Exploring the risk factors for early-life sugar consumption: A birth cohort study.

BACKGROUND: Sugar consumption in early childhood is the primary cause of negative health outcomes, including early childhood caries. AIM: To investigate risk factors associated with early-life sugar consumption. DESIGN: Explanatory variables were collected at baseline of a birth cohort in Porto Alegre, Southern Brazil. At six months of age, data were collected on child feeding practices, including the number of foods and beverages containing sugar. Multivariate Poisson regression analysis with robust variance was performed. RESULTS: Virtually all children (98.3%) had consumed sugar by the age of 6 months. Multivariable analysis showed that the number of sweet items was significantly larger in children whose mothers were less than 20 years of age (MR = 1.19; 95% CI: 1.05-1.36), those from non-nuclear families (MR = 1.12; 95% CI: 1.04-1.20), those whose mothers had less than eight years of schooling (MR = 1.34; 95% CI: 1.20-1.50) and those whose mothers smoked (MR = 1.23; 95% CI: 1.13-1.35). Moreover, the number of sweet items was significantly lower among children who breastfed in the first hour of life (MR = 0.85; 95% CI: 0.76-0.95). CONCLUSION: Sugar consumption begins very early, especially in children with no access to breastfeeding in the first hours of life and those from younger, less educated, and smoking mothers.

Factors Associated with the Occurrence of Distoclusion in the Primary Dentition: A Hierarchical Analysis.

OBJECTIVE: The aim of the present study was to identify factors associated with the occurrence of distoclusion among preschool children in southern Brazil. STUDY DESIGN: A cross-sectional study was carried out with a sample of 1026 children aged two to five years enrolled at public preschools in the city of Canoas, Southern Brazil. Interviews were held with parents/caregivers to acquire demographic, socioeconomic and behavioral data. Six examiners who had undergone a training and calibration exercise performed the oral examinations. Distoclusion was recorded when the cusp of the maxillary canine was in an anterior relation to the distal surface of the mandibular canine during centric occlusion. Statistical analysis involved simple and multivariate Poisson regression with robust variance. RESULTS: The prevalence of distoclusion was 36.5% (375/1026). This condition was more frequent in younger children, those classified as white or brown, those who were breastfed for a shorter period of time, those who used a pacifier and those who were bottle fed. The multivariate analysis demonstrated that the likelihood of exhibiting distoclusion was greater among two-year-olds (P=0.038), three-year-olds (P=0.023), those classified as white (P=0.016), those who used a pacifier (P<0.001) and those who used to use a pacifier (P<0.001). CONCLUSION: Counseling with regard to the duration of pacifier use could contribute toward reducing the prevalence of distoclusion and its consequences in preschool children.

Generation of 3 patient induced Pluripotent stem cell lines containing SORD mutations linked to a recessive neuropathy.

The SORD neuropathy has been identified as the most common autosomal recessive inherited neuropathy, occurring in thousands of patients worldwide. Fibroblast lines from 3 different patients containing the c.753delG; p.Ala253GlnfsTer27 SORD mutations were reprogrammed into induced Pluripotent Stem Cell (iPSC) lines. These iPSC lines demonstrate an apparent normal karyotype and have positive expression of pluripotency markers. These iPSC lines also stain positively for Ectoderm, Endoderm and Mesoderm markers following Embryoid body differentiation. These lines pose to serve as a valuable disease modeling resource for studying the SORD neuropathy, including studying disease phenotype and treatment efficacy.

Strategies for the improvement of home medical waste management during the COVID-19 pandemic.

Home care services (HCS) are important to assist patients with difficulties in accessing conventional health services. Nevertheless, in times of COVID-19 pandemic, the traditionally offered service needs to be restructured to protect health professionals, patients and their families. In this context, this article aims to identify the impacts resulting from the COVID-19 pandemic on home medical waste management (MWM), converting threats into opportunities, and weaknesses into management strengths. Three months before the pandemic (from October to December), a comprehensive survey was conducted on the practices of home care services and MWM with health professionals, caregivers and patients in Caruaru (Brazil). Quali-quantitative information was collected by structured and semi-structured interviews. For evaluation, the SWOT-TOWS analysis was applied to identify the threats and weaknesses of the practices of HCS and MWM, and to propose strategies to ensure the protection of public health and the environment. The results showed that the main weaknesses found were the lack of training of health professionals and the lack of guidance given by them to caregivers of patients, both related to MWM. Except for sharp waste, all other MWM practices have proved to be inadequate, posing threats, especially in a pandemic period. Four action strategies to improve HCS and MWM were identified: (i) providing MWM training to HCS personnel based on ISO standards; (ii) providing MWM information to caregivers and patients; (iii) planning actions to optimize the service during the pandemic; and (iv) sharing HCS management with municipal decision makers. Between December 2020 and January 2021, semi-structured interviews were performed only with health professionals, to verify the impacts and changes that have occurred in HCS in the COVID-19 pandemic. Comparing the results of the two surveys, improvements were achieved, including the incorporation during the pandemic of some strategies identified in the first phase of the research.Implications: Home care service plays a fundamental role in the quality of life of patients and in the sustainability of the public health system in Brazil. In the pandemic period, HCS was impacted with routine changes and the adoption of new personal protective equipment. Our results showed the need to promote strategies to improve HCS to preserve the health of professionals and patients attended, in the pandemic and post-pandemic period. The strategies identified in the study contributed to improvements in the provision of the service and in the management of medical waste that is still inadequate. Such issues are of interest to municipal health management, which has adopted some of the suggested strategies. The thousands of HCS distributed in Brazilian municipalities can also adopt the strategic actions resulting from this research.

Correction to: A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids.

[This corrects the article DOI: 10.1007/s12195-020-00624-1.].

Human Tridimensional Neuronal Cultures for Phenotypic Drug Screening in Inherited Peripheral Neuropathies.

Length-dependent axonal degeneration is the pathologic hallmark of several neurodegenerative disorders, including inherited peripheral neuropathies (Charcot-Marie-Tooth (CMT) disease). CMT is currently an untreatable disorder. This is partially due to lack of translational models suitable for drug discovery. In vitro models of CMT have been hindered by the 2D configuration of neuronal cultures, which limits visualization and orientation of axons. To overcome these limitations, we cultured induced pluripotent stem cell (iPSC)-derived spinal motor neurons as 3D spheroids, which grow axons in a centrifugal fashion when plated. Using these iPSC-derived spinal spheroids, we demonstrate neurofilament deposits in motor neuron axons of three patients with CMT2E, caused by mutations in the NEFL gene. This phenotype is partially reversed by two kinase inhibitors. In summary, we developed a human tridimensional in vitro system that models length-dependent axonopathies, recapitulates key pathophysiologic features of CMT2E, and should facilitate the identification of new therapeutic compounds for CMT.

Participación social, un factor a considerar en la evaluación clínica del adulto mayor: una revisión narrativa.

Social participation is defined as the integration of people into community activities in voluntary or mandatory, formal and informal social groups, which could have consequences concerning the health of the older population. A search was conducted on Pubmed, Scielo, Scopus and Google Scholar. For this review, 16 articles studying the impact of social participation on older adults were analyzed, including a total of 73,698,096 individuals from North America, Asia, Europe, and Latin America. Social participation is considered a protective factor for the mental and physical health of older adults, which has been associated with decreases in disability, co-morbidities, and mortality. For this reason, it is suggested that it should be evaluated in clinical practice. This would make it possible to orient and refer older adults to participate in certain community organizations, mainly those who do not have support networks, who are not linked to community groups, who have symptoms of depression or who are beginning to show physical or cognitive deterioration. In this way, public health could increase its prevention and health promotion actions through community organizations. On the other hand, the lack of instruments and consensus to evaluate social participation was discussed in this review where a questionnaire to evaluate the social participation of the older adult has been proposed to be validated and studied in the future.

La participación social es definida como la integración de las personas a actividades de la comunidad en grupos sociales voluntarios u obligatorios, formales e informales, lo cual podría tener consecuencias en la salud de la población adulta mayor. Fue realizada una búsqueda en Pubmed, Scielo, Scopus y Google Scholar. Para esta revisión se analizaron 16 artículos que estudiaban el impacto de la participación social en adultos mayores, incluyendo un total de 73 698 096 individuos de Norteamérica, Asia, Europa, y América latina. La participación social es considerada como un factor protector para la salud mental y física de los adultos mayores, la cual ha sido asociada a disminuciones de la discapacidad, comorbilidades y mortalidad. Por esta razón, se sugiere que debe ser evaluada en la práctica clínica. Esto permitiría orientar y derivar a los adultos mayores a participar de determinadas organizaciones comunitarias, principalmente aquellos que no tienen redes de apoyo, que no están vinculados a grupos comunitarios, que tienen síntomas de depresión o que están iniciando un cuadro de deterioro físico o cognitivo. De este modo, la salud pública podría aumentar sus acciones de prevención y promoción de la salud por medio de las organizaciones comunitarias. Por otro lado, la falta de instrumentos y consensos para evaluar la participación social fue discutida en esta revisión donde se ha propuesto un cuestionario de evaluación de la participación social del adulto mayor que debe ser validado y estudiado en el futuro.

A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids.

INTRODUCTION: Multicellular platforms and linked multi organ on chip devices are powerful tools for drug discovery, and basic mechanistic studies. Often, a critical constraint is defining a culture medium optimal for all cells present in the system. In this study, we focused on the key cells of the neuromuscular junction i.e., skeletal muscle and motor neurons. METHODS: Formulation of a chemically defined medium for the co-culture of C2C12 skeletal muscle cells and human induced pluripotent stem cell (hiPSC) derived spinal spheroids (SpS) was optimized. C2C12 cells in 10 experimental media conditions and 2 topographies were evaluated over a 14-day maturation period to determine the ideal medium formulation for skeletal muscle tissue development. RESULTS: During early maturation, overexpression of genes for myogenesis and myopathy was observed for several media conditions, corresponding to muscle delamination and death. Together, we identified 3 media formulations that allowed for more controlled differentiation, healthier muscle tissue, and long-term culture duration. This evidence was then used to select media formulations to culture SpS and subsequently assessed axonal growth. As axonal growth in SpS cultures was comparable in all selected media conditions, our data suggest that the neuronal basal medium with no added supplements is the ideal medium formulation for both cell types. CONCLUSIONS: Optimization using both topographical cues and culture media formulations provides a comprehensive analyses of culture conditions that are vital to future applications for in vitro NMJ models.

Enzymatically crosslinked gelatin-laminin hydrogels for applications in neuromuscular tissue engineering.

We report a water-soluble and non-toxic method to incorporate additional extracellular matrix proteins into gelatin hydrogels, while obviating the use of chemical crosslinkers such as glutaraldehyde. Gelatin hydrogels were fabricated using a range of gelatin concentrations (4%-10%) that corresponded to elastic moduli of approximately 1 kPa-25 kPa, respectively, a substrate stiffness relevant for multiple cell types. Microbial transglutaminase was then used to enzymatically crosslink a layer of laminin on top of gelatin hydrogels, resulting in 2-component gelatin-laminin hydrogels. Human induced pluripotent stem cell derived spinal spheroids readily adhered and rapidly extended axons on GEL-LN hydrogels. Axons displayed a more mature morphology and superior electrophysiological properties on GEL-LN hydrogels compared to the controls. Schwann cells on GEL-LN hydrogels adhered and proliferated normally, displayed a healthy morphology, and maintained the expression of Schwann cell specific markers. Lastly, skeletal muscle cells on GEL-LN hydrogels achieved long-term culture for up to 28 days without delamination, while expressing higher levels of terminal genes including myosin heavy chain, MyoD, MuSK, and M-cadherin suggesting enhanced maturation potential and myotube formation compared to the controls. Future studies will employ the superior culture outcomes of this hybrid substrate for engineering functional neuromuscular junctions and related organ on a chip applications.

The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation.

Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1DeltaC) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1DeltaC were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.

Protein acetylation sites mediated by Schistosoma mansoni GCN5.

The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation.

Cloning of SmNCoA-62, a novel nuclear receptor co-activator from Schistosoma mansoni: assembly of a complex with a SmRXR1/SmNR1 heterodimer, SmGCN5 and SmCBP1.

The Schistosoma mansoni nuclear receptors (NR) SmRXR1 and SmNR1 have recently been shown to form a heterodimer and to bind to canonic hormone response DNA elements. Recruitment of co-regulatory proteins to NRs is required for their transcriptional and biological activities. Here, we cloned a novel S. mansoni NR co-activator, SmNCoA-62. SmNCoA-62 is highly homologous to the human Vitamin D receptor co-activator NCoA62/SKIP. SmNCoA-62 contains the SNW nuclear receptor interaction domain and a putative C-terminus transactivation domain. By using in vitro pull-down assays, we fully mapped the interaction domains of S. mansoni NR co-activators, SmNCoA-62, SmGCN5 and SmCBP1 with SmRXR1 and SmNR1, as well as the domains that mediate interactions amongst the co-activators themselves. By mutagenesis analysis, we showed that SmCBP1 LxxLL motif 2 and LxxLL motif 3, but not LxxLL motif 1, were essential to mediate the interactions of SmCBP1 with the EF domains of SmRXR1 and SmNR1. Histone acetyltransferases SmGCN5 and SmCBP1 specifically acetylated the C/D domains of SmRXR1 and SmNR1. In addition, two acetylation sites of SmNR1 were identified. SmGCN5 and SmCBP1 also acetylated SmNCoA-62 but with significant differences in their acetylation activities. Using gel shift analysis, we were able to demonstrate, in vitro, the assembly of the co-activators on the SmRXR1/SmNR1 heterodimer bound to DNA. LxxLL motifs 2 and 3 of SmCBP1 seemed to play a crucial role for the assembly of the co-activators to the DNA-bound SmRXR1/SmNR1 heterodimer.

Analysis of Myelinating Schwann Cells in Human Skin Biopsies.

The human skin is richly innervated by nerve fibers of different calibers and functions, including thickly myelinated large fibers that act as afferents for mechanoreceptors in the dermal papillae. Skin biopsies offer minimally invasive access to these myelinated fibers, in which each internode represents an individual myelinating Schwann cell. Using this approach, human myelinated nerve fibers can be analyzed by several methods, including immunostaining, morphometric and ultrastructural analysis, and molecular biology techniques. This analysis can reveal important aspects of human Schwann cell biology in health and disease, such as in the case of demyelinating neuropathies. This technique has revealed Schwann cell phenotypes in Charcot-Marie-Tooth disease type 1 and acquired inflammatory neuropathies.

The human motor neuron axonal transcriptome is enriched for transcripts related to mitochondrial function and microtubule-based axonal transport.

Local axonal translation of specific mRNA species plays an important role in axon maintenance, plasticity during development and recovery from injury. Recently, disrupted axonal mRNA transport and translation have been linked to neurodegenerative disorders. To identify mRNA species that are actively transported to axons and play an important role in axonal physiology, we mapped the axonal transcriptome of human induced pluripotent stem cell (iPSC)-derived motor neurons using permeable inserts to obtain large amounts of enriched axonal material for RNA isolation and sequencing. Motor neurons from healthy subjects were used to determine differences in gene expression profiles between neuronal somatodendritic and axonal compartments. Our results demonstrate that several transcripts were enriched in either the axon or neuronal bodies. Gene ontology analysis demonstrated enrichment in the axonal compartment for transcripts associated with mitochondrial electron transport, microtubule-based axonal transport and ER-associated protein catabolism. These results suggest that local translation of mRNAs is required to meet the high-energy demand of axons and to support microtubule-based axonal transport. Interestingly, several transcripts related to human genetic disorders associated with axonal degeneration (inherited axonopathies) were identified among the mRNA species enriched in motor axons.

hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis.

Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo. Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the formation of the neuro-angiogenic niche.

Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT.

Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico analysis reinforced previously reported anti-inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids.

A compreensão da enfermagem acerca do cuidado compartilhado à criança com condição crônica hospitalizada / Nursing's understanding of shared care for hospitalized children with a chronic condition / La comprensión de la enfermería sobre el cuidado compartido a niños hospitalizados con enfermedades crónicas

Objetivo: compreender a visão do profissional de enfermagem sobre o cuidado compartilhado entre equipe de enfermagem e o familiar da criança com condição crônica. Método: estudo qualitativo, descritivo, exploratório realizado numa enfermaria de pediatria de um Hospital Estadual Universitário do Rio de Janeiro, com 23 profissionais de enfermagem, sendo 5 enfermeiras e 18 técnicas de enfermagem. Os dados foram analisados com base na técnica de análise de conteúdo temática segundo Bardin. Resultados: apreenderam-se três categorias: Desafios na construção do cuidado compartilhado; Maneiras de promover o cuidado compartilhado e Benefícios do cuidado compartilhado. Evidenciam aspectos positivos e que precisam ser melhorados para que o cuidado compartilhado seja efetivo e maneiras de realizá-lo. Conclusão: os resultados deste estudo evidenciaram aspectos positivos e desafios na relação profissional-familiar para efetivo cuidado compartilhado, estes poderão contribuir para assistência da enfermagem de qualidade, evidenciando o aspecto educativo do cuidado, favorecendo a interação entre profissional e familiares.

Objective: to understand the Nursing profession's view of care shared between nursing teams and relatives/caregivers of children with a chronic condition. Method: this qualitative, descriptive, exploratory study involved 23 nursing personnel (5 nurses and 18 nursing technicians) in a pediatric unit of a state university hospital. Data were analyzed using Bardin thematic content analysis. Results: three categories were identified: Challenges in constructing shared care; Ways to promote shared care; and Benefits of shared care. They highlight both positive aspects to be improved so that shared care is effective and ways to achieve that. Conclusion: this study found positive aspects and challenges in the relationship between families and health personnel with a view to effective shared care. These can contribute to quality nursing care, highlight the educational aspect of care and favor interaction between health personnel and families.

Objetivo: comprender la perspectiva del profesional de enfermería acerca del cuidado compartido entre el equipo de enfermería y el familiar del niño con enfermedad crónica. Método: estudio cualitativo, descriptivo, exploratorio, realizado en una sala de enfermería pediátrica de un Hospital Universitario del Estado en Río de Janeiro, junto a 23 profesionales de enfermería: 5 enfermeros y 18 técnicos de enfermería. Los datos se analizaron mediante la técnica de análisis de contenido temático según Bardin. Resultados: se abordaron tres categorías: Desafíos en la construcción del cuidado compartido; Formas de promover la atención compartida y Beneficios de la atención compartida. Se presentan aspectos positivos que, sin embargo, necesitan mejoras para que el cuidado compartido sea eficaz y se muestran formas de hacerlo. Conclusión: los resultados de este estudio mostraron aspectos positivos y desafíos en la relación profesional-familia para un cuidado compartido eficaz, que pueden contribuir a una atención de enfermería de calidad, destacando el aspecto educativo del cuidado, favoreciendo la interacción entre el profesional y los familiares.

Inhibition of pRB Pathway Differentially Modulates Apoptosis in Esophageal Cancer Cells.

Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear. Most of these are alterations leading to up-regulation of the activity of cyclin-dependent kinases (CDKs) to phosphorylate pRB, which suggests that keeping the wild type pRB phosphorylated might be advantageous. Besides proliferation, pRB also regulates apoptosis induced by tumor necrosis factor-alpha (TNF-α) and DNA-damage. We investigated the status of phosphorylation of pRB along esophageal tumorigenesis stages, as well as whether hyperphosphorylation of pRB could suppress apoptosis induced by cisplatin, 5-FU, or TNF-α in esophageal cancer cells. pRB phosphorylation increased progressively from normal esophageal tissue to metaplasia and adenocarcinoma, suggesting that pRB phosphorylation increases along esophageal tumor stages. When RB-1 was knocked down or CDK inhibitors reduced the levels of phosphorylated pRB, opposite apoptotic effects were observed, depending on the combination of drugs tested: whereas TNF-α- and cisplatin-induced apoptosis increased, 5-FU-induced apoptosis decreased. Taken together, these data suggest that pRB plays a role in esophageal adenocarcinoma and that, depending on the type of anti-cancer treatment, combining CDK inhibitors and chemotherapy has the potential to increase the sensitivity of esophageal cancer cells to cell death.

Harmine stimulates proliferation of human neural progenitors.

Harmine is the ß-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Participación social, un factor a considerar en la evaluación clínica del adulto mayor: una revisión narrativa

RESUMEN La participación social es definida como la integración de las personas a actividades de la comunidad en grupos sociales voluntarios u obligatorios, formales e informales, lo cual podría tener consecuencias en la salud de la población adulta mayor. Fue realizada una búsqueda en Pubmed, Scielo, Scopus y Google Scholar. Para esta revisión se analizaron 16 artículos que estudiaban el impacto de la participación social en adultos mayores, incluyendo un total de 73 698 096 individuos de Norteamérica, Asia, Europa, y América latina. La participación social es considerada como un factor protector para la salud mental y física de los adultos mayores, la cual ha sido asociada a disminuciones de la discapacidad, comorbilidades y mortalidad. Por esta razón, se sugiere que debe ser evaluada en la práctica clínica. Esto permitiría orientar y derivar a los adultos mayores a participar de determinadas organizaciones comunitarias, principalmente aquellos que no tienen redes de apoyo, que no están vinculados a grupos comunitarios, que tienen síntomas de depresión o que están iniciando un cuadro de deterioro físico o cognitivo. De este modo, la salud pública podría aumentar sus acciones de prevención y promoción de la salud por medio de las organizaciones comunitarias. Por otro lado, la falta de instrumentos y consensos para evaluar la participación social fue discutida en esta revisión donde se ha propuesto un cuestionario de evaluación de la participación social del adulto mayor que debe ser validado y estudiado en el futuro.

ABSTRACT Social participation is defined as the integration of people into community activities in voluntary or mandatory, formal and informal social groups, which could have consequences concerning the health of the older population. A search was conducted on Pubmed, Scielo, Scopus and Google Scholar. For this review, 16 articles studying the impact of social participation on older adults were analyzed, including a total of 73,698,096 individuals from North America, Asia, Europe, and Latin America. Social participation is considered a protective factor for the mental and physical health of older adults, which has been associated with decreases in disability, co-morbidities, and mortality. For this reason, it is suggested that it should be evaluated in clinical practice. This would make it possible to orient and refer older adults to participate in certain community organizations, mainly those who do not have support networks, who are not linked to community groups, who have symptoms of depression or who are beginning to show physical or cognitive deterioration. In this way, public health could increase its prevention and health promotion actions through community organizations. On the other hand, the lack of instruments and consensus to evaluate social participation was discussed in this review where a questionnaire to evaluate the social participation of the older adult has been proposed to be validated and studied in the future.