Advancing disability-inclusive climate research and action, climate justice, and climate-resilient development.

Globally, more than 1 billion people with disabilities are disproportionately and differentially at risk from the climate crisis. Yet there is a notable absence of climate policy, programming, and research at the intersection of disability and climate change. Advancing climate justice urgently requires accelerated disability-inclusive climate action. We present pivotal research recommendations and guidance to advance disability-inclusive climate research and responses identified by a global interdisciplinary group of experts in disability, climate change, sustainable development, public health, environmental justice, humanitarianism, gender, Indigeneity, mental health, law, and planetary health. Climate-resilient development is a framework for enabling universal sustainable development. Advancing inclusive climate-resilient development requires a disability human rights approach that deepens understanding of how societal choices and actions-characterised by meaningful participation, inclusion, knowledge diversity in decision making, and co-design by and with people with disabilities and their representative organisations-build collective climate resilience benefiting disability communities and society at large while advancing planetary health.

NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

Multimodal Chronic Pain Therapy for Adults via Smartphone: Randomized Controlled Clinical Trial.

BACKGROUND: Combination therapies delivered remotely via the internet or mobile devices are increasingly being used to improve and promote the self-management of chronic conditions. However, little is known regarding the long-term effects of these interventions. OBJECTIVE: The aim of this study is to evaluate the effectiveness of a multimodal intervention program that measures associated variables such as catastrophizing, pain acceptance, and quality of life using a mobile device in people with chronic pain in an outpatient setting. METHODS: A randomized controlled clinical trial was performed using parallel treatment groups. A total of 209 patients with chronic musculoskeletal pain were randomly assigned to one of the two study arms. The intervention group received a standard web-based psychosocial therapy-type program of activities through a smartphone for 6 weeks. The control group only had access to the Find out more section of the app, which contained audiovisual material for pain management based on a self-help approach. The primary outcome was catastrophizing measured using the Pain Catastrophizing Scale (PCS). Secondary outcomes were pain acceptance measured using the Chronic Pain Acceptance Questionnaire and health-related quality of life measured using the EuroQol Visual Analogue Scale. Assessments were conducted at baseline (T1), after treatment (T2), and at the 3-month follow-up (T3). The variations between the different phases were assessed using the percentage change rescaled with log base 2. The Cohen d was calculated based on the results of the linear mixed model. The investigators of the study who evaluated the results were not involved in patient recruitment and were blinded to the group assignment. RESULTS: Positive effects were found in the intervention group (T2-T1) in catastrophizing between the baseline and posttreatment phases (P<.001) and in helplessness (-0.72 vs 0.1; P=.002), rumination (-1.59 vs -0.53; P<.001), acceptance (0.38 vs 0.05; P=.001), and quality of life (0.43 vs -0.01; P=.002), although no significant changes were found for magnification (0.2 vs 0.77; P=.14) and satisfaction with health (0.25 vs -0.27; P=.13). Three months after treatment, significant differences were observed in the intervention group for the outcome variable of catastrophizing (PCS; -0.59 vs 0.2; P=.006) and the PCS subscales of helplessness (-0.65 vs 0.01; P=.07), rumination (1.23 vs -0.59; P=.04), and magnification (0.1 vs 0.86; P=.02). CONCLUSIONS: The results of our study suggest that app-based mobile multidimensional treatments for adults with chronic pain improve catastrophizing, quality of life, and psychological flexibility immediately after treatment and that the effects are maintained for the primary outcome of catastrophizing for at least 3 months following treatment. Moreover, they promote self-management and can be used to complement face-to-face pain treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04509154; https://clinicaltrials.gov/ct2/show/NCT04509154.

Multimodal Interventions to Improve the Management of Chronic Non-Malignant Pain in Primary Care Using Participatory Research.

BACKGROUND: The use of diverse therapies combined with a multidisciplinary approach and prevention initiatives for patients with chronic non-malignant pain (CNMP) can improve health and have a positive impact on psychotropic drug use and the self-management of pain. PURPOSE: This purpose of this study has been two-fold: to conduct a literature review with a view to selecting best evidence recommendations for CNMP and to prioritize self-care recommendations using a participatory methodology for the analysis and selection of interventions. METHODS: A qualitative, descriptive, and documentary method based on participatory action research was used. FINDINGS: Based on the study results, a multimodal psychosocial intervention program has been designed for CNMP that includes psychoeducational therapy, pharmacological therapy, physical exercise, and health assets. DISCUSSION: The findings are consistent with previous studies underlining the need to invest in resources for the management of CNMP, including strategies for good differential diagnoses and pharmacological treatments combined with non-pharmacological treatments to confer greater well-being for people living with pain who want to participate in their own recovery.

Conocimientos, actitudes y prácticas sobre donación y trasplante de córneas en comunidades rurales y urbanas de Honduras / Knowledge, attitudes and practices about corneal donation and transplantation in rural and urban communities in Honduras

Introducción: aproximadamente 600 personas urgen de trasplante de córnea en Honduras. La mayor dificultad para este procedimiento es que no se cuenta con banco de ojo en el país. Además, los estudios de conocimiento sobre donación y trasplante, son escasos. Objetivo: conocer las actitudes y prácticas de la población rural versus la urbana sobre la donación y trasplante de córnea, según conocimientos y factores sociodemográficos, con el fin de diseñar un plan de acción para concientizar la importancia de una conducta donante positiva para el beneficio del paciente con ceguera corneal. Metodología: estudio descriptivo realizado entre mayo y septiembre del 2019 en Comayagua, Intibucá y Francisco Morazán. Con una muestra de 350 personas por departamento, para un total de 1050 participantes mayores de 18 años y de ambos sexos. Se realizó entrevista por investigadores, bajo la escala de Likert, previamente validado. Variables agrupadas en demográficas, socio personales, laborales, conocimiento, creencias y aptitudes. Se analizaron los datos mediante razón de probabilidades y productos cruzados. Los resultados se expresaron en porcentajes, frecuencias y odd ratio. Resultados: 74.86% manifestó una actitud donante positiva, el 67.55% donaría a cualquier persona que lo necesitase, 48% conocía acerca de las características requeridas para el donante y. menos del 10% sabía qué es la córnea. Los factores negativos para la donación son la procedencia rural, la parentela y el desempleo en Intibucá y motivos religiosos en el área rural de Comayagua y población urbana de Francisco Morazán. Conclusiones: Es importante superar las limitaciones impuestas por la desinformación, para ello es necesario impulsar una cultura de donación a través de la creación de estrategias comunicativas de educación, con el fin de mejorar la salud visual y la demanda poblacional...(AU)

Predicción temporal de CD4+ en 80 pacientes con manejo antirretroviral a partir de valores de leucocitos / CD4+ temporal prediction in 80 patients with antiretroviral management from leukocyte counts

Objetivo: establecer una metodología predictiva de aplicación clínica de recuentos de CD4+ en rangos de interés clínico a partir del recuento absoluto de leucocitos. Metodología: a partir de los valores secuenciales de leucocitos y linfocitos CD4+ de 9 pacientes, se observaron patrones matemáticos que posteriormente fueron aplicados en un estudio ciego con 71 casos para confirmar su capacidad predictiva, midiendo porcentajes de especificidad y sensibilidad. Resultados: se determinaron cinco patrones matemáticos que predicen en el 99% de los casos los distintos recuentos de CD4+ a partir de recuentos de leucocitos con valores de especificidad y sensibilidad del 99%. Conclusiones: los patrones matemáticos encontrados entre recuento de leucocitos y CD4+ sugieren que este fenómeno prácticamente es determinista.

Objective: To establish a predictive methodology of CD4+ counts for clinical application in ranges of clinical interest based on the absolute leukocyte count. Methodology: From sequential values of leukocytes and CD4+ lymphocytes of nine patients, mathematical patterns were observed and applied in a blind study with 71 cases to confirm their predictive capacity, measuring percentages of specificity and sensitivity. Results: Five mathematical patterns were determined that predict 99% of the cases in which CD4+ counts are obtained from leukocyte counts with specificity and sensitivity values of 99%. Conclusions: The mathematical patterns found between leukocytes and CD4 counts suggest that this phenomenon is practically deterministic.

Comportamiento fractal de infecciones asociadas al cuidado de la salud en el Hospital de Meissen ESE II Nivel, para los años 2011, 2012 y 2013 / Fractal behavior of infections associated with health care at Meissen Hospital ESE II Level, for the years 2011, 2012 and 2013

Introducción: la dimensión fractal estadística ha sido de utilidad para la caracterización de diversos fenómenos, incluyendo la dinámica cardiaca fetal y del adulto, así como comportamientos asociados al sistema inmune. Las Infecciones Asociadas al Cuidado de la Salud son un problema de salud de alta importancia a nivel mundial. Objetivo: establecer el comportamiento fractal estadístico de la frecuencia de aparición de Infecciones Asociadas al Cuidado de la Salud. Material y métodos: Se aplicó la ley de Zipf-Mandelbrot a la distribución de frecuencias de aparición agrupadas por especialidad de Infecciones Asociadas al Cuidado de la Salud en el Hospital Meissen ESE II Nivel, para los años 2011, 2012 y 2013. Se calculó la dimensión fractal estadística para cada año, hallando los rangos en los que se desenvuelve la dinámica en estos años y posteriormente se realizaron simulaciones de estas dinámicas anuales. Resultados: Se observó un comportamiento a escala de la dinámica de aparición de Infecciones Asociadas al Cuidado de la Salud por especialidad, los valores de la dimensión fractal fue de 0,6104, 0,7560 y 0,4332 para los años 2011, 2012 y 2013 respectivamente. Conclusión: La ley de Zipf/Mandelbrot permite caracterizar de forma objetiva y reproducible el comportamiento de la frecuencia de aparición de las Infecciones Asociadas al Cuidado de la Salud en el tiempo; las dimensiones fractales acotadas consecutivas en el tiempo permitirían generar predicciones, constituyendo una herramienta de ayuda para la vigilancia epidemiológica y la clínica.

Introduction: The statistical fractal dimension has been useful for the characterization of diverse phenomena, including the fetal and adult cardiac dynamics, as well as the behaviors associated with the immune system. Health Care Associated Infections are a major health problem worldwide. Objective: to establish the statistical fractal behavior of the frequency of occurrence of Health Care Associated Infections. Material and methods: The Zipf-Mandelbrot law was applied to the frequency distribution of occurrences grouped by Health Care Associated Infections in II level at Meissen ESE Hospital for the years 2011, 2012 and 2013. The statistical fractal dimension was calculated for each year, finding the ranges in which the dynamics develops in these years and later simulations of these annual dynamics were carried out. Results: Scale behavior of the dynamics of occurrence of Health Care Associated Infections by specialty was observed; the values of fractal dimension were 0.6104, 0.7560 and 0.4332 for the years 2011, 2012 and 2013 respectively. Conclusion: The law of Zipf / Mandelbrot allows to characterize objectively and reproducibly the behavior of the frequency of occurrence of Health Care Associated Infections over time; the consecutive bounded fractal dimensions over time would allow predictions to be generated, constituting an aid tool for epidemiological and clinical surveillance.

Factores asociados a la resiliencia y adherencia terapéutica en pacientes con injerto renal funcionante / Factors associated with resilience and therapeutic adherence in patients with functioning renal graft

Introducción: El aumento en el número de trasplantes de órganos y la escasa adherencia a los tratamientos una vez realizado el trasplante suscita una actitud de alerta entre los profesionales de enfermería y un problema de salud pública. Objetivo: Conocer los factores asociados a la resiliencia que influyen sobre la adherencia al tratamiento, en este caso en el trasplante con injerto renal. Material y Método: Estudio descriptivo trasversal y retrospectivo en población adulta trasplantada con injerto funcionante desde enero de 2012 hasta junio de 2016 con edades comprendidas entre 18 y 70 años, de ambos sexos, autosuficientes en el manejo de tratamiento; y trasplantados en el Hospital Marqués de Valdecilla. Pertenecientes, como socios, a la Asociación Alcer Cantabria. Resultados: Los resultados obtenidos, aun no siendo significativos por el tamaño muestral, demuestran una influencia positiva (3% de la variabilidad) de la resiliencia en la adherencia al tratamiento. Se demuestran que existen diferencias significativas en alguna de las variables sociodemográficas como la actividad profesional, nivel de estudios y edad. Así mismo, se encuentran diferencias según el nivel de tolerancia a los efectos negativos y estrés. Conclusiones: Los datos revelan mayor riesgo de no adherencia en el grupo de menor edad, por lo que resulta necesario sensibilizar de la importancia de la adherencia al tratamiento. Sorprende la relación inversa entre baja adherencia en pacientes y mayor control situaciona

Introduction: The increase in the number of organ transplants and the poor adherence to the treatments after transplant provokes an alert attitude among the nursing professionals and a public health problem. Aim: To know the factors associated with resilience, which influence adherence to treatment, in this case in kidney graft transplantation. Material and Method: A cross-sectional and retrospective descriptive study was carried out in adult population transplanted with functioning graft, from January 2012 to June 2016 with ages between 18 and 70 years, of both sexes, self-sufficient in the treatment management; and transplanted in the Marqués de Valdecilla Hospital. Belonging, as partners, to the Alcer Cantabria Association. Results: The results obtained, although not being significant due to the sample size, demonstrate a positive influence (3% of the variability) of the resilience in the adherence to the treatment. It is shown that there are significant differences in some of the sociodemographic variables such as professional activity, educational level and age. Likewise, there are differences according to the level of tolerance to negative effects and stress. Conclusions: The data reveal a greater risk of non-adherence in the younger age group, so it is necessary to raise awareness of the importance of adherence to treatment. The inverse relationship between low adherence in patients and greater situational control is surprising

Integration-free induced pluripotent stem cells derived from a patient with autosomal recessive Alport syndrome (ARAS).

A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. This iPSC line offers a useful resource to study Alport syndrome pathomechanisms and drug testing.

Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of Bogotá.

The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.

A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.

Thiamine deficiency impairs common eider (Somateria mollissima) reproduction in the field.

The Baltic Sea population of the common eider (Somateria mollissima) has declined dramatically during the last two decades. Recently, widespread episodic thiamine (vitamin B1) deficiency has been demonstrated in feral birds and suggested to contribute significantly to declining populations. Here we show that the decline of the common eider population in the Baltic Sea is paralleled by high mortality of the pulli a few days after hatch, owing to thiamine deficiency and probably also thereby associated abnormal behaviour resulting in high gull predation. An experiment with artificially incubated common eider eggs collected in the field revealed that thiamine treatment of pulli had a therapeutic effect on the thiamine status of the brain and prevented death. The mortality was 53% in untreated specimens, whereas it was only 7% in thiamine treated specimens. Inability to dive was also linked to brain damage typical for thiamine deficiency. Our results demonstrate how thiamine deficiency causes a range of symptoms in the common eider pulli, as well as massive die-offs a few days after hatch, which probably are the major explanation of the recent dramatic population declines.

Generation of integration-free induced pluripotent stem cell lines derived from two patients with X-linked Alport syndrome (XLAS).

Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. These iPSC lines offer a useful resource to study Alport syndrome pathomechanisms and drug testing.

Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of Bogotá / Comprometimento cognitivo leve (CCL) e demência em uma amostra de adultos na cidade de bogotá

ABSTRACT The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.

RESUMO A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

INTRODUCTION: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. METHODS: NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. RESULTS: Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). CONCLUSION: The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Intrahepatic angiopoietin-2 correlates with chronic hepatitis C progression and is induced in hepatitis C virus replicon systems.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) is a major cause of cirrhosis and hepatocellular carcinoma and angiogenesis is closely related to the pathogenesis and progression of different chronic liver diseases (CLD). Thus, the intrahepatic expression of angiopoietins 1 and 2 (Ang1 and Ang2), as relevant mediators of pathological angiogenesis in several CLD, was investigated. In addition, the differential influence of structural and non-structural genomic regions of HCV on the expression of angiopoietins and the possible signalling involved were studied. METHODS: Ang1 and Ang2 expression was evaluated by western blotting and enzyme-linked immunosorbent assay (ELISA) in liver homogenates of CHC patients (n=47) and uninfected subjects (n=8). Their association with disease progression (according to METAVIR classification) was assessed by Spearman's correlation. Statistical differences among the expression of angiopoietins at different CHC stages were calculated by Mann-Whitney U-test. Finally, the in vitro expression of Angiopoietins in HCV replicons (complete or non-structural subgenomic) and the main signalling pathways involved were also examined. RESULTS: Ang2 levels were significantly higher in the liver of CHC patients compared to controls and significantly correlated with inflammation and fibrosis. Accordingly, an increased expression of Ang2 was found in all HCV replicons tested. Interestingly, the inhibition of MEK and PI3K signalling pathways exerted differential effects on Ang2 expression concerning to the genomic region of HCV. CONCLUSIONS: Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife.

Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

Aneurysmal Degeneration in Patients with Type B Aortic Dissection.

BACKGROUND: The optimal management of type B aortic dissection (TBAD) remains controversial in the era of endovascular therapies. This study reports the outcomes and complication rates of different treatment paradigms for TBAD. METHODS: A retrospective review was undertaken of all patients with TBAD from June 2006 to June 2012. Demographics, hospital course, and follow-up visits were analyzed. Patients who underwent surgical interventions were compared to those with medical therapy. Survival rates and predictors of outcome were determined using the Kaplan-Meier method with Cox proportional hazards. RESULTS: Of 261 consecutive patients who were hospitalized during this period with a confirmed thoracic dissection, 134 (51%) had TBAD. Sixty-two (46%) were women, and the mean age was 66.4 ± 14.9. Median follow-up was 22.4 (0, 184) months. Thirty-five patients underwent surgical intervention with 20 thoracic endovascular aortic repair (TEVAR) and open surgery in 15. The overall 30-day mortality was 7%, and cumulative survival rates at 1, 3, and 5 years were 85% (95% confidence interval [CI], 79-91), 68% (95% CI, 59-78), and 57% (95% CI, 47-69) with no difference between medical versus surgical groups (P = 0.8) and TEVAR versus open surgery group (P = 1.0). Sixty-six (50%) patients developed aneurysmal expansion, which required surgical intervention in 26 (hazard ratios [HR], 0.99; P = 0.96). Malperfusion and rupture only occurred in 5 (HR, 1.57; P = 0.54) and 5 (HR, 3.64; P = 0.01) patients, respectively. Multivariate analysis for overall survival found renal insufficiency (HR, 2.6; P = 0.004) and age (HR, 1.06; P < 0.0001) and rupture (HR 3.3, P = 0.04) were independent predictors of mortality. Intramural hematoma was not a significant predictor of survival (HR, 0.49; P = 0.11). CONCLUSIONS: Medical therapy remains the mainstay of treating TBAD with low morbidity. Surgical interventions are indicated in selected patients with malperfusion or aneurysmal expansion with comparable survival rates.

Deterioro cognitivo y factores de riesgo cardiovascular y metabólico en una muestra de adultos de Bogotá / Cardiovascular and metabolic risk factors, for cognitive impairment in adults from Bogotá

Introducción: la relación entre los factores de riesgo cardiovascular (FRCV) y los factores metabólicos con deterioro cognitivo (DC), definido como deterioro cognitivo leve (DCL) o demencia, es controversial. Objetivo: describir los FRCV y metabólicos relacionados con DC, en una muestra de adultos de Bogotá. Material y métodos: se diseñó un estudio de corte transversal y se evaluó el estado cognitivo en dos fases, en adultos mayores de 50 años, autónomos, no institucionalizados, aplicando pruebas neuropsicológicas y un protocolo de evaluación neuropsiquiátrica. Los FRCV y metabólicos fueron documentados por autoreporte, y se tomaron medidas antropométricas. Resultados: en 1.045 adultos estudiados, el promedio de edad fue de 68 años (DS 8.6), y de educación 8 años (DS 6.0), 76 % fueron mujeres, 56 % presentaba hipertensión arterial (HTA), 40 % dislipidemia, 37 % fueron fumadores, 37 % tenían sobrepeso, 28 % hipotiroidismo, 25 % obesidad, 17 % consumían alcohol y 16 % eran diabéticos. El DCL se asoció con escolaridad de primaria-incompleta OR:1.94 (95 % IC: 1.21- 3.14), primaria-completa OR:1.96 (95 % IC: 1.18- 3.25), bachillerato- incompleto OR:3.01 (95 % IC: 1.80-5.05), bachillerato-completo OR: 2.54 (95 % IC: 1.45- 4.45) y con edad entre 70 y 79 años OR:2.06 (95% IC: 1.32-3.23). La demencia se asoció con escolaridades de primaria-incompleta OR: 11.20 (95 % IC: 4.99- 25.12), primaria-completa OR: 7.91 (95 % IC: 3.44-18.16), bachillerato- incompleto OR: 2.87 (95 % IC: 1.17- 7.01) y con edades entre 70 -79 años OR: 2.82. (95 % IC: 1.37-5.80), o mayores de 80 años OR: 7.68 (95 % IC: 3.49- 16.90) y con sufrir HTA OR: 1.45 (95 % IC: 1.03-2.05). Conclusión: la baja escolaridad, una edad avanzada y sufrir HTA son en su orden los factores más importantes para el desarrollo de la demencia. Los adultos entre 70 y 79 años con bachillerato incompleto, tienen mayor riesgo de DCL.

Introduction: The relationship between some metabolic and cardiovascular risk factors (CVRF) and cognitive impairment (CI) defined as mild cognitive impairment (MCI) and dementia, is controversial. Objective: Describe the cardiovascular and metabolic risk factors that are associated with cognitive impairment in adults from Bogotá. Materials and methods: A cross-sectional study, where the state of cognitive functions (normal, MCI or dementia) was evaluated in two phases, in adults older than 50 years, autonomous, non-institutionalized, using neuropsychological tests and neuropsychiatric protocol. Its cardiovascular and metabolic risk by self-reported history and standardized anthropometric measurements were documented. Results: Of 1045 adults surveyed, the mean age of the group was 68 years(SD 8.6), and the mean education level was 8 years(SD 6.0), 76% were women, 56% had hypertension(HT), 40% dyslipidemia, 37% were smokers, 36% were overweight, 28% presented hypothyroidism, 25% were obese, 17% drank alcohol and 16% were diabetic. MCI was associated with incomplete high school education OR:3.01(95% CI 1.80-5.05) and aged between 70 and 79 years OR:2.06(95%CI 1.32-3.23). Dementia was associated with lower scholarity, incomplete-primary OR:11.20(95%CI 4.99-25.12), complete-primary OR 7.91(95% CI.3.44-18.16), incomplete-high school OR: 2.87(95% CI 1.17-7.01), age over 80 years OR:7.68(95%CI 3.49-16.90); and suffer hypertension OR:1.45(95%CI 1.03- 2.05) Conclusion: Low education, older age and hypertension are in order, the most important risk factors for the development of dementia in our population. Adults between 70 and 79 with incomplete high school have higher risk of MCI.

Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies.

Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.

Acuerdo intra-interobservador en las pruebas Minimental State Examination (MMSE) y Montreal Cognitive Assessment (MoCA test) aplicados por personal en entrenamiento / Intra and interrater reliability of the Minimental State Exmination (MMSE) and Montréal Cognitive Assessment (MoCA test) applied by health personnel in training

Introducción: en el proceso del diagnóstico neuropsicológico, los instrumentos de tamizaje cognitivo, son una herramienta útil en la identificación de cambios mentales del sujeto, en momentos puntuales o a través del tiempo. Su uso se fundamenta en el análisis psicométrico. Objetivo: determinar el acuerdo inter e intra-observador en el MoCA test y el MMSE, aplicado por profesores y estudiantes en procesos de entrenamiento de tamización cognitiva. Materiales y métodos: a los estudiantes y profesores en entrenamiento en la puntuación del MoCA test y el MMSE, se les presentó un video en dos sesiones, con un intervalo de 5 meses, mostrando el desempeño de dos adultos mayores, respondiendo el MoCA test y el MMSE, previo consentimiento informado. Se compararon los puntajes dados en las dos sesiones por los sujetos en entrenamiento, con los de ellos mismos (intra-observador), usando el coeficiente de concordancia y correlación de Lin(rho) y con los del grupo restante (inter-observador) usando el coeficiente de correlación intra-clase (ICC). Resultados: participaron 46 evaluadores. Se encontró alta confiabilidad inter-observador para el MoCA (ICC=0.86), pero baja para el MMSE (ICC=0.24) y baja confiabilidad intra-observador tanto para el MoCA (rho paciente 1=0.012 y rho paciente 2=0.152) como para el MMSE (rho paciente 1=0.008 y rho paciente 2=0.012). Aunque los puntajes difirieron, las clasificaciones diagnósticas realizadas por los evaluadores fueron similares a las del patrón de oro. Conclusión: la correcta aplicación del test, requiere varios entrenamientos, y aunque hubo pocas diferencias entre los puntajes, los errores cuando se está cerca del punto de corte propuesto, aumentan el riesgo de sesgo.

Introduction: The instruments for screening cognitive functions, applied to subjects in clinical settings and research, are useful for determining if this person has any trouble in cognition or show changes in the time. The usefulness of these instruments is defined with the evaluation of their psychometrics properties. Objective: This study allows to determine the intra and inter-observer agreement, when the MoCA test and MMSE were applied by a group in training process Materials and methods: The study group who attended two training sessions, with an interval of 5 months, scored the MoCA test and MMSE, from two patients which were filmed responding the tests, previous informed consent signature. We compared how close were the scores of participants among themselves by concordance correlation coefficient of Lin (rho) and with those given from the others by intra-class correlation coefficients (ICC). Results: In total, 46 participants were included. Intra-rater reliability was high for MoCA test (ICC = 0.86), but it was poor for MMSE (ICC=0.24). Inter-rater was poor for MoCA test (rho patient 1= 0.012, rho patient 2= 0.152) and MMSE (rho patient 1 = 0.008, rho patient 2 = 0.012). Although the scores between participants and gold standard were different, the diagnoses were similar. Conclusion:The correct scoring of the test, requires several trainings to clinical and research groups, and although they can be found few differences between scores applied by non-expert personnel, if the scores mistakenly given, are close to the cut-of point proposed for each test, the bias increases.