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Objectives: Knowledge, access, and use of testing and antiviral treatments is critical to managing and mitigating the continuing burden of the novel Corona Virus (COVID-19) in the United States. This study measured knowledge, attitude, behaviors, and self-reported barriers towards COVID-19 testing and outpatient anti-viral medications (OPA) treatments among Black and older individuals who face greater hospitalization and mortality from the disease. Study design: Cross-sectional structured survey. Methods: Respondents were randomly selected from an opt-in national panel in December 2022. Equal numbers of Black and White US adults over the age of 40 (n = 1037) completed the 42 item online survey. The main measures were key sociodemographic variables of respondents, race, age, political affiliation and COVID-19 attitudes, beliefs, testing behaviors, and knowledge and barriers to OPA access. Results: Overall, awareness and knowledge of COVID-19 outpatient treatments was low. Black respondents were more likely to test for COVID-19 than White respondents but less likely to know about OPA treatments. Insurance coverage was a significant factor in use of home tests. Knowledge of OPA treatments was low across groups. White respondents were more likely than Black respondents to be aware of OPA treatments (1.75, 95 % CI [1.31–2.33]) as were higher income respondents (1.13, 95 % CI [1.08–1.17]) and self-identified Liberals (1.79, 95 % CI [1.29–2.49]). Conclusions: Clinicians should know large numbers of patients may not be testing for COVID-19, nor are they aware of outpatient treatment options and may hold inaccurate beliefs about them. Developing culturally specific patient education materials are warranted to increase testing, utilization of vaccinations and OPAs.

Climate change poses a growing threat to the livestock industry, impacting animal productivity, animal welfare, and farm management practices. Thus, enhancing livestock climatic resilience (CR) is becoming a key priority in various breeding programs. CR can be defined as the ability of an animal to be minimally affected or rapidly return to euthermia under thermally stressful conditions. The primary study objectives were to perform genome-wide association studies for 12 CR indicators derived from variability in longitudinal vaginal temperature in lactating sows under heat stress conditions. A total of 31 single nucleotide polymorphisms (SNPs) located on nine chromosomes were considered as significantly associated with nine CR indicators based on different thresholds. Among them, only two SNPs were simultaneously identified for different CR indicators, SSC6:16,449,770 bp and SSC7:39,254,889 bp. These results highlighted the polygenic nature of CR indicators with small effects distributed across different chromosomes. Furthermore, we identified 434 positional genes associated with CR. Key candidate genes include SLC3A2, STX5, POLR2G, and GANAB, which were previously related to heat stress responses, protein folding, and cholesterol metabolism. Furthermore, the enriched KEGG pathways and Gene Ontology (GO) terms associated with these candidate genes are linked to stress responses, immune and inflammatory responses, neural system, and DNA damage and repair. The most enriched quantitative trait loci are related to “Meat and Carcass”, followed by “Production”, “Reproduction”, “Health”, and “Exterior (conformation and appearance)” traits. Multiple genomic regions were identified associated with different CR indicators, which reveals that CR is a highly polygenic trait with small effect sizes distributed across the genome. Many heat tolerance or HS related genes in our study, such as HSP90AB1, DMGDH, and HOMER1, have been identified. The complexity of CR encompasses a range of adaptive responses, from behavioral to cellular. These results highlight the possibility of selecting more heat-tolerant individuals based on the identified SNP for CR indicators.

Main problem: Chronic kidney disease (CKD) is a progressive condition that affects millions of people worldwide. A standardized core outcome set (COS) was developed for CKD by the International Consortium for Health Outcomes and Measurements in 2019. This study aims to evaluate the frequency of measurement for these outcomes before and after the publication of the COS. Methods: A literature search was done to gather the phase III/IV clinical trials evaluating chronic kidney disease through ClinicalTrials.gov. Data extraction of included studies was completed in a masked, duplicate fashion. The included studies were evaluated for characteristics such as survival, burden of disease, patient-reported health-related quality of life, and treatment modality-specific outcomes. Results: Our results showed that the majority of all COS domains were inadequately measured in CKD clinical trials before and after publication of the COS. Despite the increase in COS measurements following publication, the average percent of COS outcomes measured was less than 40 % per year even after four years. Conclusion: There is a notable deficiency in the complete measurement of COS among all domains both before and after COS publication. We suggest efforts be made to improve the adoption of consistent outcome measures that would benefit the growing population of patients affected by CKD.

Abstract Background Longitudinal records of automatically-recorded vaginal temperature (TV) could be a key source of data for deriving novel indicators of climatic resilience (CR) for breeding more resilient pigs, especially during lactation when sows are at an increased risk of suffering from heat stress (HS). Therefore, we derived 15 CR indicators based on the variability in TV in lactating sows and estimated their genetic parameters. We also investigated their genetic relationship with sows’ key reproductive traits. Results The heritability estimates of the CR traits ranged from 0.000 ± 0.000 for slope for decreased rate of TV (SlopeDe) to 0.291 ± 0.047 for sum of TV values below the HS threshold (HSUB). Moderate to high genetic correlations (from 0.508 ± 0.056 to 0.998 ± 0.137) and Spearman rank correlations (from 0.431 to 1.000) between genomic estimated breeding values (GEBV) were observed for five CR indicators, i.e. HS duration (HSD), the normalized median multiplied by normalized variance (Nor_medvar), the highest TV value of each measurement day for each individual (MaxTv), and the sum of the TV values above (HSUA) and below (HSUB) the HS threshold. These five CR indicators were lowly to moderately genetically correlated with shoulder skin surface temperature (from 0.139 ± 0.008 to 0.478 ± 0.048) and respiration rate (from 0.079 ± 0.011 to 0.502 ± 0.098). The genetic correlations between these five selected CR indicators and sow reproductive performance traits ranged from − 0.733 to − 0.175 for total number of piglets born alive, from − 0.733 to − 0.175 for total number of piglets born, and from − 0.434 to − 0.169 for number of pigs weaned. The individuals with the highest GEBV (most climate-sensitive) had higher mean skin surface temperature, respiration rate (RR), panting score (PS), and hair density, but had lower mean body condition scores compared to those with the lowest GEBV (most climate-resilient). Conclusions Most of the CR indicators evaluated are heritable with substantial additive genetic variance. Five of them, i.e. HSD, MaxTv, HSUA, HSUB, and Nor_medvar share similar underlying genetic mechanisms. In addition, individuals with higher CR indicators are more likely to exhibit better HS-related physiological responses, higher body condition scores, and improved reproductive performance under hot conditions. These findings highlight the potential benefits of genetically selecting more heat-tolerant individuals based on CR indicators.

Abstract Background Musculoskeletal injuries are a common occurrence in sport. The goal of sport injury epidemiology is to study these injuries at a population level to inform their prevention and treatment. Main body This review provides an overview of musculoskeletal sport injuries and the musculoskeletal system from a biological and epidemiologic perspective, including injury mechanism, categorizations and types of sport injuries, healing, and subsequent injuries. It is meant to provide a concise introductory substantive background of musculoskeletal sport injuries for epidemiologists who may not have formal training in the underlying anatomy and pathophysiology. Conclusion An understanding of sport injuries is important for researchers in sport injury epidemiology when determining how to best define and assess their research questions and measures.

Abstract Background Heat stress (HS) poses significant threats to the sustainability of livestock production. Genetically improving heat tolerance could enhance animal welfare and minimize production losses during HS events. Measuring phenotypic indicators of HS response and understanding their genetic background are crucial steps to optimize breeding schemes for improved climatic resilience. The identification of genomic regions and candidate genes influencing the traits of interest, including variants with pleiotropic effects, enables the refinement of genotyping panels used to perform genomic prediction of breeding values and contributes to unraveling the biological mechanisms influencing heat stress response. Therefore, the main objectives of this study were to identify genomic regions, candidate genes, and potential pleiotropic variants significantly associated with indicators of HS response in lactating sows using imputed whole-genome sequence (WGS) data. Phenotypic records for 18 traits and genomic information from 1,645 lactating sows were available for the study. The genotypes from the PorcineSNP50K panel containing 50,703 single nucleotide polymorphisms (SNPs) were imputed to WGS and after quality control, 1,622 animals and 7,065,922 SNPs were included in the analyses. Results A total of 1,388 unique SNPs located on sixteen chromosomes were found to be associated with 11 traits. Twenty gene ontology terms and 11 biological pathways were shown to be associated with variability in ear skin temperature, shoulder skin temperature, rump skin temperature, tail skin temperature, respiration rate, panting score, vaginal temperature automatically measured every 10 min, vaginal temperature measured at 0800 h, hair density score, body condition score, and ear area. Seven, five, six, two, seven, 15, and 14 genes with potential pleiotropic effects were identified for indicators of skin temperature, vaginal temperature, animal temperature, respiration rate, thermoregulatory traits, anatomical traits, and all traits, respectively. Conclusions Physiological and anatomical indicators of HS response in lactating sows are heritable but highly polygenic. The candidate genes found are associated with important gene ontology terms and biological pathways related to heat shock protein activities, immune response, and cellular oxidative stress. Many of the candidate genes with pleiotropic effects are involved in catalytic activities to reduce cell damage from oxidative stress and cellular mechanisms related to immune response.

Abstract Introduction Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent–child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure. Methods Long‐Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre‐mating through weaning) Pb exposure groups. From postnatal days (PNDs) 2–9, maternal care behaviors were observed, and dams were classified as low or high maternal care based on amounts of licking/grooming and arched back nursing. At weaning, pups were randomly assigned to enriched or non‐enriched environments. At PND 55, animals began trace fear conditioning and associative memory was tested on days 1, 2, and 10 postconditioning. Results Control offspring showed no significant effects of maternal care or enrichment on task performance. Females with EPN‐Pb exposure and males with PERI‐Pb exposure living in the non‐enriched environment and having an LMC mother had significant memory impairments at days 2 and 10 that were not observed in comparably housed animals with HMC mothers. Enriched animals had no deficits, regardless of maternal care status. Conclusion These results show the potential for modulatory influences of maternal care and housing environment on protecting against or reversing at least one aspect of Pb‐induced cognitive/behavioral dysfunction.

Despite a critical role for tumor-initiating cancer stem cells (CSCs) in breast cancer progression, major questions remain about the properties and signaling pathways essential for their function. Recent discoveries highlighting mechanisms of CSC-resistance to the stress caused by chromosomal instability (CIN) may provide valuable new insight into the underlying forces driving stemness properties. While stress tolerance is a well-known attribute of CSCs, CIN-induced stress is distinctive since levels appear to increase during tumor initiation and metastasis. These dynamic changes in CIN levels may serve as a barrier constraining the effects of non-CSCs and shaping the stemness landscape during the early stages of disease progression. In contrast to most other stresses, CIN can also paradoxically activate pro-tumorigenic antiviral signaling. Though seemingly contradictory, this may indicate that mechanisms of CIN tolerance and pro-tumorigenic inflammatory signaling closely collaborate to define the CSC state. Together, these unique features may form the basis for a critical relationship between CIN and stemness properties.

In recent years, a large focus has been placed on managing training load for injury prevention. To minimise injuries, training recommendations should be based on research that examines causal relationships between load and injury risk. While observational studies can be used to estimate causal effects, conventional methods to study the relationship between load and injury are prone to bias. The target trial framework is a valuable tool that requires researchers to emulate a hypothetical randomised trial using observational data. This framework helps to explicitly define research questions and design studies in a way that estimates causal effects. This article provides an overview of the components of the target trial framework as applied to studies on load and injury and describes various considerations that should be made in study design and analyses to minimise bias.

The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various disorders and aging. The brain’s energy metabolism is a dynamic and tightly regulated network that balances energy demand and supply by engaging complementary molecular pathways. The crosstalk among these pathways enables the system to switch its preferred fuel source based on substrate availability, activity levels, and cell state-related factors such as redox balance. Brain energy production relies on multi-cellular cooperation and is continuously supplied by fuel from the blood due to limited internal energy stores. Astrocytes, which interface with neurons and blood vessels, play a crucial role in coordinating the brain’s metabolic activity, and their dysfunction can have detrimental effects on brain health. This review characterizes the major energy substrates (glucose, lactate, glycogen, ketones and lipids) in astrocyte metabolism and their role in brain health, focusing on recent developments in the field.

Background The extent and consequences of ischemia in patients with chronic limb‐threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis‐to‐limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. Methods and Results In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk‐adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time 30 days, each additional 10‐day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014–1.036]). There was no association between D2L time and all‐cause death. Conclusions A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

ABSTRACTThe oral microbiome plays an important role in protecting oral health. Here, we established a controlled mixed-species in vitro biofilm model and used it to assess the impact of glucose and lactate on the ability of Streptococcus mutans, an acidogenic and aciduric species, to compete with commensal oral bacteria. A chemically defined medium was developed that supported the growth of S. mutans and four common early colonizers of dental plaque: Streptococcus gordonii, Actinomyces oris, Neisseria subflava, and Veillonella parvula. Biofilms containing the early colonizers were developed in a continuous flow bioreactor, exposed to S. mutans, and incubated for up to 7 days. The abundance of bacteria was estimated by quantitative polymerase chain reaction (qPCR). At high glucose and high lactate, the pH in bulk fluid rapidly decreased to approximately 5.2, and S. mutans outgrew other species in biofilms. In low glucose and high lactate, the pH remained above 5.5, and V. parvula was the most abundant species in biofilms. By contrast, in low glucose and low lactate, the pH remained above 6.0 throughout the experiment, and the microbial community in biofilms was relatively balanced. Fluorescence in situ hybridization confirmed that all species were present in the biofilm and the majority of cells were viable using live/dead staining. These data demonstrate that carbon source concentration is critical for microbial homeostasis in model oral biofilms. Furthermore, we established an experimental system that can support the development of computational models to predict transitions to microbial dysbiosis based on metabolic interactions.IMPORTANCEWe developed a controlled (by removing host factor) dynamic system metabolically representative of early colonization of Streptococcus mutans not measurable in vivo. Hypotheses on factors influencing S. mutans colonization, such as community composition and inoculation sequence and the effect of metabolite concentrations, can be tested and used to predict the effect of interventions such as dietary modifications or the use of toothpaste or mouthwash on S. mutans colonization. The defined in vitro model (species and medium) can be simulated in an in silico model to explore more of the parameter space.

Abstract Background Automatic and continuous recording of vaginal temperature (TV) using wearable sensors causes minimal disruptions to animal behavior and can generate data that enable the evaluation of temporal body temperature variation under heat stress (HS) conditions. However, the genetic basis of TV in lactating sows from a longitudinal perspective is still unknown. The objectives of this study were to define statistical models and estimate genetic parameters for TV in lactating sows using random regression models, and identify genomic regions and candidate genes associated with HS indicators derived from automatically-recorded TV. Results Heritability estimates for TV ranged from 0.14 to 0.20 over time (throughout the day and measurement period) and from 0.09 to 0.18 along environmental gradients (EG, − 3.5 to 2.2, which correspond to dew point values from 14.87 to 28.19 ˚C). Repeatability estimates of TV over time and along EG ranged from 0.57 to 0.66 and from 0.54 to 0.77, respectively. TV measured from 12h00 to 16h00 had moderately high estimates of heritability (0.20) and repeatability (0.64), indicating that this period might be the most suitable for recording TV for genetic selection purposes. Significant genotype-by-environment interactions (GxE) were observed and the moderately high estimates of genetic correlations between pairs of extreme EG indicate potential re-ranking of selection candidates across EG. Two important genomic regions on chromosomes 10 (59.370–59.998 Mb) and16 (21.548–21.966 Mb) were identified. These regions harbor the genes CDC123, CAMK1d, SEC61A2, and NUDT5 that are associated with immunity, protein transport, and energy metabolism. Across the four time-periods, respectively 12, 13, 16, and 10 associated genomic regions across 14 chromosomes were identified for TV. For the three EG classes, respectively 18, 15, and 14 associated genomic windows were identified for TV, respectively. Each time-period and EG class had uniquely enriched genes with identified specific biological functions, including regulation of the nervous system, metabolism and hormone production. Conclusions TV is a heritable trait with substantial additive genetic variation and represents a promising indicator trait to select pigs for improved heat tolerance. Moderate GxE for TV exist, indicating potential re-ranking of selection candidates across EG. TV is a highly polygenic trait regulated by a complex interplay of physiological, cellular and behavioral mechanisms.

ABSTRACT: l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1–3) and reduced (P2; wk 4–8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.

Abstract Background Non-additive genetic effects are often ignored in livestock genetic evaluations. However, fitting them in the models could improve the accuracy of genomic breeding values. Furthermore, non-additive genetic effects contribute to heterosis, which could be optimized through mating designs. Traits related to fitness and adaptation, such as heat tolerance, tend to be more influenced by non-additive genetic effects. In this context, the primary objectives of this study were to estimate variance components and assess the predictive performance of genomic prediction of breeding values based on alternative models and two independent datasets, including performance records from a purebred pig population and heat tolerance indicators recorded in crossbred lactating sows. Results Including non-additive genetic effects when modelling performance traits in purebred pigs had no effect on the residual variance estimates for most of the traits, but lower additive genetic variances were observed, especially when additive-by-additive epistasis was included in the models. Furthermore, including non-additive genetic effects did not improve the prediction accuracy of genomic breeding values, but there was animal re-ranking across the models. For the heat tolerance indicators recorded in a crossbred population, most traits had small non-additive genetic variance with large standard error estimates. Nevertheless, panting score and hair density presented substantial additive-by-additive epistatic variance. Panting score had an epistatic variance estimate of 0.1379, which accounted for 82.22% of the total genetic variance. For hair density, the epistatic variance estimates ranged from 0.1745 to 0.1845, which represent 64.95–69.59% of the total genetic variance. Conclusions Including non-additive genetic effects in the models did not improve the accuracy of genomic breeding values for performance traits in purebred pigs, but there was substantial re-ranking of selection candidates depending on the model fitted. Except for panting score and hair density, low non-additive genetic variance estimates were observed for heat tolerance indicators in crossbred pigs.

Abstract The major significance of the 2018 gingivitis classification criteria is utilizing a simple, objective, and reliable clinical sign, bleeding on probing score (BOP%), to diagnose gingivitis. However, studies report variations in gingivitis diagnoses with the potential to under- or over-estimating disease occurrence. This study determined the agreement between gingivitis diagnoses generated using the 2018 criteria (BOP%) versus diagnoses using BOP% and other gingival visual assessments. We conducted a retrospective study of 28,908 patients' electronic dental records (EDR) from January-2009 to December-2014, at the Indiana University School of Dentistry. Computational and natural language processing (NLP) approaches were developed to diagnose gingivitis cases from BOP% and retrieve diagnoses from clinical notes. Subsequently, we determined the agreement between BOP%-generated diagnoses and clinician-recorded diagnoses. A thirty-four percent agreement was present between BOP%-generated diagnoses and clinician-recorded diagnoses for disease status (no gingivitis/gingivitis) and a 9% agreement for the disease extent (localized/generalized gingivitis). The computational program and NLP performed excellently with 99.5% and 98% f-1 measures, respectively. Sixty-six percent of patients diagnosed with gingivitis were reclassified as having healthy gingiva based on the 2018 diagnostic classification. The results indicate potential challenges with clinicians adopting the new diagnostic criterion as they transition to using the BOP% alone and not considering the visual signs of inflammation. Periodic training and calibration could facilitate clinicians' and researchers' adoption of the 2018 diagnostic system. The informatics approaches developed could be utilized to automate diagnostic findings from EDR charting and clinical notes.

Abstract Background This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan without the need for the repeated acquisitions required for averaging. Methods Each of the healthy eyes and eyes from diabetic subjects that were prospectively enrolled in this cross-sectional study underwent four repeated 6 × 6 mm macular scans (PLEX Elite 9000 SS-OCT), and the repeated scans of each eye were co-registered to produce 4-frame averages. This prospective dataset of original (single-frame) enface scans and their corresponding averaged scans was divided into a training dataset and a validation dataset. In the training dataset, a DL algorithm (named pseudoaveraging) was trained using original scans as input and 4-frame averages as target. In the validation dataset, the pseudoaveraging algorithm was applied to single-frame scans to produce pseudoaveraged scans, and the single-frame and its corresponding averaged and pseudoaveraged scans were all qualitatively compared. In a separate retrospectively collected dataset of single-frame scans from eyes of diabetic subjects, the DL algorithm was applied, and the produced pseudoaveraged scan was qualitatively compared against its corresponding original. Results This study included 39 eyes that comprised the prospective dataset (split into 5 eyes for training and 34 eyes for validating the DL algorithm), and 105 eyes that comprised the retrospective test dataset. Of the total 144 study eyes, 58% had any level of diabetic retinopathy (with and without diabetic macular edema), and the rest were from healthy eyes or eyes of diabetic subjects but without diabetic retinopathy and without macular edema. Grading results in the validation dataset showed that the pseudoaveraged enface scan ranked best in overall scan quality, background noise reduction, and visibility of microaneurysms (p

Abstract Background Genetic selection based on direct indicators of heat stress could capture additional mechanisms that are involved in heat stress response and enable more accurate selection for more heat-tolerant individuals. Therefore, the main objectives of this study were to estimate genetic parameters for various heat stress indicators in a commercial population of Landrace × Large White lactating sows measured under heat stress conditions. The main indicators evaluated were: skin surface temperatures (SST), automatically-recorded vaginal temperature (TV), respiration rate (RR), panting score (PS), body condition score (BCS), hair density (HD), body size (BS), ear size, and respiration efficiency (Reff). Results Traits based on TV presented moderate heritability estimates, ranging from 0.15 ± 0.02 to 0.29 ± 0.05. Low heritability estimates were found for SST traits (from 0.04 ± 0.01 to 0.06 ± 0.01), RR (0.06 ± 0.01), PS (0.05 0.01), and Reff (0.03 ± 0.01). Moderate to high heritability values were estimated for BCS (0.29 ± 0.04 for caliper measurements and 0.25 ± 0.04 for visual assessments), HD (0.25 ± 0.05), BS (0.33 ± 0.05), ear area (EA; 0.40 ± 0.09), and ear length (EL; 0.32 ± 0.07). High genetic correlations were estimated among SST traits (> 0.78) and among TV traits (> 0.75). Similarly, high genetic correlations were also estimated for RR with PS (0.87 ± 0.02), with BCS measures (0.92 ± 0.04), and with ear measures (0.95 ± 0.03). Low to moderate positive genetic correlations were estimated between SST and TV (from 0.25 ± 0.04 to 0.76 ± 0.07). Low genetic correlations were estimated between TV and BCS (from − 0.01 ± 0.08 to 0.06 ± 0.07). Respiration efficiency was estimated to be positively and moderately correlated with RR (0.36 ± 0.04), PS (0.56 ± 0.03), and BCS (0.56 ± 0.05 for caliper measurements and 0.50 ± 0.05 for the visual assessments). All other trait combinations were lowly genetically correlated. Conclusions A comprehensive landscape of heritabilities and genetic correlations for various thermotolerance indicators in lactating sows were estimated. All traits evaluated are under genetic control and heritable, with different magnitudes, indicating that genetic progress is possible for all of them. The genetic correlation estimates provide evidence for the complex relationships between these traits and confirm the importance of a sub-index of thermotolerance traits to improve heat tolerance in pigs.

Abstract Cholesterol is an essential membrane structural component and steroid hormone precursor, and is involved in numerous signaling processes. Astrocytes regulate brain cholesterol homeostasis and they supply cholesterol to the needs of neurons. ATP-binding cassette transporter A1 (ABCA1) is the main cholesterol efflux transporter in astrocytes. Here we show dysregulated cholesterol homeostasis in astrocytes generated from human induced pluripotent stem cells (iPSCs) derived from males with fragile X syndrome (FXS), which is the most common cause of inherited intellectual disability. ABCA1 levels are reduced in FXS human and mouse astrocytes when compared with controls. Accumulation of cholesterol associates with increased desmosterol and polyunsaturated phospholipids in the lipidome of FXS mouse astrocytes. Abnormal astrocytic responses to cytokine exposure together with altered anti-inflammatory and cytokine profiles of human FXS astrocyte secretome suggest contribution of inflammatory factors to altered cholesterol homeostasis. Our results demonstrate changes of astrocytic lipid metabolism, which can critically regulate membrane properties and affect cholesterol transport in FXS astrocytes, providing target for therapy in FXS.

Abstract Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety. Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites. Results: We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites. Conclusion: The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group (P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Background Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population‐based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD. Methods and Results Data sources were the Canadian CHD database, a nationwide database on CHD (1999–2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan‐Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0–17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person‐years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7–15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11–2.76) among children with a syndrome and 0.79% (95% CI, 0.72–0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia. Conclusions This is the first large population‐based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk‐stratified policy recommendations for cancer surveillance in children with CHD.

Our decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor.

Abstract: The COVID-19 pandemic has significantly impacted healthcare systems worldwide, especially on the management of chronic diseases such as cancer. This study explores the effects of COVID-19 on cancer mortality trends in Brazil, Chile, and Peru. The monthly age-standardized mortality rates in different places of death (hospital/clinic or home) were estimated using vital statistics and death certificate databases. An interrupted time series analysis was performed for each country, using the date of lockdown implementation as the intervention point. Overall cancer mortality rates reduced after the implementation of pandemic restrictions, with a significant decrease in Brazil. In total, 75.3%, 55.4%, and 45.7% of deaths in Brazil, Peru, and Chile, respectively, occurred in hospitals. After lockdowns were implemented, at-home deaths increased in all countries, and in-hospital deaths correspondingly decreased only in Chile. Our results suggest that COVID-19 has significantly affected rates of cancer mortality and place of death in Latin America.

These data show the relative amount of chromosomal instability (CIN) in a diverse array of human breast cell types, including non-transformed mammary epithelial cells as well as cancer cell lines. Additional data is also provided from human embryonic and mesenchymal stem cells. To produce this dataset, we compared a published chromosomal instability gene signature against publicly available datasets containing gene expression information for each cell. We then analyzed these data with the Python GSEAPY software package to provide a CIN enrichment score. These data are useful for comparing the relative amounts of CIN in different breast cell types. This includes cells representing the major clinical (ER/PR+, HER2+ & Triple-negative) as well as intrinsic breast cancer subtypes (Luminal B, HER2+, Basal-like and Claudin-low). Our dataset has a great potential for re-use given the recent surge in interest surrounding the role of CIN in breast cancer. The large size of the dataset, coupled with the diversity of the cell types represented, provides numerous possibilities for future comparisons.

Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine–induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.

Post-COVID conditions (PCCs) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about treatment, inflammation, and PCC. Among 882 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of COVID-19 convalescent plasma (CCP) vs control plasma with available biospecimens and symptom data, the association between early CCP treatment, cytokine levels, and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14, and day 90 using a multiplexed sandwich immunoassay (Meso Scale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between CCP treatment, cytokine levels, and PCC were examined using multivariate logistic regression models. One third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and anosmia (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis, female sex (adjusted odds ratio [AOR] = 2.69 [1.93–3.81]), older age (AOR = 1.32 [1.17–1.50]), and elevated baseline levels of IL-6 (AOR = 1.59 [1.02–2.47]) were independently associated with development of PCC. Those who received early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment had statistically significant lower odds of PCC. IMPORTANCE Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.

We argue here that contemporary semiconductor computing technology poses a significant if not insurmountable barrier to the emergence of any artificial general intelligence system, let alone one anticipated by many to be “superintelligent”. This limit on artificial superintelligence (ASI) emerges from the energy requirements of a system that would be more intelligent but orders of magnitude less efficient in energy use than human brains. An ASI would have to supersede not only a single brain but a large population given the effects of collective behavior on the advancement of societies, further multiplying the energy requirement. A hypothetical ASI would likely consume orders of magnitude more energy than what is available in highly-industrialized nations. We estimate the energy use of ASI with an equation we term the “Erasi equation”, for the Energy Requirement for Artificial SuperIntelligence. Additional efficiency consequences will emerge from the current unfocussed and scattered developmental trajectory of AI research. Taken together, these arguments suggest that the emergence of an ASI is highly unlikely in the foreseeable future based on current computer architectures, primarily due to energy constraints, with biomimicry or other new technologies being possible solutions.

The study objective was to evaluate the interaction between corticotrophin releasing factor (CRF) receptor signaling and prophylactic antibiotic administration on intestinal physiology in newly weaned and transported pigs. Pigs (n = 56; 5.70 ± 1.05 kg) were weaned (20.49 ± 0.64 d), a blood sample was taken, and then pigs were given an intraperitoneal injection of saline (SAL; n = 28 pigs) or a CRF receptor antagonist (CRFA; n = 28 pigs; 30 μg/kg body weight; Astressin B), and then were transported in a livestock trailer for 12 h and 49 min. A second and third intraperitoneal injection was given at 4 h 42 min and 11 h 36 min into the transport process, respectively. Following transport, 4 SAL and 4 CRFA pigs were blood sampled and euthanized. The remaining 48 pigs were individually housed and given dietary antibiotics [AB; n = 12 SAL and 12 CRFA pigs; chlortetracycline (441 ppm) + tiamulin (38.6 ppm)] or no dietary antibiotics (NAB; n = 12 SAL and 12 CRFA pigs) for 14 d post-transport. Blood was collected at 12 h and on d 3, 7, and 14, and then pigs were euthanized on d 7 (n = 24) and d 14 (n = 24) post-weaning and transport. Circulating cortisol was reduced (p = 0.05) in CRFA pigs when compared to SAL pigs post-weaning and transport. On d 7, jejunal villus height and crypt depth was greater overall (p < 0.05) in AB-fed pigs versus NAB-fed pigs. On d 14, ileal crypt depth was reduced (p = 0.02) in CRFA pigs when compared to SAL pigs. Jejunal CRF mRNA abundance tended to be reduced (p = 0.09) on d 7 in CRFA pigs versus SAL pigs. On d 14, jejunal tumor necrosis factor-alpha was reduced (p = 0.01) in AB-fed pigs versus NAB-fed pigs. On d 7, change in glucose short-circuit current tended to be increased (p = 0.07) in CRFA pigs fed the AB diet when compared to CRFA pigs fed the NAB diet. In conclusion, CRFA pigs and pigs fed AB had some similar biological intestinal function measures post-weaning and transport.

Abstract Objective To estimate the association between Social Determinants of Health (structural and intermediate) and caries indicators in Chile's Metropolitan Region preschool children. Methods A multilevel cross-sectional study of Social Determinants of Health (SDH) and caries in children aged 1 to 6 years in Chile's Metropolitan Region was conducted in 2014–2015, with three levels: district, school and child. Caries were assessed by the dmft-index and the prevalence of untreated caries. The structural determinants analyzed were Community Human Development Index (CHDI), urban/rural location, school type, caregiver's education and family income. Poisson multilevel regression models were fit. Results The sample size was 2,275 children from 40 schools in 13 districts. While the highest CHDI district had an untreated caries prevalence of 17.1% (12.3–22.7%), in the most disadvantaged district it was 53.9% (95% CI 46.0–61.6%). As family income increased, the probability of untreated caries prevalence decreased (PR = 0.9 95% CI 0.8–1.0). Rural districts had an average dmft-index of 7.3 (95% CI 7.2–7.4), while in urban districts, it was 4.4 (95% CI 4.3–4.5). Higher probabilities of untreated caries prevalence (PR = 3.0 95% CI 2.3–3.9) were observed in rural children. Greater probabilities of untreated caries prevalence (PR = 1.3 95% CI 1.1–1.6) and prevalence of caries experience (PR = 1.3 95% CI 1.1–1.5) were observed in children whose caregivers had a secondary educational level. Conclusions A strong association was observed between the social determinants of health, specifically the structural ones, and the caries indicators studied in children of the Metropolitan Region of Chile. There were notable differences in caries between districts according to social advantage. Rurality and caregiver's education were the most consistent predictors.

Abstract Background The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. Methods We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. Results Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. Conclusions The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400–550 µm) and X-Large (550–800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.

Abstract Background Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019. Methods Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs). Results In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35–39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period. Conclusion The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region.

Abstract Background Lower respiratory infections (LRIs) cause substantial mortality and morbidity. The present study reported and analysed the burden of LRIs in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, etiology, and socio-demographic index (SDI). Methods The data used in this study were sourced from the Global Burden of Disease (GBD) study 2019. The annual incidence, deaths, and disability-adjusted life-years (DALYs) due to LRIs were presented as counts and age-standardised rates per 100,000 population, along with their 95% uncertainty intervals (UIs). The average annual percent changes (AAPC) in the age-standardised incidence, death and DALYs rates were calculated using Joinpoint software and correlations (Pearson’s correlation coefficient) between the AAPCs and SDIs were calculated using Stata software. Results In 2019, there were 34.1 million (95% UI 31.7–36.8) incident cases of LRIs in MENA, with an age-standardised rate of 6510.2 (95% UI 6063.6–6997.8) per 100,000 population. The number of regional DALYs was 4.7 million (95% UI 3.9–5.4), with an age-standardised rate of 888.5 (95% UI 761.1–1019.9) per 100,000 population, which has decreased since 1990. Furthermore, Egypt [8150.8 (95% UI 7535.8–8783.5)] and Afghanistan [61.9 (95% UI 52.1–72.6)] had the highest age-standardised incidence and death rates, respectively. In 2019, the regional incidence and DALY rates were highest in the 1–4 age group, in both females and males. In terms of deaths, pneumococcus and H. influenza type B were the most and least common types of LRIs, respectively. From 1990 to 2019, the burden of LRIs generally decreased with increasing SDI. There were significant positive correlations between SDI and the AAPCs for the age-standardised incidence, death and DALY rates (p

Abstract Background Although thermal indices have been proposed for swine, none to our knowledge differentiate by reproductive stage or predict thermal comfort using behavioral and physiological data. The study objective was to develop a behavior and physiology-based decision support tool to predict thermal comfort and stress in multiparous (3.28 ± 0.81) non-pregnant (n = 11), mid-gestation (n = 13), and late-gestation (n = 12) sows. Results Regression analyses were performed using PROC MIXED in SAS 9.4 to determine the optimal environmental indicator [dry bulb temperature (TDB) and dew point] of heat stress (HS) in non-pregnant, mid-gestation, and late-gestation sows with respiration rate (RR) and body temperature (TB) successively used as the dependent variable in a cubic function. A linear relationship was observed for skin temperature (TS) indicating that TDB rather than the sow HS response impacted TS and so TS was excluded from further analyses. Reproductive stage was significant for all analyses (P

Abstract Alcohol consumption is associated with a number of diseases and injuries, including cardiovascular diseases, cancers, mental and neurological disorders, as well as transport-related injuries. This article reports the alcohol-attributable burden of diseases and injuries at the regional and national levels in the Middle East and North Africa (MENA) region between 1990 and 2019, by sex, age, underlying cause, and Socio-demographic Index (SDI). The regional deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption were reported for the MENA region, between 1990 and 2019, using the methodological framework and analytical strategies adopted by the Global Burden of Disease (GBD) study 2019. The estimates were all reported as counts, population-attributable fractions, and age-standardised rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). Also, the average annual percentage changes were used to represent the trends of age-standardised rates. In 2019, there were an estimated 22.0 thousand deaths (95% UI: 16.1–29.4) and 1.1 million DALYs (0.8–1.3) attributable to alcohol consumption in the MENA region. The number of DALYs attributable to alcohol consumption were much higher in men (878.0 thousand, 691.4–1104.8) than among women (181.8, 138.6–232.0). The overall age-standardised death and DALY rates attributable to alcohol consumption decreased by 34.5% (13.2–48.3) and 31.9% (16.9–42.5), respectively, over the study period. Egypt (10.1 [5.7–16.6]) and Kuwait (1.1 [0.8–1.5]) had the highest and lowest age-standardised death rates attributable to alcohol consumption, respectively. In 2019, the number of deaths and DALYs in the MENA region were highest in those aged 60–64 and 50–54 years, respectively. A negative association was observed between a country’s SDI and their corresponding age-standardised DALY rates over the period 1990 to 2019. Digestive diseases were the main contributor to the alcohol-attributable burden. Over 1990–2019, the regional deaths and DALYs of diseases and injuries attributable to alcohol consumption decreased with AAPC of − 1.45 (− 1.78 to − 1.12) and − 1.31 (− 1.46 to − 1.15), respectively. The death and DALY rates attributable to alcohol consumption in the MENA region have decreased over the past three decades. Further decreases can be facilitated by implementing country-level policies and increasing public awareness.

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. The present study reported the burden of RA in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex, and socio-demographic index (SDI). Publicly available data from the Global Burden of Disease (GBD) 2019 study was used to report the modelled point prevalence, annual incidence, and disability-adjusted life-years (DALYs) of RA, as counts and age-standardised rates with their corresponding 95% uncertainty intervals (UIs). In 2019, RA had an age-standardised point prevalence of 120.6 per 100,000 population (107.0–135.7) and an annual incidence rate of 5.9 (5.2–6.6) in MENA, which have increased 28.3% and 25.2%, respectively, since 1990. In 2019, the number of DALYs due to RA in the region was 103.6 thousand (74.2–136.7), with an age-standardised rate of 19.0 (13.9–24.9) DALYs per 100,000 population, which has increased by 18.6% since 1990 (6.7–28.2). The highest point prevalence was found in females aged 50–54, and in males aged 45–49. The highest number of DALYs was observed in the 50–54 age group. The MENA DALY rate was lower than the global rate (19.0 vs. 39.6 per 100,000), but the rate was higher in all age groups in 2019, when compared with 1990. In addition, from 1990 to 2019 an increased burden from RA was associated with an increase in SDI. In line with global trends, the burden of RA in the MENA region showed a steady increase from 1990 to 2019. This highlights the increasing need for updating the available health data to design more accurate guidelines to enable the early detection and treatment of RA in the MENA countries.

Chromosomal instability (CIN) is critical for tumor evolution, yet its relationship with stemness is unclear. Here, we describe CIN as a key stress induced during tumor initiation that is uniquely tolerated by breast cancer stem cells in an activated signaling state (aCSCs). While we noted elevated CIN specifically in tumors from aCSCs, this was not intrinsic to these cells, as baseline levels were similar to non-stem cell types. This suggests that CIN is induced during tumor initiation, and that aCSCs can better tolerate this stress. Further, this increased CIN may be transient, as it was only in low-burden aCSC tumors, with levels diminishing in more established disease. Phospho-array profiling revealed specific activation of c-Jun stress signaling in aCSCs, which we hypothesized could induce genes responsible for CIN tolerance. Indeed, we identified AXL as a c-Jun dependent gene enriched in aCSCs that enhances resistance to this stress. Thus, CIN tolerance mediated by c-Jun/AXL signaling may be a defining feature of stemness, contributing to breast cancer progression.

Objective To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy.Design Population based, retrospective cohort study.Setting Ontario, Canada, from 20 December 2021 to 31 August 2022.Participants Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy.Main outcome measures Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score

Purpose: This study aimed to characterize contemporary management of Canadian patients with cardiovascular implantable electronic devices (CIEDs) undergoing radiation therapy (RT) in light of updated American Association of Physicists in Medicine guidelines. Methods and Materials: A 22-question web-based survey was distributed to members of the Canadian Association of Radiation Oncology, Canadian Organization of Medical Physicists, and Canadian Association of Medical Radiation Technologists from January to February 2020. Respondent demographics, knowledge, and management practices were elicited. Statistical comparisons by respondent demographics were performed using χ2 and Fisher exact tests. Results: In total, 155 surveys were completed by 54 radiation oncologists, 26 medical physicists, and 75 radiation therapists in academic (51%) and community (49%) practices across all provinces. The majority of respondents (77%) had managed >10 patients with CIEDs in their career. Most respondents (70%) reported using risk-stratified institutional management protocols. Respondents used manufacturer recommendations, rather than American Association of Physicists in Medicine or institutionally recommended dose limits, when the manufacturer limit was 0 Gy (44%), 0 to 2 Gy (45%), or >2 Gy (34%). The majority of respondents (86%) reported institutional policies to refer to a cardiologist for CIED evaluation both before and after completion of RT. Cumulative dose to CIED, pacing dependence, and neutron production were considered during risk stratification by 86%, 74%, and 50% of participants, respectively. Dose and energy thresholds for high-risk management were not known by 45% and 52% of respondents, with radiation oncologists and radiation therapists significantly less likely to report thresholds than medical physicists (P < .001). Although 59% of respondents felt comfortable managing patients with CIEDs, community respondents were less likely to feel comfortable than academic respondents (P = .037). Conclusions: The management of Canadian patients with CIEDs undergoing RT is characterized by variability and uncertainty. National consensus guidelines may have a role in improving provider knowledge and confidence in caring for this growing population.

In recent years, there has been a specific call to not only increase the number of engineering-trained individuals but also to address the lack of diversity in science, technology, engineering and mathematics (STEM) fields, including individuals with disabilities. In particular, students with learning disabilities (SWLDs) make up a large portion of all students and are, therefore, a crucial population on which to focus educational and career progression efforts. One potential means of promoting persistence along the STEM pipeline—engineering specifically—is through engineering career and technical education (E-CTE) coursework in high school. Using a nationally representative dataset, we explore how E-CTE participation links to college preparation and transition activities for SWLDs, including math SAT performance, dual credit course participation, college application, and FAFSA completion. Under our more rigorous school fixed-effects models, we find that E-CTE participation is associated with beneficial results across each of our outcomes. The implications are discussed.

Objectives: The purpose of this study is to determine whether or not left ventricular remodeling can be induced after septal myectomy in patients with obstructive hypertrophic cardiomyopathy, and if so, how it occurs, using gated cardiac computed tomography. Methods: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent septal myectomy along the septal band between March 2016 and July 2020 were retrospectively reviewed. Recent consecutive 19 patients underwent postoperative cardiac computed tomography. In these patients, volumes of the septal band and thickness of 17 left ventricular myocardial segments were measured to determine the changes after surgery. Results: The resection volume predicted by preoperative computed tomography and the actual resection volume were 6.7 ± 3.3 mL and 6.4 ± 2.7 mL. In-hospital mortality was 0%. Moderate or greater mitral valve regurgitation and systolic anterior motion decreased from 56% to 6% and 86% to 6%, respectively. Median preoperative ventricular septal thickness and left ventricular outflow tract pressure gradient at rest decreased from 20.0 mm (interquartile range, 17.0-24.0 mm) and 74.0 mm Hg (interquartile range, 42.5-92.5 mm Hg) to 14.0 mm (interquartile range, 11.5-16.0 mm) and 15.5 mm Hg (interquartile range, 12.1-21.5 mm Hg), respectively. Postoperative computed tomography confirmed a reduction in septal band volume of 5.7 ± 2.8 mL. Total left ventricular myocardial volume was reduced by 12.9 ± 8.8 mL, which exceeded the volume reduction of the resected septal band. All segments except the basal inferior and basal inferolateral regions showed a significant decrease in wall thickness by a median of 6.4%. Conclusions: Properly performed septal myectomy may induce remodeling of the entire left ventricle, not just the resected area.

Abstract Background Cancers are leading causes of mortality and morbidity, with smoking being recognized as a significant risk factor for many types of cancer. We aimed to report the cancer burden attributable to tobacco smoking by sex, age, socio‐demographic index (SDI), and cancer type in 204 countries and territories from 1990 to 2019. Methods The burden of cancers attributable to smoking was reported between 1990 and 2019, based upon the Comparative Risk Assessment approach used in the Global Burden of Disease (GBD) study 2019. Results Globally, in 2019 there were an estimated 2.5 million cancer‐related deaths (95% UI: 2.3 to 2.7) and 56.4 million DALYs (51.3 to 61.7) attributable to smoking. The global age‐standardized death and DALY rates of cancers attributable to smoking per 100,000 decreased by 23.0% (−29.5 to −15.8) and 28.6% (−35.1 to −21.5), respectively, over the period 1990–2019. Central Europe (50.4 [44.4 to 57.6]) and Western Sub‐Saharan Africa (6.7 [5.7 to 8.0]) had the highest and lowest age‐standardized death rates, respectively, for cancers attributable to smoking. In 2019, the age‐standardized DALY rate of cancers attributable to smoking was highest in Greenland (2224.0 [1804.5 to 2678.8]) and lowest in Ethiopia (72.2 [51.2 to 98.0]). Also in 2019, the global number of DALYs was highest in the 65–69 age group and there was a positive association between SDI and the age‐standardized DALY rate. Conclusions The results of this study clearly illustrate that renewed efforts are required to increase utilization of evidence‐based smoking cessation support in order to reduce the burden of smoking‐related diseases.

Abstract Introduction Tension-type headache (TTH) is the most prevalent neurological disorder. As there is a gap in the literature regarding the disease burden attributable to TTH in the Middle East and North Africa (MENA) region, the aim of the present study was to report the epidemiological indicators of TTH in MENA, from 1990 to 2019, by sex, age and socio-demographic index (SDI). Methods Publicly available data on the point prevalence, annual incidence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for the 21 countries and territories in MENA, between 1990 and 2019. The results were presented with numbers and age-standardised rates per 100000 population, along with their corresponding 95% uncertainty intervals (UIs). Results In 2019, the age-standardised point prevalence and annual incidence rates for TTH in the MENA region were 24504.5 and 8680.1 per 100000, respectively, which represents a 2.0% and a 0.9% increase over 1990-2019, respectively. The age-standardised YLD rate of TTH in this region in 2019 was estimated to be 68.1 per 100000 population, which has increased 1.0% since 1990. Iran [29640.4] had the highest age-standardised point prevalence rate for TTH, while Turkey [21726.3] had the lowest. In 2019, the regional point prevalence of TTH was highest in the 35-39 and 70-74 age groups, for males and females, respectively. Furthermore, the number of prevalent cases was estimated to be highest in those aged 35-39 and 25-29 years, in both males and females, respectively. Moreover, the burden of TTH was not observed to have a clear association with SDI. Conclusions While the prevalence of TTH in the MENA region increased from 1990 to 2019, the incidence rate did not change. In addition, the burden of TTH in MENA was higher than at the global level for both sexes and all age groups. Therefore, prevention of TTH would help alleviate the attributable burden imposed on the hundreds of millions of people suffering from TTH around the region.

Abstract Background and objective To examine the relationship between gene expression profile class and tumor thickness reduction as measured by ultrasonography in response to plaque brachytherapy using a single-center, retrospective cohort study. Methods A total of 15 patients with choroidal melanoma who underwent biopsy for gene expression profiling and were treated with plaque brachytherapy from a single institution from 12/8/14 through 12/19/19 were retrospectively reviewed for clinical characteristics and rate of tumor regression. Ultrasonographic B-scan tumor height was recorded just prior to plaque placement and following plaque removal in the patient’s chart to assess percent reduction in tumor thickness from baseline. Results A total of 15 patients met inclusion criteria and were analyzed in this study. Minimum follow-up was 6 months after plaque removal. The percent regression in tumor thickness from baseline as measured by ultrasonography was greater for class 2 tumors than for class 1 tumors at 12-month follow up after treatment, and this difference was statistically significant (P = 0.012). There was no statistical significance in reduction at 3 months (P = 0.46) and 9 months (P = 0.10) after plaque brachytherapy. Although not statistically significant, class 2 tumors appeared to regress more rapidly than class 1 tumors in response to radiation. Conclusions In this study, class 2 choroidal melanoma tumors show a more rapid anatomic response to treatment than class 1 tumors at 12 months post plaque brachytherapy.