Effect of estrogen receptor α on cardiopulmonary adaptation to chronic developmental hypoxia in a rat model.

Humans living at high-altitude (HA) have adapted to this environment by increasing pulmonary vascular and alveolar growth. RNA sequencing data from a novel murine model that mimics this phenotypical response to HA suggested estrogen signaling via estrogen receptor alpha (ERα) may be involved in this adaptation. We hypothesized ERα was a key mediator in the cardiopulmonary adaptation to chronic hypoxia and sought to delineate the mechanistic role ERα contributes to this process by exposing novel loss-of-function ERα mutant (ERαMut) rats to simulated HA. ERα mutant or wild-type (wt) rats were exposed to normoxia or hypoxia starting at conception and continued postnatally until 6 wk of age. Both wt and ERαMut animals born and raised in hypoxia exhibited lower body mass and higher hematocrits, total alveolar volumes (Va), diffusion capacities of carbon monoxide (DLCO), pulmonary arteriole (PA) wall thickness, and Fulton indices than normoxia animals. Right ventricle adaptation was maintained in the setting of hypoxia. Although no major physiologic differences were seen between wt and ERαMut animals at either exposure, ERαMut animals exhibited smaller mean linear intercepts (MLI) and increased PA total and lumen areas. Hypoxia exposure or ERα loss-of-function did not affect lung mRNA abundance of vascular endothelial growth factor, angiopoietin 2, or apelin. Sexual dimorphisms were noted in PA wall thickness and PA lumen area in ERαMut rats. In summary, in room air-exposed rats and rats with peri- and postnatal hypoxia exposure, ERα loss-of-function was associated with decreased alveolar size (primarily driven by hypoxic animals) and increased PA remodeling.NEW & NOTEWORTHY By exposing novel loss-of-function estrogen receptor alpha (Erα) mutant rats to a novel model of human high-altitude exposure, we demonstrate that ERα has subtle but inconsistent effects on endpoints relevant to cardiopulmonary adaptation to chronic hypoxia. Given that we observed some histologic, sex, and genotype differences, further research into cell-specific effects of ERα during hypoxia-induced cardiopulmonary adaptation is warranted.

Chronic developmental hypoxia alters rat lung immune cell transcriptomes during allergic airway inflammation.

Populations that are born and raised at high altitude develop under conditions of chronic developmental hypoxia (CDH), which results in pulmonary adaptations of increased lung volume and diffusion capacity to increase gas exchange. It is not clear how CDH may alter allergic inflammation in the lung. In this study, we sought to characterize the impact of CDH on immune cell populations in the rat lung during a murine model of asthma. Rats were bred and raised in either hypoxic (15% oxygen, CDH) or normobaric room air (20% oxygen). At 3-weeks of age, animals were sensitized to ovalbumin (OVA) or physiologic saline (phosphate-buffered saline [PBS]) as a control, followed by three consecutive days of intra-nasal OVA or PBS at 6-weeks of age. We then assessed airway reactivity and allergic-associated cytokine levels. This was followed by single-cell transcriptomic profiling of lung cell populations. In scRNA-seq analysis, we assessed differentially expressed genes, differentially enriched functional pathways, immune cell exhaustion/activation markers, and immune cell secretory products. Our results show that while OVA heightened airway reactivity, CDH suppressed airway reactivity in OVA-challenged and control animals. Through scRNA-seq analysis, we further demonstrate that CDH alters the transcriptional landscape in the lung and alters transcriptional programs in immune cells. These data define CDH-dependent changes in the lung that impact airway reactivity.

Psychologists' perspectives on the diagnostic classification of mental disorders: results from the WHO-IUPsyS Global Survey.

This study examined psychologists' views and practices regarding diagnostic classification systems for mental and behavioral disorders so as to inform the development of the ICD-11 by the World Health Organization (WHO). WHO and the International Union of Psychological Science (IUPsyS) conducted a multilingual survey of 2155 psychologists from 23 countries, recruited through their national psychological associations. Sixty percent of global psychologists routinely used a formal classification system, with ICD-10 used most frequently by 51% and DSM-IV by 44%. Psychologists viewed informing treatment decisions and facilitating communication as the most important purposes of classification, and preferred flexible diagnostic guidelines to strict criteria. Clinicians favorably evaluated most diagnostic categories, but identified a number of problematic diagnoses. Substantial percentages reported problems with crosscultural applicability and cultural bias, especially among psychologists outside the USA and Europe. Findings underscore the priority of clinical utility and professional and cultural differences in international psychology. Implications for ICD-11 development and dissemination are discussed.

The WPA-WHO Global Survey of Psychiatrists' Attitudes Towards Mental Disorders Classification.

This article describes the results of the WPA-WHO Global Survey of 4,887 psychiatrists in 44 countries regarding their use of diagnostic classification systems in clinical practice, and the desirable characteristics of a classification of mental disorders. The WHO will use these results to improve the clinical utility of the ICD classification of mental disorders through the current ICD-10 revision process. Participants indicated that the most important purposes of a classification are to facilitate communication among clinicians and to inform treatment and management. They overwhelmingly preferred a simpler system with 100 or fewer categories, and over two-thirds preferred flexible guidance to a strict criteria-based approach. Opinions were divided about how to incorporate severity and functional status, while most respondents were receptive to a system that incorporates a dimensional component. Significant minorities of psychiatrists in Latin America and Asia reported problems with the cross-cultural applicability of existing classifications. Overall, ratings of ease of use and goodness of fit for specific ICD-10 categories were fairly high, but several categories were described as having poor utility in clinical practice. This represents an important focus for the ICD revision, as does ensuring that the ICD-11 classification of mental disorders is acceptable to psychiatrists throughout the world.

Mental health services in 42 low- and middle-income countries: a WHO-AIMS cross-national analysis.

OBJECTIVE: The authors describe characteristics and capacities of mental health systems in low- and middle-income countries. METHODS: The World Health Organization Assessment Instrument for Mental Health Systems was used to assess services in 42 countries (13 low-, 24 lower-middle, and five upper-middle income). RESULTS: Of 36 countries with a mental health plan, 90% include the goal of developing community services. However, inpatient facilities are the main service providers, with less than one community contact (.70) for each inpatient day. Mental hospitals consume 80% of mental health budgets, and outpatient care is limited. CONCLUSIONS: Mental health services in participating countries are limited and often hospital based.

The role of attitudinal familism in academic outcomes: a study of urban, Latino high school seniors.

The aim of this study was to examine the role of attitudinal familism on Latino high school students' academic grades, effort, motivation, and truancy. Results in this study reveal that having high attitudinal familism predicts fewer classes missed and greater academic effort. Also, when mothers' educational level is low, attitudinal familism is positively associated to students' academic grades. This study underscores the need for additional research on cultural measures that can help us better understand Latino adolescents' educational experiences.