Search

General surgery is a dynamic and multifaceted field influenced by diverse factors, ranging from cultural norms to healthcare system structures and technological advancements. This review paper delves into a comparative exploration of the educational landscapes in Canada and India, unravelling the intricacies of training aspiring general surgeons. As two nations with distinct healthcare systems and educational frameworks, Canada and India offer unique perspectives on the journey from medical school to independent surgical practice. This article compares the residency application process, training structure, assessment methods, challenges faced during clinical training and the role of research in surgical programmes between the two nations. Through this comparative lens, we seek to provide valuable insights that may inform future developments in surgical education, fostering a global exchange of knowledge and practices to advance healthcare systems worldwide.

Abstract Glioblastoma accounts for nearly half of all primary malignant brain tumors in adults, and despite an aggressive standard of care, including excisional surgery and adjuvant chemoradiation, recurrence remains universal, with an overall median survival of 14.6 months. Recent work has revealed the importance of passenger mutations as critical mediators of metabolic adaptation in cancer progression. In our previous work, we identified a role for the epigenetic modifier ID-1 in temozolomide resistance in glioblastoma. Here, we show that ID-1-mediated glioblastoma tumourigenesis is accompanied by upregulation of one-carbon (1-C) mediated de novo purine synthesis. ID-1 knockout results in a significant reduction in the expression of 1-C metabolism and purine synthesis enzymes. Analysis of glioblastoma surgical specimens at initial presentation and recurrence reveals that 1-C purine synthesis metabolic enzymes are enriched in recurrent glioblastoma and that their expression correlates with a shorter time to tumor recurrence. Further, we show that the 1-C metabolic phenotype underlies proliferative capacity and temozolomide resistance in glioblastoma cells. Supplementation with exogenous purines restores proliferation in ID-1-deficient cells, while inhibition of purine synthesis with AICAR sensitizes temozolomide-resistant glioblastoma cells to temozolomide chemotherapy. Our data suggest that the metabolic phenotype observed in treatment-resistant glioma cells is a potential therapeutic target in glioblastoma.

Industrial hemp (Cannabis sativa) production is complex, with strict regulatory constraints and challenges associated with a lack of labeled pesticides due to its status as a novel crop in the US. Four experiments were conducted in 2020 and 2021 to establish herbicide tolerances for hemp production in the coastal plain of Georgia, USA. Objectives included evaluating hemp response to pretransplant or posttransplant herbicides, determining if planting method influenced herbicide injury from residual preplant applied herbicides, and understanding how plastic mulch may influence hemp flower yields. When applied one day prior to transplanting, maximum hemp crop visual injury was less than 12% compared to the untreated control, with acetochlor, flumioxazin, fomesafen, pendimethalin, and norflurazon while dithiopyr, halosulfuron, isoxaben, and isoxaflutole resulted in greater than 50% injury. Posttransplant applications of S-metolachlor, acetochlor, pendimethalin, and clethodim resulted in less than 15% injury while halosulfuron, metribuzin, trifloxysulfuron, imazethapyr, and prometryn applications resulted in greater than 50% injury to plants. Preplant and posttransplant applied herbicides were found to have little effect on total tetrahydrocannabinol (THC), cannabidiol (CBD), or total cannabinoids in the dry flower after harvest. In a separate experiment, injury from halosulfuron and metribuzin was 52% to 56% less when planted with a mechanical transplanter as compared to the practice of using a transplant wheel to depress a hole in the soil followed by hand transplanting. In the final experiment, hemp dry flower yield in a non-plastic mulched (bareground) system was similar to that in a plastic mulched system. However, early season plant above-ground biomass was less in the plastic mulched system, which may have been due to elevated soil temperatures inhibiting early season growth.

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.

Pseudomonas syringae pv. tomato (Pst) is the causal agent of bacterial speck disease in tomatoes. The Pto/Prf gene cluster from Solanum pimpinellifolium was introgressed into several modern tomato cultivars and provided protection against Pst race 0 strains for many decades. However, virulent Pst race 1 strains that evade Pto-mediated immunity now predominate in tomato-growing regions worldwide. Here we report the identification of resistance to a Pst race 1 strain (Pst19) in the wild tomato accession S. pimpinellifolium LA1589 (hereafter LA1589), using our rapid high-throughput seedling screen. LA1589 supports less bacterial growth than cultivars, and does not exhibit a hypersensitive response to Pst19. We tested an existing set of 87 Inbred Backcross Lines (IBLs) derived from a cross between susceptible Solanum lycopersicum E-6203 and Solanum pimpinellifolium LA1589 for resistance to Pst19. Using single-marker analysis, we identified three genomic regions associated with resistance. Bacterial growth assays on IBLs confirmed that these regions contribute to resistance in planta. We also mapped candidate genes associated with resistance in a cross between the Solanum lycopersicum var. lycopersicum cultivar Heinz BG-1706 and S. pimpinellifolium LA1589. By comparing candidates from the two mapping approaches, we were able to identify 3 QTL and 5 candidate genes in LA1589 for a role in resistance to Pst19. This work will assist in molecular marker-assisted breeding to protect tomato from bacterial speck disease.

Recent years have witnessed a surge of interest in artificial intelligence (AI). To address AI’s growing visibility and importance, the authors edited a special collection that showcases cutting-edge sociological research on AI in areas such as health and medicine, work and labor, new research methodologies, and policy. The articles collectively position AI as a sociotechnical system, recognizing that AI integrates heterogeneous elements that intertwine the social and the technical. Each article brings different aspects of sociotechnical systems to light. The authors highlight three contributions sociologists are poised to make to the study of AI: (1) critical analysis of AI hype, promotion, and adoption; (2) empirical study of AI’s co-constitution with processes of social life; and (3) identification of avenues for structural change in creating equitable AI futures. The authors call for the development of novel research methods to study distributed AI platforms and for future research on inequalities, power, and data justice.

Summary: Motivated by the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a complete workflow to reproducibly characterize cell types in complex tissues. Our approach combines a flow cytometry (FC) antibody panel with our computational pipeline CelltypeR, enabling dataset aligning, unsupervised clustering optimization, cell type annotating, and statistical comparisons. Applied to human iPSC derived midbrain organoids, it successfully identified the major brain cell types. We performed fluorescence-activated cell sorting of CelltypeR-defined astrocytes, radial glia, and neurons, exploring transcriptional states by single-cell RNA sequencing. Among the sorted neurons, we identified subgroups of dopamine neurons: one reminiscent of substantia nigra cells most vulnerable in Parkinson’s disease. Finally, we used our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets in complex tissues.

T1ρ and Quantitative Susceptibility Mapping (QSM) are evolving as substrates for quantifying the progressive nature of knee osteoarthritis. Objective: To evaluate the effects of spin lock time combinations on depth-dependent T1ρ estimation, in adjunct to QSM, and characterize the degree of shared variance in QSM and T1ρ for the quantitative measurement of articular cartilage. Design: Twenty healthy participants (10 ​M/10F, 22.2 ​± ​3.4 years) underwent bilateral knee MRI using T1ρ MAPPS sequences with varying TSLs ([0–120] ms), along with a 3D spoiled gradient echo for QSM. Five total TSL combinations were used for T1ρ computation, and direct depth-based comparison. Depth-wide variance was assessed in comparison to QSM as a basis to assess for depth-specific variation in T1ρ computations across healthy cartilage. Results: Longer T1ρ relaxation times were observed for TSL combinations with higher spin lock times. Depth-specific differences were documented for both QSM and T1ρ, with most change found at ∼60% depth of the cartilage, relative to the surface. Direct squared linear correlation revealed that most T1ρ TSL combinations can explain over 30% of the variability in QSM, suggesting inherent shared sensitivity to cartilage microstructure. Conclusions: T1ρ mapping is subjective to the spin lock time combinations used for computation of relaxation times. When paired with QSM, both similarities and differences in signal sensitivity may be complementary to capture depth-wide changes in articular cartilage.

This study is to report the demographics, incidence, and patterns of spinal injuries associated with border crossings resulting from a fall from a significant height. A retrospective cohort study was performed at a Level I trauma center from January 2016 to December 2021 to identify all patients who fell from a significant height while traversing the U.S.-Mexico border and were subsequently admitted. A total of 448 patients were identified. Of the 448 patients, 117 (26.2%) had spine injuries and 39 (33.3%) underwent operative fixation. Females had a significantly higher incidence of spine injuries (60% vs. 40%; p?15 (RR?=?3.2; p?15 sustained falls from a higher distance (median 6.1 vs. 5.5?m) and had a longer length of ICU stay (median 3 vs. 0 days). All patients with operative spine injuries had an ISS >15 relative to 50% of patients with non-operative spine injuries (median ISS 20 vs. 15; p?0.001). Patients with spine trauma requiring surgery had a higher incidence of head (RR?=?3.5; p 0.0353) and chest injuries (RR?=?6.0; p?=?0.0238), but a lower incidence of lower extremity injuries (RR?=?0.5; p?

Abstract Background Induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial function in health and disease. Yet, since differentiation and survival of iMGL are highly reliant on colony-stimulating factor 1 receptor (CSF1R) signaling, it is difficult to use iMGL to study microglial dysfunction associated with pathogenic defects in CSF1R. Methods Serial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) patient carrying a c.2350G > A (p.V784M) CSF1R variant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activities. Similarly, molecular and functional characterization of the ALSP patient-derived iMGL was carried out in comparison to healthy control iMGL. Results The newly devised protocol allowed the generation of iMGL with enhanced transcriptomic similarity to cultured primary human microglia and with higher scavenging and inflammatory competence at ~ threefold greater yield compared to the original protocol. Using this protocol, decreased CSF1R autophosphorylation and cell surface expression was observed in iMGL derived from the ALSP patient compared to those derived from healthy controls. Additionally, ALSP patient-derived iMGL presented a migratory defect accompanying a temporal reduction in purinergic receptor P2Y12 (P2RY12) expression, a heightened capacity to internalize myelin, as well as heightened inflammatory response to Pam3CSK4. Poor P2RY12 expression was confirmed to be a consequence of CSF1R haploinsufficiency, as this feature was also observed following CSF1R knockdown or inhibition in mature control iMGL, and in CSF1R WT/KO and CSF1R WT/E633K iMGL compared to their respective isogenic controls. Conclusions We optimized a pre-existing iMGL protocol, generating a powerful tool to study microglial involvement in human neurological diseases. Using the optimized protocol, we have generated for the first time iMGL from an ALSP patient carrying a pathogenic CSF1R variant, with preliminary characterization pointing toward functional alterations in migratory, phagocytic and inflammatory activities. Graphical Abstract

Pilomatricomas (PM) are benign neoplasms that arise from hair follicle matrix cells. They are one of the most frequently excised pediatric skin masses. A typical clinical presentation is a slow growing, painless, firm, superficial mass in the head and neck of a child. We present a rare presentation of PM. A preschool aged girl presented with an enlarging scalp mass following a history of minor blunt trauma to the area. Two months prior, the child sustained a ground level fall and subsequently developed a painless “bump” at the site of injury on the scalp. The ``bump” was initially the size of a “mosquito bite” and enlarged to the size of a “ping pong ball”. Given the rapid progression and history of trauma, there was a broad differential diagnosis. An extensive workup including sonography, computed tomography, MRI, and biopsy were performed. The final pathologic diagnosis was confirmed as pilomatricoma. An atypical presentation of PM in a child can mimic a wide variety of pathology. Our case demonstrates unusual features of rapid enlargement and preceding trauma. With the widespread use of sonography for evaluation of superficial lesions, the radiologist may be the first to suspect the diagnosis of PM. Knowledge of the typical imaging findings in PM can be valuable, especially in more unusual cases.

A rare subseasonal-to-seasonal phenomenon – two consecutive flash drought events interrupted by a period of recovery – occurred across eastern Oklahoma, Arkansas, and southern Missouri, spanning the summer and early fall of 2022. These flash drought events (the first in June–July, the second in August–September) led to severe (D2) and extreme (D3) drought conditions via the United States Drought Monitor across much of the region following the first period of rapid drought intensification, and extreme (D3) and exceptional (D4) drought conditions by the end of the second event. A notable driver of both flash drought events included a persistent upper-level ridge either centered over or shifted west and upstream of the flash drought region, leading to broad-scale subsidence and reduced mid-level moisture which acted to limit precipitation development and increase evaporative demand. In addition, several heatwave events developed during the warm season in 2022 and either (1) acted to drive flash drought development via increased evaporative demand or (2) were enhanced by land surface desiccation and land-atmosphere feedbacks following rapid drought intensification. Furthermore, S2S composite forecasts predicted drought development for both events. However, only 20% of the ensembles predicted rapid drought development associated with flash drought for the first event and 16% of the ensembles predicted rapid drought development during the second event. This result highlights a key challenge in S2S prediction of rapidly developing drought conditions versus that of more conventional and slower drought development. The ensembles that did predict rapid drought intensification were associated with the forecasting of positive 500 hPa geopotential height anomalies over the south-central United States (first event) or an amplified wave pattern centered over the west-central United States (second event). Lastly, the compounding effects of two flash droughts in a single warm season led to substantial impacts on agricultural, environmental, and hydrologic sectors across the region.

ABSTRACT The high-level resistance to next-generation β-lactams frequently found in Staphylococcus aureus isolates lacking mec, which encodes the transpeptidase PBP2a traditionally associated with methicillin-resistant Staphylococcus aureus (MRSA), has remained incompletely understood for decades. A new study by Lai et al. found that the co-occurrence of mutations in pbp4 and gdpP, which respectively cause increased PBP4-mediated cell wall crosslinking and elevated cyclic-di-AMP levels, produces synergistic β-lactam resistance rivaling that of PBP2a-producing MRSA (L.-Y. Lai, N. Satishkumar, S. Cardozo, V. Hemmadi, et al., mBio 15:e02889-23. 2024, https://doi.org/10.1128/mbio.02889-23). The combined mutations are sufficient to explain the high-level β-lactam resistance of some mec-lacking strains, but the mechanism of synergy remains elusive and an avenue for further research. Importantly, the authors establish that co-occurrence of these mutations leads to antibiotic therapy failure in a Caenorhabditis elegans infection model. These results underscore the need to consider this unique and novel β-lactam resistance mechanism during the clinical diagnosis of MRSA, rather than relying on mec as a diagnostic.

Stigmatization is a significant healthcare barrier among individuals who utilize substances during pregnancy. Of the 3.6 million U.S. births each year, approximately 10% are affected by perinatal substance use, an estimate which is likely underestimated due to fear of stigma and prosecution. Of those experiencing perinatal substance use, less than 11% receive treatment, while maternal deaths due to overdose during the postpartum period have increased by 81% from 2017 to 2020. Societal perception of non-pregnant individuals experiencing substance use disorders recognizes the biological basis of addiction, whereas for pregnant individuals, societal perception slides into moral failing as the basis of addiction. Many recommendations and guidelines for decreasing substance use stigmatization among non-pregnant and pregnant individuals exist. We focus on the use of mindfulness in recognizing and addressing structural and social stigma within healthcare systems. Mindfulness has been extracted from its roots as an essential element of the Eightfold Path in Buddhism, which largely centers on living ethically to reduce suffering of self and others. By acknowledging the roots of mindfulness, providers can engage mindfully in practices that help identify one’s overarching personal values and encourage one to lead healthcare encounters compassion and willingness to support help-seeking community members who are experiencing suffering. A deeper awareness of mindfulness practices within the context of ethical conduct can support healthcare shifts away from criminalization toward more patient- and family-centered approaches.

Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.

Public deliberations on artificial intelligence and machine learning (AI/ML) provoke strong interest in automation, or the perceived displacement of human labor due to general technological advances. Social science scholarship on well-compensated technology workers and a growing global underclass suggests automation remains largely a myth, with emerging technologies generating new forms of computational and emotional work. But little research has examined automation from the vantage point of community members at perceived greatest risk of displacement, such as those sustained by generations of logistics labor and physically located in racialized, underserved areas. In the United States and around the globe, logistics work is directly targeted by “automation engineers” to reduce labor costs on behalf of industry interests, posing a severe threat to port workers and their respective communities. This article examines organized community resistance to automation within the Los Angeles Harbor Area, drawing on four public hearings following the Port of LA’s planned integration of autonomous vehicles for the movement of cargo (i.e., automated straddle carriers). We find community mobilizations widely sought to enlarge public consideration of AI/ML to encompass matters of societal well-being and the collective good. These include shifting from the legality of AI integration to underscore public morality in light of anticipated harm, in addition to emphasizing the invisible social arrangements surrounding the Port and nearby community life. Our research reveals how lay people may reassert their own importance when confronted by technoscientific injustice, such as by reframing the future of work toward an insistence on “the future of our communities.”

Abstract The need for widespread occurrence data to inform species conservation has prompted interest in large, national‐scale environmental DNA (eDNA) monitoring strategies. However, targeted eDNA assays are seldom validated for use across broad geographic areas. Here, we validated 46 new and previously published probe‐based qPCR assays targeting invasive species throughout the continental United States. We drew upon current taxonomies, range maps, publicly available sequences, and tissue archives to evaluate all potentially sympatric confamilial species and genetically similar extrafamilial taxa. Out of 5276 unique assay‐nontarget taxon combinations, we were able to test 4206 (80%). We characterized levels of validation and specificity for each of eight federal geographic regions and provided an online tool with state‐level information, as well as detailed assay descriptions in an appendix. Specificity testing benefited from extensive use of eDNAssay—a machine learning classifier trained to predict qPCR cross‐amplification—which we found to be 96% accurate in 649 unique tests that underwent paired in silico and in vitro testing. Predictions of assay specificity (the true negative rate) were 98–100% accurate, depending on the classification threshold used. This work provides both an immediate resource for invasive species surveillance and demonstrates an enhanced in silico, geographically subdivided validation framework to aid in future large‐scale validation efforts.

Implication Statement Medical student-led walk and talk programs, such as Walk with a Future Doc (WWAFD), provide a means for the medical community and community at-large to interact in a non-clinical setting. This environment can increase attendance accountability, enhance patient-provider relationships, and allow medical professionals to be leading examples of healthy, active living. We demonstrate the positive interest for this program, rationale of participants for joining, and the feasibility of its setup. As one of the only WWAFD programs in Canada, we encourage other medical schools to implement this program to promote continuity of hands-on, community-engaged learning amongst their students.

Forensic anthropologists have a responsibility to appropriately relay information about a decedent in medicolegal reports and when communicating with the public. The terms ‘sex’ and ‘sex estimation’ have been applied with numerous, inconsistent definitions under the guise that sex—a broad, complex concept—can be reduced to a female/male binary. This binary does not reflect biocultural realities and harms those whose bodies do not meet social expectations of maleness or femaleness. The University of Nevada, Las Vegas’ Forensic Anthropology and Bioarchaeology Laboratory (UNLV FAB Lab) advocates for the use of the term ‘assigned sex at birth’ (ASAB) to highlight that binary sex is not biologically inherent to the body, but rather, assigned by society. Additionally, we call for the use of disclaimers in case reports to denote the limitations of ASAB estimation methods, the differentiation between those with mixed trait expression (i.e., indeterminate) and those on whom an ASAB analysis cannot be performed (i.e., unknown), and the included consideration of gender in forensic anthropology research and case reports. Such applications challenge biological normalcy, allowing forensic anthropologists to actively advocate for those whose bodies do not meet biocultural expectations.

Abstract Background Inferior vena cava (IVC) filters, while effective in preventing pulmonary embolism, can increase the risk of IVC thrombosis. IVC filter (IVCF) thrombosis can result from emboli getting trapped within the filter, extension of deep vein thrombosis (DVT), or the device’s inherent thrombogenicity causing in situ thrombosis. This condition can cause noticeable clinical symptoms and complicate the removal of the filter due to the potential for thromboembolism, often resulting in temporary filters remaining unextracted. This case report highlights a novel approach employed to mitigate the risk of thromboembolism during the procedure by capturing mobilized thrombus proximally to the entrapped IVCF. Case presentation A 54-year-old woman with a complex medical history including cerebral palsy, Crohn’s disease, and transfusion-dependent iron-deficiency anemia experienced a pulmonary embolism. Due to failed anticoagulation therapy resulting in gastrointestinal bleeding and high transfusion requirements, she underwent placement of an IVCF as a preventive measure against recurrent pulmonary embolism. Three years later, the patient presented with lower extremity swelling and a sudden decline in hemoglobin levels. Diagnostic imaging revealed adherent nonocclusive thrombus within and above the indwelling IVCF. Utilizing the novel Protrieve sheath with the self-expandable Nitinol funnel, successful endovascular removal of the embedded IVCF and adherent thrombus was performed, while mitigating the risk of intraprocedural pulmonary embolism. Conclusions The successful intraprocedural trapping and removal of mobilized thrombus from the IVCF removal was achieved using the Protrieve sheath and Nitinol funnel. This approach provides a promising solution to reduce the risk of embolization during the removal of thrombosed IVCFs, potentially outweighing the complications associated with filter removal.

Abstract Background The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized. Methods In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation. Results In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats. Conclusions Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.

Abstract Relating environmental DNA (eDNA) signal strength to organism abundance requires a fundamental understanding of eDNA production. A number of studies have demonstrated that eDNA production may scale allometrically—that is, larger organisms tend to exhibit lower mass‐specific eDNA production rates, likely due to allometric scaling in key processes related to eDNA production (e.g., surface area, excretion/egestion). While most previous studies have examined intraspecific allometry, physiological rates and organism surface area also scale allometrically across species. We therefore hypothesize that eDNA production will similarly exhibit interspecific allometric scaling. To evaluate this hypothesis, we reanalyzed previously published eDNA data from Stoeckle et al. (ICES Journal of Marine Science, 78(1), 293–304, 2021) which compared metabarcoding read count to organism count and biomass data obtained from trawl surveys off the New Jersey coast. Using a Bayesian model, we empirically estimated the value of the allometric scaling coefficient (“b”) for Northwestern Atlantic bony fishes to be 0.77 (credible interval = 0.64–0.92), although our model failed to converge for Chondrichthyan species. We found that integrating allometry significantly improved correlations between organism abundance and metabarcoding read count relative to traditional metrics of abundance (density and biomass) for bony fishes. Although substantial unexplained variation remains in the relationship between read count and organism abundance, our study provides evidence that eDNA production may scale allometrically across species in some contexts. Future studies investigating the relationship between eDNA signal strength and metrics of fish abundance could potentially be improved by accounting for allometry; to this end, we developed an online tool that can facilitate the integration of allometry in eDNA/abundance relationships.

Abstract Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Abstract The dominant benthic primary producers in coral reef ecosystems are complex holobionts with diverse microbiomes and metabolomes. In this study, we characterize the tissue metabolomes and microbiomes of corals, macroalgae, and crustose coralline algae via an intensive, replicated synoptic survey of a single coral reef system (Waimea Bay, Oʻahu, Hawaii) and use these results to define associations between microbial taxa and metabolites specific to different hosts. Our results quantify and constrain the degree of host specificity of tissue metabolomes and microbiomes at both phylum and genus level. Both microbiome and metabolomes were distinct between calcifiers (corals and CCA) and erect macroalgae. Moreover, our multi-omics investigations highlight common lipid-based immune response pathways across host organisms. In addition, we observed strong covariation among several specific microbial taxa and metabolite classes, suggesting new metabolic roles of symbiosis to further explore.

Abstract Background Upper small intestinal dietary lipids activate a gut-brain axis regulating energy homeostasis. The prebiotic, oligofructose (OFS) improves body weight and adiposity during metabolic dysregulation but the exact mechanisms remain unknown. This study examines whether alterations to the small intestinal microbiota following OFS treatment improve small intestinal lipid-sensing to regulate food intake in high fat (HF)-fed rats. Results In rats fed a HF diet for 4 weeks, OFS supplementation decreased food intake and meal size within 2 days, and reduced body weight and adiposity after 6 weeks. Acute (3 day) OFS treatment restored small intestinal lipid-induced satiation during HF-feeding, and was associated with increased small intestinal CD36 expression, portal GLP-1 levels and hindbrain neuronal activation following a small intestinal lipid infusion. Transplant of the small intestinal microbiota from acute OFS treated donors into HF-fed rats also restored lipid-sensing mechanisms to lower food intake. 16S rRNA gene sequencing revealed that both long and short-term OFS altered the small intestinal microbiota, increasing Bifidobacterium relative abundance. Small intestinal administration of Bifidobacterium pseudolongum to HF-fed rats improved small intestinal lipid-sensing to decrease food intake. Conclusion OFS supplementation rapidly modulates the small intestinal gut microbiota, which mediates improvements in small intestinal lipid sensing mechanisms that control food intake to improve energy homeostasis. Video Abstract

Abstract Background Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease. Case presentation A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient’s initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of

Forensic anthropology and, more broadly, the forensic sciences have only recently begun to acknowledge the importance of lived gender identity in the resolution of forensic cases, the epidemic of anti-transgender violence, and the need to seek practical solutions. The current literature suggests that forensic anthropologists are becoming aware of these issues and are working toward efforts to improve identification of transgender and gender diverse (TGD) persons. The scope of the problem, however, is not limited to methodology and instead can be traced to systemic anti-trans stigma ingrained within our cultural institutions. As such, we call on forensic anthropologists to counteract cisgenderism and transphobia and promote gender equity and inclusion in their practice. In this paper, we identify three areas in which forensic anthropologists may be positioned to intervene on cisgenderist practices and systems: in casework, research, and education. This paper aims to provide strategies for forensic anthropologists to improve resolution of TGD cases, produce more nuanced, gender-informed research, and promote gender equity and inclusion in the field.

Abstract Environmental DNA (eDNA) sampling is a powerful tool for rapidly characterizing biodiversity patterns for specious, cryptic taxa with incomplete taxonomies. One such group that are also of high conservation concern are North American freshwater gastropods. In particular, springsnails of the genus Pyrgulopsis (Family: Hydrobiidae) are prevalent throughout the western United States where >140 species have been described. Many of the described species are narrow endemics known from a single spring or locality, and it is believed that there are likely many additional species which have yet to be described. The distribution of these species across the landscape is of interest because habitat loss and degradation, climate change, groundwater mining, and pollution have resulted in springsnail imperilment rates as high as 92%. Determining distributions with conventional sampling methods is limited by the fact that these snails are often

IntroductionFor African American women in Houston, cervical cancer mortality is disproportionate to their racial and ethnic counterparts. Most notably, lack of human papillomavirus (HPV) screening and vaccination as well as late diagnosis increase cervical cancer mortality. However, cervical cancer is largely preventable. While previous research has identified a few social determinants that are specifically related to cervical cancer (e.g., education, income, neighborhood), there may be a host of additional social and cultural factors that contribute to a lack of preventative behavior.MethodsThe present study used concept mapping to explore sociocultural determinants of cervical cancer prevention beliefs among young African American women. N = 15 African American women, ages 18–25, participated in a group concept mapping session focused on cervical cancer knowledge, beliefs about women’s health, and how their social environment and culture play a role in their conceptualization of cervical cancer prevention.DiscussionFive overarching concepts emerged: (1) Screening, (2) Support System, (3) Cervical Cancer 101 (knowledge), (4) Fatalism, and (5) Ease of Prevention.ConclusionThe present study highlights the use of concept mapping for prevention science, particularly in exploratory studies for understanding cervical cancer screening barriers, avenues for intervention, and public health messaging. We discuss the findings and implications for public health research in cervical cancer prevention tailored for African American women.

Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.

Pinot noir is rapidly becoming a winemaking staple in the Central Coast of California. Therefore, it is important to understand how factors such as fermentation temperature and cap management affect the chemical and sensory impact of such wines. Herein, Pinot noir wines were made with three contrasting alcoholic fermentation temperature regimes (Cold, Cold/Hot, Hot) and combined factorially with two cap management regimes (with or without punch downs). The impact of these factors on colour, aroma, and the temporal retronasal aroma and mouthfeel profile was assessed by a trained sensory panel (n = 13) using descriptive analysis (DA) and time-intensity (TI), respectively. Combining a hot fermentation temperature and no punch downs led to wines with higher colour saturation and purple hue. In contrast, wines fermented at cold fermentation temperatures with no punch downs showed reduction aromas. In terms of individual main effects, wines fermented at cold temperatures had more orthonasal aroma, while wines fermented at hot temperatures had higher astringency. To understand the relationship between selected volatile aromas and perceived sensory results, a partial least square regression (PLSR) was conducted. PLSR indicated that cold fermentation temperature wines with punch downs were associated with esters, including ethyl hexanoate and ethyl heptanoate, as well as β-damascenone, which aligned with sensory results. The effect of salivary flow rate on the temporal sensory profile post-expectoration was also analysed. Low salivary flow rate panellists perceived both astringency and length significantly later and more intensely than high salivary flow rate panellists. However, the time of maximum intensity was perceived significantly later for high salivary flow rate panellists. Overall, fermentation temperature had a more significant impact on the sensory and volatile composition of Pinot noir wines than the cap management regime. However, cap management still appeared to affect sensory and volatile chemistry results through significant interactions. Therefore, the relationship between fermentation temperature and cap management was not straightforward from avolatile chemistry or sensory perspective. The importance of accounting for salivary flow rate in panellists when using time-based sensory analysis was also highlighted.

The ongoing SARS-CoV-2 (COVID-19) pandemic has affected all aspects of life in the United States and around the world. This is particularly true for marginalized and vulnerable groups who face disproportionate levels of violence and premature death within their communities. While general impacts of the pandemic have been well-studied overall, little has been done to examine the correlation between COVID-19 and the risk of suicide among older adults. Older adults are particularly at risk because they face challenges including ageism, inadequate support systems, unreliable transportation, and frequent social isolation. Medicolegal casework offers a unique vantage of these issues, as it aims to identify manner of death which may be influenced by underlying structural vulnerabilities. The current research draws upon data collected from the Clark County Office of the Coroner/Medical Examiner. A sample of 871 older adults (aged 50+), whose manner of death was deemed a suicide between the years 2017–2021, were included in this analysis. Statistical analyses investigated differences between adults aged 50–64, 65–84, and 85+ years. Results suggest statistically significant changes in mechanism of death between pre-pandemic and pandemic periods, indicating a shift in risk factors related to social isolation and the home environment. Understanding such changes in trends directly affects the interpretation of skeletal data in forensic anthropology and thus, should be taken into consideration when developing structural vulnerability profiles. Furthermore, the inclusion of a structural vulnerability approach in forensic case reports has the potential to provide additional context for deaths by suicide and may help develop policies and procedures for mitigating future risk.

Research examining episodic future thinking (EFT; i.e., imagining oneself in future contexts) in community samples has demonstrated reduced discounting of delayed rewards when personalized event cues are included to prompt EFT related to reward latencies. While this EFT effect was recently demonstrated in individuals with substance use disorders, it is not yet known if it manifests similarly in individuals with and without a significant incarceration history—the latter being at elevated risk for negative outcomes including criminal recidivism. Individuals with cocaine use disorder (n = 35) identified personally-relevant future events and participated in a computerized delay discounting task, involving decisions between smaller immediate rewards or larger delayed rewards with and without EFT cues. Individuals with (n = 19) and without (n = 16) a significant history of incarceration were identified using the Addiction Severity Index-Lite. A significant reduction in discounting rates was observed when event cues were included to promote EFT (p = 0.02); however, there was no main effect of incarceration history on discounting behavior, or interaction between episodic future thinking condition and incarceration history. Results suggest personalized cues included to evoke EFT reduce discounting behavior in individuals with cocaine use disorder, regardless of incarceration history. EFT–based interventions may therefore have promise to reduce impulsive decision-making in individuals with cocaine use disorder with and without a significant history of incarceration, potentially supporting improved outcomes with respect to both substance use and future criminality.

Stakeholders need data on health and drivers of health parsed to the boundaries of essential policy-relevant geographies. US Congressional Districts are an example of a policy-relevant geography which generally lack health data. One strategy to generate Congressional District heath data metric estimates is to aggregate estimates from other geographies, for example, from counties or census tracts to Congressional Districts. Doing so requires several methodological decisions. We refine a method to aggregate health metric estimates from one geography to another, using a population weighted approach. The method's accuracy is evaluated by comparing three aggregated metric estimates to metric estimates from the US Census American Community Survey for the same years: Broadband Access, High School Completion, and Unemployment. We then conducted four sensitivity analyses testing: the effect of aggregating counts vs. percentages; impacts of component geography size and data missingness; and extent of population overlap between component and target geographies. Aggregated estimates were very similar to estimates for identical metrics drawn directly from the data source. Sensitivity analyses suggest the following best practices for Congressional district-based metrics: utilizing smaller, more plentiful geographies like census tracts as opposed to larger, less plentiful geographies like counties, despite potential for less stable estimates in smaller geographies; favoring geographies with higher percentage population overlap.

Abstract Nutria (Myocastor coypus) is a semiaquatic rodent species that is invasive across multiple regions within the United States. Here, we evaluated a qPCR assay previously described for use in Japan for application across invasive populations in the United States. We also compared two environmental DNA sampling methodologies for this assay: field filtration of large volumes of water passed through filters versus direct sampling of small volumes of water. We validated assay specificity, generality, and sensitivity, compared assay performance between two independent laboratories, and successfully tested the assay in situ on a known wild population. The filtration method required fewer samples for environmental DNA detection than direct sampling, but the choice of methods should be assessed based on specific field conditions and time and budget considerations. Our extensive assay validation and comparison across laboratories suggest that the assay is ready to be applied in environmental DNA monitoring of nutria throughout the United States.

Abstract Brain stimulation (BStim) encompasses multiple modalities (e.g., deep brain stimulation, responsive neurostimulation) that utilize electrodes implanted in deep brain structures to treat neurological disorders. Currently, BStim is primarily used to treat movement disorders such as Parkinson’s, though indications are expanding to include neuropsychiatric disorders like depression and schizophrenia. Traditional BStim systems are “open-loop” and deliver constant electrical stimulation based on manually-determined parameters. Advancements in BStim have enabled development of “closed-loop” systems that analyze neural biomarkers (e.g., local field potentials in the sub-thalamic nucleus) and adjust electrical modulation in a dynamic, patient-specific, and energy efficient manner. These closed-loop systems enable real-time, context-specific stimulation adjustment to reduce symptom burden. Machine learning (ML) has emerged as a vital component in designing these closed-loop systems as ML models can predict / identify presence of disease symptoms based on neural activity and adaptively learn to modulate stimulation. We queried the US National Library of Medicine PubMed database to understand the role of ML in developing closed-loop BStim systems to treat epilepsy, movement disorders, and neuropsychiatric disorders. Both neural and non-neural network ML algorithms have successfully been leveraged to create closed-loop systems that perform comparably to open-loop systems. For disorders in which the underlying neural pathophysiology is relatively well understood (e.g., Parkinson’s, essential tremor), most work has involved refining ML models that can classify neural signals as aberrant or normal. The same is seen for epilepsy, where most current research has focused on identifying optimal ML model design and integrating closed-loop systems into existing devices. For neuropsychiatric disorders, where the underlying pathologic neural circuitry is still being investigated, research is focused on identifying biomarkers (e.g., local field potentials from brain nuclei) that ML models can use to identify onset of symptoms and stratify severity of disease.

Red spinach extract is high in inorganic nitrate/nitrite (NO3/NO2) which has been shown to enhance vascular function, cognition, and physical performance. To date, there have been no investigations as to whether red spinach extract serves as an effective strategy to improve repeated exercise performance, which is applicable to many sports and activities. The purpose of this study was to investigate the effect of acute red spinach extract ingestion on repeated sprint ability in female athletes. Eleven Division I NCAA female athletes (ages 18–24) were recruited. In a double-blinded, randomized, counterbalanced design, participants completed two separate visits each with a different treatment: placebo (placebo; tomato juice) or red spinach extract (~400 mg nitrate). For each trial, participants consumed their respective treatment two hours before exercise. Following a warm-up, participants completed 3 × 15 s Wingate Anaerobic Tests (WAnTs) separated by 2 min of recovery. A capillary blood sample was obtained pre-exercise to measure NO2 concentrations. Performance outcomes, heart rate (heart rate), and rate of perceived exertion were measured following each WAnT. Blood lactate (La-) was obtained prior to exercise (PRE) and after the completion of the repeated sprints (POST). Each visit was separated by a minimal recovery period of 72 h. Mean power (p = 0.204), peak power (p = 0.067), heart rate (p = 0.151), and rate of perceived exertion (p = 0.379) were not significantly different between treatments. POST La- concentration was significantly higher with red spinach extract when compared to the placebo (p = 0.030). Furthermore, the fatigue index (p = 0.018) was significantly lower with red spinach extract. The results do not support the use of red spinach extract for the enhancement of power output during repeated anaerobic exercise. However, it may result in improved La-/H+ removal from the muscle, thereby combating physical fatigue.

ABSTRACT The VirB protein, encoded by the large virulence plasmid of Shigella spp., is a key transcriptional regulator of virulence genes. Without virB, Shigella cells are avirulent. On the virulence plasmid, VirB functions to offset transcriptional silencing mediated by the nucleoid structuring protein, H-NS, which binds and sequesters AT-rich DNA, making it inaccessible for gene expression. Thus, gaining a mechanistic understanding of how VirB counters H-NS-mediated silencing is of considerable interest. VirB is unusual in that it does not resemble classic transcription factors. Instead, its closest relatives are found in the ParB superfamily, where the best-characterized members function in faithful DNA segregation before cell division. Here, we show that VirB is a fast-evolving member of this superfamily and report for the first time that the VirB protein binds a highly unusual ligand, CTP. VirB binds this nucleoside triphosphate preferentially and with specificity. Based on alignments with members of the ParB family, we identify amino acids of VirB likely to bind CTP. Substitutions in these residues disrupt several well-documented activities of VirB, including its anti-silencing activity, its ability to generate a Congo red positive phenotype, and the ability of the VirB protein to form foci in the bacterial cytoplasm when fused to GFP. Although stably produced, our CTP binding mutants do not bind DNA in vivo, likely explaining these phenotypes. Thus, this work is the first to show that VirB is a bona fide CTP-binding protein, links Shigella virulence phenotypes to the nucleoside triphosphate CTP, and provides novel insight into VirB-CTP-DNA interactions. IMPORTANCE Shigella species cause bacillary dysentery, the second leading cause of diarrheal deaths worldwide. There is a pressing need to identify novel molecular drug targets. Shigella virulence phenotypes are controlled by the transcriptional regulator, VirB. We show that VirB belongs to a fast-evolving, plasmid-borne clade of the ParB superfamily, which has diverged from versions with a distinct cellular role—DNA partitioning. We report that, like classic members of the ParB family, VirB binds a highly unusual ligand, CTP. Mutants predicted to be defective in CTP binding are compromised in a variety of virulence attributes controlled by VirB, likely because these mutants cannot engage DNA. This study (i) reveals that VirB binds CTP, (ii) provides a link between VirB-CTP interactions and Shigella virulence phenotypes, (iii) provides new insight into VirB-CTP-DNA interactions, and (iv) broadens our understanding of the ParB superfamily, a group of bacterial proteins that play critical roles in many bacteria.

The Papahānaumokuākea Marine National Monument, Hawai‘i, is one of the most isolated and protected archipelagos in the world, making it a natural laboratory to examine macroalgal-microbial diversity because of limited direct anthropogenic impacts. We collected the most abundant macroalgae from nine sites ranging from shallow subtidal (1.5 m) to mesophotic (75 m) depths around Manawai (Pearl and Hermes Atoll). We characterized the macroalgal bacterial communities via high-throughput amplicon sequencing and compared the influence of host phylum, species, site, and depth on these relationships at a single atoll. Ochrophyta species had the lowest bacterial diversity compared to Chlorophyta and Rhodophyta. Site and/or depth may influence the microbial community structure associated with Microdictyon setchellianum, indicating a possible disconnect of these microbial communities among habitats. Chondria tumulosa, a cryptogenic species with invasive traits, differed in associated microbiota compared to the native Laurencia galtsoffii, an alga from the same family collected at the same site and depth. While there was overlap of bacterial communities across sites for some algal species, the majority had minimal macroalgal-microbial community connectivity across Manawai. This mesophotic system, therefore, did not appear to be refugia for shallow water coral reefs at microscopic scales. Additional studies are required to identify other significant influences on microbial community variation.

An ionic compound consisting of a triazolium cation and bromide anion, C7H14N3+·Br−, has been synthesized and structurally characterized using single-crystal X-ray diffraction and NMR. The compound crystallizes in the monoclinic space group P21/m with the non-hydrogen atoms of one cation lying on general positions and the others lying on a mirror plane. One bromide ion also lies on the mirror. The extended structure exhibits only weak intermolecular interactions between heterocyclic C—H groups and Br− ions.

Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the root cause of T1D development has yet to be determined, enough is known about the natural history of T1D pathogenesis to allow study of interventions that may delay or even prevent the onset of hyperglycemia and clinical T1D. Primary prevention aims to prevent the onset of beta cell autoimmunity in asymptomatic people at high genetic risk for T1D. Secondary prevention strategies aim to preserve functional beta cells once autoimmunity is present, and tertiary prevention aims to initiate and extend partial remission of beta cell destruction after the clinical onset of T1D. The approval of teplizumab in the United States to delay the onset of clinical T1D marks an impressive milestone in diabetes care. This treatment opens the door to a paradigm shift in T1D care. People with T1D risk need to be identified early by measuring T1D related islet autoantibodies. Identifying people with T1D before they have symptoms will facilitate better understanding of pre-symptomatic T1D progression and T1D prevention strategies that may be effective.

Summary:. The use of negative pressure wound therapy (NPWT) continues to be an important tool for surgeons. As the use and general acceptance of NPWT have grown, so have the indications for its use. These indications have expanded to include soft tissue defects in trauma, infection, surgical wound management, and soft tissue grafting procedures. Many adjuvants have been engineered into newer generations of NPWT devices such as wound instillation of fluid or antibiotics allowing surgeons to further optimize the wound healing environment or aid in the eradication of infection. This review discusses the recent relevant literature on the proposed mechanisms of action, available adjuvants, and the required components needed to safely apply NPWT. The supporting evidence for the use of NPWT in traumatic extremity injuries, infection control, and wound care is also reviewed. Although NPWT has a low rate of complication, the surgeon should be aware of the potential risks associated with its use. Furthermore, the expanding indications for the use of NPWT are explored, and areas for future innovation and research are discussed.

Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications.

Total elbow arthroplasty (TEA) has become a well-accepted treatment option for many pathologies of the elbow joint. Its use in distal humerus fractures in elderly patients has become increasingly popular and has good clinical results. However, with the aging population and the increasing number of TEAs performed, so comes the potential for an increasing number of revision TEA cases. Revision TEA can be extremely challenging. In addition to the technical difficulties of safe exposure and implant removal, reimplantation of a cemented humeral component with loss of bone stock can be a challenging step in this procedure. The purpose of this article was to describe a novel technique to address aseptic loosening of the humeral stem and loss of humeral bone stock with revision of the humeral component using a long-stemmed cemented implant and intramedullary allograft fibular strut bone grafting.

Abstract Determining the optimal treatment course for a dermatologic burn wound requires knowledge of the wound’s severity, as quantified by the depth of thermal damage. In current clinical practice, burn depth is inferred based exclusively on superficial visual assessment, a method which is subject to substantial error rates in the classification of partial thickness (second degree) burns. Here, we present methods for direct, quantitative determination of the depth extent of injury to the dermal collagen matrix using polarization-sensitive optical coherence tomography (PS-OCT). By visualizing the depth-dependence of the degree of polarization of light in the tissue, rather than cumulative retardation, we enable direct and volumetric assessment of local collagen status. We further augment our PS-OCT measurements by visualizing adnexal structures such as hair follicles to relay overall dermal viability in the wounded region. Our methods, which we have validated ex vivo with matched histology, offer an information-rich tool for precise interrogation of burn wound severity and healing potential in both research and clinical settings.

Abstract To generalize findings on the mechanisms and prognosis in Alzheimer's disease and related dementias (ADRD), it is critical for ADRD research to be representative of the population. Sociodemographic and health characteristics across ethnoracial groups included in the National Alzheimer's Coordinating Center sample (NACC) were compared to the nationally representative Health and Retirement Study (HRS). Baseline NACC data (n = 36,639) and the weighted 2010 HRS wave (N = 52,071,840) were included. We assessed covariate balance by calculating standardized mean differences across harmonized covariates (i.e., sociodemographic, health). NACC participants were older, more educated, with worse subjective memory and hearing, but endorsed fewer depressive symptoms compared to HRS participants. While all racial and ethnic groups in NACC differed from HRS participants in the same way overall, these differences were further amplified between racial and ethnic groups. NACC participants do not represent the U.S. population in key demographic and health factors, which differed by race and ethnicity. HIGHLIGHTS We examined selection factors included in NACC studies compared to a nationally representative sample. Selection factors included demographic and health factors and self‐reported memory concerns. Results suggest that NACC participants are not representative of the U.S. population. Importantly, selection factors differed across racial and ethnic groups. Findings are suggestive of selection bias within NACC studies.

Hancy Issac,1,2 Gerben Keijzers,3– 5 Ian A Yang,6,7 Jackie Lea,1,2 Melissa Taylor,1,2 Clint Moloney1,8,9 1School of Nursing and Midwifery, University of Southern Queensland, Toowoomba, QLD, Australia; 2Centre of Health Research, University of Southern Queensland, Toowoomba, QLD, Australia; 3Department of Emergency Medicine, Gold Coast University Hospital, Gold Coast, QLD, Australia; 4Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia; 5School of Medicine, Griffith University, Gold Coast, QLD, Australia; 6Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia; 7Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; 8College of Health and Biomedicine, Nursing and Midwifery, Victoria University, Melbourne, VIC, Australia; 9Institute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaCorrespondence: Hancy Issac, School of Nursing and Midwifery, University of Southern Queensland, Toowoomba, QLD, Australia, Email hancy.issac@usq.edu.auIntroduction: Chronic obstructive pulmonary disease guideline non-adherence is associated with a reduction in health-related quality of life in patients (HRQoL). Improving guideline adherence has the potential to mitigate fragmented care thereby sustaining pulmonary function, preventing acute exacerbations, reducing economic health burdens, and enhancing HRQoL. The development of an electronic proforma stemming from expert consensus, including digital guideline resources and direct interdisciplinary referrals is hypothesised to improve guideline adherence and patient outcomes for emergency department (ED) patients with COPD.Aim: The aim of this study was to develop consensus among ED and respiratory staff for the correct composition of a COPD electronic proforma that aids in guideline adherence and management in the ED.Methods: This study adopted a mixed-method design to develop the most important indicators of care in the ED. The study involved three phases: (1) a systematic literature review and qualitative interdisciplinary staff interviews to assess barriers and solutions for guideline adherence and qualitative interdisciplinary staff interviews, (2) a modified Delphi panel to select interventions for the proforma, and (3) a consensus process through three rounds of scoring through a quantitative survey (ED and Respiratory consensus) and qualitative thematic analysis on each indicator.Results: The electronic proforma achieved acceptable and good internal consistency through all iterations from national emergency department and respiratory department interdisciplinary experts. Cronbach’s alpha score for internal consistency (α) in iteration 1 emergency department cohort (EDC) (α = 0.80 [CI = 0.89%]), respiratory department cohort (RDC) (α = 0.95 [CI = 0.98%]). Iteration 2 reported EDC (α = 0.85 [CI = 0.97%]) and RDC (α = 0.86 [CI = 0.97%]). Iteration 3 revealed EDC (α = 0.73 [CI = 0.91%]) and RDC (α = 0.86 [CI = 0.95%]), respectively.Conclusion: Electronic proformas have the potential to facilitate direct referrals from the ED leading to reduced hospital admissions, reduced length of hospital stays, holistic care, improved health care and quality of life and improved interdisciplinary guideline adherence.Keywords: COPD, electronic proforma, modified Delphi study, interdisciplinary, guideline adherence, COPD-X plan

During human embryonic development, haematopoietic stem cells of the foetal liver undergo expansion, while retaining engraftment capacity. Here the authors apply CITE-seq to profile single cells from a human foetal liver, identifying a molecular signature of engraftment potential