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Med. Sci., Volume 6, Issue 4 (December 2018) – 38 articles

Cover Story (view full-size image): This study showed that human dermal fibroblasts produce significant levels of NO depending on stimulation and glucose conditions. The nitrite level in the media is not a reliable proxy for the actual level of NO produced by the cells. Using the CellNO trap, a novel measurement system developed in our lab, we are able to accurately measure NO produced by cells grown in culture without changing established culturing protocols. If we accurately measure the actual levels of NO produced by cells cultured under specific conditions, including the temporal NO release profile, we can understand and mimic the physiological NO release at different stages of wound healing and in different pathological states. This will facilitate a smooth transition of the wound from a chronic state into resolution, consequently shortening the time to complete the healing process of diabetic foot ulcers. View this paper.
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9 pages, 439 KiB  
Article
Asymptomatic Bacteriuria and Anti-Microbial Susceptibility Patterns among Women of Reproductive Age. A Cross-Sectional Study in Primary Care, Ghana
by Prince Afoakwa, Seth Agyei Domfeh, Bright Oppong Afranie, Dorcas Ohui Owusu, Sampson Donkor, Kennedy Kormla Sakyi, Richard Akesse Adom, Godfred Kyeremeh, Bright Afranie Okyere, Emmanuel Acheampong and Beatrice Amoah
Med. Sci. 2018, 6(4), 118; https://doi.org/10.3390/medsci6040118 - 17 Dec 2018
Cited by 5 | Viewed by 3589
Abstract
Background: Asymptomatic bacteriuria (ASB) poses serious future clinical repercussions for reproductive women. The study determined the prevalence of asymptomatic bacteriuria along with anti-microbial susceptibility patterns among women of reproductive age in a primary care facility. Method: The study recruited a total of 300 [...] Read more.
Background: Asymptomatic bacteriuria (ASB) poses serious future clinical repercussions for reproductive women. The study determined the prevalence of asymptomatic bacteriuria along with anti-microbial susceptibility patterns among women of reproductive age in a primary care facility. Method: The study recruited a total of 300 women of reproductive age attending the Tetteh Quarshie Memorial Hospital at Akuapem-Mampong, Ghana, between January and March 2018. Questionnaires were administered to obtain demographic data and predisposing risk factors of ASB. An early-morning midstream urine sample was collected from participants. Urinalysis, urine culture, and anti-microbial susceptibility testing were performed. Results: The mean age of participants was 25.43 years. The overall prevalence rate of ASB was 40.3%. The prevalence was higher among pregnant women compared to non-pregnant women (33.3% vs. 7.0%). The most common bacterial isolate was E. coli (47.0%) followed by Proteus spp. (36.4%), Klebsiella spp. (8.3%), and E. faecalis (8.3%). Leukocyturia (35.0%) followed by nitrate (30.0%) were the most common urine abnormalities identified on dipstick urinalysis. Most bacteria isolates showed increased resistance to ampicillin (95.04%) and tetracycline (95.04%) while most of the bacterial isolates were sensitive to levofloxacin (94.35%). Demographic characteristics including age (p < 0.001), educational level (p < 0.001), residency (p = 0.001), and marital status (p = 0.005) were significantly associated with ASB. Lifestyle characteristics such as sexual status (p = 0.001) and frequency of washing of intimate parts after sexual intercourse (p < 0.001) were also significantly associated with ASB. Conclusion: Asymptomatic bacteriuria, particularly E. coli and Proteus spp. are prevalent in the urine of pregnant women living in Akuapem-Mampong municipality. Hence public education along with early screening of ASB is essential to reducing future risk of reproductive health complications. Future studies are required to assess the impact of public health on the rate of bacterial infections. Full article
(This article belongs to the Section Nephrology and Urology)
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8 pages, 2673 KiB  
Article
Development of a Low-Cost Wireless Phonocardiograph With a Bluetooth Headset under Resource-Limited Conditions
by Himel Mondal, Shaikat Mondal and Koushik Saha
Med. Sci. 2018, 6(4), 117; https://doi.org/10.3390/medsci6040117 - 17 Dec 2018
Cited by 9 | Viewed by 4592
Abstract
Commercially available digital stethoscopes can be used as a phonocardiograph to record heart sounds. However, procuring a costly digital stethoscope may not be possible under resource-limited conditions. A low-cost, wire connected, and mobile phone-assisted phonocardiograph has been reported previously. The aim of this [...] Read more.
Commercially available digital stethoscopes can be used as a phonocardiograph to record heart sounds. However, procuring a costly digital stethoscope may not be possible under resource-limited conditions. A low-cost, wire connected, and mobile phone-assisted phonocardiograph has been reported previously. The aim of this study was to develop a low-cost and wireless phonocardiograph for resource-limited settings. A Bluetooth headset was dismantled to find its microphone. A stethoscope ear knob was cut to make a small bell and it was attached to the microphone. This modified Bluetooth headset was capable of recording sounds while connected to a mobile device with audio recording application. The modified Bluetooth headset, mobile phone, and audio recording software can serve as a wireless phonocardiograph (WiPCGh). Heart sounds were successfully recorded with the help of the newly developed WiPCGh. The audio files were shared with a personal computer (PC) via Bluetooth. The wave form was analyzed in a PC-based audio editing application. First and second heart sounds with systolic and diastolic murmur were identified. WiPCGh can be utilized in recording heart sounds for academic and telemedicine purposes. However, the capability of WiPCGh in the diagnosis of cardiac diseases is yet to be explored in future studies. Full article
(This article belongs to the Special Issue e-Health in Cardiovascular Medicine)
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15 pages, 293 KiB  
Review
Microbiota in the Gastrointestinal Tract
by Walburga Dieterich, Monic Schink and Yurdagül Zopf
Med. Sci. 2018, 6(4), 116; https://doi.org/10.3390/medsci6040116 - 14 Dec 2018
Cited by 134 | Viewed by 9210
Abstract
Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and [...] Read more.
Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and varying environmental conditions, e.g., diets, antigen exposure, infections, or medication, as well as genetics, age, or hygiene factors, strongly influence the bacterial community. A fine interaction between the host and microbiota determines the outcome of health or disease. The gut immune system is constantly challenged to distinguish between commensal non-invasive bacteria and potential pathogens. Goblet cells produce mucins that prevent most gut bacteria from penetrating through intestinal epithelial barrier, and Paneth cells are the main supplier of anti-microbial defensins. Gut epithelial and immune cells recognize bacteria via surface markers and they initiate an adequate immune answer. A dysbiosis is noticed in several diseases, but the crucial role in pathogenesis has to be proven. Prebiotics or probiotics are discussed as valuable tools to preserve or restore a healthy gut community. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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18 pages, 357 KiB  
Review
Transglutaminases in Monocytes and Macrophages
by Huifang Sun and Mari T. Kaartinen
Med. Sci. 2018, 6(4), 115; https://doi.org/10.3390/medsci6040115 - 11 Dec 2018
Cited by 21 | Viewed by 3770
Abstract
Macrophages are key players in various inflammatory disorders and pathological conditions via phagocytosis and orchestrating immune responses. They are highly heterogeneous in terms of their phenotypes and functions by adaptation to different organs and tissue environments. Upon damage or infection, monocytes are rapidly [...] Read more.
Macrophages are key players in various inflammatory disorders and pathological conditions via phagocytosis and orchestrating immune responses. They are highly heterogeneous in terms of their phenotypes and functions by adaptation to different organs and tissue environments. Upon damage or infection, monocytes are rapidly recruited to tissues and differentiate into macrophages. Transglutaminases (TGs) are a family of structurally and functionally related enzymes with Ca2+-dependent transamidation and deamidation activity. Numerous studies have shown that TGs, particularly TG2 and Factor XIII-A, are extensively involved in monocyte- and macrophage-mediated physiological and pathological processes. In the present review, we outline the current knowledge of the role of TGs in the adhesion and extravasation of monocytes, the expression of TGs during macrophage differentiation, and the regulation of TG2 expression by various pro- and anti-inflammatory mediators in macrophages. Furthermore, we summarize the role of TGs in macrophage phagocytosis and the understanding of the mechanisms involved. Finally, we review the roles of TGs in tissue-specific macrophages, including monocytes/macrophages in vasculature, alveolar and interstitial macrophages in lung, microglia and infiltrated monocytes/macrophages in central nervous system, and osteoclasts in bone. Based on the studies in this review, we conclude that monocyte- and macrophage-derived TGs are involved in inflammatory processes in these organs. However, more in vivo studies and clinical studies during different stages of these processes are required to determine the accurate roles of TGs, their substrates, and the mechanisms-of-action. Full article
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
10 pages, 259 KiB  
Review
Early Intervention is Important to Prevent Sensitization to New Allergens
by Tetsuya Terada and Ryo Kawata
Med. Sci. 2018, 6(4), 114; https://doi.org/10.3390/medsci6040114 - 11 Dec 2018
Cited by 4 | Viewed by 2604
Abstract
We review current management for allergic rhinitis and possible new treatments for this condition. Management of allergic rhinitis includes promotion of protective factors, avoidance of allergens, and possibly immunotherapy. In recent years, the incidence of allergic rhinitis has increased in many countries. Early [...] Read more.
We review current management for allergic rhinitis and possible new treatments for this condition. Management of allergic rhinitis includes promotion of protective factors, avoidance of allergens, and possibly immunotherapy. In recent years, the incidence of allergic rhinitis has increased in many countries. Early intervention at different stages is an important part of management. Allergic disease in infants has been described as the allergic march, commencing with atopic dermatitis accompanied by infantile asthma and progressing to perennial allergic rhinitis induced by house dust mite allergy. In order to prevent polysensitization, allergen-specific immunotherapy should probably be initiated at an earlier age, especially in children with rhinitis who show monosensitization to house dust mite antigens. Full article
(This article belongs to the Special Issue Allergic Rhinitis: Epidemiology, Prevention and Management)
16 pages, 485 KiB  
Review
New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins
by Gökçe Güllü Amuran, Irem Peker Eyuboglu, Ilker Tinay and Mustafa Akkiprik
Med. Sci. 2018, 6(4), 113; https://doi.org/10.3390/medsci6040113 - 07 Dec 2018
Cited by 16 | Viewed by 3152
Abstract
Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is [...] Read more.
Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords “bladder cancer, urinary miRNA, urinary protein, urinary biomarker”. Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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13 pages, 1947 KiB  
Article
Polyamine Homeostasis in Snyder-Robinson Syndrome
by Tracy Murray-Stewart, Matthew Dunworth, Jackson R. Foley, Charles E. Schwartz and Robert A. Casero, Jr.
Med. Sci. 2018, 6(4), 112; https://doi.org/10.3390/medsci6040112 - 07 Dec 2018
Cited by 25 | Viewed by 5055
Abstract
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, [...] Read more.
Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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12 pages, 235 KiB  
Meeting Report
Report from the Scientific Poster Session at the 13th Annual Cardiometabolic Health Congress in Boston, USA, 24–27 October 2018
by Organizing Committee CMHC 2018
Med. Sci. 2018, 6(4), 111; https://doi.org/10.3390/medsci6040111 - 30 Nov 2018
Viewed by 2117
Abstract
More than one third of the population has at least one cardiometabolic risk factor-dyslipidemia, cardiovascular disease (CVD), hypertension, diabetes, and/or obesity. [...] Full article
(This article belongs to the Special Issue Cardiometabolic Health: Current Developments)
14 pages, 770 KiB  
Review
Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes
by Jaume Sauleda, Belén Núñez, Ernest Sala and Joan B. Soriano
Med. Sci. 2018, 6(4), 110; https://doi.org/10.3390/medsci6040110 - 29 Nov 2018
Cited by 81 | Viewed by 7617
Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is characterized by a chronic, progressive, fibrotic interstitial lung disease of unknown cause that occurs primarily in older adults. Its prevalence and incidence have appeared to be increasing over [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is characterized by a chronic, progressive, fibrotic interstitial lung disease of unknown cause that occurs primarily in older adults. Its prevalence and incidence have appeared to be increasing over the last decades. Despite its unknown nature, several genetic and environmental factors have been associated with IPF. Moreover, its natural history is variable, but could change depending on the currently suggested phenotypes: rapidly progressive IPF, familial, combined pulmonary fibrosis and emphysema, pulmonary hypertension, and that associated with connective tissue diseases. Early recognition and accurate staging are likely to improve outcomes and induce a prompt initiation of antifibrotics therapy. Treatment is expected to be more effective in the early stages of the disease, while developments in treatment aim to improve the current median survival of 3–4 years after diagnosis. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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12 pages, 5111 KiB  
Perspective
From Rapid Recommendation to Online Preference-Sensitive Decision Support: The Case of Severe Aortic Stenosis
by Jack Dowie and Mette Kjer Kaltoft
Med. Sci. 2018, 6(4), 109; https://doi.org/10.3390/medsci6040109 - 29 Nov 2018
Cited by 3 | Viewed by 2792
Abstract
The launch of ‘Rapid Recommendations’ by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) group, in collaboration with Making GRADE the Irresistible Choice (MAGIC) and the British Medical Journal (BMJ), is a very interesting recent development in e-healthcare. Designed to respond quickly [...] Read more.
The launch of ‘Rapid Recommendations’ by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) group, in collaboration with Making GRADE the Irresistible Choice (MAGIC) and the British Medical Journal (BMJ), is a very interesting recent development in e-healthcare. Designed to respond quickly to developments that have created new decision situations, their first project resulted from the arrival of minimally invasive Transcatheter Aortic Valve Implantation (TAVI) as an alternative to Surgical Aortic Valve Replacement (SAVR), for patients with symptomatic severe aortic stenosis. The interactive MAGIC decision aid that accompanies a Rapid Recommendation and is the main route to its clinical implementation, represents a major advance in e-health, for a cardiovascular decision in this case. However, it needs to go further in order to facilitate fully person-centred care, where the weighted preferences of the individual person are elicited at the point of decision, and transparently integrated with the best (most personalised) estimates of option performances, to produce personalised, preference-sensitive option evaluations. This can be achieved by inputting the collated GRADE evidence on the criteria relevant in the TAVI/SAVR choice into a Multi-Criteria Decision Analysis-based decision support tool, generating a personalised, preference-sensitive opinion. A demonstration version of this add-on to the MAGIC aid, divested of recommendations, is available online as proof of method. Full article
(This article belongs to the Special Issue e-Health in Cardiovascular Medicine)
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8 pages, 490 KiB  
Article
Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients
by Claudia Sestito, John J. P. Brevé, Joep Killestein, Charlotte E. Teunissen, Micha M. M. Wilhelmus, Benjamin Drukarch and Anne-Marie Van Dam
Med. Sci. 2018, 6(4), 108; https://doi.org/10.3390/medsci6040108 - 27 Nov 2018
Cited by 6 | Viewed by 2727
Abstract
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS) characterized by inflammation and immune cell infiltration in the brain parenchyma. Tissue transglutaminase (TG2), a calcium-dependent cross-linking enzyme, has been shown to be present in infiltrating MHC-II positive [...] Read more.
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS) characterized by inflammation and immune cell infiltration in the brain parenchyma. Tissue transglutaminase (TG2), a calcium-dependent cross-linking enzyme, has been shown to be present in infiltrating MHC-II positive cells in lesions of patients suffering from MS. Moreover, TG2 mRNA levels in peripheral blood mononuclear cells (PBMC)-derived from primary progressive (PP)-MS patients correlated with clinical parameters, thus highlighting the importance of TG2 in MS pathology. In the present study, we further characterized TG2 expression by measuring the mRNA levels of full-length TG2 and four TG2 alternative splice variants in PBMCs derived from PP-MS patients and healthy control (HC) subjects. In PP-MS-derived PBMCs, TG2 variant V4b was significantly higher expressed, and both V4a and V4b variants were relatively more expressed in relation to full-length TG2. These observations open new avenues to unravel the importance of TG2 alternative splicing in the pathophysiology of PP-MS. Full article
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
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13 pages, 1760 KiB  
Article
OK-432 Administration Inhibits Murine Allergic Rhinitis at the Induction Phase, through the Macrophage Activation with TLR2 Signaling Pathway
by Noriaki Aoi, Ichiro Morikura, Takafumi Fuchiwaki, Takaya Yamada, Emmanuel Prokopakis and Hideyuki Kawauchi
Med. Sci. 2018, 6(4), 107; https://doi.org/10.3390/medsci6040107 - 26 Nov 2018
Cited by 5 | Viewed by 3241
Abstract
OK-432, a preparation of a low-virulence strain (Su) of Streptococcus pyogenes (Group A) killed by a penicillin and lyophilized, is a stiff inducer of Th1 cytokines, and exerts anti-cancer effects in tumor-bearing mice. OK-432 has been reported to consist of many bacterial components, [...] Read more.
OK-432, a preparation of a low-virulence strain (Su) of Streptococcus pyogenes (Group A) killed by a penicillin and lyophilized, is a stiff inducer of Th1 cytokines, and exerts anti-cancer effects in tumor-bearing mice. OK-432 has been reported to consist of many bacterial components, such as peptidoglycan, M-protein, etc. However, it is yet to be ascertained which bacterial component induces T helper 1 (Th1) responses. For the last decade, Toll-like receptor (TLR) family proteins are well elucidated to play a role in recognizing bacterial components and inducing interleukin (IL)-12 from macrophages. Above all, peptidoglycan seems to be the agonist of TLR2 rather than the obverse. In our present study, the role of TLR2 for the recognition of OK-432 by macrophages and the effects of OK-432 are examined on murine allergic rhinitis model. Interestingly, results show IL-12 production by macrophages derived from TLR2 knock-out (ko) mice was significantly decreased, in comparison with that of macrophages derived from wild-type mice. Moreover, in TLR2 ko mice, no regulatory effect of OK-432 was observed on an allergic rhinitis model. These data indicate that TLR2 signaling is involved in regulating OK-432-induced anti-T helper 2 (Th2) immunity, and may offer a new prophylactic and therapeutic approach using OK-432 to downregulate allergic disorders, such as allergic rhinitis. Full article
(This article belongs to the Special Issue Allergic Rhinitis: Epidemiology, Prevention and Management)
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12 pages, 1958 KiB  
Article
Health and Demographic Characteristics of Patients Attending a Newly-Opened Medical Facility in a Remote Amazonian Community: A Descriptive Study
by Lucy Guile, Devon Graham and Anne Jachmann
Med. Sci. 2018, 6(4), 106; https://doi.org/10.3390/medsci6040106 - 26 Nov 2018
Cited by 3 | Viewed by 3082
Abstract
Peru is a country with wide regional disparities in health. Remote Amazonian communities have high rates of poverty and poor access to health services. There is a lack of data on morbidity and use of health services in the region. We describe a [...] Read more.
Peru is a country with wide regional disparities in health. Remote Amazonian communities have high rates of poverty and poor access to health services. There is a lack of data on morbidity and use of health services in the region. We describe a descriptive, cross-sectional study of the demographic characteristics and presenting complaints of attendees to a newly-opened primary care facility in a remote community. This was supplemented by structured interviews of adult attendees to build a picture of sociocultural determinants of health locally, including engagement with traditional forms of medicine. Our study provides novel insights into an under-studied and under-resourced area. We found a young population with a high prevalence of infectious illnesses, particularly dermatological infections - a previously under-recognised source of morbidity in these communities. Poor literacy rates and widespread use of traditional forms of medicine have important implications for the provision of healthcare in this region. Full article
(This article belongs to the Special Issue Recent Advances in Health Improvement Strategies)
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11 pages, 875 KiB  
Article
Similarities in Blood Mononuclear Cell Membrane Phospholipid Profiles during Malignancy
by Gohar Hakobyan, Hasmik Davtyan, Kristine Harutyunyan, Knarik Alexanyan, Yelizaveta Amirkhanyan, Anna L. Gharibyan, Liana Asatryan and Yuri Tadevosyan
Med. Sci. 2018, 6(4), 105; https://doi.org/10.3390/medsci6040105 - 23 Nov 2018
Cited by 3 | Viewed by 3173
Abstract
Phospholipids (PLs), key elements of cellular membranes, are regulated reciprocally with membrane proteins and can act as sensors for alterations in physiological or pathological states of cells including initiation and development of cancer. On the other hand, peripheral blood mononuclear cells (MNCs) play [...] Read more.
Phospholipids (PLs), key elements of cellular membranes, are regulated reciprocally with membrane proteins and can act as sensors for alterations in physiological or pathological states of cells including initiation and development of cancer. On the other hand, peripheral blood mononuclear cells (MNCs) play an important role in antitumor immune response by reacting to cancerous modifications in distant organs. In the current study, we tested the hypothesis that tumor initiation and development are reflected in the alteration pattern of the MNC PL component. We analyzed MNC membrane PL fractions in samples from healthy individuals and from patients with diverse types of cancers to reveal possible alterations induced by malignancy. Compared to healthy controls, the cancer samples demonstrated shifts in several membrane PL profiles. In particular, when analyzing cancer data pooled together, there were significantly higher levels in lysophosphatidylcholine, phosphatidylcholine, and phosphatidylethanolamine fractions, and significantly lower quantities in phosphatidylinositol, phosphatidylserine, and phosphatidic acid fractions in cancer samples compared to controls. The levels of sphingomyelins and diphosphatidylglycerols were relatively unaffected. Most of the differences in PLs were sustained during the analysis of individual cancers such as breast cancer and chronic lymphocytic leukemia. Our findings suggest the presence of a common pattern of changes in MNC PLs during malignancy. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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10 pages, 2048 KiB  
Article
Association between Diabetic Retinopathy and Chronic Periodontitis—A Cross-Sectional Study
by Veena H. R., Sribhargava Natesh and Sudhir R. Patil
Med. Sci. 2018, 6(4), 104; https://doi.org/10.3390/medsci6040104 - 23 Nov 2018
Cited by 19 | Viewed by 3225
Abstract
Periodontal disease (PD), a chronic inflammatory condition characterized by destruction of the supporting tissues of the teeth, increases the risk of complications in diabetics. Diabetic retinopathy (DR) is a microvascular complication of prolonged hyperglycaemia. There appears to be a similarity in the pathogenesis [...] Read more.
Periodontal disease (PD), a chronic inflammatory condition characterized by destruction of the supporting tissues of the teeth, increases the risk of complications in diabetics. Diabetic retinopathy (DR) is a microvascular complication of prolonged hyperglycaemia. There appears to be a similarity in the pathogenesis of DR and PD. Hence, this study aimed to investigate the association, if any, between DR and PD, correlate the severity of DR with the severity of PD, and investigate the association between glycated haemoglobin (HbA1c), serum creatinine and periodontal variables. The periodontal status of 200 adult diabetic patients in the age group of 30–65 years with varying severity of DR was assessed. Evaluation of the severity of PD was assessed by recording clinical parameters. Haematological investigations including glycated haemoglobin (HbA1c) and serum creatinine were estimated before the initiation of treatment for DR. A statistically significant association between the mean duration of diabetes mellitus (DM) and the severity of DR and PD was found. The severity of PD was directly correlated with the severity of DR. There was a significant association between the levels of HbA1c and serum creatinine and severity of DR and PD. There could be a plausible relationship between DR and PD. Further prospective studies on a larger population with longer follow-ups are required to ascertain whether PD and its severity directly affect the progression and severity of DR. Full article
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9 pages, 1186 KiB  
Article
Transglutaminase 2 Up-Regulation Is Associated with Inflammatory Response in PBMC from Healthy Subjects with Hypovitaminosis D
by Daniela Caccamo, Nadia Ferlazzo, Monica Currò, Sergio Ricca and Riccardo Ientile
Med. Sci. 2018, 6(4), 103; https://doi.org/10.3390/medsci6040103 - 16 Nov 2018
Cited by 2 | Viewed by 2841
Abstract
Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires [...] Read more.
Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-κB signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-α mRNA levels in PBMC of recruited patients. The mRNA levels of TG2 and TNF-α were higher in PBMC of subjects having hypovitaminosis D, namely plasma 25(OH)vitamin D3 levels lower than 50 nmol/L, than in those with normal vitamin D levels. Moreover, NF-κB up-regulation and nuclear translocation were detected, concomitantly with TG2 as well as TNF-α increased expression, in PBMC of vitamin D-deficient subjects. The present findings confirm that an increase in TG2 expression exacerbates the activation of NF-κB and the production of pro-inflammatory cytokines, and suggest a link between vitamin D deficiency, TG2 up-regulation, and inflammation. Full article
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
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9 pages, 736 KiB  
Article
Study of Antiphospholipid Antibodies in Patients with Arterial Hypertension
by Gioulia Romanidou, Theocharis G. Konstantinidis, Odysseas Koutsogiannis, Anastasia Grapsa, Konstantina Kantartzi, Stylianos Panagoutsos, Maria Panopoulou and Christina Tsigalou
Med. Sci. 2018, 6(4), 102; https://doi.org/10.3390/medsci6040102 - 13 Nov 2018
Viewed by 3015
Abstract
Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not [...] Read more.
Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not fully elucidated. The aim of our study was to determine aPL titers in hypertension patients and investigate the association of aPL with renal impairment parameters. Forty-seven patients with arterial hypertension (22 males, 46.8% and 25 females, 53.2%), aged 41–85 years old (mean 65.9 ± 10.1 years), and 21 age-sex-matched subjects without severe hypertension as control group (8 males, 13 females, 38.1% vs. 61.9%), mean age 61 ± 11.3 years, were enrolled in this study. Patients with other risk factors like Rheumatoid Arthritis and Systematic Lupus Erythematosus (SLE), both viral and bacterial acute infections, and cancer were excluded from the study. The aPL (anticardiolipin (ACA) and anti-b2GPI antibodies, IgG and IgM) were measured by ELISA (Aesculisa, Aesku Diagnostics, Wendelsheim, Germany) with a cutoff of 15 GPL/MPL for ACA and 15 U/mL for b2GPI. Serum Neutrophil gelatinase-associated lipocalin (sNGAL) was measured by ELISA kits (BioVendor, Brno, Czech Republic). Biochemical analysis such as serum creatinine (Cr), were measured by automated analyzer and finally estimated glomerular filtration rate (e-GFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Fifteen patients were positive for ACA IgG (31.9%), two for anti-b2GPI IgM (4.2%), and three for anti-b2GPI IgG (6.3%). Furthermore, three persons from control group were positive in anti-b2GPI IgG (14.27%). The serum level of anti-b2GPI IgG was significantly higher in patients compared to healthy controls (p = 0.013). The level of sNGAL (59.63 ± 41.5 ng/mL vs. 45.5 ± 21.5 ng/mL, p = 0.14) was not higher in hypertensive patients than in the age-sex-matched control group. Additionally, the sNGAL level was found to be directly and positively correlated in patients with positive ACA IgG (r2 = 0,945, p < 0.0001). These results demonstrate that autoimmunity may be one of the pathogenetic factors of hypertension and aPL antibodies might be a potential marker of renal involvement. Full article
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5 pages, 475 KiB  
Article
Usefulness of Adenosine Deaminase Assay in Diagnosis of Patients with HIV Infection and Pleural Tuberculosis
by Gabriel Yusti, Mariano Fielli, Alejandra Gonzalez, Graciela Torales, Alejandra Zapata and Adrian Ceccato
Med. Sci. 2018, 6(4), 101; https://doi.org/10.3390/medsci6040101 - 13 Nov 2018
Cited by 3 | Viewed by 2801
Abstract
The utility of the adenosine deaminase (ADA) assay in the diagnosis of patients with pleural tuberculosis (TB) and human immunodeficiency virus (HIV) infection is controversial. Forty-eight HIV positive patients with pleural effusion were evaluated; ADA assay was obtained in forty-three of them. Twenty-five [...] Read more.
The utility of the adenosine deaminase (ADA) assay in the diagnosis of patients with pleural tuberculosis (TB) and human immunodeficiency virus (HIV) infection is controversial. Forty-eight HIV positive patients with pleural effusion were evaluated; ADA assay was obtained in forty-three of them. Twenty-five patients presented diagnosis of TB. Patients with diagnosis of TB showed a median value of ADA of 70 IU/L (interquartile range (IQR) 41–89) and the non-TB group a median of 27.5 IU/L (IQR 13.5–52). Patients with diagnosis of TB had a median cluster of differentiation 4 (CD4) count of 174 (IQR 86–274) and the non-TB group had a median of 134 (IQR 71–371). Receiver operating characteristic curve was performed with an area under the curve of 0.79. The best cut-off obtained was 35 IU/L with a sensibility of 80% and a specificity of 66%. There was no correlation between CD4 lymphocytes count and the value of ADA in the TB patient group. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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13 pages, 2598 KiB  
Article
Investigative Study on Nitric Oxide Production in Human Dermal Fibroblast Cells under Normal and High Glucose Conditions
by Maria P. Kwesiga, Emily Cook, Jennifer Hannon, Sarah Wayward, Caroline Gwaltney, Smitha Rao and Megan C. Frost
Med. Sci. 2018, 6(4), 99; https://doi.org/10.3390/medsci6040099 - 09 Nov 2018
Cited by 4 | Viewed by 6417
Abstract
Diabetic foot ulcers (DFU) are a major health problem associated with diabetes mellitus. Impaired nitric oxide (NO) production has been shown to be a major contributor to the dysregulation of healing in DFU. The level of impairment is not known primarily due to [...] Read more.
Diabetic foot ulcers (DFU) are a major health problem associated with diabetes mellitus. Impaired nitric oxide (NO) production has been shown to be a major contributor to the dysregulation of healing in DFU. The level of impairment is not known primarily due to challenges with measuring NO. Herein, we report the actual level of NO produced by human dermal fibroblasts cultured under normal and high glucose conditions. Fibroblasts produce the extracellular matrix, which facilitate the migration of keratinocytes to close wounds. The results show that NO production was significantly higher in normal glucose compared to high glucose conditions. The real-time NO detected was compared to the nitrite present in the culture media and there was a direct correlation between real-time NO and nitrite in normal glucose conditions. However, real-time NO detection and nitrite measurement did not correlate under high glucose conditions. The inducible nitric oxide synthase (iNOS) enzyme responsible for NO production was upregulated in normal and high glucose conditions and the proliferation rate of fibroblasts was not statistically different in all the treatment groups. Relying only on nitrite to assess NO production is not an accurate determinant of the NO present in the wound bed in pathological states such as diabetes mellitus. Full article
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12 pages, 1780 KiB  
Review
Theranostics Applications of Nanoparticles in Cancer Immunotherapy
by Yihai Liu, Xixi Wang, Mubashir Hussain, Mu Lv, Xiaohan Dong, Tianying Wang, Xueqin Xu and Bin Liu
Med. Sci. 2018, 6(4), 100; https://doi.org/10.3390/medsci6040100 - 09 Nov 2018
Cited by 10 | Viewed by 3741
Abstract
With the advancement in the mechanism of immune surveillance and immune evasion in cancer cells, cancer immunotherapy shows promising results for treating cancer with established efficacy and less toxicity. As a result of the off-target effect, the approach for delivering vaccines, adjuvants, or [...] Read more.
With the advancement in the mechanism of immune surveillance and immune evasion in cancer cells, cancer immunotherapy shows promising results for treating cancer with established efficacy and less toxicity. As a result of the off-target effect, the approach for delivering vaccines, adjuvants, or antibodies directly to tumor sites is gaining widespread attention. An effective alternative is to utilize nanoengineered particles, functioning as drug-delivery systems or as antigens themselves. This article reviews the practical implementation of nanotechnology in cancer immunotherapy. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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8 pages, 603 KiB  
Article
Investigating Association of rs5918 Human Platelets Antigen 1 and rs1800790 Fibrinogen β Chain as Critical Players with Recurrent Pregnancy Loss
by Fatemeh Karami, Maliheh Askari and Mohammad Hossein Modarressi
Med. Sci. 2018, 6(4), 98; https://doi.org/10.3390/medsci6040098 - 31 Oct 2018
Cited by 11 | Viewed by 2968
Abstract
Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most [...] Read more.
Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most important variants including rs5918 T > C and rs1800790 G > A were selected to be studied in women affected by RPL. Three milliliters of peripheral blood were drawn from 110 women with history of at least two consecutive spontaneous abortion and 110 healthy women controls. rs5918 T > C and rs1800790 G > A of HPA-1 and FGB genes, respectively, were selected to be analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR_RFLP) following DNA isolation using QIAamp DNA Blood Mini Kit. Heterozygote genotype (TC) of HPA-1 gene rs5918 polymorphism was significantly associated with risk of RPL (p-value = 0.02). Although, rs1800790 G > A of FGB gene was not associated with RPL, its combination with rs5918 polymorphism was associated with increased risk of RPL. Owing to the critical roles of FGB and HPA-1 genes in coagulation, and thrombosis and several confinements on the meaningful association between the combination of those polymorphism with risk of RPL, including them in the thrombophilia panel may increase detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are required to shed light on the exact role of the studied gene polymorphism, especially rs1800790 G > A of FGB gene variant in pathogenesis of RPL. Full article
(This article belongs to the Section Gynecology)
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18 pages, 2073 KiB  
Review
Exercise Increases Adiponectin and Reduces Leptin Levels in Prediabetic and Diabetic Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Tarik Becic, Christian Studenik and Georg Hoffmann
Med. Sci. 2018, 6(4), 97; https://doi.org/10.3390/medsci6040097 - 30 Oct 2018
Cited by 64 | Viewed by 5999
Abstract
It is speculated that lifestyle interventions known to improve diabetic metabolic state may exert their effects via adipokines. The aim of this systematic review and meta-analysis was to evaluate the chronic effects of physical exercise on adiponectin and leptin levels in adult prediabetic [...] Read more.
It is speculated that lifestyle interventions known to improve diabetic metabolic state may exert their effects via adipokines. The aim of this systematic review and meta-analysis was to evaluate the chronic effects of physical exercise on adiponectin and leptin levels in adult prediabetic and diabetic individuals. PubMed, Embase, Scopus, The Cochrane Library, clinicaltrials.gov, and WHO Clinical Trials Registry were searched for randomized controlled trials. Pooled effects of interventions were assessed as mean difference (MD) with random effects model. Sensitivity analysis was conducted to test data robustness and subgroup analysis for study heterogeneity. Twenty-two trials with 2996 individuals were included in the meta-analysis. Physical exercise increased levels of adiponectin (MD: 0.42 µg/mL; 95% confidence interval (CI), 0.23, 0.60, p < 0.00001, n = 19 trials) and reduced leptin levels (MD: −1.89 ng/mL; 95% CI, −2.64, −1.14, p < 0.00001, n = 14 trials). These results were robust and remained significant after sensitivity analysis. Study heterogeneity was generally high. As for physical exercise modalities, aerobic exercise, but not other modalities, increased adiponectin and reduced leptin levels. In conclusion, physical exercise and, specifically, aerobic exercise, leads to higher adiponectin and lower leptin levels in prediabetic and diabetic adults. However, cautious interpretation of current findings is warranted. Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
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11 pages, 3076 KiB  
Article
Pyogenic Spondylodiscitis: Risk Factors for Adverse Clinical Outcome in Routine Clinical Practice
by John D. Widdrington, Ingrid Emmerson, Milo Cullinan, Manjusha Narayanan, Eleanor Klejnow, Alistair Watson, Edmund L. C. Ong, Matthias L. Schmid, D. Ashley Price, Ulrich Schwab and Christopher J. A. Duncan
Med. Sci. 2018, 6(4), 96; https://doi.org/10.3390/medsci6040096 - 30 Oct 2018
Cited by 16 | Viewed by 3835
Abstract
We aimed to describe the clinical features and outcomes of pyogenic spondylodiscitis and to identify factors associated with an unfavourable clinical outcome (defined as death, permanent disability, spinal instability or persistent pain). In our tertiary centre, 91 cases were identified prospectively and a [...] Read more.
We aimed to describe the clinical features and outcomes of pyogenic spondylodiscitis and to identify factors associated with an unfavourable clinical outcome (defined as death, permanent disability, spinal instability or persistent pain). In our tertiary centre, 91 cases were identified prospectively and a retrospective descriptive analysis of clinical records was performed prior to binary regression analysis of factors associated with an unfavourable outcome. A median 26 days elapsed from the onset of symptoms to diagnosis and 51% of patients had neurological impairment at presentation. A microbiological diagnosis was reached in 81%, with Staphylococcus aureus most commonly isolated. Treatment involved prolonged hospitalisation (median stay 40.5 days), long courses of antibiotics (>6 weeks in 98%) and surgery in 42%. While this was successful in eradicating infection, only 32% of patients had a favourable clinical outcome and six patients (7%) died. Diabetes mellitus, clinical evidence of neurological impairment at presentation, a longer duration of symptoms and radiological evidence of spinal cord or cauda equina compression were independent factors associated with an unfavourable outcome. Our data indicate that spondylodiscitis is associated with significant morbidity and suggest that adverse outcomes may be predicted to an extent by factors present at the time of diagnosis. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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11 pages, 208 KiB  
Review
Pharmacological Approach to Sleep Disturbances in Autism Spectrum Disorders with Psychiatric Comorbidities: A Literature Review
by Sachin Relia and Vijayabharathi Ekambaram
Med. Sci. 2018, 6(4), 95; https://doi.org/10.3390/medsci6040095 - 25 Oct 2018
Cited by 22 | Viewed by 6317
Abstract
Autism is a developmental disability that can cause significant emotional, social and behavioral dysfunction. Sleep disorders co-occur in approximately half of the patients with autism spectrum disorder (ASD). Sleep problems in individuals with ASD have also been associated with poor social interaction, increased [...] Read more.
Autism is a developmental disability that can cause significant emotional, social and behavioral dysfunction. Sleep disorders co-occur in approximately half of the patients with autism spectrum disorder (ASD). Sleep problems in individuals with ASD have also been associated with poor social interaction, increased stereotypy, problems in communication, and overall autistic behavior. Behavioral interventions are considered a primary modality of treatment. There is limited evidence for psychopharmacological treatments in autism; however, these are frequently prescribed. Melatonin, antipsychotics, antidepressants, and α agonists have generally been used with melatonin, having a relatively large body of evidence. Further research and information are needed to guide and individualize treatment for this population group. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
20 pages, 288 KiB  
Article
Community Resilience and Long-Term Impacts of Mental Health and Psychosocial Support in Northern Rwanda
by Yuko Otake
Med. Sci. 2018, 6(4), 94; https://doi.org/10.3390/medsci6040094 - 24 Oct 2018
Cited by 14 | Viewed by 4862
Abstract
Recently, discussions have considered how mental health and psychosocial support (MHPSS) can build upon local resilience in war-affected settings. To contribute to the knowledge in this field, the paper explored the gap between MHPSS and local communities in terms of perceived mental health [...] Read more.
Recently, discussions have considered how mental health and psychosocial support (MHPSS) can build upon local resilience in war-affected settings. To contribute to the knowledge in this field, the paper explored the gap between MHPSS and local communities in terms of perceived mental health problems and healing processes, and how the gap could be filled. Qualitative research was conducted in northern Rwanda with 43 participants between 2015 and 2016. Findings revealed how three particular gaps can isolate MHPSS recipients in their local community. First, whereas MHPSS applies bio-psychological frameworks to post-genocide mental health, community conceptualisations emphasise social aspects of suffering. Second, unlike MHPSS which encourages ‘talking’ about trauma, ‘practicing’ mutual support plays a major role in the community healing process. Third, MHPSS focuses on one part of the community (those who share the same background) and facilitates their healing in intervention groups. However, healing in natural communities continues in everyday life, through mutual support among different people. Despite these gaps, MHPSS recipients can be (re)integrated into the community through sharing suffering narratives and sharing life with other community members. The paper highlights the ways in which MHPSS could inclusively support different social groups in the overall geographical community, allowing members to preserve the existing reciprocity and recover collective life through their own initiatives. Full article
(This article belongs to the Special Issue Recent Advances in Health Improvement Strategies)
9 pages, 234 KiB  
Article
Demographic Pattern and Hospitalization Outcomes of Depression among 2.1 Million Americans with Four Major Cancers in the United States
by Rikinkumar S. Patel, Kuang-Yi Wen and Rashi Aggarwal
Med. Sci. 2018, 6(4), 93; https://doi.org/10.3390/medsci6040093 - 24 Oct 2018
Cited by 10 | Viewed by 2961
Abstract
Objective: To compare the prevalence of depression in the four most common cancers in the US and evaluate differences in demographics and hospital outcomes. Methods: This was a cross-sectional study using the Nationwide Inpatient Sample (2010–2014). We selected patients who had received ICD-9 [...] Read more.
Objective: To compare the prevalence of depression in the four most common cancers in the US and evaluate differences in demographics and hospital outcomes. Methods: This was a cross-sectional study using the Nationwide Inpatient Sample (2010–2014). We selected patients who had received ICD-9 codes of breast, lung, prostate, and colorectal cancers and major depressive disorder (MDD). Pearson’s chi-square test and independent sample t-test were used for categorical and continuous data, respectively. Results: MDD prevalence rate was highest in lung cancer (11.5%), followed by breast (10.3%), colorectal (8.1%), and prostate cancer (4.9%). Within colorectal and lung cancer groups, patients with MDD were significantly older (>80 years, p < 0.001) than non-MDD patients. Breast, lung, and colorectal cancer showed a higher proportion of female and Caucasian in the MDD group. Severe morbidity was seen in a greater proportion of the MDD group in all cancer types. The mean inpatient stay and cost were higher in the MDD compared to non-MDD group. Conclusion: Particular attention should be given to elderly, female, and to lung cancer patients with depression. Further studies of each cancer type are needed to expand our understanding of the different risk factors for depression as a higher proportion of patients had severe morbidity. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
13 pages, 477 KiB  
Review
Dietary Effects on Microbiota—New Trends with Gluten-Free or Paleo Diet
by Yurdagül Zopf, Dejan Reljic and Walburga Dieterich
Med. Sci. 2018, 6(4), 92; https://doi.org/10.3390/medsci6040092 - 18 Oct 2018
Cited by 19 | Viewed by 13893
Abstract
A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, [...] Read more.
A well-balanced diet is the basis for a healthy life. Both the western diet and special diets can have a relevant impact on the microbiome and promote the development of various diseases. There has been an increase in food-related disorders in recent years, largely associated with dramatic changes in food consumption trends and main nutrients. A major response to food intolerances has been the adoption of new dietary trends involving the reduction or exclusion of specific food ingredients. Especially gluten-containing, but also gluten-free cereals are in the cross-fire. Supporters of the gluten-free diet argue that gluten triggers inflammation and related diseases, while followers of the Paleo diet drastically impeach all cereals as dangerous for human health. To date, no controlled studies support or reject a positive health effect of a gluten-free or cereal-free diet. Future large-scale studies need to evaluate the effect of gluten-containing and gluten-free cereals and the various diets on human health, inflammatory parameters, clinical symptoms, and the gut microbiota (including the bacteria, fungi, and viruses). Dietary-associated changes in compositional and functional microbiota traits should be correlated with the health status for the future development of dietary recommendations and potential clinical interventions. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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11 pages, 1266 KiB  
Article
Differences in Hypotensive vs. Non-Hypotensive Sepsis Management in the Emergency Department: Door-to-Antibiotic Time Impact on Sepsis Survival
by Leonor Ballester, Rafael Martínez, Juan Méndez, Gloria Miró, Manel Solsona, Elisabeth Palomera, Josep Anton Capdevila, Alejandro Rodriguez and Juan Carlos Yébenes
Med. Sci. 2018, 6(4), 91; https://doi.org/10.3390/medsci6040091 - 10 Oct 2018
Cited by 7 | Viewed by 8263
Abstract
Background: Sepsis diagnosis can be incorrectly associated with the presence of hypotension during an infection, so the detection and management of non-hypotensive sepsis can be delayed. We aimed to evaluate how the presence or absence of hypotension, on admission at the emergency department, [...] Read more.
Background: Sepsis diagnosis can be incorrectly associated with the presence of hypotension during an infection, so the detection and management of non-hypotensive sepsis can be delayed. We aimed to evaluate how the presence or absence of hypotension, on admission at the emergency department, affects the initial management and outcomes of patients with community-onset severe sepsis. Methods: Demographic, clinical, laboratory, process of care, and outcome variables were recorded for all patients, at the emergency department of our university hospital, who presented with community-onset severe sepsis, between 1 March and 31 August in three consecutive years. Patient management consisted of standardized bundled care with five measures: Detection, blood cultures and empirical antibiotics, oxygen supplementation and fluid resuscitation (if needed), clinical monitoring, and noradrenalin administration (if needed). We compared all variables between patients who had hypotension (mean arterial pressure <65 mmHg), on admission to the emergency department, and those who did not. Results: We identified 153 episodes (84 (54.5%) men; mean age 73.6 ± 1.2; mean Sequential Organ Failure Assessment (SOFA) score 4.9 ± 2.7, and 41.2% hospital mortality). Hypotension was present on admission to the emergency department in 57 patients (37.2%). Hemodynamic treatment was applied earlier in patients who presented hypotension initially. Antibiotics were administered 48 min later in non-hypotensive sepsis (p = 0.08). A higher proportion of patients without initial hypotension required admission to the intensive care unit (ICU) (43.1% for patients initially hypotensive vs. 56.9% in those initially non-hypotensive, p < 0.05). Initial hypotension was not associated with mortality. A delay in door-to-antibiotic administration time was associated with mortality [OR 1.150, 95%CI: 1.043–1.268). Conclusions: Initial management of patients with community-onset severe sepsis differed according to their clinical presentation. Initial hypotension was associated with early hemodynamic management and less ICU requirement. A non-significant delay was observed in the administration of antibiotics to initially non-hypotensive patients. The time of door-to-antibiotic administration was related to mortality. Full article
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17 pages, 689 KiB  
Review
Sleep and Delirium in Pediatric Critical Illness: What Is the Relationship?
by Amy Calandriello, Joanna C. Tylka and Pallavi P. Patwari
Med. Sci. 2018, 6(4), 90; https://doi.org/10.3390/medsci6040090 - 10 Oct 2018
Cited by 19 | Viewed by 6609
Abstract
With growing recognition of pediatric delirium in pediatric critical illness there has also been increased investigation into improving recognition and determining potential risk factors. Disturbed sleep has been assumed to be one of the key risk factors leading to delirium and is commonplace [...] Read more.
With growing recognition of pediatric delirium in pediatric critical illness there has also been increased investigation into improving recognition and determining potential risk factors. Disturbed sleep has been assumed to be one of the key risk factors leading to delirium and is commonplace in the pediatric critical care setting as the nature of intensive care requires frequent and invasive monitoring and interventions. However, this relationship between sleep and delirium in pediatric critical illness has not been definitively established and may, instead, reflect significant overlap in risk factors and consequences of underlying neurologic dysfunction. We aim to review the existing tools for evaluation of sleep and delirium in the pediatric critical care setting and review findings from recent investigations with application of these measures in the pediatric intensive care unit. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
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19 pages, 3872 KiB  
Review
Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications
by Bruno Ramos-Molina, Ana Lambertos and Rafael Peñafiel
Med. Sci. 2018, 6(4), 89; https://doi.org/10.3390/medsci6040089 - 09 Oct 2018
Cited by 12 | Viewed by 5605
Abstract
The intracellular levels of polyamines, cationic molecules involved in a myriad of cellular functions ranging from cellular growth, differentiation and apoptosis, is precisely regulated by antizymes and antizyme inhibitors via the modulation of the polyamine biosynthetic and transport systems. Antizymes, which are mainly [...] Read more.
The intracellular levels of polyamines, cationic molecules involved in a myriad of cellular functions ranging from cellular growth, differentiation and apoptosis, is precisely regulated by antizymes and antizyme inhibitors via the modulation of the polyamine biosynthetic and transport systems. Antizymes, which are mainly activated upon high polyamine levels, inhibit ornithine decarboxylase (ODC), the key enzyme of the polyamine biosynthetic route, and exert a negative control of polyamine intake. Antizyme inhibitors (AZINs), which are proteins highly homologous to ODC, selectively interact with antizymes, preventing their action on ODC and the polyamine transport system. In this review, we will update the recent advances on the structural, cellular and physiological functions of AZINs, with particular emphasis on the action of these proteins in the regulation of polyamine metabolism. In addition, we will describe emerging evidence that suggests that AZINs may also have polyamine-independent effects on cells. Finally, we will discuss how the dysregulation of AZIN activity has been implicated in certain human pathologies such as cancer, fibrosis or neurodegenerative diseases. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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