Digital Educational Game "O Jardim do Ferro": A Tool for the Prevention of Iron Deficiency Anemia in Childhood.

Objective: To create and evaluate a digital educational game (DEG) for preschool children for the prevention of iron deficiency and iron deficiency anemia. Methodology: The DEG software was developed by a multidisciplinary team, according to Chandler's methodology, in Engine Unity. The game is a 2D platformer, for Android, with three different phases. A quiz was developed for parents/caregivers about iron absorption and anemia. The quiz content was evaluated by experts. The evaluation of the game was carried out through a questionnaire applied in the school for children from 4 to 6 years of age. Results: For the construction of the game, programming, team planning, art, and soundtrack were necessary. The game was registered at the National Institute of Industrial Property. The quiz was evaluated by 14 experts and all questions had more than 80% agreement. The questionnaire was answered by 32 children with a mean age of 5.0 ± 0.7 years, and ∼70% evaluated the game positively. Thus, the acceptability of the software was favored by most players. Conclusion: The "O Jardim do Ferro" software, from its conception to evaluation, proved to be a promising tool to contribute to food and nutrition education actions, providing opportunities for the construction of knowledge about iron-rich foods for the prevention of iron deficiency and iron deficiency anemia in childhood.

Tools of genomic medicine for clinical practice: The example of psychiatry. / Herramientas de la medicina genómica para la práctica clínica: el ejemplo de la psiquiatría.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.

Herramientas de la medicina genómica para la práctica clínica: el ejemplo de la psiquiatría / Tools of genomic medicine for clinical practice: The example of psychiatry

La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

Non-Chinese herbal medicines for functional dyspepsia.

BACKGROUND: One-third of people with gastrointestinal disorders, including functional dyspepsia, use some form of complementary and alternative medicine, including herbal medicines. OBJECTIVES: The primary objective is to assess the effects of non-Chinese herbal medicines for the treatment of people with functional dyspepsia. SEARCH METHODS: We searched the following electronic databases on 22 December 2022: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Allied and Complementary Medicine Database, Latin American and Caribbean Health Sciences Literature, among other sources, without placing language restrictions. SELECTION CRITERIA: We included RCTs comparing non-Chinese herbal medicines versus placebo or other treatments in people with functional dyspepsia. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references, extracted data and assessed the risk of bias from trial reports. We used a random-effects model to calculate risk ratios (RRs) and mean differences (MDs). We created effect direction plots when meta-analysis was not possible, following the reporting guideline for Synthesis without Meta-analysis (SWiM). We used GRADE to assess the certainty of the evidence (CoE) for all outcomes. MAIN RESULTS: We included 41 trials with 4477 participants that assessed 27 herbal medicines. This review evaluated global symptoms of functional dyspepsia, adverse events and quality of life; however, some studies did not report these outcomes. STW5 (Iberogast) may moderately improve global symptoms of dyspepsia compared with placebo at 28 to 56 days; however, the evidence is very uncertain (MD -2.64, 95% CI -4.39 to -0.90; I2 = 87%; 5 studies, 814 participants; very low CoE). STW5 may also increase the improvement rate compared to placebo at four to eight weeks' follow-up (RR 1.55, 95% CI 0.98 to 2.47; 2 studies, 324 participants; low CoE). There was little to no difference in adverse events for STW5 compared to placebo (RR 0.92, 95% CI 0.52 to 1.64; I2 = 0%; 4 studies, 786 participants; low CoE). STW5 may cause little to no difference in quality of life compared to placebo (no numerical data available, low CoE). Peppermint and caraway oil probably result in a large improvement in global symptoms of dyspepsia compared to placebo at four weeks (SMD -0.87, 95% CI -1.15 to -0.58; I2 = 0%; 2 studies, 210 participants; moderate CoE) and increase the improvement rate of global symptoms of dyspepsia (RR 1.53, 95% CI 1.30 to 1.81; I2 = 0%; 3 studies, 305 participants; moderate CoE). There may be little to no difference in the rate of adverse events between this intervention and placebo (RR 1.56, 95% CI 0.69 to 3.53; I2 = 47%; 3 studies, 305 participants; low CoE). The intervention probably improves the quality of life (measured on the Nepean Dyspepsia Index) (MD -131.40, 95% CI -193.76 to -69.04; 1 study, 99 participants; moderate CoE). Curcuma longa probably results in a moderate improvement global symptoms of dyspepsia compared to placebo at four weeks (MD -3.33, 95% CI -5.84 to -0.81; I2 = 50%; 2 studies, 110 participants; moderate CoE) and may increase the improvement rate (RR 1.50, 95% CI 1.06 to 2.11; 1 study, 76 participants; low CoE). There is probably little to no difference in the rate of adverse events between this intervention and placebo (RR 1.26, 95% CI 0.51 to 3.08; 1 study, 89 participants; moderate CoE). The intervention probably improves the quality of life, measured on the EQ-5D (MD 0.05, 95% CI 0.01 to 0.09; 1 study, 89 participants; moderate CoE). We found evidence that the following herbal medicines may improve symptoms of dyspepsia compared to placebo: Lafonesia pacari (RR 1.52, 95% CI 1.08 to 2.14; 1 study, 97 participants; moderate CoE), Nigella sativa (SMD -1.59, 95% CI -2.13 to -1.05; 1 study, 70 participants; high CoE), artichoke (SMD -0.34, 95% CI -0.59 to -0.09; 1 study, 244 participants; low CoE), Boensenbergia rotunda (SMD -2.22, 95% CI -2.62 to -1.83; 1 study, 160 participants; low CoE), Pistacia lenticus (SMD -0.33, 95% CI -0.66 to -0.01; 1 study, 148 participants; low CoE), Enteroplant (SMD -1.09, 95% CI -1.40 to -0.77; 1 study, 198 participants; low CoE), Ferula asafoetida (SMD -1.51, 95% CI -2.20 to -0.83; 1 study, 43 participants; low CoE), ginger and artichoke (RR 1.64, 95% CI 1.27 to 2.13; 1 study, 126 participants; low CoE), Glycyrrhiza glaba (SMD -1.86, 95% CI -2.54 to -1.19; 1 study, 50 participants; moderate CoE), OLNP-06 (RR 3.80, 95% CI 1.70 to 8.51; 1 study, 48 participants; low CoE), red pepper (SMD -1.07, 95% CI -1.89 to -0.26; 1 study, 27 participants; low CoE), Cuadrania tricuspidata (SMD -1.19, 95% CI -1.66 to -0.72; 1 study, 83 participants; low CoE), jollab (SMD -1.22, 95% CI -1.59 to -0.85; 1 study, 133 participants; low CoE), Pimpinella anisum (SMD -2.30, 95% CI -2.79 to -1.80; 1 study, 107 participants; low CoE). The following may provide little to no difference compared to placebo: Mentha pulegium (SMD -0.38, 95% CI -0.78 to 0.02; 1 study, 100 participants; moderate CoE) and cinnamon oil (SMD 0.38, 95% CI -0.17 to 0.94; 1 study, 51 participants; low CoE); moreover, Mentha longifolia may increase dyspeptic symptoms (SMD 0.46, 95% CI 0.04 to 0.88; 1 study, 88 participants; low CoE). Almost all the studies reported little to no difference in the rate of adverse events compared to placebo except for red pepper, which may result in a higher risk of adverse events compared to placebo (RR 4.31, 95% CI 1.56 to 11.89; 1 study, 27 participants; low CoE). With respect to the quality of life, most studies did not report this outcome. When compared to other interventions, essential oils may improve global symptoms of dyspepsia compared to omeprazole. Peppermint oil/caraway oil, STW5, Nigella sativa and Curcuma longa may provide little to no benefit compared to other treatments. AUTHORS' CONCLUSIONS: Based on moderate to very low-certainty evidence, we identified some herbal medicines that may be effective in improving symptoms of dyspepsia. Moreover, these interventions may not be associated with important adverse events. More high-quality trials are needed on herbal medicines, especially including participants with common gastrointestinal comorbidities.

Posibles mecanismos de acción de la terapia electroconvulsiva en trastornos afectivos: revisión de la evidencia disponible en investigación con seres humanos

The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1β). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.

Estudio prospectivo descriptivo de las trayectorias de respuesta terapéutica en una cohorte de pacientes con trastorno depresivo mayor

Introducción: El trastorno depresivo mayor (TDM) constituye un problema de salud pública por su alta prevalencia y consecuencias biopsicosociales. Es un desorden clínicamente heterogéneo, complejo y de curso fluctuante. En Chile, no existen estudios sobre trayectorias terapéuticas en TDM. Objetivo: Describir las trayectorias de respuesta clínica en pacientes con TDM en tratamiento en centros de Atención Primaria de Salud (APS) en Chile. Método: Estudio de cohorte prospectiva de cinco meses de seguimiento. Se incluyeron pacientes ingresados en el Programa de Garantías Explícitas en Salud de Depresión de siete centros de APS de la Región de Valparaíso, Chile. Se realizaron cuatro evaluaciones (semanas 0, 4, 12 y 20) para describir variables clínicas y sociodemográficas relacionadas con la evolución. Se elaboraron trayectorias de respuesta en relación con el curso de los síntomas depresivos. Resultados: Se incluyeron 159 participantes (93% fueron mujeres), con un promedio de 43 años de edad. Las condiciones de riesgo para TDM más frecuentemente reportadas fueron el aislamiento social o la escasa red de apoyo y haber presenciado violencia intrafamiliar durante la infancia. Se obtuvo 12 trayectorias de respuesta de un total de 16 patrones posibles. Se observan diferencias al analizar las respuestas terapéuticas entre las semanas 0 y 12 y 0 y 20. Las trayectorias más frecuentes fueron el mantenimiento o empeoramiento de la sintomatología depresiva (37,7%). Conclusiones: Los resultados muestran una variabilidad sintomática durante el transcurso de un TDM. En este seguimiento de cinco meses, más de un tercio de las participantes no mejoraron sus síntomas depresivos.

Introduction: Major depressive disorder (MDD) is a public health problem due to its high prevalence and biopsychosocial consequences. It is a clinically heterogeneous and complex disorder with a fluctuating course. In Chile, there are no studies on clinical trajectories in MDD. Objective: To describe the clinical response trajectories in patients with MDD under treatment in primary care centers (PCC) in Chile. Method: We conducted a prospective cohort study with a five-month follow-up, including patients treated in the Explicit Guarantees in Healthcare program for depression at seven PCC in the Valparaíso Region, Chile. We carried out four evaluations (weeks 0, 4, 12 and 20) to describe various clinical and sociodemographic variables related to the therapeutic evolution. We elaborated response trajectories in relation to the course of depressive symptoms. Results: 159 participants were included (93% women), with an average age of 43 years old. The most frequently reported risk conditions for MDD were social isolation or poor support network and having witnessed domestic violence during childhood. Twelve response trajectories were obtained from a total of 16 possible patterns. Differences were observed when analyzing the therapeutic responses between weeks 0 and 12 and 0 and 20. The most frequent trajectories were the maintenance or worsening of depressive symptoms (37.7%). Conclusions: The results show a symptomatic variability during the course of MDD. In this five-month follow-up, more than a third of the participants did not improve their depressive symptoms.

[Putative mechanisms of action of electronvulsive therapy in affective disorders, a review]. / Posibles mecanismos de acción de la terapia electroconvulsiva en trastornos afectivos: revisión de la evidencia disponible en investigación con seres humanos.

The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1ß). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.

Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos / A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

Secondary respiratory early and late infections in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with COVID-19 receiving mechanical ventilation may become aggravated with a secondary respiratory infection. The aim of this study was to describe secondary respiratory infections, their predictive factors, and outcomes in patients with COVID-19 requiring mechanical ventilation. METHODS: A cohort study was carried out in a single tertiary hospital in Santiago, Chile, from 1st June to 31st July 2020. All patients with COVID-19 admitted to the intensive care unit that required mechanical ventilation were included. RESULTS: A total of 175 patients were enrolled, of which 71 (40.6%) developed at least one secondary respiratory infection during follow-up. Early and late secondary infections were diagnosed in 1.7% and 31.4% respectively. Within late secondary infections, 88% were bacterial, 10% were fungal, and 2% were of viral origin. One-third of isolated bacteria were multidrug-resistant. Bivariate analysis showed that the history of corticosteroids used before admission and the use of dexamethasone during hospitalization were associated with a higher risk of secondary infections (p = 0.041 and p = 0.019 respectively). Multivariate analysis showed that for each additional day of mechanical ventilation, the risk of secondary infection increases 1.1 times (adOR = 1.07; 95% CI 1.02-1.13, p = 0.008) CONCLUSIONS: Patients with COVID-19 admitted to the intensive care unit and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay. The number of days on MV was a risk factor for acquiring secondary respiratory infections.

Aspectos neurobiológicos en la toma de decisiones afectivas y sociales e influencia del estrés: posibles implicancias en la toma de decisiones clínicas / Neurobiological aspects in affective and social decision-making: possible implications on clinical decision-making

RESUMEN: La toma de decisiones está influenciada por múltiples factores muchas veces no conscientes. En este artículo se sintetizan algunos correlatos neurobiológicos del componente afectivo y social sobre la toma de decisiones, incluyendo el impacto del estrés agudo y crónico y la perspectiva cognitiva de las heurísticas y los sesgos en la práctica clínica. A nivel afectivo, la hipótesis del marcador somático ha asociado la respuesta corporal periférica con estructuras nerviosas centrales en la configuración de las decisiones; intervienen estructuras como la corteza orbitofrontal y el hipocampo. En la toma de decisiones sociales se involucran las dimensiones recompensa y motivación. En este tipo de decisiones es crucial la capacidad de mentalizar a otro e integrar su perspectiva en la toma de decisiones. Esta función se ha relacionado con el surco temporal posterosuperior, la unión temporoparietal, la corteza cingulada anterior y la corteza prefrontal medial. No obstante, en la toma de decisiones sociales también se integra el cumplimiento de normas socialmente establecidas. El estrés agudo o crónico puede afectar la toma de decisiones, positiva o negativamente. En estos procesos se han involucrado al eje hipotálamo-hipófiso-adrenal junto con circuitos corticoestriados, prefrontales, amigdalinos e hipocampales. En la toma de decisiones clínicas se conjugan factores "prerreflexivos" emocionales, sociales y cognitivos que influyen directamente en las conductas adoptadas con los pacientes. Recomendamos enfatizar la investigación en esta área y fortalecer su enseñanza para reconocerlos adecuadamente.

ABSTRACT Decision-making is influenced by multiple unaware factors. We synthesize some neurobiological correlates of the affective and social components on decision-making, including the impact of acute and chronic stress. We also address the impact of heuristics and biases on clinical practice from the cognitive perspective. At an affective level, the hypothesis of the somatic marker has associated the peripheral body response with central nervous structures in the configuration of decisions; structures such as the orbitofrontal cortex and the hippocampus intervene. The reward and motivation dimensions are involved in social decision-making. In these types of decisions, the ability to mentally engage others and integrate their perspective into decision making is crucial. This function has been related to the posterior superior temporal sulcus, the temporoparietal junction, the anterior cingulate cortex, and the medial prefrontal cortex. However, compliance with socially established norms is also integrated into social decision-making. Acute or chronic stress may affect decision-making, positively or negatively. The hypothalamic-pituitary-adrenal axis has been involved in these processes together with corticostriatal, prefrontal, amygdala and hippocampal circuits. In clinical decision-making, "pre-reflective" emotional, social and cognitive factors are combined, influencing the decisions towards patients. We recommend emphasizing research in this field and strengthening education in this area to recognize these aspects adequately.

[A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research]. / Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos.

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

Diet and depressive disorders

ABSTRACT Background: The importance of foods or food constituents in mental health is increasingly recognized, and "nutritional psychiatry" is a growing discipline. Objective: This narrative review aims to present work supporting associations between food or food constituents and mental health, specifically depressive disorders. Methods: The data presented is derived from preclinical and clinical work, including in vitro and in vivo assays, as well as observational studies and randomized clinical trials of dietary interventions. The focus of the review is the mediation of inflammatory processes and oxidative stress by dietary constituents that are an integral part of a healthy diet, such as the Mediterranean diet and similar. Results and Discussion: We present evidence for the role of the diet in prevention and management of depressive disorders, beyond the effect of individual nutrients. The findings indicate that among the dietary components with higher degree of evidence to influence depressive disorders are long chain n-3 polyunsaturated fatty acids (EPA and DHA), and various dietary bioactive compounds, especially plant-derived secondary metabolites represented by polyphenols such as flavonoids and resveratrol. Conclusion: Diet exerts an important role on mental health, and evidence indicates that some dietary constituents contribute to the prevention of depressive disorders.

A pilot trial of human amniotic fluid for the treatment of COVID-19.

OBJECTIVE: Vertical transmission from SARS CoV-2-infected women is uncommon and coronavirus has not been detected in amniotic fluid. Human amniotic products have a broad immune-mediating profile. Observing that many COVID-19 patients have a profound inflammatory response to the virus, we sought to determine the influence of human amniotic fluid (hAF) on hospitalized patients with COVID-19. RESULTS: A 10-patient case series was IRB-approved to study the impact of hAF on hospitalized patients with documented COVID-19. Nine of the 10 patients survived to discharge, with one patient succumbing to the disease when enrolled on maximal ventilatory support and severe hypoxia. The study design was altered by the IRB such that the last 6 patients received higher dose of intravenous hAF. In this latter group, patients that had observed reductions in C-reactive protein were associated with improved clinical outcomes. No hAF-related adverse events were noted. Acknowledging some of the inherent limitations of this case series, these results inform and catalyze a larger scaled randomized prospective trial to further investigate hAF as a therapy for COVID-19. Trial Registration ClinicalTrials.gov: NCT04319731; March 23, 2020.

Gender, women and scientific research. / Género, mujeres e investigación científica.

Gender is a psychosocial construct referring to the socially built roles, behaviors, expressions and identities of girls, women, boys, men and people with gender diversity, while sex is related to the biological attributes of a woman or a man. Even though the terms sex and gender are often used in a binary way, there is considerable diversity in the way individuals and groups understand, experiment and express them. This narrative review describes some relevant aspects of the subjective difference that exists and favors men over women in the fields of sciences and research, starting from a historical perspective in the light of feminist movements. In particular, women are described as researchers - crea-tors of scientific knowledge, as well as the subjects of analysis. Some conflicts arising from sex bias, applied to biomedical research, are also analyzed, and cases are delivered that exemplify the disarray that has historically accompanied the female gender in this area, its ignorance and little cultural recognition. This review is the last article in a methodological series on general concepts in biostatistics and clinical epidemiology developed by the Chair of Methodology of Scientific Research of the School of Medicine of the Universidad de Valparaiso, Chile, which aims to address a contingent and cross-cutting theme to all scientific research.

El género es una construcción psicosocial referida a los roles, comportamientos, expresiones e identidades socialmente construidos de niñas, mujeres, niños, hombres y personas con diversidad de género, mientras que el sexo se relaciona con los atributos biológicos de una mujer o un hombre. Aun cuando los términos “sexo” y “género” suelen utilizarse de forma binaria, existe una diversidad considerable en la forma en que los individuos y los grupos los entienden, experimentan y expresan. En esta revisión narrativa se describen algunos aspectos relevantes acerca de la diferencia subjetiva que existe y favorece a los hombres frente a las mujeres en el ámbito de las ciencias e investigación, iniciando desde una perspectiva histórica a la luz de los movimientos feministas. En particular, se describe a la mujer en cuanto investigadora y creadora de conocimiento científico, como también en su calidad de sujeto de análisis. Se analizan además algunos conflictos derivados del sesgo de sexo aplicados a la investigación biomédica, y se entregan casos que ejemplifican el desmedro que ha acompañado históricamente al género femenino en este ámbito, su desconocimiento y poco reconocimiento cultural. Esta revisión es la última entrega de una serie metodológica sobre conceptos generales en bioestadística y epidemiología clínica desarrollada por la Cátedra de Metodología de la Investigación Científica de la Escuela de Medicina de la Universidad de Valparaíso, Chile, que pretende abordar una temática contingente y transversal a toda la investigación científica.

Targeting Peripheral Vascular Pulsatility in Heart Failure Patients with Continuous-Flow Left Ventricular Assist Devices: The Impact of Pump Speed.

Current continuous-flow left ventricular assist devices (LVADs) decrease peripheral vascular pulsatility, which may contribute to side effects such as bleeding and thrombotic events. However, the actual impact of manipulating LVAD pump speed, revolutions per minute (rpm), on peripheral (brachial) pulsatility index (brachial PI), in patients with heart failure implanted with a HeartWare (HVAD) or HeartMateII (HMII) LVAD is unknown. Therefore, blood velocities (Doppler ultrasound) in the brachial artery were recorded and brachial PI calculated across rpm manipulations which spanned the acceptable clinical outpatient range: 360 rpm (HVAD, n = 10) and 1200 rpm (HMII, n = 10). Left ventricular assist device-derived PIs were also recorded: HVAD maximal blood flow (HVADV max), HVAD minimum blood flow (HVADV min), and HMII PI (HMIIPI). Brachial PI changed significantly with rpm manipulations, from 2.3 ± 0.6 to 4.1 ± 0.8 (HVAD) and from 1.8 ± 0.5 to 3.6 ± 1.0 (HMII). Multilevel linear modeling with random intercepts revealed a 180 rpm decrease of the HVAD resulted in a 0.9 ± 0.1 (37 ± 4%, d = 2.65) increase in brachial PI and a 600 rpm decrease in the HMII resulted in a 0.8 ± 0.1 (38 ± 3%, d = 4.66) increase. Furthermore, a reduction in rpm resulted in a 20.0 ± 0.3% power savings, and a reduction in device reported blood flow of 9 ± 1%. Brachial PI was linearly related to HVADV max, HVADV min, their difference (R = 0.42, R = 0.65, and R = 0.54, respectively), and HMIIPI (R = 0.86). Manipulating LVAD pump speed, within a clinically acceptable outpatient range, resulted in a significant change in brachial PI, which was reflected by pump indices, documenting the potential for LVAD pump speed manipulations to improve LVAD outcomes.

Dosis de células madre en el tratamiento de osteoartritis de rodilla / Stem cell doses in knee osteoarthritis

Resumen La osteoartritis (OA) es una enfermedad degenerativa, cuyo tratamiento convencional incluye medicamentos, fisioterapia o prótesis. Las células madre con Plasma Rico en Plaquetas y factores de crecimiento son una opción que promete controlar los síntomas, mejorar la función y regenerar el cartílago; sin embargo, no se han especificado muchos detalles del tratamiento, como el tipo y la cantidad de células madre que se deben aplicar para obtener mejores resultados. En este estudio buscamos comparar la efectividad, la seguridad y los costos de dos dosis (1X107vs 3X107) de células madre derivadas de tejido adiposo (ADSC), aplicadas por vía intraarticular. Diez pacientes, con OA de rodilla grados II y III, fueron aleatorizados para recibir 10 (n = 5) o 30 millones (n = 5) de ADSC autólogos. Al inicio y 6 a 10 meses después de la inyección, se evaluaron de acuerdo con los criterios clínicos (evaluación médica, escala WOMAC, calidad de vida) y paraclínicos (artroscopia, resonancia, biopsia). En términos de efectividad y seguridad no se observaron diferencias entre los dos grupos de dosificación, ya que todos los pacientes tuvieron una mejoría de acuerdo con los criterios médicos y la escala WOMAC (P = 0,001); en el control artroscópico, 7 pacientes tuvieron una respuesta "buena / muy buena", 1 "neutral" y 2 abandonaron el control; Las biopsias confirman la regeneración articular, aunque no hubo diferencias en las resonancias magnéticas anteriores y posteriores. En la osteoartritis de rodilla, la aplicación de 10 o 30 millones de ADSC fue igualmente efectiva y segura; sin embargo, el protocolo con 10 millones de células no requiere expansión in vitro, requiere menos tiempo, es más simple y tiene un costo menor. Este estudio muestra una buena razón para realizar ensayos clínicos aleatorios para obtener evidencia de mayor calidad.

Abstract Osteoarthritis (OA) is a degenerative disease where conventional treatment includes drugs, physiotherapy, or prostheses. Stem cells and growth factors are a promising option in controlling symptoms, functional improvement and cartilage regeneration; however, many treatment details have not been specified, such as type and number of stem cells that should be applied to obtain optimal results. In this study we sought to compare effectiveness, safety and costs of two doses (1X107vs 3X107) of adipose tissue derived stem cells (ADSC), applied intra-articularly. Ten patients, with knee OA grades II and III, were randomized to receive 10 (n=5) or 30 million (n=5) of autologous ADSCs. At baseline and 6 to 10 months after injection, they were evaluated according to clinical (medical evaluation, WOMAC scale, quality of life) and paraclinical criteria (arthroscopy, resonance, biopsy). In terms of effectiveness and safety there were no differences observed among the two dosage groups since all patients had improvement according to medical criteria and the WOMAC scale (P=0,001); in the arthroscopic control, 7 patients had "good/very good" response, 1 "neutral" and 2 forwent control; biopsies confirm joint regeneration, although there were no differences in the before and after magnetic resonances. In knee osteoarthritis, the application of 10 or 30 million ADSCs was equally effective and safe; however, the protocol with 10 million cells does not require in vitro expansion, requires less time, is simpler and has a lower cost. This study shows good reason to undertake randomized clinical trials to gain higher quality evidence.

Cerebral palsy: association between nutritional status and occurrence of oropharyngeal dysphagia / Paralisia cerebral: associação entre estado nutricional e ocorrência de disfagia orofaríngea

ABSTRACT Objective: to verify the association between nutritional status and the occurrence of oropharyngeal dysphagia in individuals with cerebral palsy. Methods: a cross-sectional, quantitative study with people aged between two and 20 years. Neuromotor impairment, occurrence and degree of dysphagia, anthropometry, food consumption, feeding route, diet fractionation and consistency were evaluated. Swallowing evaluation was performed by a skilled speech-language-hearing therapist, through the Clinical Evaluation Protocol of Pediatric Dysphagia (PAD-PED, Portuguese acronym).The statistical analysis was performed adopting p<0.05%. Results: 40 subjects with a median of 8.7 (5.45-14.5) years, 65% of whom were males. Concerning neuromotor impairment, 72.5% were classified at levels IV and V. The prevalence of dysphagia was 70%, the feeding route being predominantly oral (77.5%) with a normal diet consistency (55%). In the growth curves, all of them were classified within an adequate height for their age. As for weight, body mass index and skinfolds, 82.5%, 85% and 62.5% were eutrophic, respectively. Statistically significant association was found between dysphagia and body mass index (p=0.018). The mean daily caloric and proteic intake was 1427.29±338.62 kcal and 56.86±17.57 grams, respectively. Statistically significant association was found between the feeding route and the amount of protein ingested daily (p=0.041). Conclusion: most subjects presented oropharyngeal dysphagia and more severe motor impairment; they were fed orally with a normal diet consistency. It was observed that the greater the difficulty in swallowing, the greater the impairment of nutritional status.

RESUMO Objetivo: verificar a associação entre estado nutricional e ocorrência de disfagia orofaríngea em indivíduos com paralisia cerebral. Métodos: estudo transversal, quantitativo, realizado com indivíduos entre dois e 20 anos. Foi avaliado comprometimento neuromotor, ocorrência e grau de disfagia, antropometria, consumo alimentar, via alimentar, fracionamento e consistência da dieta. A avaliação da deglutição foi realizada por fonoaudióloga capacitada, por meio do Protocolo para Avaliação Clínica da Disfagia Pediátrica. Foi realizada análise estatística pertinente, adotando p<0,05%. Resultados: participaram 40 indivíduos com mediana de 8,7 (5,45-14,5) anos, sendo 65% do sexo masculino. Quanto ao comprometimento neuromotor, 72,5% foram classificados no nível IV e V. A prevalência de disfagia foi de 70%, via alimentar predominantemente oral (77,5%) e consistência da dieta normal (55%). Nas curvas de crescimento, todos foram classificados com estatura adequada para idade. Para peso, índice de massa corporal e dobras cutâneas houve, respectivamente, 82,5%, 85% e 62,5% em eutrofia. Foi encontrada associação estatisticamente significante entre disfagia e índice de massa corporal (p=0,018). A média diária de ingestão calórica e proteica foi de 1427,29±338,62 kcal e 56,86±17,57 gramas, respectivamente. Foi encontrada associação estatisticamente significante entre via alimentar e quantidade de proteína ingerida diariamente (p=0,041). Conclusão: a maioria dos indivíduos apresentou disfagia orofaríngea e comprometimento motor mais grave, alimentavam-se por via oral com consistência de dieta normal. Observou-se que quanto maior a dificuldade de deglutição, maior o comprometimento do estado nutricional.

Achieving biodiversity benefits with offsets: Research gaps, challenges, and needs.

Biodiversity offsets are becoming increasingly common across a portfolio of settings: national policy, voluntary programs, international lending, and corporate business structures. Given the diversity of ecological, political, and socio-economic systems where offsets may be applied, place-based information is likely to be most useful in designing and implementing offset programs, along with guiding principles that assure best practice. We reviewed the research on biodiversity offsets to explore gaps and needs. While the peer-reviewed literature on offsets is growing rapidly, it is heavily dominated by ecological theory, wetland ecosystems, and U.S.-based research. Given that majority of offset policies and programs are occurring in middle- and low-income countries, the research gaps we identified present a number of risks. They also present an opportunity to create regionally based learning platforms focused on pilot projects and institutional capacity building. Scientific research should diversify, both topically and geographically, in order to support the successful design, implementation, and monitoring of biodiversity offset programs.

Relação entre prontidão para início da alimentação oral e desempenho alimentar em recém-nascidos pré-termo / Association between readiness for oral feeding and feeding performance in preterm neonates

RESUMO Objetivo Verificar se a presença de prontidão para iniciar a alimentação oral, obtida por meio do Preterm Oral Feeding Readiness Scale (POFRAS) se relaciona com o desempenho alimentar na primeira oferta oral de leite, com o tempo de transição da sonda para a via oral plena e o tempo de internação hospitalar. Métodos Estudo longitudinal, que envolveu 65 recém-nascidos pré-termo. Foi realizada a avaliação da prontidão para início da alimentação oral, por meio do POFRAS, constituindo-se dois grupos: com e sem prontidão para iniciar a alimentação por via oral, em dois estratos de idade gestacional ao nascer: de 28 a 33 semanas e de 34 a 36 semanas. Em cada estrato, os grupos foram comparados entre si, quanto ao desempenho alimentar na primeira oferta oral de leite (por meio das variáveis proficiência, taxa de transferência e desempenho alimentar oral) e quanto ao tempo de transição da sonda para a via oral plena e o tempo de internação hospitalar. O teste t-Student ou o teste de Wilcoxon foram utilizados para comparar as variáveis contínuas e o teste exato de Fisher, para as variáveis categóricas. Resultados A prontidão para iniciar a alimentação por via oral se relacionou com melhores resultados de proficiência e taxa de transferência na primeira alimentação, contribuindo para a transição mais rápida da sonda para a via oral plena, nas crianças nascidas com idade gestacional entre 28 a 33 semanas. Conclusão a avaliação por meio do POFRAS permite estabelecer um prognóstico da alimentação oral em recém-nascidos pré-termo, menores de 34 semanas. No entanto, não exclui a necessidade de avaliação da biomecânica da deglutição.

ABSTRACT Purpose To verify whether readiness for oral feeding as evaluated by the Preterm Oral Feeding Readiness Scale (POFRAS) is associated with performance on the first oral feeding; length of transition from tube to full oral feeding, and duration of hospitalization. Methods This was a longitudinal study involving 65 preterm infants. Participants were divided into groups according to readiness for oral feeding as determined by the POFRAS, and gestational age (29-33 weeks and 34-36 weeks). Performance on the first oral feeding (proficiency, transfer rate and overall transfer), number of days from introduction to full independent oral feeding, and length of hospital stay were compared between groups. Continuous variables were compared using Student's t-test or Wilcoxon's signed-rank test. Categorical variables were compared using Fisher's exact test. Results Readiness for oral feeding was associated with higher proficiency and transfer rates on the first oral feeding, resulting in a shorter transition from tube to independent oral feeding in preterm infants with 29 to 33 weeks of gestational age at birth. Conclusion The POFRAS contributed to the prognosis of oral feeding outcomes in preterm neonates with less than 34 weeks of gestational age at birth. However, its use does not eliminate the need for an assessment of swallowing mechanisms.

Premature: growth and its relation to oral skills.

OBJECTIVE: To evaluate the influence of oral motor skills of premature infants on their oral feeding performance and growth, during neonatal hospitalization. METHODS: Fifty-one newborns hospitalized in the neonatal intensive care unit of a hospital in Southern Brazil, between July 2012 and March 2013, were evaluated. The evaluation of oral feeding skills, according to Lau and Smith, was applied after prescription for starting oral feeding. The oral feeding performance was analyzed using the following variables: days taken to start independent oral feeding and hospital discharge. Growth was measured by weight, length, and head circumference, using the curves of Fenton, at birth, first and independent oral feeding, and hospital discharge. RESULTS: At birth, 71% preterm infants were proper for gestational age, most of them were males (53%), with average of 33.6 (±1.5) weeks of gestational age. The gestational age in the assessment did not influence the oral feeding performance of the premature infant and did not differ between levels. Time of transition from tube feeding to oral feeding and hospital stay was shorter when the oral skills were higher. At birth, there was a tendency of low weight and low oral feeding performance. Level IV premature infants in the release of oral feeding presented higher weights. CONCLUSION: The level of oral skills of the premature infant interfered positively on time of feeding transition from tube to independent oral feeding and hospital stay. Growth, represented by weight gain, was not affected by the level of oral skill.