HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington’s, Parkinson’s diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies imply that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated that constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S).

Introduction: Although recommended, adolescent depression screening with appropriate initial management is challenging. This project aimed to improve adolescent depression screening rates during preventive care visits in 12 primary care clinics from 65.4% to 80%, increase the proportion of documented initial management for those with a positive screen from 69.5% to 85%, then sustain improvements for 12 months. Methods: This quality improvement project involved 12 urban primary care clinics serving >120,000 mostly Medicaid-enrolled patients and targeted adolescents 12-17 years. Interventions included standardized depression screening using tablets with electronic health record (EHR) capture and automated scoring, embedding screening results and initial management actions into the EHR, provider education, and individual clinician and clinic performance feedback. Results: After standardizing the approach to screening, the process mean depression screening rate was 91.9%. However, after adopting tablets into the clinic flow, there was an unexpected initial decrease in proportion with appropriately documented initial management plans, from 89.7% to 67.6%. In response to this special cause variation, there was additional provider feedback and education, and a redesign of the EHR flow related to the presentation of results and prompts for action after a positive screen. As a result, the proportion with appropriately documented initial management was 87.3% by project completion. Conclusions: Tablet-based screening with EHR scoring capture effectively increased depression screening rates but required significant additional work to improve initial management after a positive screen. A full system approach, including EHR modification, clinician education, and performance feedback, is needed to make meaningful, sustained improvements in comprehensive adolescent depression screening.

CONTEXT Anxiety is common, screening tools are available, and treatment can be effective. Recently, anxiety screening has been recommended for adolescent girls beginning at 13 years of age. OBJECTIVE To evaluate the evidence regarding anxiety screening test accuracy in primary care for children and adolescents and assess the effectiveness of treatment of individuals identified through screening. DATA SOURCES We searched PubMed, the Cochrane library, and references to potentially eligible studies cited in other articles. STUDY SELECTION Screening studies were included if they were conducted in primary care or a similar population and employed a reference standard based on DSM criteria. Treatment studies were included if subjects were identified through screening and there was at least 1 comparator intervention or a placebo arm. DATA EXTRACTION At least 2 reviewers evaluated each identified reference. RESULTS Two screening studies (1 with low risk of bias and 1 with high risk of bias) and 1 treatment study with a low risk of bias were included. The screening study with a low risk of bias reported a sensitivity of 56% and specificity of 80%. The treatment study found individual cognitive behavioral therapy to be effective for screen-detected adolescents with social phobia. LIMITATIONS This review only included screening or treatment studies with clear evidence that the study populations were derived from an unselected population reflective of typical primary care. Relevant studies not indexed in PubMed or the Cochrane library could have been missed. CONCLUSIONS There are significant gaps in evidence related to anxiety screening in the primary care setting.

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