Ovarian Hyperthecosis in a 12-year-old Chinese Girl Presenting With Virilization.

All girls presenting with virilization (which signifies severe hyperandrogenism) warrant thorough investigation. Ovarian hyperthecosis (OHT) is a rare cause of virilization in premenopausal women. Here, we report the case of a previously healthy 12-year-old Chinese girl with signs of virilization at puberty. Her serum total testosterone was elevated at 5.1 nmol/L (146.97 ng/dL) (normal: <1.4 nmol/L, <40.35 ng/dL). Workup for Cushing syndrome, sex development disorders, congenital adrenal hyperplasia, and adrenal and ovarian androgen-secreting tumors was unrevealing. Ovarian and adrenal venous sampling demonstrated ovarian hyperandrogenism without lateralization. Ovarian biopsy revealed nests of theca cells in the stroma of the right ovary, substantiating the diagnosis of OHT. A single dose of a GnRH analog resulted in the complete suppression of serum testosterone, supporting the diagnosis of OHT. Medical treatment with hormonal replacement therapy normalized serum testosterone levels. Our case report illustrates the diagnostic approach to virilization among girls at puberty and the diagnosis of OHT as the underlying pathology.

Military service branch differences in alcohol use, tobacco use, prescription drug misuse, and mental health conditions.

INTRODUCTION: Rates of substance use and mental health conditions vary across military service branches, yet branches also differ notably in terms of demographics and deployment experiences. This study examines whether branch differences in substance use and mental health outcomes persist after adjustment for a comprehensive set of demographic and deployment-related factors. METHODS: Data on 16,699 Armed Forces Active Duty service members were from the 2015 Department of Defense Health Related Behaviors Survey. Service branch-specific prevalences were estimated for self-reports of heavy episodic drinking (HED), possible alcohol use disorder (AUD), current smoking, e-cigarette use, smokeless tobacco use, prescription drug misuse, probable post-traumatic stress disorder (PTSD), probable depression, and probable anxiety. Using logistic regression, we assessed whether branch differences persisted after adjusting for an extensive array of demographic factors (among full sample) and deployment/combat factors (among ever-deployed subgroup). RESULTS: HED, AUD, smoking, e-cigarette use, smokeless tobacco use, depression, and anxiety were highest in the Marine Corps; prescription drug misuse and PTSD were highest in the Army. HED, AUD, smoking, smokeless tobacco use, PTSD, depression, and anxiety were lowest in the Air Force; e-cigarette use and prescription drug misuse were lowest in the Coast Guard. Demographics and deployment/combat experiences differed across branches. After adjustment, service members in the Army, Marine Corps and Navy exhibited nearly 2-3 times the odds of multiple mental health conditions and substance use behaviors relative to the Air Force. CONCLUSION: Service branch differences were not fully explained by variation in demographics and deployment/combat experiences.

Co-occurring alcohol and mental health problems in the military: Prevalence, disparities, and service utilization.

OBJECTIVE: To examine the prevalence of co-occurring alcohol and mental health (MH) problems (COPs), perceived MH service need, and MH service utilization among active duty service members, and to identify differences in gender, race/ethnicity, age, and sexual orientation and gender identity. METHOD: 16,699 active duty service members participated in the Department of Defense's 2015 Health Related Behaviors Survey. Measures included demographics, combat deployment, smoking status, problematic alcohol use (Alcohol Use Disorders Identification Test-C, AUDIT-C), posttraumatic stress disorder (PTSD Checklist, Civilian Version, PCL-C), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder-7, GAD-7), and perceived need for and use of MH services. We examined groups of service members with probable: COP, alcohol problem only, MH problem only, and neither. RESULTS: Eight percent of service members reported COPs, 26.89% reported alcohol use problem only, and 9.41% reported a MH condition only. COPs were more common among those who were lesbian, gay, bisexual, and transgender (LGBT), those who had three or more combat deployments, and smokers, and less common among those aged 35 years and older, Asian or Black, and in the Air Force and Coast Guard (relative to Navy). Those reporting a probable MH problem only were significantly less likely to report use of past year MH counseling than those with probable COPs; otherwise, patterns of service utilization and perceived need were similar. CONCLUSIONS: COPs are common enough that screening for and attention to their co-occurrence are needed in the military, and some subgroups of service members are at particularly high risk for COPs. Future research and policy should delve deeper into how the needs of service members with COPs can be addressed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

State medical marijuana laws, cannabis use and cannabis use disorder among adults with elevated psychological distress.

BACKGROUND: Cannabis use and cannabis use disorder are more prevalent in U.S. states with medical marijuana laws (MMLs), as well as among individuals with elevated psychological distress. We investigated whether adults with moderate and serious psychological distress experienced greater levels of cannabis use and/or disorder in states with MMLs compared to states without MMLs. METHODS: National Survey of Drug Use and Health data (2013-2017) were used to compare past-month cannabis use, daily cannabis use, and cannabis use disorder prevalence among adults with moderate and serious psychological distress in states with versus without MMLs. We executed pooled multivariable logistic regression analyses to test main effects of distress, MMLs and their interaction, after adjustment. RESULTS: Compared to states without MMLs, states with MMLs had higher adjusted prevalence of past-month use (11.1 % vs. 6.8 %), daily use (4.0 % vs. 2.2 %), and disorder (1.7 % vs. 1.2 %). Adults with moderate and serious psychological distress had greater adjusted odds of any use (AORs of 1.72 and 2.22, respectively) and of disorder (AORs of 2.17 and 2.94, respectively), compared to those with no/mild distress. We did not find evidence of an interaction between MMLs and distress category for any outcome. CONCLUSIONS: Associations between elevated distress and cannabis use patterns are no greater in states with MML. However, cannabis use is more prevalent in MML states. Thus, higher base rates of cannabis use and disorder among adults with elevated distress are proportionally magnified in these states.

Targeted Molecular Iron Oxide Contrast Agents for Imaging Atherosclerotic Plaque.

Overview: Cardiovascular disease remains a leading cause of death worldwide, with vulnerable plaque rupture the underlying cause of many heart attacks and strokes. Much research is focused on identifying an imaging biomarker to differentiate stable and vulnerable plaque. Magnetic Resonance Imaging (MRI) is a non-ionising and non-invasive imaging modality with excellent soft tissue contrast. However, MRI has relatively low sensitivity (micromolar) for contrast agent detection compared to nuclear imaging techniques. There is also an increasing emphasis on developing MRI probes that are not based on gadolinium chelates because of increasing concerns over associated systemic toxicity and deposits1. To address the sensitivity and safety concerns of gadolinium this project focused on the development of a high relaxivity probe based on superparamagnetic iron oxide nanoparticles for the imaging of atherosclerotic plaque with MRI. With development, this may facilitate differentiating stable and vulnerable plaque in vivo.Aim: To develop a range of MRI contrast agents based on superparamagnetic iron oxide nanoparticles (SPIONs), and test them in a murine model of advanced atherosclerosis. Methods: Nanoparticles of four core sizes were synthesised by thermal decomposition and coated with poly(maleicanhydride-alt-1-octadecene) (PMAO), poly(ethyleneimine) (PEI) or alendronate, then characterised for core size, hydrodynamic size, surface potential and relaxivity. On the basis of these results, one candidate was selected for further studies. In vivo studies using 10 nm PMAO-coated SPIONs were performed in ApoE-/- mice fed a western diet and instrumented with a perivascular cuff on the left carotid artery. Control ApoE-/- mice were fed a normal chow diet and were not instrumented. Mice were scanned on a 3T MR scanner (Philips Achieva) with the novel SPION contrast agent, and an elastin-targeted gadolinium agent that was shown previously to enable visualisation of plaque burden. Histological analysis was undertaken to confirm imaging findings through staining for macrophages, CX3CL1, elastin, tropoelastin, and iron. Results: The lead SPION agent consisted of a 10 nm iron oxide core with poly(maleicanhydride-alt-1-octadecene), (-36.21 mV, r2 18.806 mmol-1/s-1). The irregular faceting of the iron oxide core resulted in high relaxivity and the PMAO provided a foundation for further functionalisation on surface -COOH groups. The properties of the contrast agent, including the negative surface charge and hydrodynamic size, were designed to maximise circulation time and evade rapid clearance through the renal system or phagocytosis. In vitro testing showed that the SPION agent was non-toxic. In vivo results show that the novel contrast agent accumulates in similar vascular regions to a gadolinium-based contrast agent (Gd-ESMA) targeted to elastin, which accumulates in plaque. There was a significant difference in SPION signal between the instrumented and the contralateral non-instrumented vessels in diseased mice (p = 0.0411, student's t-test), and between the instrumented diseased vessel and control vessels (p = 0.0043, 0.0022, student's t-test). There was no significant difference between the uptake of either contrast agent between stable and vulnerable plaques (p = 0.3225, student's t-test). Histological verification was used to identify plaques, and Berlin Blue staining confirmed the presence of nanoparticle deposits within vulnerable plaques and co-localisation with macrophages. Conclusion: This work presents a new MRI contrast agent for atherosclerosis which uses an under-explored surface ligand, demonstrating promising properties for in vivo behaviour, is still in circulation 24 hours post-injection with limited liver uptake, and shows good accumulation in a murine plaque model.

Hematoma Resolution In Vivo Is Directed by Activating Transcription Factor 1.

RATIONALE: The efficient resolution of tissue hemorrhage is an important homeostatic function. In human macrophages in vitro, heme activates an AMPK (AMP-activated protein kinase)/ATF1 (activating transcription factor-1) pathway that directs Mhem macrophages through coregulation of HO-1 (heme oxygenase-1; HMOX1) and lipid homeostasis genes. OBJECTIVE: We asked whether this pathway had an in vivo role in mice. METHODS AND RESULTS: Perifemoral hematomas were used as a model of hematoma resolution. In mouse bone marrow-derived macrophages, heme induced HO-1, lipid regulatory genes including LXR (lipid X receptor), the growth factor IGF1 (insulin-like growth factor-1), and the splenic red pulp macrophage gene Spic. This response was lost in bone marrow-derived macrophages from mice deficient in AMPK (Prkab1-/-) or ATF1 (Atf1-/-). In vivo, femoral hematomas resolved completely between days 8 and 9 in littermate control mice (n=12), but were still present at day 9 in mice deficient in either AMPK (Prkab1-/-) or ATF1 (Atf1-/-; n=6 each). Residual hematomas were accompanied by increased macrophage infiltration, inflammatory activation and oxidative stress. We also found that fluorescent lipids and a fluorescent iron-analog were trafficked to lipid-laden and iron-laden macrophages respectively. Moreover erythrocyte iron and lipid abnormally colocalized in the same macrophages in Atf1-/- mice. Therefore, iron-lipid separation was Atf1-dependent. CONCLUSIONS: Taken together, these data demonstrate that both AMPK and ATF1 are required for normal hematoma resolution. Graphic Abstract: An online graphic abstract is available for this article.

A Community-Partnered Approach to Developing Church-Based Interventions to Reduce Health Disparities Among African-Americans and Latinos.

Faith and public health partnerships offer promise to addressing health disparities, but examples that incorporate African-Americans and Latino congregations are lacking. Here we present results from developing a multi-ethnic, multi-denominational faith and public health partnership to address health disparities through community-based participatory research (CBPR), focusing on several key issues: (1) the multi-layered governance structure and activities to establish the partnership and identify initial health priority (obesity), (2) characteristics of the congregations recruited to partnership (n = 66), and (3) the lessons learned from participating congregations' past work on obesity that informed the development of a multi-level, multi-component, church-based intervention. Having diverse staff with deep ties in the faith community, both among researchers and the primary community partner agency, was key to recruiting African-American and Latino churches. Involvement by local health department and community health clinic personnel provided technical expertise and support regarding health data and clinical resources. Selecting a health issue-obesity-that affected all subgroups (e.g., African-Americans and Latinos, women and men, children and adults) garnered high enthusiasm among partners, as did including some innovative aspects such as a text/e-mail messaging component and a community mapping exercise to identify issues for advocacy. Funding that allowed for an extensive community engagement and planning process was key to successfully implementing a CBPR approach. Building partnerships through which multiple CBPR initiatives can be done offers efficiencies and sustainability in terms of programmatic activities, though long-term infrastructure grants, institutional support, and non-research funding from local foundations and health systems are likely needed.

Epithelial Cell Packing Induces Distinct Modes of Cell Extrusions.

The control of tissue growth, which is a key to maintain the protective barrier function of the epithelium, depends on the balance between cell division and cell extrusion rates [1, 2]. Cells within confluent epithelial layers undergo cell extrusion, which relies on cell-cell interactions [3] and actomyosin contractility [4, 5]. Although it has been reported that cell extrusion is also dependent on cell density [6, 7], the contribution of tissue mechanics, which is tightly regulated by cell density [8-12], to cell extrusion is still poorly understood. By measuring the multicellular dynamics and traction forces, we show that changes in epithelial packing density lead to the emergence of distinct modes of cell extrusion. In confluent epithelia with low cell density, cell extrusion is mainly driven by the lamellipodia-based crawling mechanism in the neighbor non-dying cells in connection with large-scale collective movements. As cell density increases, cell motion is shown to slow down, and the role of a supracellular actomyosin cable formation and its contraction in the neighboring cells becomes the preponderant mechanism to locally promote cell extrusion. We propose that these two distinct mechanisms complement each other to ensure proper cell extrusion depending on the cellular environment. Our study provides a quantitative and robust framework to explain how cell density can influence tissue mechanics and in turn regulate cell extrusion mechanisms.

Validation of a brief PTSD screener for underserved patients in federally qualified health centers.

OBJECTIVE: The objective was to validate the reliability and efficiency of alternative cutoff values on the abbreviated six-item Posttraumatic Stress Disorder (PTSD) Checklist (PCL-6) [1] for underserved, largely minority patients in primary care settings of Federally Qualified Health Centers (FQHCs). METHOD: Using a sample of 760 patients recruited from six FQHCs in the New York City and New Jersey metropolitan area from June 2010 to April 2013, we compared the PCL-6 with the Clinician Administered PTSD Scale (CAPS) for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We used reliability statistics for single cutoff values on PCL-6 scores. We examined the relationship between probabilities of meeting CAPS diagnostic criteria and PCL-6 scores by nonparametric regression. RESULTS: PCL-6 scores range between 6 and 30. Reliability and efficiency statistics for cutoff between 12 and 26 were reported. There is a strong monotonic relationship between PCL-6 scores and the probability of meeting CAPS diagnostic criteria. CONCLUSION: No single cutoff on PCL-6 scores has acceptable reliability on both false positive and false negative simultaneously. An ordinal decision rule (low risk: 12 or less, medium risk: 13 to 16, high risk: 17 to 25 and very high risk: 26 and above) can differentiate the risk of PTSD. A single cutoff (17 or higher as positive) may be suitable for identifying those with the greatest need for care given limited mental health capacity in FQHC settings.

A comparison of Cambodian-American adolescent substance use behavior to national and local norms.

INTRODUCTION: This study was designed to compare rates of alcohol, marijuana, and cigarette use in Cambodian-American adolescents with norms from nationally- and regionally-representative peers. METHODS: Substance use data from 439 10th grade Cambodian-American adolescents in Long Beach, California were compared to grade- and gender-matched nationally representative data from the Monitoring the Future study and data from the California Healthy Kids Survey of students within the same school district. RESULTS: Overall, the Cambodian-American youth were less likely than nationally- and regionally-representative youth to use alcohol, marijuana, and cigarettes. Specifically, relative to estimates obtained for the general population and students attending school in the same school district, Cambodian-American youth were significantly less likely to use alcohol and marijuana. Cambodian-American youth were also less likely than youth in the general population to smoke cigarettes, but did not differ statistically from youth within their same school district. CONCLUSIONS: As a group, Cambodian-American youth may not be at especially high risk for substance use. As is the case with virtually all populations, some individuals within the Cambodian-American group are likely to have more difficulty than others with substance use concerns. Thus, additional research is needed to identify factors that might help to identify high users with potential service needs.

How many adenocarcinoma lung cancers come from bronchioloalveolar carcinoma?

BACKGROUND: There is emerging evidence that bronchioloalveolar carcinoma (BAC) is the forerunner of peripheral adenocarcinoma lung cancers (ALC). Since advanced stage ALC is often diagnosed on cytology alone, we hypothesized that the incidence of BAC is underreported and that a large proportion of ALC in our population are part of the BAC-adenocarcinoma sequence. METHODS: We reviewed the pretreatment computed tomographic (CT) scans of 69 patients with ALC and looked for characteristic features of BAC. RESULTS: The median patient age was 63, and the majority were of Chinese descent (75.4%). Women comprised 43.5% of the patients (30 patients) and never-smokers comprised 47.8% (33 patients). Only 15 patients (21.7%) had surgical specimens. The presence of BAC components was reported in the pathology of 16 patients (23.2%). CT features classically associated with BAC were found in 35 patients (50.7%). These included air bronchograms or bubble-like lucencies in 24 patients (34.8%), ground-glass opacities in 19 (27.5%), consolidation or pneumonic picture in 11 (15.9%), diffuse small or miliary nodules in 10 (14.5%), and the CT angiogram sign in 4 (5.8%). CONCLUSIONS: We found provocative radiologic evidence that a large proportion of our ALC cases arise from BAC. The CT findings are consistent with current understanding of the likely pathogenesis of peripheral ALC.

Targeted therapy at the end of life for patients with lung cancer.

The use of chemotherapy at the end of life is increasing. We characterized the use of targeted therapies in relation to the end of life in non-small cell lung cancer (NSCLC) patients who died in our institution. The frequency of systemic anticancer therapy usage at the end of life was consistent with that reported in other recent studies. The use of targeted therapies, especially epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), was strikingly more common than that of conventional chemotherapy. Targeted therapy was frequently initiated within the last 3 months of life. Targeted agents were also used in sequence, in combination, and in investigational protocols. We conclude that targeted agents, in particular EGFR TKIs, are now the drugs of choice in the systemic treatment of NSCLC at the end of life.

Barriers to the collaborative care of patients with orofacial injury.

Collaborative care interventions show significant promise in facilitating integrative care, which addresses the physical and mental health needs of patients with orofacial trauma. Ensuring the successful implementation of collaborative care interventions depends on having an adequate understanding of the potential barriers to the provision and receipt of mental health services within specific clinical settings. This article reviews recent findings on the patients' and providers' perceptions of barriers to psychosocial aftercare services in oral and maxillofacial trauma care settings. These findings indicate that although patients and providers recognize the need for psychosocial aftercare, they report substantial barriers to these services. Structural barriers, such as not knowing where to obtain services and financial cost, are the major obstacles among patients. Among providers, structural barriers also serve as significant impediments to the provision of psychosocial services. Some of the most common structural barriers reported by providers include a shortage of financial resources, trained clinical staff, and space. Although collaborative care interventions may be well suited to capitalize on patients' and providers' interests in psychosocial aftercare programs, further research is needed to determine the viability of this promising aftercare model within oral and maxillofacial trauma care settings.

Ethnic identity, spirituality, and self-efficacy influences on treatment outcomes among Hispanic American methadone maintenance clients.

There is increasing concern over whether standard health care services, such as substance abuse treatment, adequately account for important cultural influences, yet studies focusing on the impact of cultural influences on substance abuse treatment continue to be limited. The current study prospectively examined the effects of two cultural factors (ethnic identity and spirituality) on substance abuse treatment outcomes among Hispanic American clients (N=114) enrolled in methadone maintenance treatment. In addition, this study examined whether a commonly studied treatment factor (i.e., self-efficacy) significantly influenced treatment outcomes. Higher levels of self-efficacy at intake were related to increased odds of reported heroin abstinence and a lower number of drugs used at 1-year follow-up. Greater levels of ethnic identity were related to a greater number of drugs used at follow-up. No significant effects were found for spirituality.