Med. Sci., Volume 7, Issue 4 (April 2019) – 13 articles

Type 2 diabetes affects over 340 million people worldwide. This condition can go unnoticed and undiagnosed for years, leading to a late stage where high glycaemia produces complications such as delayed wound healing. Studies have shown that 12-HHT through BLT2, accelerates keratinocyte migration and wound healing. Additionally, evidence has shown the role of nitric oxide as a pro-regenerative mediator, which is decreased in diabetes. Our main goal was to study the association between the 12-HHT/BLT2 axis and the nitric oxide production in wound healing under different glycaemia conditions. For that purpose, we used in vivo and in vitro models. Our results show that the skin from diabetic mice showed reduced BLT2 and iNOS mRNA, TEER, 12-HHT, nitrites, and tight junction levels, accompanied by higher MMP9 mRNA levels. Furthermore, a positive correlation between BLT2 mRNA and nitrites was observed. In vitro, HaCaT-BLT2 cells showed higher nitric oxide and tight junction levels, and reduced MMP9 mRNA levels, compared to mock-keratinocytes under low and high glucose condition. The wound healing capacity was associated with higher nitric oxide production and was affected by the NOS inhibition. We suggest that the BLT2 expression improves the keratinocyte response to hyperglycaemia, associated with the production of nitric oxide. Full article

This study reports (for the first time) the staining ability of vital (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) dyes to differentiate between live and dead Schistosoma haematobium (S. haematobium) eggs in human urine samples. Since S. haematobium egg is important in disease pathology, diagnosis, transmission, and drug development research, it is essential to be able to easily distinguish live eggs from dead ones. Staining is considered a way of enhancing the identification of live and dead eggs. Urine samples from school children were examined for the presence of S. haematobium eggs. Vital and fluorescent dyes were used to stain the samples that contained S. haematobium eggs, after which they were observed using light and fluorescent microscopes, respectively. The Hoechst 33258 provided a good staining outcome for differentiation between live and dead eggs, followed by 0.4% Trypan blue. Regarding the 1% neutral red stain, even though it provided some evidence of which egg was alive or dead, the distinction was not very clear; therefore, it could be useful when used in combination with other stains for egg viability determination. The benefits of this study will include assessing the effect of drugs on S. haematobium eggs in Schistosomiasis research. Full article

The aim of this study was to investigate the impact of bedside discharge education on activity levels and healthcare utilization for patients with acute coronary syndrome (ACS) in the first 30 days post-discharge. Knowledge recall and objective activity and location data were collected by global positioning systems (GPS). Participants were asked to carry the tracking applications (apps) for 30–90 days. Eighteen participants were recruited (6 metropolitan 12 rural) 61% ST elevation myocardial infarction (STEMI), mean age 55 years, 83% male. Recall of discharge education included knowledge of diagnosis (recall = 100%), procedures (e.g., angiogram = 40%), and comorbidities (e.g., hypertension = 60%, diabetes = 100%). In the first 30 days post-discharge, median steps per day was 2506 (standard deviation (SD) ± 369) steps (one participant completed 10,000 steps), 62% visited a general practitioner (GP) 16% attended cardiac rehabilitation, 16% visited a cardiologist, 72% a pharmacist, 27% visited the emergency department for cardiac event, and 61% a pathology service (blood tests). Adherence to using the activity tracking apps was 87%. Managing Big Data from the GPS and physical activity tracking apps was a challenge with over 300,000 lines of raw data cleaned to 90,000 data points for analysis. This study was an example of the application of objective data from the real world to help understand post-ACS discharge patient activity. Rates of access to services in the first 30 days continue to be of concern. Full article

The present study was performed to evaluate the clinical symptoms and cardiovascular complications in patients with typical and atypical Kawasaki disease (KD). This retrospective study was conducted on the medical records of 176 patients with KD for three years. The study population was divided into two groups of typical and atypical based on the KD clinical criteria. The two groups were compared in terms of demographic data, clinical symptoms, cardiac lesions, and laboratory markers. Based on the diagnostic criteria, 105 (60%) and 71 (40%) patients were diagnosed with typical and atypical KD, respectively. The mean age of the typical patients (38.16 months) was higher than that of the atypical group (24.03 months) at the time of diagnosis (p < 0.05). The results revealed no significant difference between the two groups regarding the seasonal distribution of KD onset (p = 0.422). However, the most common season for the diagnosis of the disease was spring, followed by winter. There was no significant difference between the two groups in terms of fever duration (p = 0.39). Furthermore, vomiting was more common in the atypical patients than in the typical group (p = 0.017). In terms of the cardiac lesions, ectasia (p = 0.005) and lack of tapering of the distal coronary vessels (p = 0.015) were more frequently detected in the atypical group than in the typical group. Considering the laboratory findings, thrombocytosis (p = 0.010) and anemia (p = 0.048) were more common in the atypical group, compared to those in the typical group. On the other hand, the typical group had a higher serum alanine aminotransferase level (adjusted for age) (p = 0.012) and Hyponatremia (serum sodium concentration ≤130 mmol/L) (p = 0.034). Based on the findings of the current study, the fever duration from onset to diagnosis was slightly more in atypical KD patients than in the typical group, but not statistically significant, possibly due to more timely diagnosis of atypical KD. There was no difference in coronary aneurysm between the two groups at the time of diagnosis. The atypical group had a higher frequency of coronary ectasia and lack of tapering, indicating cardiac involvement. Consequently, these conditions should be given more attention in the atypical patients. Furthermore, the higher frequency of anemia and thrombocytosis in the atypical patients can be useful for diagnosis of this kind of KD. Full article

Persistent itch (pruritus) accompanying dermatologic and systemic diseases can significantly impair the quality of life. It is well known that itch is broadly categorized as histaminergic (sensitive to antihistamine medications) or non-histaminergic. Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs) mediate histamine-independent itch. These receptors have been shown to bind selective pruritogens in the periphery and mediate non-histaminergic itch. For example, mouse MrgprA3 responds to chloroquine (an anti-malarial drug), and are responsible for relaying chloroquine-induced scratching in mice. Mouse MrgprC11 responds to a different subset of pruritogens including bovine adrenal medulla peptide (BAM8–22) and the peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). On the other hand, the possibility that itch mediators also influence pain is supported by recent findings that most non-histaminergic itch mediators require the transient receptor potential ankyrin 1 (TRPA1) channel. We have recently found a significant increase of thermal and mechanical hyperalgesia induced by non-histaminergic pruritogens chloroquine and BAM8–22, injected into mice hindpaw, for the first 30–45 min. Pretreatment with TRPA1 channel antagonist HC-030031 did significantly reduce the magnitude of this hyperalgesia, as well as significantly shortened the time-course of hyperalgesia induced by chloroquine and BAM8–22. Here, we report that MrgprC11-mediated itch by their agonist SLIGRL is accompanied by heat and mechanical hyperalgesia via the TRPA1 channel. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds bilaterally in mice at various time points following intra-plantar injection of SLIGRL producing hyperalgesia. When pretreated with the TRPA1 antagonist HC-030031, we found a significant reduction of thermal and mechanical hyperalgesia. Full article

Lipoxygenase-derived lipid mediators can modulate inflammation and are stimulated in response to influenza infections. We report an effect of 8-lipoxygenase (ALOX8) on the recovery of mice after infection with Influenza virus X31. We compared the responses of 3- and 6-month-old mice with a deletion of ALOX8 (ALOX8^−/−) to influenza infections with those of age-matched littermate wild-type mice (ALOX8^+/+). The duration of illness was similar in 3-month-old ALOX8^−/− and ALOX8^+/+ mice. However, the 6-month-old ALOX8^−/− mice showed a prolonged state of illness compared with ALOX8^+/+ mice, as evidenced by reduced body temperatures, reduced locomotor activities, and delayed weight recovery. Although residual viral RNA in the lungs at day 10 post-inoculation was significantly influenced by the age of the ALOX8^−/− mice, there were no significant differences between ALOX8^−/− and ALOX8^+/+ mice within the same age groups. The levels of cytokines interleukin 6 (IL-6) and keratinocyte chemoattractant (KC) differed significantly between 6-month-old ALOX8^−/− and ALOX8^+/+ mice 10 days after viral inoculation. Our data suggest that ALOX8 deficiency in mice leads to impaired recovery from influenza infection in an age-dependent manner. Full article

Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling. Full article

Background: Hypertension is a main risk factor for premature death. Although blood pressure is a complex trait, we have shown that the activity of the ATP-generating enzyme creatine kinase (CK) is a significant predictor of blood pressure and of failure of antihypertensive drug therapy in the general population. In this report, we systematically review the evidence on the association between this new risk factor CK and blood pressure outcomes. Method: We used a narrative synthesis approach and conducted a systematic search to include studies on non-pregnant adult humans that address the association between plasma CK and blood pressure outcomes. We searched electronic databases and performed a hand search without language restriction. We extracted data in duplo. The main outcome was the association between CK and blood pressure as continuous measures. Other outcomes included the association between CK and blood pressure categories (normotension and hypertension, subdivided in treated controlled, treated uncontrolled, and untreated hypertension). Results: We retrieved 139 reports and included 11 papers from 10 studies assessing CK in 34,578 participants, men and women, of African, Asian, and European ancestry, aged 18 to 87 years. In 9 reports, CK was associated with blood pressure levels, hypertension (vs. normotension), and/or treatment failure. The adjusted increase in systolic blood pressure (mmHg/log CK increase) was reported between 3.3 [1.4 to 5.2] and 8.0 [3.3 to 12.7] and the odds ratio of hypertension with high vs. low CK ranged between 1.2 and 3.9. In addition, CK was a strong predictor of treatment failure in the general population, with an adjusted odds ratio of 3.7 [1.2 to 10.9]. Discussion: This systematic review largely confirms earlier reports that CK is associated with blood pressure and failure of antihypertensive therapy. Further work is needed to address whether this new risk factor is useful in clinical medicine. Full article

Cystic fibrosis patients frequently develop chronic rhinosinusitis as a result of their propensity to form inspissated mucus and impairment of mucociliary clearance. They exhibit variable symptom burden even in the setting of positive radiographic and endoscopic findings. Current evidence suggests a positive effect of managing sinonasal disease on pulmonary health. Topical antimicrobial and mucolytic therapies are frequently required to manage the disease with surgery reserved for refractory cases. Endoscopic sinus surgery has been demonstrated to be safe and efficacious in controlling symptoms of chronic rhinosinusitis in patients with comorbid cystic fibrosis. However, the impact of surgery on pulmonary health remains an active area of investigation. In addition, a growing body of research has suggested a more extended surgical approach creating large sinonasal cavities with gravity-dependent drainage pathways, followed by adjuvant medical therapies, as an ideal strategy to optimally control disease and prevent pulmonary exacerbations. In this manuscript, we provide an up-to-date review of current evidence in the surgical management of chronic rhinosinusitis in cystic fibrosis patients. Full article

Magnesium is the fourth most abundant cation in the body and the second most abundant intracellular cation. It plays an important role in different organ systems at the cellular and enzymatic levels. Despite its importance, it still has not received the needed attention either in the medical literature or in clinical practice in comparison to other electrolytes like sodium, potassium, and calcium. Hypomagnesemia can lead to many clinical manifestations with some being life-threatening. The reported incidence is less likely than expected in the general population. We present a comprehensive review of different aspects of magnesium physiology and hypomagnesemia which can help clinicians in understanding, identifying, and treating this disorder. Full article

Caroli syndrome, characterized by saccular dilatation of intrahepatic ducts and congenital hepatic fibrosis, is without therapy in part due to its ultra-rare prevalence and the apparent lack of availability of a suitable experimental model. While the PCK rat has long been used as a model of fibropolycystic kidney disease, hepatobiliary biophysics in this animal model is incompletely characterized. Compared to age-matched, wild-type controls, the PCK rat demonstrated severe hepatomegaly and large saccular dilated intrahepatic ducts. Nevertheless, hepatic density was greater in the PCK rat, likely due to severe duct wall sclerosis accompanied by scarring across the hepatic parenchyma. Extracellular matrix accumulation appeared proportional to duct cross-sectional area and liver volume and appeared compensatory in nature. The PCK rat livers exhibited both cholangiocarcinoma and hepatocellular carcinoma coincident with areas of increased extracellular matrix deposition. Together, these data suggest that the PCK rat model mimics at least in part the spectrum of hepatobiliary pathology observed in Caroli syndrome and highlights the attendant risk associated with this disease. Full article

It has been shown that the better outcomes of chronic obstructive pulmonary disease (COPD) are closely associated with adherence to drug therapy, independent of the treatment administered. The clinical trial Towards a Revolution in COPD Health (TORCH) study clearly showed in a three year follow up that patients with good adherence to their inhaler treatment presented a longer time before the first exacerbation, a lower susceptibility to exacerbation and lower all-cause mortality. The Latin American Study of 24-h Symptoms in Chronic Obstructive Pulmonary Disease (LASSYC), a real-life study, evaluated the self-reported inhaler adherence in COPD patients in seven countries in a cross-sectional non-interventional study and found that approximately 50% of the patients had good adherence, 30% moderate adherence and 20% poor adherence. Adherence to inhaler may be evaluated by the specific inhaler adherence questionnaire, the Test of Adherence to Inhalers (TAI). Several factors may predict the incorrect use of inhalers or adherence in COPD outpatient, including the number of devices and the daily dosing frequency. Ideally, patient education, simplicity of the device operation, the use of just one device for multiple medications and the best adaptation of the patient to the inhaler should guide the physician in prescribing the device. Full article

Asthma is a prevalent inflammatory condition of the lower airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchial hyperresponsiveness (BHR). Symptomatically, these patients may demonstrate wheezing, breathlessness, chest tightness, and coughing. This disease is a substantial burden to a growing population worldwide that currently exceeds 300 million individuals. This is a condition that is frequently encountered, but often overlooked in the field of otolaryngology. In asthma, comorbid conditions are routinely present and contribute to respiratory symptoms, decreased quality of life, and poorer asthma control. It is associated with otolaryngic diseases of the upper airways including allergic rhinitis (AR) and chronic rhinosinusitis (CRS). These conditions have been linked epidemiologically and pathophysiologically. Presently, they are considered in the context of the unified airway theory, which describes the upper and lower airways as a single functional unit. Thus, it is important for otolaryngologists to understand asthma and its complex relationships to comorbid diseases, in order to provide comprehensive care to these patients. In this article, we review key elements necessary for understanding the evaluation and management of asthma and its interrelatedness to CRS. Full article