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Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravaginal ring (IVR) delivering TDF and FTC at independently controlled rates was evaluated for efficacy at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques. Six macaques received pod-IVRs containing TDF (65 mg) and FTC (68 mg) every two weeks, and weekly vaginal exposures to 50 TCID50 of SHIV162p3 began one week after the first pod-IVR insertion. All pod-IVR-treated macaques were fully protected throughout the study (P = 0.0002, Log-rank test), whereas all control animals became infected with a median of 4 exposures to infection. The topical, sustained release of TDF and FTC from the pod-IVR maintained protective drug levels in macaques over four months of virus exposures. This novel and versatile delivery system has the capacity to deliver and maintain protective levels of multiple drugs and the protection observed here warrants clinical evaluation of this pod-IVR design.

CONTEXT : Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp-carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors. To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance. Published literature focused on serrated polyps and their association with colorectal cancer. Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps.

Glycans are one of the 4 major macromolecules essential for life and are the most abundant family of organic molecules. However, in contrast with DNA and RNA, glycan structures have no template; this results in limited tools to study this challenging macromolecule with a diversity of glycan structures. A central bottleneck in studying glycosylation in vivo is that inhibitors and complete KOs are lethal. In a forward genetic screen, we identified a viable, hypomorphic mutation at a conserved site in mannose phosphate isomerase (Mpi) that causes a multisystemic phenotype affecting RBCs, liver, stomach, intestines, skin, size, fat, and fluid balance in mice. The phenotype could be rescued with mannose. Analyses of glycopeptides in mice with this mutation showed a 500% increase in unoccupied N-glycan sites. This is equivalent to a \"glycan knockdown,\" which would be useful for examining the role of glycans in biology and disease. Therefore, we report an in vivo tool to study global N-glycosylation deficiency with tissue-specific targeting and a rescue mechanism with mannose.

Introduction: Esophageal Crohn's disease (CD) is rare but must be recognized and distinguished from other esophageal diseases and treated accordingly. Case Report: A 35-year-old Caucasian man with CD presented with solid food dysphagia with associated odynophagia, heartburn and weight loss. He had a 20-year history of severe ileocolonic and perianal CD requiring subtotal colectomy and end ileostomy, subsequent ileal resection and ileostomy revision and multiple perianal drainage procedures. There was no history of upper gastrointestinal involvement. He previously lost response to infliximab and certolizumab and was then maintained successfully on adalimumab. An upper endoscopy revealed multiple deep, longitudinal ulcers coursing the length of the esophagus (Figure 1) with biopsies showing severe, non-specific inflammation and ulceration. A 12-week trial of twice daily proton pump inhibitor (PPI) resulted in partial relief of symptoms. A subsequent endoscopy showed no mucosal healing, and biopsies revealed dense inflammation and multiple small, non-caseating granulomas (Figure 2). Adalimumab and twice daily PPI were continued, and a prednisone taper followed by twice daily swallowed viscous budesonide resulted in significant improvement in symptoms as well as in endoscopic and histologic healing on follow-up endoscopy (Figure 3). Discussion: CD of the esophagus was first described in 1950 and is the least common location of disease in the GI tract. The prevalence among those with CD is estimated to be between 0.2-6.8% in adults with slightly higher prevalence reported in children, possibly because routine upper endoscopy is recommended in pediatric but not adult CD guidelines. Approximately 80% of patients have localizing symptoms including dysphagia and odynophagia. Non-specific inflammatory changes and ulcers are common on endoscopy and histology, but approximately 20% have detectable non-caseating granulomas. Care must be taken to rule out acid reflux, herpetic or tuberculous infection, pill esophagitis and infiltrative disease. PPI's, systemic and topical steroids and biologic therapies are the mainstays of management, while stricturing or fistulizing disease may require endoscopic dilation or surgery.

Cooperative learning is commonly used to promote prosocial outcomes. It is often assumed that all types of cooperative learning are equal. One way in which cooperative learning procedures differ is in the role of conflict. This study compares the relative impact of two types of cooperative learning (concurrence-seeking which emphasizes harmony among students and academic controversy which emphasizes intellectual conflict among students) on outcomes of a health education program focusing on tobacco use, alcohol use, and AIDS. Participants were 37 students from grades 9-12 in a career-education track in a suburban mid-western high school. The students were classified as being low performing academically and at risk for destructive health habits. Students in the controversy condition, compared with those in the concurrence-seeking condition, significantly improved in knowledge about AIDS, developed healthier attitudes related towards safe sex and cigarettes, developed higher academic self-esteem, generated greater social influence, and improved in constructive conflict skills.[PUBLICATION ABSTRACT]

Primary prevention guidelines recommend calculation of lifetime cardiovascular disease (CVD) predicted risk in patients who may not meet criteria for high short-term (10-year) Adult Treatment Panel III risk for coronary heart disease (CHD). Extreme obesity and bariatric surgery are more common in women who often have low short-term predicted CHD risk. The distribution and correlates of lifetime CVD predicted risk, however, have not yet been evaluated in bariatric surgical candidates. Using established 10-year (Adult Treatment Panel III) CHD and lifetime CVD risk prediction algorithms and presurgery risk factors, participants from the Longitudinal Assessment of Bariatric Surgery-2 study without prevalent CVD (n = 2,070) were stratified into 3 groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10%) predicted risk or diagnosed diabetes. Participants were predominantly white (86%) and women (80%) with a median age of 45 years and median body mass index of 45.6 kg/m2. High 10-year CHD predicted risk was common (36.5%) and associated with diabetes, male gender, and older age, but not with higher body mass index or high-sensitivity C-reactive protein. Most participants (76%) with low 10-year predicted risk had high lifetime CVD predicted risk, which was associated with dyslipidemia and hypertension but not with body mass index, waist circumference, high-density lipoprotein cholesterol, or high-sensitivity C-reactive protein. In conclusion, bariatric surgical candidates without diabetes or existing CVD are likely to have low short-term, but high lifetime CVD predicted risk. Current data support the need for long-term monitoring and treatment of increased CVD risk factors in bariatric surgical patients to maximize lifetime CVD risk decrease (clinical trial registration, Long-term Effects of Bariatric Surgery, indentifier NCT00465829, available at: http://www.clinicaltrials.gov/ct2/results?term=NCT00465829).