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Abstract Background The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer’s disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD. Results Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits. Conclusions Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use. Graphical abstract

Abstract Background To evaluate the predictive value of individual components of the R.E.N.A.L scoring system for Laparoscopic (LPN) and Robotic Partial Nephrectomy (RPN). Methods Patients that had undergone a Laparoscopic (LPN) or Robotic Partial Nephrectomy (RPN) between 2018 and 2023 were reviewed. Our data collection included Race, Ethnicity, Age, BMI, R.E.N.A.L nephrometry score, and complications. Cases that achieved trifecta outcomes were designated as “Group A” and cases that did not achieve trifecta were “Group B”. All the data were collected using REDCap database. Results A total of 111 cases were included, Group A consisted of 82% of all cases, whereas Group B 18%. Radius score demonstrated significant distinction concerning trifecta attainment and was the most predictive component of the 5 scoring metrics of the nephrometry system. In a subgroup analysis, R-score of 3 or a renal mass measuring ≥ 7 cm, was a significant independent negative predictor for trifecta outcomes, as well as tumor size at presentation. Conclusion Renal nephrometry score is predictive of trifecta outcomes for patients undergoing laparoscopic or robotic partial nephrectomy. Radius of mass was the most effective predictive component of the nephrometry score for trifecta prediction.

Background: Several strategies were implemented during the Covid-19 pandemic to enhance residency training and patient care. Objective: This study aims to assess the post-pandemic landscape of neurosurgical training and practice. Method: A survey consisting of 28 questions examining the challenges faced in neurosurgery and the adaptive measures was conducted among US neurosurgery residents from May 2022 to May 2023. Results: This study encompassed 59 neurosurgical residents, predominantly male (72.9%) and in later years of training (66.1%) and were distributed across 25 states. Telemedicine and tele-education were pivotal during the pandemic, with virtual lecture series, standalone lectures, and virtual discussions highly favored. Remote didactic learning increased for nearly half of the residents, while 54.2% resumed in-person instruction. Telemedicine was deemed effective by 86.4% for evaluating neurosurgical patients. Access to teaching environments was restricted for 61.0% of residents, impacting their training. The pandemic significantly influenced elective surgeries, with complete cancellations reported by 42.4%. Reduced faculty engagement was noted by 35.6% of residents, while 47.5% reported a negative impact on the overall resident experience. The majority (76.3%) considered changes to their training reasonable given the global health situation. Conclusions: Strategies implemented during the peak of the pandemic remain crucial in shaping neurosurgery training. Telemedicine has become indispensable, with widespread adoption. Tele-education has also expanded, providing additional learning opportunities. However, traditional didactic courses and hands-on experiences remain essential for comprehensive training. Balancing technology-driven methods with established approaches is crucial for optimizing neurosurgical education and maintaining high-quality patient care.

Therapeutic antibodies such as monoclonal antibodies (mAbs), bispecific and multispecific antibodies are pivotal in therapeutic protein development and have transformed disease treatments across various therapeutic areas. The integrity of therapeutic antibodies, however, is compromised by sequence liabilities, notably deamidation, where asparagine (N) and glutamine (Q) residues undergo chemical degradations. Deamidation negatively impacts the efficacy, stability, and safety of diverse classes of antibodies, thus necessitating the critical need for the early and accurate identification of vulnerable sites. In this article, a comprehensive antibody deamidation-specific dataset (n = 2285) of varied modalities was created by using high-throughput automated peptide mapping followed by supervised machine learning to predict the deamidation propensities, as well as the extents, throughout the entire antibody sequences. We propose a novel chimeric deep learning model, integrating protein language model (pLM)-derived embeddings with local sequence information for enhanced deamidation predictions. Remarkably, this model requires only sequence inputs, eliminating the need for laborious feature engineering. Our approach demonstrates state-of-the-art performance, offering a streamlined workflow for high-throughput automated peptide mapping and deamidation prediction, with the potential of broader applicability to other antibody sequence liabilities.

ObjectiveThe objective of this study was to examine the impact of the introduction of the Universal Anaesthesia Machine (UAM), a device designed for use in clinical environments with limited clinical perioperative resources, on the choice of general anesthesia technique and safe anesthesia practice in a tertiary-care hospital in Sierra Leone.MethodsWe introduced an anesthesia machine (UAM) into Connaught Hospital, Freetown, Sierra Leone. We conducted a prospective observational study of anesthesia practice and an examination of perioperative clinical parameters among surgical patients at the hospital to determine the usability of the device, its impact on anesthesia capacity, and changes in general anesthesia technique.FindingsWe observed a shift from the use of ketamine total intravenous anesthesia to inhalational anesthesia. This shift was most demonstrable in anesthesia care for appendectomies and surgical wound management. In 10 of 17 power outages that occurred during inhalational general anesthesia, anesthesia delivery was uninterrupted because inhalational anesthesia was being delivered with the UAM.ConclusionAnesthesia technologies tailored to overcome austere environmental conditions can support the delivery of safe anesthesia care while maintaining fidelity to recommended international anesthesia practice standards.

Summary: Background: In June 2023, a local cluster of 15 Zika cases was reported in a neighbourhood in Northeastern Singapore. The last significant local transmission of Zika virus (ZIKV) with more than 450 cases was in 2016–2017. To monitor the situation and mitigate further transmission, case, entomological and wastewater-based surveillance were carried out. Methods: Primary healthcare practitioners and the community were alerted to encourage timely case identification. Surveillance was enhanced through testing of Aedes mosquitoes collected from the National Gravitrap surveillance system, and wastewater samples were collected from a network of autosamplers deployed at manholes across the country. Findings: ZIKV RNA was detected in mosquito pools (3/43; 7%) and individual mosquitoes (3/82; 3.7%) captured, and in wastewater samples (13/503) collected from the vicinity of the cluster of cases. Respective samples collected from other sites across the country were negative. The peak detection of ZIKV RNA in mosquitoes and wastewater coincided temporally with the peak in the number of cases in the area (15–25 May 2023). Interpretation: The restriction of ZIKV signals from wastewater and mosquitoes within the neighbourhood suggested limited ZIKV transmission. The subsequent waning of signals suggested effectiveness of control measures. We demonstrate the utility of wastewater-based surveillance of ZIKV, which complements existing case- and entomological-based surveillance. The non-intrusive approach is particularly useful to monitor diseases such as Zika, which generally causes silent or mild infections, but may cause severe outcomes such as congenital Zika syndrome. Funding: This study was funded by Singapore’s Ministry of Finance and the National Environment Agency, Singapore.

Abstract For hemodialysis patients, arteriovenous fistula (AVF) patency determines whether adequate hemofiltration can be achieved, and directly influences clinical outcomes. Here, we report the development and performance of a deep learning model for automated AVF stenosis screening based on the sound of AVF blood flow using supervised learning with data validated by ultrasound. We demonstrate the importance of contextualizing the sound with location metadata as the characteristics of the blood flow sound varies significantly along the AVF. We found the best model to be a vision transformer trained on spectrogram images. Our model can screen for stenosis at a performance level comparable to that of a nephrologist performing a physical exam, but with the advantage of being automated and scalable. In a high-volume, resource-limited clinical setting, automated AVF stenosis screening can help ensure patient safety via early detection of at-risk vascular access, streamline the dialysis workflow, and serve as a patient-facing tool to allow for at-home, self-screening.

We report efficiencies of >24% being consistently achieved in mass-production of passivating-contact solar cells. Furthermore, the certified efficiency of cells from our pilot line has reached 25.3% with 730 mV open-circuit voltage. An analysis of the cell performance, including simulations, shows that the cells’ rear-side is nearly ideal, while there remains potential for further optimization of the front emitter and passivation.

Alcohol is the most frequently consumed toxic substance in the world and remains a major global public health issue, with one in three adults consuming it worldwide. Alcohol use is a leading risk factor for disease, contributing to over 60 acute and chronic health conditions, with a particularly complex association with cardiovascular disease. Chronic excessive alcohol consumption is associated with a range of cardiac complications, including decreased myocardial contractility, hypertension, arrhythmias, MI and heart failure. However, low-level alcohol consumption is believed to have a protective effect against ischaemic heart disease and diabetes. In most cohort studies, small to moderate amounts of alcohol consumption have not been linked to heart failure, indicating a threshold effect of alcohol with individual (possibly genetic) predisposition rather than a continuous effect of exposure. This review article explores the potential benefits of alcohol on the heart, the association between alcohol use and alcoholic cardiomyopathy and the epidemiology, clinical correlates and management of alcoholic cardiomyopathy.

OBJECTIVES/GOALS: Study the regulatory role of sodium glucose co-transporter 1 (SGLT1) in cardiomyocytes and the therapeutic potential of sotagliflozin in hypertrophic cardiomyopathy (HCM) by (a) quantifying SGLT1 expression in HCM and (b) examining the impact of sotagliflozin on cardiac mechanics. METHODS/STUDY POPULATION: * Use Western Blot in cardiac tissue from HCM and non-HCM patients and pre-existing RNA seq and proteomics datasets to quantify SGLT1 levels in HCM. Hypothesis: SGLT1 is upregulated in HCM * Determine how SGLT1/2 inhibition by sotagliflozin will affect cardiac mechanics using living myocardial slice (LMS) preparations. A vibratome creates 200um-thick slices from (a) failing HCM heart explants, (b) septal myectomy samples from HCM patients, and (c) nonfailing rejected donor hearts. LMS are mounted on a force transducer and work-loops are stimulated under varying pre- and after-loads. Collecting baseline and post-drug work loops allows each slice to function as its own control. Hypothesis: sotagliflozin will improve diastolic mechanics by reducing stiffness in the end-diastolic pressure-volume relationship RESULTS/ANTICIPATED RESULTS: * Preliminary results from RNA seq data indicate that SLC5A1 mRNA (encoding gene for SGLT1) is significantly decreased in HCM. No proteomics study examined thus far has detected SLC5A1, indicating that overall SGLT1 levels in cardiac tissue are quite low. We will examine SGLT1 levels in our own HCM and non-HCM tissue samples with both mass-spectrometry and Western Blot. * We analyze six slices from each heart and expect 15 donor hearts and 15 HCM hearts/myectomy samples. We visualize the work loop by plotting stress/strain. Stress/strain at mitral valve closure represents exponential end diastolic pressure-volume relationship; Stress/strain at aortic valve closure represents linear end systolic pressure volume relationship. A two-sample paired t-test will compare change in stiffness and elastance. DISCUSSION/SIGNIFICANCE: This project contributes to a growing body of research surrounding the currently unknown cardioprotective mechanism of SGLT 1/2 inhibitors, furthers the technique of using living myocardial slices to study cardiac mechanics, and supports a trial examining sotagliflozin in HCM, for which disease modifying therapy remains a prevailing unmet need.

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case–control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity.

Despite significant progress in recent decades toward ameliorating the excess burden of diarrheal disease globally, childhood diarrhea remains a leading cause of morbidity and mortality in low-and-middle-income countries (LMICs). Recent large-scale studies of diarrhea etiology in these populations have revealed widespread co-infection with multiple enteric pathogens, in both acute and asymptomatic stool specimens. We applied methods from network science and ecology to better understand the underlying structure of enteric co-infection among infants in two large longitudinal birth cohorts in Bangladesh. We used a configuration model to establish distributions of expected random co-occurrence, based on individual pathogen prevalence alone, for every pathogen pair among 30 enteropathogens detected by qRT-PCR in both diarrheal and asymptomatic stool specimens. We found two pairs, Enterotoxigenic E. coli (ETEC) with Enteropathogenic E. coli (EPEC), and ETEC with Campylobacter spp., co-infected significantly more than expected at random (both pairs co-occurring almost 4 standard deviations above what one could expect due to chance alone). Furthermore, we found a general pattern that bacteria-bacteria pairs appear together more frequently than expected at random, while virus-bacteria pairs tend to appear less frequently than expected based on model predictions. Finally, infants co-infected with leading bacteria-bacteria pairs had more days of diarrhea in the first year of life compared to infants without co-infection (p-value

This article explores the quantitative and qualitative dimensions of volatility and their implications for cultural analysis in a range of fields. From quantitative finance, it takes the notion of ‘delta-hedging’, the suspension or neutralization of directionality to get access to volatility, and applies this to qualitative areas such as surfing, dance, cinema, and language.

The term ‘volatility’ applies to changeability: both that which can be measured, such as temperatures and stock prices, and that which cannot be easily measured, such as affects and emotions. Quantitative financial volatility has typically been studied quite separately from art, culture, and everyday life. Randy Martin's work, which addressed the resonances between volatility in dance and finance, was a notable exception. Martin focused on derivatives, which played a critical role in the development of financialized capitalism, especially between 1973-2008. Arguably, however, derivatives are no longer the key drivers of volatility as a social and cultural logic. New assemblages of asset managers, rentiers, and online platforms - along with a pandemic, new banking crises, and ongoing climate emergency - are reshaping how volatility is produced and navigated. How might we rethink volatility in order to better grasp its changing logics? This introduction unpacks existing debates on volatility in finance, art, and culture, suggesting several directions in which new work in this area might depart from existing frameworks - some of which are pursued in this special issue. We focus on three broad lines of exploration: rethinking the intellectual histories of volatility; rethinking volatility across disparate post-2008 contexts; and imagining volatile futures through art practice.

Abstract Restoring and sustaining anadromous fish populations is a grand challenge in the conservation of freshwater ecosystems. Alewife Alosa pseudoharengus and Blueback Herring Alosa aestivalis are two closely related anadromous fish for which responses to fish passage restoration are poorly known. We used a targeted environmental DNA method to sample 17 major tributaries of the Chesapeake Bay, USA, to determine the spatial extent of habitat use during the spawning season and the associations of habitat use with watershed characteristics. To help understand responses to restoration of fish passage, the study included portions of eight watersheds where dam removals, fish ladders, or dam failures provided access to habitats that were previously inaccessible to anadromous fish. Overall, 27.5% of samples showed positive detections for river herring, including at least one sample in 16 of 17 tributaries sampled. The presence of both species combined was negatively associated with elevation (relative influence [RI] = 29.8%) and positively associated with a watershed area (RI = 14.5%) and percent cropland (13.6%) of the watershed. In species‐specific analyses, both Alewife (RI = 24.8%) and Blueback Herring (26.2%) presence was negatively associated with elevation, Alewife were more common in watersheds with high percentages of cropland (RI = 19.1%), whereas Blueback Herring were more common in streams with large watersheds (23.2%). The use of formerly blocked spawning habitats was generally greater upstream of sites where dams were removed (2%–100% of habitat used) compared with sites where fish ladders were installed (0%–66.8% of habitat used). The broad‐scale sampling enabled by eDNA methods made it possible to identify habitat use patterns that can be applied to prioritize future restoration efforts and predict species‐specific responses.

Abstract Background Altered adipose tissue (AT) metabolism in cancer‐associated weight loss via inflammation, lipolysis, and white adipose tissue (WAT) browning is primarily implicated from rodent models; their contribution to AT wasting in cancer patients is unclear. Methods Energy expenditure (EE), plasma, and abdominal subcutaneous WAT were obtained from men (aged 65 ± 8 years) with cancer, with (CWL, n = 27) or without (CWS, n = 47) weight loss, and weight‐stable non‐cancer patients (CON, n = 26). Clinical images were assessed for adipose and muscle area while plasma and WAT were assessed for inflammatory, lipolytic, and browning markers. Results CWL displayed smaller subcutaneous AT (SAT; P = 0.05) and visceral AT (VAT; P = 0.034) than CWS, and displayed higher circulating interleukin (IL)‐6 (P = 0.01) and WAT transcript levels of IL‐6 (P = 0.029), IL‐1β (P = 0.042), adipose triglyceride lipase (P = 0.026), and browning markers (Dio2, P = 0.03; PGC‐1a, P = 0.016) than CWS and CON. There was no difference across groups in absolute REE (P = 0.061), %predicted REE (P = 0.18), circulating free fatty acids (FFA, P = 0.13) or parathyroid hormone‐related peptide (PTHrP; P = 0.88), or WAT protein expression of inflammation (IL‐6, P = 0.51; IL‐1β, P = 0.29; monocyte chemoattractant protein‐1, P = 0.23) or WAT protein or gene expression of browning (uncoupling protein‐1, UCP‐1; P = 0.13, UCP‐1, P = 0.14). In patients with cancer, FFA was moderately correlated with WAT hormone‐sensitive lipase transcript (r = 0.38, P = 0.018, n = 39); circulating cytokines were not correlated with expression of WAT inflammatory markers and circulating PTHrP was not correlated with expression of WAT browning markers. In multivariate regression using cancer patients only, body mass index (BMI) directly predicted SAT (N = 25, R2 = 0.72, P

Historical loss of river and stream habitats due to impassable dams has contributed to the severe decline of many fish species. Anadromous fishes that migrate from the sea to freshwater streams to spawn have been especially impacted as dams restrict these fish from accessing ancestral spawning grounds. In 2018, Bloede Dam was removed from the Patapsco River near Baltimore, Maryland, restoring approximately 100 km of potential habitat for migratory fish. We assessed the response of anadromous river herring, alewife (Alosa pseudoharengus) and blueback herring (Alosa aestivalis), to this dam removal by monitoring environmental DNA (eDNA) and eggs from 2015 to 2021 at locations upstream and downstream of the dam site during their spawning migrations. We additionally assessed the presence of fish by collecting electrofishing samples and tracked the movements of individual adult fish within the river using passive integrated transponder (PIT) tags. No adult river herring, eDNA, or eggs were detected upstream of Bloede Dam in the four years prior to its removal despite the presence of a fish ladder. Our results suggest initial habitat use recovery by spawning river herring in the first year post-removal, although a relatively small proportion of the population in the river used the newly accessible habitat. In the three years post-removal, the likelihood of detecting river herring eDNA upstream of the former dam site increased to 5% for alewife and 13% for blueback herring. Two adult fish were also collected in electrofishing samples upstream of the dam site in 2021. We found no evidence of changes in egg abundance and no tagged fish were detected upstream of the dam site post-removal. While long term monitoring is needed to assess population changes, this study highlights the value of integrating methods for comprehensive understanding of habitat use following dam removal.

5xFAD transgenic (TG) mice are used widely in AD preclinical trials; however, data on sample sizes are largely unaddressed. We therefore performed estimates of sample sizes and effect sizes for typical behavioural and neuropathological outcome measures in TG 5xFAD mice, based upon data from single-sex (female) groups. Group-size estimates to detect normalisation of TG body weight to WT littermate levels at 5.5m of age were N = 9-15 depending upon algorithm. However, by 1 year of age, group sizes were small (N = 1 -

Influenza vaccination and antiviral therapeutics may attenuate disease, decreasing severity of illness in vaccinated and treated persons. Standardized assessment tools, definitions of disease severity, and clinical endpoints would support characterizing the attenuating effects of influenza vaccines and antivirals. We review potential clinical parameters and endpoints that may be useful for ordinal scales evaluating attenuating effects of influenza vaccines and antivirals in hospital-based studies. In studies of influenza and community-acquired pneumonia, common physiologic parameters that predicted outcomes such as mortality, ICU admission, complications, and duration of stay included vital signs (hypotension, tachypnea, fever, hypoxia), laboratory results (blood urea nitrogen, platelets, serum sodium), and radiographic findings of infiltrates or effusions. Ordinal scales based on these parameters may be useful endpoints for evaluating attenuating effects of influenza vaccines and therapeutics. Factors such as clinical and policy relevance, reproducibility, and specificity of measurements should be considered when creating a standardized ordinal scale for assessment.

Abstract Group A rotaviruses (RVA) remain a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries. Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which RVA immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of RVA diarrhea through 2 years of life (RR 0.616, 95% CI 0.392–0.968). Further development of controlled human infection models for group A rotaviruses, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.

With a growing geriatric population estimated to triple by 2050, minimally invasive procedures that are image-guided are becoming both more popular and necessary for treating a variety of diseases. To lower the learning curve for new procedures, it is necessary to develop better guidance systems and methods to analyze procedure performance. Since fluoroscopy remains the primary mode of visualizations, the ability to perform catheter tracking from fluoroscopic images is an important part of this endeavor. This paper explores the use of deep learning to perform the landmark detection of a catheter from fluoroscopic images in 3D-printed heart models. We show that a two-stage deep-convolutional-neural-network-based model architecture can provide improved performance by initially locating a region of interest before determining the coordinates of the catheter tip within the image. This model has an average error of less than 2% of the image resolution and can be performed within 4 milliseconds, allowing for its potential use for real-time intraprocedural tracking. Coordinate regression models have the advantage of directly outputting values that can be used for quantitative tracking in future applications and are easier to create ground truth values (~50× faster), as compared to semantic segmentation models that require entire masks to be made. Therefore, we believe this work has better long-term potential to be used for a broader class of cardiac devices, catheters, and guidewires.

In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs, significant yet incomplete progress has been made toward reducing the burden of rotavirus in low- to middle-income countries (LMIC). ORVs continue to demonstrate effectiveness and impact in LMIC, yet numerous factors hinder optimal performance and evaluation of these vaccines. This review will provide an update on ORV performance in LMIC, the increasing body of literature regarding factors that affect ORV response, and the status of newer and next-generation rotavirus vaccines as of early 2020. Fully closing the gap in rotavirus prevention between LMIC and high-income countries will likely require a multifaceted approach accounting for biological and methodological challenges and evaluation and roll-out of newer and next-generation vaccines.

Abstract Background Mathematical modeling studies have suggested that pre-emptive school closures alone have little overall impact on SARS-CoV-2 transmission, but reopening schools in the background of community contact reduction presents a unique scenario that has not been fully assessed. Methods We adapted a previously published model using contact information from Shanghai to model school reopening under various conditions. We investigated different strategies by combining the contact patterns observed between different age groups during both baseline and “lockdown” periods. We also tested the robustness of our strategy to the assumption of lower susceptibility to infection in children under age 15 years. Results We find that reopening schools for all children would maintain a post-intervention R0

Background: Oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED. Methods: We measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED. Findings: Among 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups. Interpretation: We found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions.

Reduced symptomatology and access to testing in children have led to underestimates of paediatric COVID-19 prevalence and raised concerns about school safety. To explore COVID-19 prevalence and risk factors in school settings, we conducted a SARS-CoV-2 serosurvey in a Vermont, USA school district in December 2020. Among 336 students (63%) and 196 teachers/staff (37%), adjusted seroprevalence was 4.7% (95% CI 2.9 to 7.2) and was lowest in preK-5 students (4–10 Years). Seroprevalence was 10-fold higher than corresponding state PCR data but was low overall with no evidence of onward transmissions. These results further support feasibility of in-person learning during COVID-19 with appropriate mitigation measures.

Asian elephants are a principal cause of human-wildlife conflict. This results in the death/injury of elephants and humans and large-scale crop and property damage. Most current human-elephant conflict (HEC) mitigation tools lack the flexibility to accommodate the ecological needs of elephants and are ineffective at reducing HEC in the long-term. Here we review common HEC mitigation tools used in Asia and the potential of Aversive Geofencing Devices (AGDs) to manage problem elephants. AGDs can be configured to monitor animal movements in real-time and deliver auditory warnings followed by electric stimuli whenever animals attempt to move across user-specified virtual boundaries. Thus, AGDs are expected to condition elephants to avoid receiving shocks and keep them away from virtually fenced areas, while providing alternative routes that can be modified if required. Studies conducted using AGDs with other species provide an overview of their potential in conditioning wild animals. We recommend that the efficacy and welfare impact of AGDs be evaluated using captive elephants along with public perception of using AGDs on elephants as a means of addressing the inherent deficiencies of common HEC mitigation tools. If elephants could be successfully conditioned to avoid virtual fences, then AGDs could resolve many HEC incidents throughout Asia.

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary out-come was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15–1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson–Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04–1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.

The COVID-19 pandemic and its associated vaccine have highlighted vaccine hesitancy among healthcare workers (HCWs). Vaccine hesitancy among this group existed prior to the pandemic and particularly centered around influenza vaccination. Being a physician, having more advanced education, and previous vaccination habits are frequently associated with vaccine acceptance. The relationship between age and caring for patients on COVID-19 vaccination is unclear, with studies providing opposing results. Reasons for hesitancy include concerns about safety and efficacy, mistrust of government and institutions, waiting for more data, and feeling that personal rights are being infringed upon. Many of these reasons reflect previous attitudes about influenza vaccination as well as political beliefs and views of personal autonomy. Finally, several interventions to encourage vaccination have been studied, including education programs and non-monetary incentives with the most effective studies using a combination of methods.

Background Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. Methods We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010–2013 seasons. Results We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2–8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation 24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or 24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation 15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). Conclusion We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

A collection of results is given regarding whether a prime can be the sum or difference of two polyhedral numbers, as well as some primality restrictions on several sequences.

Streptococcus pseudoporcinus is a beta-hemolytic Gram-positive, catalase-negative, nonmotile coccus arranged in short chains, usually found in the female genitourinary tract and differentiated from Streptococcus porcinus in 2006. Only two human infections associated with this organism have been reported to date: one in a patient with a first digit wound infection and another with lower extremity cellulitis. We describe two novel cases of Streptococcus pseudoporcinus causing endocarditis in one and pneumonia with empyema in another, illustrating the potential of these bacteria to cause severe invasive and life-threatening disease.

Objective. Refractive surgery volume has not rebounded despite economic recovery and literature describing safety, efficacy, and high patient satisfaction. We sought to examine characteristics of consultation seekers and status after consultation. Methods. Charts of patients seeking refractive surgery at Johns Hopkins University from 2013 through 2016 were retrospectively reviewed for age, gender, refractive characteristics, and outcome: surgery (photorefractive keratectomy, laser in-situ keratomileusis, implantable collamer lens, or refractive lens exchange); no surgery—“lost candidate” (good candidates who were lost after consultation); noncandidates based on technological limitations or contraindications; or no surgery—possessing expectations that surgery would not meet. Associations between characteristics and status after consultation were examined. Results. Twenty percent (142/712) of all patients were “lost candidates”; 57% (408/712) completed surgery. More women (56% or 401/712) sought consultation, but a greater percentage (63% or 195/311) of men completed surgery than women did (53% or 213/401) p=0.02. Of consultation seekers, 60% were low myopes, 29% were high myopes (>6 diopters of myopic spherical equivalent), and 11% were hyperopes. Surgical patients’ mean age was 34.2 ± 10.2 (standard deviation) years; for each additional year of age, patients were less likely to have surgery p

Purpose: To describe a case of Achromobacter xylosoxidans keratitis with deep involvement of the corneal stroma and discuss its management. Observations: A 73 year-old monocular male with infectious keratitis of the right eye was referred to the Wilmer Eye Institute after a month of empiric treatment with besifloxacin. On presentation, slit lamp examination of the right eye demonstrated a diffusely edematous cornea with three areas of corneal infiltrates and an overlying epithelial defect and a 1.3 mm hypopyon in the anterior chamber. The corneal culture performed grew A. xylosoxidans. Empiric antibiotic regimen was adjusted once corneal culture susceptibility results were available. Seven days later, slit lamp examination demonstrated a resolving epithelial defect, stable infiltrates, and resolution of the hypopyon. After approximately two months of follow up with his primary ophthalmologist, he was noted to have recurrent hypopyon and infiltrates and was referred back to Wilmer. Slit lamp examination again demonstrated an epithelial defect, diffuse corneal haze, deep stromal infiltrates, and a 1 mm hypopyon. Corneal infiltrates were too deep to culture. Ultimately, the patient underwent a therapeutic penetrating keratoplasty with anterior chamber washout resulting in improvement of vision. Conclusions and importance: The indolent progression of A. xylosoxidans keratitis may predispose patients to delayed presentation and treatment. This can result in deep stromal infection that complicates management due to poor antibiotic penetration. Deep stromal infections in A. xylosoxidans keratitis warrant the consideration of intrastromal antibiotic injection or early therapeutic penetrating keratoplasty. Keywords: Achromobacter, Alcaligenes, Bacterial keratitis, Penetrating keratoplasty

Influenza is a common respiratory virus that infects between 5 and 20% of the US population and results in 30,000 deaths annually. A primary cause of influenza-associated death is secondary bacterial pneumonia. We have previously shown that influenza induces type I interferon (IFN)-mediated inhibition of Type 17 immune responses, resulting in exacerbation of bacterial burden during influenza and Staphylococcus aureus super-infection. In this study, we investigated the role of STAT2 signaling during influenza and influenza-bacterial super-infection in mice. Influenza-infected STAT2−/− mice had increased morbidity, viral burden, and inflammation when compared to wild-type mice. Despite an exaggerated inflammatory response to influenza infection, we found increased bacterial control and survival in STAT2 deficient mice during influenza-MRSA super-infection compared to controls. Further, we found that increased bacterial clearance during influenza-MRSA super-infection is not due to rescue of Type 17 immunity. Absence of STAT2 was associated with increased accumulation of M1, M2 and M1/M2 co-expressing macrophages during influenza-bacterial super-infection. Neutralization of IFNγ (M1) and/or Arginase 1 (M2) impaired bacterial clearance in Stat2−/− mice during super-infection, demonstrating that pulmonary macrophages expressing a mixed M1/M2 phenotype promote bacterial control during influenza-bacterial super-infection. Together, these results suggest that the STAT2 signaling is involved in suppressing macrophage activation and bacterial control during influenza-bacterial super-infection. Further, these studies reveal novel mechanistic insight into the roles of macrophage subpopulations in pulmonary host defense.

In 2006, the Institute of Medicine published a report titled "Emergency Care for Children: Growing Pains," in which it described pediatric emergency care as uneven at best. Since then, telehealth has emerged as one of the great equalizers in care of children, particularly for those in rural and underresourced communities. Clinicians in these settings may lack pediatric-specific specialization or experience in caring for critically ill or injured children. Telehealth consultation can provide timely and safe management for many medical problems in children and can prevent many unnecessary and often long transport to a pediatric center while avoiding delays in care, especially for time-sensitive and acute interventions. Telehealth is an important component of pediatric readiness of hospitals and is a valuable tool in facilitating health care access in low resourced and critical access areas. This paper provides an overview of meaningful applications of telehealth programs in pediatric emergency medicine, discusses the impact of the COVID-19 pandemic on these services, and highlights challenges in setting up, adopting, and maintaining telehealth services.

Objectives: To evaluate the concordance between self-reported data and variables obtained from Medicare administrative data in terms of chronic conditions and health care utilization. Design: Retrospective observational study. Participants: We analyzed data from a sample of Medicare beneficiaries who were part of the National Study of Chronic Disease Self-Management Program (CDSMP) and were eligible for the Centers for Medicare and Medicaid Services (CMS) pilot evaluation of CDSMP (n = 119). Methods: Self-reported and Medicare claims-based chronic conditions and health care utilization were examined. Percent of consistent numbers, kappa statistics (κ), and Pearson’s correlation coefficient were used to evaluate concordance. Results: The two data sources had substantial agreement for diabetes and COPD (κ = 0.75 and κ = 0.60, respectively), moderate agreement for cancer and heart disease (κ = 0.50 and κ = 0.47, respectively), and fair agreement for depression (κ = 0.26). With respect to health care utilization, the two data sources had almost perfect or substantial concordance for number of hospitalizations (κ: 0.69 – 0.79), moderate concordance for ED care utilization (κ: 0.45 – 0.61), and generally low agreement for number of physician visits (κ ≤ 0.31). Conclusions: Either self-reports or claim-based administrative data for diabetes, COPD, and hospitalizations can be used to analyze Medicare beneficiaries in the U.S. Yet, caution must be taken when only one data source is available for other types of chronic conditions and health care utilization.

With the growing popularity of Mixed Martial Arts (MMA) as a competitive sport, questions regarding the dynamic response and properties of MMA gloves arise. High-energy impacts from punches are very similar to boxing yet MMA competition requires the use of 4 oz fingerless glove, compared to the larger full enclosure boxing glove. This work assessed the kinetic properties and strike dynamics of MMA gloves and compared findings with traditional boxing gloves. Gloves mounted on a molded fist were impacted repetitively on an instrumental anvil designed for impact, over a 5 hour period resulting in 10,000 continuous and consistent strikes. Kinetic data from impacts were sampled at the beginning of the data collection and subsequently every 30 minutes (every 1,000 strikes). MMA gloves produced 4-5 times greater peak force and 5 times faster load rate compared to the boxing glove. However, MMA gloves also showed signs of material fatigue, with peak force increasing by 35% and rate of loading increasing by 60% over the duration of the test. Boxing glove characteristics did deteriorate but to a lesser extent. In summary, the kinetic properties of MMA glove differed substantially from the boxing glove resulting in impacts characterized by higher peak forces and more rapid development of force. Material properties including stiffness and thickness play a role in the kinetic characteristics upon impact, and can be inferred to alter injury mechanisms of blunt force trauma.

This paper presents a set of testimonies from three LGBTQ families about the advocacy work they took up in their schools. The stories they share are part of an interview study undertaken from 2014-2020. Each family responded to the cisheteronormative cultures of their schools by challenging ideas teachers and principals held about gender, sexuality, and families and some of their everyday practices. The advocacy work the families undertook is discussed through two analytic lenses, the Triangle Model (McCaskell, 2005; Thomas, 1987) and intersectionality (Crenshaw, 1989), demonstrating how middle-class economic resources and professional education were key to parents' success.

Transepithelial potential (TEP) is the voltage across a polarized epithelium. In epithelia that have active transport functions, the force for transmembrane flux of an ion is dictated by the electrochemical gradient in which TEP plays an essential role. In epithelial injury, disruption of the epithelial barrier collapses the TEP at the wound edge, resulting in the establishment of an endogenous wound electric field (∼100 mV/mm) that is directed towards the center of the wound. This endogenous electric field is implicated to enhance wound healing by guiding cell migration. We thus seek techniques to enhance the TEP, which may increase the wound electric fields and enhance wound healing. We report a novel technique, termed synchronization modulation (SM) using a train of electric pulses to synchronize the Na/K pump activity, and then modulating the pumping cycles to increase the efficiency of the Na/K pumps. Kidney epithelial monolayers (MDCK cells) maintain a stable TEP and transepithelial resistance (TER). SM significantly increased TEP over four fold. Either ouabain or digoxin, which block Na/K pump, abolished SM-induced TEP increases. In addition to the pump activity, basolateral distribution of Na/K pumps is essential for an increase in TEP. Our study for the first time developed an electrical approach to significantly increase the TEP. This technique targeting the Na/K pump may be used to modulate TEP, and may have implication in wound healing and in diseases where TEP needs to be modulated.

Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.