Examining the effects of parental migration on youth mental health and substance use: a qualitative study in rural Yucatán, México.

Background: Parental migration is common in Mexico and Latin America, where individuals pursue work to improve their family's economic opportunities and children remain home in their community under the care of the remaining parent or extended family. A research gap remains about the impact of parental migration on mental health and substance use in children who remain at home. The current study explored risk and resilience factors relating to mental health and substance use among Mexican youth remaining at home when one or more parents migrate. Methods: This qualitative study applied attachment theory and thematic analysis to analyze 26 in-depth interviews with youth (17-21 years old), parents, and a focus group with high-school teachers in a town with history of migration both domestically and internationally (Yucatan, México). Results: Respondents across groups perceived that parental migration was related to 1) less parental/caregiver oversight and support due to family demands on the remaining parent and 2) the deterioration of youth mental health. Lack of youth oversight and the poor mental health of youth were perceived as drivers of youth seeking out and consuming alcohol and substances. In terms of parental remittances, youth reported observing among their peers increased access to material goods such as clothing and technology (e.g., smartphones) and increased access to alcohol. Resilience factors included parental awareness of the role of good communication with youth and teachers and youth access to and utilization of self-care resources such as mutual aid meetings for substance use recovery. Conclusion: Poor mental health and substance use among youth and parents were perceived to be related to parental absence, stressors on the remaining parent or family, and undermined healthy parent-child attachment. Youth themselves are a source of insight for recommendations on interventions to reduce youth isolation and substance use risk. We recommend the intentional engagement of youth in developing intervention research and tailoring evidence-based interventions to mitigate parental absence's impact and promote parent-child attachment for youth and families remaining at home.

Metabolic changes in the subtropical frog Boana pulchella during experimental cooling and recovery conditions.

Frogs have developed biochemical and physiological adaptations to occupy diverse ecological niches on Earth successfully. Survival in frozen states is a fascinating strategy made possible by evolving adaptations to produce cryoprotectant solutes. The hylid frog Boana pulchella thrives in South American regions with cold climates, remaining active while enduring sporadic subzero temperatures during winter. The species' metabolic changes during subzero exposure remain unclear. Therefore, we exposed B. pulchella to cooling and recovery, assessing plasma and tissue metabolite changes. Cooling significantly reduced urea concentrations in plasma (P = 0.033), muscle (P = 0.001), heart (P = 0.009), and brain (P = 0.041) compared to acclimation. Liver glucose oxidation and glycogen synthesis were lower in cooling and recovery than in acclimation (P < 0.0001 and P = 0.0117, respectively). Muscle glycogen synthesis was lower in recovery than acclimation (P = 0.0249). These results demonstrate B. pulchella's physiological strategies during subzero exposure, likely reflecting species-specific evolutionary adaptations for brief subzero exposures that enable winter survival in its natural habitat.

Thermostabilizing mechanisms of canonical single amino acid substitutions at a GH1 ß-glucosidase probed by multiple MD and computational approaches.

ß-glucosidases play a pivotal role in second-generation biofuel (2G-biofuel) production. For this application, thermostable enzymes are essential due to the denaturing conditions on the bioreactors. Random amino acid substitutions have originated new thermostable ß-glucosidases, but without a clear understanding of their molecular mechanisms. Here, we probe by different molecular dynamics simulation approaches with distinct force fields and submitting the results to various computational analyses, the molecular bases of the thermostabilization of the Paenibacillus polymyxa GH1 ß-glucosidase by two-point mutations E96K (TR1) and M416I (TR2). Equilibrium molecular dynamic simulations (eMD) at different temperatures, principal component analysis (PCA), virtual docking, metadynamics (MetaDy), accelerated molecular dynamics (aMD), Poisson-Boltzmann surface analysis, grid inhomogeneous solvation theory and colony method estimation of conformational entropy allow to converge to the idea that the stabilization carried by both substitutions depend on different contributions of three classic mechanisms: (i) electrostatic surface stabilization; (ii) efficient isolation of the hydrophobic core from the solvent, with energetic advantages at the solvation cap; (iii) higher distribution of the protein dynamics at the mobile active site loops than at the protein core, with functional and entropic advantages. Mechanisms i and ii predominate for TR1, while in TR2, mechanism iii is dominant. Loop A integrity and loops A, C, D, and E dynamics play critical roles in such mechanisms. Comparison of the dynamic and topological changes observed between the thermostable mutants and the wildtype protein with amino acid co-evolutive networks and thermostabilizing hotspots from the literature allow inferring that the mechanisms here recovered can be related to the thermostability obtained by different substitutions along the whole family GH1. We hope the results and insights discussed here can be helpful for future rational approaches to the engineering of optimized ß-glucosidases for 2G-biofuel production for industry, biotechnology, and science.

A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers.

The main-protease (Mpro) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (MCoV2pro) with 12 mutations compared to SARS-CoV (MCoV1pro). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications. We use metadynamics simulations and a sort of computational analysis to probe the dynamic, pharmacophoric and catalytic environment differences between the monomers of both enzymes. So, we verify how much intrinsic distinctions are preserved in the functional dimer of MCoV2pro, as well as its implications for ligand accessibility and optimized drug screening. We find a significantly higher accessibility to open binding conformers in the MCoV2pro monomer compared to MCoV1pro. A higher hydration propensity for the MCoV2pro S2 loop with the A46S substitution seems to exercise a key role. Quantum calculations suggest that the wider conformations for MCoV2pro are less catalytically active in the monomer. However, the statistics for contacts involving the N-finger suggest higher maintenance of this activity at the dimer. Docking analyses suggest that the ability to vary the active site width can be important to improve the access of the ligand to the active site in different ways. So, we carry out a multiconformational virtual screening with different ligand bases. The results point to the importance of taking into account the protein conformational multiplicity for new promissors anti MCoV2pro ligands. We hope these results will be useful in prospecting, repurposing and/or designing new anti SARS-CoV-2 drugs.Communicated by Ramaswamy H. Sarma.

Propedia: a database for protein-peptide identification based on a hybrid clustering algorithm.

BACKGROUND: Protein-peptide interactions play a fundamental role in a wide variety of biological processes, such as cell signaling, regulatory networks, immune responses, and enzyme inhibition. Peptides are characterized by low toxicity and small interface areas; therefore, they are good targets for therapeutic strategies, rational drug planning and protein inhibition. Approximately 10% of the ethical pharmaceutical market is protein/peptide-based. Furthermore, it is estimated that 40% of protein interactions are mediated by peptides. Despite the fast increase in the volume of biological data, particularly on sequences and structures, there remains a lack of broad and comprehensive protein-peptide databases and tools that allow the retrieval, characterization and understanding of protein-peptide recognition and consequently support peptide design. RESULTS: We introduce Propedia, a comprehensive and up-to-date database with a web interface that permits clustering, searching and visualizing of protein-peptide complexes according to varied criteria. Propedia comprises over 19,000 high-resolution structures from the Protein Data Bank including structural and sequence information from protein-peptide complexes. The main advantage of Propedia over other peptide databases is that it allows a more comprehensive analysis of similarity and redundancy. It was constructed based on a hybrid clustering algorithm that compares and groups peptides by sequences, interface structures and binding sites. Propedia is available through a graphical, user-friendly and functional interface where users can retrieve, and analyze complexes and download each search data set. We performed case studies and verified that the utility of Propedia scores to rank promissing interacting peptides. In a study involving predicting peptides to inhibit SARS-CoV-2 main protease, we showed that Propedia scores related to similarity between different peptide complexes with SARS-CoV-2 main protease are in agreement with molecular dynamics free energy calculation. CONCLUSIONS: Propedia is a database and tool to support structure-based rational design of peptides for special purposes. Protein-peptide interactions can be useful to predict, classifying and scoring complexes or for designing new molecules as well. Propedia is up-to-date as a ready-to-use webserver with a friendly and resourceful interface and is available at: https://bioinfo.dcc.ufmg.br/propedia.

VTR: A Web Tool for Identifying Analogous Contacts on Protein Structures and Their Complexes.

Evolutionarily related proteins can present similar structures but very dissimilar sequences. Hence, understanding the role of the inter-residues contacts for the protein structure has been the target of many studies. Contacts comprise non-covalent interactions, which are essential to stabilize macromolecular structures such as proteins. Here we show VTR, a new method for the detection of analogous contacts in protein pairs. The VTR web tool performs structural alignment between proteins and detects interactions that occur in similar regions. To evaluate our tool, we proposed three case studies: we 1) compared vertebrate myoglobin and truncated invertebrate hemoglobin; 2) analyzed interactions between the spike protein RBD of SARS-CoV-2 and the cell receptor ACE2; and 3) compared a glucose-tolerant and a non-tolerant ß-glucosidase enzyme used for biofuel production. The case studies demonstrate the potential of VTR for the understanding of functional similarities between distantly sequence-related proteins, as well as the exploration of important drug targets and rational design of enzymes for industrial applications. We envision VTR as a promising tool for understanding differences and similarities between homologous proteins with similar 3D structures but different sequences. VTR is available at http://bioinfo.dcc.ufmg.br/vtr.

A transnational approach to understanding indicators of mental health, alcohol use and reproductive health among indigenous mexican migrants.

The three studies presented in this Special Topics in Immigrant Health report findings from a novel transnational, mixed-methods study with indigenous Mayans in Yucatán, Mexico, and their satellite communities in Southern California. Indigenous migrants comprise the largest proportion of recent, first-time migrants from Mexico to the United States and are among the migrant populations most vulnerable to discrimination (e.g. work place) and health disparities. The studies presented focus on three topics: perceived discrimination and mental health among indigenous migrants and non-migrants, risky alcohol use behaviors associated with migration to the U.S. and within Mexico, and gendered power dynamics related to sexual health care access and utilization. This transnational research sheds new light on health issues and gender differences affecting indigenous Mexican migrant men, women and their families. Findings can serve to inform intervention research to improve migrant health in the U.S. and Mexico as well as transnational collaboration between countries.

Helicobacter pylori: una década de controversias / Helicobacter pylori: a decade of controversies

El Helicobacter Pylori es un bacilo Gram (-) que coloniza la mucosa gástrica, adherido a su epitelio de revestimiento y recubierto por el mucus luminal. Su cultivo se comunica por primera vez en Lancet, junio 1993. Desde entonces, más de 2000 publicaciones se han ocupado de su participación en la etiopatogenia de la gastritis crónica tipo B, úlcera péptica, cáncer gástrico y dispepsia no ulcerosa, junto a su presencia en otras enfermedades. La vía de infección más probable es la oro-fecal, con una mayor incidencia en las poblaciones de niveles socio-económicos bajos. Las tasas de prevalencia son muy altas en la población general de los países en vías de desarrollo. El papel que pudiera desempeñar en las enfermedades señaladas es motivo de controversias: ¿asociación o factor patógeno? Su erradicación con diversos esquemas de tratamiento, determina una marcada disminución en las recidivas de la úlcera péptica, mientras que los riesgos de reinfección son variables: muy bajos en países industrializados y altos en áreas geográficas más pobres. La información disponible no aconseja erradicar Helicobacter Pylori en grandes grupos de población para reducir la incidencia de cáncer gástrico. La adopción de esta conducta necesita su ánalisis individual en los pacientes con enfermedad ulcerosa. Se requieren mayores estudios nacionales para precisar la importancia clínica y epidemiológica del Helicobacter Pylori en Chile

Paracentesis diagnóstica: nuevos aportes de un antiguo procedimiento / Diagnostic paracentesis: new contributions of an old procedure

La paracentesis diagnóstica es un procedimiento inocuo que proporciona novedosos e importantes elementos para el estudio del síndrome ascítico. La clásica división en exudados y transudados, parece estar perdiendo vigencia. La gradiente de albúmina suero/ascitis, representa una ayuda importante al diagnóstico etiológico de las ascitis. Otros parámetros del líquido, a veces comparados con sus niveles en el suero, serían de menor utilidad. Se exponen algunas generalidades de las infecciones del líquido ascítico, estableciendo los elementos de mayor ayuda para el diagnóstico de peritonitis bacteriana espontánea, peritonitis bacteriana secundaria y bacterioascitis. Se analizan algunos factores que predisponen a la recurrencia de la peritonitis bacteriana espontánea y se reseña un algoritmo aplicable al diagnóstico diferencial de las infecciones del líquido ascítico. Se enumeran algunas recomendaciones para la toma de muestra en la paracentesis diagnóstica, especialmente en aquellos pacientes en los que se sospecha una carcinomatosis peritoneal

Citoprotección gastroduodenal: concepto y aplicaciones / Gastroduodenal cytoprotection: concepts and applications

La mucosa gastroduodenal posee un conjunto de mecanismos fisiológicos, encargados de su protección frente a la acción de agentes agresivos endógenos o exógenos. Las prostaglandinas participan activamente en la regulación de estos recursos, cuyo incremento constituye la base de los mecanismos de citoprotección. Mayor citoprotección de la mucosa gastroduodenal se puede alcanzar por estimulación de la síntesis de prostaglandinas o mediante su administración en forma de análogos metilados. También se han identificado otras sustancias con efecto citoprotector tales como el factor de crecimiento epidérmico; algunos antiácidos, antioxidantes, sucralfato, etc. La experiencia alcanzada con ellos en animales de experimentación se proyecta al hombre, en quien se han iniciado ensayos clínicos destinados a objetivar sus beneficios. Actualmente la citoprotección aparece como una alternativa interesante en la búsqueda reiterada de recursos dirigidos a suprimir la acción de factores agresivos, en el manejo de las lesiones agudas o crónicas de la mucosa gastroduodenal

Tratamiento médico de la úlcera péptica: ¿nuevas alternativas? / Medical treatment of peptic ulcer: new perspectives?

La úlcera péptica es una enfermedad crónica y frecuente. De origen multifactorial, obedece a un desbalance entre factores agresivos y defensivos de la mucosa gastroduodenal. Su tratamiento médico se fundamenta en reducir la concentración de HCI en el jugo gástrico, empleando fármacos que interfieren alguna de las fases de producción ácida por la célula parietal: bloqueadores de sus receptores, de mediadores intracelulares o de la bomba de protones. Se señalan las dosis y formas de administración de estos preparados, junto con destacar sus principales efectos adversos. Como alternativa, los mecanismos defensivos se pueden reforzar mediante drogas capaces de estimular la integridad de la barrera mucosa. La úlcera refractaria, se puede tratar con varios esquemas. Las dosis de mantención reducen las recidivas sintomáticas de la enfermedad. Se analiza el rol de algunos factores ambientales que intervienen en la patogenia y curso evolutivo de la enfermedad ulcerosa junto a la forma de reducir su importancia