Sulfur Amino Acid Restriction Enhances Exercise Capacity in Mice by Boosting Fat Oxidation in Muscle.

Dietary restriction of the sulfur-containing amino acids methionine and cysteine (SAAR) improves body composition, enhances insulin sensitivity, and extends lifespan; benefits seen also with endurance exercise. Yet, the impact of SAAR on skeletal muscle remains largely unexplored. Here we demonstrate that one week of SAAR in sedentary, young, male mice increases endurance exercise capacity. Indirect calorimetry showed that SAAR increased lipid oxidation at rest and delayed the onset of carbohydrate utilization during exercise. Transcriptomic analysis revealed increased expression of genes involved in fatty acid catabolism especially in glycolytic muscle following SAAR. These findings were functionally supported by increased fatty acid circulatory turnover flux and muscle ß-oxidation. Reducing lipid uptake from circulation through endothelial cell (EC)-specific CD36 deletion attenuated the running phenotype. Mechanistically, VEGF-signaling inhibition prevented exercise increases following SAAR, without affecting angiogenesis, implicating noncanonical VEGF signaling and EC CD36-dependent fatty acid transport in regulating exercise capacity by influencing muscle substrate availability.

Ileum Proteomics Identifies Distinct Pathways Associated with Different Dietary Doses of Copper-Fructose Interactions: Implications for the Gut-Liver Axis and MASLD.

The interactions of different dietary doses of copper with fructose contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) via the gut-liver axis. The underlying mechanisms remain elusive. The aim of this study was to identify the specific pathways leading to gut barrier dysfunction in the ileum using a proteomics approach in a rat model. Male weanling Sprague Dawley rats were fed diets with adequate copper (CuA), marginal copper (CuM), or supplemented copper (CuS) in the absence or presence of fructose supplementation (CuAF, CuMF, and CuSF) for 4 weeks. Ileum protein was extracted and analyzed with an LC-MS. A total of 2847 differentially expressed proteins (DEPs) were identified and submitted to functional enrichment analysis. As a result, the ileum proteome and signaling pathways that were differentially altered were revealed. Of note, the CuAF is characterized by the enrichment of oxidative phosphorylation and ribosome as analyzed with the KEGG; the CuMF is characterized by an enriched arachidonic acid metabolism pathway; and focal adhesion, the regulation of the actin cytoskeleton, and tight junction were significantly enriched by the CuSF. In conclusion, our proteomics analysis identified the specific pathways in the ileum related to the different dietary doses of copper-fructose interactions, suggesting that distinct mechanisms in the gut are involved in the development of MASLD.

Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism.

BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized. METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts. RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD. CONCLUSION: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.

Establishing African genomics and bioinformatics programs through annual regional workshops.

The African BioGenome Project (AfricaBP) Open Institute for Genomics and Bioinformatics aims to overcome barriers to capacity building through its distributed African regional workshops and prioritizes the exchange of grassroots knowledge and innovation in biodiversity genomics and bioinformatics. In 2023, we implemented 28 workshops on biodiversity genomics and bioinformatics, covering 11 African countries across the 5 African geographical regions. These regional workshops trained 408 African scientists in hands-on molecular biology, genomics and bioinformatics techniques as well as the ethical, legal and social issues associated with acquiring genetic resources. Here, we discuss the implementation of transformative strategies, such as expanding the regional workshop model of AfricaBP to involve multiple countries, institutions and partners, including the proposed creation of an African digital database with sequence information relating to both biodiversity and agriculture. This will ultimately help create a critical mass of skilled genomics and bioinformatics scientists across Africa.

Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome.

Sweet's syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweet's syndrome revealed a prominent interferon signature in Sweet's syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweet's syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweet's syndrome through recognition of type I interferons.

Associations Between PTSD Features and Firearm Ownership and Storage: Results From the PRImary Care Screening Methods (PRISM) Study.

INTRODUCTION: Veterans and active duty service members are significantly more likely to die by suicide using firearms compared to the general population. Not-secure firearm storage (e.g., keeping guns loaded/in an unlocked location) is associated with greater risk for suicide and a third of veteran firearm owners store at least 1 personal firearm unsecured. Veterans and active duty service members are also significantly more likely to be diagnosed with posttraumatic stress disorder (PTSD) than the general population. Symptoms of PTSD are divided into 4 criteria: reexperiencing, avoidance, negative affect, and hyperarousal. Research has suggested that endorsement of hyperarousal symptoms is positively associated with unsecure firearm storage and that avoidance symptoms might be negatively associated with unsecure storage practices. The present study examined the relationship between self-reported firearm ownership and storage practices among each item from the Primary Care PTSD Screening for DSM-IV-TR (PC-PTSD-IV) to explore associations between PTSD features and firearm ownership and storage. MATERIALS AND METHODS: Participants were recruited from primary care clinics across 5 military installations in the United States as part of a larger study (Mage = 45.4, SD = 16.9). Among participants (n = 2,685), most of our sample identified as male (51.3%) and white (67.3%) with 61.6% currently serving in the military, 16.8% retirees, and 21.6% family members. PTSD symptoms were assessed using the PC-PTSD-IV and a quarter met the clinical threshold for PTSD. Binomial and multinomial logistic regression analyses were used. RESULTS: Among completed responses, 989 (38.1%) people reported owning guns; among gun owners, 386 (39.0%) reported that they were loaded, and 352 (35.6%) reported they were loaded and unlocked. Endorsement of specific items on the PC-PTSD-IV, including those specific to hyperarousal and avoidance, was not significantly associated with storing firearms loaded and/or in nonsecure locations when controlling for military service. Non-responses to items around firearm storage practices were significantly associated with those individuals meeting the clinical threshold for PTSD according to the PC-PTSD-IV and participants currently serving had higher odds of storing at least 1 personal firearm loaded and both loaded and unlocked. CONCLUSIONS: Results from our study highlight similarities and departures from the previous literature on the connection between PTSD and non-secure firearm storage practices. Further research may examine (1) the relation between PTSD symptoms and firearm storage between active duty service members, retirees, and family members and (2) whether non-response to items regarding firearm ownership is systematic.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Classification of dry eye disease subtypes.

PURPOSE: The current subclassifications of dry eye disease (DED) are aqueous deficient (ADDE) and evaporative (EDE) forms, but there lacks consistency in the clinical characteristics used to define each of these. This study used clinical data to inform cut-off values for the subclassification of ADDE and EDE, to allow more consistent study of the epidemiology of both DED subtypes. METHODS: The study enrolled 261 residents from the UK, extracted from a cohort with demographics representing the population (mean 42.4 ± 18.7 years, 56 % females). The TFOS DEWS II diagnostic criteria were used to identify those with DED. Meibomian gland loss/drop-out (from meibography), lipid layer thickness (LLT - from interferometry graded on the Guillon-Keeler scale), and tear meniscus height (TMH - Keratograph 5M) along with tear evaporation (Delfin Vapometer) were used to characterise the subclassification. The Dry Eye Risk Factor Survey was used to assess risk factors associated with each DED subtype. RESULTS: Compared to individuals who were not diagnosed with DED, EDE was characterized by signs of meibomian gland loss of > 28 %, LLT grade < 3 and tear evaporation > 46 g/m2/h. In contrast, ADDE was best characterized by a reduced TMH < 0.2 mm. Based on these criteria, the prevalence of ADDE was 6.2 %, EDE was 64.2 %, and 11.1 % exhibited features of both ADDE and EDE, with 18.5 % unclassified despite having a DED diagnosis. Contact lens wear and computer use were risk factors for ADDE (p < 0.05), whereas age was a positive risk factor for EDE (p < 0.01). Meibomian gland loss (occurring in 27.9 %) was the most commonly observed sign in EDE. CONCLUSIONS: Data driven-classification of DED confirms that the evaporative form is most prevalent and identified that in a generalisable UK population, ADDE alone occurs only in approximately 1 in 16 cases of DED.

Revision Hip Arthroplasty Performed by Fellowship-Trained Versus Non-Fellowship-Trained Surgeons: A Comparison of Perioperative Management and Complications.

INTRODUCTION: Successful revision hip arthroplasty (rTHA) requires major resource allocation and a surgical team adept at managing these complex cases. The purpose of this study was to compare the results of rTHA performed by fellowship-trained and non-fellowship-trained surgeons. METHODS: A national administrative database was utilized to identify 5,880 patients who underwent aseptic rTHA and 1,622 patients who underwent head-liner exchange for infection by fellowship- and non-fellowship-trained surgeons from 2010 to 2020 with a 5-year follow-up. Postoperative opioid and anticoagulant prescriptions were compared among surgeons. Patients treated by fellowship- and non-fellowship-trained surgeons had propensity scores matched based on age, sex, comorbidity index, and diagnosis. The five-year surgical complications were compared using descriptive statistics. Multivariable analysis was performed to determine the odds of failure following head-liner exchange when performed by a fellowship-trained versus non-fellowship-trained surgeon. RESULTS: Aseptic rTHA patients treated by fellowship-trained surgeons received fewer opioids (132 versus 165 milligram morphine equivalents per patient) and non-aspirin anticoagulants (21.4 versus 32.0%, P < 0.001). Fellowship-training was associated with lower dislocation rates (9.9 versus 14.2%, P = 0.011), fewer postoperative infections, and fewer periprosthetic fractures and re-revisions (15.2 versus 21.3%, P < 0.001). Head-liner exchange for infection performed by fellowship-trained surgeons was associated with lower odds of failure (31.2 versus 45.7%, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62 to 0.91, P < 0.001). CONCLUSIONS: Revision THA performed by adult reconstruction fellowship-trained surgeons results in fewer re-revisions in aseptic cases and head-liner exchanges. Variations in resources, volumes, and perioperative protocols may account for some of the differences.

Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.

Quantitative predictive modeling of cancer growth, progression, and individual response to therapy is a rapidly growing field. Researchers from mathematical modeling, systems biology, pharmaceutical industry, and regulatory bodies, are collaboratively working on predictive models that could be applied for drug development and, ultimately, the clinical management of cancer patients. A plethora of modeling paradigms and approaches have emerged, making it challenging to compile a comprehensive review across all subdisciplines. It is therefore critical to gauge fundamental design aspects against requirements, and weigh opportunities and limitations of the different model types. In this review, we discuss three fundamental types of cancer models: space-structured models, ecological models, and immune system focused models. For each type, it is our goal to illustrate which mechanisms contribute to variability and heterogeneity in cancer growth and response, so that the appropriate architecture and complexity of a new model becomes clearer. We present the main features addressed by each of the three exemplary modeling types through a subjective collection of literature and illustrative exercises to facilitate inspiration and exchange, with a focus on providing a didactic rather than exhaustive overview. We close by imagining a future multi-scale model design to impact critical decisions in oncology drug development.

Perspective on oral processing of plant-based beverages.

Around the world, the market for plant-derived beverages is one of the fastest-expanding segments in the functional and specialty beverage areas of newer food product development. Consumers are increasingly likely to choose alternatives to bovine beverages due to factors including lactose intolerance, hypercholesterolemia prevalence, allergies to bovine beverages, and preference for vegan diets that contain functionally active ingredients with health-promoting characteristics. Due to health, ecological, and ethical concerns, many customers are interested in reducing their usage of animal products like bovine milk. A variety of plant-based beverage substitutes are being created by the food sector as a result. To create viable alternatives, it is first necessary to provide an overview of the chemical composition, structure, features, and nutritional attributes of ordinary bovine milk. Sensory acceptability in the case of substitutes for beverages made from legumes is a significant barrier to their widespread acceptance, and thus saliva acts as a sophisticated fluid that serves a variety of purposes in the cavity of the mouth. Designing and producing next-generation plant-based beverages that mimic the physicochemical and functional qualities of conventional bovine-based beverages is gaining popularity, and many of these products can be thought of as colloidal materials that contain the particles or polymers that give them their unique qualities NG-PB foods can have a wide range of rheological qualities, such as fluids with low viscosity (such as plant-based beverages), high-viscosity liquids (like creams), soft liquids (like yogurt), as well as hard solids (such as some cheeses).

Automatic Segmentation for Analysis of Murine Cardiac Ultrasound and Photoacoustic Image Data Using Deep Learning.

OBJECTIVE: Although there are methods to identify regions of interest (ROIs) from echocardiographic images of myocardial tissue, they are often time-consuming and difficult to create when image quality is poor. Further, while myocardial strain from ultrasound (US) images can be estimated, US alone cannot obtain functional information, such as oxygen saturation (sO2). Photoacoustic (PA) imaging, however, can be used to quantify sO2 levels within tissue non-invasively. METHODS: Here, we leverage deep learning methods to improve segmentation of the anterior wall of the left ventricle and apply both strain and oxygen saturation analysis via segmentation of murine US and PA images. RESULTS: Data revealed that training on US/PA images using a U-Net deep neural network can be used to create reproducible ROIs of the anterior wall of the left ventricle in a murine image dataset. Accuracy and Dice score metrics were used to evaluate performance of the neural network on each image type. We report an accuracy of 97.3% and Dice score of 0.84 for ultrasound, 95.6% and 0.73 for photoacoustic, and 96.5% and 0.81 for combined ultrasound and photoacoustic images. CONCLUSION: Rapid segmentation via such methods can assist in quantification of strain and oxygenation.

In Vivo Three-Dimensional Geometric Reconstruction of the Mouse Aortic Heart Valve.

Aortic valve (AV) disease is a common valvular lesion in the United States, present in about 5% of the population at age 65 with increasing prevalence with advancing age. While current replacement heart valves have extended life for many, their long-term use remains hampered by limited durability. Non-surgical treatments for AV disease do not yet exist, in large part because our understanding of AV disease etiology remains incomplete. The direct study of human AV disease remains hampered by the fact that clinical data is only available at the time of treatment, where the disease is at or near end stage and any time progression information has been lost. Large animal models, long used to assess replacement AV devices, cannot yet reproduce AV disease processes. As an important alternative mouse animal models are attractive for their ability to perform genetic studies of the AV disease processes and test potential pharmaceutical treatments. While mouse models have been used for cellular and genetic studies of AV disease, their small size and fast heart rates have hindered their use for tissue- and organ-level studies. We have recently developed a novel ex vivo micro-CT-based methodology to 3D reconstruct murine heart valves and estimate the leaflet mechanical behaviors (Feng et al. in Sci Rep 13(1):12852, 2023). In the present study, we extended our approach to 3D reconstruction of the in vivo functional murine AV (mAV) geometry using high-frequency four-dimensional ultrasound (4DUS). From the resulting 4DUS images we digitized the mAV mid-surface coordinates in the fully closed and fully opened states. We then utilized matched high-resolution µCT images of ex vivo mouse mAV to develop mAV NURBS-based geometric model. We then fitted the mAV geometric model to the in vivo data to reconstruct the 3D in vivo mAV geometry in the closed and open states in n = 3 mAV. Results demonstrated high fidelity geometric results. To our knowledge, this is the first time such reconstruction was ever achieved. This robust assessment of in vivo mAV leaflet kinematics in 3D opens up the possibility for longitudinal characterization of murine models that develop aortic valve disease.

A link between evolution and society fostering the UN sustainable development goals.

Given the multitude of challenges Earth is facing, sustainability science is of key importance to our continued existence. Evolution is the fundamental biological process underlying the origin of all biodiversity. This phylogenetic diversity fosters the resilience of ecosystems to environmental change, and provides numerous resources to society, and options for the future. Genetic diversity within species is also key to the ability of populations to evolve and adapt to environmental change. Yet, the value of evolutionary processes and the consequences of their impairment have not generally been considered in sustainability research. We argue that biological evolution is important for sustainability and that the concepts, theory, data, and methodological approaches used in evolutionary biology can, in crucial ways, contribute to achieving the UN Sustainable Development Goals (SDGs). We discuss how evolutionary principles are relevant to understanding, maintaining, and improving Nature Contributions to People (NCP) and how they contribute to the SDGs. We highlight specific applications of evolution, evolutionary theory, and evolutionary biology's diverse toolbox, grouped into four major routes through which evolution and evolutionary insights can impact sustainability. We argue that information on both within-species evolutionary potential and among-species phylogenetic diversity is necessary to predict population, community, and ecosystem responses to global change and to make informed decisions on sustainable production, health, and well-being. We provide examples of how evolutionary insights and the tools developed by evolutionary biology can not only inspire and enhance progress on the trajectory to sustainability, but also highlight some obstacles that hitherto seem to have impeded an efficient uptake of evolutionary insights in sustainability research and actions to sustain SDGs. We call for enhanced collaboration between sustainability science and evolutionary biology to understand how integrating these disciplines can help achieve the sustainable future envisioned by the UN SDGs.

Is Hospital-Based Outpatient Revision Total Knee Arthroplasty Safe? An Analysis of 2,171 Outpatient Aseptic Revision Procedures.

BACKGROUND: Outpatient primary total knee arthroplasty (TKA) has been well-established as a safe and effective procedure; however, the safety of outpatient revision TKA remains unclear. Therefore, this study utilized a large database to compare outcomes between outpatient and inpatient revision TKA. METHODS: An all-payor database was queried to identify patients undergoing revision TKA from 2010 to 2022. Patients who had diagnosis codes related to periprosthetic joint infection (PJI) were excluded. Outpatient surgery was defined as a length of stay < 24 hours. Cohorts were matched by age, sex, Elixhauser Comorbidity Index, comorbidities (diabetes, obesity, tobacco use), components revised (1-versus 2-component), and revision etiology. Medical complications at 90 days and surgical complications at 1 and 2 years postoperatively were evaluated through multivariate logistic regression. A total of 4,342 aseptic revision TKAs were included. RESULTS: No differences in patient characteristics, procedure type, or revision etiologies were seen between groups. The outpatient cohort had a lower risk of PJI (odds ratio (OR): 0.547, 95% confidence interval (CI): 0.337 to 0.869; P = .012), wound dehiscence (OR: 0.393, 95% CI: 0.225 to 0.658; P < .001), transfusion (OR: 0.241, 95% CI: 0.055 to 0.750; P = .027), reoperation (OR: 0.508, 95% CI: 0.305 to 0.822; P = .007), and any complication (OR: 0.696, 95% CI: 0.584 to 0.829; P < .001) at 90 days postoperatively. At 1 year and 2 years postoperatively, outpatient revision TKA patients had a lower incidence of revision for PJI (OR: 0.332, 95% CI: 0.131 to 0.743; P = .011 and OR: 0.446, 95% CI; 0.217 to 0.859; P = .020, respectively) and all-cause revision (OR: 0.518, 95% CI: 0.377 to 0.706; P < .001 and OR: 0.548, 95% CI: 0.422 to 0.712; P < .001, respectively). CONCLUSIONS: Our findings suggest that revision TKA can be safely performed on an outpatient basis in appropriately selected patients who do not have an increased risk of adverse events relative to inpatient revision TKA. However, we could not ascertain case complexity in either cohort, and despite controlling for several potential confounders, other less tangible differences could exist between groups.

Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes.

BACKGROUND: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM. METHODS: Patients with T2DM (n = 17) and non-diabetic controls (NDC; n = 11) aged 25-80 yrs. participated in this study. Serum levels of endotoxin, calprotectin, soluble CD14 and CD163, and several inflammatory cytokines were measured. In addition to standard liver injury markers, ALT and AST, novel serum markers of liver injury, keratin 18 (K-18) M30 (apoptosis-associated caspase-cleaved keratin 18), and M65 (soluble keratin 18) were evaluated. Statistical analyses were performed using the Mann-Whitney test to assess differences between study groups. Pearson's correlation analysis was performed to determine the strength of association between two variables using GraphPad Prism 9.5.0 software. RESULTS: Patients with T2DM had significantly higher levels of sCD14 in comparison to NDC, suggesting an increase in gut permeability, microbial translocation, and monocyte/macrophage activation. Importantly, relevant to the ensuing inflammatory responses, the increase in sCD14 in patients with T2DM was accompanied by a significant increase in sCD163, a marker of hepatic Kupffer cell activation and inflammation. Further, a positive correlation was observed between sCD163 and endotoxin and sCD14 in T2DM patients but not in NDC. In association with these changes, keratin 18 (K-18)-based serum markers (M65 and M30) that reflect hepatocyte death were significantly higher in the T2DM group indicating ongoing liver injury. Notably, both M65 and M30 levels correlated with sCD14 and sCD163, suggesting that immune cell activation and hepatic inflammation may be linked to the development of liver injury in T2DM. CONCLUSIONS: These findings suggest that the pathogenic changes in the gut-liver axis, marked by increased microbial translocation, may be a major component in the etiology of hepatocyte inflammation and injury in patients with T2DM. However, larger longitudinal studies, including histological evidence, are needed to confirm these observations.

Novel Insights Into the Architecture of Macro and Microstructures in Cattle Ossa Cordis.

Ossa cordis, bones located within the heart trigones, are often classified as heterotopic or ectopic bones. Despite their high prevalence in cattle and some other bovids, little is known about their structure or development. Scanning electron microscopy, X-ray microtomography, gross dissections, and measurements showed the anatomical locations, prevalence, shapes, and measurements of the cardiac bones in both Egyptian Baladi cattle and Holstein-Friesians. All cattle (n = 12) had an Ossa cordis dextrum (average = 50.70 × 20.91 × 5.40 mm). Additionally, 80% Egyptian Baladi and 57% Holstein-Friesian had a smaller Ossa cordis sinistrum (average = 24.94 × 12.75 × 4.12 mm). Egyptian Baladi Ossa cordis were smaller than observed in Holstein-Friesians. Energy-dispersive X-ray analysis showed the elemental constitution (carbon, oxygen, calcium, nitrogen, phosphorus, sodium, and magnesium) of Ossa cordis and Cartilago cordis. These imaging techniques, plus four histological stains (hematoxylin and eosin, Crossman's trichrome, Alcian blue with Van Gieson, and Sirius Red) and microscopy, demonstrated osteoblasts, osteocytes, osteoclasts, astrocytes, blood vessels, bone marrow, lamellar and woven bone, cortical bone, trabeculations with pores and canaliculi, and fibrous components including collagen in the Ossa cordis dextrum and sinistrum. Hyaline cartilage and fibrocartilage (chondrocytes and cartilage matrix) were found within and surrounding the Ossa cordis. These findings were additionally compared against other cattle breeds and species.

Distant relatives of a eukaryotic cell-specific toxin family evolved a complement-like mechanism to kill bacteria.

Cholesterol-dependent cytolysins (CDCs) comprise a large family of pore-forming toxins produced by Gram-positive bacteria, which are used to attack eukaryotic cells. Here, we functionally characterize a family of 2-component CDC-like (CDCL) toxins produced by the Gram-negative Bacteroidota that form pores by a mechanism only described for the mammalian complement membrane attack complex (MAC). We further show that the Bacteroides CDCLs are not eukaryotic cell toxins like the CDCs, but instead bind to and are proteolytically activated on the surface of closely related species, resulting in pore formation and cell death. The CDCL-producing Bacteroides is protected from the effects of its own CDCL by the presence of a surface lipoprotein that blocks CDCL pore formation. These studies suggest a prevalent mode of bacterial antagonism by a family of two-component CDCLs that function like mammalian MAC and that are wide-spread in the gut microbiota of diverse human populations.

Collaboration matters: A randomized controlled trial of patient-clinician collaboration in suicide risk assessment and intervention.

BACKGROUND: Clinician collaboration can help high-risk individuals to manage their suicidal crises. However, limited research has directly examined how higher patient-clinician collaboration during assessment and intervention can effectively reduce suicidal ideation. This novel randomized clinical trial compared a high vs. low level of patient-clinician collaboration by pairing commonly used assessment (Structured Interview vs. Narrative Assessment) and intervention approaches (Safety Planning Intervention vs. Crisis Response Planning). We hypothesized that the interventions involving higher (than lower) patient-clinician collaboration during assessment (Narrative Assessment) or intervention (Crisis Response Planning) would lead to larger reductions in suicidal ideation. METHODS: Eighty-two participants with a history of suicide ideation and/or attempts were randomly assigned to one of the four interventions varying in patient-clinician collaboration. After attrition, sixty-six participants completed the study. Suicidal ideation via ecological momentary assessment was measured 14 days before and 14 days after treatment. RESULTS: Although the severity of suicidal ideation decreased in all groups, the two groups that included highly collaborative assessment had larger pre-post reductions in suicidal ideation (Narrative Assessment+Safety Plan; dwithin = 0.26, and Narrative Assessment+Crisis Response Plan; dwithin = 0.19) than the groups that included a checklist-based assessment (Structured Interview). LIMITATIONS: Longer follow-up periods with a larger sample would have provided an understanding of the durability of intervention effects. CONCLUSION: Results suggest that the inclusion of higher patient-clinician collaboration techniques during suicide risk assessment can effectively reduce suicidal thoughts. Thus, clinician-led collaborative risk assessment approaches can enhance the effects of safety planning-type interventions among patients with elevated risk for suicide versus checklist-based assessment approaches.