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Sensorineural hearing loss is genetically heterogeneous. Here we report that mutations in CIB2, encoding a Ca2+- and integrin-binding protein, are associated with nonsyndromic deafness (DFNB48) and Usher syndrome type 1J (USH1J). There is one mutation of CIB2 that is a prevalent cause of DFNB48 deafness in Pakistan; other CIB2 mutations contribute to deafness elsewhere in the world. In rodents, CIB2 is localized in the mechanosensory stereocilia of inner ear hair cells and in retinal photoreceptor and pigmented epithelium cells. Consistent with molecular modeling predictions of Ca2+ binding, CIB2 significantly decreased the ATP-induced Ca2+ responses in heterologous cells, while DFNB48 mutations altered CIB2 effects on Ca2+ responses. Furthermore, in zebrafish and Drosophila, CIB2 is essential for the function and proper development of hair cells and retinal photoreceptor cells. We show that CIB2 is a new member of the vertebrate Usher interactome.

The college years are stressful for many students. Identifying the sources of stress and their relative importance in leading to clinically significant emotional problems may assist in the development of targeted stress management interventions. The current report examines the distribution and associations of perceived stress across major life areas with 12-month prevalence of common mental disorders in a cross-national sample of first-year college students. The 20,842 respondents were from 24 universities in 9 countries that participated in the World Health Organization World Mental Health International College Student Initiative. Logistic regression analysis examined associations of current perceived stress in six life areas (financial situation, health, love life, relationships with family, relationships at work/school, problems experienced by loved ones) with six types of 12-month mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder). Population attributable risk proportions (PARPs) were calculated to estimate the upper-bound potential effects of interventions focused on perceived stress in reducing prevalence of mental disorders. The majority of students (93.7%) reported at least some stress in at least one of the six areas. A significant dose-response association was found between extent of stress in each life area and increased odds of at least one of the six disorders. The multivariable models that included all stress measures were significant for all disorders ( F = 20.6–70.6, p < 0.001). Interpretation of PARPs as representing causal effects of stresses on disorders suggests that up to 46.9–80.0% of 12-month disorder prevalence might be eliminated if stress prevention interventions were developed to block the associations of stress with these disorders.

Objectives Comorbidity is a common feature of mental disorders. However, needs assessment surveys focus largely on individual disorders rather than on comorbidity even though the latter is more important for predicting suicidal thoughts and behaviors. In the current report, we take a step beyond this conventional approach by presenting data on the prevalence and correlates (sociodemographic factors, college‐related factors, and suicidal thoughts and behaviors) of the main multivariate profiles of common comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV disorders among students participating in the first phase of the World Health Organization World Mental Health International College Student initiative. Method A web‐based mental health survey was administered to first year students in 19 colleges across eight countries (Australia, Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain, United States; 45.5% pooled response rate) to screen for seven common DSM‐IV mental disorders: major depression, mania/hypomania, generalized anxiety disorder, panic disorder, attention‐deficit/hyperactivity disorder, alcohol use disorder, and drug use disorder. We focus on the 14,348 respondents who provided complete data; 38.4% screened positive for at least one 12‐month disorder. Results Multivariate disorder profiles were detected using latent class analysis (LCA). The least common class (C1; 1.9% of students) was made up of students with high comorbidity (four or more disorders, the majority including mania/hypomania). The remaining 12‐month cases had profiles of internalizing–externalizing comorbidity (C2; 5.8%), internalizing comorbidity (C3; 14.6%), and pure disorders (C4; 16.1%). The 1.9% of students in C1 had much higher prevalence of suicidal thoughts and behaviors than other students. Specifically, 15.4% of students in C1 made a suicide attempt in the 12 months before the survey compared with 1.3–2.6% of students with disorders in C2–4, 0.2% of students with lifetime disorders but no 12‐month disorders (C5), and 0.1% of students with no lifetime disorders (C6). Conclusions In line with prior research, comorbid mental disorders were common; however, sociodemographic correlates of LCA profiles were modest. The high level of comorbidity underscores the need to develop and test transdiagnostic approaches for treatment in college students.

Background: Human APOE effects on RXR agonist activity are unclear. Results: In RXR agonist-treated EFAD mice, beneficial effects in APOE4 hippocampus include ABCA1/ABCG1-induced apoE lipoprotein association/lipidation. Detrimental effects in APOE3 and APOE4 cortex might be from systemic hepatomegaly. Conclusion: A␤ pathology and APOE genotype modulate RXR agonist effects. Significance: Although promising for later stage Alzheimer disease, detrimental side effects limit translational application of RXR agonists.