Embryonic stem (ES) cells undergo extended proliferation while remaining poised for multilineage differentiation. A unique network of transcription factors may characterize self-renewal and simultaneously suppress differentiation. We applied expression cloning in mouse ES cells to isolate a self-renewal determinant. Nanog is a divergent homeodomain protein that directs propagation of undifferentiated ES cells. Nanog mRNA is present in pluripotent mouse and human cell lines, and absent from differentiated cells. In preimplantation embryos, Nanog is restricted to founder cells from which ES cells can be derived. Endogenous Nanog acts in parallel with cytokine stimulation of Stat3 to drive ES cell self-renewal. Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels. Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision. These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity.

Introduction: Mental health is a critical and neglected global health challenge for adolescents infected with HIV. The prevalence of mental and behavioural health issues among HIV-infected adolescents may not be well understood or addressed as the world scales up HIV prevention and treatment for adolescents. The objective of this narrative review is to assess the current literature related to mental health challenges faced by adolescents living with HIV, including access to mental health services, the role of mental health challenges during transition from paediatric to adult care services and responsibilities, and the impact of mental health interventions.Methods: For each of the topics included in this review, individual searches were run using Medline and PubMed, accompanied by scans of bibliographies of relevant articles. The topics on which searches were conducted for HIV-infected adolescents include depression and anxiety, transition from paediatric to adult HIV care and its impact on adherence and mental health, HIV-related, mental health services and interventions, and the measurement of mental health problems. Articles were included if the focus was consistent with one of the identified topics, involved HIV-infected adolescents, and was published in English.Results and Discussion: Mental and behavioural health challenges are prevalent in HIV-infected adolescents, including in resource-limited settings where most of them live, and they impact all aspects of HIV prevention and treatment. Too little has been done to measure the impact of mental health challenges for adolescents living with HIV, to evaluate interventions to best sustain or improve the mental health of this population, or to create healthcare systems with personnel or resources to promote mental health.Conclusions: Mental health issues should be addressed proactively during adolescence for all HIV-infected youth. In addition, care systems need to pay greater attention to how mental health support is integrated into the care management for HIV, particularly throughout lifespan changes from childhood to adolescence to adulthood. The lack of research and support for mental health needs in resource-limited settings presents an enormous burden for which cost-effective solutions are urgently needed.

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (<5 g͞day) and iron-normal (800 g͞day) rats and in both groups after daily high-iron supplementation (8,000 g͞day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with ironnormal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 g) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 ؋ nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

Introduction: Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care. Methods: We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculum's impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes. Results: Three core themes emerged from analysis of participants' comments. First, participants valued the curriculum's focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions. Discussion: This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health.

Purpose To develop a semi-quantitative MR-based hip osteoarthritis (OA) evaluation system (Scoring hip osteoarthritis with MRI, SHOMRI), and to test its reproducibility and face validity. Material and Methods The study involved 98 subjects with informed consent. Three-Tesla MR imaging of hip was performed in three planes with intermediate-weighted fat saturated FSE sequences. Two radiologists assessed cartilage loss, bone marrow edema pattern, subchondral cyst in 10 subregions, and assessed labrum in 4 subregions. In addition, presence or absence of ligamentum teres integrity, paralabral cysts, intraarticular body, and effusion in the hip joint were analyzed using the SHOMRI system. The reproducibility was assessed with intra-class correlation coefficient (ICC), Cohen’s Kappa values and percent agreement. SHOMRI scores were correlated with radiographic Kellgren-Lawrence (KL) and OARSI atlas gradings, and clinical parameters, the hip osteoarthritis outcome score (HOOS) and hip range of motion (ROM), using Spearman’s rank correlation and ordinal logistic regression. Results ICC values were in excellent ranging from 0.91 to 0.97. Cohen’s Kappa values and percent agreement ranged from 0.55 to 0.79 and 66 to 99 %, respectively. SHOMRI demonstrated significant correlations with KL and OARSI gradings as well as with clinical parameters, HOOS and ROM (P < 0 .05). Among the SHOMRI features, subchondral cyst and bone marrow edema pattern showed the highest correlation with HOOS and ROM. Conclusion SHOMRI demonstrated moderate to excellent reproducibility and significant correlation with radiographic gradings and clinical parameters.

Objective To evaluate the relationship of hip radiographic osteoarthritis (ROA) and MR findings of cartilage lesions, labral tears, bone marrow edema like lesions (BMEL) and subchondral cysts with self-reported and physical function. Design Eighty five subjects were classified as controls (n= 55, KL 0, 1) or having mild-moderate ROA (n = 30, KL 2, 3). T2-weighted MR images at 3-Tesla were graded for presence of cartilage lesions, labral tears, BMELs and subchondral cysts. Posterior wall sign, cross-over sign, center-edge angle and alpha angle were also recorded. Function was assessed using Hip Osteoarthritis Outcome Score (HOOS), Timed-Up and Go (TUG) test and Y-Balance Test (YBT). Analysis compared function between subjects with and without ROA and those with and without femoral or acetabular cartilage lesions, adjusted for age. Non-parametric correlations were used to assess the relationship between radiographic scores, MR scores and function. Results Subjects with acetabular cartilage lesions had worse HOOS (Difference = 5–10%, P = 0.036–0.004), but not TUG or YBT, scores. Acetabular cartilage lesions, BMELs and subchondral cysts were associated with worse HOOS scores (ρ= 0.23–0.37, P = 0.041–0.001). Differences in function between subjects with and without ROA or femoral cartilage lesions were not significant. Other radiologic findings were not associated with function. Conclusions Acetabular cartilage defects, but not femoral cartilage defects or ROA, were associated with greater self-reported pain and disability. BMELs and subchondral cysts were related to greater hip related self-reported pain and disability. None of the radiographic or MR features were related to physical function.

Purpose To evaluate a chemical shift-based fat quantification technique in the rotator cuff muscles in comparison with the semi-quantitative Goutallier fat infiltration classification (GC) and to assess their relationship with clinical parameters. Materials and Methods The shoulders of 57 patients were imaged using a 3T MR scanner. The rotator cuff muscles were assessed for fat infiltration using GC by two radiologists and an orthopedic surgeon. Sequences included oblique-sagittal T1-, T2- and proton density-weighted fast spin echo, and six-echo gradient echo. The iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) was used to measure fat fraction. Pain and range of motion of the shoulder were recorded. Results Fat fraction values were significantly correlated with GC grades (p< 0.0001, kappa>0.9) showing consistent increase with GC grades (grade=0, 0%–5.59%; grade=1, 1.1%–9.70%; grade=2, 6.44%–14.86%; grade=3, 15.25%–17.77%; grade=4, 19.85%–29.63%). A significant correlation between fat infiltration of the subscapularis muscle quantified with IDEAL versus a) deficit in internal rotation (Spearman Rank Correlation Coefficient=0.39, 95% CI 0.13–0.60, p<0.01) and b) pain (Spearman Rank Correlation coefficient=0.313, 95% CI 0.049–0.536, p=0.02) was found but was not seen between the clinical parameters and GC grades. Additionally, only quantitative fat infiltration measures of the supraspinatus muscle were significantly correlated with a deficit in abduction (Spearman Rank Correlation Coefficient=0.45, 95% CI 0.20–0.60, p<0.01). Conclusion We concluded that an accurate and highly reproducible fat quantification in the rotator cuff muscles using water-fat MRI techniques is possible and significantly correlates with shoulder pain and range of motion.

Objective To measure rates of ART use and virologic suppression among perinatally infected (PIY) and behaviorally infected youth (BIY) linked to care in the United States, and examine the effects of demographic, biomedical, and psychosocial factors on those rates. Methods Between 2009–2012, 649 PIY and 1,547 BIY in 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions sites completed cross-sectional surveys via audio computer- assisted self-interviews. Viral load data were collected from chart abstraction or blood draw. Results Overall 82.4% of PIY and 49.1% of BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were virologically suppressed. Virologic suppression rates did not vary as a function of time since HIV diagnosis in either group. Consistent HIV care and no current substance abuse were significant correlates of ART use among PIY. These variables and non-African American race were some factors associated with virologic suppression for PIY (ORs Ps < .05). Among BIY, older age, heterosexuals, employment, and education were significantly related to ART use (ORs Ps < .05); suppression was related to ART use >6 months, >90% ART adherence, and consistent HIV care (ORs Ps < .05). Nearly 75% (n = 498) of non-suppressed youth reported unprotected sex in the past 3 months. Conclusions There are continued challenges with successfully treating youth even once diagnosed and linked to HIV care. Strategies targeting barriers to ART access, use and virologic suppression are needed to optimize the impact of the "Treatment as Prevention" paradigm among PIY and BIY.