Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non‐SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3‐7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ²(1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.     

DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐value_pooled = 4 × 10^?17), cg03636183 in the F2RL3 gene (p‐value_pooled = 2 × 10 ^{? 13}), cg21566642 and cg05951221 in 2q37.1 (p‐value_pooled = 7 × 10^?16 and 1 × 10^?11 respectively), cg06126421 in 6p21.33 (p‐value_pooled = 2 × 10^?15) and cg23387569 in 12q14.1 (p‐value_pooled = 5 × 10^?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐values_{heterogeneity} ≤ 1.8 x10 ^{? 7}), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.     

Elucidating the associations between sleep disturbance and depression,fatigue, and pain in older adults with cancer

Objectives

Sleep disturbance is prevalent and often coexists with depression, fatigue, and pain in the cancer population. The aim of this study was to describe the prevalence of sleep disturbance with co-existing depression, fatigue, and pain in older patients with cancer. We also examined the associations of several socio-demographic and clinical variables with sleep disturbance.

Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.     

WIC Participants’ Perceptions of the Cash-Value Benefit Increase during the COVID-19 Pandemic

Recent changes to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Cash-Value Benefit (CVB), which provides participants with money to spend on fruits and vegetables, have the potential to reduce disparities in healthy food access and food insecurity that were exacerbated by the COVID-19 pandemic. However, few studies have examined how the changes to the CVB allotment that occurred during the pandemic influenced WIC participants’ perceptions of the benefit or their fruit and vegetable purchasing and consumption. To address this gap, we conducted semi-structured interviews with 51 WIC participants in Wilmington, Delaware. Survey measures included demographic questions, the Hunger Vital Sign food insecurity screener, and open-ended questions regarding perceptions of the CVB increase and its influence on participants’ fruit and vegetable purchasing and consumption. Data were analyzed using a hybrid inductive and deductive coding approach. The results demonstrate that higher CVB allotments increased WIC participants’ purchasing and consumption of fruits and vegetables, increased the frequency of their shopping occasions, and enhanced their dietary variety. Our findings also suggest that WIC participants highly value the increased CVB. Consequently, maintaining the increased CVB allotment could improve the nutritional outcomes of low-income mothers, infants, and children participating in WIC.     

High contrast,isotropic, and uniform 3D-imaging of centimeter-scale scattering samples using structured illumination light-sheet microscopy with axial sweeping

Light-sheet fluorescent microscopy (LSFM) has, in recent years, allowed for rapid 3D-imaging of cleared biomedical samples at larger and larger scale. However, even in cleared samples, multiple light scattering often degrades the imaging contrast and widens the optical sectioning. Accumulation of scattering intensifies these negative effects as light propagates inside the tissue, which accentuates the issues when imaging large samples. With axially swept light-sheet microscopy (ASLM), centimeter-scale samples can be scanned with a uniform micrometric optical sectioning. But to fully utilize these benefits for 3D-imaging in biomedical tissue samples, suppression of scattered light is needed. Here, we address this by merging ASLM with light-sheet based structured illumination into Structured Illumination Light-sheet Microscopy with Axial Sweeping (SILMAS). The SILMAS method thus enables high-contrast imaging, isotropic micrometric resolution and uniform optical sectioning in centimeter-scale scattering samples, creating isotropic 3D-volumes of e.g., whole mouse brains without the need for any computation-heavy post-processing. We demonstrate the effectiveness of the approach in agarose gel phantoms with fluorescent beads, and in an PFF injected alpha-synuclein transgenic mouse model tagged with a green fluorescent protein (SynGFP). SILMAS imaging is compared to standard ASLM imaging on the same samples and using the same optical setup, and is shown to increase contrast by as much as 370% and reduce widening of optical sectioning by 74%. With these results, we show that SILMAS improves upon the performance of current state-of-the-art light-sheet microscopes for large and imperfectly cleared tissue samples and is a valuable addition to the LSFM family.     

An Anterior Cruciate Ligament (ACL) Injury Risk Screening and Reduction Program for High School Female Athletes: A Pilot Study

BackgroundAnterior cruciate ligament (ACL) injury causes physical, mental, and financial burdens. Therefore, it is imperative to screen, identify, and educate athletes who are at high-risk. The combination of screening and education could identify those at risk and potentially reduce future injuries.PurposeThe purpose was to conduct a feasible community pre-season screening program for high school female athletes for the presence of known modifiable risk factors that predispose them to sustaining a non-contact ACL injury.Study DesignNon-experimental prospective studyMethodsA convenience sample of 15 healthy female athletes were recruited from local high schools, consisting of 11 soccer players and four basketball players.  A pre-season screening program was designed encompassing four stations that addressed modifiable neuromuscular and biomechanical risk factors including range of motion (ROM), jump-landing technique, strength, and balance. Athletes were categorized into high-risk versus low-risk groups based on cutoff scores previously established in the literature.ResultsEvery athlete met the high-risk cutoff score for at least one extremity during the ROM screening, and some met high-risk cutoff scores for more than one ROM. Out of all four categories tested, lower extremity ROM demonstrated the greatest deficits.ConclusionThis study identified athletes as having multiple modifiable risk factors that can be addressed with training and exercises. This supports implementing a pre-season program aimed at screening for injury risk factors.Level of EvidenceLevel 3