Allergy and skin diseases in musicians

In order to define a standard diagnostic protocol for managing allergic dis-eases in musicians, we conducted a literature search on this topic. The most frequent allergic disease in this special category of workers was contact dermatitis, always described in stringed and wind instruments players, involving the mouth and the hands. No other allergic disease directly related to musical instruments was reported. The most frequently reported culprit substances were: colophony, exotic woods, nickel sulphate, varnishes, and propolis (bee glue). Thus, being contact dermatitis the most frequent disease, a correct diagnostic approach to this problem in musicians should involve, in addition to clinical history and examination, the patch test with a specific panel of substances. Finally, allergy in musicians involves additional problems: the virtual impossibility to avoid the offending substance, and the poor adherence to therapy due to lifestyle. In general, this specific allergologic problem seems to be underestimated, underdiagnosed and, as a conquence, poorly managed.     

DA1 receptor mediates dopamine-induced relaxation of opossum lower esophageal sphincter in vitro

The objective of the present experiments was to determine the specific receptor subtype through which dopamine (DA) receptor agonists relax the lower esophageal sphincter in vitro. Opossum lower esophageal sphincter smooth muscle strips were placed in oxygenated Krebs' solution containing propranolol and cocaine. The tissues were placed at a tension that gave maximum relaxation to electrical field stimulation and were then pretreated with phenoxybenzamine. The effects of DA, and the DA receptor agonists epinine and apomorphine were determined. In addition, agonist responses were studied in the presence of the selective DA2 receptor antagonist domperidone, a mixed DA1/DA2 receptor antagonist metoclopramide, and the selective DA1 receptor antagonists bulbocapnine and SK&F 83566. The DA agonists relaxed the smooth muscle strips in the following order of potency: DA greater than epinine greater than apomorphine. Domperidone did not antagonize DA- or apomorphine-induced relaxation. Metoclopramide failed to alter DA-induced relaxation. Bulbocapnine and SK&F 83566 significantly inhibited the relaxation induced by DA. These data indicate that DA-induced lower esophageal sphincter relaxation in vitro is mediated by DA1 receptors.     

Truncal fat determined by dual-energy X-ray absorptiometry is an independent predictor of coronary artery disease extension

BACKGROUND: Controversy prevails regarding the existence of a correlation between the severity of coronary artery disease (CAD) and the extent and distribution of obesity. PURPOSE: To assess the correlation between total fat, truncal fat (TF), and lean mass, obtained with dual-energy X-ray absorptiometry (DEXA) and standard anthropomorphic indices (body mass index, waist circumference, waist-to-hip ratio) and to verify whether DEXA indices can predict the extent and severity of CAD. MATERIALS AND METHODS: Fifty-eight patients (19 females) consecutively referred for coronary angiography underwent physical examination and DEXA assessment of body composition. RESULTS: Of the 58 patients enrolled, 22 were overweight and 13 were obese. Significant CAD was found in 39 (67%) patients. DEXA-derived total mass and fat mass enabled us to distinguish overweight from obese patients (P<0.005), whereas just TF mass correlated with the number of diseased vessels after adjusting for body mass index, sex, age, and smoking habit (odds ratio, 8.68; 95% confidence interval: 1.02-74.10). CONCLUSION: TF determined by DEXA is independently related with CAD extension.     

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

Electron Microscopy Analysis of Early Localization of Cisplatin in Ovarian Carcinoma Cells

Taking advantage of the electron-dense nature of platinum, in this study the authors used an electron microscopy approach to investigate the cellular localization of cisplatin in an ovarian carcinoma cell line. Platinum spots were detected in contact with the plasma membrane and the nuclear envelope as well as in the cytoplasm and nuclear matrices. Contact with the plasma membrane was through a single blunt contact or spanning through the membrane. No sequestration in intracellular vescicles was observed, thereby supporting that phagocytosis and receptor-mediated endocytosis were not occurring. A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin. The present data suggest that cisplatin rapidly accumulates in the cell through endocytosis-independent membrane translocation and are consistent with passive diffusion.     

Potential role of brivaracetam in pediatric epilepsy

Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to levetiracetam (LEV), BRV works by binding SV2A vesicles with a high affinity and a linear pharmacokinetic profile. Retrospective studies and randomized clinical trials have already proven the efficacy of BRV, even in patients who failed treatment with LEV. Most studies about the efficacy and tolerability conducted so far were performed in adult cohorts, whereas few studies have been performed in children; however, BRV was proven to be a useful ASM for pediatric focal epilepsies, with fewer studies and conflicting results among patients with generalized epilepsies and epileptic syndromes. Retention rates were high in the cohorts analyzed, and no serious treatment‐emergent adverse events were reported in the majority of patients, with somnolence, drowsiness, irritability, aggression, and decreased appetite being the most frequently reported side effects. Although there are few original papers published on the subject so far, the analysis of the literature data demonstrated the efficacy and safety of BRV in pediatric patients, with more evidence for children aged 4‐16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by encephalopathic epilepsies (eg, Jeavons' epilepsy, Dravet syndrome, Lennox‐Gastaut syndrome, and juvenile myoclonic epilepsy), and ongoing studies are now testing BRV in order to widen its application to other forms of epilepsy and to test its effectiveness when used in monotherapy. This review aims to provide a comprehensive analysis of the literature surrounding the efficacy and tolerability of BRV for pediatric patients.     

Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma

Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome‐wide scan for early‐onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early‐onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early‐onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.     

Rapid review of virus risk communication interventions: Directions for COVID-19

ObjectiveIn response to COVID-19, we conducted a rapid review of risk communication interventions to mitigate risk from viruses to determine if such interventions are efficacious.MethodsWe searched for risk communication interventions in four databases: Medline, PsycInfo, the ProQuest Coronavirus Research Database, and CENTRAL. The search produced 1572 articles. Thirty-one articles were included in the final review.ResultsResults showed risk communication interventions can produce cognitive and behavior changes around viruses. Results were more consistently positive for interventions focused on HIV/AIDS as compared to influenza. There was no consistent best intervention approach when comparing peer health, audio/visual, and intensive multi-media interventions. Tailoring risk communication toward a target population, in comparison to not tailoring, was related to better outcomes.ConclusionThe results suggest that risk communication interventions can be efficacious at reducing risk from viruses. They also highlight the complexity of risk communication interventions. Additional research is needed to understand the mechanisms that lead risk communication to reduce risk from viruses.Practical valueResults support risk communication interventions to reduce risk from viruses.     

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy

Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM.