Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Cognitive interviewing to improve women's empowerment questions in surveys: Application to the health and nutrition and intrahousehold relationships modules for the project‐level Women's Empowerment in Agriculture Index

In 2015, the United Nations adopted the Sustainable Development Goals, which include fostering gender equality and women's empowerment and ending hunger and malnutrition. To monitor progress and evaluate programmes that aim to achieve these goals, survey instruments are needed that can accurately assess related indicators. The project‐level Women's Empowerment in Agriculture Index (pro‐WEAI) is being developed to address the need for an instrument that is sensitive to changes in empowerment over the duration of an intervention. The pro‐WEAI includes new modules with previously untested survey questions, including a health and nutrition module (focused on women's agency in this area) and an intrahousehold relationships module. This study uses cognitive interviewing to identify how new survey questions might be misinterpreted and to understand what experiences women are referencing when they respond to these questions. This was undertaken with the goal of informing revision to the modules. The study was conducted in Bangladesh with women from nuclear, extended, and migrant‐sending households and from two regions of the country to identify difficulties with interpretation and response formulation across these groups. Findings revealed that questions were generally understood, but participants occasionally responded to the wrong part of the question, did not understand key phrases, or were uncomfortable with questions. The findings also suggested ways to revise the modules and strengthen the pro‐WEAI. The revised pro‐WEAI health and nutrition and intrahousehold relationships modules will advance the ability to measure changes in these domains and their relationship with the health and nutritional status of women and their children.     

Associations of Drug Use,Violence, and Depressive Symptoms with Sexual Risk Behaviors Among Women with Alcohol Misuse

Background

Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic.