The tumor suppressor BRCA2 protects stalled forks from degradation to maintain genome stability. However, the molecular mechanism(s) whereby unprotected forks are stabilized remains to be fully characterized. Here, we demonstrate that WRN helicase ensures efficient restart and limits excessive degradation of stalled forks in BRCA2-deficient cancer cells. In vitro, WRN ATPase/helicase catalyzes fork restoration and curtails MRE11 nuclease activity on regressed forks. We show that WRN helicase inhibitor traps WRN on chromatin leading to rapid fork stalling and nucleolytic degradation of unprotected forks by MRE11, resulting in MUS81-dependent double-strand breaks, elevated non-homologous end-joining and chromosomal instability. WRN helicase inhibition reduces viability of BRCA2-deficient cells and potentiates cytotoxicity of a poly (ADP)ribose polymerase (PARP) inhibitor. Furthermore, BRCA2-deficient xenograft tumors in mice exhibited increased DNA damage and growth inhibition when treated with WRN helicase inhibitor. This work provides mechanistic insight into stalled fork stabilization by WRN helicase when BRCA2 is deficient.

Background A major focus in cystic fibrosis (CF) care aims to increase weight gain. Rates of overweight and obese people with CF have gradually increased over the past decade. Obesity could be a risk for restriction of lung volumes and airway obstruction as well as increase rates of pulmonary exacerbations in people with CF. Aim To assess the relationship between weight categories and pulmonary outcomes in children and adults with CF. Methods Patients 6 years of age and older were categorized into weight categories based on the Centers for Disease Control and Prevention (CDC) definitions. A retrospective chart review was conducted to obtain lung function testing and other outcomes. Results One hundred five patients with a median age of 20.6 years were included in this analysis. 8.4%, 64%, 18%, and 10% of patients were underweight, normal/healthy weight, overweight, and obese, respectively. Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) (% predicted) did not differ between patients with weights in the normal range versus patients in the overweight/obese categories. Linear regression analysis showed a direct correlation between body mass index (BMI) and FEV 1 that continued as BMI entered overweight and obese categories in both pediatric and adult patients. Overweight/obese patients did not have increased rates of pulmonary exacerbations compared to those in the normal/healthy weight category. Conclusion As CF therapies continue to improve, an increasing number of people with CF are exceeding the CDC's normal‐weight range. Gaining weight past the normal range does not appear to negatively impact pulmonary health of people with CF. If this trend of increased weight gain continues, it remains to be seen if it will eventually negatively affect lung health.

Updates on travel vaccine recommendations including vaccine-specific interactions with immunosuppressive agents, advances in Zika virus and dengue virus vaccine development, new diagnostic criteria for neurocysticercosis, updates on treatment approaches for tuberculosis meningitis. Increasing rates of travel are leading to the spread of known infectious diseases and the emergence of new diseases in travel medicine. Among these infections, neuroinfectious diseases carry significant morbidity and mortality. To reduce the effect of travel-related illness, appropriate pre-travel measures and up-to-date diagnostic and treatment strategies are essential for optimal outcomes. This review highlights important travel information relevant to neuroinfectious diseases for several populations including immunocompetent, immunocompromised, pregnant, and infant/children travelers. It also outlines the travel risk, clinical presentation, diagnosis, and management of a select list of neuroinfectious diseases by region, including neurocysticercosis, Zika virus, tuberculosis meningitis, rabies, and tick-borne encephalitis.

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Arab Americans (AA) face increased risk for colorectal cancer (CRC), the third leading cause of cancer-related death in the US, due to low utilization of preventative care and socioeconomic disparities. This study explores associations with the receipt of CRC screening among AA in New York City. A cross-sectional survey was conducted among 100 individuals attending religious and community organizations with interviewer-administered surveys in Arabic and English. Results from 100 participants showed they were more likely to complete CRC screening with a doctor recommendation (74%) and were more likely to get a recommendation with a high school education or higher (86%). Uninsured participants and those with public insurance were the least likely to complete screening. Those with a higher mean score in Spiritual Life/Faith (13.34 vs. 11.67) were less likely to complete screening. Findings suggest the need for culturally sensitive interventions to increase CRC screening rates among AA.