BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either BRCA1 or BRCA2 carry germline BACH1 coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase. In two patients with early-onset breast cancer who carry distinct germline BACH1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development

; on behalf of the American Thoracic Society Assembly on Sleep and Respiratory Neurobiology THIS OFFICIAL CLINICAL PRACTICE GUIDELINE OF THE AMERICAN THORACIC SOCIETY WAS APPROVED MAY 2019 Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS). Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations. Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level ,27 mmol/L to exclude the diagnosis of OHS in obese patients with sleepdisordered breathing when suspicion for OHS is not very high (,20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery). Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

No abstract

Regardless of how REM-related SDB is defined, it was highly prevalent in our large clinical cohort. Compared to non-stage-specific OSA, these patients were equally hypersomnolent and adherent to CPAP therapy despite having overall significantly milder OSA. Further research is needed to better establish whether these patients will derive any benefit from long-term CPAP therapy.

Type 2 diabetes is a chronic illness that is increasing in epidemic proportions worldwide. Major factors contributing to the development of type 2 diabetes include obesity and poor lifestyle habits (e.g., excess dietary intake and limited physical activity). Despite the proven efficacy of lifestyle interventions and the use of multiple pharmacological agents, the economic and public health burden of type 2 diabetes remains substantial. Obstructive sleep apnea (OSA) is a treatable sleep disorder that is pervasive among overweight and obese adults, who represent about two thirds of the U.S. population today. An ever-growing number of studies have shown that OSA is associated with insulin resistance, glucose intolerance and type 2 diabetes, independent of obesity. Evidence from animal and human models that mimic OSA provides potential mechanisms for how OSA may alter glucose metabolism. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is associated with worsening glucose control. However, it is still unclear whether OSA may lead to the development of diabetes over time. More data from large-scale longitudinal studies with rigorous assessments of diabetes and OSA are needed. In addition, there is still controversy whether continuous positive airway pressure (CPAP) treatment of OSA improves glucose metabolism. Large-scale randomized-controlled trials of CPAP treatment of OSA with well-validated assessments of insulin sensitivity and glucose tolerance are needed. These studies may reveal that OSA represents a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes.