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IntroductionSpecial Operations Forces (SOF) often conduct operations in physiologically stressful environments such as severe heat, cold, or hypoxia, which can induce decreases in a variety of cognitive abilities. Given the promising empirical demonstration of the efficacy of exogenous ketone monoester (KME) supplementation in attenuating cognitive performance decrease during hypoxia at rest in a laboratory setting, we conducted a real-world, field experiment examining KME’s efficacy during high-altitude mountaineering, an austere environment in which US SOF have conducted increasing numbers of operations over the past two decades.MethodsSpecifically, 34 students and cadre at the US Army 10th Special Forces Group Special Operations Advanced Mountaineering School (SOAMS) participated in a randomized, double-blind, placebo (PLA)–controlled crossover trial (KME vs. PLA) over 2 days of tactical mountain operations training. The participants ascended from 7,500 ft in altitude (basecamp) to 12,460 ft on 1 day and 13,627 ft the other day (in randomized order), while performing various training activities inducing high physical and cognitive loads over 8–12 h, and consumed six doses of KME or PLA 2–3 h apart throughout each training day.Results and DiscussionWhile KME increased blood ketone levels and decreased glucose levels, there were no clear indications that the elevated ketone level enhanced physical or cognitive performance. KME also produced a greater incidence of heartburn, nausea, and vomiting. In these elite operators, high-altitude mountaineering had a limited impact on cognitive performance, and KME supplementation did not demonstrate any benefit.

Abstract Background Immigration is a disruptive event with multiple implications for health. Stressors, including family separation, acculturation, job insecurity, restricted mobility, sojourns, dangerous border crossings, stigmatization, and marginalization, shape immigrant health in ways we are only beginning to untangle. Around the world, there are over 200 million international migrants. In 2015, there were 43.2 million immigrants living in the US, 26.8% of whom were born in Mexico. Investigating how stress affects health among migrants facilitates better understanding of their experiences. Methods Here, we review existing research on stress and how allostatic load varies among migrants with specific attention to Mexican migrants in the US. Next, we explore research incorporating biomarkers of allostasis and narratives of migration and settlement to examine disease risks of Mexican migrants residing in Columbus, Ohio. This mixed-methods approach allowed us to examine how social stressors may influence self-reports of health differentially from associations with assessed discrimination and physiological biomarkers of health. Results These data sources are not significantly associated. Neither narratives nor self-reports of health provide significant proxies for participants’ physiological health. Conclusions We propose, the pairing of objectively assessed health profiles with narratives of migration better illustrate risks migrants face, while allowing us to discern pathways through which future health challenges may arise. Immigration and acculturation to a new nation are biologically and culturally embedded processes, as are stress and allostatic responses. To understand how the former covary with the latter requires a mixed-methods bioethnographic approach. Differences across multiple social and physiological systems, affect individual health over time. We propose incorporating physiological biomarkers and allostatic load with migrants’ narratives of their migration to unravel complex relationships between acculturation and health.

The transcriptome of porcine peripheral blood mononuclear cells (PBMC) at single cell (sc) resolution is well described, but little is understood about the cis-regulatory mechanism behind scPBMC gene expression. Here, we profiled the open chromatin landscape of porcine PBMC that define cis-regulatory elements and mechanism contributing to the transcription using single nucleus ATAC sequencing (snATAC-seq). Approximately 22 % of the identified peaks overlapped with annotated transcription start sites (TSS). Using clustering based on open chromatin pattern similarity, we demonstrate that cell type annotations using snATAC-seq are highly concordant to that reported for sc RNA sequencing (scRNA-seq). The differentially accessible peaks (DAPs) for each cell type were characterized and the pattern of accessibility of the DAPs near cell type markers across cell types was similar to that of the average gene expression level of corresponding marker genes. Additionally, we found that peaks identified in snATAC-seq have the potential power to predict the cell type specific transcription starting site (TSS). We identified both transcription factors (TFs) whose binding motif were enriched in cell type DAPs of multiple cell types and cell type specific TFs by conducting transcription factor binding motif (TFBM) analysis. Furthermore, we identified the putative enhancer or promoter regions bound by TFs for each differentially expressed gene (DEG) with a DAP that overlapped with its TSS by generating cis-co-accessibility networks (CCAN). To predict the regulators of such DEGs, TFBM analysis was performed for each CCAN. The regulator TF-target DEG pairs predicted in this way were largely consistent with the results reported in the ENCODE Transcription Factor Targets Dataset (TFTD). This snATAC-seq approach provides insights into the regulation of chromatin accessibility landscape of porcine PBMCs and enables discovery of TFs predicted to control DEG through binding regulatory elements whose chromatin accessibility correlates with the DEG promoter region., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Disease resilience is the ability of an animal to maintain productive performance under disease conditions and is an important selection target. In pig breeding programs, disease resilience must be evaluated on selection candidates without exposing them to disease. To identify potential genetic indicators for disease resilience that can be measured on selection candidates, we focused on the blood transcriptome of 1594 young healthy pigs with subsequent records on disease resilience. Transcriptome data were obtained by 3'mRNA sequencing and genotype data were from a 650 K genotyping array., Results: Heritabilities of the expression of 16,545 genes were estimated, of which 5665 genes showed significant estimates of heritability (p < 0.05), ranging from 0.05 to 0.90, with or without accounting for white blood cell composition. Genes with heritable expression levels were spread across chromosomes, but were enriched in the swine leukocyte antigen region (average estimate > 0.2). The correlation of heritability estimates with the corresponding estimates obtained for genes expressed in human blood was weak but a sizable number of genes with heritable expression levels overlapped. Genes with heritable expression levels were significantly enriched for biological processes such as cell activation, immune system process, stress response, and leukocyte activation, and were involved in various disease annotations such as RNA virus infection, including SARS-Cov2, as well as liver disease, and inflammation. To estimate genetic correlations with disease resilience, 3205 genotyped pigs, including the 1594 pigs with transcriptome data, were evaluated for disease resilience following their exposure to a natural polymicrobial disease challenge. Significant genetic correlations (p < 0.05) were observed with all resilience phenotypes, although few exceeded expected false discovery rates. Enrichment analysis of genes ranked by estimates of genetic correlations with resilience phenotypes revealed significance for biological processes such as regulation of cytokines, including interleukins and interferons, and chaperone mediated protein folding., Conclusions: These results suggest that expression levels in the blood of young healthy pigs for genes in biological pathways related to immunity and endoplasmic reticulum stress have potential to be used as genetic indicator traits to select for disease resilience., (© 2023. The Author(s).)

Transplantation of human xenografts onto immunocompromised mice is a powerful research tool for studying wound healing. However, differences in healing between humans and mice and their small size limit this model. We determined whether human cadaver skin xenografts transplanted onto pigs with severe combined immune deficiency (SCID) would survive and not be rejected. Meshed (1:1.5), cryopreserved human cadaver skin was transplanted onto 10 partial thickness dermatome wounds in each of two normal domestic pigs and two SCID pigs. Autografts (n = 2/animal) from the four animals were used as controls. In normal pigs, all autografts were engrafted and healed with a minimal, if any, inflammation and scarring. All human xenografts were rejected by the normal pigs within 5-11 days and associated with an intense T-cell inflammatory response. In contrast, both autografts and xenografts were engrafted and survived the 28-day study in the SCID pigs with a minimal inflammation and no gross scarring., (© 2019 by the Wound Healing Society.)

Surgical diseases of the thyroid in the pediatric population represent a diverse set of both benign and malignant conditions. Overall, incidence is rare. Benign conditions include Graves' disease, toxic adenomas, congenital hyperthyroidism, and goiter. Differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC), with its related familial cancer syndromes, are the most common malignancies. Near-total or total thyroidectomy is the appropriate surgery for thyroid cancer, with/out central lymph node dissection. Emerging practice guidelines from professional societies are helpful, although they generally have not addressed surgical management of the pediatric patient. Thyroidectomy in children is associated with a higher rate of complications, such as recurrent laryngeal nerve injury and hypoparathyroidism, as compared to the surgery in adults. Therefore, it is essential that pediatric thyroidectomy be performed by high-volume thyroid surgeons, regardless of specialty. Case volume to support surgical expertise usually must be borrowed from the adult experience, given the relative paucity of pediatric thyroidectomies at an institutional level. These surgeons should work as part of a multidisciplinary team that includes pediatric endocrinologists and anesthesiologists, pediatricians, nuclear medicine physicians, and pathologists to afford children the best clinical outcomes.

Treatment of bipolar disorder often results in patients taking several drugs in an attempt to alleviate residual depressive symptoms, which can lead to an accumulation of side effects. New treatments for bipolar depression that do not increase the side effect burden are needed. One nonpharmacological treatment with few side effects, bright light therapy, has been shown to be an effective therapy for seasonal affective disorder, yet has not been extensively studied for other forms of depression. Forty-four adults with bipolar disorder, depressed phase were randomized to treatment with bright light therapy, low-density or high-density negative ion generator for 8 weeks. The primary measure of efficacy was the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS). Adverse events were assessed using the Young Mania Rating Scale (YMRS) and Systematic Assessment for Treatment Emergent effects (SAFTEE). All outcome variables were statistically analyzed using a mixed model repeated measure analysis of variance (ANOVA). The results showed no statistically significant differences between groups in any outcome measures at study end point; adverse events, including switches into hypomania, were rare. Further research is needed to determine the efficacy of bright light therapy in this population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

To determine annotations of the sequence elements on microarrays used for transcriptional profiling experiments in livestock species, currently researchers must either use the sparse direct annotations available for these species or create their own annotations. ANEXdb ( http://www.anexdb.org ) is an open-source web application that supports integrated access of two databases that house microarray expression (ExpressDB) and EST annotation (AnnotDB) data. The expression database currently supports storage and querying of Affymetrix-based expression data as well as retrieval of experiments in a form ready for NCBI-GEO submission; these services are available online. AnnotDB currently houses a novel assembly of approximately 1.6 million unique porcine-expressed sequence reads called the Iowa Porcine Assembly (IPA), which consists of 140,087 consensus sequences, the Iowa Tentative Consensus (ITC) sequences, and 103,888 singletons. The IPA has been annotated via transfer of information from homologs identified through sequence alignment to NCBI RefSeq. These annotated sequences have been mapped to the Affymetrix porcine array elements, providing annotation for 22,569 of the 23,937 (94%) porcine-specific probe sets, of which 19,253 (80%) are linked to an NCBI RefSeq entry. The ITC has also been mined for sequence variation, providing evidence for up to 202,383 SNPs, 62,048 deletions, and 958 insertions in porcine-expressed sequence. These results create a single location to obtain porcine annotation of and sequence variation in differently expressed genes in expression experiments, thus permitting possible identification of causal variants in such genes of interest. The ANEXdb application is open source and available from SourceForge.net.

Objective: To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity., Methods: This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (

In order to expand the comparative map between human chromosome 3 (HSA3) and porcine chromosome 13 (SSC13), seven genes from HSA3 were mapped on SSC13 by fluorescence in situ hybridisation (FISH), viz. ACAA1, ACPP, B4GALT4, LTF, MYLK, PDHB and RARB. With a view to integrating this expanded comparative map with the existing SSC13 linkage map, we used the INRA-University of Minnesota porcine Radiation Hybrid panel (IMpRH) to localize more precisely and to order 15 genes on the SSC13 map, viz. ACPP, ADCY5, APOD, BCHE, CD86, DRD3, GAP43, PCCB, RAF1, RHO, SI, TF, TFRC, TOP2B and ZNF148. In this way, we were able to create an integrated map, containing 38 type I and 81 type II markers, by correlating the linkage, radiation hybrid (RH) and cytogenetic maps of SSC13. This integrated map will give us the opportunity to take maximal advantage of the comparative mapping strategy for positional candidate cloning of genes responsible for economically important traits., (Copyright 2001 S. Karger AG, Basel)

Identification of individual major genes affecting quantitative traits in livestock species has been limited to date. By using a candidate gene approach and a divergent breed cross involving the Chinese Meishan pig, we have shown that a specific allele of the estrogen receptor (ER) locus is associated with increased litter size. Female pigs from synthetic lines with a 50% Meishan background that were homozygous for this beneficial allele produced 2.3 more pigs in first parities and 1.5 more pigs averaged over all parities than females from the same synthetic lines and homozygous for the undesirable allele. This beneficial ER allele was also found in pigs with Large White breed ancestory. Analysis of females with Large White breed background showed an advantage for females homozygous for the beneficial allele as compared to females homozygous for the other allele of more than 1 total pig born. Analyses of growth performance test records detected no significant unfavorable associations of the beneficial allele with growth and developmental traits. Mapping of the ER gene demonstrated that the closest known genes or markers were 3 centimorgans from ER. To our knowledge, one of these, superoxide dismutase gene (SOD2), was mapped for the first time in the pig. Analysis of ER and these linked markers indicated that ER is the best predictor of litter size differences. Introgression of the beneficial allele into commercial pig breeding lines, in which the allele was not present, and marker-assisted selection for the beneficial allele in lines with Meishan and Large White background have begun.