Protocol for the establishment of a serine integrase-based platform for functional validation of genetic switch controllers in eukaryotic cells.

Serine integrases (Ints) are a family of site-specific recombinases (SSRs) encoded by some bacteriophages to integrate their genetic material into the genome of a host. Their ability to rearrange DNA sequences in different ways including inversion, excision, or insertion with no help from endogenous molecular machinery, confers important biotechnological value as genetic editing tools with high host plasticity. Despite advances in their use in prokaryotic cells, only a few Ints are currently used as gene editors in eukaryotes, partly due to the functional loss and cytotoxicity presented by some candidates in more complex organisms. To help expand the number of Ints available for the assembly of more complex multifunctional circuits in eukaryotic cells, this protocol describes a platform for the assembly and functional screening of serine-integrase-based genetic switches designed to control gene expression by directional inversions of DNA sequence orientation. The system consists of two sets of plasmids, an effector module and a reporter module, both sets assembled with regulatory components (as promoter and terminator regions) appropriate for expression in mammals, including humans, and plants. The complete method involves plasmid design, DNA delivery, testing and both molecular and phenotypical assessment of results. This platform presents a suitable workflow for the identification and functional validation of new tools for the genetic regulation and reprogramming of organisms with importance in different fields, from medical applications to crop enhancement, as shown by the initial results obtained. This protocol can be completed in 4 weeks for mammalian cells or up to 8 weeks for plant cells, considering cell culture or plant growth time.

Trabajadoras comunitarias de salud: experiencias en el abordaje de la salud mental en zonas rurales de Chiapas.

OBJETIVO: Analizar, desde la perspectiva de las trabajadoras comunitarias de salud (TCS), los conocimientos y experiencias en la atención de la salud mental (SM) en comunidades rurales de Chiapas. Material y métodos. Se utilizó el enfoque fenomenológico descriptivo. Se realizaron 18 entrevistas semiestructuradas a TCS, las cuales fueron audiograbadas, transcritas, codificadas y analizadas utilizando como técnica, el análisis cualitativo de contenido con ayuda del software Atlas ti. RESULTADOS: Las TCS mental tienen una amplia comprensión de la cultura, el lenguaje y los problemas de sus comunidades, permitiéndoles fungir como enlace entre los servicios de salud y la población. Identifican que hay buena SM cuando "una persona tiene ánimo de realizar su trabajo diario" y enfermedad cuando "las personas sufren o tienen pensamientos chuecos". Sus experiencias de trabajo están ligadas con el acompañamiento individual (psico-educación) y el apoyo de actividades realizadas por profesionales de Compañeros En Salud (CES). Conclusión. Las TCS mental que trabajan con CES desarrollan un papel importante en la promoción de la SM, de riesgos y acompañamiento de pacientes con trastornos mentales. Estos hallazgos consolidan la evidencia e importancia del desarrollo de las intervenciones comunitarias en SM a través de este personal, en contextos de escasa disponibilidad de servicios de salud.

Evaluation of Health Promotion Program at the Community Level in Mexico: Is the Program Efficient and Effective?

CONTEXT: Health promotion programs have been encouraged in the Americas since 1990. In Mexico, health program promotion at the community level was implemented by the Ministry of Health in 2001 to encourage community health status improvement. Despite the longtime of its implementation, evaluations of its efficiency and effectiveness are scarce. OBJECTIVE: To evaluate the efficiency of the Healthy Environments and Communities Program (HECP) through 2 means: (1) efficiency of the implementation and (2) technical efficiency, as well as to evaluate its effectiveness. SETTING: Target communities of the HECP of 32 Mexican states during 2013-2017. The HECP developed community interventions to improve community organization, health behaviors, and family and communitarian sanitation. METHODOLOGY: We conducted a cross-sectional study to evaluate the efficiency of HECP implementation and estimated the inclusion of target communities (focalization index), the retention of communities (continuity index), and the desertion of communities in the program (desertion index). To evaluate the adequate use of the program resources (technical efficiency), we used data-enveloped analysis and the Tobit regression model to identify external factors that can influence results. Finally, to evaluate the program's effectiveness, we estimated the index of the communities that improved their health indicators and were certified as healthy (community certification). RESULTS: The median rate of focalization was 3.44 (1.31-85.13); the continuity of communities' rate was 0.50 (0.16-2.67). Regarding technical efficiency to reach healthy communities, only 2 states reached the optimal efficiency (score 1); where the efficiency was adjusted for external factors, 6 states reached a score of 1. The median of global effectiveness was 0.19 (0.01-0.78). We found differences in efficiency and effectiveness scores among states. CONCLUSION: We found lower efficiency of the implementation and technical efficiency, as well as poor effectiveness of the program to reach healthy communities. To achieve HECP purpose, it is necessary to revise its guidelines, improve its strategies to work in communities, and establish the right mechanisms to monitor its implementation. It is essential to focus on the resources used to enhance technical efficiency and effectiveness at the community level.

Mitochondrial respiratory chain activity is associated with severity, corticosteroid response and prognosis of alcoholic hepatitis.

BACKGROUND AND AIMS: Little is known about the extent of mitochondrial respiratory chain (MRC) activity dysfunction in patients with alcoholic hepatitis (AH). We aimed to assess the hepatic MRC activity in AH patients and its potential impact on the severity and prognosis of this life-threatening liver disease. METHODS: MRC complexes were measured in liver biopsies of 98 AH patients (non-severe, 17; severe, 81) and in 12 histologically normal livers (NL). Severity was assessed according to Maddrey's Index and MELD score. Corticosteroid response rate and cumulative mortality were also evaluated. RESULTS: The activity of the five MRC complexes was markedly decreased in the liver of AH patients compared with that of NL subjects, being significantly lower in patients with severe AH than in those with non-severe AH. There was a negative correlation between the activity of all MRC complexes and the severity of AH. Interestingly, only complex I and III activities showed a significant positive correlation with the corticosteroid response rate and a significant negative correlation with the mortality rate at all-time points studied. In a multivariate regression analysis, besides the MELD score and the corticosteroid response rate, complex I activity was significantly associated with 3-month mortality (OR = 6.03; p = 0.034) and complex III activity with 6-month mortality (OR = 4.70; p = 0.041) in AH patients. CONCLUSION: Our results indicate that MRC activity is markedly decreased in the liver of AH patients, and, particularly, the impairment of MRC complexes I and III activity appears to have a significant impact on the clinical outcomes of patients with AH.

Impact of SARS-Cov-2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry.

AIMS: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. METHODS AND RESULTS: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). CONCLUSIONS: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.

Prevalencia y factores asociados a neumonía nosocomial en la unidad de cuidado intensivo / Prevalence and Associated Factors of Nosocomial Pneumonia in the Intensive Care Unit / Prevalência e fatores associados à pneumonia nosocomial na unidade de terapia intensiva

Introducción. La neumonía nosocomial o neumonía adquirida en el hospital, es una causa importante de infección intrahospitalaria que conlleva una alta morbimortalidad. Ocurre a una tasa de 5 a 10 por cada 1,000 ingresos hospitalarios y se considera la causa más común de infección intrahospitalaria en Europa y Estados Unidos. Más del 90% de los episodios de neumonía que se desarrollan en las unidades de cuidados intensivos (UCI) ocurren en pacientes ventilados. El objetivo del presente estudio es describir la prevalencia y los factores asociados como estancia hospitalaria en UCI, enfermedades concomitantes y situaciones en pacientes mayores de 18 años con neumonía nosocomial con estancia en unidad de cuidados intensivos en una clínica de tercer nivel de la ciudad de Cali, en el periodo enero 2015 y enero 2016. Metodología. Estudio observacional de corte transversal con componente analítico. Se revisaron 353 historias clínicas enfocadas en los factores asociados de neumonía nosocomial en la UCI, con una estancia mayor o igual a 48 horas. El análisis estadístico se realizó con Epi Info versión 7. Resultados. La edad promedio de los casos estudiados fue de 55.17 años. La prevalencia estimada para neumonía nosocomial fue de 26%, con un promedio de estancia en UCI de 9.94 días, una desviación estándar de 8.30 días y días de ventilación mecánica invasiva de 4.27, con una desviación estándar de 7.38 días, en la cual el 26.35% (IC 95%: 22.0-31.1) adquirió neumonía nosocomial en UCI, el 43.06%: (IC 95%: 38.0-48.2) fueron mujeres, requiriendo de ventilación mecánica invasiva el 37.68% (IC 95%: 32.7-42.8). Como antecedentes patológicos de importancia se observó una asociación entre las variables con respecto a la neumonía nosocomial evidenciándose una relación significativa con diabetes mellitus (OR: 25.6; IC: 95% 13.4-48.7), enfermedad renal crónica (OR: 8.4; IC 95%: 4.49-16.0), enfermedad pulmonar obstructiva crónica (OR: 22.2; IC 95% 11.7-42.1), antecedente patológico de sinusitis (OR: 30.9; IC 95%: 7-46.2), utilización de sonda nasogástrica (OR: 13; IC 95%: 5-32) y, finalmente, al correlacionar la mortalidad con este tipo de infección pulmonar (OR: 26.1; IC 95%: 13 -49.1), evidenciando una relación entre las variables. Discusión. Los hallazgos muestran alta frecuencia de esta patología, lo que conlleva múltiples implicaciones en los pacientes como estancia prolongada y mortalidad, las cuales son condiciones que han sido identificadas por diferentes autores. Conclusiones. La neumonía nosocomial es un proceso infeccioso frecuente en la UCI, que tiene una alta morbimortalidad, relacionándose con los días de estancia y ventilación mecánica invasiva.

Introduction. Nosocomial pneumonia, or hospital-acquired pneumonia, is a significant cause of in-hospital infection that leads to high morbimortality. It occurs at a rate of 5 to 10 for every 1,000 hospital admissions and is considered the most common cause of in-hospital infection in Europe and the United States. Over 90% of episodes of pneumonia developed in intensive care units (ICUs) occur in ventilated patients. The objective of this study is to describe the prevalence and associated factors, such as hospitalization in the ICU, concomitant illnesses, and situations in patients older than 18 years of age with nosocomial pneumonia and hospital stay in an intensive care unit in a third-level clinic in the city of Cali, during the period between January 2015 and January 2016. Methodology. A cross-sectional, observational study with an analytical component. 353 medical records were reviewed, focusing on the factors associated with nosocomial pneumonia in the ICU, with hospital stay greater than or equal to 48 hours. The statistical analysis was performed with Epi Info version 7. Results. The average age of the studied cases was 55.17 years. The estimated prevalence for nosocomial pneumonia was 26%, with an average ICU hospital stay of 9.94 days and standard deviation of 8.30 days, and 4.27 days of invasive mechanical ventilation, with a standard deviation of 7.38 days, in which 26.35% (CI 95%: 22.0-31.1) acquired nosocomial pneumonia in the ICU. 43.06%: (CI 95%: 38.0-48.2) were women, of which 37.68% required invasive mechanical ventilation (CI 95%: 32.7-42.8). As an important pathological background, an association was observed between the variables with respect to nosocomial pneumonia, showing a significant relationship with diabetes mellitus (OR: 25.6; CI: 95% 13.4-48.7), chronic kidney disease (OR: 8.4; CI 95%: 4.49-16.0), chronic obstructive pulmonary disease (OR: 22.2; CI 95% 11.7-42.1), pathological backgrounds of sinusitis (OR: 30.9; CI 95%: 7-46.2), the use of nasogastric tube (OR: 13; CI 95%: 5-32) and, finally, correlating mortality with this type of pulmonary infection (OR: 26.1; CI 95%: 13-49.1), showing a relationship between the variables. Discussion. The findings show a high frequency of this pathology, which leads to multiple implications in patients, such as prolonged hospital stay and mortality, which are conditions that have been identified by different authors. Conclusions. Nosocomial pneumonia is a frequent infectious process in the ICU, which has a high morbimortality and is related to hospital stay and invasive mechanical ventilation.

Introdução. A pneumonia nosocomial, ou pneumonia adquirida no hospital, é uma importante causa de infecção hospitalar com alta morbidade e mortalidade. Ocorre a uma taxa de 5 a 10 por 1,000 internações hospitalares e é considerada a causa mais comum de infecção hospitalar na Europa e nos Estados Unidos. Mais de 90% dos episódios de pneumonia que se desenvolvem em unidades de terapia intensiva (UTIs) ocorrem em pacientes ventilados. O objetivo deste estudo é descrever a prevalência e fatores associados, como permanência hospitalar na UTI, doenças concomitantes e situações em pacientes maiores de 18 anos com pneumonia nosocomial internados em unidade de terapia intensiva de uma clínica de nível terciário da cidade de Cali, no período de janeiro de 2015 e janeiro de 2016. Metodologia. Estudo observacional transversal com componente analítico. Foram revisados 353 prontuários com foco em fatores associados de pneumonia nosocomial na UTI, com permanência maior ou igual a 48 horas. A análise estatística foi realizada com o Epi Info versão 7. Resultados. A média de idade dos casos estudados foi de 55.17 anos. A prevalência estimada para pneumonia nosocomial foi de 26%, com média de permanência na UTI de 9.94 dias, desvio padrão de 8.30 dias, e dias de ventilação mecânica invasiva de 4.27, com desvio padrão de 7.38 dias, em que 26.35% (IC 95%: 22.0-31.1) adquiriram pneumonia nosocomial na UTI; 43.06%: (IC 95%: 38.0-48.2) eram mulheres, necesitando de ventilação mecânica invasiva 37.68% (IC 95%: 32.7-42.8). Como antecedentes patológicos importantes, observou-se associação entre as variáveis referentes à pneumonia nosocomial, mostrando relação significativa com diabetes mellitus (OR: 25.6; IC: 95% 13.4-48.7), doença renal crônica (OR: 8.4; IC 95%: 4.49-16.0), doença pulmonar obstrutiva crônica (OR: 22.2; IC 95% 11.7-42.1), história patológica de sinusite (OR: 30.9; IC 95%: 7-46.2), uso de sonda nasogástrica (OR: 13; IC 95%: 5-32) e, por fim, correlação da mortalidade com este tipo de infecção pulmonar (OR: 26.1; IC 95%: 13-49.1), mostrando relação entre as variáveis. Discussão. Os resultados mostram uma alta frequência dessa patologia, que tem múltiplas implicações para os pacientes, como permanência prolongada e mortalidade, que são condições identificadas por diferentes autores. Conclusões. A pneumonia nosocomial é um processo infeccioso frequente na UTI, que apresenta alta morbimortalidade, relacionada aos dias de internação e ventilação mecânica invasiva.

Knowledge about COVID-19 and vaccine acceptability among priority groups defined for vaccination: A cross-sectional study in Araba/Alava, Spain, before the vaccination against SARS-CoV-2.

Background: The acceptability of COVID-19 vaccine varies depending on the time, place, type of vaccine and information available at the time. Knowledge of attitudes and practices towards COVID-19 among the population at high risk of developing the disease would help to tailor the strategy to improve adherence to vaccination recommendations. Aim: To analyze the willingness, knowledge and risk perception of patients and health care workers (HCW) to get the vaccines against SARS-CoV-2. Methods: Cross-sectional survey in Araba/Álava province (Spain). Subjects who met the criteria for the influenza vaccination in 2019 and HCWS from the Basque Public Health Service were included. The participants answered a questionnaire on the knowledge, attitudes and practices towards COVID-19 before starting vaccination against SARS-CoV-2. The intention to vaccinate was compared using the chi-squared test. Results: 316 HCWs and 389 patients responded to the survey. Around 90% of the patients and 80% of HCW would accept vaccination in all scenarios according to the questionnaire (p < 0.001). Only 3-12% hesitated about the COVID-19 vaccines. Compared to 40-70% of patients, 60-80% of HCWs perceived a high risk of COVID-19 (p < 0.001). Statistically significant differences were found in 10 of the 17 questions regarding the mechanism of transmission and symptoms. Conclusion: HCWs had a better knowledge and risk perception of COVID-19 than the surveyed patients. They had a higher proportion of hesitancy to get COVID-19 vaccine, probably related to doubts about the effectiveness of the new vaccines and the scientific evidence.

Biodisponibilidad de fósforo en alimentos y su efecto en la enfermedad renal crónica / Bioavailability of phosphorus in food and its effect in chronic kidney disease

Resumen Introducción: el objetivo del presente trabajo se centra en reconocer la importancia de las investigaciones que relacionan la biodisponibilidad de fósforo en diferentes grupos de alimentos de origen animal, vegetal e industrial y su efecto en la progresión de la enfermedad renal crónica (ERC). Metodología: la revisión se sustentó en la búsqueda literaria en páginas web como PUBMED, Redalyc, SciELO, SCIHUB y Google Academic. Se seleccionó cada estudio, descartando aquellos que no fueran cuantitativos u originales, estuvieran incompletos, sin metodología clara, realizados en mamíferos o si los resultados no se especificaban en porcentajes. La lectura puso especial énfasis en el índice de biodisponibilidad de fósforo derivado del consumo de distintos productos alimenticios. Se elaboraron tres matrices de acuerdo con el origen del comestible y la biodisponibilidad de fósforo que absorbe el organismo. Resultados: se encontró que los alimentos industrializados y los aditivos muestran una biodisponibilidad de fósforo del 90 % al 100 %, los de origen animal del 40 % al 80 % y los de origen vegetal del 30 %. Conclusiones: los aditivos de los alimentos industrializados promueven la hiperfosfatemia y, con ello, aceleran la progresión de la enfermedad renal crónica, a diferencia de los de origen animal y vegetal, menos perjudiciales para la salud. Esto da pauta a la formación del sector salud para ampliar su conocimiento sobre el tratamiento nutricional del paciente.

Abstract Introduction: to know the importance of the investigations that relate the bioavailability of phosphorus in different groups of foods of animal, vegetable and industrialized origin and its effect on the progression in patients with Chronic Kidney Disease (CKD). Methodology: the review is based on a literary search that was carried out on web pages such as: PUBMED, Redalyc, SciELO, SCIHUB and Google Academic. Each of the studies was selected discarding those that were not quantitative, original, complete, with clear methodology, carried out in mammals, and that in their results specified the bioavailability of phosphorus in percentages. All the studies were read, placing main emphasis and interest on the percentage of phosphorus bioavailability when consuming different food groups. Three matrices were made according to the origin of the food and the bioavailability of phosphorus that is absorbed in the body; grouping them into foods of animal, vegetable and industrialized origin and additives. Results: it was found that industrialized foods and additives show a phosphorus bioavailability of 90-100%, those of animal origin 40-80%, those of plant origin 30%. Conclusions: The additives used in industrialized foods promote hyperphosphatemia and thus accelerate the progression of chronic kidney disease, unlike foods of animal and vegetable origin that are less harmful to health. This guides the training of the health sector, expanding its knowledge in the nutritional treatment of the patient.

Clinician Wire Puncture Injury to the Hand from Chest Compressions on a Patient with a Median Sternotomy: A Case Report.

Standard precautions, including protections from blood and body fluid exposure, are designed to protect health care providers from infections. Sharps safety practices rarely include the potential for the unconscious patient's own body to be a potential source of clinician percutaneous injury from sharp objects outside of the perioperative setting. This case report reviews a percutaneous injury to the hand of a physician who was performing chest compressions on a patient with an out-of-hospital cardiac arrest. The 76-year-old patient in cardiac arrest had undergone a medial sternotomy surgery 15 years before the arrest. The sternal wire rotated owing to the initial chest compressions, breaking the clinician's nitrile glove and producing an open wound on the thenar region of the clinician's right hand. Application of a 10 × 10 12-ply gauze pack on the chest of the patient in cardiac arrest allowed the resuscitation team to continue with the compressions with no further wounds from the wire. This case report is a novel contribution to the published literature and advances standard precautions considerations in patients with out-of-hospital cardiac arrest, with the sternotomy wire from previous surgery as a source of percutaneous clinician injury during chest compression.

Neuropsychiatric Aspects in a Patient Diagnosed with Frontotemporal Dementia: Clinical Case of Low Incidence and Prevalence Disease in Colombia.

Frontotemporal dementia (FTD) is a neuropsychiatric pathology characterized by dysfunctions in the frontal lobe of the brain, especially in planning, execution, and inhibition tasks, with an inability to make decisions and handle different sequences, also affecting the temporal lobe. The patient presents alterations to store, consolidate, and recall information. These neurocognitive deficits are accompanied by neurobehavioral disorders such as depression, anxiety, and apathy that contribute to the worsening of the quality of life, with a high impact on the individual, social, and family level. To identify the neurobehavioral disorders and neurocognitive deterioration that present a patient diagnosed with FTD: clinical case of low incidence and prevalence disease in Colombia. A 40-year-old man, with progressive deterioration of his immediate verbal memory, low verbal fluency, aberrant motor behavior, sexual impulsivity, alterations in his executive functions, especially in planning tasks, decision-making, and inhibition was found to have a lesser degree of affectation in his visuospatial functioning and visuoconstructive abilities. It was found that the patient presents a severe dysexecutive syndrome associated with a clinical picture of FTD, correlated with an inability to process and recall information, accompanied by disorders such as depression, anxiety, and apathy. It is necessary to generate a functional neurorehabilitation plan that aims to improve the quality of life in these patients. In the same way, it is necessary to create new lines of research and intervention that have the purpose to create a greater field of heuristics or new questions in this type of neurodegenerative pathologies.

Being for Others and Material Conditions: The Limits of the "Healthy Lifestyles" Notion for Chilean Women.

Public policies to prevent non-communicable diseases (NCDs) by promoting health lifestyles began in Chile in the 1990 s, yet NCDs are still highly prevalent. We draw on the theoretical approaches of the Latin American Collective Health (LACH) and critical medical anthropology (CAM) to elucidate why these polices have not had the desired effects. Women with low socioeconomic status and participating in the Choose Healthy Living Program identified obstacles to healthy living and the subjective tensions resulting from the healthy lifestyles ethic. Their experiences demonstrate how lifestyles emerge from the intersection of agency and structure, so it cannot result from individual action alone.

Manejo del trastorno depresivo ¿Qué tratamiento elegir? / Management of depressive disorder. What treatment to choose?

Resumen A lo largo de la historia, el ser humano ha buscado mejorar y tratar las diferentes patologías mentales. Con los avances en investigación, actualmente hay una amplia variedad de opciones terapéuticas que pueden resultar un factor de confusión a la hora de escoger el tratamiento más adecuado para combatir el trastorno depresivo. Por tanto, en el presente trabajo se realiza una revisión de las principales opciones de tratamiento para la depresión con el fin de brindar pautas que mejoren la toma de decisiones al abordar esta patología.

Abstract Throughout history, the human being has sought to improve and treat different mental pathologies, with advances in research, currently there is a wide variety of therapeutic options that can be a confounding factor when choosing the most appropriate treatment. This paper reviews the main treatment options for depression in order to provide guidelines that improve decision-making when addressing this pathology.

Prevalence of Depression and Generalized Anxiety Disorder Among Mexican Indigenous Adolescents and Young Adults: Challenges for Healthcare.

Providing evidence on mental disorders in indigenous adolescents is critical to achieving universal health coverage (UHC). The prevalence of symptoms of depression and generalized anxiety disorder symptoms were estimated for 2082 adolescents aged 14-20 years in Chiapas, Mexico. Mental disorders were assessed using the 9-item Patient-Health Questionnaire and the 7-item Generalized Anxiety Disorder Scale. Among the adolescents evaluated, 35.8% suffered from depression or generalized anxiety disorder. Of those, 6.1% reported a previous diagnosis. 32.1% of adolescents with both mental disorders reported having attempted suicide. Gender, substance use, adverse living experiences and living conditions were correlated to the presence of depression and/or generalized anxiety disorder. It is mandatory for Mexican health authorities to develop effective instruments aiming to screen and diagnose mental health conditions in adolescents, as well as to provide timely treatment in primary health-care units.

Cancer survivorship needs in Brazil: Patient and family perspective.

INTRODUCTION: Cancer Survivorship is a growing public health challenge. Effective responses from health care and social services depend on appropriate identification of survivors and their families´ specific needs. There are few studies on survivorship in low and middle-income countries, therefore, more evidence-based studies are necessary to develop a comprehensive approach to cancer survivorship. OBJECTIVES: Identify the needs of cancer survivors and their relatives, specifically those of individuals with breast, cervical or prostate cancer, and with acute lymphocytic leukemia (ALL). METHODS: A qualitative, exploratory study conducted in two referral institutions in Brazil, located in Rio de Janeiro (Southeast region) and Fortaleza (Northeast region). The study included 47 patients of public and private health services and 12 family members. We used script-based semi-structured interviews. The discursive material obtained was categorized and analyzed using the Thematic Analysis approach. RESULTS: The analysis identified three central themes: 1) consequences of cancer treatment; 2) Changes in daily life associated with cancer survivorship; and 3) Unmet structural needs in cancer survivorship. CONCLUSION: Social and cancer control policies in Brazil should provide resources, specific care standards and clinical, psychological and social support. Cancer survivors should also receive rehabilitation and work reintegration guidelines. This matter requires broader access to qualified cancer information, development of an integrated patient-centered care and care model, and more research resources for the country's post-treatment cancer period.

Advances and challenges on the path toward the SDGs: subnational inequalities in Mexico, 1990-2017.

BACKGROUND: The sustainable development goals (SDGs) have generated momentum for global health, aligning efforts from governments and international organisations toward a set of goals that are expected to reflect improvements in life conditions across the globe. Mexico has huge social inequalities that can affect access to quality care and health outcomes. The objective of this study is to analyse inequalities among Mexico's 32 states on the health-related SDG indicators (HRSDGIs) from 1990 to 2017. METHODS: These analyses rely on the estimation of HRSDGIs as part of the Global Burden of Disease study 2017. We estimated the concentration index for 40+3 HRSDGI stratified by Socio-demographic Index and marginalisation index, and then for indicators where inequalities were identified, we ran decomposition analyses using structural variables such as gross domestic product per capita, poverty and health expenditure. FINDINGS: Mexico has made progress on most HRSDGIs, but current trends in improvement do not appear to fast enough to meet 2030 targets. Out of 43 HRSDGIs, we identified evidence of inequality between Mexico's states for 30 indicators; of those, 23 HRSDGIs were unequal distributed affecting states with lower development and seven affecting states with higher development. The decomposition analysis indicates that social determinants of health are major drivers of HRSDGI inequalities in Mexico. INTERPRETATION: Modifying current trends for HRSDGIs will require subnational-level and national-level policy action, of which should be informed by the latest available data and monitoring on the health-related SDGs. The SDGs' overarching objective of leaving no-one behind should be prioritised not only for individuals but also for communities and other subnational levels.

Health care trajectories and barriers to treatment for patients with end-stage renal disease without health insurance in Mexico: a mixed methods approach.

BACKGROUND: Mexico has the sixth-highest premature death rate from chronic kidney disease (CKD) in the world. From 1990 to 2017, the age-standardized CKD mortality rate jumped from 28.7 to 58.1 per 100,000 inhabitants, making it the second-leading cause of death that year. Medical care for the disease is inequitable, as those without health insurance have limited access to renal replacement therapy (RRT). The objective of this study is to describe the healthcare trajectories of patients with end-stage renal disease (ESRD) in a public hospital in Mexico City and the barriers they face in receiving peritoneal dialysis and haemodialysis. METHODS: This study uses a convergent mixed methods approach and is predominantly qualitative. Patients completed 199 surveys, and 42 semi-structured interviews with patients having ESRD and their families were conducted. The quantitative data were analysed using descriptive statistics, and the qualitative data were processed using a phenomenological approach. RESULTS: It was found that 76.9% of the patients received peritoneal dialysis or haemodialysis as their first RRT. Over 30% began their treatment at least a month after a health professional prescribed it. Almost 50% had been hospitalized for complications related to the disease in the previous year, and 36% had uncertainties about their treatment. Close to 64% of the haemodialysis patients received treatment intermittently. Barriers to accessing treatment, information, contact with health services, and treatment availability were identified. Patients and their families encountered economic and emotional difficulties at every phase of their search for medical care and treatment. CONCLUSION: Mexico urgently needs to implement public policies related to CKD that are primarily directed at its prevention but should also implement policies directed at slowing its progression, reducing its complications, and providing funding for uninsured patients who require RRT. These policies must be based on the perspectives of human rights and equality, and the perspectives of patients, their families and the general population should be included in the policy creation process.

Self-identity, lived experiences, and challenges of breast, cervical, and prostate cancer survivorship in Mexico: a qualitative study.

BACKGROUND: Qualitative research on cancer patients' survivor-identity and lived experiences in low- and middle-income countries is scarce. Our study aimed at exploring the concept and experience of survivorship for Mexicans living with breast, cervical, and prostate cancer. METHODS: We conducted a qualitative study in Mexico City, Morelos, Nuevo León, and Puebla. The participants were breast, cervical, and prostate cancer patients ≥18 years of age with completed primary cancer treatment. Data were collected via in-depth interviews and analyzed using an inductive thematic approach. RESULTS: The study included 22 participants with a history of breast, 20 cervical, and 18 prostate cancer. Participants accepted the term "cancer survivor" as a literal interpretation of being alive, medical confirmation of treatment completion, or achievement of a clinical result possibly indicative of cure. The majority of respondents perceived that the future is out of their control and under God's will. They linked cure to divine intervention and did not demonstrate the sense of empowerment that is often associated with the survivorship term. The principal themes of their narratives encompass: 1) adverse physical and sexual experiences; 2) emotional problems; 3) cancer-related stigma; 4) challenges to obtaining health-related information; 5) financial hardship; and 6) experience of strengthening family ties in order to provide them with support. In addition, women with breast cancer reported distress caused by changes in body image and positive experience with support groups. CONCLUSION: In Mexico, cancer patients report complex survivorship experiences that demand post-treatment follow-up and support. There is the need to implement comprehensive, culturally-relevant survivorship programs focused on emotional, informational, and in-kind support and empowerment of cancer patients.

Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy.

OBJECTIVE: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. METHODS: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. RESULTS: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). CONCLUSION: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

Genetic switches designed for eukaryotic cells and controlled by serine integrases.

Recently, new serine integrases have been identified, increasing the possibility of scaling up genomic modulation tools. Here, we describe the use of unidirectional genetic switches to evaluate the functionality of six serine integrases in different eukaryotic systems: the HEK 293T cell lineage, bovine fibroblasts and plant protoplasts. Moreover, integrase activity was also tested in human cell types of therapeutic interest: peripheral blood mononuclear cells (PBMCs), neural stem cells (NSCs) and undifferentiated embryonic stem (ES) cells. The switches were composed of plasmids designed to flip two different genetic parts driven by serine integrases. Cell-based assays were evaluated by measurement of EGFP fluorescence and by molecular analysis of attL/attR sites formation after integrase functionality. Our results demonstrate that all the integrases were capable of inverting the targeted DNA sequences, exhibiting distinct performances based on the cell type or the switchable genetic sequence. These results should support the development of tunable genetic circuits to regulate eukaryotic gene expression.