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Background: Cardiovascular disease is a leading cause of illness and death globally, primarily due to atherosclerosis. This disease reduces blood flow and oxygen delivery to organs, and when it affects the carotid arteries, it can lead to cognitive impairment and dementia. In a population of 104 individuals, comprising both healthy controls and individuals at elevated risk for developing cardiovascular diseases (CVD) due to identified risk factors, we used PET imaging with 18F-fluorodeoxyglucose (FDG) to assess cerebral glucose metabolism and 18F-sodium fluoride (NaF) to detect atherosclerotic calcification. Our statistical analysis revealed significant differences in metabolic activity between healthy and at-risk individuals in specific brain regions. 18F-FDG uptake in the brain varied inversely with respect to the clinical assessment of cardiovascular risk in regions such as the cuneus (β = −0.030, SE = 0.014, p = 0.035), middle occipital gyrus (β = −0.032, SE = 0.011, p = 0.005), and posterior cingulate gyrus (β = −0.032, SE = 0.015, p = 0.044). In contrast, areas including the basis pontis (β = 0.025, SE = 0.012, p = 0.038) and the pons (β = 0.034, SE = 0.013, p = 0.008) exhibited direct correlations. Notably, carotid 18F-NaF uptake had inverse associations with 18F-FDG uptake in the cerebellum (β = −0.825, SE = 0.354, p = 0.021), medulla (β = −0.888, SE = 0.405, p = 0.029), and posterior cingulate gyrus (β = −1.253, SE = 0.567, p = 0.028), while increased carotid calcification influenced metabolic activity in the fusiform gyrus (β = 1.660, SE = 0.498, p = 0.001) and globus pallidus (β = 1.505, SE = 0.571, p = 0.009). We observed that atherosclerotic plaque accumulation, especially in the carotid arteries, has potential implications for metabolic changes in brain regions governing cognition, emotion, sensory perception, and motor activities. Our findings underscore the possible early interventions that can be used to preempt or delay cognitive deterioration linked with cardiovascular ailments.

Bemisia tabaci (whitefly) is a polyphagous agroeconomic pest species complex. Two members of this species complex, Mediterranean (MED) and Middle-East-Asia Minor 1 (MEAM1), have a worldwide distribution and have been shown to manipulate plant defenses through effectors. In this study, we used three different strategies to identify three MEAM1 proteins that can act as effectors. Effector B1 was identified using a bioinformatics-driven effector-mining strategy, whereas effectors S1 and P1 were identified in the saliva of whiteflies collected from artificial diet and in phloem exudate of tomato on which nymphs were feeding, respectively. These three effectors were B. tabaci specific and able to increase whitefly fecundity when transiently expressed in tobacco plants (Nicotiana tabacum). Moreover, they reduced growth of Pseudomonas syringae pv. tabaci in Nicotiana benthamiana. All three effectors changed gene expression in planta, and B1 and S1 also changed phytohormone levels. Gene ontology and KEGG pathway enrichment analysis pinpointed plant–pathogen interaction and photosynthesis as the main enriched pathways for all three effectors. Our data thus show the discovery and validation of three new B. tabaci MEAM1 effectors that increase whitefly fecundity and modulate plant immunity. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results Seven gut bacterial genera were identified to be associated with diabetes (FDR-q

Abstract Background Past research describes robust associations between education and health, yet findings have generally been limited to the examination of education as the number of years of education or educational attainment. Little is known about the specific features or processes underpinning education that are health protective. The objective of the current study was to address this gap by examining specific aspects of early education pertaining to student characteristics and experiences, as well as features of the classroom environment, in predicting cardiometabolic health in adulthood. Methods Subjects were 1364 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD, 1991–2009) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE, 2018–2022). Models examined individual education indicators (student social skills, student-teacher relationship quality, and classroom emotional and instructional quality in the period of elementary school and student academic performance between ages 54 months and 15 years) in relation to a composite of cardiometabolic risk in adulthood (ages 26–31), reflecting central adiposity, blood pressure, insulin resistance, inflammation, and dyslipidemia. Models were adjusted for key explanatory factors including socio-demographics, infant characteristics, parental socioeconomic status (SES), and child health status. Follow-up analyses were performed to test potential mediators of early education effects on adult health, including adult SES (educational attainment, household income) and health behaviors (diet quality, activity level, sleep duration, smoking). Results In adjusted models, results showed greater student social skills, indexed by a mean of annual teacher ratings between kindergarten and 6th grade, predicted lower cardiometabolic risk in adulthood (β=-0.009, p 0.05). Conclusions Findings point to the potential significance of early student social competence as a link to long-term health, possibly via the acquisition of resources needed for the maintenance of health, as well as through engagement in health behaviors supporting healthy eating. However, more research is needed to replicate these findings and to elaborate on the role of early student social competence and the pathways explaining its effects on cardiometabolic health in adulthood.

Abstract Background Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. Methods We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. Results We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Conclusions Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

Abstract Wildlife species and populations are being driven toward extinction by a combination of historic and emerging stressors (e.g., overexploitation, habitat loss, contaminants, climate change), suggesting that we are in the midst of the planet’s sixth mass extinction. The invisible loss of biodiversity before species have been identified and described in scientific literature has been termed, memorably, dark extinction. The critically endangered Southern Resident killer whale (Orcinus orca) population illustrates its contrast, which we term bright extinction; namely the noticeable and documented precipitous decline of a data-rich population toward extinction. Here we use a population viability analysis to test the sensitivity of this killer whale population to variability in age structure, survival rates, and prey-demography functional relationships. Preventing extinction is still possible but will require greater sacrifices on regional ocean use, urban development, and land use practices, than would have been the case had threats been mitigated even a decade earlier.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design, setting, and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered “proficient” when attending surgeons’ rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3–7] and 3 [2–4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27–0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

Abstract We describe solutions of asymptotically AdS3 Einstein gravity that are sourced by the insertion of operators in the boundary CFT2, whose dimension scales with the central charge of the theory. Previously, we found that the geometry corresponding to a black hole two-point function is simply related to an infinite covering of the Euclidean BTZ black hole [1]. However, here we find that the geometry sourced by the presence of a third black hole operator turns out to be a Euclidean wormhole with two asymptotic boundaries. We construct this new geometry as a quotient of empty AdS3 realized by domes and doors. The doors give access to the infinite covers that are needed to describe the insertion of the operators, while the domes describe the fundamental domains of the quotient on each cover. In particular, despite the standard fact that the Fefferman-Graham expansion is single-sided, the extended bulk geometry contains a wormhole that connects two asymptotic boundaries. We observe that the two-sided wormhole can be made single-sided by cutting off the wormhole and gluing on a “Lorentzian cap”. In this way, the geometry gives the holographic description of a three-point function, up to phases. By rewriting the metric in terms of a Liouville field, we compute the on-shell action and find that the result matches with the Heavy-Heavy-Heavy three-point function predicted by the modular bootstrap. Finally, we describe the geometric transition between doors and defects, that is, when one or more dual operators describe a conical defect insertion, rather than a black hole insertion.

Abstract Background Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences. This comparison could clarify whether elevated circulating interferon-alpha (IFNα) promotes widespread immune cell alterations and persists post-therapy, furthering understanding of why non-EC patients continue to need treatment. Methods Levels of IFNα in HIV-infected EC and treated non-EC patients were compared, along with blood immune cell subset distribution and phenotype, and functional capacities in some cases. In addition, we assessed mechanisms potentially associated with IFNα overload. Results Treatment of non-EC patients results in restoration of IFNα control, followed by marked improvement in distribution numbers, phenotypic profiles of blood immune cells, and functional capacity. These changes still do not lead to EC status, however, and IFNα can induce these changes in normal immune cell counterparts in vitro. Hypothesizing that persistent alterations could arise from inalterable effects of IFNα at infection onset, we verified an IFNα-related mechanism. The protein induces the HIV coreceptor CCR5, boosting HIV infection and reducing the effects of anti-HIV therapies. EC patients may avoid elevated IFNα following on infection with a lower inoculum of HIV or because of some unidentified genetic factor. Conclusions Early control of IFNα is essential for better prognosis of HIV-infected patients.

Abstract Background A complete understanding of the different steps of HIV replication and an effective drug combination have led to modern antiretroviral regimens that block HIV replication for decades, but these therapies are not curative and must be taken for life. “Elite controllers” (ECs) is a term for the 0.5% of HIV-infected persons requiring no antiretroviral therapy, whose status may point the way toward a functional HIV cure. Defining the mechanisms of this control may be key to understanding how to replicate this functional cure in others. Methods In ECs and untreated non-EC patients, we compared IFNα serum concentration, distribution of immune cell subsets, and frequency of cell markers associated with immune dysfunction. We also investigated the effect of an elevated dose of IFNα on distinct subsets within dendritic cells, natural killer cells, and CD4+ and CD8 + T cells. Results Serum IFNα was undetectable in ECs, but all immune cell subsets from untreated non-EC patients were structurally and functionally impaired. We also show that the altered phenotype and function of these cell subsets in non-EC patients can be recapitulated when cells are stimulated in vitro with high-dose IFNα. Conclusions Elevated IFNα is a key mediator of HIV pathogenesis.

Abstract Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer’s disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased β-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.

Abstract Membrane-enclosed organelles are defining features of eukaryotes in distinguishing these organisms from prokaryotes. Specification of distinct membranes is critical to assemble and maintain discrete compartments. Small GTPases and their regulators are the signaling molecules that drive membrane-modifying machineries to the desired location. These signaling molecules include Rab and Rag GTPases, roadblock and longin domain proteins, and TRAPPC3-like proteins. Here, we take a structural approach to assess the relatedness of these eukaryotic-like proteins in Asgard archaea, the closest known prokaryotic relatives to eukaryotes. We find that the Asgard archaea GTPase core domains closely resemble eukaryotic Rabs and Rags. Asgard archaea roadblock, longin and TRAPPC3 domain-containing proteins form dimers similar to those found in the eukaryotic TRAPP and Ragulator complexes. We conclude that the emergence of these protein architectures predated eukaryogenesis, however further adaptations occurred in proto-eukaryotes to allow these proteins to regulate distinct internal membranes.

Abstract Background Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. Results The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p

Abstract Background Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses. Methods To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. fermentans DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells’ survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified F. nucleatum as a CAB carrying DnaK with an amino acid composition highly similar to M. fermentans DnaK. Therefore, we investigated the effect of F. nucleatum DnaK on the anti-cancer activity of cisplatin and 5FU. Results Our results show that both M. fermentans and F. nucleatum DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy. Conclusions Our findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.

Abstract Background Iatrogenic blood contamination during cerebrospinal fluid (CSF) centesis is common, which can limit the diagnostic usefulness of the sample. A novel ultrasound‐guided CSF collection technique is described in horses, by which CSF is obtained from the atlantoaxial (AA) space. Hypothesis/Objectives To compare ultrasound‐guided AA centesis with lumbosacral (LS) centesis in South American camelids (SAC). The hypotheses were that AA centesis would yield samples with less blood contamination although being technically more challenging than LS centesis. Animals Eight clinically healthy adult SAC from a university‐owned teaching herd. Methods Single‐blinded, randomized, 4‐way, 4‐period crossover study in which 2 veterinarians each performed both centesis techniques on each animal once. Cytological sample analysis was performed, and the technical difficulty of sample acquisition was assessed. Results The CSF was collected successfully and without complications by either technique during all collection attempts. Aspects of technical difficulty and concentrations of CSF analytes did not vary significantly between techniques. Median total nucleated cell and red blood cell counts were 1/μL and 0.5/μL and 167.5/μL and 155/μL for AA and LS techniques, respectively. The median total protein concentration was 32.9 mg/dL and 38 mg/dL for AA and LS centeses. A median of 1 attempt was necessary for both centesis techniques and the median number of needle repositioning events was 1 for AA and 0 for LS. Conclusion and Clinical Importance Depending on clinical circumstances, ultrasound‐guided AA centesis appears to be an acceptable alternative to other techniques for collection of CSF from SAC.

TWIST1 (TW) is a pro‐oncogenic basic helix–loop–helix (bHLH) transcription factor and promotes the hallmark features of malignancy (e.g., cell invasion, cancer cell stemness, and treatment resistance), which contribute to poor prognoses of glioblastoma (GBM). We previously reported that specific TW dimerization motifs regulate unique cellular phenotypes in GBM. For example, the TW:E12 heterodimer increases periostin (POSTN) expression and promotes cell invasion. TW dimer‐specific transcriptional regulation requires binding to the regulatory E‐box consensus sequences, but alternative bHLH dimers that balance TW dimer activity in regulating pro‐oncogenic TW target genes are unknown. We leveraged the ENCODE DNase I hypersensitivity data to identify E‐box sites and tethered TW:E12 and TW:TW proteins to validate dimer binding to E‐boxes in vitro. Subsequently, TW knockdown revealed a novel TCF4:TCF12 bHLH dimer occupying the same TW E‐box site that, when expressed as a tethered TCF4:TCF12 dimer, markedly repressed POSTN expression and extended animal survival. These observations support TCF4:TCF12 as a novel dimer with tumor‐suppressor activity in GBM that functions in part through displacement of and/or competitive inhibition of pro‐oncogenic TW dimers at E‐box sites.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch’s membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The gut microbiota-brain axis has been associated with the pathogenesis of numerous disorders, but the mechanism(s) underlying these links are generally poorly understood. Accumulating evidence indicates the involvement of gut microbe-derived metabolites. Circulating levels of the gut microbe/host co-metabolite p-cresol sulfate (pCS) correlate with cerebrovascular event risk in individuals with chronic kidney disease (CKD), but whether this relationship is mechanistic is unclear. We hypothesized that pCS would impair the function of the blood–brain barrier (BBB), the primary brain vasculature interface. We report that pCS exposure impairs BBB integrity in human cells in vitro and both acutely (≤6 hours) and chronically (28 days) in mice, enhancing tracer extravasation, disrupting barrier-regulating tight junction components and ultimately exerting a suppressive effect upon whole-brain transcriptomic activity. In vitro and in vivo mechanistic studies showed that pCS activated epidermal growth factor receptor (EGFR) signaling, sequentially activating the intracellular signaling proteins annexin A1 and STAT3 to induce mobilization of matrix metalloproteinase MMP-2/9 and disruption to the integrity of the BBB. This effect was confirmed as specific to the EGFR through the use of both pharmacological and RNA interference approaches. Confirming the translational relevance of this work, exposure of the cerebromicrovascular endothelia to serum from hemodialysis patients in vitro led to a significant increase in paracellular permeability, with the magnitude of permeabilization closely correlating with serum pCS, but not most other uremic toxin, content. Notably, this damaging effect of hemodialysis patient serum was prevented by pharmacological blockade of the EGFR. Our results define a pathway linking the co-metabolite pCS with BBB damage and suggest that targeting the EGFR may mitigate against cerebrovascular damage in CKD. This work further provides mechanistic evidence indicating the role of gut microbe-derived metabolites in human disease.

ABSTRACT: Background: Mind-body treatments have the potential to manage pain, yet their effectiveness when delivered online for the treatment of low back pain (LBP) is unknown. We sought to evaluate whether a virtually delivered mind-body program integrating tai chi, qigong, and meditation (VDTQM) is effective for treating LBP. Methods: This randomized controlled trial compared VDTQM (n=175) to waitlist control (n=175). Eligible participants were at least 18 years old, had LBP for at least 6 weeks, were not pregnant, had not previously taken tai chi classes, and had not undergone spine surgery within 6 months. The treatment group received a 12-week VDTQM program in live online 60-minute twice-weekly group classes from September 2022 to December 2022. All participants continued their usual activities and care. Primary outcome was pain-related disability assessed by the Oswestry Disability Index (ODI) score. Secondary outcomes included pain intensity, sleep quality, and quality of life (QOL). Intent-to-treat analyses were conducted. Results: Of the 350 participants 278 (79%) were female, mean age was 58.8 years (range: 21–92), 244 (69.7%) completed the 8-week survey, 248 (70.9%) the 12-week, and 238 (68%) the 16 -week. No participants withdrew due to adverse treatment effects. Compared with control group, treatment group experienced statistically and clinically significant improvement in ODI score by −4.7 (95% CI: −6.24 to −3.16, p

Glucocorticoids are understood to represent useful biomarkers of stress and can be measured in saliva, hair, and breastmilk. The collection of such biosamples is increasingly included in biobank and cohort studies. While collection is considered “non-invasive” by biomedical researchers (compared to sampling blood), community perspectives may differ. This cross-sectional, qualitative study utilising eight focus groups aimed to determine the feasibility and acceptability of collecting ostensibly “non-invasive” biological samples in Malawi. Breastfeeding women, couples, field workers, and healthcare providers were purposively sampled. Data about prior understandings of, barriers to, and feasibility of “non-invasive” biosampling were analysed. Participants described biomaterials intended for “non-invasive” collection as sometimes highly sensitive, with sampling procedures raising community concerns. Sampling methods framed as physically “non-invasive” within biomedicine can consequently be considered socially “invasive” by prospective sample donors. Biomedical and community framings of “invasiveness’ can therefore diverge, and the former must respond to and be informed by the perspectives of the latter. Further, considerations of collection procedures are shaped by therapeutic misconceptions about the immediate health-related utility of biomedical and public health research. When researchers engage with communities about biosampling, they must ensure they are not furthering therapeutic misconceptions and actively seek to dispel these.

Background Topical treatments are the foundation for patients with psoriasis; however, adherence can be limited by patient preferences and treatment burden.Methods The Harris Poll conducted an online survey of US patients with psoriasis who use prescription topical therapy to examine their preferences and perspectives on topical treatments.Results Among patients with psoriasis who use topical treatment (n = 507), most participants described their psoriasis symptoms as mild (31%) or moderate (59%). The body areas most often reported to be affected by psoriasis were the scalp, elbows, legs, intertriginous areas, arms, and knees. Participants reported psoriasis affecting the scalp (39%), elbows (20%), and legs (excluding knees; 19%) caused the greatest impact on quality of life. Most participants (76%) preferred topical therapies to treat their psoriasis, while 20% preferred pills, and 4% preferred injections. The most common product attributes that participants wanted in a topical psoriasis treatment and that would help them to continue to use the treatment were: improvement in plaques (68%), itch relief (68%), and easy to apply (63%).Conclusion The respondents to this survey reported that they prefer topical treatments to pills or injections (76%) and most (89%) reported they are interested in trying a new topical treatment.

Patients with schizophrenia show substantial cognitive deficits and abnormalities in neurotransmitter-related levels of mRNA in brain or peripheral blood lymphocytes. However, the relationship of cognitive deficits as measured by the MATRICS battery and mRNA levels in brain or lymphocytes has not been sufficiently explored. We measured levels of methylation or neurotransmitter-related mRNAs in lymphocytes of 38 patients with chronic schizophrenia (CSZ) and 33 non-psychotic controls (controls) by qPCR using TaqMan probes. We assessed cognitive function in these patients and controls with the MATRICS battery. We used correlation analysis and scatter plots to assess the relationship of lymphocyte mRNA levels to MATRICS domain and composite scores. CSZ subjects had a consistently negative correlation between mRNA levels in lymphocytes and MATRICS cognitive variables of speed of processing, attention-vigilance, working memory, visual learning, and overall composite score. It is uncertain whether these negative correlations represent a causative relation between specific mRNA levels and cognitive deficits. Controls had either positive correlations or non-significant correlations between mRNA and most of the MATRICS variables. There were statistically significant differences in the correlations between mRNA and MATRICS variables between CSZ vs controls for several mRNAs (DNMT1, DNMT3A, BDNF, NR3C1, FPRF3, CNTNAP2). Our data show a different relationship between mRNA levels in peripheral blood lymphocytes and MATRICS cognitive variables in CSZ vs controls. The substantive significance of these differences needs further investigation.

AbstractObjective To determine the incidence rates (IRs) of catastrophic injuries and exertional medical events in lacrosse athletes.Methods Catastrophic injuries and exertional medical events in lacrosse in the US among youth or amateur, high school and college athletes were analysed from the National Center for Catastrophic Sport Injury Research (NCCSIR) database from 1982/83 to 2019/20. Frequencies, IRs per 100,000 athlete-seasons (AS) with 95% confidence intervals (CIs), and incidence rate ratios (IRRs) with 95% CIs were calculated. Participation data were gathered from the National Federation of State High School Associations (NFHS), National Collegiate Athletic Association (NCAA) and USA Lacrosse.Results Sixty-nine catastrophic events (16 youth or amateur, 36 high school and 17 college; 84% male) occurred in US lacrosse from 7/1/1982 to 6/30/2020. Thirty-six percent of all incidents were fatal. The overall IR was 0.5 per 100,000 AS (95% CI: 0.4–0.7). There were 15 cases of non-traumatic sudden cardiac arrests (SCAs) and 15 incidents of commotio cordis. Fatality rates from SCA and commotio cordis decreased 95% (IRR = 0.05; 95% CI: 0, 0.2) from 1982/83–2006/07 to 2007/08–2019/20. Incidence rates were higher for collegiate versus high school 1982/83–2019/20 (IRR = 3.2; 95% CI: 1.8, 5.7) and collegiate versus youth 2005/06–2019/20 (IRR = 8.0; 95% CI: 3.0, 21.4) level. Contact with a stick or ball (41%) and contact with another player (20%) were the primary mechanisms of injury.Conclusions The incidence of catastrophic events during lacrosse was higher among collegiate than high school or youth athletes. SCA from an underlying cardiac condition or from commotio cordis was the most common catastrophic event. Fatality rates from catastrophic injuries have declined significantly over the study period, perhaps driven by protective measures adopted by lacrosse governing bodies.

Fresh, nutritious, palatable produce for crew consumption on long-duration spaceflight missions may provide health-promoting, bioavailable nutrients and enhance the dietary experience. VEG-04A and VEG-04B explored growing leafy greens on the International Space Station using the Veggie Vegetable Production System. Two flight tests with ground controls were conducted in 2019 growing mizuna mustard, where Veggie chambers were set to different red-to-blue-to-green light formulations. Light quality affects plant growth, nutrition, microbiology, and organoleptic characteristics on Earth, and we examined how these vary in microgravity and under different harvest scenarios. Astronauts harvested and weighed mizuna and completed organoleptic evaluations. Flight samples were returned to Earth for nutritional quality and microbial food safety analyses. Yield and chemistry differed between ground and flight samples and light treatments, and bacterial and fungal counts were lower in ground than in flight samples. This research helps increase our understanding of the requirements for growing high-quality crops in spaceflight.

Background The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults. Methods and Results We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association “Life's Essential 8,” we built a score of ideal CVH at baseline and the 6‐year follow‐up. Linear mixed‐effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (β for high school versus high school versus

Abstract Climate change is projected to alter the structure of plant communities due to increasing temperatures and changes to precipitation patterns, particularly in midlatitude dryland ecosystems. Modifications to climatic suitability may lead to major community changes such as altered dominant plant functional types. Previous studies have indicated that climatic suitability is likely to increase for C4 grasses and decrease for C3 grasses in the Western United States. However, if no C4 grass species currently exist to serve as a propagule source, expansion into areas of increased suitability will be limited. We conducted a field and modeling study in the Upper Green River Basin (UGRB) of Western Wyoming to determine if (1) C4 grasses are present to provide a propagule source and (2) C4 grasses are likely to increase in importance relative to C3 grasses due to climatic changes. We searched 44 sites for C4 grasses to establish presence, and modeled suitability at 35 sites using 17 Global Climate Models, two greenhouse gas Representative Concentration Pathways (RCPs; 4.5 and 8.5), and two time periods (mid‐ and late century; 2030–2060 and 2070–2099, respectively). We found C4 grasses at 10 of the 44 sites, indicating that there is a present propagule source. Our model projected increases in suitability for both C3 and C4 grasses across sites for all RCPs and time periods. In the mid‐century RCP 4.5 scenario, the C3 functional type increased in projected biomass in 29 of 35 sites, and the C4 type increased in 31 sites. In this scenario, C3 grasses increased in projected biomass by a median 4 g m−2 (5% change), and C4 grass biomass increased by a median 8 g m−2 (21% change). Our study suggests that climate change will increase climatic suitability for grasses across the UGRB, and that all requirements are in place for C4 grasses to increase in abundance.

Background:. It is increasingly apparent that plastic surgery residency applications with lengthy research publications are the new standard in applicant competitiveness. This study aims to evaluate the research history of plastic surgery program faculty leadership to understand the trends and evolution of research expectations. Methods:. The curriculum vitaes of faculty involved in residency admissions among all US Accreditation Council for Graduate Medical Education-accredited integrated and independent plastic surgery programs were reviewed. Doximity, program websites, and Scopus were used to gather information. H-index and publication count at the time of medical school and residency graduations were collected. Student t test and Pearson product-moment correlation were used for analysis. Results:. Of the 236 plastic surgeons considered, faculty averaged one publication by medical school graduation, two by general surgery residency graduation, and six by plastic surgery residency graduation. Integrated residents held more publications after medical school (1.67 versus 0.56; P = 0.09) and plastic surgery residency (8.48 versus 4.89; P = 0.01) compared with independent residents. Later plastic surgery residency graduation year correlated with more publications (P < 0.001). Chairs had higher h-indices compared with program directors and associate positions (chair: 23.7, program director: 14.7, associate: 12.2; P < 0.001). Conclusions:. The majority of faculty leaders’ research was published after residency. The emerging trend of increased research volume among plastic surgeons-in-training may be a consequence of competitive research requirements to matriculate into residency. Longer-term career follow-up of newer graduates will need to be assessed to determine whether this predicts future postgraduate productivity or if it is just the price of admission to train as a plastic surgeon.

Gas flow rates in Directed Energy Deposition (DED) Additive Manufacturing (AM) can significantly affect the quality of built parts by altering melt pool geometry. Using a DED process replicator and in situ synchrotron radiography, together with analogous experiments in an industrial DED machine, we investigate the impact of carrier gas and shield gas flow rates on build quality. The results reveal that there is a critical shield gas flow rate above which melt pools are flattened, tracks widen, and thus layer thickness decreases. The reduction in layer thickness is most prominent in conditions with low carrier gas flow rate, as the highly turbulent shield gas flow may divert slow moving powder particles away from the melt pool, decreasing capture efficiency. Very high flow rates increase internal porosity, as fast-moving particles impacting the melt pool surface can entrain chamber gas behind them. High gas flow rates also cool the melt pool, creating shallower melt pools with increased thermal gradients near the solidification front, increasing pore entrapment in the solidified track.

Despite being a legume, snap bean (Phaseolus vulgaris L.) lacks nodulation genes, restricting its ability for nitrogen (N) fixation through rhizobia, making N fertilization essential for maximizing yields. However, conventional fertilizer application may lead to N losses due to a lack of synchronization between plant uptake and N availability. A promising option could be controlled-release fertilizers (CRFs), which can be custom-formulated to synchronize nutrient release with plant growth needs, promoting efficient resource use. Field studies were conducted at the North Florida Research and Education Center-Suwannee Valley (NFREC-SV) in Live Oak, FL, during the spring of 2021 and 2022. The experiments also investigated broadcasting and banding application methods of the University of Florida’s recommended N rate (112 kg·ha−1). The experimental design comprised 10 treatments, including five N rates (0, 56, 112, 168, and 224 kg·ha−1 N) and two fertilizer sources (ammonium nitrate and CRF), applied to ‘Caprice’ in a randomized complete block design with four replications. Results showed a significant yield improvement with N fertilization vs. the zero-N control. However, no yield increase was observed beyond 56 kg·ha−1. This finding could be due to the residual N from a preceding peanut crop rotation in both years. No notable variation in quality metrics (pod length and width) occurred above the 56 kg·ha−1 threshold. The results also revealed that the choice between conventional or CRF did not exert any statistically significant differences in snap bean yield. In addition, fertilizer broadcast and banding treatments yielded the same results.

Naturally occurring diabetes mellitus (NODM) is one of the most common endocrine disorders in dogs and its etiology closely resembles type 1 diabetes mellitus (T1DM) in people. Human patients with T1DM commonly have cellular derangements consistent with inflammation, impaired immune function, and hypovitaminosis D. There is little information available regarding inflammatory biomarkers, immune function, and vitamin D status in diabetic dogs. Therefore, our objectives were to assess inflammatory biomarkers, vitamin D metabolites, and phagocytic capacity in diabetic dogs and determine whether associations exist with these variables and the level of clinical control or vitamin D metabolites. This was a prospective case–control study that included 20 otherwise healthy diabetic dogs (clinically controlled, n = 10; uncontrolled, n = 10) and 20 non-diabetic, healthy, age (± 2 years), breed, and sex matched controls. Complete blood count, biochemical panel, urinalysis, and fructosamine were performed at a single commercial reference laboratory. Basal plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured using a canine-specific multiplex bead-based assay. Serum C-reactive protein (CRP) was measured using a commercially available ELISA kit. Serum 25-hydroxyvitamin (OH)D3 and 24,25-dihydroxyvitamin (OH)2D3 were measured with HPLC. Phagocytosis of opsonized-Escherichia coli (E. coli) was evaluated with flow cytometry. Diabetic dogs had higher serum CRP concentrations than controls (p = 0.02). Plasma IL-8 concentrations were higher in diabetic dogs with uncontrolled clinical disease compared to controls (p = 0.02). Diabetic dogs had a lower percentage of leukocytes that phagocytized opsonized-E. coli (p = 0.02), but an increased number of bacteria phagocytized per cell (p

This study investigated the relationship between stress exposure and subsequent ethanol use, focusing on individual differences among male rats. We combined operant self-administration with behavioral economics to assess how intermittent swim stress affects ethanol consumption. This approach allowed for a nuanced analysis of the transition from regular ethanol intake to stress-induced escalation in economic demand. Results showed a consistent rise in ethanol demand post-stress among subjects, irrespective of exposure to actual swim stress or a sham procedure. This increase may result from a two-week abstinence or an inherent rise in demand over time. Significantly, we identified a direct link between post-stress corticosterone levels and the demand for ethanol, considering baseline levels. This correlation was particularly pronounced when examining the shifts in both corticosterone levels and demand for ethanol post-stress. However, neither post-stress corticosterone levels nor their change over time correlated significantly with changes in ethanol demand following a forced swim test that was administered 24 h after the intermittent swim stress test. This suggests potential context-specific or stressor-specific effects. Importantly, pre-stress ethanol demand did not significantly predict the corticosterone response to stress, indicating that high ethanol-demand rats do not inherently exhibit heightened stress sensitivity. Our research brings to light the complex interplay between stress and ethanol consumption, highlighting the critical role of individual differences in this relationship. This research introduces a nuanced perspective, underscoring the need for future studies in the realm of stress and substance use to give greater consideration to individual variability.

Abstract River bedforms and their deposits—fluvial cross strata— respond to floods. However, it is unclear if all floods are equally represented in cross strata. Here, using a series of physical experiments in which bedforms were subjected to equivalent flood magnitudes over varying durations, we demonstrate the existence of a lower bound on flood durations that are represented in cross strata. We show that the scour depths and preserved set thickness are indistinguishable from baseflow conditions when the rising‐limb duration of floods is shorter than the baseflow‐equilibrated bedform turnover timescale—time required to displace the volume of a single bedform at baseflow conditions. In contrast, scour depth and preserved set thickness distributions deviate from baseflow conditions when flood rising‐limb duration exceeds the baseflow‐equilibrated bedform turnover timescale, causing preferential preservation of falling‐limb bedform dynamics. Our work provides a previously unrecognized quantitative bound on flood durations that are represented in fluvial cross strata.

BackgroundWhile numeric scales to represent pain intensity have been well validated, individuals use various conceptualizations when assigning a number to pain intensity, referred to as pain rating schema. The 18-item Pain Schema Inventory (PSI-18) quantifies pain rating schema by asking for numeric values for multiple mild, moderate or severe pain conditions. This study aimed to assess the validity and reliability of a shortened form of the PSI, using only 6 items (PSI-6).MethodsA secondary analysis was performed on two existing datasets. The first (n = 641) involved a community-based population that completed the PSI-18. The second (n = 182) included participants with chronic pain who completed the PSI-6 twice, one week apart. We assessed face validity, convergent validity, offset biases, test-retest reliability, and internal consistency of the PSI-6 compared to the PSI-18.ResultsBoth the PSI-18 and PSI-6 demonstrated excellent face validity. The PSI-6 demonstrated excellent convergent validity relative to the PSI-18, with correlations from r = 0.88 to 0.92. Bland-Altman plots revealed offset biases near zero (< 0.22 on 0–10 scale) across all categories of mild, moderate, severe and average pain. Internal consistency was excellent, with Cronbach's Alpha = 0.91 and 0.80, for PSI-18 and PSI-6 respectively. Test-retest reliability of the PSI-6 was high with correlations from r = 0.70–0.76.ConclusionThe PSI-6 is a valid and reliable tool to assess pain rating schema with reduced subject burden, to better interpret individuals’ pain ratings and adjust for inter-individual variability.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged

Abstract Parturition timing has long been a topic of interest in ungulate research. However, few studies have examined parturition timing at fine scale (e.g.,

Abstract Canonical understanding based on general circulation models (GCMs) is that the atmospheric circulation response to midlatitude sea‐surface temperature (SST) anomalies is weak compared to the larger influence of tropical SST anomalies. However, the ∼100‐km horizontal resolution of modern GCMs is too coarse to resolve strong updrafts within weather fronts, which could provide a pathway for surface anomalies to be communicated aloft. Here, we investigate the large‐scale atmospheric circulation response to idealized Gulf Stream SST anomalies in Community Atmosphere Model (CAM6) simulations with 14‐km regional grid refinement over the North Atlantic, and compare it to the responses in simulations with 28‐km regional refinement and uniform 111‐km resolution. The highest resolution simulations show a large positive response of the wintertime North Atlantic Oscillation (NAO) to positive SST anomalies in the Gulf Stream, a 0.4‐standard‐deviation anomaly in the seasonal‐mean NAO for 2°C SST anomalies. The lower‐resolution simulations show a weaker response with a different spatial structure. The enhanced large‐scale circulation response results from an increase in resolved vertical motions with resolution and an associated increase in the influence of SST anomalies on transient‐eddy heat and momentum fluxes in the free troposphere. In response to positive SST anomalies, these processes lead to a stronger and less variable North Atlantic jet, as is characteristic of positive NAO anomalies. Our results suggest that the atmosphere responds differently to midlatitude SST anomalies in higher‐resolution models and that regional refinement in key regions offers a potential pathway to improve multi‐year regional climate predictions based on midlatitude SSTs.

Spontaneous intracerebral hemorrhage (sICH) is associated with significant morbidity and mortality, with subsequent hematoma expansion (HE) linked to worse neurologic outcomes. Accurate, real-time predictions of the risk of HE could enable tailoring management—including blood pressure control or surgery—based on individual patient risk. Although multiple radiographic markers of HE have been proposed based on standard imaging, their clinical utility remains limited by a reliance on subjective interpretation of often ambiguous findings and a poor overall predictive power. Radiomics refers to the quantitative analysis of medical images that can be combined with machine-learning algorithms to identify predictive features for a chosen clinical outcome with a granularity beyond human limitations. Emerging data have supported the potential utility of radiomics in the prediction of HE after sICH. In this review, we discuss the current clinical management of sICH, the impact of HE and standard imaging predictors, and finally, the current data and potential future role of radiomics in HE prediction and management of patients with sICH.

Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

Summary: The astrocyte-neuron lactate shuttle (ANLS) model posits that astrocyte-generated lactate is transported to neurons to fuel memory processes. However, neurons express high levels of lactate dehydrogenase A (LDHA), the rate-limiting enzyme of lactate production, suggesting a cognitive role for neuronally generated lactate. It was hypothesized that lactate metabolism in neurons is critical for learning and memory. Here transgenic mice were generated to conditionally induce or knockout (KO) the Ldha gene in CNS neurons of adult mice. High pattern separation memory was enhanced by neuronal Ldha induction in young females, and by neuronal Ldha KO in aged females. In older mice, Ldha induction caused cognitive deficits whereas Ldha KO caused cognitive improvements. Genotype-associated cognitive changes were often only observed in one sex or oppositely in males and females. Thus, neuronal-generated lactate has sex-specific cognitive effects, is largely indispensable at young age, and may be detrimental to learning and memory with aging.

The rotator cuff, comprising the subscapularis, supraspinatus, infraspinatus, and teres minor muscles, plays a crucial role in stabilizing the glenohumeral joint by securing the head of the humerus within the glenoid cavity of the scapula. The tendinous insertions of these muscles generate tension within the capsule, enhancing joint stability during muscular activity. The rotator cuff is susceptible to damage from disease, injury, or trauma, which can result in tears or ruptures of one or more tendons. The evaluation of the infraspinatus muscle and tendon is vital for diagnosing and managing various shoulder pathologies. Accurate imaging to determine the specific muscle involvement and injury severity significantly impacts treatment decisions. Diagnostic musculoskeletal ultrasound (MSK-US) has emerged as a valuable tool for assessing the infraspinatus muscle and tendon, offering real-time, dynamic assessment capabilities essential for precise diagnosis and effective rehabilitation planning. This article reviews the utility and advantages of MSK-US in evaluating the infraspinatus muscle and tendon, emphasizing technique specifics, diagnostic accuracy, and comparative efficacy against other imaging modalities. It details a systematic approach to the ultrasound examination technique for the infraspinatus, including patient positioning and identification of common pathologies such as tears, tendinopathy, and calcifications. With recent advancements in transducer strength, image resolution, and operator training, ultrasound serves as an excellent alternative imaging modality for diagnosing rotator cuff tears. This article aims to equip rehabilitation professionals with a comprehensive understanding of MSK-US as a diagnostic tool for the infraspinatus, promoting more precise diagnosis, treatment planning and improved patient outcomes.

Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.

Background: Volvulus of the large intestine is a relatively uncommon cause of bowel obstruction. A rare complication is abdominal compartment syndrome, which can manifest as multisystem organ failure. Case Report: We present a case of a 62-year-old hemiparetic man who presented intubated for respiratory distress, and later became unstable, with profound hypotension and hypoxia. He was found to have a large sigmoid volvulus causing acute abdominal compartment syndrome with compression of bilateral lower lungs and mediastinal structures, and ultimately survived to undergo an exploratory laparotomy with sigmoidectomy. Why should an emergency physician be aware of this? Respiratory distress and abdominal pain are some of the most common chief complaints presenting to the ED. Emergency physicians must be aware of the potential sequelae of bowel obstruction, and recall that not all respiratory failure is caused by a primary cardiopulmonary process.

Transcription factors (TFs) regulate the process of transcription through the modulation of different kinetic steps. Although models can often describe the observed transcriptional output of a measured gene, predicting a TFs role on a given promoter requires an understanding of how the TF alters each step of the transcription process. In this work, we use a simple model of transcription to assess the role of promoter identity, and the degree to which TFs alter binding of RNAP (stabilization) and initiation of transcription (acceleration) on three primary characteristics: the range of steady-state regulation, cell-to-cell variability in expression, and the dynamic response time of a regulated gene. We find that steady state regulation and the response time of a gene behave uniquely for TFs that regulate incoherently, i.e that speed up one step but slow the other. We also find that incoherent TFs have dynamic implications, with one type of incoherent mode configuring the promoter to respond more slowly at intermediate TF concentrations. We also demonstrate that the noise of gene expression for these TFs is sensitive to promoter strength, with a distinct non-monotonic profile that is apparent under stronger promoters. Taken together, our work uncovers the coupling between promoters and TF regulatory modes with implications for understanding natural promoters and engineering synthetic gene circuits with desired expression properties.

Spinal cord injury (SCI) leads to significant sublesional bone loss and high fracture rates. While loss of mechanical loading plays a significant role in SCI-induced bone loss, animal studies have demonstrated mechanical loading alone does not fully account for loss of bone following SCI. Indeed, we have shown that bone loss occurs below the level of an incomplete moderate contusion SCI, despite the resumption of weight-bearing and stepping. As systemic factors could also impact bone after SCI, bone alterations may also be present in bone sites above the level of injury. To examine this, we assessed bone microarchitecture and bone turnover in the supralesional humerus in male and female rats at two different ages following a moderate contusion injury in both sub-chronic (30 days) and chronic (180 days) time points after injury. At the 30-day timepoint, we found that both young and adult male SCI rats had decrements in trabecular bone volume at the supralesional proximal humerus (PH), while female SCI rats were not different from age-matched shams. At the 180-day timepoint, there were no statistical differences between SCI and sham groups, irrespective of age or sex, at the supralesional proximal humerus. At the 30-day timepoint, all SCI rats had lower BFR and higher osteoclast-covered trabecular surfaces in the proximal humerus compared to age-matched sham groups generally matching the pattern of SCI-induced changes in bone turnover seen in the sublesional proximal tibia. However, at the 180-day timepoint, only male SCI rats had lower BFR at the supralesional proximal humerus while female SCI rats had higher or no different BFR than their age-matched counterparts. Overall, this preclinical study demonstrates that a moderate contusion SCI leads to alterations in bone turnover above the level of injury within 30-days of injury; however male SCI rats maintained lower BFR in the supralesional humerus into long-term recovery. These data further highlight that bone loss after SCI is not driven solely by disuse. Additionally, these data allude to potential systemic factors exerting influence on bone following SCI and highlight the need to consider treatments for SCI-induced bone loss that impact both sublesional and systemic factors.

Abstract Bedform evolution and preserved cross strata are known to respond to floods. However, it is unclear if autogenic dynamics mask the flood signal in bedform evolution and cross strata. To address this, we characterize the temporal structure of autogenic noise in steady‐state bedform evolution in a physical experiment. Results reveal the existence of bedform groups—quasi‐stable collections of bedforms—that migrate at a similar speed as bedforms. We find that bedform and bedform‐group turnover timescales are the key autogenic timescales of bed evolution that set the transition time‐periods between different noise regimes in bedform evolution. Results suggest that bedform‐group turnover timescale sets the lower limit for detecting flood signals in bedform evolution, and floods with duration shorter than bedform turnover timescale can be severely degraded in bedform evolution and cross strata. Our work provides a new framework for interrogating fluvial cross strata for reconstruction of past floods.

Granulomatous dermatitis is a common tissue reaction pattern seen in the skin or systematically in various presentations. Granulomatous dermatitis can be subclassified into infectious and non-infectious categories. This article focuses on a patient with non-infectious granulomatous dermatitis followed for many years. Past medical history included bilateral total shoulder arthroplasty complicated by prosthetic joint infections. In its early stages, the axillary rash was painful and had many fluid-filled blisters. Ultimately, the histology of the rash deemed the lesion non-infectious and mostly due to an inflammatory process. Specifically, ionizing radiation was used for this patient. The category of granulomatous processes is broad and there are many subtypes. Other treatment options for non-infectious granulomatous processes may include corticosteroids, phototherapy, and interferon-gamma injections. The differential for granulomatous processes is extensive and treatment should be decided on a case-by-case basis.

PurposeRaoultella spp. is a genus of bacteria that is known to be closely related to Klebsiella. It has been debated whether Raoultella should be reclassified as a subgroup of Klebsiella. The aim of this study is to compare clinical aspects of Raoultella and Klebsiella oxytoca, a species of Klebsiella that is known to be bacteriologically similar to Raoultella spp.MethodsUsing data collected at a tertiary care hospital in the United States, we identified 43 patients with Raoultella infection and 1173 patients with Klebsiella oxytoca infection. We compared patient demographics (age and sex), hospitalization status, isolation sites and antibiotic resistance profiles between the two species.ResultsThere was no significant difference in patient demographics between the two bacteria species. The proportions of intensive care unit (ICU) admission were higher among patients with Raoultella infection (p=0.008). The most common site of isolation was urine for both species (39.5% of all patients with Raoultella spp. vs. 59.3% for K. oxytoca). The second most common site of isolation was blood stream for Raoultella spp. (23.3%) and respiratory tract for K. oxytoca (10.8%). Except for the high proportion of resistant isolates of Raoultella spp. for Trimethoprim/sulfamethoxazole, the antibiotic susceptibility profiles were similar between the two bacteria species. Both were susceptible to ciprofloxacin and meropenem.ConclusionWhile there are no significant differences in the patient demographics and antibiotic susceptibility profiles between Raoultella spp. and K. oxytoca, Raoultella may cause more serious infection requiring ICU admissions. Also, Raoultella may cause blood stream infection more frequently than K. oxytoca.

Piriformis Syndrome (PS) is a neuromuscular condition caused by the entrapment of the sciatic nerve at the level of the piriformis muscle (PM) and can cause significant discomfort and disability. PS is often misdiagnosed due to its overlapping symptoms with other lumbar and sciatic issues and as such, diagnosing PS remains challenging despite recent invasive and non-invasive diagnostic methods. Diagnostic musculoskeletal ultrasound (MSK US) offers a non-invasive, cost-effective alternative for the identification and evaluation of PS, providing dynamic, real-time imaging of the PM and adjacent structures. This article reviews the applications, advantages, and procedural insights of MSK US in the diagnosis of PS, emphasizing its relevance in rehabilitation settings. We discuss the technical aspects of ultrasound use, interpretation of findings, and integration into clinical practice, aiming to enhance the diagnostic accuracy and therapeutic outcomes for patients with suspected PS.