Annual Meeting of the European Venous Forum (25 June 2021), which examined edema classification within clinical practice, provided guidance on making differential diagnoses and reviewed evidence for the use of the treatment combination of Ruscus extract, hesperidin methyl chalcone and vitamin C. Results: The understanding of the pathophysiologic mechanisms underlying fluid build-up in chronic venous disease (CVD) is limited. Despite amendments to the classic Starling Principle, discrepancies exist between the theories proposed and real-world evidence. Given the varied disease presentations seen in edema patients, thorough clinical examinations are recommended in order to make a differential diagnosis. The recent CEAP classification update states that edema should be considered a sign of CVD. The combination of Ruscus extract, hesperidin methyl chalcone and vitamin C improves venous tone and lymph contractility and reduces macromolecule permeability and inflammation. Conclusions: Data from randomized controlled trials support guideline recommendations for the use of Ruscus extract, hesperidin methyl chalcone and vitamin C to relieve major CVD-related symptoms and edema.
]]>Medicines doi: 10.3390/medicines9070040
Authors: Mariko Nishikitani Mutsuhiro Nakao Mariko Inoue Shinobu Tsurugano Eiji Yano
Precarious employment can negatively affect health, but workers may be healthy if they earn enough income. This study uses equivalent disposable income and examines the interaction between income classes and employment types to clarify whether workers’ health improves as the income classes rise. In Japan, nonstandard workers, called nonregular employees, have remained high since 2013. Therefore, using data from the national cross-sectional Comprehensive Survey of Living Conditions 2013, an official survey performed in Japan, we targeted a sample of employees aged 18 to 45 who graduated during the economic recession. Our final sample included 8282 employees (4444 males and 3838 females). The health (general and mental) status indicators used the dichotomized self-rated health and scores of the K6 questionnaires scored in the national survey. The association between income and health was almost proportional. Female workers tended to improve their health as their income class increased; however, this tendency was not observed in male workers, especially nonregular employees. Although the associations were weakened by added income information on the regression models, nonregular employees always showed inferior health to regular employees. The health status of nonregular employees, especially female nonregular employees, is statistically significantly lower than that of regular employees, even when the economic class is similar. In conclusion, improving low incomes for nonregular employees could improve health challenges, but income alone may not result in the same health status for regular and nonregular employees.
]]>Medicines doi: 10.3390/medicines9070039
Authors: Taichi Sayanagi Yumiko Ohishi Makoto Katayama Ryota Tamura
Complication of leptomeningeal carcinomatosis (LMC) is critical. It causes rapid neurological deterioration, and subsequently, discontinuation of the ineffective treatment even in body tumor dormancy. Large molecular chemotherapeutic agents that are unlikely to penetrate the CSF space, are more likely to not treat LMC, typically in chemo-sensitive tumors. With the introduction of novel regimens, significant advances in overall survival have been observed even in formerly chemo-resistant tumors, such as pancreatic cancer. Although such cases are still rare, the number of pancreatic cancer patients complicated with LMC are increasing, and this therefore needs more recognition. A 49-year-old woman was diagnosed with stage IVa pancreatic cancer. She underwent surgery, and subsequent adjuvant chemotherapy. After three lines of chemotherapy over a 3-year period, where the body disease remained dormant, the patient was complicated by LMC. The diagnosis was made 4 months after the onset of headache. The patient received intrathecal methotrexate treatment but succumbed shortly after treatment induction. Pancreatic cancer is still relatively chemo-resistant and is one of the least likely types of tumor to be complicated by LMC due to patients dying of the primary tumor. Advancements in treatments have led to a prolonged period of primary tumor control, but not in the CNS due to the poor penetration of chemo-agents to this site. The present case seems to be a typical result of modern era anti-cancer therapy. Therefore, we emphasize the necessity of earlier recognition of this complication so that we can initiate specific treatment targeting the CSF space, especially in this formerly chemo-resistant tumor in order to improve its prognosis.
]]>Medicines doi: 10.3390/medicines9070038
Authors: Abrar-Ahmad Zulfiqar Perla Habchi Ibrahima Amadou Dembele
Background: Obesity is a chronic pathology that affects people of all ages, from infants to the elderly, residing in both developed and developing countries. Objective: Our aim is to study the link between obesity and frailty in the elderly. Method: A prospective study was carried out in 12 General Medicine practices in Champagne-Ardenne, in the Departments of Marne and the Ardennes, France, for a period of 12 months (from 2 May 2019 through 30 April 2020). All patients included were aged 65 or older, in consultation with a general practitioner, and had an ADL (Activity of Daily Living) greater than or equal to 4. Frailty was measured using the Fried scale and the simplified ZULFIQAR frailty scale. Results: 268 patients aged 65 and over were included, with an average age of 77.5 years. A total of 100 were obese according to BMI. The mean Fried (/5) in the series was 1.57, and the mean sZFS (/5) was 0.91. Our study shows that obesity is not significantly correlated with frailty according to the FRIED sarcopenic scale, but is significantly correlated with frailty according to the sZFS scale. Conclusions: The link between obesity and frailty remains much debated, with the underlying emergence of sarcopenic obesity equally prevalent among the elderly. This is a preliminary study that should be followed by large-scale outpatient studies to better clarify the links between sarcopenia and obesity.
]]>Medicines doi: 10.3390/medicines9060037
Authors: Israel Diniz-Lima Leonardo Marques da Fonseca Jhenifer Santos dos Reis Marcos André Rodrigues da Costa Santos Kelli Monteiro da Costa Carlos Antonio do Nascimento Santos Pedro Marçal Barcelos Kamila Guimarães-Pinto Alessandra Almeida Filardy Marco Edilson Freire-de-Lima Debora Decote-Ricardo Alexandre Morrot Celio Geraldo Freire-de-Lima Leonardo Freire-de-Lima
Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. What are the factors that are currently contributing to this new possible epidemiological dynamic? Could these be of a structural nature? Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections.
]]>Medicines doi: 10.3390/medicines9060036
Authors: Evgenia Lymperaki Konstantina Kazeli Georgia Variti Magda Gerothanasi Argyrios Gkinoudis Ioannis Tsamesidis Eleni Vagdatli
COVID-19 disease is still a major global concern because of its morbidity and its mortality in severe disease. Certain biomarkers including Reactive Oxygen Species (ROS), vitamins, and trace elements are known to play a crucial role in the pathophysiology of the disease. The aim of our study was to evaluate how certain biomarkers, such as ROS, biochemical indicators, trace elements in serum blood of 139 COVID-19 hospitalized patients, and 60 non-COVID cases according to age and sex variations, can serve as the predictors for prognosis of COVID-19 outcome. An attempt of correlating these biomarkers with the severity of the disease as well as with each other is represented. All subjects were hospitalized from April 2021 until June 2021. A statistically significant increase of B12 levels (p = 0.0029) and ROS levels (p < 0.0001) as well as a decrease in albumin and Total Protein (T.P.) levels (p < 0.001) was observed especially in the early stage of the disease before CRP and ferritin elevation. Additionally, a statistically significant increase in ferritin (p = 0.007), B12 (p = 0.035, sALT p = 0.069, Glucose p = 0.012 and urea p = 0.096 and a decrease in Ca p = 0.005, T.P p = 0.052 albumin p = 0.046 between stage B (CRP values 6–30 mg/L) and C (CRP values 30–100 mg/L) was evident. Thus, this study concludes that clinicians could successfully employ biomarkers such as vitamin B12, ROS and albumin as possible prognosis tools for an early diagnosis. In addition, the total biochemical profile can assist in the understanding of the severity of COVID-19 disease, and could potentially lead to a better diet or early pharmaceutical treatment to prevent some of the more acute symptoms.
]]>Medicines doi: 10.3390/medicines9060035
Authors: Mohammad Hossain Praveen K. Roayapalley Hiroshi Sakagami Keitaro Satoh Kenjiro Bandow Umashankar Das Jonathan R. Dimmock
A series of 3,5-bis(benzylidene)-1-dichloroacetyl-4-piperidones 1a–l was evaluated against Ca9-22, HSC-2, HSC-3, and HSC-4 squamous cell carcinomas. Virtually all of the compounds displayed potent cytotoxicity, with 83% of the CC50 values being submicromolar and several CC50 values being in the double digit nanomolar range. The compounds were appreciably less toxic to human HGF, HPLF, and HPC non-malignant cells, which led to some noteworthy selectivity index (SI) figures. From these studies, 1d,g,k emerged as the lead molecules in terms of their potencies and SI values. A Quantitative Structure-Activity Relationship (QSAR) study revealed that cytotoxic potencies and potency–selectivity expression figures increased when the magnitude of the sigma values in the aryl rings was elevated. The modes of action of the representative cytotoxins in Ca9-22 cells were found to include G2/M arrest and stimulation of the cells to undergo mitosis and cause poly(ADP-ribose) polymerase (PARP) and procaspase 3 cleavage.
]]>Medicines doi: 10.3390/medicines9060034
Authors: Jhenifer Santos dos Reis Marcos André Rodrigues da Costa Santos Daniella Pereira Mendonça Stefani Ingrid Martins do Nascimento Pedro Marçal Barcelos Rafaela Gomes Correia de Lima Kelli Monteiro da Costa Celio Geraldo Freire-de-Lima Alexandre Morrot Jose Osvaldo Previato Lucia Mendonça Previato Leonardo Marques da Fonseca Leonardo Freire-de-Lima
Cancer development and progression is associated with aberrant changes in cellular glycosylation. Cells expressing altered glycan-structures are recognized by cells of the immune system, favoring the induction of inhibitory immune processes which subsequently promote tumor growth and spreading. Here, we discuss about the importance of glycobiology in modern medicine, taking into account the impact of altered glycan structures expressed in cancer cells as potential glycobiomarkers of disease, as well as on cancer development and progression.
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