Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1Ldlr mice.

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models.

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice.

Background & Aims: Non-absorbable inhibitors of the apical sodium-dependent bile acid transporter (ASBT; also called ileal bile acid transporter [IBAT]) are recently approved or in clinical development for multiple cholestatic liver disorders and lead to a reduction in pruritus and (markers for) liver injury. Unfortunately, non-absorbable ASBT inhibitors (ASBTi) can induce diarrhoea or may be ineffective if cholestasis is extensive and largely precludes intestinal excretion of bile acids. Systemically acting ASBTi that divert bile salts towards renal excretion may alleviate these issues.

Differential and organ-specific functions of organic solute transporter α and β in experimental cholestasis.

Background & Aims: Organic solute transporter (OST) subunits OSTα and OSTβ facilitate bile acid efflux from the enterocyte into the portal circulation. Patients with deficiency of OSTα or OSTβ display considerable variation in the level of bile acid malabsorption, chronic diarrhea, and signs of cholestasis. Herein, we generated and characterized a mouse model of OSTβ deficiency.

The Lipid Raft Component Stomatin Interacts with the Na Taurocholate Cotransporting Polypeptide (NTCP) and Modulates Bile Salt Uptake.

The sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the basolateral membrane of hepatocytes, where it mediates the uptake of conjugated bile acids and forms the hepatocyte entry receptor for the hepatitis B and D virus. Here, we aimed to identify novel protein-protein interactions that could play a role in the regulation of NTCP. To this end, NTCP was precipitated from HA-tagged hNTCP-expressing HepG2 cells, and chloride channel CLIC-like 1 (CLCC1) and stomatin were identified as interacting proteins by mass spectrometry.

Overall outcomes of laparoscopic-assisted ERCP after Roux-en-Y gastric bypass and sphincter of Oddi dysfunction subgroup analysis.

 Biliary access following Roux-en-Y gastric bypass (RYGB) anatomy presents a significant challenge. Long-term outcomes of laparoscopic-assisted trans-gastric ERCP (LA-ERCP) including sphincter of Oddi dysfunction (SOD) subtypes have not been thoroughly examined. Our study aims to present our overall outcomes of trans-gastric LAERCP and examine a significant subgroup of patients with SOD after RYGB.

Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling.

Objective: Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined.

Is age a real or perceived discriminator for bariatric surgery? A long-term analysis of bariatric surgery in the elderly.

Background: Bariatric surgery is the most effective treatment of obesity. There are few studies evaluating long-term outcomes in elderly patients.

Objectives: Our study was designed to evaluate the safety and long-term outcomes of bariatric surgery in the elderly compared with a contemporary medically managed cohort.

Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content.

Objectives: Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA.

Multimodal Postoperative Pain Control Is Effective and Reduces Opioid Use After Laparoscopic Roux-en-Y Gastric Bypass.

Background: Opioids have been the mainstay for postoperative pain relief for many decades. Recently, opioid-related adverse events and death have been linked to postoperative dependency. Multimodal approaches to postoperative pain control may be part of the solution to this health care crisis.

The Relationship Among Online Sexually Explicit Material Exposure to, Desire for, and Participation in Rough Sex.

The broad accessibility of online sexually explicit material (SEM) exposes viewers to a wide scope of sexual behaviors. Social concern tends to be heightened over SEM that incorporates highly graphic, "rough" sex. This study assessed the associations among exposure to rough sex in SEM, desire for rough sex, and participation in rough sex while accounting for gender, sexual orientation, and perceived realism of SEM.

Loving Oneself: The Associations Among Sexually Explicit Media, Body Image, and Perceived Realism.

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The readmission contradiction: toward clarifying common misconceptions about bariatric readmissions and quality improvement.

Background: Efforts to improve quality in U.S. medicine have included reimbursement penalties for readmissions.

Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis.

Background: MicroRNAs (miRNAs) are epigenetically involved in regulating gene expression. They may be of importance in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to determine the role of miRNAs by their specific blocking in the CD4+CB45RBhi T-cell transfer model of chronic experimental colitis.

Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease.

Background And Aim: T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy.

Methods: Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease.

Crossbow injuries to the thumb.

Archery injuries resulting in significant digital impairment are uncommon. The purpose of this study was to review seven patients treated at our institution for injuries of the left thumb sustained during recreational use of a crossbow. We reviewed all thumb injuries caused by crossbow use treated at Geisinger Health System between August 2011 and November 2012.

Effect of interleukin-17 on gene expression profile of fibroblasts from Crohn's disease patients.

Background And Aim: The expression of interleukin (IL)-17 is upregulated in inflammatory bowel disease (IBD). Since fibroblasts are known to be responsive to IL-17, they may play a role in the modulation of inflammatory responses in IBD. Here, the effects of IL-17 on ileum and colon fibroblasts from Crohn's disease (CD) and ulcerative colitis (UC) patients are investigated, as compared to controls.

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn's disease patients.

Aim: To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn's disease (CD).

Methods: In this study, we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls. As both autophagy related like 1 (ATG16L1) and immunity-related guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleotide-binding ligomerization domain-containing protein 2 (NOD2) has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.

Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

Background & Aims: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with the occurrence of AZA-related toxicity. The aim of our study was to determine the relative contribution of ITPA and TPMT mutations to the development of toxicity induced by AZA treatment in IBD patients.

Consequence of functional Nod2 and Tlr4 mutations on gene transcription in Crohn's disease patients.

The concept that mutations in germ-line encoded pattern recognition receptors with immune activating functions are associated with an increased incidence in Crohn's disease (CD) is gaining acceptance. Whether these mutations have similar or distinct effects on cellular physiology remains obscure. The incidence of three single nucleotide polymorphisms (SNPs) within the Nod2 gene and one functional SNP within both the Tlr4 and Tlr5 gene in a Dutch cohort of 637 patients with inflammatory bowel disease and 127 controls was investigated.

Sex differences in cardiovascular disease: are women with low socioeconomic status at high risk?

Background: Cardiovascular disease is still portrayed as a typical male disease, and men are more often submitted to invasive procedures or referred earlier.

Aim: To explore sex differences in morbidity and referral patterns in cardiovascular disease in general practice, and the role of age and socioeconomic status.

Method: Data were obtained from a continuous morbidity registration project in the Netherlands from 1986 to 1995 in which 12,000 patients were followed over 10 years.

[Angina pectoris and myocardial infarction: sex differences in risk profile, prognosis and referral by family physician].

Objective: To detect possible sex differences in risk factors, referrals and prognosis after angina pectoris (AP) and myocardial infarction (MI).

Design: Retrospective.

Method: From 4 general practices in/around Nijmegen, the Netherlands, patients were selected who in 1985-1989 had a first episode of AP or a first MI.

Use of the direct RNA amplification technique NASBA to detect factor V Leiden, a point mutation associated with APC resistance.

APC resistance is a common and strong hereditary risk factor for venous thrombosis. This plasma abnormality appears to be almost always caused by the same defect in the coagulation factor V gene (a G --> A transition at nucleotide 1691 leading to replacement of 506 Arg by Gln; factor V Leiden). Therefore, it is possible to consider a simple and specific genetic test as an alternative to a plasma APC resistance test that is compromised by treatment and other factors.