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SARS-CoV-2 mainly infects the respiratory tract but can also target other organs, including the central nervous system. While it was recently shown that cells of the blood-brain-barrier are permissive to SARS-CoV-2 infection in vitro, it remains debated whether neurons can be infected. In this study, we demonstrate that vesicular stomatitis virus particles pseudotyped with the spike protein of SARS-CoV-2 variants WT, Alpha, Delta and Omicron enter the neuronal model cell line SH-SY5Y. Cell biological analyses of the pseudo-virus treated cultures showed marked alterations in microtubules of SH-SY5Y cells. Because the changes in β-tubulin occurred in most cells, but only few were infected, we further asked whether interaction of the cells with spike protein might be sufficient to cause molecular and structural changes. For this, SH-SY5Y cells were incubated with trimeric spike proteins for time intervals of up to 24 h. CellProfiler™-based image analyses revealed changes in the intensities of microtubule staining in spike protein-incubated cells. Furthermore, expression of the spike protein-processing protease cathepsin L was found to be up-regulated by wild type, Alpha and Delta spike protein pseudotypes and cathepsin L was found to be secreted from spike protein-treated cells. We conclude that the mere interaction of the SARS-CoV-2 with neuronal cells can affect cellular architecture and proteolytic capacities. The molecular mechanisms underlying SARS-CoV-2 spike protein induced cytoskeletal changes in neuronal cells remain elusive and require future studies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Medical students report low confidence in their ability to perform pelvic exams. Pelvic exams under anesthesia (EUA) are one way for students to practice the exam, but this needs to be balanced with patients' bodily autonomy through explicit disclosure and consent. This study seeks to characterize U.S. medical schools' policies regarding the consent process for students to perform pelvic EUA. Materials and Methods: Obstetrics and gynecology clerkship directors were anonymously surveyed about their medical school affiliated hospitals' (MSAH) consent policies for pelvic EUA in general and explicitly for medical students. Chi-square and Fisher's exact test were used to test for differences between categorical variables and thematic analysis was used to review qualitative responses. Results: A total of 87 clerkship directors completed the survey (44.4% response rate). Most MSAH explicitly consent patients for pelvic EUA (80.2%), and specifically for performance by medical students (79.1%). Sixty-nine respondents (79.3%) stated that performing pelvic EUA is important for medical student education. Five themes were identified from review of qualitative responses, including consent policy details, the importance of pelvic EUA, other opportunities for pelvic exam teaching, barriers to standardization, and outside guidance. Conclusions: The pelvic EUA is a necessary part of both surgical care and medical education but patient dignity must be protected too. Most MSAH have consent policies for students to perform pelvic EUA. Still, these policies need to be further strengthened and standardized across institutions to protect patients' rights while continuing to teach students the pelvic exam.

Introduction: Approximately 1.6 million people in the US identify as transgender, many of whom undergo gender-affirming medical or surgical therapies. While transgender individuals are diagnosed with cancer at similar rates as those who are cisgender, the impacts of radiation therapy on outcomes of gender-affirming care in transgender, nonbinary, and gender-expansive people with cancer are understudied. We report on the experiences and outcomes of transgender and gender-expansive patients receiving radiation therapy for cancer treatment., Methods: This study is a multi-institutional retrospective review of patients evaluated from 2005-2019 identified as transgender or gender-expansive in the medical record and treated with radiation therapy., Results: We identified 23 patients who received radiation to 32 sites, including 12 (38%) to the brain, head, or neck, 8 (25%) to the thorax, and 7 (22%) to the pelvis. Seventeen patients (74%) received gender-affirming hormone therapy and 13 patients (57%) underwent gender-affirming surgery. Four patients had pelvic radiation before or after gender-affirming pelvic surgery, including two trans women who had pelvic radiation after vaginoplasty. Four patients had radiation to the chest or thorax and gender-affirming chest or breast surgery, including two trans men with breast cancer. Two pediatric patients developed hypopituitarism and hypogonadism secondary to radiation therapy and, as adults, changed their hormone replacement therapy to affirm their transgender identities., Discussion: Transgender people with cancer undergo radiation therapy for a wide range of cancers. Understanding their prior gender-affirming medical or surgical treatments and future gender affirmation goals may identify important considerations for their oncologic care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mansur, Kempf, Bitterman, Patel, Dyer, Haas-Kogan, Liu and Smart.)

Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan interactions. We hypothesize that polyvalent nano-lectins with flexibly linked carbohydrate recognition domains (CRDs) can adjust their relative positions and bind multivalently to S protein glycans, potentially exerting potent antiviral activity. Herein, we displayed the CRDs of DC-SIGN, a dendritic cell lectin known to bind to diverse viruses, polyvalently onto 13 nm gold nanoparticles (named G13-CRD). G13-CRD bound strongly and specifically to target glycan-coated quantum dots with sub-nM K d . Moreover, G13-CRD neutralized particles pseudotyped with the S proteins of Wuhan Hu-1, B.1, Delta variant and Omicron subvariant BA.1 with low nM EC 50 . In contrast, natural tetrameric DC-SIGN and its G13 conjugate were ineffective. Further, G13-CRD potently inhibited authentic SARS-CoV-2 B.1 and BA.1, with <10 pM and <10 nM EC 50 , respectively. These results identify G13-CRD as the 1st polyvalent nano-lectin with broad activity against SARS-CoV-2 variants that merits further exploration as a novel approach to antiviral therapy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells, and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts as to whether TMPRSS2 inhibitors would be suitable for the treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to the spread of SARS-CoV-2 in the infected host is largely unclear. In this study, we show that the loss of TMPRSS2 strongly reduced the replication of the Beta variant in the nose, trachea and lung of C57BL/6 mice, and protected the animals from weight loss and disease. The infection of mice with the Omicron variant did not cause disease, as expected, but again, TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify the key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection, and highlight TMPRSS2 as an attractive target for antiviral intervention.

Although aluminium acetylacetonate, Al(C5H7O2)3, is a common precursor for chemical vapor deposition (CVD) of aluminium oxide, its gas-phase decomposition is not well-known. Here, we studied its thermal decomposition in a microreactor by double imaging photoelectron photoion coincidence spectroscopy (i2PEPICO) between 325 and 1273 K. The reactor flow field was characterized by CFD. Quantum chemical calculations were used for the assignment of certain species. The dissociative ionization of the room temperature precursor molecule starts at a photon energy of 8.5 eV by the rupture of the bond to an acetylacetonate ligand leading to the formation of the Al(C5H7O2)2+ ion. In pyrolysis experiments, up to 49 species were detected and identified in the gas-phase, including reactive intermediates and isomeric/isobaric hydrocarbons, oxygenated species as well as aluminium containing molecules. We detected aluminium bis(diketo)acetylacetonate-H, Al(C5H7O2)C5H6O2, at m/z 224 together with acetylacetone (C5H8O2) as the major initial products formed at temperatures above 600 K. A second decomposition channel affords Al(OH)2(C5H7O2) along with the formation of a substituted pentalene ring species (C10H12O2) as assigned by Franck-Condon simulations and quantum chemical calculations. Acetylallene (C5H6O), acetone (C3H6O) and ketene (C2H2O) were major secondary decomposition products, formed upon decomposition of the primary products. Three gas-phase aromatic hydrocarbons were also detected and partially assigned for the first time: m/z 210, m/z 186 (C14H18 or C12H10O2) and m/z 146 (C11H14 or C9H6O2) and their formation mechanism is discussed. Finally, Arrhenius parameters are presented on the gas-phase decomposition kinetics of Al(C5H7O2)3, aided by numerical simulation of the flow field.

This paper presents an optical diagnostic technique based on seeded thermographic phosphor particles, which allows the simultaneous two-dimensional measurement of gas temperature, velocity and mixture fraction in turbulent flows. The particle Mie scattering signal is recorded to determine the velocity using a conventional PIV approach and the phosphorescence emission is detected to determine the tracer temperature using a two-color method. Theoretical models presented in this work show that the temperature of small tracer particles matches the gas temperature. In addition, by seeding phosphorescent particles to one stream and non-luminescent particles to the other stream, the mixture fraction can also be determined using the phosphorescence emission intensity after conditioning for temperature. The experimental technique is described in detail and a suitable phosphor is identified based on spectroscopic investigations. The joint diagnostics are demonstrated by simultaneously measuring temperature, velocity and mixture fraction in a turbulent jet heated up to 700 K. Correlated single shots are presented with a precision of 2 to 5% and an accuracy of 2%.

Telephone surveys are critical for examining cross-sectional characteristics of population subgroups, tracking trends in prevalence of conditions and risk behaviors over time, identifying risk factors associated with multiple health conditions, and assessing the effects of interventions. Technology has aided telephone research through advances such as computer-assisted telephone interviewing. However, technology such as answering machines and caller ID has contributed to declines in response rates and has increased costs of conducting telephone surveys. The exponential increase in cell phone utilization presents a challenge to the tradition of random digit dial (RDD) surveys of households. Because telephone surveys are used by other industries such as marketing and public opinion polling, the marketplace may help drive innovation and adaptation. Cell phones have made telephone communication an even greater part of the everyday culture and could make potential telephone survey respondents even more accessible to public health researchers.

Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin was strongly correlated with total fat mass (r = .67, p <.001), percentage body fat (r= .81, p < .001), and to a lesser degree Body Mass Index, or BMI, (r = .23, p < .02). Leptin was associated with fasting insulin (beta+/-SE = 0.30+/-0.06, p < .001) and insulin resistance (beta+/-SE = 0.41+/-0.20, p < .001) independent of total fat, gender, and age, suggesting other mechanisms of leptin and insulin regulation besides obesity. Leptin resistance is present even among young and normal-weight college students. Leptin, even more so than BMI, is an important marker of adiposity and hyperinsulinemia in normal-weight college students and may potentially be used to predict type 2 diabetes.