Validity Evidence for Using Virtual, Interactive Patient Encounters to Teach and Assess Clinical Reasoning for First-Year Medical Students.

Purpose: Despite universal agreement on the importance of clinical reasoning skills, inadequate curricular attention to these skills remains a problem. To facilitate integration of clinical reasoning instruction and assessment into the preclerkship phase, the authors created a clinical reasoning curriculum using technology-enhanced patient simulations.

Method: In 2023, first-year medical students at Duke University School of Medicine were enrolled in a biomedical science course using diagnostic reasoning sessions and 16 virtual, interactive patient (VIP) encounters to teach and assess clinical reasoning.

The transcriptional regulator Lrp activates the expression of genes involved in the biosynthesis of tilimycin and tilivalline enterotoxins in .

The toxigenic strains secrete tilymicin and tilivalline enterotoxins, which cause antibiotic-associated hemorrhagic colitis. Both enterotoxins are non-ribosomal peptides synthesized by enzymes encoded in two divergent operons clustered in a pathogenicity island. The transcriptional regulator Lrp (eucine-responsive egulatory rotein) controls the expression of several bacterial genes involved in virulence.

Draft genome sequences of strains isolated from ocular surface of CD36-knockout mice (B6.129S1-/J) with keratitis.

Three strains were cultured from the eyes of CD36-knockout mice (B6.129S1-/J) with and without keratitis housed at a biomedical research institute. Bacteria were sequenced using Illumina MiSeq technology for subsequent phylogenetic characterization and identification of virulence factor genes conferring pathogenic potential.

Prevalence and Pathologic Characterization of Mouse Kidney Parvovirus in Sentinel CD1 Mice.

Mouse kidney parvovirus (MKPV) infection can cause significant morbidity and mortality by inducing moderate to severe inclusion body nephropathy and kidney fibrosis in aged immunodeficient mice. However, MKPV infection in immunocompetent mice is associated with histopathologic findings ranging from absent to minimal or moderate lymphoplasmacytic interstitial nephritis without inclusion body in most cases. We surveyed the prevalence of MKPV via PCR from August 2019 through January 2021, using feces, kidneys, and livers collected and pooled from 2 sentinel mice [Crl:CD1(ICR)] (CD1) per surveillance cage (a total of 212 cages).

Links between climatic histories and the rise and fall of a Pacific chiefdom.

Sea level rise and climate change are shaping present societies, particularly those on oceanic islands. Few historical examples could serve as references for these changes. One such potential model is the Saudeleur Dynasty with its capital Nan Madol on the Pacific Island of Pohnpei.

Public Mass Shootings: Counterfactual Trend Analysis of the Federal Assault Weapons Ban.

Background: Assault weapon and large-capacity magazine bans are potential tools for policy makers to prevent public mass shootings. However, the efficacy of these bans is a continual source of debate. In an earlier study, we estimated the impact of the Federal Assault Weapons Ban (FAWB) on the number of public mass shooting events in the United States.

Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium.

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.

Lower hepatocellular carcinoma surveillance in metabolic dysfunction-associated steatotic liver disease: Impact on treatment eligibility.

Background And Aim: This study aimed to compare the determinants and impact of hepatocellular carcinoma (HCC) surveillance rates for people with metabolic dysfunction-associated steatotic liver disease (MASLD) versus other chronic liver diseases.

Methods: A dataset of HCC patients from a UK hospital (2007-2022) was analyzed. The Mann-Whitney U-test compared continuous variables.

Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.

Background: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by and gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome.

Titin is a nucleolar protein in neurons.

Titin is the largest protein produced by living cells and its function as a molecular spring in striated muscle is well characterized (1, 2). Here we demonstrate that titin isoforms in the same size range as found in muscle are prominent neuronal proteins in both the central and peripheral nervous systems, including motor neurons in the spinal cord and brain. Within these neurons, titin localizes to the dense fibrillar component of the nucleolus, the site of ribosomal RNA biogenesis and modification, and a critical site of dysfunction in neurodegenerative disease (3-5).

Gastric coinfection with thiopeptide-positive decreases FOXM1 and pro-inflammatory biomarker expression in a murine model of -induced gastric cancer.

infects half of the world population and is the leading cause of gastric cancer. We previously demonstrated that gastric cancer risk is associated with gastric microbiota. Specifically, gastric urease-positive and had contrasting effects on -associated gastric pathology and immune responses in germ-free INS-GAS mice.

Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS.

The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the CNS environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes.

Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.

Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients.

Evaluating the effects of moonlight on the vertical flight profiles of three western palaearctic swifts.

Recent studies have suggested the presence of moonlight mediated behaviour in avian aerial insectivores, such as swifts. Here, we use the combined analysis of state-of-the-art activity logger data across three swift species, the common, pallid and alpine swifts, to quantify flight height and activity in responses to moonlight-driven crepuscular and nocturnal light conditions. Our results show a significant response in flight heights to moonlight illuminance for common and pallid swifts, i.

IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.

Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett's esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive.

Evaluation and comparison of pharmacokinetic profiles and safety of two extended-release buprenorphine formulations in common marmosets (Callithrix jacchus).

While sustained-release buprenorphine (BSR) is used as a long-lasting opioid analgesic in common marmosets (Callithrix jacchus), there are no published studies on pharmaceutical-grade extended-release buprenorphine options such as Ethiqa XR (EXR) for this species. However, BSR is a compounded product and has been reported to cause injection site reactions in multiple species, including marmosets. Additionally, now with the availability of EXR, a pharmaceutical-grade veterinary product, the use of BSR in laboratory animals is not compliant with the Guide for the Care and Use of Laboratory Animals (Guide) unless scientifically justified and approved by the IACUC.

Molecular origins of mutational spectra produced by the environmental carcinogen -nitrosodimethylamine and S1 chemotherapeutic agents.

DNA-methylating environmental carcinogens such as -nitrosodimethylamine (NDMA) and certain alkylators used in chemotherapy form -methylguanine (m6G) as a functionally critical intermediate. NDMA is a multi-organ carcinogen found in contaminated water, polluted air, preserved foods, tobacco products, and many pharmaceuticals. Only ten weeks after exposure to NDMA, neonatally-treated mice experienced elevated mutation frequencies in liver, lung and kidney of ∼35-fold, 4-fold and 2-fold, respectively.

Motility of Different Gastric spp.

spp., including the well-known human gastric pathogen , can cause gastric diseases in humans and other mammals. They are Gram-negative bacteria that colonize the gastric epithelium and use their multiple flagella to move across the protective gastric mucus layer.

Megakaryocytes respond during sepsis and display innate immune cell behaviors.

Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known to participate in immune responses and play significant functions during infections, the role of MKs within the immune system remains largely unexplored. Histological studies of sepsis patients identified increased nucleated CD61 cells (MKs) in the lungs, and CD61 staining (likely platelets within microthrombi) in the kidneys, which correlated with the development of organ dysfunction.

Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America.

Along with infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres ( = 10, -positive = 7) and low-risk town of Tumaco ( = 10, -positive = 6).

A protocol for a cluster randomized trial of care delivery models to improve the quality of smoking cessation and shared decision making for lung cancer screening.

Background: Patients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening.

Methods: We will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be delivered on the same platform, and are implemented in real-world clinical settings; 2) examine barriers and facilitators of implementing the two approaches to delivering smoking cessation and SDM for LCS; and 3) determine the economic implications of implementation by assessing the healthcare resources required to increase smoking cessation for the two approaches by delivering smoking cessation within the context of LCS.

The IL-10 receptor inhibits cell extrinsic signals necessary for STAT1-dependent macrophage accumulation during colitis.

The loss of IL-10R function leads to severe early onset colitis and, in murine models, is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed, STAT1 mice exhibit defects in colonic macrophage accumulation after Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNγR, an inducer of STAT1 activation.

Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer.

Local environmental factors influence CD8 T cell priming in lymph nodes (LNs). Here, we sought to understand how factors unique to the tumor-draining mediastinal LN (mLN) impact CD8 T cell responses toward lung cancer. Type 1 conventional dendritic cells (DC1s) showed a mLN-specific failure to induce robust cytotoxic T cells responses.

Exercise reduces the anxiogenic effects of meta-chlorophenylpiperazine: The role of 5-HT2C receptors in the bed nucleus of the stria terminalis.

Introduction: Two weeks of voluntary exercise in group-housed mice produces a reduction in anxiety-like behaviors across a number of different measures, including a reduction in the anxiety levels typically produced by the anxiogenic serotonergic drug m-chlorophenylpiperazine (mCPP), an agonist at 5-HT2C/2b receptors. We have previously demonstrated that 2-weeks of voluntary exercise blunted the anxiogenic effects of systemic mCPP, and we have also shown that mCPP infused into the bed nucleus of the stria terminalis (BNST) is anxiogenic. Here we follow up on these reports.