MECP2-related disorders while gene-based therapies are on the horizon.

The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes MECP2 Duplication Syndrome (MDS). MDS is found mostly in males and presents with developmental delay, hypotonia, autistic features, refractory epilepsy, and recurrent respiratory infections. While these two disorders share several characteristics, their differences (e.g., affected sex, age of onset, genotype/phenotype correlations) are important to distinguish in the light of gene-based therapy because they require opposite solutions. This review explores the clinical features of both disorders and highlights these important clinical differences.

Meta-Analysis of the Alzheimer's Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.

A Portal to Visualize Transcriptome Profiles in Mouse Models of Neurological Disorders.

Target nomination for drug development has been a major challenge in the path to finding a cure for several neurological disorders. Comprehensive transcriptome profiles have revealed brain gene expression changes associated with many neurological disorders, and the functional validation of these changes is a critical next step. Model organisms are a proven approach for the elucidation of disease mechanisms, including screening of gene candidates as therapeutic targets. Frequently, multiple models exist for a given disease, creating a challenge to select the optimal model for validation and functional follow-up. To help in nominating the best mouse models for studying neurological diseases, we developed a web portal to visualize mouse transcriptomic data related to neurological disorders: http://mmad.nrihub.org. Users can examine gene expression changes across mouse model studies to help select the optimal mouse model for further investigation. The portal provides access to mouse studies related to Alzheimer's diseases (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebellar ataxia (SCA), and models related to aging.

Barreras de acceso a la atención de la salud según la nacionalidad peruana ­ venezolana, en puérperas de un Hospital Público del Perú / Barriers to access to health care according to Peruvian-Venezuelan nationality in postpartum women in a public hospital in Peru

Objetivo: Analizar las barreras de acceso a la atención de la salud según la nacionalidad peruana ­ venezolana, en puérperas de un Hospital Público del Perú, 2022 - 2023. Métodos: Estudio observacional, analítico, prospectivo y transversal; incluyó una muestra de 284 puérperas de nacionalidad peruana y venezolana, del Hospital San Juan de Lurigancho, seleccionadas por muestreo estratificado. La técnica de recolección de datos fue una encuesta y el instrumento un cuestionario válido y confiable. La prueba chi cuadrado de Pearson o exacta de Fisher se usó para determinar la diferencia. La asociación se evaluó con la prueba de regresión de Poisson y el sentido de esta mediante la razón de prevalencia cruda y ajustada. Resultados: El 87,3 % de puérperas fueron peruanas y 12,7 % venezolanas. Las barreras de acceso a la atención de salud más frecuentes en peruanas fueron de disponibilidad: el no contar con todos los servicios necesarios para una atención (p < 0,001) y el de aceptabilidad: sentir que sus creencias o costumbres fueron afectadas (p < 0,001). Las puérperas venezolanas reportaron como barreras de aceptabilidad: haber recibido un trato diferente por ser migrante (p < 0,001) y haber sentido discriminación durante la atención (p = 0,007). Conclusión. Existe diferencia significativa en las barreras de acceso a la atención de la salud en puérperas, presentándose barreras de disponibilidad y aceptabilidad en peruanas y la última en venezolanas(AU)

Objective: Analyze the barriers to access to health care according to Peruvian - Venezuelan nationality in postpartum women in a Public Hospital of Peru 2022 ­ 2023. Methods: Observational, analytical, prospective and cross-sectional study; included a sample of 284 postpartum women of Peruvian and Venezuelan nationality, from the San Juan de Lurigancho Hospital, selected by stratified sampling. The data collection technique was a survey and the instrument was a valid and reliable questionnaire. Pearson's chi-square or Fisher's exact test was used to determine the difference. The association was assessed using the Poisson regression test and the sense of regression using the crude and adjusted prevalence ratio. Results: 87,3 % of postpartum women were Peruvian and 12,7 % Venezuelan. The most frequent barriers to access to health care in Peruvians were availability: not having all the services necessary for care (p < 0,001) and acceptability: feeling that their beliefs or customs were affected (p < 0,001). Venezuelan postpartum women reported as barriers to acceptability: having received different treatment for being a migrant (p < 0,001) and having felt discrimination during care (p = 0,007). Conclusions: There is a significant difference in the barriers to access to health care in postpartum women, with availability and acceptability barriers occurring in Peruvian women and the latter in Venezuelan women(AU)