Optimizing cell therapy by sorting cells with high extracellular vesicle secretion.

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.

Uncovering multi-level mental healthcare barriers for migrants: a qualitative analysis across China, Germany, Netherlands, Romania, and South Africa.

BACKGROUND: Forced displacement is a significant issue globally, and it affected 112 million people in 2022. Many of these people have found refuge in low- and middle-income countries. Migrants and refugees face complex and specialized health challenges, particularly in the area of mental health. This study aims to provide an in-depth qualitative assessment of the multi-level barriers that migrants face in accessing mental health services in Germany, Macao (Special Administrative Region of China), the Netherlands, Romania, and South Africa. The ultimate objective is to inform tailored health policy and management practices for this vulnerable population. METHODS: Adhering to a qualitative research paradigm, the study centers on stakeholders' perspectives spanning microsystems, mesosystems, and macrosystems of healthcare. Utilizing a purposive sampling methodology, key informants from the aforementioned geographical locations were engaged in semi-structured interviews. Data underwent thematic content analysis guided by a deductive-inductive approach. RESULTS: The study unveiled three pivotal thematic barriers: language and communication obstacles, cultural impediments, and systemic constraints. The unavailability of professional interpreters universally exacerbated language barriers across all countries. Cultural barriers, stigmatization, and discrimination, specifically within the mental health sector, were found to limit access to healthcare further. Systemic barriers encompassed bureaucratic intricacies and a conspicuous lack of resources, including a failure to recognize the urgency of mental healthcare needs for migrants. CONCLUSIONS: This research elucidates the multifaceted, systemic challenges hindering equitable mental healthcare provision for migrants. It posits that sweeping policy reforms are imperative, advocating for the implementation of strategies, such as increasing the availability of language services, enhancing healthcare providers' capacity, and legal framework and policy change to be more inclusive. The findings substantially contribute to scholarly discourse by providing an interdisciplinary and international lens on the barriers to mental healthcare access for displaced populations.

Mental health and psychosocial interventions to limit the adverse psychological effects of disasters and emergencies in China: a scoping review.

Exposure to disasters and public health emergencies negatively affects mental health. Research documenting the psychosocial responses to these calamities in China increased dramatically after the 2008 Wenchuan earthquake. However, there is no comprehensive assessment of the available literature on China's mental health and psychosocial support (MHPSS) responses to these events. This scoping review systematically maps existing published research and grey literature sources regarding MHPSS to disasters and emergencies in China. We examined relevant literature in English and Chinese from six databases and official websites from Jan 1, 2000, to Aug 13, 2021, and included 77 full-text records in this review. The main types of interventions reported included a) stepped care intervention models, b) individual structured psychotherapy and pharmacotherapy, c) mental health education, d) psychological counselling, and e) government-based policy interventions. Most interventions were evaluated using quantitative methods that assessed the treatment of common mental disorders. The review found that rapid national mobilization, emphasis on resilience-strengthening interventions, and the widespread use of step-care models were essential components of reducing the adverse psychosocial effects of disasters. The review also identified remaining gaps, including a) a lack of integration of disaster-related services with the pre-existing health care system, b) inadequate supervision of MHPSS providers, and c) limited monitoring and evaluation of the services provided. These results show where additional research is needed in China to improve mental health services. It also provides a framework that other countries can adapt when developing and evaluating MHPSS policies and plans in response to disasters.

Effectiveness of a WHO self-help psychological intervention to alleviate stress among healthcare workers in the context of COVID-19 in China: a randomised controlled trial.

AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.

The prevalence of intimate partner violence and risk factors for women and men in China during the Shanghai 2022 lockdown.

AIMS: Intimate partner violence (IPV) is a global public health concern with negative effects on individuals and families. The present study investigated the prevalence, risk factors and gender disparities associated with IPV during the Shanghai 2022 Covid-19 lockdown - a public health emergency which may have exacerbated IPV. METHODS: We estimated the total IPV prevalence and prevalence of physical, sexual and verbal IPV by using an adapted version of the Extended-Hurt, Insult, Threaten, Scream scale. This cross-sectional study was carried out using a population quota-based sampling of Shanghai residents across 16 districts during the 2022 Shanghai lockdown (N = 2026; 1058 men and 968 women). RESULTS: We found a distinct gendered dynamic, where women reported a significantly higher prevalence of experienced IPV (27.1%, 95% confidence interval [CI]: 23.1-31.4) compared to men (19.8%, 95% CI: 16.1-24.0). Notably, the prevalence estimate mirrored the national lifetime IPV prevalence for women but was over twice as high for men. In multivariable logistic regression analyses, economic stress (income loss: adjusted OR [aOR] = 2.42, 95% CI: 1.28-4.56; job loss: aOR = 1.73, 95% CI: 1.02-2.92; financial worry much more than usual: aOR = 1.89, 95% CI: 1.00-3.57) and household burden (one child at home: aOR = 1.81, 95% CI: 1.12-2.92; not enough food: aOR = 1.67, 95% CI: 1.04-2.70) were associated with increased odds of overall IPV victimization among women but not men. With regard to more serious forms of IPV, job loss (aOR = 2.27, 95% CI: 1.09-4.69) and household burden (two or more children at home: aOR = 2.95, 95% CI: 1.33-7.69) were associated with increased odds of physical IPV against men. For women, a lack of household supplies was associated with increased odds of physical IPV (water: aOR = 3.33, 95% CI: 1.79-6.25; daily supplies: aOR = 2.27, 95% CI: 1.18-4.35). Lack of daily supplies (aOR = 2.17, 95% CI: 1.03-4.55) and job loss (aOR = 2.66, 95% CI: 1.16-6.12) were also associated with increased odds of sexual IPV. CONCLUSIONS: Although a larger proportion of women reported IPV, men experienced greater IPV during the lockdown than previously estimated before the pandemic. Economic stressors, including job loss, and household burden were critical risk factors for serious forms of IPV. Improving gender equality that my account for disparities in IPV in China is critically needed. Policies that mitigate the impact of economic losses during crises can potentially reduce IPV.

The social determinants of migrant domestic worker (MDW) health and well-being in the Western Pacific Region: A Scoping Review.

The health and well-being of transnational migrant domestic workers (MDWs) is a pressing but largely neglected public health concern. The Asia Pacific region is home to over 20% of the global MDW population. Living and working conditions, social contexts, political environments, and migration regimes are recognized as consequential to the health of this population, but currently no synthesis of available literature to prioritize research or policy agenda setting for MDW has yet been conducted. This scoping review screened 6,006 peer-reviewed articles and 1,217 gray literature sources, identifying 173 articles and 276 gray literature sources that reported key MDW health outcomes, social determinants of health, and related interventions. The majority of identified studies were observational and focused on the prevalence of common mental disorders and chronic physical conditions, with most studies lacking population representativeness. Identified social determinants of health were primarily concerned with personal social and financial resources, and health knowledge and behaviors, poor living and working conditions, community resources, experienced stigma and discrimination, poor healthcare access, exploitation within the MDW employment industry, and weak governance. Six interventional studies were identified that targeted individual-level health determinants such as financial and health knowledge with mixed effectiveness. Future population representative epidemiological and respondent driven sampling studies are needed to estimate population health burdens. In addition, randomized control trials and public health intervention studies are needed to improve women's health outcomes and address proximal health determinants to reduce health inequalities. Leveraging social networks and community facing non-governmental organizations (NGOs) are promising directions to overcome access to care for this population.

A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial.

Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges' g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges' g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges' gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges' gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges' g = 0.26), but not at three-month follow-up (p = 0.265, Hedges' g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214.

Association between maltreatment, hair cortisol concentration, positive parent-child interaction, and psychosocial outcomes in Chinese preschool children.

Children now are facing an increasing risk of early life stress (ELS), which leads to detrimental psychosocial outcomes. Behavior studies suggested that positive parental interactions might moderate the negative impact of ELS, but the related biological alteration remains unclear. This study aims to investigate whether positive parent-child interactions moderate the association between maltreatment (as a severe form of ELS) and hair cortisol concentration (HCC), as well as between HCC and psychosocial outcomes in young children. Participants were 6-year-old Chinese children (N = 257, Mage = 6.2, 121 were male) selected by stratified cluster random sampling from a Shanghai population representative cohort. Proximal 3 cm hair strands were analyzed using liquid chromatography coupled with tandem mass spectrometry for HCC. Children's psychosocial outcome was evaluated using the parental report Strengths and Difficulties Questionnaire (SDQ). Parents also reported the frequency of positive parent-child interactions using the Chinese Parent-Child Interaction Scale (CPCIS) as well as the history of maltreatment. Multi-level logistic regression models adjusting for individual, kindergarten, and district confounders were used to evaluate the associations between maltreatment, HCC, and psychosocial outcomes. Interactions terms tested whether more frequent positive parent-child interactions moderates the association between maltreatment and HCC, as well as between HCC and psychosocial outcomes. Maltreated children exhibited higher levels of HCC (B = 1.20, 95% CI: 0.38,2.02; p = 0.004), and children with higher HCC exhibited poorer psychosocial outcomes (B = 0.34, 95% CI: 0.18,0.51; p < 0.001). Positive parent-child interactions did not have a moderating effect on the association between maltreatment and HCC, but they demonstrated a moderating effect on the association between increased HCC and psychosocial outcomes (interaction term: B = -0.42, 95% CI: -0.75,-0.10; p = 0.01). These findings provide evidence that positive parental interaction may serve as a moderator between chronic cortisol exposure and psychosocial problems. It highlights the importance of frequent parent-child interactions, especially among children under a high risk of ELS.

Homoprejudiced Violence Experiences and High-Risk Sexual Behaviors among Chinese Men Who Have Sex with Men: Depression Severity and Recreational Drug Usage as Potential Mediators.

Homoprejudiced violence is a type of aggression against an individual or a community based on their actual or perceived sexual orientation. It may be linked to risks of acquiring HIV/STI via psychosocial variables. This study explored the association between homoprejudiced violence experiences and high-risk sexual behaviors, and potential psychosocial mediators. Using cross-sectional survey data collected in China through Blued among men who have sex with men (MSM) in January 2021, this study conducted multiple mediation analyses. Standard instruments were used to collect data on depressive symptoms in the last two weeks (PHQ-9), recreational drug usage in the last three months, and ever experiencing homoprejudiced violence (12-item survey instrument). Dependent variables were having condomless anal sex and having three or more sexual partners in the last three months. Among 1828 MSM, nearly half (847, 46%) had experienced homoprejudiced violence. Twenty-three percent (427) reached a score that suggested moderate or severe depression and 35% (644) had used recreational drugs. In the last three months, 40% (731) had condomless anal sex and 34% (626) had three or more sexual partners. The indirect mediational coefficients through depression on condomless anal sex and multiple sexual partners were 0.04 (95% CI: [0.02, 0.07]) and 0.02 (95% CI: [0.001, 0.05]), respectively. The indirect mediational coefficient of homoprejudiced violence experience on multiple sexual partners through recreational drug use was 0.05 (95% CI: [0.03, 0.08]). These findings suggest that more comprehensive interventions are needed to address the syndemic of homoprejudiced violence, mental health issues, and HIV/STI-related risks.

Assessing the Feasibility of Partnering with a Home Visiting Program for Early Childhood Obesity Prevention.

PURPOSE: Little empirical data exists evaluating the feasibility of partnering with established home visiting programs to implement early childhood obesity prevention programs, despite the recommendation to do so. To inform this gap, we evaluated the feasibility of collecting anthropometric measurements of children by home visitors across multiple sites, and the alignment of these measurements with children in need, including with adverse family experiences (AFEs) given emerging evidence suggests an association with childhood obesity. DESCRIPTION: Our proof-of-concept study included primary data collection of child anthropometric measurements through an established home visiting program in four states. This sample included 248 children ages 6 months to 5 years. ASSESSMENT: In the sample, 37.1% of the children had overweight or obesity, 50% were female, 64.2% Hispanic/Latinx, 15.8% non-Hispanic Black, and 42.3% from rural/small towns. Households included substantial needs: 87.1% were low income, 73.8% low education, and 59.3% underemployment. Regarding AFEs, 38.3% of the children had at least one, with the most common being mothers who were treated violently. A multivariable model revealed community type, not AFEs, was significantly associated with overweight/obesity status, suggesting children in suburban and especially rural/small town residences (odds ratio 5.11; 95% CI [1.59, 16.39]) could be priority populations for childhood obesity prevention programs. CONCLUSION: Findings of this multi-site study inform the feasibility of partnering with home visiting programs to reach and measure a diverse sample of children and families in need of childhood obesity prevention.

On artificial intelligence and global mental health.

Artificial intelligence (AI) is affecting global societies and reshaping the status quo. AI technologies possess great potential to tackle some of mankind's most pressing problems, although much of what can be achieved is still a matter of imagination and critical discussion (e.g., AI might also be a source of harm). In the present short communication, we outline AI's potential for addressing several core issues in global mental health including its application in psychotherapeutic settings.

Understanding the protective effect of social support on depression symptomatology from a longitudinal network perspective.

BACKGROUND: Higher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role. OBJECTIVE: To investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach. METHODS: A total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network. FINDINGS: The results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A higher number of close confidants and accessible practical help was associated with decreased anhedonia (weight=-0.033) and negative self-appraisal symptoms (weight=-0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreased depressed mood (weight=0.086) and negative self-appraisal (weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men's network. CONCLUSIONS: Reductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women. CLINICAL IMPLICATIONS: Building community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.

Bereavement issues and prolonged grief disorder: A global perspective.

The death of a loved one - bereavement - is a universal experience that marks the human mental health condition. Grief - the cognitive, emotional, and behavioral responses to bereavement - is thus experienced by virtually everyone at some point in life, while mourning is a process through which grievers come to terms with the loss envisioning life without the deceased. Although distress subsides over time among most bereaved individuals, a minority will develop a condition recently identified as prolonged grief disorder (PGD). The present review provides a global perspective on bereavement, grief reactions, and PGD. Although the loss of a loved one and grief reactions are in general experienced consistently across different cultures, differences and variations in their expression may exist across cultures. Especially within specific populations that may be more at risk for PGD, possibly due to risk factors associated with the mechanisms of loss (e.g., refugees, migrants, and conflict survivors). The diagnostic criteria for PGD are mostly based on Western grieving populations, and cultural adaptations of PGD treatments are limited. Therefore, cross-cultural development and validation of PGD screening/assessment is critical to support future research on grief reactions and PGD, especially in non-Western contexts, and concerning the potential future global changes and challenges that appear to have a major impact on PGD. More transcultural research on PGD is needed to contextualize and will lead to culture-bound symptom identification of PGD, and the adaptation of current treatment protocols, which may ultimately improve health at the individual level, and health-care systems.

Kansa talk: mapping cancer terminologies in Bagamoyo, Tanzania towards dignity-based practice.

This paper reports and examines the results of qualitative research on the use of local cancer terminology in urban Bagamoyo, Tanzania. Following recent calls to unify evidence and dignity-based practices in global health, this research locates local medical sociolinguistics as a key place of entry into creating epistemologically autonomous public health practices. We used semistructured ethnographic interviews to reveal both the contextual and broader patterns related to use of local cancer terminologies among residents of Dunda Ward in urban Bagamoyo. Our findings suggest that people in Bagamoyo employ diverse terms to describe and make meanings about cancer that do not neatly fit with biomedical paradigms. This research not only opens further investigation about how ordinary people speak and make sense of the emerging cancer epidemic in places like Tanzania, but also is a window into otherwise conceptualisations of 'intervention' onto people in formerly colonised regions to improve a health situation. We argue that adapting biomedical concepts into local sociolinguistic and knowledge structures is an essential task in creating dignity-based, evidence-informed practices in global health.

Prevalence and determinants of food insecurity during the 2022 COVID-19 related lockdown in Shanghai.

The SARS-CoV-2 coronavirus pandemic has led to increased food insecurity levels. This cross-sectional study examines the prevalence and determinants of food insecurity during the two-month (1 April to 1 June 2022) city-wide lockdown in Shanghai. The data was collected via an online questionnaire from 3230 adult Shanghai residents during the lockdown. Food insecurity was measured using an adapted version of the Household Food Insecurity Access Scale. Nearly 70% of participants reported being exposed to food insecurity. Using multivariable logistic regressions, we examined the associations between key correlates (i.e. age, income, lockdown-related income loss, migration, employment status, social capital, preparedness, and received social support) and overall food insecurity while adjusting for ethnicity, gender, education, household size, and marital status. Results showed that compared to local Shanghai residents, migrants (i.e, permanent migrants with Hukou (OR = 2.16), permanent migrants without Hukou (OR = 2.06), temporary migrants (OR = 2.74)), and participants with less than or greather than 50% lockdown-related income loss (OR = 2.60, OR = 3.09), were associated with higher odds of overall food insecurity. Participants with greater preparedness (OR = 0.66), greater bonding social capital (OR = 0.93), and greater bridging social capital (OR = 0.94), had lower odds of overall food insecurity. Targeted interventions are needed to enhance food resilience and health equity among vulnerable populations.

Deformity or variation? Phenotypic diversity in the zebrafish vertebral column.

Vertebral bodies are composed of two types of metameric elements, centra and arches, each of which is considered as a developmental module. Most parts of the teleost vertebral column have a one-to-one relationship between centra and arches, although, in all teleosts, this one-to-one relationship is lost in the caudal fin endoskeleton. Deviation from the one-to-one relationship occurs in most vertebrates, related to changes in the number of vertebral centra or to a change in the number of arches. In zebrafish, deviations also occur predominantly in the caudal region of the vertebral column. In-depth phenotypic analysis of wild-type zebrafish was performed using whole-mount stained samples, histological analyses and synchrotron radiation X-ray tomographic microscopy 3D reconstructions. Three deviant centra phenotypes were observed: (i) fusion of two vertebral centra, (ii) wedge-shaped hemivertebrae and (iii) centra with reduced length. Neural and haemal arches and their spines displayed bilateral and unilateral variations that resemble vertebral column phenotypes of stem-ward actinopterygians or other gnathostomes as well as pathological conditions in extant species. Whether it is possible to distinguish variations from pathological alterations and whether alterations resemble ancestral conditions is discussed in the context of centra and arch variations in other vertebrate groups and basal actinopterygian species.

Optimizing Cell Therapy by Sorting Cells with High Extracellular Vesicle Secretion.

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. We developed a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach was applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibited distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintained high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improved heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.