Pitfalls in interpreting red blood cell parameters in elite high-altitude and sea-level athletes:A unique case series

Standard routine hematological measurements are commonly used to investigate differences in blood parameters between high-altitude athletes (HAA) and sea-level athletes (SLA), and to monitor the effect of high-altitude training. In this way, red blood cell (RBC) parameters are usually expressed as relative parameters (concentration) rather than absolute parameters (total amount). In this unique case series of elite HAA and SLA, we describe how different ways of parameter expression can affect the interpretation of blood tests. In a group of 42 elite athletes, relative and absolute RBC parameters were compared between HAA and SLA. Absolute parameters were calculated by multiplying relative values with formula-based estimated blood volume (BV-e). Additionally, in two individual athletes, one HAA and one SLA, absolute parameters were also calculated with blood volume (BV) obtained by measurement with a dilution method (BV-m). In men, HAA had a significantly higher hemoglobin (Hb) concentration (+7.8%; p = 0.001) and total Hb mass per kg body weight (BW) (+12.0%; p = 0.002). When not corrected for BW, HAA had a lower, non-significant, total Hb mass (-7.8%; p = 0.055). In women, no significant differences between HLA and SLA were observed. The two individual athletes showed that, based on BV-m, in the HAA, total Hb mass and total Hb mass per kg BW were respectively 14.1 and 31.0% higher than in the SLA, whereas based on BV-e, in the HAA, total Hb mass was 20.8% lower and total Hb mass per kg BW was only 2.4% higher. Similar inconsistencies were observed for total RBC count. Thus, different ways of parameter expression, and different methods of BV assessment for the calculation of absolute parameter values, influence the interpretation of blood tests in athletes, which may lead to misinterpretation and incorrect conclusions

Mechanical design and development of TES bolometer detector arrays for the Advanced ACTPol experiment

The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling ~5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline profile leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes and Instrumentation conference proceeding

Impulse control disorders in Parkinson and RBD:a longitudinal study of severity.

Objective To describe the prevalence, natural history, and risk factors for impulse control behaviors (ICBs) among people with Parkinson disease (PD), those with REM sleep behavior disorder (RBD), and controls. Methods Participants with early PD (within 3.5 years of diagnosis), those with RBD, and controls were clinically phenotyped and screened for ICBs longitudinally (with the Questionnaire for Impulsivity in Parkinson's Disease). ICB-positive individuals were invited for a semistructured interview, repeated 1 year later. The severity of the ICB was assessed with the Parkinson's Impulse Control Scale. Multiple imputation and regression models were used to estimate ICB prevalence and associations. Results Data from 921 cases of PD at baseline, 768 cases at 18 months, and 531 cases at 36 months were included, with 21% to 25% screening positive for ICBs at each visit. Interviews of ICB screen–positive individuals revealed that 10% met formal criteria for impulse control disorders (ICD), while 33% had subsyndromal ICD (ICB symptoms without reaching the formal diagnostic criteria for ICD). When these data were combined through the use of multiple imputation, the prevalence of PD-ICB was estimated at 19.1% (95% confidence interval 10.1–28.2). On follow-up, 24% of cases of subsyndromal ICD had developed full symptoms of an ICD. PD-ICD was associated with dopamine agonist use, motor complications, and apathy but not PD-RBD. ICD prevalence in the RBD group (1%) was similar to that in controls (0.7%). Conclusions ICBs occur in 19.1% of patients with early PD, many persisting or worsening over time. RBD is not associated with increased ICD risk. Psychosocial drivers, including mood and support networks, affect severity

Predisposing factors for admission to intensive care units of patients with COVID-19 infection-Results of the German nationwide inpatient sample

BACKGROUND Intensive care units (ICU) capacities are one of the most critical determinants in health-care management of the COVID-19 pandemic. Therefore, we aimed to analyze the ICU-admission and case-fatality rate as well as characteristics and outcomes of patient admitted to ICU in order to identify predictors and associated conditions for worsening and case-fatality in this critical ill patient-group. METHODS We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January and December 2020. All hospitalized patients with confirmed COVID-19 infection during the year 2020 were included in the present study and were stratified according ICU-admission. RESULTS Overall, 176,137 hospitalizations of patients with COVID-19-infection (52.3% males; 53.6% aged ≥70 years) were reported in Germany during 2020. Among them, 27,053 (15.4%) were treated in ICU. COVID-19-patients treated on ICU were younger [70.0 (interquartile range (IQR) 59.0-79.0) vs. 72.0 (IQR 55.0-82.0) years, P < 0.001], more often males (66.3 vs. 48.8%, P < 0.001), had more frequently cardiovascular diseases (CVD) and cardiovascular risk-factors with increased in-hospital case-fatality (38.4 vs. 14.2%, P < 0.001). ICU-admission was independently associated with in-hospital death [OR 5.49 (95% CI 5.30-5.68), P < 0.001]. Male sex [OR 1.96 (95% CI 1.90-2.01), P < 0.001], obesity [OR 2.20 (95% CI 2.10-2.31), P < 0.001], diabetes mellitus [OR 1.48 (95% CI 1.44-1.53), P < 0.001], atrial fibrillation/flutter [OR 1.57 (95% CI 1.51-1.62), P < 0.001], and heart failure [OR 1.72 (95% CI 1.66-1.78), P < 0.001] were independently associated with ICU-admission. CONCLUSION During 2020, 15.4% of the hospitalized COVID-19-patients were treated on ICUs with high case-fatality. Male sex, CVD and cardiovascular risk-factors were independent risk-factors for ICU admission

Doublecortin expression in CD8+ T-cells and microglia at sites of amyloid-β plaques:A potential role in shaping plaque pathology?

Abstract INTRODUCTION: One characteristic of Alzheimer's disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells. METHODS: Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-β plaques in various transgenic amyloid mouse models and in human brains with plaque pathology. RESULTS: The plaque-associated DCX+ cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (ionized calcium-binding adapter molecule 1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX+ cells was negative for ionized calcium-binding adapter molecule 1 but was highly positive for the pan-leukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells. DISCUSSION: Peculiarly, the DCX+/ionized calcium-binding adapter molecule 1+ microglia and DCX+/CD8+ T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology

Exploring variability in basal ganglia connectivity with functional MRI in healthy aging.

Changes in functional connectivity (FC) measured using resting state fMRI within the basal ganglia network (BGN) have been observed in pathologies with altered neurotransmitter systems and conditions involving motor control and dopaminergic processes. However, less is known about non-disease factors affecting FC in the BGN. The aim of this study was to examine associations of FC within the BGN with dopaminergic processes in healthy older adults. We explored the relationship between FC in the BGN and variables related to demographics, impulsive behavior, self-paced tasks, mood, and motor correlates in 486 participants in the Whitehall-II imaging sub-study using both region-of-interest- and voxel-based approaches. Age was the only correlate of FC in the BGN that was consistently significant with both analyses. The observed adverse effect of aging on FC may relate to alterations of the dopaminergic system, but no unique dopamine-related function seemed to have a link with FC beyond those detectable in and linearly correlated with healthy aging

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo

The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC_(80) value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics