Microtubules (MTs) are essential components of the cytoskeleton that play critical roles in neurodevelopment and adaptive central nervous system functioning. MTs are essential to growth cone advance and ultrastructural events integral to synaptic plasticity; these functions figure significantly into current pathophysiologic conceptualizations of schizophrenia. To date, no study has directly investigated MT dynamics in humans with schizophrenia. We therefore compared the stability of MTs in olfactory neuroepithelial (OE) cells between schizophrenia cases and matched nonpsychiatric comparison subjects. For this purpose, we applied nocodazole (Nz) to cultured OE cells obtained from tissue biopsies from seven living schizophrenia patients and seven matched comparison subjects; all schizophrenia cases were on antipsychotic medications. Nz allows MT depolymerization to be followed but prevents repolymerization, so that in living cells treated for varying time intervals, the MTs that are stable for a given treatment interval remain. Our readout of MT stability was the time at which fewer than 10 MTs per cell could be distinguished by anti-β-tubulin immunofluorescence. The percentage of cells with ≥10 intact MTs at specified intervals following Nz treatment was estimated by systematic uniform random sampling with Visiopharm software. These analyses showed that the mean percentages of OE cells with intact MTs were significantly greater for schizophrenia cases than for the matched comparison subjects at 10, 15, and 30 minutes following Nz treatment indicating increased MT stability in OE cells from schizophrenia patients (p=.0007 at 10 minutes; p=.0008 at 15 minutes; p=.036 at 30 minutes). In conclusion, we have demonstrated increased MT stability in nearly all cultures of OE cells from individuals with schizophrenia who received several antipsychotic treatments, versus comparison subjects matched for age and sex. While we cannot rule out a possible confounding effect of antipsychotic medications, these findings may reflect analogous neurobiological events in at least a subset of immature neurons or other cell types during gestation, or newly generated cells destined for the olfactory bulb or hippocampus, suggesting a mechanism that underlies findings of postmortem and neuroimaging investigations of schizophrenia. Future studies aimed at replicating these findings, including samples of medication-naïve subjects with schizophrenia, and reconciling the results with other studies, will be necessary. Although the observed abnormalities may suggest one of a number of putative pathophysiologic anomalies in schizophrenia, this work may ultimately have implications for an improved understanding of pathogenic processes related to this disorder.
Objective To evaluate implementation of a community-engaged approach to scale up COVID-19 mass testing in low-income, majority-Latino communities. Methods In January 2021, we formed a community-academic “Latino COVID-19 Collaborative” with residents, leaders, and community-based organizations (CBOs) from majority-Latinx, low-income communities in three California counties (Marin/Merced/San Francisco). The collaborative met monthly to discuss barriers/facilitators for COVID-19 testing, and plan mass testing events informed by San Francisco’s Unidos en Salud “test and respond” model, offering community-based COVID-19 testing and post-test support in two US-census tracts: Canal (Marin) and Planada (Merced). We evaluated implementation using the RE-AIM framework. To further assess testing barriers, we surveyed a random sample of residents who did not attend the events. Results Fifty-five residents and CBO staff participated in the Latino collaborative. Leading facilitators identified to increase testing were extended hours of community-based testing and financial support during isolation. In March-April 2021, 1,217 people attended mass-testing events over 13 days: COVID-19 positivity was 3% and 1% in Canal and Planada, respectively. The RE-AIM evaluation found: census tract testing coverage of 4.2% and 6.3%, respectively; 90% of event attendees were Latino, 89% had household income <$50,000/year, and 44% first-time testers (reach), effectiveness in diagnosing symptomatic cases early (median isolation time: 7 days) and asymptomatic COVID-19 (41% at diagnosis), high adoption by CBOs in both counties, implementation of rapid testing (median: 17.5 minutes) and disclosure, and post-event maintenance of community-based testing. Among 265 non-attendees surveyed, 114 (43%) reported they were aware of the event: reasons for non-attendance among the 114 were insufficient time (32%), inability to leave work (24%), and perceptions that testing was unnecessary post-vaccination (24%) or when asymptomatic (25%). Conclusion Community-engaged mass “test and respond” events offer a reproducible approach to rapidly increase COVID-19 testing access in low-income, Latinx communities.
HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health.
HEARTS en las Américas es el programa insignia de la Organización Panamericana de la Salud para acelerar la reducción de la carga de enfermedades cardiovasculares (ECV) mediante la mejora del control de la hipertensión y la prevención secundaria de las ECV en la atención primaria de salud. Es necesaria una plataforma de monitoreo y evaluación (M&E) para ejecutar el programa, establecer puntos de referencia y notificar a los responsables de las políticas. En este artículo se describen las bases conceptuales de la plataforma de M&E de HEARTS, como los principios de diseño del software, la contextualización de los módulos de recopilación de datos, la estructura de los datos, la presentación de información y la visualización. Se escogió la plataforma web District Health Information Software 2 (DHIS2) para ejecutar el ingreso de los datos agregados de los indicadores de resultados, procesos y factores de riesgo estructurales de las ECV. Además, se eligió PowerBI para la visualización de datos y la elaboración del panel de control para el análisis del desempeño y las tendencias más allá del nivel de los centros de atención médica. El desarrollo de esta nueva plataforma de información se centró en el ingreso de datos de los centros de atención primaria de salud, la presentación oportuna de datos, las visualizaciones y, en última instancia, el uso activo de los datos para impulsar la toma de decisiones en la ejecución del programa con equidad y la mejora de calidad de la atención. Además, se evaluaron las enseñanzas extraídas y las consideraciones programáticas con la experiencia del desarrollo de software de M&E. Lograr el apoyo y la voluntad política es esencial para desarrollar y poner en marcha una plataforma flexible en múltiples países que sea contextualmente específica según las necesidades de las diversas partes interesadas y los niveles del sistema de atención de la salud. La plataforma de M&E de HEARTS brinda apoyo para la ejecución del programa y muestra las limitaciones estructurales y gerenciales, así como las brechas en la atención. Esta plataforma será fundamental para monitorear e impulsar nuevas mejoras a nivel de la población en lo que respecta a las ECV y otras enfermedades no transmisibles relacionadas.
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