Association of pulmonary black carbon accumulation with cardiac fibrosis in residents of Sao Paulo, Brazil.

Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post-mortem samples. This study examined whether long-term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbon-based particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long-term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.

Assessing the efficacy of the 'Bicho De 7 Cabeças' B-learning school-based program in enhancing mental health literacy and reducing stigma.

The prevalence of mental disorders in adolescents has a considerable impact on daily life, restricting tasks and diminishing overall quality of life while potentially leading to stigmatization. This study aims to measure the impact of a mental health literacy intervention program, called "Bicho de 7 Cabeças" project, in b-learning format, on the increase of knowledge and the decrease of stigma in young people from Póvoa de Varzim, in Portugal. A quasi-experimental study was conducted, from November 2022 to May 2023, involving an experimental group ("Bicho de 7 Cabeças" protocol) and an active control group (informational brochures), utilizing a pre-test/post-test design. Mental Health Literacy Measure-MHLM, Mental Health Promoting Knowledge Scale-MHPK-10, Mental Illness Knowledge Schedule-MAKS, Reported and Intended Behaviour Scale-RIBS, and Community Attitudes toward People with Mental Illness-CAMI were used. A total of 504 young students from the 9th grade enroll in this study, with a mean age around 14 years old. There is a significant difference between stigma (p <.001) and knowledge (p <.001) scores at baseline and follow-up. The results of this study shows that interventions aimed at young people for the promotion of mental health literacy and stigma reduction are needed and more initiatives should be implemented in schools to address these problems.

Nature-Based Interventions Targeting Elderly People's Health and Well-Being: An Evidence Map.

BACKGROUND: Healthy aging encompasses more than the absence of disease, emphasizing the preservation of functional abilities for enhanced well-being and quality of life. Nature-based interventions are scientifically proven contributors to healthy aging. OBJECTIVE: To develop an evidence map showcasing nature-based interventions targeting older individuals' health and well-being. METHODS: The evidence map was developed through critical analysis of systematic reviews and clinical trials utilizing the tools AMSTAR2 and CONSORT. A systematic search spanning the past decade was conducted across databases: Cochrane, SCOPUS, PubMed, Web of Science, Embase, and LILACS. RESULTS: Twelve articles met the eligibility criteria. Nature-based interventions such as forest bathing, hiking, therapeutic gardens, virtual reality, and forest sounds were identified. Outcomes were categorized into physical aspects (cardiovascular and pulmonary; neuro-immuno-endocrinological) and mental/behavioral aspects. The final map integrated interventions, outcomes, and quality assessments. CONCLUSIONS: The survey highlights the positive impact of nature-based interventions on the health of the elderly. This study provides insights across various domains, fostering the development of programs and policies in management to promote healthy aging. Regarding healthcare, it encourages discourse among professionals regarding the integration of nature-based practices for equitable care in both individual and group settings. Furthermore, it underscores the need for research in the Southern Hemisphere, particularly in Brazil, where the study was conducted.

Healthcare Professionals' Resilience During the COVID-19 and Organizational Factors That Improve Individual Resilience: A Mixed-Method Study.

Healthcare workers are a susceptible population to be psychologically affected during health crises, such as the recent COVID-19 pandemic. Resilience has been pointed out in the literature as a possible protective factor against psychological distress in crisis situations. This can be influenced by internal and external factors, such as individual characteristics and organizational factors. Thus, this study aims to characterize the overall resilience levels among healthcare professionals in Portugal and to understand the perspectives of this healthcare workers regarding organizational factors that improve individual resilience. This is a mixed-method study: a first quantitative study using a cross-sectional design to administer the Resilience Scale for Adults (RSA) to 271 healthcare professionals (Mage 33.90, SD = 9.59 years, 90.80% female), followed by a qualitative study through 10 in-depth interviews. The mean score for the total RSA was 178.17 (SD = 22.44) out of a total of 231. Qualitative analysis showed 4 major themes on factors that enhance resilience: "Professional's Training," "Support and Wellbeing Measures," "Reorganization of Services" and "Professional Acknowledgment." The findings may contribute to the development of targeted interventions and support systems to enhance resilience and well-being among healthcare workers.

Mental Health Literacy and Stigma in a Municipality in the North of Portugal: A Cross-Sectional Study.

Portugal has Europe's second-highest prevalence of psychiatric illnesses, and this is the reason why mental health literacy (MHL) and stigma should be addressed. This study aimed to investigate the mental health literacy and stigma levels among different groups of people from Póvoa de Varzim, a municipality in the north of Portugal. Students, retired people, and professionals (education, social, and healthcare fields) were recruited using a convenience sample from June to November 2022. Participants' MHL levels were evaluated using the Mental Health Promoting Knowledge Scale (MHPK), Mental Health Literacy Measure (MHLM) and Mental Health Knowledge Schedule (MAKS). Stigma levels were evaluated using Community Attitudes towards Mental Illness (CAMI) and the Reported and Intended Behaviour Scale (RIBS). A total of 928 questionnaires were filed. The respondents included 65.70% of women, a mean age of 43.63 (±26.71) years and 9.87 (±4.39) years of school education. MHL increased with age, education level and was higher in women (p < 0.001). A higher level of MHL was seen in health professionals (p < 0.001). Findings revealed that older people stigmatized people with mental illness more (p < 0.001), and the female gender stigmatize less (p < 0.001). In addition, results showed that stigma decreased with higher mental health literacy (r between 0.11 and 0.38; p < 0.001). To conclude, specific campaigns that promote mental health literacy should be tailored to specific profiles within this population to address those that have more stigma.

Identification of a Novel Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase: In Vitro and In Silico Studies.

The enhancement of cholinergic functions via acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition is considered a valuable therapeutic strategy for the treatment of Alzheimer's disease. This study aimed to evaluate the in vitro effect of ZINC390718, previously filtered using computational approaches, on both cholinesterases and to characterize, using a molecular dynamics (MD) simulation, the possible binding mode of this compound inside the cholinesterase enzymes. The in vitro cytotoxicity effect was also investigated using a primary astrocyte-enriched glial cell culture. ZINC390718 presented in vitro dual inhibitory activity against AChE at a high micromolar range (IC50 = 543.8 µM) and against BuChE (IC50 = 241.1 µM) in a concentration-dependent manner, with greater activity against BuChE. The MD simulation revealed that ZINC390718 performed important hydrophobic and H-bond interactions with the catalytic residue sites on both targets. The residues that promoted the hydrophobic interactions and H-bonding in the AChE target were Leu67, Trp86, Phe123, Tyr124, Ser293, Phe295, and Tyr341, and on the BuChE target, they were Asp70, Tyr332, Tyr128, Ile442, Trp82, and Glu197. The cytotoxic effect of Z390718, evaluated via cell viability, showed that the molecule has low in vitro toxicity. The in vitro and in silico results indicate that ZINC390718 can be used as chemotype for the optimization and identification of new dual cholinesterase inhibitors.

Impact of a Virtual Reality-Based Simulation on Empathy and Attitudes Toward Schizophrenia.

Virtual Reality (VR) has been identified as one of the most promising resources for developing empathy towards stigmatized groups as it allows individuals to experience a situation close to reality from another person's perspective. This quasi-experimental study aimed to examine the impact on empathy, knowledge, and attitudes towards people with schizophrenia of a VR simulation that reproduces the experience of psychotic symptoms while performing a cognitive task compared with watching a 2D video and, thus, how these experiences could reduce stigma towards people diagnosed with schizophrenia. The sample comprised of 102 higher education health students, distributed by the experimental and control groups. The impact of the program was measured by completing multiple questionnaires on levels of empathy, attitudes, and mental health knowledge. Both methods (VR and 2D video) were, to a certain extent, effective. However, VR was more effective at eliciting attitudes and knowledge change compared to the control group. These findings suggest that not only VR but also 2D videos could be interesting strategies to enhance empathy and improve attitudes towards people with schizophrenia in higher education health students.

Virtual Reality Exposure Therapy for Armed Forces Veterans with Post-Traumatic Stress Disorder: A Systematic Review and Focus Group.

Virtual reality exposure therapy (VRET) is an emerging treatment for people diagnosed with Post-Traumatic Stress Disorder (PTSD) due to the limited accessibility of psychotherapies. This research aims to determine the guidelines for developing a Virtual Reality-War Scenario program for Armed Forces veterans with PTSD and encompasses two studies: Study 1, a systematic electronic database review; Study 2, a focus group of twenty-two Portuguese Armed Forces veterans. Results showed a positive impact of VRET on PTSD; however, there were no group differences in most of the studies. Further, according to veterans, new VRET programs should be combined with the traditional therapy and must consider as requirements the sense of presence, dynamic scenarios, realistic feeling, and multisensorial experience. Regardless, these findings suggest VRET as a co-creation process, which requires more controlled, personalized, and in-depth research on its clinical applicability.

A Review on the In Vitro Evaluation of the Anticholinesterase Activity Based on Ellman's Method.

Inhibition of cholinesterases is a common strategy for the treatment of several disorders, especially Alzheimer´s disease. In vitro assays represent a critical step towards identifying molecules with potential anticholinesterase effect. This study aimed at providing a comprehensive review of the methodologies used in vitro for the anticholinesterase activity based on the spectrophotometry of Ellman's method. This work used two databases (PubMed and ScienceDirect) to search for original articles and selected publications between 1961 and 2019, which reported in vitro spectrophotometry assays for anticholinesterase activity. After the search process and the selection of publications, the final sample consisted of 146 articles published in several journals submitted by researchers from different countries. Although the studies analyzed in this work are all within the same conception of in vitro tests based on Ellman's method, one can observe a wide divergence in the origin and concentration of enzyme, the choice and pH of the buffer, the concentration of the substrate, the sample diluent, incubation time, temperature, and time of the spectrophotometric reading interval. There is no consensus in the methodology of studies with in vitro tests for anticholinesterase assessment. The methodological variations related to kinetic parameters may interfere in the characterization of cholinesterase inhibitors.

User engagement in mobile apps for people with schizophrenia: A scoping review.

Over the past decade, there has been an increase in the number of mobile apps designed for mental health proposes and mHealth has been perceived as a promising approach to help people with schizophrenia to manage their condition. However, adoption rates are relatively low and long-term user engagement is a major issue. The aim of this study is to identify and better understand what strategies and factors may influence user engagement and facilitate prolonged use of apps for people with schizophrenia to better manage their illness. A scoping review was conducted in accordance with the Arksey and O'Malley scoping review framework and following PRISMA ScR guidelines. The sources consisted of searching four electronic databases. Rayyan software was used for this study selection process and a narrative approach was used to synthesize the extracted data. A total of 28 studies which met the inclusion criteria were identified. The engagement strategies included push notifications, message prompts, personalization, application customization, goal setting, game-like features, use of different multimedia formats, social connectedness, support (peers and professionals), reliability of content and quality of feedback received. Some demographic factors may influence adherence such as age, gender, education level and socioeconomic status. Other factors also may play a role impacting engagement: health status, data privacy and security, involvement in design process, incentives for participation, app usage fitting in the user routines, initial training, and constant technical support. Included studies present high heterogeneity in outcome measures and thresholds criteria to assess engagement. Understanding what influences engagement and how to measure it is essential to enhance the design of mobile apps and deliver scalable solutions to help people with schizophrenia better manage their illness in their real-world uptake.

Validation of the Portuguese version of community attitudes toward people with mental illness (CAMI).

Abstract: Stigma remains a feature that influences the lifestyle of people with mental illness. Negative attitudes, stereotypes, and discrimination are still prevalent in these people's life. Stigma is considered a public health problem that occurs unconsciously in society, categorizing people. Portugal is the seventh-worst country concerning stigma in Mental Health. There have been few improvements in reducing stigma over time, and there is a great need to create investigations and validate instruments that measure stigma in the population. Aim: This study aims to address the gaps in the level of studies and normative instruments that measure the stigma of the Portuguese population in the face of mental illness. It, therefore, aims to adapt and validate community attitudes toward people with mental illness (CAMI) culturally and examine its psychometric properties. Method: The 27-item version of CAMI was translated and back-translated into English, which was analyzed and evaluated by a panel of experts. A sociodemographic survey and CAMI were applied in an online format, in which participated 427 adults representing the Portuguese population in general. Finally, the reliability and validity of the instrument were analyzed. Results: CAMI showed positive values of reliability and validity but not optimal. The confirmatory factor analysis values satisfactory values that indicate good quality of fit: x2/df=3.296; comparative fit index = 0.601; goodness of fit index = 0.817; and root mean square error of approximation = 0.073, indicates good quality of fit. Cronbach alpha was different for each factor, but it was positive. Spearman coefficient (ρ = -0.343) obtained a negative but consistent value. Conclusions: This study contributed to the achievement and validation of new measures to assess the stigma of the general population related to people with mental illness. We must continue to analyze this theme, complete the validation of this instrument, and understand the existing levels of stigma, its predominance in society, and the possible creation and implementation of new measures that support literacy in mental illness and anti-stigma.

Methylmalonic Acid Compromises Respiration and Reduces the Expression of Differentiation Markers of SH-SY5Y Human Neuroblastoma Cells.

Methylmalonic acidemia is a rare metabolic disorder caused by the deficient activity of l-methylmalonyl-CoA mutase or its cofactor 5-deoxyadenosylcobalamin and is characterized by accumulation of methylmalonic acid (MMA) and alternative metabolites. The brain is one of the most affected tissues and neurologic symptoms, characterized by seizures, mental retardation, psychomotor abnormalities, and coma, commonly appear in newborns. The molecular mechanisms of neuropathogenesis in methylmalonic acidemia are still poorly understood, specifically regarding the impairments in neuronal development, maturation, and differentiation. In this study, we investigated the effects of MMA in both undifferentiated and differentiated phenotypes of SH-SY5Y human neuroblastoma cells. We observed an increase in glucose consumption and reduction in respiratory parameters of both undifferentiated and differentiated cells after exposition to MMA, suggesting that differentiated cells are slightly more prone to perturbations in respiratory parameters by MMA than undifferentiated cells. Next, we performed qPCR of mature neuronal-specific gene markers and measured mitochondrial functioning to evaluate the role of MMA during differentiation. Our results showed that MMA impairs the respiratory parameters only at the late stage of differentiation and downregulates the transcriptional gene profile of mature neuronal markers neuron-specific enolase (ENO2) and synaptophysin (SYP). Altogether, our findings point out important changes observed during neuronal maturation and energetic stress vulnerability that can play a role in the neurological clinical symptoms at the newborn period and reveal important molecular mechanisms that could help the screening of targets to new approaches in the therapies of this disease.

Pharmacophore-based virtual screening and molecular docking to identify promising dual inhibitors of human acetylcholinesterase and butyrylcholinesterase.

The dual inhibition of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) plays an important role in Alzheimer's disease treatment. Thus, this study aims identify promising dual inhibitors against hAChE and hBuChE by in silico approaches (pharmacophore-based virtual screening and molecular docking). Ten 3 D pharmacophore models for dual inhibitors using default genetic parameters were built by GALAHAD™ available on SYBYL-X 2.0. Validation steps were carried out according to Energy (<100.0 kcal/mol), Pareto = 0, Area under the ROC Curve (>0.70), Boltzmann-Enhanced Discrimination of ROC curve (BEDROC >0.50) and structure-activity relationship (SAR) for known inhibitors. The best dual pharmacophore model based on internal/external statistical parameters and SAR data (one hydrogen bond acceptor, two hydrogen bond donors and four hydrophobic centers) was employed in virtual screening at Sigma-Aldrich® subset (n = 214,446) of ZINC database by UNITY module of SYBYL-X 2.0. According to superposition values (QFIT), the best ranked compounds were prioritized for molecular docking and partition coefficient analysis (clog p < 5.0). 37 top-ranked compounds (QFIT > 64.22) from pharmacophore model showed affinity in hAChE (-10.2 < Affinity energy < -6.3 kcal/mol) and hBuChE (-10.9 < Affinity energy < -2.3 kcal/mol) binding sites. Next, liposolubity prediction and commercially available showed that ZINC43198636, ZINC43198637 and ZINC00390718 can be potential dual inhibitors against hAChE and hBuChE.Communicated by Ramaswamy H. Sarma.

Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic?

BACKGROUND: Infection by nematodes is a problem for human health, livestock, and agriculture, as it causes deficits in host health, increases production costs, and incurs a reduced food supply. The control of these parasites is usually done using anthelmintics, which, in most cases, have not been fully effective. Therefore, the search for new molecules with anthelmintic potential is necessary. METHODS: In the present study, we isolated and characterized molecules from the nematophagous fungus Pochonia chlamydosporia and tested these compounds on three nematodes: Caenorhabditis elegans; Ancylostoma ceylanicum; and Ascaris suum. RESULTS: The ethyl acetate extract showed nematicidal activity on the nematode model C. elegans. We identified the major substance present in two sub-fractions of this extract as ketamine. Then, we tested this compound on C. elegans and the parasites A. ceylanicum and A. suum using hamsters and mice as hosts, respectively. We did not find a difference between the animal groups when considering the number of worms recovered from the intestines of animals treated with ketamine (6 mg) and albendazole (P > 0.05). The parasite burden of larvae recovered from the lungs of mice treated with ketamine was similar to those treated with ivermectin. CONCLUSIONS: The results presented here demonstrate the nematicidal activity of ketamine in vitro and in vivo, thus confirming the nematicidal potential of the molecule present in the fungus P. chlamydosporia may consist of a new method of controlling parasites.

Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives.

Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sources, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3-dipolar cycloaddition reactions with several azides afforded the derivatives 2-19 with yields in the range of 40-87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4-12.1 µM. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L. infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 µM, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51Li.

Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L.

Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22-24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1-21, 25-60) carrying different groups at C-28 previously reported by our group, and the results of their in vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50 = 9.7 µM), 4 (12 µM), 44 (11 µM) and 49 (2 µM), to prevent proliferation of intracellular amastigote forms of L. infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50 = 80 µM, SI = 0.1), make these compounds promising candidates for the treatment of leishmaniasis.