Assessing the Usability and Feasibility of Digital Assistant Tools for Direct Support Professionals: Participatory Design and Pilot-Testing.

BACKGROUND: The United States is experiencing a direct support professional (DSP) crisis, with demand far exceeding supply. Although generating documentation is a critical responsibility, it is one of the most wearisome aspects of DSPs' jobs. Technology that enables DSPs to log informal time-stamped notes throughout their shift could help reduce the burden of end-of-shift documentation and increase job satisfaction, which in turn could improve the quality of life of the individuals with intellectual and developmental disabilities (IDDs) whom DSPs support. However, DSPs, with varied ages, levels of education, and comfort using technology, are not likely to adopt tools that detract from caregiving responsibilities or increase workload; therefore, technological tools for them must be relatively simple, extremely intuitive, and provide highly valued capabilities. OBJECTIVE: This paper describes the development and pilot-testing of a digital assistant tool (DAT) that enables DSPs to create informal notes throughout their shifts and use these notes to facilitate end-of-shift documentation. The purpose of the pilot study was to assess the usability and feasibility of the DAT. METHODS: The research team applied an established user-centered participatory design process to design, develop, and test the DAT prototypes between May 2020 and April 2023. Pilot-testing entailed having 14 DSPs who support adults with IDDs use the first full implementation of the DAT prototypes during 2 or 3 successive work shifts and fill out demographic and usability questionnaires. RESULTS: Participants used the DAT prototypes to create notes and help generate end-of-shift reports. The System Usability Scale score of 81.79 indicates that they found the prototypes easy to use. Survey responses imply that using the DAT made it easier for participants to produce required documentation and suggest that they would adopt the DAT if this tool were available for daily use. CONCLUSIONS: Simple technologies such as the DAT prototypes, which enable DSPs to use mobile devices to log time-stamped notes throughout their shift with minimal effort and use the notes to help write reports, have the potential to both reduce the burden associated with producing documentation and enhance the quality (level of detail and accuracy) of this documentation. This could help to increase job satisfaction and reduce turnover in DSPs, both of which would help improve the quality of life of the individuals with IDDs whom they support. The pilot test results indicate that DSPs found the DAT easy to use. Next steps include (1) producing more robust versions of the DAT with additional capabilities, such as storing data locally on mobile devices when Wi-Fi is not available; and (2) eliciting input from agency directors, families, and others who use data about adults with IDDs to help care for them to ensure that data produced by DSPs are relevant and useful.

"You get what you need when you need it": A mixed methods examination of the feasibility and acceptability of a tailored digital tool to promote physical activity among women in midlife.

During midlife (ages 40-60), women experience myriad changes that elevate their risk for cardiovascular disease (CVD), including decreased physical activity (PA). Women cite lack of social support for PA and lack of active peers who can serve as role models as key barriers. Digital tools such as web applications can provide exposure to these social inputs; they are also accessible in daily life and require modest time investment. However, as few tools have been designed to meet the unique needs of women in midlife with CVD risk, our research team previously built a web application that is tailored for this population. In the present study, we used a convergent mixed methods design to develop a deep understanding of the feasibility, usability, and acceptability of this web application in a sample of identified end users. Participants (N = 27, MAge = 53 years, MBMI = 32.6 kg/m2) used the web application at the start of each day for 7 days and completed a 1-hour qualitative interview at the end of this test period. Integration of findings from two-level multilevel models (quantitative) and thematic analysis (qualitative) indicated support for the feasibility, usability, and acceptability of the new web application among women in midlife with CVD risk conditions and identified critical opportunities for improving the user experience. Findings also speak to the utility of options for content selection that can meet women's needs in daily life and highlight women's desire for PA resources that prioritize their perspectives.

Direct Support Professionals' Perspectives on Using Technology to Help Support Adults With Autism Spectrum Disorder: Mixed Methods Study.

BACKGROUND: Documentation is a critical responsibility for direct support professionals (DSPs) who work with adults with autism spectrum disorder (ASD); however, it contributes significantly to their workload. Targeted efforts must be made to mitigate the burden of necessary data collection and documentation, which contributes to high DSP turnover rates and poor job satisfaction. OBJECTIVE: This mixed methods study aimed to explore how technology could assist DSPs who work with adults with ASD and prioritize aspects of technology that would be most useful for future development efforts. METHODS: In the first study, 15 DSPs who worked with adults with ASD participated in 1 of the 3 online focus groups. The topics included daily tasks, factors that would influence the adoption of technology, and how DSPs would like to interact with technologies to provide information about their clients. Responses were thematically analyzed across focus groups and ranked by salience. In the second study, 153 DSPs across the United States rated the usefulness of technology features and data entry methods and provided qualitative responses on their concerns regarding the use of technology for data collection and documentation. Quantitative responses were ranked based on their usefulness across participants, and rank-order correlations were calculated between different work settings and age groups. The qualitative responses were thematically analyzed. RESULTS: In study 1, participants described difficulties with paper-and-pencil data collection, noted benefits and concerns about using technology instead, identified benefits and concerns about particular technology features, and specified work-environment factors that impact data collection. In study 2, participants rated multiple features of technology as useful, with the highest usefulness percentages endorsed for task views (ie, by shift, client, and DSP), logging completed tasks, and setting reminders for specific tasks. Participants also rated most data entry methods (eg, typing on a phone or tablet, typing on a keyboard, and choosing from options on a touch screen) as useful. Rank-order correlations indicated that the usefulness of technology features and data entry methods differed across work settings and age groups. Across both studies, DSPs cited some concerns with technology, such as confidentiality, reliability and accuracy, complexity and efficiency, and data loss from technology failure. CONCLUSIONS: Understanding the challenges faced by DSPs who work with adults with ASD, and their thoughts about using technology to meet those challenges, represents an essential first step toward developing technology solutions that can increase DSPs' effectiveness and job satisfaction. The survey results indicate that technology innovations should incorporate multiple features to account for different needs across DSPs, settings, and age groups. Future research should explore barriers to adopting data collection and documentation tools and elicit input from agency directors, families, and others interested in reviewing data about adults with ASD.

Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models.

Ischemic stroke is a leading cause of death worldwide, mainly in western countries. So far, approved therapies rely on reperfusion of the affected brain area, by intravenous thrombolysis or mechanical thrombectomy. The last approach constitutes a breakthrough in the field, by extending the therapeutic window to 16-24 h after stroke onset and reducing stroke mortality. The combination of pharmacological brain-protective strategies with reperfusion is the future of stroke therapy, aiming to reduce brain cell death and decrease patients' disabilities. Recently, a brain-protective drug-nerinetide-reduced brain infarct and stroke mortality, and improved patients' functional outcomes in clinical trials. The success of new therapies relies on bringing preclinical studies and clinical practice close together, by including a functional outcome assessment similar to clinical reality. In this review, we focused on recent upgrades of in vitro and in vivo stroke models for more accurate and effective evaluation of therapeutic strategies: from spheroids to organoids, in vitro models that include all brain cell types and allow high throughput drug screening, to advancements in in vivo preclinical mouse stroke models to mimic the clinical reality in surgical procedures, postsurgical care, and functional assessment.

High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models.

Characterization of brain infarct lesions in rodent models of stroke is crucial to assess stroke pathophysiology and therapy outcome. Until recently, the analysis of brain lesions was performed using two techniques: (1) histological methods, such as TTC (Triphenyltetrazolium chloride), a time-consuming and inaccurate process; or (2) MRI imaging, a faster, 3D imaging method, that comes at a high cost. In the last decade, high-resolution micro-CT for 3D sample analysis turned into a simple, fast, and cheaper solution. Here, we successfully describe the application of brain contrasting agents (Osmium tetroxide and inorganic iodine) for high-resolution micro-CT imaging for fine location and quantification of ischemic lesion and edema in mouse preclinical stroke models. We used the intraluminal transient MCAO (Middle Cerebral Artery Occlusion) mouse stroke model to identify and quantify ischemic lesion and edema, and segment core and penumbra regions at different time points after ischemia, by manual and automatic methods. In the transient-ischemic-attack (TIA) mouse model, we can quantify striatal myelinated fibers degeneration. Of note, whole brain 3D reconstructions allow brain atlas co-registration, to identify the affected brain areas, and correlate them with functional impairment. This methodology proves to be a breakthrough in the field, by providing a precise and detailed assessment of stroke outcomes in preclinical animal studies.

Development and Initial Testing of a Personalized, Adaptive, and Socially Focused Web Tool to Support Physical Activity Among Women in Midlife: Multidisciplinary and User-Centered Design Approach.

BACKGROUND: Women in midlife are vulnerable to developing cardiovascular disease, particularly those who have conditions such as hypertension. Physical activity (PA) can reduce risk, but efforts to promote PA in this population have been only modestly effective. More attention to social influences on PA behavior may be useful, particularly social support and social comparison processes. Activating these processes with digital tools can provide easy access that is flexible to the needs of women in midlife. OBJECTIVE: This paper describes the user-centered design processes of developing and conducting initial evaluation of a personalized and adaptive web application, tailored to the social needs of women in midlife. The goal was to gather feedback from the population of interest, before and during the design process. METHODS: This study was conducted in 4 stages. The first and second authors (DA and AFL) developed technical specifications, informed by their experience with the population of interest. We collected feedback on potential content for the web application with women in midlife using both interviews (5/10, 50%; mean age 47.4, SD 6.66 years; mean BMI 35.3, SD 9.55 kg/m2) and surveys (5/10, 50%; mean age 51, SD 6.60 years; mean BMI 32.7, SD 8.39 kg/m2). We used their feedback to inform support messages and peer profiles (ie, sources of social comparison information). Nine members of the behavioral science team and 3 testers unfamiliar with the web application completed internal testing. We conducted naturalistic functionality testing with a different group of women in midlife (n=5; mean age 50, SD 6.26 years; mean BMI 30.1, SD 5.83 kg/m2), who used the web application as intended for 4 days and provided feedback at the end of this period. RESULTS: Iterative storyboard development resulted in programming specifications for a prototype of the web application. We used content feedback to select and refine the support messages and peer profiles to be added. The following 2 rounds of internal testing identified bugs and other problems regarding the web application's functioning and full data collection procedure. Problems were addressed or logged for future consideration. Naturalistic functionality testing revealed minimal further problems; findings showed preliminary acceptability of the web application and suggested that women may select different social content across days. CONCLUSIONS: A multidisciplinary and user-centered design approach led to a personalized and adaptive web application, tailored to the social needs of women in midlife. Findings from testing with this population demonstrated the feasibility and acceptability of the new application and supported further development toward its use in daily life. We describe several potential uses of the web application and next steps for its development. We also discuss the lessons learned and offer recommendations for future collaborations between behavioral and computer scientists to develop similar tools.

Bridging the Transient Intraluminal Stroke Preclinical Model to Clinical Practice: From Improved Surgical Procedures to a Workflow of Functional Tests.

Acute ischemic stroke (AIS) remains a leading cause of mortality, despite significant advances in therapy (endovascular thrombectomy). Failure in developing novel effective therapies is associated with unsuccessful translation from preclinical studies to clinical practice, associated to inconsistent and highly variable infarct areas and lack of relevant post-stroke functional evaluation in preclinical research. To outreach these limitations, we optimized the intraluminal transient middle cerebral occlusion, a widely used mouse stroke model, in two key parameters, selection of appropriate occlusion filaments and time of occlusion, which show a significant variation in the literature. We demonstrate that commercially available filaments with short coating length (1-2 mm), together with 45-min occlusion, results in a consistent affected brain region, similar to what is observed in most patients with AIS. Importantly, a dedicated post-stroke care protocol, based on clinical practice applied to patients who had stroke, resulted in lower mortality and improved mice welfare. Finally, a battery of tests covering relevant fine motor skills, sensory functions, and learning/memory behaviors revealed a significant effect of tMCAO brain infarction, which is parallel to patient symptomatology as measured by relevant clinical scales (NIH Stroke Scale, NIHSS and modified Rankin Scale, mRS). Thus, in order to enhance translation to clinical practice, future preclinical stroke research must consider the methodology described in this study, which includes improved reproducible surgical procedure, postoperative care, and the battery of functional tests. This will be a major step s closing the gap from bench to bedside, rendering the development of novel effective therapeutic approaches.

Neuron-Microglia Contact-Dependent Mechanisms Attenuate Methamphetamine-Induced Microglia Reactivity and Enhance Neuronal Plasticity.

Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP3R2-Ca2+-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.

[Perinatal mortality in Brazil in 2018: an epidemiological analysis according to the modified Wigglesworth classification]. / Mortalidade perinatal no Brasil em 2018: análise epidemiológica segundo a classificação de Wiggleworth modificada.

Perinatal mortality includes fetal mortality and early neonatal mortality (0 to 6 days of life). The study described perinatal deaths in Brazil in 2018 according to the modified Wigglesworth classification. The data sources were the Brazilian Mortality Information System and the Brazilian Information System on Live Births. Fetal mortality and perinatal mortality rates were calculated per 1,000 total births (live births plus stillbirths) and the early neonatal mortality rate per 1,000 live births, compared using their respective 95% confidence intervals (95%CI). Perinatal deaths were classified in groups of antepartum causes, congenital anomalies, prematurity, asphyxia, and specific causes. For each group of causes, the study calculated the number of deaths by weight group, in addition to mortality rates and respective 95%CI, besides the spatial distribution of mortality rates by state of Brazil. A total of 35,857 infant deaths were recorded, of which 18,866 (52.6%) were early neonatal deaths, while stillbirths totaled 27,009. Perinatal deaths totaled 45,875, for a mortality rate of 15.5‰ births. The highest mortality rate (7.6‰; 7.5‰-7.7‰) was observed in the antepartum group, followed by prematurity (3.6‰; 3.6‰-3.7‰). In the antepartum group, 14 of the 27 states (eight of which in the Northeast and four in the North) presented perinatal mortality rates above the national rate. Perinatal mortality in Brazil was high, and most deaths could have been prevented with investment in prenatal and childbirth care.

A mortalidade perinatal engloba a mortalidade fetal e a neonatal precoce (0 a 6 dias). Este estudo descreveu os óbitos perinatais ocorridos no Brasil em 2018, segundo a classificação de Wigglesworth modificada. As fontes de dados foram os Sistemas de Informações sobre Mortalidade e sobre Nascidos Vivos. Foram calculadas as taxas de mortalidade fetal e perinatal por mil nascimentos totais (nascidos vivos mais natimortos) e a taxa de mortalidade neonatal precoce por mil nascidos vivos, e comparadas usando seus respectivos intervalos de 95% de confiança (IC95%). Os óbitos perinatais foram classificados nos grupos de causas anteparto, anomalias congênitas, prematuridade, asfixia e causas específicas. Foi calculado, para cada grupo de causas, o número de óbitos por faixa de peso, além das taxas de mortalidade e os respectivos IC95%, e feita a distribuição espacial das taxas de mortalidade por Unidade da Federação (UF). Foram registrados 35.857 óbitos infantis, sendo 18.866 (52,6%) neonatais precoces; os natimortos somaram 27.009. Os óbitos perinatais totalizaram 45.875, perfazendo uma taxa de mortalidade de 15,5‰ nascimentos. A maior taxa de mortalidade (7,6‰; 7,5‰-7,7‰) foi observada no grupo anteparto, seguido da prematuridade (3,6‰; 3,6‰-3,7‰). No grupo anteparto, 14 das 27 UFs (sendo oito na Região Nordeste e quatro na Região Norte) apresentaram as taxas de mortalidade perinatal acima da nacional. A taxa de mortalidade perinatal no Brasil mostrou-se elevada, e a maioria dos óbitos poderia ser prevenida com investimento em cuidados pré-natais e ao nascimento.

La mortalidad perinatal engloba la mortalidad fetal y neonatal precoz (0 a 6 días). Este estudio describió los óbitos perinatales ocurridos en Brasil en 2018, según la clasificación de Wigglesworth modificada. Las fuentes de datos fueron los Sistemas de Información sobre Mortalidad y sobre Nacidos Vivos. Se calcularon las tasas de mortalidad fetal y perinatal por 1.000 nacimientos totales (nacidos vivos más mortinatos) y la tasa de mortalidad neonatal precoz por 1.000 nacidos vivos, y se compararon usando sus respectivos intervalos de 95% de confianza (IC95%). Los óbitos perinatales se clasificaron en los grupos de causas: anteparto, anomalías congénitas, prematuridad, asfixia y causas específicas. Se calculó, para cada grupo de causas, el número de óbitos por franja de peso, además de las tasas de mortalidad y los respectivos IC95%, y se realizó la distribución espacial de las tasas de mortalidad por Unidad de la Federación (UF). Se registraron 35.857 óbitos infantiles, siendo 18.866 (52,6%) neonatales precoces; los mortinatos sumaron 27.009. Los óbitos perinatales totalizaron 45.875, ascendiendo a una tasa de mortalidad de un 15,5‰ nacimientos. La mayor tasa de mortalidad (7,6‰; 7,5‰-7,7‰) se observó en el grupo anteparto, seguido de la prematuridad (3,6‰; 3,6‰-3,7‰). En el grupo anteparto, 14 de las 27 UFs (estando ocho en la región Nordeste y cuatro en la región Norte) presentaron tasas de mortalidad perinatal por encima de la nacional. La tasa de mortalidad perinatal en Brasil se mostró elevada y la mayoría de los óbitos podría ser prevenido con inversión en cuidados prenatales y en el nacimiento.

Unexpected slowdown in the decline of tuberculosis mortality rates in Brazil from 1997 to 2017: an ecological study.

BACKGROUND: Brazil is a signatory to the World Health Organization End TB Strategy and the United Nations Sustainable Development Goals. This study aims to characterize tuberculosis (TB) deaths and TB mortality rates in Brazil for the period 1997-2017. METHODS: We performed an ecological study based on information for TB deaths between 1997 and 2017 extracted from the Mortality Information System of the Brazilian Ministry of Health. Data included gender, age group and geographic regions. The trends in mortality rates were estimated using Joinpoint regression analysis, which identifies years in which there is a change in slope of the time series by the Monte Carlo permutation. RESULTS: Between 1997 and 2017 there were 104 172 recorded TB deaths in Brazil and the mortality rates were higher for men and the elderly. The age-adjusted mortality rate decreased from 4.2 per 100 000 in 1997 to 3.0 per 100 000 in 2003 to 2.0 per 100 000 in 2017. The average percentage reduction from 1997 to 2003 was 6.2% (95% confidence interval [CI] -7.7 to -4.7) per year, while from 2003 to 2017 it was 3.0% (95% CI -3.4 to -2.5) per year, representing a slowdown in the rate of decline. CONCLUSION: The high number of deaths and the slowdown in the decline of mortality rates from TB in Brazil maintain the disease as an important public health concern and an obstacle to reaching goals set by international commitments.

Mortalidade perinatal no Brasil em 2018: análise epidemiológica segundo a classificação de Wiggleworth modificada / Perinatal mortality in Brazil in 2018: an epidemiological analysis according to the modified Wigglesworth classification / Mortalidad perinatal en Brasil en 2018: análisis epidemiológico según la clasificación de Wiggleworth modificada

Resumo: A mortalidade perinatal engloba a mortalidade fetal e a neonatal precoce (0 a 6 dias). Este estudo descreveu os óbitos perinatais ocorridos no Brasil em 2018, segundo a classificação de Wigglesworth modificada. As fontes de dados foram os Sistemas de Informações sobre Mortalidade e sobre Nascidos Vivos. Foram calculadas as taxas de mortalidade fetal e perinatal por mil nascimentos totais (nascidos vivos mais natimortos) e a taxa de mortalidade neonatal precoce por mil nascidos vivos, e comparadas usando seus respectivos intervalos de 95% de confiança (IC95%). Os óbitos perinatais foram classificados nos grupos de causas anteparto, anomalias congênitas, prematuridade, asfixia e causas específicas. Foi calculado, para cada grupo de causas, o número de óbitos por faixa de peso, além das taxas de mortalidade e os respectivos IC95%, e feita a distribuição espacial das taxas de mortalidade por Unidade da Federação (UF). Foram registrados 35.857 óbitos infantis, sendo 18.866 (52,6%) neonatais precoces; os natimortos somaram 27.009. Os óbitos perinatais totalizaram 45.875, perfazendo uma taxa de mortalidade de 15,5‰ nascimentos. A maior taxa de mortalidade (7,6‰; 7,5‰-7,7‰) foi observada no grupo anteparto, seguido da prematuridade (3,6‰; 3,6‰-3,7‰). No grupo anteparto, 14 das 27 UFs (sendo oito na Região Nordeste e quatro na Região Norte) apresentaram as taxas de mortalidade perinatal acima da nacional. A taxa de mortalidade perinatal no Brasil mostrou-se elevada, e a maioria dos óbitos poderia ser prevenida com investimento em cuidados pré-natais e ao nascimento.

Abstract: Perinatal mortality includes fetal mortality and early neonatal mortality (0 to 6 days of life). The study described perinatal deaths in Brazil in 2018 according to the modified Wigglesworth classification. The data sources were the Brazilian Mortality Information System and the Brazilian Information System on Live Births. Fetal mortality and perinatal mortality rates were calculated per 1,000 total births (live births plus stillbirths) and the early neonatal mortality rate per 1,000 live births, compared using their respective 95% confidence intervals (95%CI). Perinatal deaths were classified in groups of antepartum causes, congenital anomalies, prematurity, asphyxia, and specific causes. For each group of causes, the study calculated the number of deaths by weight group, in addition to mortality rates and respective 95%CI, besides the spatial distribution of mortality rates by state of Brazil. A total of 35,857 infant deaths were recorded, of which 18,866 (52.6%) were early neonatal deaths, while stillbirths totaled 27,009. Perinatal deaths totaled 45,875, for a mortality rate of 15.5‰ births. The highest mortality rate (7.6‰; 7.5‰-7.7‰) was observed in the antepartum group, followed by prematurity (3.6‰; 3.6‰-3.7‰). In the antepartum group, 14 of the 27 states (eight of which in the Northeast and four in the North) presented perinatal mortality rates above the national rate. Perinatal mortality in Brazil was high, and most deaths could have been prevented with investment in prenatal and childbirth care.

Resumen: La mortalidad perinatal engloba la mortalidad fetal y neonatal precoz (0 a 6 días). Este estudio describió los óbitos perinatales ocurridos en Brasil en 2018, según la clasificación de Wigglesworth modificada. Las fuentes de datos fueron los Sistemas de Información sobre Mortalidad y sobre Nacidos Vivos. Se calcularon las tasas de mortalidad fetal y perinatal por 1.000 nacimientos totales (nacidos vivos más mortinatos) y la tasa de mortalidad neonatal precoz por 1.000 nacidos vivos, y se compararon usando sus respectivos intervalos de 95% de confianza (IC95%). Los óbitos perinatales se clasificaron en los grupos de causas: anteparto, anomalías congénitas, prematuridad, asfixia y causas específicas. Se calculó, para cada grupo de causas, el número de óbitos por franja de peso, además de las tasas de mortalidad y los respectivos IC95%, y se realizó la distribución espacial de las tasas de mortalidad por Unidad de la Federación (UF). Se registraron 35.857 óbitos infantiles, siendo 18.866 (52,6%) neonatales precoces; los mortinatos sumaron 27.009. Los óbitos perinatales totalizaron 45.875, ascendiendo a una tasa de mortalidad de un 15,5‰ nacimientos. La mayor tasa de mortalidad (7,6‰; 7,5‰-7,7‰) se observó en el grupo anteparto, seguido de la prematuridad (3,6‰; 3,6‰-3,7‰). En el grupo anteparto, 14 de las 27 UFs (estando ocho en la región Nordeste y cuatro en la región Norte) presentaron tasas de mortalidad perinatal por encima de la nacional. La tasa de mortalidad perinatal en Brasil se mostró elevada y la mayoría de los óbitos podría ser prevenido con inversión en cuidados prenatales y en el nacimiento.

Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.

Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies.

COVID-19 in Brazil: evolution of the epidemic up until epidemiological week 20 of 2020. / COVID-19 no Brasil: evolução da epidemia até a semana epidemiológica 20 de 2020.

Objective to describe the evolution of COVID-19 in Brazil up until epidemiological week 20 of 2020. Methods this is an ecological study based on data and official documents from the Brazilian Ministry of Health and international organizations; comparisons were made between Brazil and other countries and incidence and mortality rates were calculated. Results by the end of epidemiological week 20, 233,142 cases, and 15,633 deaths had been confirmed for Brazil as a whole and 3,240 (58.2%) of the country's municipalities had reported at least one case; Brazil was at an earlier phase of the pandemic when compared to other countries, except Russia and Turkey, regarding cumulative cases, and except Canada regarding cumulative deaths; the highest rates were found in Brazil's Northern Region states, where Amazonas state had the highest incidence rates(4,474.6/1,000,000) and mortality rates (331.8/1,000,000). Conclusion Brazil is one of the countries with the highest number of confirmed cases and deaths, with marked regional differences.

COVID-19 epidemic in Brazil: Where are we at?

OBJETIVE: To analyze the trends of COVID-19 in Brazil in 2020 by Federal Units (FU). METHOD: Ecological time-series based on cumulative confirmed cases of COVID-19 from March 11 to May 12. Joinpoint regression models were applied to identify points of inflection in COVID-19 trends, considering the days since the 50th confirmed case as time unit. RESULTS: Brazil reached its 50th confirmed case of COVID-19 in 11 March 2020 and, 63 days after that, on May 12, 177,589 cases had been confirmed. The trends for all regions and FU are upward. In the last segment, from the 31st to the 63rd day, Brazil presented a daily percentage change (DPC) of 7.3% (95%CI= 7.2;7.5). For the country the average daily percentage change (ADPC) was 14.2% (95%CI: 13.8;14.5). The highest ADPC values were found in the North, Northeast and Southeast regions. CONCLUSIONS: In summary, our results show that all FUs in Brazil present upward trends of COVID-19. In some FUs, the slowdown in DPC in the last segment must be considered with caution. Each FU is at a different stage of the pandemic and, therefore, non-pharmacological measures should be adopted accordingly.

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons.

Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.

COVID-19 no Brasil: evolução da epidemia até a semana epidemiológica 20 de 2020 / COVID-19 en Brasil: evolución de la epidemia hasta la semana epidemiológica 20 de 2020 / COVID-19 in Brazil: evolution of the epidemic up until epidemiological week 20 of 2020

Objetivo: descrever a evolução da COVID-19 no Brasil até a Semana Epidemiológica (SE) 20 de 2020. Métodos: estudo ecológico baseado em dados e documentos do Ministério da Saúde brasileiro e órgãos internacionais; foram realizadas comparações do Brasil com outros países e calculadas taxas de incidência e de mortalidade. Resultados: até o fim da SE 20, no país havia 233.142 casos, 15.633 óbitos confirmados e 3.240 (58,2%) dos municípios apresentavam pelo menos um caso; o Brasil estava em uma fase anterior da pandemia quando comparado aos demais países, exceto Rússia e Turquia, em casos acumulados, e Canadá, em óbitos acumulados; as maiores taxas foram encontradas em Unidades da Federação da Região Norte, com o Amazonas apresentando as maiores taxas de incidência (4.474,6/1 milhão) e mortalidade (331,8/1 milhão). Conclusão: o Brasil está entre os países com maiores números de casos e óbitos confirmados, exibindo notáveis diferenças regionais.

Objetivos: describir la evolución de COVID-19 en Brasil hasta la Semana Epidemiológica (SE) 20 de 2020. Métodos: estudio ecológico basado en datos y documentos del Ministerio de Salud Brasileño y organismos internacionales; se hicieron comparaciones entre Brasil y otros países y fueran calculadas las tasas de incidencia y mortalidad. Resultados: al final de la SE 20, en el país había 233.142 casos, 15.633 muertes confirmadas y 3.240 (58.2%) de los municipios tenían al menos un caso; Brasil se encuentra en una fase anterior de la pandemia en comparación con otros países, excepto Rusia y Turquía, para los casos acumulados y Canadá, en muertes acumuladas; las tasas más altas se encontraron en las Unidades Federativas en la Región Norte, con Amazonas con las tasas de incidencia más altas (4.474.6/1.000.000) y mortalidad (331.8/1.000.000). Conclusión: Brasil es uno de los países con el mayor número de casos y muertes, con notables diferencias regionales.

Objective: to describe the evolution of COVID-19 in Brazil up until epidemiological week 20 of 2020. Methods: this is an ecological study based on data and official documents from the Brazilian Ministry of Health and international organizations; comparisons were made between Brazil and other countries and incidence and mortality rates were calculated. Results: by the end of epidemiological week 20, 233,142 cases, and 15,633 deaths had been confirmed for Brazil as a whole and 3,240 (58.2%) of the country's municipalities had reported at least one case; Brazil was at an earlier phase of the pandemic when compared to other countries, except Russia and Turkey, regarding cumulative cases, and except Canada regarding cumulative deaths; the highest rates were found in Brazil's Northern Region states, where Amazonas state had the highest incidence rates(4,474.6/1,000,000) and mortality rates (331.8/1,000,000). Conclusion: Brazil is one of the countries with the highest number of confirmed cases and deaths, with marked regional differences.

Progress toward eliminating TB and HIV deaths in Brazil, 2001-2015: a spatial assessment.

BACKGROUND: Brazil has high burdens of tuberculosis (TB) and HIV, as previously estimated for the 26 states and the Federal District, as well as high levels of inequality in social and health indicators. We improved the geographic detail of burden estimation by modelling deaths due to TB and HIV and TB case fatality ratios for the more than 5400 municipalities in Brazil. METHODS: This ecological study used vital registration data from the national mortality information system and TB case notifications from the national communicable disease notification system from 2001 to 2015. Mortality due to TB and HIV was modelled separately by cause and sex using a Bayesian spatially explicit mixed effects regression model. TB incidence was modelled using the same approach. Results were calibrated to the Global Burden of Disease Study 2016. Case fatality ratios were calculated for TB. RESULTS: There was substantial inequality in TB and HIV mortality rates within the nation and within states. National-level TB mortality in people without HIV infection declined by nearly 50% during 2001 to 2015, but HIV mortality declined by just over 20% for males and 10% for females. TB and HIV mortality rates for municipalities in the 90th percentile nationally were more than three times rates in the 10th percentile, with nearly 70% of the worst-performing municipalities for male TB mortality and more than 75% for female mortality in 2001 also in the worst decile in 2015. The same municipality ranking metric for HIV was observed to be between 55% and 61%. Within states, the TB mortality rate ratios by sex for municipalities in the worst decile versus the best decile varied from 1.4 to 2.9, and HIV varied from 1.4 to 4.2. The World Health Organization target case fatality rate for TB of less than 10% was achieved in 9.6% of municipalities for males versus 38.4% for females in 2001 and improved to 38.4% and 56.6% of municipalities for males versus females, respectively, by 2014. CONCLUSIONS: Mortality rates in municipalities within the same state exhibited nearly as much relative variation as within the nation as a whole. Monitoring the mortality burden at this level of geographic detail is critical for guiding precision public health responses.

Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.

The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical Rho GTPases express mRNAs with alternative 3' UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3' UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3' UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3' UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation.

Inquérito domiciliar de prevalência de tracoma em crianças do Distrito Federal, Brasil, julho/2010 / Survey of prevalence trachoma of children in Distrito Federal, Brazil, july/2010

Realizamos um estudo de corte transversal na Vila Estrutural (DF), utilizando amostragem por conglomerados. Os objetivos do estudo foram estimar a prevalência de tracoma em crianças de um a nove anos, descrever o perfil sociodemográfico dos casos e identificar possíveis fatores de risco associados à doença. A medida de associação foi razão de prevalência estimada pela odds ratio e o intervalo de confiança 95% (IC95%). Foram amostradas 766 crianças de 1 a 9 anos e encontrada prevalência de tracoma ativo de 12,5%. A alta prevalência observada reforça que a doença permanece como um problema de saúde pública, sendo necessária a adoção de medidas de controle, com vistas à eliminação da doença, enquanto causa de cegueira. Recomendamos capacitar profissionais da área para detecção e monitoramento de situação epidemiológica e adotar atividades de educação em saúde com enfoque em medidas de controle e prevenção.

We conducted a cross-sectional study in Vila Estrutural (DF) using cluster sampling. This study aimed to estimate prevalence of trachoma in children aged one to nine years, to describe the socio-demographic profile of cases, and to identify possible risk factors associated with the disease. The association measure was prevalence ratio estimated by odds ratio and 95% confidence interval (CI95%). We sampled 766 children aged 1 to 9 years and found a prevalence of active trachoma of 12.5%. The high prevalence reinforces that the disease remains a public health problem, being necessary to adopt control measures, in order to eliminate the disease as a cause of blindness. We recommend enabling professionals to detect and to monitor the epidemiological situation and adopt health education activities focusing on prevention and control measures.

Tuberculosis, HIV, and poverty: temporal trends in Brazil, the Americas, and worldwide.

OBJECTIVE: To analyze the temporal trends of the incidence and prevalence of tuberculosis, with and without HIV co-infection, as well as of the associated mortality, in Brazil, the Americas, and worldwide. METHODS: We collected data related to tuberculosis, with and without HIV co-infection, between 1990 and 2010, in Brazil, the Americas, and worldwide. Temporal trends were estimated by linear regression. RESULTS: We identified a trend toward a decrease in tuberculosis prevalence and mortality, and that trend was more pronounced in Brazil and the Americas than worldwide. There was also a trend toward an increase in the incidence of tuberculosis/HIV co-infection, as well as in the rates of detection of new cases of active and latent tuberculosis. The incidence of tuberculosis was found to trend downward in Brazil, whereas it trended upward worldwide. Tuberculosis incidence rates correlated positively with poverty rates and with HIV incidence rates. CONCLUSIONS: Social inequality and the advent of AIDS are the major factors that aggravate the current situation of tuberculosis. In this context, methodical approaches to the assessment of surveillance activities are welcome, because they will identify situations in which the reported tuberculosis data do not reflect the true incidence of this disease.