A novel, patient-derived RyR1 mutation impairs muscle function and calcium homeostasis in mice.

RYR1 is the most commonly mutated gene associated with congenital myopathies, a group of early-onset neuromuscular conditions of variable severity. The functional effects of a number of dominant RYR1 mutations have been established; however, for recessive mutations, these effects may depend on multiple factors, such as the formation of a hypomorphic allele, or on whether they are homozygous or compound heterozygous. Here, we functionally characterize a new transgenic mouse model knocked-in for mutations identified in a severely affected child born preterm and presenting limited limb movement. The child carried the homozygous c.14928C>G RYR1 mutation, resulting in the p.F4976L substitution. In vivo and ex vivo assays revealed that homozygous mice fatigued sooner and their muscles generated significantly less force compared with their WT or heterozygous littermates. Electron microscopy, biochemical, and physiological analyses showed that muscles from RyR1 p.F4976L homozygous mice have the following properties: (1) contain fewer calcium release units and show areas of myofibrillar degeneration, (2) contain less RyR1 protein, (3) fibers show smaller electrically evoked calcium transients, and (4) their SR has smaller calcium stores. In addition, single-channel recordings indicate that RyR1 p.F4976L exhibits higher Po in the presence of 100 µM [Ca2+]. Our mouse model partly recapitulates the clinical picture of the homozygous human patient and provides significant insight into the functional impact of this mutation. These results will help understand the pathology of patients with similar RYR1 mutations.

Quantitative proteomic analysis of skeletal muscles from wild-type and transgenic mice carrying recessive Ryr1 mutations linked to congenital myopathies.

Skeletal muscles are a highly structured tissue responsible for movement and metabolic regulation, which can be broadly subdivided into fast and slow twitch muscles with each type expressing common as well as specific sets of proteins. Congenital myopathies are a group of muscle diseases leading to a weak muscle phenotype caused by mutations in a number of genes including RYR1. Patients carrying recessive RYR1 mutations usually present from birth and are generally more severely affected, showing preferential involvement of fast twitch muscles as well as extraocular and facial muscles. In order to gain more insight into the pathophysiology of recessive RYR1-congential myopathies, we performed relative and absolute quantitative proteomic analysis of skeletal muscles from wild-type and transgenic mice carrying p.Q1970fsX16 and p.A4329D RyR1 mutations which were identified in a child with a severe congenital myopathy. Our in-depth proteomic analysis shows that recessive RYR1 mutations not only decrease the content of RyR1 protein in muscle, but change the expression of 1130, 753, and 967 proteins EDL, soleus and extraocular muscles, respectively. Specifically, recessive RYR1 mutations affect the expression level of proteins involved in calcium signaling, extracellular matrix, metabolism and ER protein quality control. This study also reveals the stoichiometry of major proteins involved in excitation contraction coupling and identifies novel potential pharmacological targets to treat RyR1-related congenital myopathies.

Patrones de consumo de alcohol en trabajadores de la termoeléctrica "Antonio Guiteras" de Matanzas

Introducción: El enfrentamiento a los problemas relacionados con el alcohol se puede desarrollar desde múltiples contextos, incluidos los relacionados con la atención a trabajadores en instituciones de generación de energía. Para esto es primordial el diagnóstico de los patrones de consumo, como vía para el desarrollo efectivo de los procesos de intervención. Objetivo: Examinar las características del consumo de alcohol en trabajadores de la termoeléctrica "Antonio Guiteras" de Matanzas. Métodos: Investigación descriptiva, entre septiembre de 2018 y agosto de 2019, en una muestra de 126 trabajadores. Se analizaron los patrones de consumo, los niveles de conocimientos, actitudes afines con la ingestión de bebidas alcohólicas y su relación con algunas variables sociodemográficas. Se aplicó un cuestionario de identificación de los trastornos debidos al consumo de alcohol, así como un cuestionario para la exploración de los conocimientos y las actitudes acerca de dicha ingestión. Resultados: Predominaron los patrones de consumo de bajo riesgo. Los patrones de consumo de riesgo se asociaron al sexo masculino, las personas menores de 40 años y el estado conyugal soltero. Se apreciaron altos niveles de conocimientos sobre la peligrosidad de la ingestión de bebidas alcohólicas y la presencia de actitudes beneficiosas hacia estas. Conclusiones: Los resultados acerca del consumo de alcohol son favorables, pero obligan al desarrollo de nuevas líneas de investigación para el enfrentamiento a las adicciones desde la psicología laboral y de las organizaciones, con técnicas, herramientas y esquemas de intervención propios de la atención primaria de salud o de la psicología de la salud.

Introduction: Coping with alcohol-related problems can be developed from multiple contexts, including those related to care for workers in power generation institutions. Thus, the diagnosis of consumption patterns is essential, as a way for the effective development of intervention processes. Objective: To examine the characteristics of alcohol consumption in workers of Antonio Guiteras thermoelectric plant in Matanzas. Methods: A descriptive research, from September 2018 and August 2019, was carried out in a sample of 126 workers. Consumption patterns, levels of knowledge, attitudes related to the ingestion of alcoholic beverages and their relationship with some sociodemographic variables were analyzed. A questionnaire for the identification of disorders due to alcohol consumption was applied, as well as a questionnaire for the exploration of knowledge and attitudes about said ingestion. Results: Low-risk consumption patterns predominated. Risky consumption patterns were associated with male sex, people under 40 years of age, and single marital status. High levels of knowledge about the danger of drinking alcoholic beverages and the presence of beneficial attitudes towards them were observed. Conclusions: The results regarding alcohol consumption are favorable, but new lines of research are required to confront addictions from occupational and organizational psychology, with techniques, tools and intervention schemes typical of primary care for health or health psychology.

Screening of GPCR drugs for repurposing in breast cancer.

Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on ß-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of ß3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.

Quality versus emergency: How good were ventilation fittings produced by additive manufacturing to address shortages during the COVID19 pandemic?

OBJECTIVE: The coronavirus disease pandemic (COVID-19) increased the risk of shortage in intensive care devices, including fittings with intentional leaks. 3D-printing has been used worldwide to produce missing devices. Here we provide key elements towards better quality control of 3D-printed ventilation fittings in a context of sanitary crisis. MATERIAL AND METHODS: Five 3D-printed designs were assessed for non-intentional (junctional and parietal) and intentional leaks: 4 fittings 3D-printed in-house using FDeposition Modelling (FDM), 1 FDM 3D-printed fitting provided by an independent maker, and 2 fittings 3D-printed in-house using Polyjet technology. Five industrial models were included as controls. Two values of wall thickness and the use of coating were tested for in-house FDM-printed devices. RESULTS: Industrial and Polyjet-printed fittings had no parietal and junctional leaks, and satisfactory intentional leaks. In-house FDM-printed fittings had constant parietal leaks without coating, but this post-treatment method was efficient in controlling parietal sealing, even in devices with thinner walls (0.7 mm vs 2.3 mm). Nevertheless, the use of coating systematically induced absent or insufficient intentional leaks. Junctional leaks were constant with FDM-printed fittings but could be controlled using rubber junctions rather than usual rigid junctions. The properties of Polyjet-printed and FDM-printed fittings were stable over a period of 18 months. CONCLUSIONS: 3D-printing is a valid technology to produce ventilation devices but requires care in the choice of printing methods, raw materials, and post-treatment procedures. Even in a context of sanitary crisis, devices produced outside hospitals should be used only after professional quality control, with precise data available on printing protocols. The mechanical properties of ventilation devices are crucial for efficient ventilation, avoiding rebreathing of CO2, and preventing the dispersion of viral particles that can contaminate health professionals. Specific norms are still required to formalise quality control procedures for ventilation fittings, with the rise of 3D-printing initiatives and the perspective of new pandemics.

Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors.

To date there are no therapies for patients with congenital myopathies, muscle disorders causing poor quality of life of affected individuals. In approximately 30% of the cases, patients with congenital myopathies carry either dominant or recessive mutations in the ryanodine receptor 1 (RYR1) gene; recessive RYR1 mutations are accompanied by reduction of RyR1 expression and content in skeletal muscles and are associated with fiber hypotrophy and muscle weakness. Importantly, muscles of patients with recessive RYR1 mutations exhibit increased content of class II histone deacetylases and of DNA genomic methylation. We recently created a mouse model knocked-in for the p.Q1970fsX16+ p.A4329D RyR1 mutations, which are isogenic to those carried by a severely affected child suffering from a recessive form of RyR1-related multi-mini core disease. The phenotype of the RyR1 mutant mice recapitulates many aspects of the clinical picture of patients carrying recessive RYR1 mutations. We treated the compound heterozygous mice with a combination of two drugs targeting DNA methylases and class II histone deacetylases. Here, we show that treatment of the mutant mice with drugs targeting epigenetic enzymes improves muscle strength, RyR1 protein content, and muscle ultrastructure. This study provides proof of concept for the pharmacological treatment of patients with congenital myopathies linked to recessive RYR1 mutations.

The Risk Perception COVID-19 Scale (RP-COVID19-S): Initial Validation and Its Relationship with Gender and Age in a Cuban Population Sample.

BACKGROUND: Risk perception about COVID-19 constitutes an important variable contributing to promotion of personal protection practices. The aims of this study were to exploring the factorial structure of the risk perception COVID-19 scale (RP-COVID19-S) in a sample of Cuban adults and to identify its relationship with variables such as gender and age. METHODS: A cross-sectional web-based survey design was conducted. The sample comprised 394 Cuban participants. Categorical Principal Component Analysis (CATPCA) was used to explore internal factorial structure of the scale. Logistic regression was modeling to identify variables independently associated with RP about COVID-19. RESULTS: CATPCA allowed identifying a three-dimensional factorial structure into the scale: knowledge and beliefs, emotional reactions and behavioral dissonance, and motivations for change. The odds of a woman with middle RP compared to low RP was 2.17 times more than for a man. Also, the odds of a woman with high knowledge and beliefs compared to low knowledge and beliefs were 1.96 times more than for a man. The odds of a person in older group, with middle risk perception compared with low level, was 5.0 (global risk perception), 3.33 (knowledge and beliefs), and 3.13 (emotional reactions and behavioral dissonance) times more than for a person in younger group, respectively. CONCLUSION: The Risk Perception to COVD-19 Scale (RP-COVID-19-S) showed satisfactory psychometric properties to evaluated risk perception related to COVID-19 in Cuban population sample. Middle level of global risk perception was found in the sample. High level of risk perception about COVID-19 was found on participants older than 42 years old and in woman.

Acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19 / Family educational actions with schoolers during COVID-19 confinement

Introducción: El confinamiento por la COVID-19 ha generado un desafío en la crianza de los escolares. Objetivo: Examinar el desempeño de acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19. Métodos: Investigación descriptiva, muestreo no probabilístico,112 familias. que cumplían aislamiento social en la comunidad Ramón López Peña, San Cristóbal, Artemisa en 2020. Instrumento utilizado: Escala de acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19, construida y validada por los investigadores con alfa de Cronbach= 0,970). Resultados: Las acciones educativas: cumplir los horarios de alimentación y sueño (70,6 por ciento), distribuir los roles en el cuidado del menor (70,6 por ciento), apoyo emocional (70,6 por ciento), apoyar con las teleclases (70,6 por ciento), siempre se realizaron por las familias con desempeño favorable. Las acciones: ayudar a recuperarse de una emoción negativa (72,7 por ciento), alejar al escolar de las preocupaciones y tensiones del hogar (72,7 por ciento), explicar si no entiende los contenidos o buscar ayuda (72,7 por ciento), casi nunca fueron realizadas por las familias con desempeño desfavorable. Conclusiones: La mayoría de las familias presentaron desempeño favorable de acciones educativas. La dimensión Cuidados del menor fue la mejor expresada. Enseñar al escolar las medidas higiénicas de protección; brindar información a los escolares sobre cómo protegerse; enseñar y practicar formas de saludar y de mantenerse conectados con seres queridos y amigos, fueron las acciones educativas más realizadas por ambos grupos de familia. La complejidad del aprendizaje en casa y el manejo afectivo del niño requieren especial atención(AU)

Introduction: COVID-19 confinement has created a challenge in raising schoolers. Objective: Examine the performance of educational actions of the family with the school during the confinement by COVID-19. Methods: Descriptive research, non-probabilistic sampling, 112 families who complied with social isolation in Ramón López Peña community, San Cristobal, Artemisa province in 2020. Instrument used: Scale of educational actions of the family with school children during confinement by COVID-19, built and validated by researchers with Cronbach´s alpha = 0.970. Results: Educational actions as meeting food and sleep schedules (70.6 percent), distributing roles in child care (70.6 percent), emotional support (70.6 percent), supporting with teleclasses (70.6 percent) were always carried out by families with favorable performance. Actions like helping to recover from negative emotions (72.7 percent), keeping the schooler away from household concerns and tensions (72.7 percent), explaining whether they don't understand the contents or looking for help (72.7 percent) were almost never made by families with unfavorable performance. Conclusions: Most families had a favorable performance in educational actions. The Child Care dimension was the best performed one. Teaching the schoolchildren the hygienic protective measures, provide information to schoolchildren on how to protect themselves, teaching and practicing ways to greet and stay connected with loved ones and friends were the most performed educational actions by both family groups. The complexity of home learning and the child's affective management require special attention(AU)

Falta de rigor científico de dos investigaciones de series de casos sobre diplomáticos estadounidenses en La Habana / Lack of scientific consistency in two investigations of case series of United States diplomats in Havana

Introducción: Con el propósito de justificar la decisión diplomática de los Estados Unidos, se publicaron dos artículos científicos en revistas médicas que intentan sostener la idea de que en La Habana hubo un ataque dirigido a personal de la embajada estadounidense. Objetivo: Demostrar la falta de rigor científico en dos investigaciones de series de casos no independientes sobre los síntomas de salud de diplomáticos de los Estados Unidos en La Habana. Método: Se realiza un análisis documental de dos publicaciones de series de casos. Se evalúan hipótesis diagnósticas. Resultados: Existe superposición amplia entre las dos series en cuanto a pacientes compartidos y en contraste se presentan algunas diferencias en los datos clínicos que superan lo esperado. Conclusiones: En ambas publicaciones se desaprovecha la riqueza semiográfica de síntomas y la información psicosocial. Se enfatiza más en argumentos asociados al fetichismo de la tecnología expresado en la interpretación de hallazgos inespecíficos. El análisis de datos clínicos permitió ver que se trata de un grupo heterogéneo de personas cuyas quejas de salud han sido reunidas por la interacción de otros factores psicosociales contextuales(AU)

Introduction: In order to justify the diplomatic decision of the United States, two scientific articles were published in medical journals that attempt to support the idea that, in Havana, there was an attack aimed at US embassy personnel. Objective: To prove the lack of scientific consistency in two investigations of non-independent case series on the health symptoms of United States diplomats in Havana. Method: A documentary analysis of two publications of case series is carried out. Diagnostic hypotheses are evaluated. Results: There is wide overlap between the two series in terms of shared patients and in contrast there are some differences in the clinical data that exceed what was expected. Conclusions: In both publications the semiographic wealth of symptoms and psychosocial information are wasted. More emphasis is placed on arguments associated with the fetishism of technology expressed in the interpretation of nonspecific findings. The analysis of clinical data allowed us to see that it is a heterogeneous group of people whose health complaints have been brought together by the interaction of other contextual psychosocial factors(AU)

Epidemiology, clinical aspects, outcomes and prognostic factors associated with Trichosporon fungaemia: results of an international multicentre study carried out at 23 medical centres.

BACKGROUND: Trichosporon fungaemia (TF) episodes have increased in recent years and mortality rates remain high despite the advances in the management of sepsis. New concepts about its clinical course, treatment and microbiology need to be investigated for the better management of this infection. OBJECTIVES: To describe the aetiology, natural history, clinical management and prognostic factors of TF. METHODS: TF episodes documented between 2005 and 2018 in 23 South American centres were retrospectively investigated by using a standard clinical form. Molecular identification, antifungal susceptibility testing and biofilm production were also performed. RESULTS: Eighty-eight TF episodes were studied. Patients had several underlying conditions, including haematological diseases (47.7%), post-operative status (34%), solid organ transplants (n = 7, 7.9%), among others. Seventy-three (82.9%) patients had a central venous catheter (CVC) at TF diagnosis. The 30 day mortality rate was 51.1%. Voriconazole-based therapy was given to 34 patients (38.6%), with a 30 day mortality rate of 38.2%. Multivariate predictors of 30 day mortality were age (OR 1.036), mechanical ventilation (OR 8.25) and persistent neutropenia (OR 9.299). CVC removal was associated with over 75% decreased risk of 30 day mortality (OR 0.241). Microbiological analyses revealed that 77.7% of the strains were identified as Trichosporon asahii, and voriconazole showed the strongest in vitro activity against Trichosporon spp. Most of the strains (63%) were considered medium or high biofilm producers. CONCLUSIONS: Older age, mechanical ventilation and persistent neutropenia were associated with poor prognosis. CVC may play a role in the pathogenicity of TF and its removal was associated with a better prognosis.

Mental health stigma and professional help-seeking attitudes a comparison between Cuba and Germany.

Globally the burden due to mental disorders is continuously increasing. Still, professional help-seeking behavior is not fully understood. To conceive cultural determinants of help-seeking is crucial to reduce personal and social costs of (untreated) mental disorders. The current study investigates mental health stigma and help-seeking attitudes in a Cuban (n = 195) and a German (n = 165) sample. In a questionnaire survey we asked for attitudes towards mental illness and professional help-seeking in the general Cuban and German populations. The cultural context was associated with mental health stigma and professional help-seeking attitudes. Interestingly, Cuban participants reported stronger mental health stigma and more willingness to seek help. In multiple hierarchical regression analyses, community attitudes towards the mentally ill significantly predicted help-seeking attitudes, especially in the Cuban sample. Only in the German sample, more negative individual beliefs about mental illness predicted more self-stigma on help-seeking. Beyond that, cultural context moderated the association between mental health stigma and help-seeking attitudes with a stronger association between the measures in the German sample. However, gender did not predict help-seeking attitudes and self-stigma on help-seeking and no interactions between community attitudes, cultural context, and gender were found in the prediction of help-seeking attitudes. Similarities and differences between the samples are discussed in the light of the cultural contexts and peculiarities of the current samples. Concluding, implications of the current findings are reviewed.

Learning about mental healthcare in today's Cuba: An interview with the president of the Cuban society of psychology.

PURPOSE: Little is known about Cuba's mental healthcare system. We present background information and an interview with the President of the Cuban Society of Psychology to learn about current mental healthcare in today's Cuba. CONCLUSIONS: Mental and medical healthcare are free and fully integrated. Early diagnosis and intervention is standard as each patient is known by their community doctor/nurse team from infancy through old age and by yearly home visits. PRACTICE IMPLICATIONS: Free and integrated medical and mental healthcare facilitates early detection and intervention. Individuals in Cuba are assisted in maintaining job and schooling during treatment. Therapy is multimodal and eclectic.

Posttraumatic growth indicators in Brazilian and Pakistani samples / Indicadores de crecimiento postraumático en una muestra brasileña y pakistaní / Indicadores de crescimento pós-traumático em amostra brasileira e paquistanesa

We investigated indicators of posttraumatic growth (PTG) in victims of disasters. Six hypotheses were tested: the symptoms of re-experiencing and avoidance, typical of posttraumatic stress disorder (PTSD), would be positive predictors of PTG (h1); the Pakistanis would have lower PTG rates when compared to Brazilians (h2); higher number of traumatic events (h3), bombings and terrorism (h4) and pathological personality traits (h5) would be negative predictors of PTG; and the religiosity factor would be a positive indicator of PTG (h6). Participants included 202 subjects, 64.9% male with age ranges between 18 and 66 years (M = 28.07; SD = 8.82). Instruments used included the Posttraumatic Growth Inventory, the PTSD Checklist for DSM-5 and the Clinical Dimensional Personality Inventory-Screening. All hypotheses were partially corroborated. We discuss the implications of the transposition of Western evaluation methods and the posttraumatic perspective to Non-Western contexts.

Investigou-se indicadores de crescimento pós-traumático (CPT) em vítimas de desastres por meio de seis hipóteses: os sintomas de reexperimentação e evitação, típicos do transtorno de estresse pós-traumático (TEPT), seriam preditores positivos de CPT (h1); os paquistaneses teriam menores taxas de CPT quando comparados a brasileiros (h2), maior número de eventos traumáticos (h3), bombardeios e terrorismo (h4) e traços patológicos de personalidade (h5) seriam preditores negativos de CPT e o fator religiosidade seria um indicador positivo do CPT (h6). Participaram do estudo 202 indivíduos, 64,9% homens com idades entre 18 e 66 anos (M = 28,07; DP = 8,82). Os instrumentos utilizados incluíram o Inventário de Crescimento Pós-Traumático, o PTSD Checklist for DSM-5 e o Inventário Dimensional Clínico da Personalidade-Versão Triagem. As hipóteses foram parcialmente corroboradas. Se discute a transposição de métodos de avaliação ocidentais e perspectiva pós-traumática para contextos orientais.

Se han investigado indicadores de crecimiento postraumático (CPT) en víctimas de desastres a través de seis hipótesis: los síntomas de re experimentación y evitación, típicos del trastorno de estrés postraumático (TEPT), serían predictores positivos de CPT (h1); los paquistaníes tendrían menores tasas de CPT cuando comparados a brasileños (h2), mayor número de eventos traumáticos (h3), bombardeos y terrorismo (h4) y rasgos patológicos de personalidad (h5) serían predictores negativos de CPT y el factor religiosidad sería un indicador positivo del CPT (h6). Participaron 202 individuos, 64,9% hombres con edades entre 18 y 66 años (M = 28,07, DP = 8,82). Los instrumentos utilizados incluyeron el Inventario de Crecimiento Post-traumático, la lista de verificación del PTSD para el Checklist for DSM-5 y el Inventario Dimensional Clínico de la Personalidad - Versión EvaluaciónTriage. Las hipótesis fueron parcialmente corroboradas. Se discute la transposición de métodos de evaluación occidentales y perspectiva post-traumática para contextos orientales.

Bi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice.

Mutations in the ryanodine receptor 1 (RYR1) gene are associated with several human congenital myopathies, including the dominantly inherited central core disease and exercise-induced rhabdomyolysis, and the more severe recessive phenotypes, including multiminicore disease, centronuclear myopathy, and congenital fiber type disproportion. Within the latter group, those carrying a hypomorphic mutation in one allele and a missense mutation in the other are the most severely affected. Because of nonsense-mediated decay, most hypomorphic alleles are not expressed, resulting in homozygous expression of the missense mutation allele. This should result in 50% reduced expression of the ryanodine receptor in skeletal muscle, but its observed content is even lower. To study in more detail the biochemistry and pathophysiology of recessive RYR1 myopathies, here we investigated a mouse model we recently generated by analyzing the effect of bi-allelic versus mono-allelic expression of the RyR1 p.A4329D mutation. Our results revealed that the expression of two alleles carrying the same mutation or of one allele with the mutation in combination with a hypomorphic allele does not result in functionally equal outcomes and impacts skeletal muscles differently. In particular, the bi-allelic RyR1 p.A4329D mutation caused a milder phenotype than its mono-allelic expression, leading to changes in the biochemical properties and physiological function only of slow-twitch muscles and largely sparing fast-twitch muscles. In summary, bi-allelic expression of the RyR1 p.A4329D mutation phenotypically differs from mono-allelic expression of this mutation in a compound heterozygous carrier.

Bienestar psicológico en cuidadores de pacientes con enfermedad oncológica / Psychological well-being in caregivers of patients with oncological disease

Introducción: La psicología otorga una gran relevancia a los estudios relacionados con el bienestar psicológico y la atención clínica de los cuidadores informales primarios, por constituir un grupo vulnerable a sufrir afectaciones físicas y psicológicas. Objetivo: Caracterizar el bienestar psicológico en cuidadores informales primarios de pacientes con cáncer de cabeza y cuello. Métodos: Se realizó un estudio descriptivo-correlacional, con una metodología mixta. La muestra estuvo conformada por 100 cuidadores informales primarios de pacientes con cáncer de cabeza y cuello, hospitalizados en el Instituto Nacional de Oncología y Radiobiología de La Habana, desde diciembre de 2016 a marzo de 2017, los que cumplieron con los criterios de inclusión. Para la recolección de información se aplicó la entrevista a sujetos tipos y como instrumento la Escala de Bienestar Psicológico para Adultos (BIEPS-A). Se solicitó el consentimiento informado para la participación de los cuidadores. Resultados: Los resultados revelaron bajos niveles de bienestar psicológico, siendo la autonomía la dimensión más deteriorada en los cuidadores del estudio; se evidenció una interacción inversamente proporcional, entre esta dimensión y el vínculo emocional con el paciente. Conclusiones: El bienestar psicológico de los cuidadores disminuye debido a las afectaciones en su salud física y psíquica, por las limitaciones a las que están sujeto en el contexto personal y laboral y por el predominio de estados emocionales negativos. Sus expresiones positivas solo están relacionadas con los motivos que los movilizaron a asumir el rol de cuidador, a la experticia adquirida durante el cuidado y la posibilidad de acompañar al familiar durante la enfermedad y el tratamiento(AU)

Introduction: Psychology gives great importance to the studies related to psychological well-being, and the clinical care of primary informal caregivers, as they constitute a group vulnerable to suffer physical and psychological effects. Objective: To characterize the psychological well-being in primary informal caregivers of patients with head and neck cancer. Methods: A descriptive-correlational study, with a mixed methodology was carried out. The sample consisted of 100 primary informal caregivers of patients with head and neck cancer hospitalized in the National Institute of Oncology and Radiobiology of Havana, from December 2016 to March 2017, who met the inclusion criteria. For the collection of information it was applied the interview with subject types and as instrument the Scale of Psychological well-being for Adults (BIEPS-A). Informed consent was requested for caregiver's participation. Results: The results revealed low levels of psychological well-being, being autonomy the most deteriorated dimension in caregivers of the study and it was evidenced an inversely proportional interaction between this dimension and the emotional bond with the patient. Conclusions: The psychological well-being of carers decreases due to the damages to their physical and mental health caused by the limitations to which they are subject in the personal and work context and due to the predominance of negative emotional states. Their positive expressions are only related to reasons that moved them to assume the role of caregiver, to the expertise gained during the care and to the possibility to accompany their relative during the illness and treatment(AU)

Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations.

Mutations in the RYR1 gene are the most common cause of human congenital myopathies, and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle (EOM) involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in EOMs from compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutant mice was significantly reduced compared with that observed in wild-type, single heterozygous mutant carriers or homozygous RyR1p.A4329D mice. The decrease in muscle force was also accompanied by approximately a 40% reduction in RyR1 protein content, a decrease in electrically evoked calcium transients, disorganization of the muscle ultrastructure and a decrease in the number of calcium release units. Unexpectedly, the superfast and ocular-muscle-specific myosin heavy chain-EO isoform was almost undetectable in RyR1p.Q1970fsX16+p.A4329D mutant mice. The results of this study show for the first time that the EOM phenotype caused by the RyR1p.Q1970fsX16+p.A4329D compound heterozygous Ryr1 mutations is complex and due to a combination of modifications including a direct effect on the macromolecular complex involved in calcium release and indirect effects on the expression of myosin heavy chain isoforms.

Autocuidado en mujeres de mediana edad con obesidad / Self-care in middle-aged women with obesity

RESUMEN Introducción: El énfasis del autocuidado recae en la responsabilidad de la persona sobre su propia salud y enfermedad. Los cuidados brindados a si mismo desde el punto de vista físico, psicológico y social resultan pertinentes ante la prevalencia creciente de enfermedades crónicas no transmisibles como la obesidad, que va más allá de una cuestión estética y ocasiona graves consecuencias para la salud. Objetivo: Caracterizar la dimensión física, psicológica y social del autocuidado en mujeres de mediana edad con obesidad que se atienden en el Instituto Nacional de Endocrinología. Métodos: Se realizó un estudio exploratorio-descriptivo con una metodología cualitativa, haciendo uso del método de estudio de casos múltiples y la integración de diferentes técnicas. Se realizó un análisis de contenido que permitió identificar regularidades y rupturas entre los casos de estudio. Fueron considerados y aplicados los aspectos éticos. Resultados: Se encontró que el conocimiento de la enfermedad, la ausencia de hábitos nocivos y el buen control de la salud, fueron los aspectos del autocuidado físico más promovidos. Se mostró un pobre desarrollo del autocuidado psicológico mediante un afrontamiento pasivo de la enfermedad, emociones negativas e insatisfacción con la imagen corporal que afectaba la esfera autovalorativa, junto a una escasa proyección futura. El autocuidado social se vio favorecido por la red de apoyo familiar y las actividades en el tiempo libre. Conclusiones: Las dimensiones física y social del autocuidado son las más atendidas por las mujeres, en cambio, la psicológica es la de mayor vulnerabilidad(AU)

ABSTRACT Introduction: The emphasis of self-care lies in the responsibility of each person on their own health and diseases. The self-care given from the physical, psychological and social perspectives are relevant in view of the increasing prevalence of chronic non-communicable diseases such as obesity, which goes beyond an aesthetic issue and causes serious health consequences. Objective: To characterize the physical, psychological and social dimensions of self-care in middle-aged women with obesity, that are treated in the National Institute of Endocrinology. Methods: It was carried out a descriptive exploratory study with a qualitative methodology by using the method of multiple case studies and the integration of different techniques. It was conducted an analysis of content that made possible to identify regularities and ruptures between the cases of study. The ethical aspects were considered and applied. Results: It was found that the knowledge of this disease, the absence of harmful habits and the good control of health were the most promoted physical aspects of self-care. It was shown a poor development of psychological self-care through a passive coping with the disease, negative emotions and dissatisfaction with the body image that affected the self-evaluative area, along together to a short future projection. The social self-care was favoured by a family support network and activities in the spare time. Conclusions: The physical and social dimensions of self-care are the most cared by women; on the other hand, the psychological dimension is of greater vulnerability(AU)

Causal attribution for mental illness in Cuba: A thematic analysis.

Explanatory models (EMs) for illness are highly relevant for patients, and they are also important for clinical diagnoses and treatment. EMs serve to capture patients' personal illness narratives and can help reveal how culture influences these narratives. While much research has aimed to understand EMs in the Western hemisphere, less research has been done on other cultures. Therefore, we investigated local causal attributions for mental illness in Cuba because of its particular history and political system. Although Cuban culture shares many values with Latin American cultures because of Spanish colonization, it is unique because of its socialist political and economic context, which might influence causal attributions. Thus, we developed a qualitative interview outline based on the Clinical Ethnographic Interview and administered interviews to 14 psychiatric patients in Havana. We conducted a thematic analysis to identify repeated patterns of meaning. Six patterns of causal attribution for mental illness were identified: (1) Personal shortcomings, (2) Family influences, (3) Excessive demands, (4) Cultural, economic, and political environment in Cuba, (5) Physical causes, and (6) Symptom-related explanations. In our sample, we found general and Cuba-specific patterns of causal attributions, whereby the Cuba-specific themes mainly locate the causes of mental illness outside the individual. These findings might be related to Cubans' socio-centric personal orientation, the cultural value of familismo and common daily experiences within socialist Cuban society. We discuss how the findings may be related to social stigma and help-seeking behavior.

Carga en cuidadores informales primarios de personas adultas con enfermedades neurológicas crónicas / Burden in primary informal caregivers of adults with chronic neurological diseases

RESUMEN Introducción: Aunque el envejecimiento de las poblaciones humanas es un fenómeno universal, en Cuba los cambios demográficos son significativos. El incremento de la esperanza de vida y el desarrollo de enfermedades neurológicas crónicas aumentan el número de cuidadores informales primarios. Objetivos: Caracterizar la carga en cuidadores informales primarios de personas con enfermedades neurológicas crónicas de expresión clínica en el adulto. Método: Se trata de un estudio descriptivo, correlacional, transversal y no experimental, concebido desde una metodología mixta. La muestra quedó conformada por 19 cuidadores informales primarios con una edad aproximada de 46 años, se le aplicaron técnicas como la entrevista inicial de caracterización del cuidador y de la persona a quien cuida, la entrevista semiestructurada y la Escala de carga del cuidador de Zarit. Para el análisis de los resultados se utilizó el análisis de contenido, la triangulación metodológica y la estadística descriptiva e inferencial. Resultados: Se identificó una tendencia a percibir carga en el proceso de cuidado debido a la presencia de estresores como: el validismo disminuido del enfermo; la modificación de la actividad laboral; los años de duración de la enfermedad; las horas diarias dedicadas al cuidado; la multiplicidad de roles paralelos al de cuidador y las múltiples tareas de cuidado. Conclusiones: Se concluye, que los resultados del proceso de cuidado asociados a la carga se expresan como tendencia en: la disminución del tiempo libre de los cuidadores, el deterioro de su salud psíquica, estados emocionales negativos y un aumento de sus responsabilidades, siendo el impacto del cuidado la dimensión más significativa.

ABSTRACT Introduction: Although human population's aging is a global phenomenon, in Cuba the demographic changes are significant. The increase of the life expectancy and the development of chronic neurological diseases rise the number of primary informal caregivers. Objective: The aim of this paper was to characterize the burden in primary informal caregivers of people with chronic neurological diseases that have clinical expression in adults. Methods: Descriptive, correlational, transversal and non-experimental study that was conceived from a mixed methodology. The sample was formed of 19 primary informal caregivers with an average age of 46 years, and some techniques were used with them such as the Initial interview for characterizing the caregiver and the person they care, the semi-structured interview and the Zarit´s Burden Scale. For the analysis of the results, content analysis, methodological triangulation and descriptive and inferential statistics were used. Results: It was possible to identify a trend to perceive burden in the care process due to the presence of stressors such as: the decreased validity of the patient; the modification of work activity; the years of duration of the disease; the daily hours dedicated to care; the multiplicity of roles parallel to that of the caregiver and the multiple tasks of care. Conclusions: The results of the care process linked with the burden are expressed as a trend in: a decrease in the free time of the caregivers; a deterioration of their psychic health; negative mood and an increase of their responsibilities, being the impact of the care the most significant dimension.