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Background Orthostatic intolerance occurs following immobilization in patients on Earth and in astronauts after spaceflight. Head‐down tilt bedrest is a terrestrial model for weightlessness and induces orthostatic intolerance. We hypothesized that lower‐body negative pressure (LBNP) or cycling followed by wearing venous constrictive thigh cuffs mitigates orthostatic intolerance after head‐down tilt bedrest. Methods and Results We enrolled 47 healthy individuals (20 women, 35±9 years) to a 30‐day strict head‐down tilt bedrest study. During bedrest, they were assigned to 6 hours of 25 mm Hg LBNP (n=12) per day and 1 hour of supine cycling followed by 6 hours of venous constriction through thigh cuffs 6 days per week (n=12), 6 hours of daily upright sitting (positive control, n=11), or no countermeasure (negative control, n=12). We measured orthostatic tolerance as the time to presyncope during 80° head‐up tilt testing with incremental LBNP before and immediately after bedrest. We determined plasma volume with carbon monoxide rebreathing before and at the end of bedrest. After bedrest, orthostatic tolerance decreased 540±457 seconds in the control group, 539±68 seconds in the cycling group, 217±379 seconds in the LBNP group, and 289±89 seconds in the seated group (P

Summary: Acetylcholine (ACh) is thought to play a role in driving the rapid, spontaneous brain-state transitions that occur during wakefulness; however, the spatiotemporal properties of cortical ACh activity during these state changes are still unclear. We perform simultaneous imaging of GRAB-ACh sensors, GCaMP-expressing basal forebrain axons, and behavior to address this question. We observed a high correlation between axon and GRAB-ACh activity around periods of locomotion and pupil dilation. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, and local ACh activity decreased at farther distances from an axon. Deconvolution of GRAB-ACh traces allowed us to account for sensor kinetics and emphasized rapid clearance of small ACh transients. We trained a model to predict ACh from pupil size and running speed, which generalized well to unseen data. These results contribute to a growing understanding of the precise timing and spatial characteristics of cortical ACh during fast brain-state transitions.

Abstract Agricultural producers adopt management practices that positively and negatively affect the lives of non-producers in their communities. CRB has important environmental and human health implications, and local non-producers might have different perceptions and attitudes from agricultural producers about crop residue burning. In this paper, we use a multi-stakeholder approach to study the issue of crop residue burning (CRB). Survey data were collected from a sample of producers in Arkansas who burn crop residue and a sample of non-producers who resided in the same counties as the producers. Non-producers may not be willing to compensate producers at an amount that would reduce the use of CBR. Non-producers do not fully understand some of the benefits of CRB, like reduced tillage or equipment savings cost, and producers are less likely to perceive increased greenhouse gas (GHG) emissions as a negative externality associated with CRB. A multi-stakeholder approach can provide more depth and breadth to understanding complex decisions about farm management practices, and these results have implications for policies that incentivize adopting best farm management practices.

The second Sustainable Development Goal of Zero Hunger, defined by the United Nations, broadly focuses on several dimensions of food access and availability, including measures of hunger and undernourishment, food insecurity, and malnutrition. Progress toward the Zero Hunger goal is monitored using indicators like the Prevalence of Undernourishment and the prevalence of moderate or severe food insecurity. These indicators are widely regarded as accurately portraying the underlying phenomena of concern. There are, however, other considerations one may want to include when considering the broader food system, including the role of food access and sovereignty in the rural areas of low-income countries. This paper reviews measurements of food insecurity and reflects on how food access and sovereignty may improve food security and, conversely, how it may impede advances toward alleviating food insecurity. These considerations can be helpful in tracking the need and progress toward the Sustainable Development Goal of Zero Hunger.

The highly structured nature of the SARS-CoV-2 genome provides many promising antiviral drug targets. One particularly promising target is a cis-acting RNA pseudoknot found within a critical region called the frameshifting stimulatory element (FSE). In this study, peptide nucleic acids (PNAs) binding to stem 2 of FSE RNA inhibited protein translation and frameshifting, as measured by a cell-free dual luciferase assay, more effectively than PNAs binding to stem 1, stem 3, or the slippery site. Surprisingly, simple antisense PNAs were stronger disruptors of frameshifting than PNA tail-clamps, despite higher thermal stability of the PNA-RNA-PNA triplexes formed by the latter. Another unexpected result was a strong and sequence non-specific enhancement of frameshifting inhibition when using a cationic triplex-forming PNA in conjunction with an antisense PNA targeting key regions of the frameshifting element. Our results illustrate both the potential and the challenges of using antisense PNAs to target highly structured RNAs, such as SARS-CoV-2 pseudoknots. While triplex forming PNAs, including PNA tail-clamps, are emerging as promising ligands for RNA recognition, the binding affinity enhancements when using cationic modifications in triplex-forming PNAs must be carefully balanced to avoid loss of sequence specificity in complex biological systems.

We experimentally study the statistics of the transition path time taken by a submicron bead to successfully traverse an energy barrier created by two optical tweezers in two prototypical viscoelastic fluids, namely, aqueous polymer and micellar solutions. We find a very good agreement between our experimental distributions and a theoretical expression derived from the generalized Langevin equation for the particle motion. Our results reveal that the mean transition path times measured in such viscoelastic fluids have a nontrivial dependence on the barrier curvature and they can be significantly reduced when compared with those determined in Newtonian fluids of the same zero-shear viscosity. We verify that the decrease of the mean transition path time can be described in terms of an effective viscosity that quantitatively coincides with that measured by linear microrheology at a frequency determined by the reactive mode that gives rise to the unstable motion over the barrier. Therefore our results uncover the linear response of the particle during its thermally activated escape from a metastable state even when taking place in a non-Markovian bath.

Plastics are very versatile materials that have contributed to the development of society since the 19th century; however, their mismanagement has led to an accumulation of plastic waste in almost every ecosystem, affecting the fauna of the planet. However, recently, some studies have shown that some insects might be able to adapt, consuming a wide range of hydrocarbon base polymers. In this work, the adaptive capacity of Zophobas morio larvae when feeding on different synthetic polymers derived from petroleum was studied. Four different thirty-day larval feeding treatments were carried out with synthetic polymers, including expanded polystyrene (PS), low-density polyethylene (LDPE), polyisoprene (PI), and butyl rubber (BR); in addition, a positive control of organic diet was included. Intestinal bacteria were isolated from the treatments and identified by Sanger sequencing. To analyze the chemical composition and physical form of the frass produced, Fourier transform infrared spectroscopy (FITR) was performed, and images of the feces’ surfaces were taken with scanning electron microscopy (SEM), respectively. Zophobas morio larvae were able to consume 54% of PS in 30 days, equivalent to 3.2 mg/d/larva. Nine culturable bacterial strains associated with the decomposition of synthetic polymers were identified in the intestine of the larvae. As for the physicochemical analysis of the feces, FTIR spectra showed the scission of bands corresponding to functional groups of the synthetic polymers in the comparison of the plastic diet treatments versus the feces of antibiotic-treated and plastic-fed larvae, while the comparison of spectra of the plastic and control treatments also identified differences in the absorption peaks. SEM imaging demonstrated that superworm feces differed in dependence on the substrate consumed. The findings demonstrated that Zophobas morio larvae possess a gut biological complex that allows them to feed and survive by consuming various petroleum-derived polymers.

Abstract Objectives This study aimed to assess the effectiveness of a continuous quality improvement initiative at the University of Florida Health Physicians practice in reducing the time to administer factor replacement therapy (FRT) for hemophilia patients presenting with bleeding in the emergency department (ED). Methods The study, a quasi‐experimental, interventional design, was conducted between January 2020 and January 2023. The intervention, implemented in September 2021, involved training ED physicians, creating a specialized medication order set within the electronic health record (EHR), and a rapid triage system. The effectiveness was measured by comparing the time from ED arrival to factor administration before and after the intervention and benchmarking it against the National Bleeding Disorders Foundation's Medical and Scientific Advisory Council (MASAC)‐recommended 1‐hour timeline for factor administration. An interrupted time series (ITS) analysis with a generalized least squares model assessed the intervention's impact. Results A total of 43 ED visits (22 pre‐intervention and 21 post‐intervention) were recorded. Post‐intervention, the average time from ED arrival to factor administration decreased from 5.63 to 3.15 hours. There was no significant increase (27% vs. 29%) in the patients receiving factor within 1‐hour of ED arrival. The ITS analysis predicted a 20‐hour reduction in the average quarterly time to administer factor by the end of the study, an 84% decrease. Conclusions The quality improvement program decreased the time to administer FRT for patients with hemophilia in the ED. However, the majority of patients did not achieve the 1‐hour MASAC‐recommended timeline for factor administration after ED arrival.

Summary: There is substantial evidence that neuromodulatory systems critically influence brain state dynamics; however, most work has been purely descriptive. Here, we quantify, using data combining local inactivation of the basal forebrain with simultaneous measurement of resting-state fMRI activity in the macaque, the causal role of long-range cholinergic input to the stabilization of brain states in the cerebral cortex. Local inactivation of the nucleus basalis of Meynert (nbM) leads to a decrease in the energy barriers required for an fMRI state transition in cortical ongoing activity. Moreover, the inactivation of particular nbM sub-regions predominantly affects information transfer in cortical regions known to receive direct anatomical projections. We demonstrate these results in a simple neurodynamical model of cholinergic impact on neuronal firing rates and slow hyperpolarizing adaptation currents. We conclude that the cholinergic system plays a critical role in stabilizing macroscale brain state dynamics.

The U.S. Food and Drug Administration (FDA) has proposed updates to the definition of “healthy,” including distinctions between types of sugar and fats and limits on added sugar, saturated fat, and sodium. To communicate the updated standards, the FDA is developing a Healthy symbol to display on food packages, which could reduce knowledge gaps by assisting U.S. consumers in meeting recommended nutritional guidelines. This study aimed to explore the potential for the label to increase consumers' ability to correctly identify a food product that met the FDA's criteria for a healthy symbol. To complete the study objective, 1018 adults were recruited to represent the U.S. population regarding gender, age, income, and geographic region, and a randomized group experiment was used to determine the potential communication value of an FDA Healthy symbol. Respondents were randomized to a group shown either a healthy yogurt with the FDA symbol, a healthy yogurt without the symbol, or an unhealthy yogurt. Respondents were then asked whether they considered the yogurt shown to be healthy, a question examining the desired criteria for the Healthy symbol, willingness to accept various costs to implement the symbol, and questions to measure objective dietary knowledge. Adding the symbol to yogurt that already met the healthy criteria only yielded about a 4 percentage point increase in the proportion of respondents identifying it as healthy. However, 53 % of participants still identified a yogurt too high in added sugars as healthy. For the desired label criteria, 64 % of respondents selected limits on added sugars, 57 % selected limits on sodium, and 54 % selected limits on saturated fats, which all align with the proposed updates to the definition of healthy. Over half of the participants supported the implementation of the label, even at a cost of $40 annually, and 86 % supported implementation at no cost.

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.

Abstract Background Exercise is an effective treatment for establishing and maintaining skeletal muscle health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to skeletal muscle health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human skeletal muscle cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for skeletal muscle atrophy. Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis. Results We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis and found that 21 genes were altered in response to formoterol, thus affecting related skeletal muscle pathways. Additionally, formoterol stimulation resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation. Robust, yet distinctive effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation occurred. For instance, MYF5 increased in D6 FORM compared to other groups (p

Abstract The human brain displays a rich repertoire of states that emerge from the microscopic interactions of cortical and subcortical neurons. Difficulties inherent within large-scale simultaneous neuronal recording limit our ability to link biophysical processes at the microscale to emergent macroscopic brain states. Here we introduce a microscale biophysical network model of layer-5 pyramidal neurons that display graded coarse-sampled dynamics matching those observed in macroscale electrophysiological recordings from macaques and humans. We invert our model to identify the neuronal spike and burst dynamics that differentiate unconscious, dreaming, and awake arousal states and provide insights into their functional signatures. We further show that neuromodulatory arousal can mediate different modes of neuronal dynamics around a low-dimensional energy landscape, which in turn changes the response of the model to external stimuli. Our results highlight the promise of multiscale modelling to bridge theories of consciousness across spatiotemporal scales.

A new monotypic genus of ichneumonine parasitoid wasps (Hymenoptera, Ichneumonidae, Ichneumoninae) is described from Peru; Capitojoppa gen. nov. is described to accommodate Capitojoppa amazonica sp. nov. The new genus is morphologically very distinctive and can be easily separated from all known ichneumonine genera. By describing Capitojoppa from the lowland rain forests of Peru, we aim to draw attention to the considerable diversity and morphological variation of the Amazonian ichneumonine fauna.

L10 FePd is increasingly recognized as a potential candidate for magnetic tunnel junctions (MTJs), yet there remains room for enhancing device performance. In this work, we fabricated fully-integrated L10 FePd-based perpendicular MTJ devices and achieved a significant increase in tunnel magnetoresistance, reaching ∼65%, compared to the previous record of 25%. Notably, we observed bi-directional switching with a low switching current density of about 1.4 × 105 A/cm2, which outperforms the typical spin-transfer torque (STT) MTJ by about one order of magnitude. We propose two possible mechanisms to elucidate the switching process and associated device performance: (1) The voltage-controlled exchange coupling-driven switching of the bottom CoFeB layer; (2) The STT-driven switching of the exchange-coupled L10 FePd–CoFeB composite. While additional research is necessary, these findings may further advance the integration of L10 FePd into spintronic devices, potentially enabling low-energy memory and logic technologies.

Introduction: Implementation of gene editing in agriculture and medicine hinges on public acceptance. The objectives of this study were to explore U.S. public opinion about gene editing in agricultural and medical fields and to provide more insight into the relationship between opinions about the safety of gene editing and the potential impact of evidence to improve opinions about safety.Methods: Data were from two samples of U.S. respondents: 1,442 respondents in 2021 and 3,125 respondents in 2022. Survey respondents provided their opinions about the safety of gene editing in the agricultural and medical fields and answered questions about the number of studies or length of time without a negative outcome to improve opinions about the safety of gene editing in the agricultural and medical fields.Results: Results indicated that respondents in both samples were more familiar, more likely to have an opinion about safety, and more positive about the safety of gene editing in the agricultural field than in the medical field. Also, familiarity was more closely associated with opinions about safety than the strength of opinions.Discussion: These findings add to the literature examining perceptions of gene editing in the agricultural or medical fields separately. Opinions about the safety of gene editing were generally more favorable for respondents who were aware of the use of gene editing. These results support a proactive approach for effective communication strategies to inform the public about the use of gene editing in the agricultural and medical fields.

Introduction: During early development in most male mammals the testes move from a position near the kidneys through the abdomen to eventually reside in the scrotum. The transabdominal phase of this migration is driven by insulin-like peptide 3 (INSL3) which stimulates growth of the gubernaculum, a key ligament connecting the testes with the abdominal wall. While all marsupials, except the marsupial mole (Notoryctes typhlops), have a scrotum and fully descended testes, it is unclear if INSL3 drives this process in marsupials especially given that marsupials have a different mechanism of scrotum determination and position relative to the phallus compared to eutherian mammals.Methods: To understand if INSL3 plays a role in marsupial testicular descent we have sequenced and curated the INSL3 gene and its receptor (RXFP2) in a range of marsupials representing every order. Furthermore, we looked at single cell RNA-seq and qPCR analysis of INSL3 in the fat-tailed dunnart testis (Sminthopsis crassicaudata) to understand the location and timing of expression during development.Results: These data show a strong phylogenetic similarity between marsupial and eutherian orthologues, but not with monotreme INSL3s which were more similar to the ancestral RLN3 gene. We have also shown the genomic location of INSL3, and surrounding genes is conserved in a range of marsupials and eutherians. Single cell RNA-seq and qPCR data show that INSL3 mRNA is expressed specifically in Leydig cells and expressed at higher levels during the testicular descent phase in developing marsupials.Discussion: Together, these data argue strongly for a therian origin of INSL3 mediated testicular descent in mammals and suggests that a coordinated movement of the testes to the abdominal wall may have preceded externalization in marsupials and therian mammals.

Pancreatic ductal adenocarcinoma (PDAC) presents at advanced stages and is refractory to most treatment modalities. Wnt signaling activation plays a critical role in proliferation and chemotherapeutic resistance. Minimal media conditions, growth factor dependency, and Wnt dependency were determined via Wnt inhibition for seven patient derived organoids (PDOs) derived from pancreatic tumor organoid libraries (PTOL). Organoids demonstrating response in vitro were assessed in vivo using patient-derived xenografts. Wnt (in)dependent gene signatures were identified for each organoid. Panc269 demonstrated a trend of reduced organoid growth when treated with ETC-159 in combination with paclitaxel or gemcitabine as compared with chemotherapy or ETC-159 alone. Panc320 demonstrated a more pronounced anti-proliferative effect in the combination of ETC-159 and paclitaxel but not with gemcitabine. Panc269 and Panc320 were implanted into nude mice and treated with ETC-159, paclitaxel, and gemcitabine as single agents and in combination. The combination of ETC-159 and paclitaxel demonstrated an anti-tumor effect greater than ETC-159 alone. Extent of combinatory treatment effect were observed to a lesser extent in the Panc320 xenograft. Wnt (in)dependent gene signatures of Panc269 and 320 were consistent with the phenotypes displayed. Gene expression of several key Wnt genes assessed via RT-PCR demonstrated notable fold change following treatment in vivo. Each pancreatic organoid demonstrated varied niche factor dependencies, providing an avenue for targeted therapy, supported through growth analysis following combinatory treatment of Wnt inhibitor and standard chemotherapy in vitro. The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.

Abstract Background To help ensure adequate hemostasis immediately following potassium titanyl phosphate (KTP) laser treatment, many centres treating hereditary hemorrhagic telangiectasia (HHT) routinely use nasal packing post‐operatively. The purpose of this study was to compare hemostatic thrombin matrix with standard packing for postoperative bleeding, patient pain, and comfort. Methods A prospective, randomized, double‐blinded, non‐inferiority study was conducted with participants at an HHT centre of excellence (COE) and randomized to the treatment group with reconstituted thrombin gelatin matrix (Surgiflo®) or control group with a biodegradable synthetic polyurethane foam (NasoPore®). Adult subjects with confirmed HHT and moderate to severe epistaxis (a minimum calculated epistaxis severity score [ESS] of 4.0) warranting KTP laser treatment were recruited. Data was collected 2 weeks post operatively by a blinded reviewer completing a visual outcomes evaluation and each patient completing a subjective symptoms questionnaire. Non‐parametric statistical analysis was employed. Results Twenty‐eight adult patients were randomized to the treatment and control arms with comparable preoperative epistaxis severity scores. Postoperative nasal bleeding was equivalent. Significantly less pain was found in the treatment arm (p = .005). While there were trends towards less obstruction and increased satisfaction in the treatment group as well as less crusting in the control group, these findings were not statistically significant. Allocation to the treatment group was associated with an approximately $75 higher cost. Conclusions When compared to NasoPore® for hemostasis, Surgiflo® hemostatic matrix performed equivalently while causing less discomfort in HHT patients following nasal KTP treatment. Level of evidence 1b.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants’ (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Objectives To compare the agreement between percentile ranks from 4 multi-morbidity scores. Design Population-based descriptive study. Setting Olmsted County, Minnesota (USA). Participants We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org ) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years). Methods For each person, we calculated 4 multi-morbidity scores using readily available diagnostic code lists from the US Department of Health and Human Services, the Clinical Classifications Software, and the Elixhauser Comorbidity Index. We calculated scores using diagnostic codes received in the 5 years before the index birthday and fit quantile regression models across age and separately by sex to transform unweighted, simple counts of conditions into percentile ranks as compared to peers of same age and of same sex. We compared the percentile ranks of the 4 multi-morbidity scores using intra-class correlation coefficients (ICCs). Results We assessed agreement in 181,553 persons who reached a total of 1,075,433 birthdays at ages 18 years through 85 years during the study period. In general, the percentile ranks of the 4 multi-morbidity scores exhibited high levels of agreement in 6 score-to-score pairwise comparisons. The agreement increased with older age for all pairwise comparisons, and ICCs were consistently greater than 0.65 at ages 50 years and older. Conclusions The assignment of percentile ranks may be a simple and intuitive way to assess the underlying trait of multi-morbidity across studies that use different measures.

Repeated stresses applied to the rider may contribute to the documented physical and psychosocial outcomes from equine-assisted services. In this brief review, a summary of neuroendocrine markers of stress, including immunoglobulin A, serotonin, cortisol, progesterone, and oxytocin, is presented within the context of the physiology of stress modulation. Results are mixed with regard to the effects of these hormones on rider physiology before, during, and after equine-assisted services. However, some results from existing studies are promising with regard to the attenuation of stress. Future research should include a cross-disciplinary approach when conducting well-controlled studies with proper treatment and experimental fidelity, while also considering exogenous and endogenous factors that influence rider physiology.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Stochastic computing (SC) has emerged as a promising solution for performing complex functions on large amounts of data to meet future computing demands. However, the hardware needed to generate random bit-streams using conventional CMOS-based technologies drastically increases the area and delay cost. Area costs can be reduced using spintronics-based random number generators (RNGs), and however, this will not alleviate the delay costs since stochastic bit generation is still performed separately from the computation. In this article, we present an SC method of embedding stochastic bit generation and processing in a computational random access memory (CRAM) array, which we refer to as SC-CRAM. We demonstrate that SC-CRAM is a resilient and low-cost method for image processing, Bayesian inference systems, and Bayesian belief networks.

Institutions of higher education have distanced themselves from teaching anything related to the sacred in architectural education. While the education of the architect has remained a critical focus for practitioners since Vitruvius, architecture’s historical ties to the sacred have been forgotten and dismissed. Many are beginning to realize the importance of this topic for contemporary architectural education. Architects have an ethical task of defending the authenticity of human experience as well as creating a beautiful world that uplifts the human spirit and nourishes cognitive, behavioral, and emotional health. As the co-founder of a new architecture program, I discuss both the practical and operational experiences of teaching and developing curricula with sacred pedagogy in mind. The paper also reviews “where” and “how” academic programs might attempt to deal with the sacred in curricular development. The success of any pedagogical intent will ultimately take years to manifest itself in the built works of students. Integrating the sacred into architectural education is critical for the profession because it helps future architects cultivate their empathic imagination, increase their compassion for the building user, and nourish their love for humanity.

Past research has shown that healthcare workers (HCWs) experience high levels of psychological distress during epidemics and pandemics, resulting in cascading effects that have led to chronically understaffed hospitals and healthcare centers. Due to the nature of their responsibilities and workplace stress, HCWs are among vulnerable groups especially during global health crises. During COVID-19 many healthcare workers reported greater symptoms of anxiety, depression, and COVID-19 related worries. Furthermore, adverse childhood experiences increase vulnerability for psychological conditions, especially during pandemics. This study sets out to (1) investigate the moderating effects of adverse childhood experiences on healthcare workers’ COVID-19 related stressors and depression/anxiety symptoms, and (2) investigate the moderating effects of adverse childhood experiences on proximity to the COVID-19 virus and depression/anxiety symptoms. Participants included 438 employed HCWs recruited from academic medical centers and smaller healthcare agencies in northcentral Florida between October to December 2020. Mean age of participants was 38.23 (SD = 11.5) with most of the HCWs being white (72.1%), non-Hispanic (86.8%) and female (82%). Healthcare workers completed several online questionnaires, including the Adverse Childhood Experiences scale, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, a COVID-19 specific worries scale, and a Social Proximity to COVID-19 scale. Healthcare workers experiencing specific COVID-19 worries reported experiencing anxiety and depressive symptoms. A significant positive interaction was seen between childhood adverse experiences globally and COVID-19 worries on anxiety symptoms. A significant positive interaction was observed between childhood maltreatment specifically and COVID-19 worries on depressive symptoms. Additionally, a positive interaction effect was seen between childhood adverse experiences and COVID-19 social proximity for both depression symptoms and anxiety symptoms. Findings from the present study indicate that adverse childhood experiences strengthen the relationship between COVID-19 worry/proximity and negative psychological symptoms. Vulnerable populations such as individuals who have experienced ACEs could benefit from targeted and specific interventions to cope with the collective trauma experienced globally due to COVID-19. As COVID-19 becomes endemic, hospital leadership and authorities should continue addressing COVID-19 worries and HCWs’ psychological symptoms through mental health support and organizational interventions.

IntoductionTo cross-validate skinfold (SKF) equations, impedance devices, and air-displacement plethysmography (ADP) for the determination of fat-free mass (FFM).MethodsMale and female youth athletes were evaluated (n = 91[mean ± SD] age: 18.19 ± 2.37 year; height: 172.1 ± 9.8 cm; body mass: 68.9 ± 14.5 kg; BMI: 23.15 ± 3.2 kg m−2; body fat: 19.59 ± 6.9%) using underwater weighing (UWW), ADP, and SKF assessments. A 3-compartment (3C) model (i.e., UWW and total body water) served as the criterion, and alternate body density (Db) estimates from ADP and multiple SKF equations were obtained. Validity metrics were examined to establish each method's performance. Bioelectrical impedance analysis (BIA), bioimpedance spectroscopy (BIS), and the SKF equations of Devrim-Lanpir, Durnin and Womersley, Jackson and Pollock (7-site), Katch, Loftin, Lohman, Slaughter, and Thorland differed from criterion.ResultsFor females, Pearson's correlations between the 3C model and alternate methods ranged from 0.51 to 0.92, the Lin's concordance correlation coefficient (CCC) ranged from 0.41 to 0.89, with standard error of the estimate (SEE) ranges of 1.9–4.6 kg. For SKF, the Evans 7-site and J&P 3 Site equations performed best with CCC and SEE values of 0.82, 2.01 kg and 0.78, 2.21 kg, respectively. For males, Pearson's correlations between the 3C model and alternate methods ranged from 0.50 to 0.95, CCC ranges of 0.46–0.94, and SEE ranges of 3.3–7.6 kg. For SKF, the Evans 3-site equation performed best with a mean difference of 1.8 (3.56) kg and a CCC of 0.93.DiscussionThe Evans 7-site and 3-site SKF equations performed best for female and male athletes, respectively. The field 3C model can provide an alternative measure of FFM when necessary.

Summary: The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of large-scale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.

Abstract Background The American College of Cardiology Core Cardiovascular Training Statement (COCATS) defined echocardiography core competencies and set the minimum recommend number of echocardiograms to perform (150) and interpret (300) for independent practice in echocardiography (level 2 training). Fellows may lack exposure to key pathologies that are relatively infrequent, however, even when achieving an adequate number of studies performed and interpreted. We hypothesized that cardiology fellows would lack exposure to 1 or more cardiac pathologies related to core competencies in COCATS when performing and interpreting the minimum recommend number of studies for level 2 training. Methods We retrospectively reviewed 11,250 reports from consecutive echocardiograms interpreted (7,500) and performed (3,750) by 25 cardiology fellows at a University tertiary referral hospital who graduated between 2015 and 2019. The first 300 echocardiograms interpreted and the first 150 echocardiograms performed by each fellow were included in the analysis. Echocardiography reports were reviewed for cardiac pathologies relating to core competencies defined in COCATS. Results All 25 fellows lacked exposure to 1 or more cardiac pathologies related to echocardiography core competencies despite meeting COCATS minimum recommended numbers for echocardiograms performed and interpreted. Pathologies for which 1 or more fellows encountered 0 cases despite meeting the minimum recommended numbers for both echocardiograms performed and interpreted included: pericardial constriction (16/25 fellows), aortic dissection (15/25 fellows), pericardial tamponade (4/25 fellows), valvular mass/thrombus (2/25 fellows), prosthetic valve dysfunction (1/25 fellows), and cardiac chamber mass/thrombus (1/25 fellows). Conclusions Cardiology fellows who completed the minimum recommend number of echocardiograms performed and interpreted for COCATS level 2 training frequently lacked exposure to cardiac pathologies, even in a University tertiary referral hospital setting. These data suggest that fellowship programs should monitor pathology case counts for each fellow in training, in addition to the minimum recommend number of echocardiograms defined by COCATS, to ensure competency for independent practice in echocardiography.

Modern computing schemes require large circuit areas and large energy consumption for neuromorphic computing applications, such as recognition, classification, and prediction. This is because these tasks require parallel processing on large datasets. Stochastic computing (SC) is a promising alternative to conventional binary computing schemes due to its low area cost, low processing power, and robustness to noise. However, the large area and energy costs for random number generation with CMOS-based circuits make SC impractical for most hardware implementations. For this reason, beyond-CMOS approaches to random number generation have been investigated in recent years. Spintronics is one of the most promising approaches due to the intrinsic stochasticity of the magnetic tunnel junction (MTJ). In this review article, we provide an overview of the literature published in recent years investigating the tunable, intrinsic stochasticity of MTJs and proposing practical methods for random number generation using spintronic hardware.

AbstractMost human neuroscience research to date has focused on statistical approaches that describe stationary patterns of localized neural activity or blood flow. While these patterns are often interpreted in light of dynamic, information-processing concepts, the static, local, and inferential nature of the statistical approach makes it challenging to directly link neuroimaging results to plausible underlying neural mechanisms. Here, we argue that dynamical systems theory provides the crucial mechanistic framework for characterizing both the brain’s time-varying quality and its partial stability in the face of perturbations, and hence, that this perspective can have a profound impact on the interpretation of human neuroimaging results and their relationship with behavior. After briefly reviewing some key terminology, we identify three key ways in which neuroimaging analyses can embrace a dynamical systems perspective: by shifting from a local to a more global perspective, by focusing on dynamics instead of static snapshots of neural activity, and by embracing modeling approaches that map neural dynamics using “forward” models. Through this approach, we envisage ample opportunities for neuroimaging researchers to enrich their understanding of the dynamic neural mechanisms that support a wide array of brain functions, both in health and in the setting of psychopathology.

Objectives Obesity is a potentially modifiable risk factor that has been consistently associated with the development and progression of multi-morbidity (MM). However, obesity may be more problematic for some persons compared to others because of interactions with other risk factors. Therefore, we studied the effect of interactions between patient characteristics and overweight and obesity on the rate of accumulation of MM. Methods We studied 4 cohorts of persons ages 20-, 40-, 60-, and 80-years residing in Olmsted County, Minnesota between 2005 and 2014 using the Rochester Epidemiology Project (REP) medical records-linkage system. Body mass index, sex, race, ethnicity, education, and smoking status were extracted from REP indices. The rate of accumulation of MM was calculated as the number of new chronic conditions accumulated per 10 person years through 2017. Poisson rate regression models were used to identify associations between characteristics and rate of MM accumulation. Additive interactions were summarized using relative excess risk due to interaction, attributable proportion of disease, and the synergy index. Results Greater than additive synergistic associations were observed between female sex and obesity in the 20- and 40-year cohorts, between low education and obesity in the 20-year cohort (both sexes), and between smoking and obesity in the 40-year cohort (both sexes). Conclusions Interventions targeted at women, persons with lower education, and smokers who also have obesity may result in the greatest reduction in the rate of MM accumulation. However, interventions may need to focus on persons prior to mid-life to have the greatest effect.

Background:. Three-dimensional imaging can be used to obtain objective assessments of facial morphology that is useful in a variety of clinical settings. The VECTRA H1 is unique in that it is relatively inexpensive, handheld, and does not require standardized environmental conditions for image capture. Although it provides accurate measurements when imaging relaxed facial expressions, the clinical evaluation of many disorders involves the assessment of facial morphology when performing facial movements. The aim of this study was to assess the accuracy and reliability of the VECTRA H1, specifically when imaging facial movement. Methods:. The accuracy, intrarater, and interrater reliability of the VECTRA H1 were assessed when imaging four facial expressions: eyebrow lift, smile, snarl, and lip pucker. Fourteen healthy adult subjects had the distances between 13 fiducial facial landmarks measured at rest and the terminal point of each of the four movements by digital caliper and by the VECTRA H1. Intraclass correlation and Bland–Altman limits of agreement were used to determine agreement between measures. The agreement between measurements obtained by five different reviewers was evaluated by intraclass correlation to determine interrater reliability. Results:. Median correlation between digital caliper and VECTRA H1 measurements ranged from 0.907 (snarl) to 0.921 (smile). Median correlation was very good for both intrarater (0.960–0.975) and interrater reliability (0.997–0.999). The mean absolute error between modalities, and both within and between raters was less than 2 mm for all movements tested. Conclusion:. The VECTRA H1 met acceptable standards for the assessment of facial morphology when imaging facial movements.

Abstract Background The CADILLAC risk score was developed to identify patients at low risk for adverse cardiovascular events following ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). Methods We performed a single center retrospective review of STEMI hospitalizations treated with PPCI from 2014 to 2018. Patients were stratified using the CADILLAC risk score into low risk, intermediate risk and high risk groups. Patients presenting with cardiac arrest or cardiogenic shock were excluded from the study. The primary outcome was adverse clinical events during initial hospitalization. Secondary outcomes were adverse clinical events at 30 days and 1 year following index hospitalization. Results The study included 341 patients. Compared to patients with a low CADILLAC score, adverse clinical events were similar in the intermediate risk group during hospitalization (OR 1.23, CI 0.37–4.05, p 0.733) and at 30 days (OR 2.27, CI 0.93–5.56, p 0.0733) while adverse clinical events were significantly elevated in the high risk group during hospitalization (OR 4.75, CI 1.91–11.84, p 0.0008) and at 30 days (OR 8.73, CI 4.02–18.96, p

Models of brain organisation can overlook the role of the autonomic nervous system in cognitive processes. Here the authors show a link between the ascending arousal system and both low dimensional neural dynamics and internal shifts in conscious awareness.

Abstract Background Mutations involving BRAF and TERT are important predictors of disease severity in thyroid cancer, but molecular testing is limited by cost and lack of adequate tissue sample. This study aimed to assess the utility of BRAFV600E and TERT testing using droplet digital PCR (ddPCR) as a diagnostic and prognostic tool for thyroid fine needle aspirate biopsy (FNAB). Methods Patients with thyroid nodules were prospectively enrolled from March 2015 to September 2018. Pre-operative FNAB was collected for standard cytology and molecular testing. BRAFV600E and TERT levels were analyzed by ddPCR. Cytology (Bethesda system) and ddPCR results were correlated to surgical pathology. Results A total of 222 patients were enrolled, of which 124 received thyroid surgery. Pre-operative cytology alone with Bethesda ≥5 was 100% specific and 70% sensitive for malignancy on final surgical pathology. BRAFV600E positivity or TERT overexpression was 100% specific and 60.0% sensitive. Combining cytology (Bethesda ≥5) with BRAFV600E and TERT testing increased the sensitivity of a malignant diagnosis to 80.0%. High TERT levels and/or BRAFV600E was associated with aggressive or advanced stage pathology. Conclusions Combining cytology with ddPCR analysis of BRAFV600E and TERT can improve the diagnostic accuracy of thyroid FNAB, and help predict aggressive pathology.

Neuroscience has had access to high-resolution recordings of large-scale cortical activity and structure for decades, but still lacks a generally adopted basis to analyze and interrelate results from different individuals and experiments. Here it is argued that the natural oscillatory modes of the cortex—cortical eigenmodes—provide a physically preferred framework for systematic comparisons across experimental conditions and imaging modalities. In this framework, eigenmodes are analogous to notes of a musical instrument, while commonly used statistical patterns parallel frequently played chords. This intuitive perspective avoids problems that often arise in neuroimaging analyses, and connects to underlying mechanisms of brain activity. We envisage this approach will lead to novel insights into whole-brain function, both in existing and prospective datasets, and facilitate a unification of empirical findings across presently disparate analysis paradigms and measurement modalities.

Our case report describes a man in his 6th decade of life who presented for difficulty hearing out of his left ear for the past three years, predominantly in loud settings. The patient denied vertigo, facial weakness, pain, blood, or drainage out of either ear. His past medical history was significant for hypertension and hyperlipidemia. Physical examination revealed a normal appearing left pinna and a soft erythematous cyst in the left external auditory canal (EAC) obscuring the left tympanic membrane (TM). The right ear, pinna, EAC, and TM all appeared normal. An audiogram of both ears showed conductive hearing loss on the left. CT scan of the left temporal bone showed a lobular lesion with a central hyperdensity arising from the anterior wall of the left EAC and extending into the EAC. Surgical excision of the mass revealed a large cyst originating in the superior ear canal and extending towards the TM. A second cyst was found and excised along the central part of the TM. Immunohistochemical staining of both cysts confirmed a paraganglioma of the EAC. The purpose of our report is to highlight a case of a rare site for a head and neck paraganglioma arising in the external auditory canal and causing hearing loss. We aimed to clarify the characteristics of glomus cell neoplasms to enable physicians to make a clinical diagnosis and initiate appropriate treatment.

Proper monitoring of fatigue and muscular damage may be used to decrease the high levels of cardiovascular disease, overuse musculoskeletal injuries, and workers compensation claims within the profession of firefighting. The purpose of this study was to examine muscle damage, muscular fatigue, and inflammation responses following a typical firefighting shift. Twenty-four professional firefighters completed two Physical Ability Tests to standardize the tasks typically performed in a day of work, and to elicit similar physiological responses. Participants were then monitored for 48 h. Prior to, and 48 h following the Physical Ability Tests, participants were evaluated for changes in strength, power, range-of-motion, as well as blood markers including myoglobin and c-reactive protein. Following the Physical Ability Tests, significant differences in myoglobin (p < 0.05), grip strength (p < 0.05), vertical jump (p < 0.05), and sit-and-reach (p < 0.05) were observed. No difference in c-reactive protein was observed (p > 0.05). After 24 hours following a shift, firefighters exhibited decreased strength, power, and range-of-motion. This may lead to decreases in performance and an increased risk of injury.

Abstract Background The Coronavirus disease of 2019 (COVID‐19) has impacted physician practices in many ways with some ENT clinics reporting around a 50% drop in completed scheduled ENT visits during the first wave of the pandemic compared to 2019. Aims This study surveyed first round PPP loan disbursement to otolaryngology practices in the United States in response to COVID‐19. Methods A cross‐sectional study was conducted using publicly available data published on PPP by the SBA. Otolaryngology clinics receiving loans greater than $0.15M were filtered using the following terms: “otolaryngology”, “otolaryngologist”,“sinus”, “head and neck”, “throat”, “ENT”, and “facial plastic”. 481 ENT clinics that received loans greater than $0.15 M from the Paycheck Protection Program (PPP) were identified. Loan amount, business type, geographicregion, owner race, owner gender, and the number of jobs per business were recorded for each clinic. Chi‐square analysis was performed to determine significance (P < 0.05) of each characteristic. Results Loan distribution was significantly different based on jobs reported (P

Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2?-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.

Astronauts suffer from a loss of bone mass at a rate of 1.5% per month from lower regions of the body during the course of long-duration (>30 days) spaceflight, a phenomenon that poses important risks for returning crew. Conversely, a gain in bone mass may occur in non-load bearing regions of the body as related to microgravity-induced cephalad fluid shift. Representing non-load bearing regions with mouse calvaria and leveraging the STS-131 (15-day) and BION-M1 (30-day) flights, we examined spatial and temporal calvarial vascular remodeling and gene expression related to microgravity exposure compared between spaceflight (SF) and ground control (GC) cohorts. We examined parasagittal capillary numbers and structures in calvaria from 16 to 23 week-old C57BL/6 female mice (GC, n = 4; SF, n = 5) from STS-131 and 19–20 week-old C57BL/6 male mice (GC, n = 6; SF, n = 6) from BION-M1 using a robust isolectin-IB4 vessel marker. We found that the vessel diameter reduces significantly in mice exposed to 15 days of spaceflight relative to control. Capillarization increases by 30% (SF vs. GC, p = 0.054) in SF mice compared to GC mice. The vessel numbers and diameter remain unchanged in BION-M1 mice calvarial section. We next analyzed the parietal pro-angiogenic (VEGFA) and pro-osteogenic gene (BMP-2, DMP1, RUNX2 and OCN) expression in BION-M1 mice using quantitative RT-PCR. VEGFA gene expression increased 15-fold while BMP-2 gene expression increased 11-fold in flight mice compared to GC. The linkage between vascular morphology and gene expression in the SF conditions suggests that angiogenesis may be important in the regulation of pathological bone growth in non-weight bearing regions of the body. Short-duration microgravity-mediated bone restructuring has implications in planning effective countermeasures for long-duration flights and extraterrestrial human habitation.

A principle of neuroanatomy, namely diffuse connectivity, is modeled using a large-scale network of corticothalamic neural masses. We demonstrate that increases in diffuse coupling transition the system through a quasi-critical regime, which coincides with known signatures of complex adaptive brain dynamics, and model fits to human imaging data orient task states to higher levels of diffusivity, consistent with the influence of arousal systems.

Abstract Women mobilize up to 10% of their bone mass during lactation to provide milk calcium. About 8%–13% of mothers use selective serotonin reuptake inhibitors (SSRI) to treat peripartum depression, but SSRIs independently decrease bone mass. Previously, peripartal use of the SSRI fluoxetine reduced maternal bone mass sustained post‐weaning and reduced offspring bone length. To determine whether these effects were fluoxetine‐specific or consistent across SSRI compounds, we examined maternal and offspring bone health using the most prescribed SSRI, sertraline. C57BL/6 mice were given 10 mg/kg/day sertraline, from the beginning of pregnancy through the end of lactation. Simultaneously, we treated nulliparous females on the same days as the primiparous groups, resulting in age‐matched nulliparous groups. Dams were euthanized at lactation day 10 (peak lactation, n = 7 vehicle; n = 9 sertraline), lactation day 21 (weaning, n = 9 vehicle; n = 9 sertraline), or 3m post‐weaning (n = 10 vehicle; n = 10 sertraline) for analysis. Offspring were euthanized at peak lactation or weaning for analysis. We determined that peripartum sertraline treatment decreased maternal circulating calcium concentrations across the treatment period, which was also seen in nulliparous treated females. Sertraline reduced the bone formation marker, procollagen 1 intact N‐terminal propeptide, and tended to reduce maternal BV/TV at 3m post‐weaning but did not impact maternal or offspring bone health otherwise. Similarly, sertraline did not reduce nulliparous female bone mass. However, sertraline reduced immunofluorescence staining of the tight junction protein, zona occludens in the mammary gland, and altered alveoli morphology, suggesting sertraline may accelerate mammary gland involution. These findings indicate that peripartum sertraline treatment may be a safer SSRI for maternal and offspring bone rather than fluoxetine.

Summary:. Necrotizing soft tissue infections (NSTIs) cause rapidly progressing destruction of skin and soft tissue, leaving large soft tissue defects and necessitating complex reconstruction. RECELL, an autologous cell harvesting device, provides a regenerative epidermal suspension (RES) from a small split-thickness skin biopsy for the substitution of (or in addition to) split-thickness skin grafting (STSG). We present a case of a 56-year-old man with extensive NSTI managed by serial debridement, leading to a degloving injury to the right upper extremity, axilla, flank and back, which was later reconstructed using RES application in conjunction with STSG and Integra placement. At his 2-week hospital follow-up, the patient was healing well with limited right upper extremity range of motion, but continued improvement seen with physical and occupational therapy. Due to the patient’s significant soft tissue defect, a unique reconstructive plan was required using both Integra and RECELL in conjunction with STSG. RECELL, in conjunction with STSG, should be considered for the treatment of significant soft tissue defects such as those found in NSTI.

Background. The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. Methods. Abdominal solid organs from SARS-CoV-2–infected donors were transplanted into uninfected recipients. Results. Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2–infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. Conclusions. Transplanting nonlung organs from SARS-CoV-2–infected donors into uninfected recipients demonstrated no evidence of virus transmission.