Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability and preventing carcinogenesis. Additionally, in neurodevelopment, folate is essential for neural tube closure and central nervous system formation. Thus, dysregulation of folate metabolism can contribute to pathologies such as cancer, severe birth defects, and neurodegenerative diseases. Epidemiological evidence highlights folate's impact on disease risk and its potential as a therapeutic target. In cancer, antifolate drugs that inhibit key enzymes of folate-dependent 1C metabolism and strategies targeting folate receptors are current therapeutic options. However, folate's impact on cancer risk is complex, varying among cancer types and dietary contexts. In neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, folate deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing to neuronal damage. Clinical trials of folic acid supplementation show mixed outcomes, underscoring the complexities of its neuroprotective effects. This review integrates current knowledge on folate metabolism in cancer and neurodegeneration, exploring molecular mechanisms, clinical implications, and therapeutic strategies, which can provide crucial information for advancing treatments.

Feasibility of At-Home Hand Arm Bimanual Intensive Training in Virtual Reality: Case Study.

This single-participant case study examines the feasibility of using custom virtual reality (VR) gaming software in the home environment for low-dose Hand Arm Bimanual Intensive Training (HABIT). A 10-year-old with right unilateral cerebral palsy participated in this trial. Fine and gross motor skills as well as personal goals for motor outcomes were assessed before and after the intervention using the Box and Blocks Test, Nine-Hole Peg Test, and Canadian Occupational Performance Measure. Movement intensities collected via the VR hardware accelerometers, VR game scores, and task accuracy were recorded via the HABIT-VR software as indices of motor performance. The child and family were instructed to use the HABIT-VR games twice daily for 30 minutes over a 14-day period and asked to record when they used the system. The child used the system and completed the 14-hour, low-dose HABIT-VR intervention across 22 days. There was no change in Box and Blocks Test and Nine-Hole Peg Test scores before and after the intervention. Canadian Occupational Performance Measure scores increased but did not reach the clinically relevant threshold, due to high scores at baseline. Changes in motor task intensities during the use of VR and mastery of the VR bimanual tasks suggested improved motor efficiency. This case study provides preliminary evidence that HABIT-VR is useful for promoting adherence to HABIT activities and for the maintenance of upper extremity motor skills in the home setting.

Depth and Quality of Recommendations in Popular Sources About How to Play with Infants: Content Analysis.

AIM: Systematically evaluate the depth and quality of play recommendations provided in popular sources for parents of infants in the first year of life. METHODS: This represents the second stage of a larger analysis of educational content available to parents. Two coders (>90% agreement) extracted and coded play activities from popular websites, applications, and books screened from a systematic online search. Depth of instruction variables were extracted. Activity quality was rated based on opportunities for child-initiated movement, problem-solving with objects, and responsive communication. RESULTS: 4370 play activities from 214 sources were analyzed. Activities were likely to suggest specific ages for infants and that a caregiver be present. Less than half of the activities incorporated toys or provided guidance about how to position or physically support infants. Activity quality was low; most activities did not explicitly encourage parents to provide opportunities for child-initiated movement, problem-solving with objects, or quality communication. CONCLUSIONS: Parents may encounter a large number of play activities in popular sources, but the depth of instruction and quality of those activities could be improved. Provision of higher-quality education to parents may enhance parent-child play interactions to positively impact parent and child outcomes, especially for children at risk for delays.

Evaluation of Antitumor Activity of Xanthones Conjugated with Amino Acids.

Cancer is a complex disease characterized by several alterations, which confer, to the cells, the capacity to proliferate uncontrollably and to resist cellular death. Multiresistance to conventional chemotherapy drugs is often the cause of treatment failure; thus, the search for natural products or their derivatives with therapeutic action is essential. Chiral derivatives of xanthones (CDXs) have shown potential inhibitory activity against the growth of some human tumor cell lines. This work reports the screening of a library of CDXs, through viability assays, in different cancer cell lines: A375-C5, MCF-7, NCI-H460, and HCT-15. CDXs' effect was analyzed based on several parameters of cancer cells, and it was also verified if these compounds were substrates of glycoprotein-P (Pgp), one of the main mechanisms of resistance in cancer therapy. Pgp expression was evaluated in all cell lines, but no expression was observed, except for HCT-15. Also, when a humanized yeast expressing the human gene MDR1 was used, no conclusions could be drawn about CDXs as Pgp substrates. The selected CDXs did not induce significant differences in the metabolic parameters analyzed. These results show that some CDXs present promising antitumor activity, but other mechanisms should be triggered by these compounds.

The impact of severity of motor delay, timing of task mastery, and START-play intervention on the development of means-end problem solving in young children.

BACKGROUND: Children with motor delays are at increased risk for delayed means-end problem-solving (MEPS) performance. OBJECTIVES: To evaluate children with motor delays: 1) the impact of motor delay severity and MEPS mastery timing on developmental trajectories of MEPS; and 2) the effectiveness of Sitting Together And Reaching To Play (START-Play) intervention for improving MEPS. METHODS: This represents a secondary analysis from a multi-site randomized controlled trial, with blinded assessors and prospective registration. Children with mild or significant motor delays (n = 112, mean age=10.80, SD=2.59 months at baseline) were randomly assigned to START-Play or usual care early intervention (UC-EI) and assessed at five visits across one year using the Means-End Problem-Solving Assessment Tool that included three 30-second MEPS trials per visit. Task mastery occurred at the first visit the child achieved the highest level of performance in at least two of the three trials. Multilevel analyses evaluated trajectories of MEPS outcomes dependent upon the timing of MEPS mastery, motor delay severity, and intervention group. RESULTS: At baseline, children with mild motor delays demonstrated better MEPS than children with significant delays, but this difference was only observed for children who achieved mastery late. Children with significant delays demonstrated greater improvements in MEPS in the post-intervention phase compared to children with mild delays. No MEPS differences were found between START-Play and UC-EI. CONCLUSION: Motor delay severity and timing of task mastery impacted MEPS trajectories, whereas START-Play intervention did not impact MEPS for children with motor delays. CLINICAL TRIALS REGISTRY IDENTIFIER: NCT02593825 (https://clinicaltrials.gov/ct2/show/NCT02593825).

Neurodevelopment of Children Whose Mothers Were Randomized to Low-Dose Aspirin During Pregnancy.

OBJECTIVE: Because low-dose aspirin is now commonly prescribed in pregnancy, we sought to assess the association between early antenatal exposure and child neurodevelopment. METHODS: We performed a noninferiority, masked, neurodevelopmental follow-up study of children between age 33 and 39 months whose mothers had been randomized to daily low-dose aspirin (81 mg) or placebo between 6 0/7 and 13 6/7 weeks of gestation through 37 weeks. Neurodevelopment was assessed with the Bayley-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) and the ASQ-3 (Ages and Stages Questionnaire, 3rd Edition). The primary outcome was the Bayley-III cognitive composite score with a difference within 4 points demonstrating noninferiority. RESULTS: A total of 640 children (329 in the low-dose aspirin group, 311 in the placebo group) were evaluated between September 2021 and June 2022. The Bayley-III cognitive composite score was noninferior between the two groups (-1, adjusted mean -0.8, 95% CI, -2.2 to 0.60). Significant differences were not seen in the language composite score (difference 0.7, 95% CI, -0.8 to 2.1) or the motor composite score (difference -0.6, 95% CI, -2.5 to 1.2). The proportion of children who had any component of the Bayley-III score lower than 70 did not differ between the two groups. Similarly, the communication, gross motor, fine motor, problem-solving, and personal-social components of the ASQ-3 did not differ between groups. Maternal characteristics, delivery outcomes, breastfeeding rates, breastfeeding duration, and home environment as measured by the Family Care Indicators were similar. CONCLUSION: Antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04888377.

Effectiveness and Users' Perceptions of Upper Extremity Exoskeletons and Robot-Assisted Devices in Children with Physical Disabilities: Systematic Review.

AIM: Systematically determine the effectiveness and users' perceptions of upper extremity (UE) exoskeletons and robot-assisted devices for pediatric rehabilitation. METHODS: PubMed/Medline, Web of Science, Scopus, and Cochrane Library were searched for studies with "exoskeletons"/"robot-assisted devices", children with disabilities, effectiveness data, and English publication. Intervention effectiveness outcomes were classified within components of the International Classification of Functioning, Disability, and Health, Children and Youth Version (ICF-CY). Secondary data (users' perceptions; implementation setting) were extracted. Risk of bias and methodological quality were assessed. Descriptive analyses were performed. RESULTS: Seventy-two articles were included. Most evaluated body structure and function and activity outcomes with less emphasis on participation. Most effects across all ICF-CY levels were positive. Devices were primarily evaluated in clinical or laboratory rather than natural environments. Perceptions about device effectiveness were mostly positive, while those about expression, accessibility, and esthetics were mostly negative. A need for increased rigor in research study design was detected. CONCLUSIONS: Across populations, devices, settings, interventions, and dosing schedules, UE exoskeletons and robot-assisted devices may improve function, activity, and perhaps participation for children with physical disabilities. Future work should transition devices into natural environments, design devices and implementation strategies to address users' negative perceptions, and increase research rigor.

Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance.

The "Warburg effect" consists of a metabolic shift in energy production from oxidative phosphorylation to glycolysis. The continuous activation of glycolysis in cancer cells causes rapid energy production and an increase in lactate, leading to the acidification of the tumour microenvironment, chemo- and radioresistance, as well as poor patient survival. Nevertheless, the mitochondrial metabolism can be also involved in aggressive cancer characteristics. The metabolic differences between cancer and normal tissues can be considered the Achilles heel of cancer, offering a strategy for new therapies. One of the main causes of treatment resistance consists of the increased expression of efflux pumps, and multidrug resistance (MDR) proteins, which are able to export chemotherapeutics out of the cell. Cells expressing MDR proteins require ATP to mediate the efflux of their drug substrates. Thus, inhibition of the main energy-producing pathways in cancer cells, not only induces cancer cell death per se, but also overcomes multidrug resistance. Given that most anticancer drugs do not have the ability to distinguish normal cells from cancer cells, a number of drug delivery systems have been developed. These nanodrug delivery systems provide flexible and effective methods to overcome MDR by facilitating cellular uptake, increasing drug accumulation, reducing drug efflux, improving targeted drug delivery, co-administering synergistic agents, and increasing the half-life of drugs in circulation.

Biological and environmental factors may affect children's executive function through motor and sensorimotor development: Preterm birth and cerebral palsy.

Disruptive biological and environmental factors may undermine the development of children's motor and sensorimotor skills. Since the development of cognitive skills, including executive function, is grounded in early motor and sensorimotor experiences, early delays or impairments in motor and sensorimotor processing often trigger dynamic developmental cascades that lead to suboptimal executive function outcomes. The purpose of this perspective paper is to link early differences in motor/sensorimotor processing to the development of executive function in children born preterm or with cerebral palsy. Uncovering such links in clinical populations would improve our understanding of developmental pathways and key motor and sensorimotor skills that are antecedent and foundational for the development of executive function. This knowledge will allow the refinement of early interventions targeting motor and sensorimotor skills with the goal of proactively improving executive function outcomes in at-risk populations.

Information Available to Parents Seeking Education about Infant Play, Milestones, and Development from Popular Sources.

Parents commonly seek information about infant development and play, yet it is unclear what information parents find when looking in popular sources. Play, Milestone, and Development Searches in Google identified 313 sources for content analysis by trained researchers using a standardized coding scheme. Sources included websites, books, and apps created by professional organizations, commercial entities, individuals, the popular press, and government organizations/agencies. The results showed that for popular sources: (1) author information (i.e., qualifications, credentials, education/experience) is not consistently provided, nor is information about the developmental process, parents' role in development, or determining an infant's readiness to play; (2) milestones comprise a majority of the content overall; (3) search terminology impacts the information parents receive; (4) sources from the Milestone and Development Searches emphasized a passive approach of observing developmental milestones rather than suggesting activities to actively facilitate learning and milestone development. These findings highlight the need to discuss parents' online information-gathering process and findings. They also highlight the need for innovative universal parent-education programs that focus on activities to facilitate early development. This type of education has potential to benefit all families, with particular benefits for families with children who have unidentified or untreated developmental delays.

Trends in the morbidity and mortality of coronavirus disease 2019 in different ethnic groups and gender in a large Brazilian city.

As the coronavirus disease 2019 (COVID-19) outbreak spread, evidence has emerged that gender and race would bear a disproportionate impact on the morbimortality of COVID-19. Here, we conducted a retrospective observational study using the TabNet/Departamento de informática do sistema único de saúde platform of the city of São Paulo. COVID-19 records from March 2020 through December 2021 were included, and we evaluated the temporal trends of confirmed cases and case fatality rate by gender and ethnicity. Statistical analysis was performed using the R-software and BioEstat-software, considering p < 0.05 significant. From March/2020 to December/2021, 1 315 160 COVID-19 confirmed cases were recorded (57.1% females), and 2973 deaths were due to COVID-19. Males presented higher median mortality (0.44% vs. 0.23%; p < 0.05) and intensive care unit (ICU) admission rates (0.34% vs. 0.20%; p < 0.05). Men were also associated with a higher risk of death (risk ratio [RR] = 1.28; p < 0.05) and a higher chance of requiring ICU care (RR = 1.29; p < 0.05). Black ethnicity was associated with a higher risk of death (RR = 1.19; p < 0.05). White patients were more likely to require ICU admission (RR = 1.13; p < 0.05), whereas Browns were associated with a protective effect (RR = 0.86; p < 0.05). Furthermore, men presented a higher chance of death than women across the three major ethnic groups: Whites (RR = 1.33; p < 0.05), Blacks (RR = 1.24; p < 0.05), and Browns (RR = 1.35; p < 0.05). In this study of COVID-19 in São Paulo, men were associated with worse outcomes, including in the three major ethnicities in the population. Blacks exhibited a higher risk of death, Whites were more likely to require intensive care, and Browns were at protection from ICU hospitalization.

START-Play Physical Therapy Intervention Indirectly Impacts Cognition Through Changes in Early Motor-Based Problem-Solving Skills.

PURPOSE: This study tested whether the Sitting Together and Reaching to Play (START-Play) physical therapy intervention indirectly impacts cognition through changes in perceptual-motor skills in infants with motor delays. METHODS: Participants were 50 infants with motor delays randomly assigned to START-Play plus Usual Care Early Intervention (UC-EI) or UC-EI only. Infants' perceptual-motor and cognitive skills were assessed at baseline and 1.5, 3, 6, and 12 months post-baseline. RESULTS: Short-term changes in sitting, fine motor skills, and motor-based problem-solving, but not reaching, predicted long-term changes in cognition. START-Play indirectly impacted cognition through motor-based problem-solving but not sitting, reaching, or fine motor skills. CONCLUSIONS: This study provided preliminary evidence that early physical therapy interventions that blend activities across developmental domains and are supported by an enriched social context can place infants on more optimal developmental trajectories.

How do parents and early intervention professionals utilize educational resources about infant development and play?

BACKGROUND: Parents utilize online sources to learn about health information, however few studies have examined where parents look for information about development or play for young children. AIMS: Investigate parents' and early intervention (EI) providers' practices and preferences regarding parent education about infant development and play. STUDY DESIGN: Cross-sectional survey design. SUBJECTS: 112 parents and 138 EI providers participated. OUTCOME MEASURES: One survey probed where parents look for information and preferred methods for receiving information about infant development and play. A second survey identified the parent education sources used and perceived quality of sources available by EI providers. Descriptive and inferential analyses were conducted. RESULTS: 112 parents and 138 EI providers participated. A greater proportion of parents sought information about development than play. Overall, parents used internet searches and preferred websites for education about development and play; however, parents of infants at risk for developmental delay preferred receiving developmental information through home visits or classes. Most EI providers have not asked parents where they look for information. A greater proportion of EI providers agreed existing sources about development, rather than about play, are high quality, but identified the need to develop high-quality sources about both topics. CONCLUSIONS: There are a variety of methods that parents access and prefer for education about infant development and play. EI providers and other healthcare professionals should discuss the methods with parents to support parents in their quest for information and ensure parents receive high-quality information.

Development and Initial Evaluation of a Soft Ankle Support for Children With Ankle Impairments.

PURPOSE: Develop and initially evaluate a soft ankle support (SAS) garment for children with ankle impairments. DESCRIPTION OF CASES: Two participants were evaluated at baseline and interviews with their parent(s) to identify wants and needs for the SAS. The SAS was developed and evaluated via participant report and functional measures in barefoot, ankle-foot orthosis (AFO), and SAS conditions. OUTCOMES: Children and parents expressed dissatisfaction with AFOs' dimensions, weight, adjustability, comfort, and ease of use. Gait and gross motor function were similar for SAS and AFOs' conditions; however, participants rated the SAS better for weight and bulk, integration with shoes, adjustability, comfort, cost, and washability. DISCUSSION: The SAS and AFOs performed similarly in this initial testing, yet the SAS also met participants' needs across key metrics not well addressed by AFOs. Ankle support devices that meet users' broad needs may support improved adherence and user satisfaction.

The Effect of START-Play Intervention on Reaching-Related Exploratory Behaviors in Children with Neuromotor Delays: A Secondary Analysis of a Randomized Controlled Trial.

AIMS: Children with neuromotor delays are at risk for reaching and object exploration impairments, which may negatively affect their cognitive development and daily activity performance. This study evaluated the effectiveness of the Sitting Together And Reaching To Play (START-Play) intervention on reaching-related exploratory behaviors in children with neuromotor delays. METHODS: In this randomized controlled clinical trial, 112 children (Mean = 10.80, SD = 2.59 months old at baseline) with motor delays were randomly assigned to receive START-Play intervention or usual care-early intervention. Performance for ten reaching-related exploratory behaviors was assessed at baseline and 1.5, 3, 6, 12 months post-baseline. Piecewise linear mixed-effects modeling was used to evaluate short- and long-term effects of the intervention. RESULTS: Benefits of START-Play were observed for children with significant motor delays, but not for those with mild delays. START-Play was especially beneficial for children with significant motor delays who demonstrated early mastery in the reaching assessment (i.e., object contact ≥65% of the time within 3 months after baseline); these children showed greater improvements in manual, visual, and multimodal exploration, as well as intensity of exploration across time. CONCLUSIONS: START-Play advanced the performance of reaching-related exploratory behaviors in children with significant motor delays.

Ensino remoto emergencial na Medicina: aspectos positivos e negativos no ensino e na aprendizagem em tempos de pandemia / Emergency distance learning in Medicine: positive and negative aspects in teaching and learning during the pandemic

Resumo: Introdução: O ensino remoto surgiu como ferramenta emergencial no processo de educação superior durante a pandemia da Covid-19. Nesse cenário, amplia-se a possibilidade de ensinar e aprender por meio das tecnologias da informação e comunicação (TIC) nos cursos de Medicina. Objetivo: Este estudo teve como objetivo realizar uma revisão integrativa que esclareça os principais aspectos positivos e negativos encontrados no exercício do ensino médico, nessas condições atípicas. Método: A busca dos artigos se deu nas seguintes bases: Biblioteca Virtual em Saúde (BVS), Embase, Education Resources Information Center (ERIC), Medline (via PubMed), Scopus e Web of Science. Resultado: Ao final dos processos de triagem e seleção, incluíram-se 69 artigos, dos quais foram extraídas informações quanto às características dos aspectos positivos e negativos de cada experiência de ensino remoto médico ofertado nesse período pandêmico. Entre os principais aspectos positivos, destacam-se a avaliação positiva do componente curricular pelos estudantes, a maior autonomia do aluno, a maior participação e comunicação entre os alunos, e a ausência de déficit de aprendizado. Entre os principais pontos negativos, observam-se a suspensão das aulas práticas, as complicações decorrentes do uso das tecnologias (conectividade, capacitação e organização) e a ausência de contato social. Conclusão: Observa-se que a autonomia e a autodisciplina discentes são fatores cruciais para o aproveitamento pleno de abordagem de aprendizagem remotamente, e talvez o aluno presencial clássico não estivesse preparado para tal mudança brusca. Ainda, percebe-se que, pela urgência de implantação dessa nova forma de aprendizagem, o ensino remoto não tenha tido tempo e maturidade o suficiente para que fosse aperfeiçoado ao ponto de ser considerado uma estratégia de educação médica aplicável em longo prazo. O ensino remoto foi crucial para que a formação de novos médicos não fosse descontinuada por um período de tempo tão extenso. Porém, o ensino remoto precisa ser reavaliado e aperfeiçoado como estratégia pedagógica que utiliza TIC para o ensino médico.

Abstract: Introduction: Distance learning emerged as an emergency tool used in Higher Education during the COVID-19 pandemic. These circumstances led to the increased use of Information and Communication Technologies (ICTs) for teaching and learning in Medicine courses. Objective: To conduct an integrative review to clarify the main positive and negative aspects found in the exercise of medical education in these atypical conditions. Method: Articles were searched on the following databases: Virtual Health Library (VHL), Embase, Education Resources Information Center (ERIC), Medline (via PubMed), Scopus and Web of Science Result: At the end of the screening and selection processes, 69 articles were included, from which information was extracted regarding the characteristics, positive and negative aspects of each remote medical teaching experience offered during the pandemic. Among the main positive aspects, we highlight the positive evaluation of the curricular component by the students, greater student autonomy, greater participation and communication among students and the absence of any learning deficit. The main negative points include the suspension of practical classes, complications arising from the use of technologies (connectivity, training and organization) and lack of social contact. Conclusion: It is observed that student autonomy and self-discipline is a crucial factor in taking full advantage of the distance learning approach, and perhaps the classic face-to-face student was not prepared for such a sudden change. Still, it is clear that, due to the urgency of implementing this new form of learning, distance learning has not had enough time to mature and be perfected to the point of being considered a medical education strategy applicable in the long term. Distance learning was crucial for the continued training of new doctors for an extended period of time. However, it needs to be reassessed and improved as a pedagogical strategy that uses ICTs for medical education.

Glycolytic Inhibitors Potentiated the Activity of Paclitaxel and Their Nanoencapsulation Increased Their Delivery in a Lung Cancer Model.

Antiglycolytic agents inhibit cell metabolism and modify the tumor's microenvironment, affecting chemotherapy resistance mechanisms. In this work, we studied the effect of the glycolytic inhibitors 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) on cancer cell properties and on the multidrug resistance phenotype, using lung cancer cells as a model. All compounds led to the loss of cell viability, with different effects on the cell metabolism, migration and proliferation, depending on the drug and cell line assayed. DCA was the most promising compound, presenting the highest inhibitory effect on cell metabolism and proliferation. DCA treatment led to decreased glucose consumption and ATP and lactate production in both A549 and NCI-H460 cell lines. Furthermore, the DCA pretreatment sensitized the cancer cells to Paclitaxel (PTX), a conventional chemotherapeutic drug, with a 2.7-fold and a 10-fold decrease in PTX IC50 values in A549 and NCI-H460 cell lines, respectively. To increase the intracellular concentration of DCA, thereby potentiating its effect, DCA-loaded poly(lactic-co-glycolic acid) nanoparticles were produced. At higher DCA concentrations, encapsulation was found to increase its toxicity. These results may help find a new treatment strategy through combined therapy, which could open doors to new treatment approaches.

Perfil epidemiológico dos pacientes hospitalizados com covid-19 no município de Mossoró - RN / Epidemiological profile of COVID-19 hospitalized patients in the municipality of Mossoró-RN / Perfil Epidemiológico de pacientes con COVID-19 en el municipio de Mossoró-RN

Introdução: Assim como observado no cenário nacional, o município de Mossoró apresentou altas taxas de letalidade nos primeiros meses de pandemia. Todavia, o conhecimento epidemiológico em torno da COVID-19 no município tem ocorrido, sobretudo, através de documentos institucionais das Secretarias de Saúde. Desse modo, a finalidade deste estudo é fornecer evidências que permitam ampliar a compreensão da ocorrência da doença em nível local, ofertar dados e informações que venham a subsidiar as políticas públicas de saúde municipais e gerar hipóteses sobre a morbimortalidade da doença para futuras investigações científicas. Objetivo: Analisar o perfil epidemiológico dos casos internados e confirmados de COVID-19 no município de Mossoró no estado do Rio Grande do Norte/Brasil. Metodologia: Estudo observacional transversal, baseado em dados secundários de casos internados de COVID-19 registrados no Sistema Único de Saúde entre março e outubro de 2020.Resultados:Foram incluídos na amostra 664 pacientes, dos quais 46,5% evoluíram para óbito. Entre as internações, 63,1% resultaram em internações em unidades de terapia intensiva. Observamos diferenças estatísticas significativas entre 'admissão na unidade de terapia intensiva e evolução para óbito' e 'faixa etária e evolução para óbito' e, maior risco entre idosos acima de 60 anos, com comorbidades, dispneia e saturação de O2 <95%. A necessidade de suporte ventilatório invasivo foi considerada fator predisponente para óbito. O risco de internação na unidade de terapia intensiva foi maior entre as idosas. Conclusões: A hospitalização e o óbito de pacientes com COVID-19foram maiores em pacientes idosos com comorbidades (AU).

Introduction:As observed in the national scenario, the city of Mossoró showed high lethality rates in the first months of the pandemic. However, the epidemiological knowledge around COVID-19 in the municipality has occurred mostly through institutional documents from the Health Secretariats. Thus, the purpose of this study is to provide evidence to broaden the understanding of the occurrence of the disease at the local level, provide data and information that will support municipal health public policies and generate hypotheses about the morbidity and mortality of the disease for future scientific investigations. Objective: To analyze the epidemiological profile of hospitalized and confirmed cases of COVID-19 in the municipality of Mossoró in the state of Rio Grande do Norte/Brazil. Methodology:This is a cross-sectional and observational study, based on secondary data from the hospitalized COVID-19 cases recorded in the Unified Health System (Sistema Unificado de Saúde, SUS) between March and October 2020. Results:664 patients were included in the sample, of which 46.5% evolved to death. Among hospitalizations, 63.1% resulted in intensive care units admissions. We observed significant differences between intensive care unit admission and evolution to death' and 'age group and evolution to death' and, higher risk among elderly individuals over 60 years, with comorbidities, dyspnea and O2 saturation<95%. Need for invasive ventilatory support was considered a predisposing factor for death. The risk of intensive care unit admission was higher among eldery women.Conclusions:Hospitalization and death of patients with COVID-19 were higher in elderly patients with comorbidities (AU).

Introducción: Como se observó en el escenario nacional, el municipio de Mossoró presentó altas tasas de letalidad en los primeros meses de la pandemia. Sin embargo, el conocimiento epidemiológico en torno al COVID-19 en el municipio se ha dado principalmente a través dedocumentos institucionales de las Secretarías de Salud. Por lo tanto, el objetivo de este estudio es proporcionar evidencias para ampliar el conocimiento de la ocurrencia de la enfermedad en el ámbito local, proporcionar datos e informaciones que apoyen las políticas públicas municipales de salud y generar hipótesis sobre la morbilidad y mortalidad de la enfermedad para futuras investigaciones científicas. Objetivo: Analizar el perfil epidemiológico de los casos hospitalizados y confirmados de COVID-19 en el municipio de Mossoró en el estado de Rio Grande do Norte/Brasil.Metodología: Se trata de un estudio transversal y observacional, basado en datos secundarios de los casos hospitalizados de COVID-19 registrados en el Sistema Unificado de Salud (SUS) entre marzo y octubre de 2020. Resultados: La muestra incluyó 664 pacientes, de los cuales el 46,5% falleció. Entre los ingresos, el 63,1% resultaron en ingresos en la unidad de cuidados intensivos. Se observaron diferencias estadísticas significativas entre el "ingreso en la unidad de cuidados intensivos y la evolución hasta la muerte" y el "grupo de edad y la evolución hasta la muerte", y un mayor riesgo entre los pacientes mayores de 60 años, con comorbilidades, disnea y saturación de O2 <95%. La necesidad de soporte ventilatorio invasivo se consideró un factor predisponente para la muerte. El riesgo de ingreso en la unidad de cuidados intensivos fue mayor entre las mujeres de edad avanzada. Conclusiones: La hospitalización y la muerte de los pacientes con COVID-19 fueron mayores en los pacientes de edad avanzada con comorbilidades (AU).

The Effect of Early-Life Seizures on Cognitive and Motor Development: A Case Series.

PURPOSE: This case series documents developmental changes over time and in response to a novel intervention, Sitting Together and Reaching to Play (START-Play), in children with early-life seizures. METHODS: Thirteen children with early-life seizures were included from a subset of participants in the START-Play multisite, randomized controlled trial. Seven received 3 months of twice weekly START-Play intervention; 6 continued with usual care early intervention. Bayley Scales of Infant Development-III (Cognitive Composite), Gross Motor Function Measure-66 Item Set, Assessment of Problem-Solving in Play, and reaching assessments were administered at baseline, 3, 6, and 12 months postbaseline. Change scores are reported at 3 and 12 months postbaseline. RESULTS: Over time, plateau or decline was noted in standardized cognition measures; motor development improved or was stable. Children receiving START-Play showed positive trends in problem-solving (71.4%) and reaching behaviors (57.2%). CONCLUSIONS: Interventions such as START-Play that combine motor and cognitive constructs may benefit children with early-life seizures.

A model for using developmental science to create effective early intervention programs and technologies to improve children's developmental outcomes.

Children born with a variety of environmental or medical risk factors may exhibit delays in global development. Very often, such delays are identified at preschool or school age, when children are severely overdue for effective early interventions that can alleviate the delays. This chapter proposes a conceptual model of child development to inform the creation of interventions and rehabilitative technologies that can be provided very early in development, throughout the first year of life, to optimize children's future developmental outcomes. The model suggests that early sensorimotor skills are antecedent and foundational for future motor, cognitive, language, and social development. As an example, this chapter describes how children's early postural control and exploratory movements facilitate the development of future object exploration behaviors that provide enhanced opportunities for learning and advance children's motor, cognitive, language, and social development. An understanding of the developmental pathways in the model can enable the design of effective intervention programs and rehabilitative technologies that target sensorimotor skills in the first year of life with the goal of minimizing or ameliorating the delays that are typically identified at preschool or school age. Specific examples of early interventions and rehabilitative technologies that have effectively advanced children's motor and cognitive development by targeting early sensorimotor skills and behaviors are provided.