Effects of new anti-adhesion polyvinyl alcohol gel on healing of colon anastomoses in rats

Background: Adhesions follow abdominal surgery with an incidence as high as 95%, resulting in invalidating complications such as bowel obstruction, female infertility, and chronic pain. Searches have been performed for a safe and effective adhesion barrier; however, such barriers have impaired anastomotic site healing. The primary aim of this study was to investigate the effect of a new adhesion barrier, polyvinyl alcohol gel, on healing of colonic anastomoses using a rat model. Methods: Thirty-two Wistar rats were divided in two groups. In all animals, an anastomosis was constructed in the ascending colon. The first group received no adhesion barrier, whereas in the second group, 2mL of polyvinyl alcohol gel (A-Part Gel®; Aesculap AG, Tuttlingen, Germany) was applied circularly around the anastomosis. All animals were sacrificed on the seventh post-operative day, and the abdomen was inspected for signs of anastomotic leakage. The anastomotic bursting pressure, the adhesions around the anastomosis, and the collagen content of the excised anastomosis were measured. Results: No significant differences were observed between the two groups in the incidence of anastomotic leakage, the anastomotic bursting pressure (p=0.08), or the collagen concentration (p=0.91). No significant reduction in amount of adhesions was observed in the rats receiving polyvinyl alcohol gel. Conclusions: This experimental study showed no significant differences in anastomotic leakage, anastomotic bursting pressure, or collagen content of the anastomosis when using the adhesion barrier polyvinyl alcohol around colonic anastomoses. The barrier did not prevent adhesion formation

Reproductive function and outcomes in female survivors of childhood, adolescent and young adult cancer: a review

Some survivors of childhood, adolescent, and young adult cancer are at increased risk of gonadal dysfunction and adverse pregnancy outcomes. We reviewed currently available literature that evaluated reproductive function and pregnancy outcomes of female cancer survivors diagnosed before the age of 25 years. High-dose alkylating agent chemotherapy and abdominal/pelvic radiotherapy adversely affect gonadal function in a dose-related fashion, with older age at exposure conferring greater risk as a result of the age-related decline in ovarian reserve. Gonadal injury clinically manifests as ovarian hormone insufficiency (delayed or arrested puberty, premature ovarian insufficiency, or premature menopause) and infertility. The effect of molecular-targeted agents on ovarian function has not been established. For female cancer survivors who maintain fertility, overall pregnancy (relative risk, 0.67 to 0.81) and live birth rates (hazard ratio, 0.79 to 0.82) are lower than those in the general public. Pregnancy in cancer survivors also may be associated with risks to both the mother and the fetus related to miscarriage; preterm birth; and, rarely, cardiomyopathy. Women at risk for these complications require preconception assessment and counseling from both obstetricians and oncology providers. The risk for inherited genetic disease in offspring conceived after cancer treatment exposure is not increased. The optimization of reproductive outcomes and minimization of risks of pregnancy complications in survivors requires informed, risk-based assessment and monitoring

The Amsterdam Studies of Acute Psychiatry I (ASAP-I); A prospective cohort study of determinants and outcome of coercive versus voluntary treatment interventions in a metropolitan area

Background The overall number of involuntary admissions is increasing in many European countries. Patients with severe mental illnesses more often progress to stages in which acute, coercive treatment is warranted. The number of studies that have examined this development and possible consequences in terms of optimizing health care delivery in emergency psychiatry is small and have a number of methodological shortcomings. The current study seeks to examine factors associated with compulsory admissions in the Amsterdam region, taking into account a comprehensive model with four groups of predictors: patient vulnerability, social support, responsiveness of the health care system and treatment adherence. Methods/Design This paper describes the design of the Amsterdam Study of Acute Psychiatry-I (ASAP-I). The study is a prospective cohort study, with one and two-year follow-up, comparing patients with and without forced admission by means of a selected nested case-control design. An estimated total number of 4,600 patients, aged 18 years and over, consecutively coming into contact with the Psychiatric Emergency Service Amsterdam (PESA) are included in the study. From this cohort, a randomly selected group of 125 involuntary admitted subjects and 125 subjects receiving non-coercive treatment are selected for further evaluation and comparison. First, socio-demographic, psychopathological and network characteristics, and prior use of health services will be described for all patients who come into contact with PESA. Second, the in-depth study of compulsory versus voluntary patients will examine which patient characteristics are associated with acute compulsory admission, also taking into account social network and healthcare variables. The third focus of the study is on the associations between patient vulnerability, social support, healthcare characteristics and treatment adherence in a two-year follow-up for patients with or without involuntarily admittance at the index consultation. Discussion The current study seeks to establish a picture of the determinants of acute compulsory admissions in the Netherlands and tries to gain a better understanding of the association with the course of illness and patient's perception of services and treatment adherence. The final aim is to find specific patient and health care factors that can be influenced by adjusting treatment programs in order to reduce the number of involuntary admissions

A generalized invariant imbedding equation II

Research into fetal development and medicin

SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection

Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Goutières syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

Background: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy. The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). Methods/Design: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and powe

A worldwide survey on incidence, management and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: The POTTER-AF study.

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management and outcome are sparse. METHODS AND RESULTS This international multicenter registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553,729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed at 214 centers in 35 countries. In 78 centers 138 patients (0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (p<0.0001)) were diagnosed with an oesophageal fistula. Periprocedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8%, and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) (odds ratio 7.463 (2.414, 23.072) p<0.001). CONCLUSIONS Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

Genome sequence of the tsetse fly (Glossina morsitans):Vector of African trypanosomiasis

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.IS

DNA methylation signatures of aggression and closely related constructs : A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.Peer reviewe