TGFß superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids.

Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are a promising system for studying the distinct features of the developing human brain and the underlying causes of many neurological disorders. While organoid technology is steadily advancing, many challenges remain, including potential batch-to-batch and cell-line-to-cell-line variability, and structural inconsistency. Here, we demonstrate that a major contributor to cortical organoid quality is the way hPSCs are maintained prior to differentiation. Optimal results were achieved using particular fibroblast-feeder-supported hPSCs rather than feeder-independent cells, differences that were reflected in their transcriptomic states at the outset. Feeder-supported hPSCs displayed activation of diverse transforming growth factor ß (TGFß) superfamily signaling pathways and increased expression of genes connected to naive pluripotency. We further identified combinations of TGFß-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enhance the formation of well-structured brain tissues suitable for disease modeling.

Identification of neural oscillations and epileptiform changes in human brain organoids.

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.

Causal analysis of fetal death in high-risk pregnancies.

OBJECTIVES: To determine the causes of fetal death among the stillbirths using two classification systems from 22 weeks of gestation in a period of three years in high-risk pregnancies. This is a retrospective observational study. METHODS: The National Institute of Perinatal Health in Mexico City is a Level 3 care referral center attending high-risk pregnancies from throughout the country. The population consisted of patients with fetal death during a three-year period. Between January 2016 and December 2018, all stillbirths were examined in the Pathology Department by a pathologist and a medical geneticist. Stillbirth was defined as a fetal death occurring after 22 weeks of gestation. RESULTS: Main outcome measures: Causal analysis of fetal death using the International Statistical Classification of Disease and Related Health Problems-Perinatal Mortality (ICD-PM) and initial causes of fetal death (INCODE) classification systems. A total of 297 stillborn neonates were studied. The distribution of gestational age in antepartum stillbirths (55.2%) showed a bimodal curve, 36% occurred between 24 and 27 weeks and 32% between 32 and 36 weeks. In comparison, the majority (86%) of intrapartum deaths (44.8%) were less than 28 weeks of gestation. Of the 273 women enrolled, 93 (34%) consented to a complete fetal autopsy. The INCODE system showed a present cause in 42%, a possible cause in 54% and a probable cause in 93% of patients. CONCLUSIONS: The principal causes of antepartum death were fetal abnormalities and pathologic placental conditions and the principal causes of intrapartum death were complications of pregnancy which caused a premature labor and infections.

Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study.

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. RESULTS: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Prevalence and characterization of carbapenem-resistant bacteria in water bodies in the Los Angeles-Southern California area.

Carbapenems are ß-lactam antibiotics used in healthcare settings as last resort drugs to treat infections caused by antibiotic-resistant bacteria. Carbapenem-resistant bacteria are increasingly being isolated from healthcare facilities; however, little is known about their distribution or prevalence in the environment, especially in the United States, where their distribution in water environments from the West Coast has not been studied before. The aim of this study was to determine the prevalence of carbapenem-resistant bacteria and carbapenemase genes in water bodies from the Los Angeles area (California, USA). All samples that were analyzed contained carbapenem-resistant bacteria with a frequency of between 0.1 and 324 carbapenem-resistant cfu per 100 mls of water. We identified 76 carbapenem-resistant or -intermediate isolates, most of which were also resistant to noncarbapenem antibiotics, as different strains of Enterobacter asburiae, Aeromonas veronii, Cupriavidus gilardii, Pseudomonas, and Stenotrophomonas species. Of them, 52 isolates were carbapenemase-producers. Furthermore, PCR and sequence analysis to identify the carbapenemase gene of these carbapenemase-producing isolates revealed that all Enterobacter asburiae isolates had a blaIMI-2 gene 100% identical to the reference sequence, and all Stenotrophomonas maltophlia isolates had a blaL1 gene 83%-99% identical to the reference blaL1 . Our findings indicate that water environments in Southern California are an important reservoir of bacteria-resistant to carbapenems and other antibiotics, including bacteria carrying intrinsic and acquired carbapenemase genes.

Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections.

BACKGROUND: Human Ebola infection is characterized by a paralysis of the immune system. A signature of αß T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014-2015 occurred in West Africa, and to assess their association with the clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. CONCLUSIONS/SIGNIFICANCES: Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells.

El chi kung cómo herramienta terapéutica de la medicina tradicional y natural / Chi kung as a Therapeutic Tool for Traditional and Natural Medicine

El conocimiento de la medicina tradicional china, desde el punto de vista de la bioenergética, se vincula estrechamente con el empleo del chi kung (qigong) como herramienta terapéutica de esta medicina ancestral. Según las fuentes encontradas, queda claro que surge en China como una terapia médica para la prevención y curación de enfermedades. Las formas del chi kung implican una regulación de la respiración y la mente con los movimientos que se realizan y consiste en un conjunto de técnicas energéticas realizadas desde tiempos remotos con el objetivo de desarrollar la salud, la vitalidad y la conciencia espiritual.

Análisis por conglomerados para evaluar el control metabólico de pacientes diabéticos tipo 2 / Analysis by Cluster for assessment of metabolic control in type 2 diabetics

Objetivo: Evaluar el descontrol metabólico (DMtb) en pacientes con diabetes mellitus tipo 2 (DM2), aplicando codificación geométrica de variables y clasificación por conglomerados. Diseño: Estudio observacional, prospectivo, transversal, descriptivo y analítico. Emplazamiento: Institución de Salud de Ciudad del Carmen, Campeche. Sujetos: Se evaluaron 39 pacientes con DM2, ambulatorias derechohabientes, sin tratamiento farmacológico y que acuden por primera vez a consulta nutricional. Métodos: Codificación de variables vinculadas al DMtb en la DM2, aplicando progresión geométrica. Fueron codificadas: presión arterial (PA), glucemia en ayunas (GA), Índice de Masa Corporal (IMC), colesterol total (CT) y triglicéridos (TGs) en ayunas. Criterios para categorización y análisis, en la Norma Oficial Mexicana (NOM-015-SSA2-2010). Se calculó el porcentaje de la muestra en cada conglomerado, evaluándose similitud y diferencia entre ellos. Se determinó correlación y concordancia entre variables, y sus combinaciones. Resultados: El 87.2% de los pacientes mostró DMtB. Se observó que el IMC elevado se vincula con la alteración de otros indicadores de DMtB. Los conglomerados IMC-GA alterada, e IMC-TGs-GA alterada, representan cada uno el 20,5% de la muestra. Se identificó asociación y concordancia entre DMtb y edad del paciente (V de Cramer = 0.37, p=0.002 y Tau-b de Kendall=0.037, p=0.001), no así para DMtb y sexo (V de Cramer = 0.60, p=0.71 y Tau-b de Kendall=0.037, p=0.71). Conclusión: El DMtb se presenta como condición frecuente en pacientes con DM2, mostrando asociación con la edad, más no con el sexo. El IMC elevado está vinculado con otros indicadores de DMtb, y se muestra particularmente conglomerado con GA y TGs (AU)

Objective: To evaluate the metabolic descontrol (DM tb) in patients with type 2 diabetes mellitus (DM2), using geometric coding of variables and classification by cluster. Design: observational, prospective, transversal, descriptive and analytical study. Location: Institution of Health of Ciudad del Carmen, Campeche. Subjects: 39 patients with DM2, outpatient successors, were evaluated without drug treatment and attending for the first time nutritional consultation. Methods: Coding of variables related to DMtb in DM2, applying geometric progression. They were coded: blood pressure (BP), fasting blood glucose (GA), Body Mass Index (BMI), total cholesterol (TC) and triglycerides (TGs) fasting. Criteria for categorization and analysis in the Official Mexican Norm (NOM-015-SSA2-2010). The percentage of the sample in each cluster, were evaluated similarity and was calculated difference between them. Correlation and concordance between variables was determined, and combinations thereof. Results: 87.2% of patients showed DMtb. It was observed that high BMI is associated with the alteration of other indicators of DMtb. The altered of conglomerates IMC-GA and BMI-TGs-GA each represent 20.5% of the sample. Was identified association and concordance between DMtb and patient age (Cramer’s V = 0.37, p = 0.002 and Tau-b of Kendall = 0.037, p = 0.001), but not for DMtb and sex (Cramer’s V = 0.60, p = 0.71 and Tau-b of Kendall = 0.037, p = 0.71). Conclusion: The DMtb is presented as frequent condition in patients with DM2, showing association with age, but not with sex. Elevated BMI is linked to other indicators DMtb, and it shows particularly conglomerate with GA and TGs (AU)

Planificación de los recursos humanos para la salud / Health manpower planning

El presente trabajo describe en apretada síntesis la experiencia cubana en el proceso de planificación de recursos humanos para la salud y analiza este proceso sobre la base del enfoque estratégico del Sistema Unico de Salud y como parte integrante e inseparable del desarrollo económico y social del país. En él se describen, además, las tres etapas fundamentales del desarrollo del sistema de salud y la evolución de la planificación y formación de los recursos humanos, así como la disponibilidad actual de recursos y lo que se espera alcanzar para el año 2000. Se explican la metodología para la elaboración de planes y los procedimientos que garantizan la participación e integración funcional de las diferentes áreas del Ministerio de Salud Pública y los territorios, ya que ambos son fundamentales para lograr los principales objetivos del desarrollo de la salud. Al mismo tiempo, se abordan los procesos de selección para el ingreso a la red de centros de educación médica, donde se lleva a cabo la formación de los recursos humanos de salud, así como los elementos fundamentales para garantizar el cumplimiento de los diferentes planes de pregrado y especialización. Se presentan cifras sobre el personal de salud en formación y los egresados de estos centros, destacándose la colaboración de Cuba con otros países en la formación de sus recursos para la salud. Finalmente se emiten consideraciones sobre los resultados obtenidos en este campo

Planificación de los recursos humanos para la salud / Health manpower planning

El presente trabajo describe en apretada síntesis la experiencia cubana en el proceso de planificación de recursos humanos para la salud y analiza este proceso sobre la base del enfoque estratégico del Sistema Unico de Salud y como parte integrante e inseparable del desarrollo económico y social del país. En él se describen, además, las tres etapas fundamentales del desarrollo del sistema de salud y la evolución de la planificación y formación de los recursos humanos, así como la disponibilidad actual de recursos y lo que se espera alcanzar para el año 2000. Se explican la metodología para la elaboración de planes y los procedimientos que garantizan la participación e integración funcional de las diferentes áreas del Ministerio de Salud Pública y los territorios, ya que ambos son fundamentales para lograr los principales objetivos del desarrollo de la salud. Al mismo tiempo, se abordan los procesos de selección para el ingreso a la red de centros de educación médica, donde se lleva a cabo la formación de los recursos humanos de salud, así como los elementos fundamentales para garantizar el cumplimiento de los diferentes planes de pregrado y especialización. Se presentan cifras sobre el personal de salud en formación y los egresados de estos centros, destacándose la colaboración de Cuba con otros países en la formación de sus recursos para la salud. Finalmente se emiten consideraciones sobre los resultados obtenidos en este campo (AU)

Recursos humanos en salud de Cuba / Health manpower in Cuba

Desde 1959, Cuba triplicó el número de instalaciones médicas, equipo y servicios de salud que atienden a la población. En ese contexto, los recursos humanos en salud son adecuados para lograr los objetivos del plan de salud pública. La disponibilidad de recursos humanos en 1985 fue del 100% (247,2 integrantes del personal de salud por 10000 habitantes). La distribución geográfica presenta el desequilibrio urbano-rural que es habitual, pero que tiende a mejorar; se señala el caso de La Habana que en 1959 concentraba el 63% de los médicos y que actualmente concentra el 29,9%. Debido a que los recursos humanos en salud en Cuba son suficientes y de nivel adecuado a las necesidades, las recomendaciones tienden a mejorar algunos aspectos como: la asimilación de la tecnología moderna, dar mayor importancia a la prevención y a la atención primaria y prover un médico por 120 familias o 600 personas a través de la creación de la especialidad de la medicina general integral