Stigma towards mental illness and substance use issues in primary health care: Challenges and opportunities for Latin America

Stigma towards mental illness and addictive disorders is a global problem and one of the main obstacles in tackling this issue remains the effective integration of mental health services into primary health care (PHC). In Latin America, information has significantly increased on the existence of stigma; however, little is known about effective interventions to prevent stigma and promote recovery-oriented practices in PHC. The aim of this study is to understand the existing evidence regarding mental health stigma in PHC with a special focus on the Latin American region. A scoping review of the literature related to mental health stigma in PHC was conducted. Two hundred and seventeen articles were evaluated; 74 met inclusion criteria and 14 additional articles were selected from references of search results. Results were subdivided into five different perspectives: users, family members and significant others, health professionals, contextual factors, and potential effective interventions. Only nine studies were based in Latin America, and only one described an intervention to reduce stigma in mental health services, not specifically in PHC. We found an urgent need to develop interventions to understand and reduce stigma in PHC settings, especially in Latin America.     

Dissection of the components for PIP2 activation and thermosensation in TRP channels

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 and temperature activation. A chimera in which the proximal part of the C-terminal of TRPV1 replaces an equivalent section of TRPM8 C-terminal is activated by PIP2 and confers the phenotype of heat activation. PIP2, but not temperature sensitivity, disappears when positively charged residues contained in the exchanged region are neutralized. Shortening the exchanged segment to a length of 11 aa produces voltage-dependent and temperature-insensitive channels. Our findings suggest the existence of different activation domains for temperature, PIP2, and voltage. We provide an interpretation for channel-PIP2 interaction using a full-atom molecular model of TRPV1 and PIP2 docking analysis.     

In Vitro Study of Isoflavones and Isoflavans as Potent Inhibitors of Human 12‐ and 15‐Lipoxygenases

In this study, we have investigated 16 isoflavone and isoflavan derivatives as potential inhibitors of human lipoxygenase (platelet 12‐lipoxygenase, reticulocyte 15‐lipoxygenase‐1, and epithelial 15‐lipoxygenase‐2). The flavonoid baicalein, a known lipoxygenase inhibitor, was used as positive control. Four compounds, 6,7‐dihydroxy‐3′‐chloroisoflavone ( 1c ), 7‐hydroxy‐8‐methyl‐4′‐chloroisoflavan ( 5a ), 7,8‐dihydroxy‐4′‐methylisoflavan ( 5b ), and 7,8‐dihydroxy‐3′‐methylisoflavan ( 5c ), were effective inhibitors of 12‐lipoxygenases and 15‐lipoxygenase‐1 with IC₅₀'s <10 μm , while 6,7‐dihydroxy‐4′‐nitroisoflavone ( 1b ) was a selective inhibitor of 12‐lipoxygenases. Docking studies, antioxidant assays, and kinetic measurements were carried out for the three best inhibitors ( 1b , 5b , 5c ). The results showed that a catechol group in ring A is critical for the antioxidant properties of these compounds, and probably essential for their inhibitory activity. Kinetic assays showed that compounds 1b , 5b , and 5c are competitive inhibitors with K_i values in the range of 0.3–3 μm .     

Effects of natural flavones and flavonols on the kinase activity of Cdk5

A number of natural and synthetic flavonoids have been assessed previously with regard to their effects on the activity of cyclin-dependent kinases (Cdk1 and -2) related to the inhibition of cell cycle progression. On the other hand, the Cdk5/p35 system is of major importance in neuronal migration phenomena and brain development, and its deregulation is implicated in neurodegenerative diseases, particularly Alzheimer's. Here we show that some natural flavonoids inhibit the activity of the Cdk5/p35 system in the micromolar range, while others are practically inactive. Ring B-unsubstituted and highly methoxylated flavones were inactive or gave irreproducible results, and 6-methoxyapigenin and 6-methoxyluteolin were the most potent Cdk5 complex inhibitors within this series, while the common flavonols kaempferol and quercetin showed intermediate behavior. The reported crystal structure of the Cdk5 complex with its activator p25 was used for docking studies, which also led to the identification of the two 6-methoxyflavones, kaempferol and quercetin, as well as the untested 6-methoxy derivatives of kaempferol and quercetin and the corresponding 6-hydroxy analogues as compounds exhibiting a good fit to the active site of the enzyme.     

Understanding Users’ Perspectives of Psychosocial Mechanisms Underpinning Peer Support Work in Chile

This study explores the beliefs and attitudes about the psychosocial mechanisms of peer support work among users who participated in Critical Time Intervention-Task Shifting (CTI-TS), which tested the acceptability and feasibility of a peer support work model to improve community-based mental health care for individuals with psychosis in Latin America. We conducted a secondary analysis of 15 in-depth interviews with CTI-TS participants in Chile, using the framework method and defined the framework domains based on five major mechanisms of peer support work identified by a recent literature review. The analysis revealed that users’ perceptions of peer support work mechanisms were strongly shaped by personal motivations, beliefs about professional hierarchies, familial support, and the Chilean mental health system’s incipient recovery orientation. The findings underscore the importance of adopting culturally tailored strategies to promote peer support work, such as involving mental health professionals and fostering equal-powered relationships between PSWs and users.

     

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

Continuing our search to find more potent and selective 5‐LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones ( IR ) and nine isoflavans ( HIR ), and their in vitro and in cellulo potency against human leukocyte 5‐LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5‐LOX (IR‐2, HIR‐303, and HIR‐309), with IC₅₀ values at least 10 times lower than those of 12‐LOX, 15‐LOX‐1, and 15‐LOX‐2. Of these three, IR‐2 (6,7‐dihydroxy‐4‐methoxy‐isoflavone, known as texasin) was the most selective 5‐LOX inhibitor, with over 80‐fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7‐dihydroxy versus 7,8‐dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5‐LOX. Two of the most potent/selective inhibitors (HIR‐303 and HIR‐309) were reductive inhibitors and were potent against 5‐LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5‐LOX in vitro and in cellulo.     

The impact of the COVID-19 pandemic on the mental health of healthcare workers: study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study

Background

Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia.

Methods

Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country’s income level.

Results

As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly.

Conclusions

This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings.

     

30 years from the Caracas Declaration: the situation of psychiatric hospitals in Latin America and the Caribbean prior,during and after the COVID-19 pandemic

Social Psychiatry and Psychiatric Epidemiology -