Notes

Vesicular Acetylcholine Transporter Adjusts Cholinergic Sculpt along with Synaptic Plasticity within DYT1 Dystonia.
Male BMVECs secreted more ET-1. Hypoxia increased ET-1 in both cell types. There are sex differences in the stroke and diabetes-mediated changes in the brain ET system at endothelial and tissue levels.Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib's effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms (P = .007), corrected QT interval shortening using Bazett's formula from 446 ms to 437 ms (P = .04), and corrected QT interval shortening using Fridericia's formula from 425 ms to 407 ms (P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.A longitudinal study was carried out to investigate the prevalence and risk factors (including haemoglobin levels) for gestational diabetes mellitus (GDM) in Khartoum, Sudan. The study was carried out at Saad Abuelela Hospital (Khartoum, Sudan) during February to November 2017. Pregnant women in early pregnancy (gestational age 10.8 g/dl were at a higher risk of GDM (OR = 2.52, 95% CI = 1.02 - 6.27, p = .044). There is a high prevalence of GDM, especially among women with high haemoglobin levels.Impact statementWhat is already known on this subject? Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, contributing significantly to maternal, perinatal morbidity and mortality and can lead to adverse consequences for the health of both mother and offspring later in life. The rate of GDM varies with the various settings and populations, and a prevalence of 1-14% has been reported depending on the population studied. MC903 Vitamin chemical High haemoglobin levels were recently reported to be associated with GDM.What do the results of this study add? There is a high prevalence of GDM in Khartoum, Sudan, especially among women with high haemoglobin levels in early pregnancy.What are the implications of these findings for clinical practice and/or further research? Haemoglobin levels could be used as reliable markers to detect GDM. These markers could be used in the prevention of GDM.Acromegaly is an endocrine disease caused by the excess secretion of growth hormone and is responsible for the development of multiple comorbidities that can reduce physiologic reserve. The hypersecretion of growth hormone (GH) affects virtually every organ in the body and can predispose an individual to frailty; a state of vulnerability resulting from cumulative decline across multiple systems. Frailty results in a loss of physiologic reserve and vulnerability to adverse outcomes such as morbidity and mortality. Case Description The patient was a 73-year-old male with acromegaly who declined into a cycle of frailty following coronary artery bypass graft (CABG) and aortic valve replacement surgery. Prolonged hospitalization and lack of adequate physical stress led to the depletion of reserve in the cardiopulmonary, cognitive, musculoskeletal, and neuromuscular systems, leaving a previously independent adult fully dependent for mobility. Outcomes The patient participated in a twelve-week multicomponent physical therapy program in a skilled nursing facility. The exercise program was designed and administered to impact multiple systems and provide the necessary overload for adaptation. The patient demonstrated significant improvement in the Berg Balance Scale (BBS), Tinetti (POMA), Functional Outcome Scale (FOS), and returned to independent community ambulation.. Discussion The case illustrates the effectiveness of a multicomponent functional-based exercise program to improve markers of frailty and reverse functional decline in a frail older adult with acromegaly.The development of alternative approaches for safety and efficacy testing that avoid the use of animals is a worldwide trend, which relies on the improvement of current models and tools so that they better reproduce human biology. Human skin from elective plastic surgery is a promising experimental model to test the effects of topically applied products. As the structure of native skin is maintained, including cell population (keratinocytes, melanocytes, Langerhans cells and fibroblasts) and dermal matrix (containing collagen, elastin, glycosaminoglycans, etc.), it most closely matches the effects of substances on in vivo human skin. In this review, we present a collection of results that our group has generated over the last years, involving the use of human skin and scalp explants, demonstrating the feasibility of this model. The development of a test system with ex vivo skin explants, of standard size and thickness, and cultured at the air-liquid interface, can provide an important tool for understanding the mechanisms involved in several cutaneous disorders.Cyclophosphamide is associated with chemotherapy-related ovarian failure (CROF) in breast cancer survivors, however little is known about predicting individual risks. We sought to identify genetic alleles as biomarkers for risk of CROF after cyclophosphamide treatment. One hundred fifteen premenopausal women with newly diagnosed breast cancer were genotyped for single nucleotide polymorphisms (SNPs) in genes involved in cyclophosphamide activation (CYP3A4 and CYP2C19) and detoxification (GSTP1 and GSTA1). Patients prospectively completed menstrual diaries. With median follow up of 808 days, 28% experienced CROF. Survivors homozygous for the GSTA1 minor allele had lower hazards for developing CROF (HR 0.22 [95% CI 0.05-0.94], p=.04), while survivors homozygous for the CYP2C19 minor allele had higher hazards for developing CROF (HR 4.5 [95% CI 1.5-13.4], p=.007) compared to patients with at least one major allele. In separate multivariable models adjusting for age and tamoxifen use, the associations were no longer statistically significant (GSTA1 HR 0.
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