Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.

Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses.

12,13-diHOME Promotes Inflammatory Macrophages and Epigenetically Modifies Their Capacity to Respond to Microbes and Allergens.

Elevated infant fecal concentrations of the bacterial-derived lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) increase the risk for childhood atopy and asthma. However, the mechanisms by which this lipid contributes to disease development are largely unknown. We hypothesized that macrophages, which are key to both antimicrobial and antigen responses, are functionally and epigenetically modified by 12,13-diHOME leading to short- and long-term dysfunction with consequences for both antimicrobial and antigenic responses.

Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk.

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort ( = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals.

Microbiome-Immune Interactions in Allergy and Asthma.

The human microbiota has been established as a key regulator of host health, in large part owing to its constant interaction with and impact on host immunity. A range of environmental exposures spanning from the prenatal period through adulthood are known to affect the composition and molecular productivity of microbiomes across mucosal and dermal tissues with short- and long-term consequences for host immune function. Here we review recent findings in the field that provide insights into how microbial-immune interactions promote and sustain immune dysfunction associated with allergy and asthma.

Manual Therapy for Patients With Radiation-Associated Trismus After Head and Neck Cancer.

Importance: Trismus is highly prevalent in head and neck cancer (HNC) survivorship. Current standards for trismus treatment include various stretch-based exercise protocols as a primary and single treatment modality with limited evidence regarding the role of manual therapy (MT) for this indication.

Objective: To assess the effect size and associations of response to MT to increase oral opening in the setting of radiation-associated trismus.

Manual Therapy for Fibrosis-Related Late Effect Dysphagia in head and neck cancer survivors: the pilot MANTLE trial.

Introduction: Late dysphagia that develops or persists years after head and neck cancer (HNC) is a disabling survivorship issue. Fibrosis is thought to stiffen connective tissues and compress peripheral nerve tracts, thereby contributing to diminished strength, flexibility, and in some cases denervation of swallowing muscles. Manual therapy (MT) is used in cancer survivors for pain and other indications, but it is unknown if increasing blood flow, flexibility and cervical range of motion (CROM) in the head and neck may improve late dysphagia.

Obesity results in adipose tissue T cell exhaustion.

Despite studies implicating adipose tissue T cells (ATT) in the initiation and persistence of adipose tissue inflammation, fundamental gaps in knowledge regarding ATT function impedes progress toward understanding how obesity influences adaptive immunity. We hypothesized that ATT activation and function would have tissue-resident-specific properties and that obesity would potentiate their inflammatory properties. We assessed ATT activation and inflammatory potential within mouse and human stromal vascular fraction (SVF).

Acute Aerobic Exercise Remodels the Adipose Tissue Progenitor Cell Phenotype in Obese Adults.

Adipose tissue pathology in obese patients often features impaired adipogenesis, angiogenesis, and chronic low-grade inflammation, all of which are regulated in large part by adipose tissue stromal vascular cells [SVC; i.e., non-adipocyte cells within adipose tissue including preadipocytes, endothelial cells (ECs), and immune cells].

Weight Regain in Formerly Obese Mice Hastens Development of Hepatic Steatosis Due to Impaired Adipose Tissue Function.

Objective: Weight regain after weight loss is common, and there is evidence to suggest negative effects on health because of weight cycling. This study sought to investigate the impact of weight regain in formerly obese mice on adipose tissue architecture and stromal cell function.

Methods: A diet-switch model was employed for obesity induction, weight loss, and weight regain in mice.

Adipose tissue dendritic cell signals are required to maintain T cell homeostasis and obesity-induced expansion.

Adipose tissue derived chronic inflammation is a critical component of obesity induced type II diabetes. Major histocompatibility complex II (MHCII) mediated T cell activation within adipose tissue is one mechanism that contributes to this phenotype. However, the contribution of dendritic cells as professional antigen presenting cells in adipose issue has not previously been explored.

The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.

Objective: Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their significance in adipose tissue metabolism and physiology has not been demonstrated in vivo. We previously identified Blnc1 as a conserved lncRNA regulator of brown and beige adipocyte differentiation.

Correction: Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

[This corrects the article DOI: 10.1371/journal.pone.

Sevelamer Improves Steatohepatitis, Inhibits Liver and Intestinal Farnesoid X Receptor (FXR), and Reverses Innate Immune Dysregulation in a Mouse Model of Non-alcoholic Fatty Liver Disease.

Bile acid sequestrants are synthetic polymers that bind bile acids in the gut and are used to treat dyslipidemia and hyperphosphatemia. Recently, these agents have been reported to lower blood glucose and increase insulin sensitivity by altering bile acid signaling pathways. In this study, we assessed the efficacy of sevelamer in treating mice with non-alcoholic fatty liver disease (NAFLD).

Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.

Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity.

Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line.

Echoes from the past: a healthy Baltic Sea requires more effort.

Integrated sediment multiproxy studies and modeling were used to reconstruct past changes in the Baltic Sea ecosystem. Results of natural changes over the past 6000 years in the Baltic Sea ecosystem suggest that forecasted climate warming might enhance environmental problems of the Baltic Sea. Integrated modeling and sediment proxy studies reveal increased sea surface temperatures and expanded seafloor anoxia (in deep basins) during earlier natural warm climate phases, such as the Medieval Climate Anomaly.

Echocardiographic evidence of left ventricular hypertrophy in obese dogs.

Background: Cardiomyopathy of obesity occurs in humans, but the gross and cellular myocardial response to obesity in dogs is not well defined.

Objectives: To characterize in vivo myocardial morphology and function in normotensive obese dogs, and quantitate collagen, triglyceride and myocyte cross-sectional area (CSA) in postmortem tissues from obese dogs.

Animals: Echocardiographic-Doppler measurements of normotensive obese dogs (n = 19) without historical or physical examination evidence of disease, and lean healthy dogs (n = 19) matched for age and ideal weight.

Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1.

Precursor cells of the embryonic cortex sequentially generate neurons and then glial cells, but the mechanisms regulating this neurogenic-to-gliogenic transition are unclear. Using cortical precursor cultures, which temporally mimic this in vivo differentiation pattern, we demonstrate that cortical neurons synthesize and secrete the neurotrophic cytokine cardiotrophin-1, which activates the gp130-JAK-STAT pathway and is essential for the timed genesis of astrocytes in vitro. Our data indicate that a similar phenomenon also occurs in vivo.

Variable extent of clopidogrel responsiveness in patients after coronary stenting.

Clopidogrel is an effective and specific inhibitor of ADP-induced platelet aggregation. After metabolic activation, the active clopidogrel metabolite irreversibly impairs the human platelet P2Y12 ADP receptor. Gialpha-protein activation and inhibition of vasodilator-stimulated phosphoprotein (VASP) phosphorylation are two key elements of the P2Y12 receptor pathway suitable for quantitation of clopidogrel effects.

Assessment of vessel wall thickness in carotid atherosclerosis using spiral CT angiography.

Objectives: the purpose of this study was to evaluate the amount of vessel wall thickening in the internal and common carotid arteries in patients undergoing spiral CT angiography for the investigation of significant atherosclerotic disease.

Materials And Methods: forty-five carotid systems in patients with a 70% or greater stenosis (according to carotid duplex) were imaged with CT spiral angiography using a standardised protocol. The vessel wall thickness of the distal common and mid internal carotid artery was measured using axial CT sections.

Evaluation of cross-sectional luminal morphology in carotid atherosclerotic disease by use of spiral CT angiography.

Background And Purpose: This study sought to determine the frequency of noncircular lumens in patients with significant carotid atherosclerotic disease and to evaluate the effect of noncircular lumens on stenosis measurement derived from angiographic projections.

Methods: One hundred consecutive patients presenting with an internal carotid artery stenosis of at least 50% were imaged with spiral CT angiography. The transverse morphology of the diseased lumen was assessed on axial images, and the frequency of noncircular lumens was determined.

Telomerase activity in malignant and benign renal tumors.

Objectives: An important characteristic of malignant cells is their unlimited replicative potential, their immortality. In conferring this immortality, the enzyme telomerase is believed to play a crucial role. The detection of telomerase activity provides new knowledge regarding the biologic growth behavior of tumors and offers new diagnostic and therapeutic tools.