Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).     

Family history differs between young women with myocardial infarction and ischemic stroke: results from the RATIO case-control study

BackgroundFamily history may help in risk stratification, especially in the young. This study assesses the predictive value of a positive family history of cardiovascular disease for myocardial infarction (MI) and ischemic stroke (IS).Methods/ResultsThe RATIO study case–control study includes women with MI (N = 248), IS (N = 203) and 925 healthy matched controls. Odds ratios (ORs) and 95% confidence intervals (95%CI) were calculated with logistic regression. The risk of MI was almost fourfold increased in women with a family history positive for MI (OR 3.70, 95%CI 2.68–5.10), whereas the risk of IS was, if anything, only slightly elevated (1.25, 0.83–1.87). A family history of stroke (ischemic and hemorrhagic) was associated with a twofold increase in MI risk (2.00, 1.29–3.12), whereas the IS risk was again not clearly associated (1.37, 0.79–2.40).ConclusionsThe predictive value of a family history for cardiovascular disease differs between MI and IS.     

Global epidemiology of HIV infection in men who have sex with men

Epidemics of HIV in men who have sex with men (MSM) continue to expand in most countries. We sought to understand the epidemiological drivers of the global epidemic in MSM and why it continues unabated. We did a comprehensive review of available data for HIV prevalence, incidence, risk factors, and the molecular epidemiology of HIV in MSM from 2007 to 2011, and modelled the dynamics of HIV transmission with an agent-based simulation. Our findings show that the high probability of transmission per act through receptive anal intercourse has a central role in explaining the disproportionate disease burden in MSM. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiological data show substantial clustering of HIV infections in MSM networks, and higher rates of dual-variant and multiple-variant HIV infection in MSM than in heterosexual people in the same populations. Prevention strategies that lower biological transmission and acquisition risks, such as approaches based on antiretrovirals, offer promise for controlling the expanding epidemic in MSM, but their potential effectiveness is limited by structural factors that contribute to low health-seeking behaviours in populations of MSM in many parts of the world.     

Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients

Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute. Here we demonstrate that hematopoietic progenitors from GSD-1b patients are not impaired in their capacity to develop into mature neutrophils. However, optimal survival of neutrophil progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl⁻¹), suggesting that even under normoglycemic conditions these cells are more prone to apoptosis. Furthermore, analysis of cytokine levels in peripheral blood suggests an inflammatory state with an inverse correlation between the level of inflammation and the number of neutrophils. Finally, in some patients, with low numbers of peripheral blood neutrophils, high numbers of neutrophils were observed in the intestine. Together, these results suggest that the neutropenia observed in GSD-1b patients is not caused by impaired maturation, but may be caused by both increased levels of apoptosis and egress of neutrophils from the blood to the inflamed tissues.     

One year postoperative hard and soft tissue volumetric changes after a BSSO mandibular advancement

In this study, cone beam computed tomography (CBCT) and three dimensional (3D) stereophotogrammetry are used to compare the 3D skeletal and soft tissue changes caused by a bilateral sagittal split osteotomy (BSSO) 1 year after a mandibular advancement. Eighteen consecutive patients with a hypoplastic mandible were treated with a BSSO according to the Hunsuck modification. Preoperatively and 1 year postoperatively, a CBCT scan was acquired and a 3D photograph. The pre- and postoperative CBCT scans were matched using voxel based registration. After registration, the mandible could be segmented in the pre- and postoperative scans. The preoperative scan was subtracted from the postoperative scan, resulting in the hard tissue difference. To investigate the soft tissue changes, the pre- and postoperative 3D photographs were registered using surface based registration. After registration the preoperative surface could be subtracted from the postoperative surface, resulting in the overall volumetric difference. As expected, a correlation between mandibular advancent and volumetric changes of the hard tissues was found. The correlation between advancement and soft tissues was weak. The labial mental fold stretched after surgery. This study proved that using 3D imaging techniques it is possible to document volumetric surgical changes accurately and objectively.     

High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women

VWF and ADAMTS13 are major determinants of platelet adhesion after vessel injury. In the present study, we aimed to determine whether VWF or ADAMTS13 plasma antigen levels influence the risks of ischemic stroke (IS) or myocardial infarction (MI) in young women and how these risks are affected by oral contraceptive (OC) use. VWF and ADAMTS13 plasma antigen levels were measured in a frequency-matched case-control study of 1018 young (18-49 years) women including 175 IS patients and 205 MI patients. Increasing levels of VWF and decreasing levels of ADAMTS13 were associated with the risk of IS and MI in a dose-dependent manner. Having both high VWF and low ADAMTS13 resulted in an odds ratio (OR) of 6.9 (95% confidence interval [95% CI], 2.0-23.0) for IS and 11.3 (95% CI, 3.6-35.2) for MI. Use of OCs increased the risk of IS and MI associated with high VWF (OR = 12; 95% CI, 5.5-26.2 and OR = 7.5, 95% CI, 3.6-15.7, respectively) and the risk of IS associated with low ADAMTS13 (OR = 5.8, 95% CI, 2.7-12.4). We conclude that high VWF and low ADAMTS13 plasma levels both increase the risk of IS and MI. The risks associated with high VWF or low ADAMTS13 levels are further increased by the use of OCs.     

Candidate gene polymorphisms and the risk for pregnancy-related venous thrombosis

Venous thrombosis (VT) is one of the leading causes of maternal death in the western world, but the genetic causes of pregnancy-related VT are insufficiently understood. The aim of this study was to investigate the association between common genetic variations in candidate genes and pregnancy-related VT. We undertook a hospital based case-control study of women with VT during pregnancy or puerperium; controls were women giving birth without having VT. Single nucleotide polymorphisms (SNPs) were selected in 49 pre-specified candidate genes involved in coagulation, inflammation, and hormonal metabolism in 313 cases and 353 controls. We found new associations between SNPs and total pregnancy-related VT in the genes encoding coagulation factors V and VIII, and p-selectin. Additional new associations between SNPs and antenatal VT were found in the genes encoding the epidermal growth factor receptor, the pregnane X receptor, and protein S. Of 21 SNPs previously associated with thrombotic disease, rs2289252 in F11 and rs3917643 in F3 were associated with pregnancy-related VT, while rs4524 in F5 was associated with antenatal VT.     

Pregnancy and liver adenoma management: PALMstudy

ABSTRACT: BACKGROUND: Hepatocellular adenoma (HCA) in pregnant women requires special considerations because of the risk of hormone induced growth and spontaneous rupture, which may threaten the life of both mother and child. Due to scarcity of cases there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. Most experts advocate that women with HCA should not get pregnant or advise surgical resection before pregnancy. Whether it is justified to deny a young woman a pregnancy, as the biological behavior may be less threatening than presumed depends on the incidence of HCA growth and the subsequent clinical events during pregnancy. We aim to investigate the management and outcome of HCA during pregnancy and labor based on a prospectively acquired online database in the Netherlands. Methods/design The Pregnancy And Liver adenoma Management (PALM) - study is a multicentre prospective study in three cohorts of pregnant patients. In total 50 pregnant patients, [greater than or equal to] 18 years of age with a radiologically and/or histologically proven diagnosis of HCA will be included in the study. Radiological diagnosis of HCA will be based on contrast enhanced MRI. Lesions at inclusion must not exceed 5 cm. The study group will be compared to a healthy control group of 63 pregnant patients and a group of 63 pregnant patients with diabetes mellitus without HCA. During their pregnancy HCA patients will be closely monitored by means of repetitive ultrasound (US) at 14, 20, 26, 32 and 38 weeks of gestation and 6 and 12 weeks postpartum. Both control groups will undergo US of the liver at 14 weeks of gestation to exclude HCA lesions in the liver. All groups will be asked to fill out quality of life related questionnaires. DISCUSSION: The study will obtain information about the behaviour of HCA during pregnancy, the clinical consequences for mother and child and the impact of having a HCA during pregnancy on the health related quality of life of these young women. As a result of this study we will propose a decision-making model for the management of HCA during pregnancy. Trial registration Dutch trial register: NTR3034.