Glycemic Benefits with Adherence to testosterone therapy in men with hypogonadism and type 2 diabetes mellitus.

BACKGROUND: While previous studies have demonstrated testosterone\u27s beneficial effects on glycemic control in men with hypogonadism and Type 2 Diabetes, the extent to which these improvements are observed based on the degree of treatment adherence has been unclear. OBJECTIVES: To evaluate the effects of long-term testosterone therapy in A1C levels in men with Type 2 Diabetes Mellitus and hypogonadism, controlling for BMI, pre-treatment A1C, and age among different testosterone therapy adherence groups. MATERIALS AND METHODS: We performed a retrospective analysis of 1737 men with diabetes and hypogonadism on testosterone therapy for 5 years of data from 2008-2018, isolating A1C, lipid panels, and BMI results for analysis. Subjects were categorized into adherence groups based on quartiles of the proportion of days covered (\u3e 75% of days, 51-75% of days, 26-50% of days and 0-25% of days), with \u3e75% of days covered considered adherent to therapy. RESULTS: Pre-treatment median A1C was 6.8%. Post-treatment median A1C was 7.1%. The adherent group, \u3e75%, was the only group notable for a decrease in A1C, with a median decrease of -0.2 (p = 0.0022). BMI improvement was associated with improved post-treatment A1C (p = 0.007). When controlling for BMI, age, and pre-treatment A1C, the \u3e75% adherence group was associated with improved post-treatment A1C (p \u3c 0.001). DISCUSSION: When controlling for all studied variables, testosterone adherence was associated with improved post-treatment A1C. The higher the initial A1C at the initiation of therapy, the higher the potential for lowering the patient\u27s A1C with \u3e75% adherence. Further, all groups showed some reduction in BMI, which may indicate that testosterone therapy may affect A1C independent of weight loss. CONCLUSION: Even when controlling for improved BMI, pre-treatment A1C, and age, testosterone positively impacted glycemic control in diabetes patients with hypogonadism, with the most benefit noted in those most adherent to therapy (\u3e75%)

Cesium and Strontium Contamination of Nuclear Plant Stainless Steel : Implications for Decommissioning and Waste Minimization

Stainless steels can become contaminated with radionuclides at nuclear sites. Their disposal as radioactive waste would be costly. If the nature of steel contamination could be understood, effective decontamination strategies could be designed and implemented during nuclear site decommissioning in an effort to release the steels from regulatory control. Here, batch uptake experiments have been used to understand Sr and Cs (fission product radionuclides) uptake onto AISI Type 304 stainless steel under conditions representative of spent nuclear fuel storage (alkaline ponds) and PUREX nuclear fuel reprocessing (HNO3). Solution (ICP-MS) and surface measurements (GD-OES depth profiling, TOF-SIMS, and XPS) and kinetic modeling of Sr and Cs removal from solution were used to characterize their uptake onto the steel and define the chemical composition and structure of the passive layer formed on the steel surfaces. Under passivating conditions (when the steel was exposed to solutions representative of alkaline ponds and 3 and 6 M HNO3), Sr and Cs were maintained at the steel surface by sorption/selective incorporation into the Cr-rich passive film. In 12 M HNO3, corrosion and severe intergranular attack led to Sr diffusion into the passive layer and steel bulk. In HNO3, Sr and Cs accumulation was also commensurate with corrosion product (Fe and Cr) readsorption, and in the 12 M HNO3 system, XPS documented the presence of Sr and Cs chromates.Peer reviewe

Nanorheology of viscoelastic shells: Applications to viral capsids

We study the microrheology of nanoparticle shells [Dinsmore et al. Science 298, 1006 (2002)] and viral capsids [Ivanovska et al. PNAS 101, 7600 (2004)] by computing the mechanical response function and thermal fluctuation spectrum of a viscoelastic spherical shell that is permeable to the surrounding solvent. We determine analytically the damped dynamics of the shear, bend, and compression modes of the shell coupled to the solvent both inside and outside the sphere in the zero Reynolds number limit. We identify fundamental length and time scales in the system, and compute the thermal correlation function of displacements of antipodal points on the sphere and the mechanical response to pinching forces applied at these points. We describe how such a frequency-dependent antipodal correlation and/or response function, which should be measurable in new AFM-based microrheology experiments, can probe the viscoelasticity of these synthetic and biological shells constructed of nanoparticles.Comment: 17 page

Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease: A Systematic Review

RATIONALE: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis in response to an inhalational exposure. OBJECTIVE: To determine the value of bronchoalveolar lavage (BAL) fluid lymphocyte cellular analysis in the detection of HP among patients with newly detected ILD. METHODS: This systematic review was undertaken in the context of development of an American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT) clinical practice guideline. The clinical question was, should patients with newly detected ILD undergo BAL fluid lymphocyte analysis to diagnose HP? Medline, Embase, and grey literature were searched through October 2019. Studies that reported the percentage of BAL fluid lymphocytes for various ILDs were selected for inclusion. Meta-analyses compared the mean percentage of BAL fluid lymphocytes among patients with HP to that among patients with Idiopathic Pulmonary Fibrosis (IPF) or sarcoidosis. The sensitivity and specificity by which various percentages of BAL fluid lymphocytes distinguish HP from IPF and sarcoidosis were also evaluated. RESULTS: Eighty-four articles were selected. No randomized trials or observational studies were identified that compared BAL fluid lymphocyte analysis to no BAL fluid lymphocyte analysis in patients with ILD. Included studies were case series describing BAL fluid cell differentials in patients with various ILDs. The percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to IPF. Similarly, the percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to sarcoidosis. A threshold of 20% BAL fluid lymphocytes distinguished fibrotic HP from IPF with a sensitivity and specificity of 69% and 61% respectively, and nonfibrotic HP from IPF with a sensitivity and specificity of 95% and 61% respectively. It distinguished fibrotic HP from sarcoidosis with a sensitivity and specificity of 69% and 26% respectively, and nonfibrotic HP from sarcoidosis with a sensitivity and specificity of 95% and 26% respectively. CONCLUSION: The percentage of BAL fluid lymphocytes is higher in HP than IPF or sarcoidosis. However, a threshold that distinguishes HP from IPF or sarcoidosis with both high sensitivity and high specificity was not identified

Patient-related outcomes in patients referred to a respiratory clinic with persisting symptoms following non-hospitalised COVID-19

Survivors of COVID-19 can present with varied and persisting symptoms, regardless of hospitalisation. We describe the ongoing symptoms, quality of life and return to work status in a cohort of non-hospitalised COVID-19 survivors with persisting respiratory symptoms presenting to clinic, who consented and completed patient-reported outcome measures. We identified fatigue, reduced quality of life and dysregulated breathing alongside the breathlessness. Those with co-existent fatigue had worse mood and quality of life and were less likely to have returned to normal working arrangements compared to those without fatigue. For non-hospitalised people with persisting symptoms following COVID-19 referred to a respiratory assessment clinic, there was a need for a wider holistic assessment, including return to work strategies

Patient-reported respiratory outcome measures in the recovery of adults hospitalised with COVID-19: A systematic review and meta-analysis

Background Acute COVID-19 clinical symptoms have been clearly documented, but long-term functional and symptomatic recovery from COVID -19 is less well described.Methods A systematic review and meta-analysis were conducted to describe patient-reported outcome measures (PROMs) in adults at least 8 weeks post hospital discharge for COVID-19. Comprehensive database searches in accordance with the PRISMA statement were carried out up till 31/05/2021. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method.Results From 49 studies, across 14 countries with between 2-12 months follow up, the most common persisting symptom reported was fatigue with meta-analysis finding 36.6% (95 % CI 27.6 to 46.6, n=14) reporting it at 2-4 months, decreasing slightly to 32.5% still reporting it at >4 months (95% CI 22.6 to 44.2, n=15). This was followed by dyspnoea. Modified MRC score (mMRC) ≥1 was reported in 48% (95% CI 30 to 37, n=5) at 2-4months reducing to 32% (95% CI 22 to 43, n=7) at 4 months. Quality of life (QOL) as assessed by the EQ-5D-5L VAS remained reduced at >4 months (73.6 95% CI 68.1 to 79.1, n=6). Hospitalisation with COVID-19 also resulted in persisting sick leave, change in scope of work, and continued use of primary and secondary healthcare.Conclusion The symptomatic and functional impact of COVID-19 continues to be felt by patients months after discharge from hospital. This widespread morbidity points towards a multi-disciplinary approach to aid functional recovery

Injury, Interiority, and Isolation in Men’s Suicidality

Men’s high suicide rates have been linked to individual risk factors including history of being abused as a child, single marital status, and financial difficulties. While it has also been suggested that the normative influences of hegemonic masculinities are implicated in men’s suicide, the gendered experiences of male suicidality are poorly understood. In the current photovoice study, 20 men who previously had suicidal thoughts, plans, and/or attempts were interviewed as a means to better understanding the connections between masculinities and their experiences of suicidality. The study findings revealed injury, interiority, and isolation as interconnected themes characterizing men’s suicidality. Injury comprised an array of childhood and/or cumulative traumas that fueled men’s ruminating thoughts inhibiting recovery and limiting hopes for improved life quality. In attempting to blunt these traumas, many men described self-injuring through the overuse of alcohol and other drugs. The interiority theme revealed how suicidal thoughts can fuel hopelessness amid summonsing remedies from within. The challenges to self-manage, especially when experiencing muddled thinking and negative thought were evident, and led some participants to summons exterior resources to counter suicidality. Isolation included separateness from others, and was linked to abandonment issues and not having a job and/or partner. Self-isolating also featured as a protection strategy to avoid troubling others and/or reducing exposure to additional noxious stimuli. The study findings suggest multiple intervention points and strategies, the majority of which are premised on promoting men’s social connectedness. The destigmatizing value of photovoice methods is also discussed

ColdZyme® Mouth Spray reduces duration of upper respiratory tract infection symptoms in endurance athletes under free living conditions

Upper respiratory tract infection (URTI) can compromise athlete preparation and performance, so countermeasures are desirable. The aim of this study was to assess the effects of ColdZyme® Mouth Spray (ColdZyme) on self-reported upper respiratory tract infection in competitive endurance athletes under free-living conditions. One hundred and twenty-three endurance-trained, competitive athletes (recruited across 4 sites in England, UK) were randomised to control (no treatment, n = 61) or ColdZyme (n = 62) for a 3-month study period (between December 2017 – February 2018; or December 2018 – April 2019). They recorded daily training and illness symptoms (Jackson common cold questionnaire) during the study period. A total of 130 illness episodes were reported during the study with no difference in incidence between groups (episodes per person: 1.1 ± 0.9 Control, 1.0 ± 0.8 ColdZyme, P = 0.290). Episode duration was significantly shorter in ColdZyme compared to Control: Control 10.4 ± 8.5 days vs ColdZyme 7.7 ± 4.0 days, P = 0.016). Further analysis to compare episodes with poor vs good compliance with ColdZyme instructions for use (IFU) within the ColdZyme group showed a further reduction in duration of URTI when compliance was good (9.3 ± 4.5 days in ColdZyme poor IFU compliance vs 6.9 ± 3.5 days in ColdZyme good IFU compliance, P = 0.040). ColdZyme may be an effective countermeasure to reduce URTI duration, which was significantly lower (by 26-34%) in the ColdZyme treatment group (with no influence on incidence). This may have implications for athlete performance

Synaptotagmin‐7 enhances calcium‐sensing of chromaffin cell granules and slows discharge of granule cargos

Synaptotagmin‐7 (Syt‐7) is one of two major calcium sensors for exocytosis in adrenal chromaffin cells, the other being synaptotagmin‐1 (Syt‐1). Despite a broad appreciation for the importance of Syt‐7, questions remain as to its localization, function in mediating discharge of dense core granule cargos, and role in triggering release in response to physiological stimulation. These questions were addressed using two distinct experimental preparations—mouse chromaffin cells lacking endogenous Syt‐7 (KO cells) and a reconstituted system employing cell‐derived granules expressing either Syt‐7 or Syt‐1. First, using immunofluorescence imaging and subcellular fractionation, it is shown that Syt‐7 is widely distributed in organelles, including dense core granules. Total internal reflection fluorescence (TIRF) imaging demonstrates that the kinetics and probability of granule fusion in Syt‐7 KO cells stimulated by a native secretagogue, acetylcholine, are markedly lower than in WT cells. When fusion is observed, fluorescent cargo proteins are discharged more rapidly when only Syt‐1 is available to facilitate release. To determine the extent to which the aforementioned results are attributable purely to Syt‐7, granules expressing only Syt‐7 or Syt‐1 were triggered to fuse on planar supported bilayers bearing plasma membrane SNARE proteins. Here, as in cells, Syt‐7 confers substantially greater calcium sensitivity to granule fusion than Syt‐1 and slows the rate at which cargos are released. Overall, this study demonstrates that by virtue of its high affinity for calcium and effects on fusion pore expansion, Syt‐7 plays a central role in regulating secretory output from adrenal chromaffin cells.Syt‐7 is a high‐affinity calcium sensor expressed on chromaffin cell dense core granules. The purpose of this study was to assess the role of Syt‐7 in regulating the secretory response to cholinergic stimulation. Acetylcholine elicits secretion by elevating cytosolic calcium. The calcium sensitivity of exocytosis in cells lacking Syt‐7 is impaired. Cells that lack Syt‐7 also release peptide hormones at faster rates, implicating a role for Syt‐7 in regulating the exocytotic fusion pore. These data demonstrate that Syt‐7 has an important role in triggering exocytosis in cells and is likely to play a role in controlling hormone output, in situ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/3/jnc14986.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/2/jnc14986-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162737/1/jnc14986_am.pd