Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases.

Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD.

Differential Impact of Smoking on Methylome and Transcriptome in Crohn's Disease and Ulcerative Colitis.

Background: Smoking is an environmental factor that differentially impacts Crohn's disease (CD) and ulcerative colitis (UC). The mechanism of impact of smoking on disease risk and clinical outcomes remains to be established.

Methods: This study used a prospective cohort of patients with CD or UC.

Multi-modal skin atlas identifies a multicellular immune-stromal community associated with altered cornification and specific T cell expansion in atopic dermatitis.

In healthy skin, a cutaneous immune system maintains the balance between tolerance towards innocuous environmental antigens and immune responses against pathological agents. In atopic dermatitis (AD), barrier and immune dysfunction result in chronic tissue inflammation. Our understanding of the skin tissue ecosystem in AD remains incomplete with regard to the hallmarks of pathological barrier formation, and cellular state and clonal composition of disease-promoting cells.

The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status.

The CD4 T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease.

Reciprocal interactions between host T helper cells and gut microbiota enforce local immunological tolerance and modulate extra-intestinal immunity. However, our understanding of antigen-specific tolerance to the microbiome is limited. Here, we developed a systematic approach to predict HLA class-II-specific epitopes using the humanized bacteria-originated T cell antigen (hBOTA) algorithm.

Cloxacillin-induced acute vanishing bile duct syndrome: A case study and literature review.

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One aetiology is drug-induced liver injury. Cloxacillin, an antistaphylococcal penicillin, typically causes "bland" cholestasis.

Questionnaire and Portable Sleep Test Screening of Sleep Disordered Breathing in Acute Stroke and TIA.

Sleep disordered breathing (SDB) is highly prevalent, but frequently unrecognized among stroke patients. Polysomnography (PSG) is difficult to perform soon after a stroke. We evaluated the use of screening questionnaires and portable sleep testing (PST) for patients with acute stroke, subarachnoid hemorrhage, or transient ischemic attack to expedite SDB diagnosis and management.

Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease.

The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy.

Chronic Kidney Disease as Risk Factor for Enlarged Perivascular Spaces in Patients With Stroke and Relation to Racial Group.

Background And Purpose: Enlarged perivascular spaces (EPVS) are considered subclinical markers of small vessel disease, associated with increased risk of stroke and dementia. Increasing evidence links chronic kidney disease (CKD) to small vessel disease. We explored the relationship between CKD and EPVS burden and the influence of racial group in this relation.

Perihematomal edema surrounding spontaneous intracerebral hemorrhage by CT: Ellipsoidal versus morphometric volumetry.

Perihematomal edema (PHE) surrounding intracerebral hemorrhage (ICH) may contribute to disease-associated morbidity. Before quantifying PHE's effects on morbidity, a fast, accurate, and reproducible method for measuring PHE volume is needed. The aim of this study is to demonstrate the use of a semiautomated dual clustering segmentation algorithm to generate PHE volumetrics on noncontrast computed tomography (CT) of the head and compare this technique to physicians' manual calculations.

High Prevalence of Cerebral Microbleeds in Inner City Young Stroke Patients.

Background: Data on cerebral microbleeds (CMBs) in younger populations are lacking, particularly in young stroke patients. We sought to characterize CMBs in an inner city cohort of young adults with stroke.

Methods: CMB presence, count, and topography were assessed on magnetic resonance imaging (MRI) scans of 104 young stroke patients (≤49 years) presenting to Boston Medical Center between January 2006 and February 2010.

Delay in Diagnosis of Basilar Artery Stroke.

Background: Basilar artery stroke causes substantial morbidity and mortality. Although its unusual clinical presentation potentially contributes to a delay in diagnosis, this problem has not been systematically studied. We compared intervals between symptom onset, initial presentation, and diagnosis in stroke due to basilar artery (BA) versus left middle cerebral artery (LMCA) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke.

Recurrent vascular events in lacunar stroke patients with metabolic syndrome and/or diabetes.

Objectives: We used a prospective clinical trial to examine the risks conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort.

Methods: The SPS3 trial enrolled 3,020 patients with lacunar strokes. Participants were stratified into groups of METS only, DM only, both, or neither using American Heart Association/National Heart, Lung, and Blood Institute and World Health Organization guidelines.

Can blood pressure be lowered safely in older adults with lacunar stroke? The Secondary Prevention of Small Subcortical Strokes study experience.

Objectives: To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke.

Design: Cohort study.

Setting: The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for secondary stroke prevention.

Larger A1/M1 diameter ratio predicts embolic anterior cerebral artery territorial stroke.

Background And Purpose: In contrast to middle cerebral artery territory strokes, anterior cerebral artery strokes (ACAS) occur rarely. The low frequency of ACAS, in relation to middle cerebral artery territory strokes, may be explained by differences in ACA and middle cerebral artery anatomy influencing their respective flow-directed embolism rates. We aimed to determine whether variability in ACA anatomy, and in particular A1 segment diameter, is associated with embolic ACAS.

Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes study.

Background: We sought to describe the course and predictors of quality of life (QOL) after lacunar stroke. We hypothesized that there is a decline in QOL after recovery from lacunar stroke.

Methods: The Secondary Prevention of Small Subcortical Strokes is a clinical trial in lacunar stroke patients with annual assessments of QOL with the stroke-specific QOL score.

The effect of a neurocritical care service without a dedicated neuro-ICU on quality of care in intracerebral hemorrhage.

Background: Introduction of neurocritical care services to dedicated neuro-ICUs is associated with improved quality of care. The impact of a neurocritical care service without a dedicated neuro-ICU has not been studied.

Methods: We retrospectively identified all patients admitted to our institution with intracerebral hemorrhage (ICH) in two 12-month periods: immediately before the arrival of the first neurointensivist ("before") and after the neurocritical care service was established ("after").

SNAP-25, a SNARE protein, inhibits two types of K channels in esophageal smooth muscle.

Background & Aims: The plasma membrane-associated soluble N-ethylmaleimide-sensitive factors attachment protein receptors (SNAREs), synaptosome-associated protein of 25 kilodaltons (SNAP-25), and syntaxin 1A, have been found to physically interact with and functionally modify membrane-spanning ion channels. Studies were performed in cat esophageal body and lower esophageal sphincter (LES) smooth muscle to (1) show the presence of SNAP-25, and (2) determine whether SNAP-25 affects K+ channel activity.

Methods: Single circular muscle cells from the esophageal body and sphincter were studied.