Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells. One structure that does not form de novo with neural organoids is the meninges, a tri-layered structure that surrounds the CNS and secretes key signaling molecules required for mammalian brain development. Most studies of meninges-brain signaling have been performed in mice or using two-dimensional (2D) cultures of human cells, the latter not recapitulating the architecture and cellular diversity of the tissue. To overcome this, we developed a co-culture system of neural organoids generated from human iPSCs fused with fetal leptomeninges from mice with fluorescently labeled meninges (Col1a1-GFP). These proof-of-concept studies test the stability of the different cell types in the leptomeninges (fibroblast and macrophage) and the fused brain organoid (progenitor and neuron), as well as the interface between the organoid and meningeal tissue. We test the longevity of the fusion pieces after 30 days and 60 days in culture, describe best practices for preparing the meninges sample prior to fusion, and examine the feasibility of single or multiple meninges pieces fused to a single organoid. We discuss potential uses of the current version of the LMNO fusion model and opportunities to improve the system.

Assessing pandemic preparedness, response, and lessons learned from the COVID-19 pandemic in four south American countries: agenda for the future.

Introduction: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths. Methods: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers. Results: The results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries' health agendas. Discussion: We recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries' national public health agendas.

Adoption of Electronic Medical Records for Chronic Disease Care in Kenyan Refugee Camps: Quantitative and Qualitative Prospective Evaluation.

Background: Noncommunicable disease (NCD) prevention and control in humanitarian emergencies is a well-recognized need, but there is little evidence to guide responses, leading to varying care delivery. The Sana.NCD mobile health (mHealth) app, initially developed in Lebanon, is the only known mHealth tool for NCD management designed to increase care quality and coverage for providers in humanitarian settings. Objective: We evaluated a specialized mHealth app consisting of an abbreviated medical record for patients with hypertension or diabetes, adapted for a Kenyan refugee camp setting. Methods: We tested an adapted version of the Sana.NCD app (diabetes and hypertension medical record) in an 11-month (May 2021 to March 2022) quantitative and qualitative prospective evaluation in Kenya's Hagadera refugee camp. Leveraging the rollout of a general electronic medical record (EMR) system in the Kakuma refugee camp, we compared a specialized NCD management app to a general EMR. We analyzed secondary data collected from the Sana.NCD app for 1539 patients, EMR data for 68 patients with NCD from Kakuma's surgical and outpatient departments, and key informant interviews that focused on Hagadera clinic staff perceptions of the Sana.NCD app. Results: The Hagadera NCD clinic reported 18,801 consultations, 42.1% (n=7918) of which were reported in the NCD app. The Kakuma EMR reported 350,776 visits, of which 9385 (2.7%) were for NCDs (n=4264, 1.2% hypertension; n=2415, 0.7% diabetes). The completeness of reporting was used as a quality-of-care metric. Age, sex, prescribed medicines, random blood sugar, and smoking status were consistently reported in both the NCD app (>98%) and EMR (100%), whereas comorbidities, complications, hemoglobin A1c, and diet were rarely reported in either platform (≤7% NCD app; 0% EMR). The number of visits, BMI, physical activity, and next visit were frequently reported in the NCD app (≥99%) but not in the EMR (≤15%). In the NCD app, the completeness of reporting was high across the implementation period, with little meaningful change. Although not significantly changed during the study, elevated blood sugar (P=.82) and blood pressure (P=.12) were reported for sizable proportions of patients in the first (302/481, 62.8%, and 599/1094, 54.8%, respectively) and last (374/602, 62.1%, and 720/1395, 51.6%, respectively) study quarters. Providers were satisfied with the app, as it standardized patient information and made consultations easier. Providers also indicated that access to historic patient information was easier, benefiting NCD control and follow-up. Conclusions: A specialized record for NCDs outperformed a more general record intended for use in all patients in terms of reporting completeness. This CommCare-based NCD app can easily be rolled out in similar humanitarian settings with minimal adaptation. However, the adaptation of technologies to the local context and use case is critical for uptake and ensuring that workflows and time burden do not outweigh the benefits of EMRs.

Slippery lubricant-infused silica nanoparticulate film processing for anti-biofouling applications.

Microbial biofilm build-up in water distribution systems can pose a risk to human health and pipe material integrity. The impact is more devastating in space stations and to astronauts due to the isolation from necessary replacement parts and medical resources. As a result, there is a need for coatings to be implemented onto the inner region of the pipe to minimize the adherence and growth of biofilms. Lubricant-infused surfaces has been one such interesting material for anti-biofouling applications in which their slippery property promotes repellence to many liquids and thus prevents bacterial adherence. Textured and porous films are suitable substrate candidates to infuse and contain the lubricant. However, there is little investigation in utilizing a nanoparticulate thin film as the substrate material for lubricant infusion. A nanoparticulate film has high porosity within the structure which can promote greater lubricant infusion and retention. The implementation as a thin film structure aids to reduce material consumption and cost. In our study, we utilized a well-studied nanoporous thin film fabricated via layer-by-layer assembly of polycations and colloid silica and then calcination for greater stability. The film was further functionalized to promote fluorinated groups and improve affinity with a fluorinated lubricant. The pristine nanoporous film was characterized to determine its morphology, thickness, wettability, and porosity. The lubricant-infused film was then tested for its lubricant layer stability upon various washing conditions and its performance against bacterial biofilm adherence as a result of its slippery property. Overall, the modified silica nanoparticulate thin film demonstrated potential as a base substrate for lubricant-infused surface fabrication that repelled against ambient aqueous solvents and as an anti-biofouling coating that demonstrated low biofilm coverage and colony forming unit values. Further optimization to improve lubricant retention or incorporation of a secondary function can aid in developing better coatings for biofilm mitigation.

Peripheral arterial disease in hemodialysis patients 10 years later.

BACKGROUND AND OBJECTIVE: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported. MATERIAL AND METHODS: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. RESULTS: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ±â€¯16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ±â€¯3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp ß: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp ß: 1.73; P = 0.006; CI (1.17-2.56). CONCLUSIONS: A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis.

Human Papillomavirus-Related Recurrent Multiphenotypic Sinonasal Carcinoma With HPV Genotype 56 Detected by HPV Direct Flow CHIP.

Human Papillomavirus-related multiphenotypic sinonasal carcinoma is a rare, and recently described neoplasm, defined by its association with high-risk Human Papillomavirus, which exclusively affects the sinonasal tract and simulates salivary gland tumors. Due to the infrequency of this neoplasm and the lack of knowledge of its pathological characteristics, it is susceptible to diagnostic error. We describe the clinical-radiological findings of a 54-year-old man with multiphenotypic sinonasal carcinoma related to Human Papillomavirus genotype 56. The diagnosis of multiphenotypic sinonasal carcinoma was suspected by light microscopy and was corroborated by immunohistochemistry and polymerase chain reaction (PCR) analysis. The patient was subsequently treated with 63.6 gray radiotherapies. He is currently alive after a follow-up of 20 months, with a recurrence of the disease. In conclusion, multiphenotypic sinonasal carcinoma is an unusual neoplasm, which is not well recognized and can be confused with adenoid cystic carcinoma. However, multiphenotypic sinonasal carcinoma should be included in the differential diagnosis as we encounter sinonasal tumors, which by histology present tubular, cribriform, and solid growth patterns, accompanied by dysplasia or carcinoma in situ in the superficial mucosa. In this case, it is necessary to perform immunohistochemistry for p16INK4A or PCR to confirm the presence of high-risk Human Papilloma Virus, which would confirm the diagnosis.

Enfermedad arterial periférica en pacientes en hemodiálisis 10 años después / Peripheral arterial disease in hemodialysis patients 10 years later

Antecedentes y objetivo: Los pacientes con enfermedad renal crónica en hemodiálisis presentan gran comorbilidad cardiovascular. La enfermedad arterial periférica (EAP) se asocia a mayor mortalidad y ha incrementado el interés en su detección precoz y tratamiento. El objetivo del presente trabajo es determinar la frecuencia y gravedad de EAP sintomática, establecer su relación con la mortalidad en pacientes en hemodiálisis que han sido tratados precozmente y compararlos con una cohorte de nuestro centro ya reportada. Material y métodos:Estudio retrospectivo sobre una cohorte de todos los pacientes incidentes desde 2014 y seguidos hasta diciembre de 2019. Se recogieron datos demográficos, riesgo cardiovascular, la presencia de EAP sintomática basal y durante el seguimiento. Con la escala Rutherford se graduaron los síntomas o lesiones tróficas.Resultados: Inicialmente eran 91 pacientes y se perdió seguimiento de 7 casos que no incluyeron en el estudio. Edad 64±16 años, hombres 51,6% (47/91)). El porcentaje de EAP basal fue del 10,7% (9/84). Durante una mediana de seguimiento de 35 meses (20-57), el diagnóstico de EAP aumentó al 25% (21/84). La mitad de los enfermos con EAP (52,38% [11/21]) obtuvo una puntuación mayor de 3 de la clasificación clínica de Rutherford que corresponde con estadios severos. Requirieron reintervención por reaparición de los síntomas 13/21 pacientes (61,9% de los casos con EAP).El desarrollo de EAP se asoció de forma significativa con la presencia de un índice de Charlson elevado (3,9±2,1 vs. 7,7±3,5; p:0,001), con ser varón (19 vs. 2; p=0,001), diabético (no: 7; sí: 15; p=0,001) y con el antecedente de cardiopatía isquémica crónica (no: 13; sí:8; p=0,001), de forma que un 38,1% (8/21) presentó cardiopatía isquémica en los pacientes que desarrollaron EAP mientras que en ausencia de EAP la presencia de cardiopatía isquémica fue de un 9,5% (6/63). Además, más de la mitad (66,7% [14/21]) de los que desarrollaron EAP eran diabéticos (AU)

Background and objective: Patients with chronic kidney disease on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in hemodialysis patients that have received treated early and compare them with a cohort of our center already reported. Material and methods: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. Results: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64±16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20–57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD (52.38% [11/21]) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with the presence of an elevated index of Charlson (3.9±2.1 vs 7.7±3.5; P=.001) with being male (19 vs 2; P=.001), diabetic (no: 7; yes: 15; P=.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P=.001), so that 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. (AU)

Ocular thelaziosis: an emerging human parasitosis in Europe.

Ocular thelaziosis is a parasitosis distributed mainly in East Asia, but increasingly described in Europe in different domestic and wild animals, including dogs, different wild canids and lagomorphs, and exceptionally in humans. In Spain, in some areas, a high infection prevalence rate has been described in domestic canids, which may lead to an increase in human cases. However, the description of human cases is still exceptional, which suggests that they are probably underdiagnosed. A case of ocular thelaziosis in a 2-year-old girl from an urban environment is described.

Impact of preoperative exercise in not initially candidates to native arteriovenous fistulas.

BACKGROUND: Native autologous arteriovenous fistula (AVFn) is the preferred vascular access for hemodialysis due to its long term patency and low complication rate. A challenging limitation is the anatomical inability to perform AVFn and failure of maturation. Preoperative isometric exercise (PIE) can increase vascular calibers and improve the rate of distal AVF. However, it is unknown whether PIE might enhance the performance of AVFn in patients who are not initially candidates. METHODS: A retrospective observational study was conducted over a population of 45 patients evaluated in vascular access clinic, 23 were not initially candidates for radiocephalic (NRC-AVF) and 22 were not candidates for autologous fistula at all (NA-AVF). They were assigned to perform PIE with handgrip device and revaluated. RESULTS: After 4-8 weeks of PIE, a AVFn was performed in 16 patients from NA-AVF group and a radiocephalic AVFn was performed in 21 patients from NRC-AVF group. Both groups experienced a significant and similar increase in venous caliber 0.91 ± 0.43 mm in NA-AVF versus 0.76 ± 0.47 mm in NRC-AVF (p = 0.336) and arterial caliber 0.18 ± 0.24 mm versus 0.18 ± 0.21 mm (p = 0.928), respectively. Nevertheless, primary failure rate was significantly higher in NA-AVF (n = 8, 50%) than in NRC-AVF group (n = 3, 14.3%) (p = 0.030). After 6 months, the fistula usability for dialysis was only 50% in NA-AVF, while 86.7% were dialyzed by fistula in NRC-AVF group (p = 0.038). CONCLUSIONS: PIE allowed the allocation of an AVFn in patients not initially candidates, but entailed a high rate of maturation failure. Patients not candidates to radiocephalic AVF benefited from PIE and preserved a long term usability of AVF for dialysis.

Prolonged Computer Use by Office Workers Induces Ocular Symptoms Associated With Tear Film Alterations and Overexpression of Mucin 5 AC and Catalase.

OBJECTIVE: The aim of the study was to evaluate office workers for symptoms of computer vision syndrome (CVS) and alterations in the tear film relate to the hours of daily computer use. METHODS: Sixty-seven volunteers were divided into 2 groups: 2 to 6 and 7 to 12 hours of daily computer use. Computer vision syndrome symptoms, tear film stability by tear film break-up time test, and composition of mucin 5 AC, catalase, and IL-6 was assessed by relative gene expression of conjunctival impression cytology samples were examined. RESULTS: All participants exhibited moderate symptoms of CVS, whereas 90% showed reduced tear film stability. For the 7- to 12-hour (vs 2- to 6-hour) group, these effects were more pronounced and overexpression of mucin 5 AC and catalase was detected. CONCLUSIONS: Prolonged computer use induced an overexpression of mucin 5 AC and catalase and instability of the tear film, associated with ocular symptoms.

Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells. One structure that does not form de novo with neural organoids is the meninges, a tri-layered structure that surrounds the CNS and secretes key signaling molecules required for mammalian brain development. Most studies of meninges-brain signaling have been performed in mice or using two-dimensional (2D) cultures of human cells, the latter not recapitulating the architecture and cellular diversity of the tissue. To overcome this, we developed a co-culture system of neural organoids generated from human iPSCs fused with fetal leptomeninges from mice with fluorescently labeled meninges (Col1a1-GFP). These proof-of-concept studies test the stability of the different cell types in the leptomeninges (fibroblast and macrophage) and the fused brain organoid (progenitor and neuron), as well as the interface between the organoid and meningeal tissue. We test the longevity of the fusion pieces after 30 days and 60 days in culture, describe best practices for preparing the meninges sample prior to fusion, and examine the feasibility of single or multiple meninges pieces fused to a single organoid. We discuss potential uses of the current version of the LMNO fusion model and opportunities to improve the system.

Utilizing hiPSC-derived oligodendrocytes to study myelin pathophysiology in neuropsychiatric and neurodegenerative disorders.

Oligodendrocytes play a crucial role in our central nervous system (CNS) by myelinating axons for faster action potential conduction, protecting axons from degeneration, structuring the position of ion channels, and providing nutrients to neurons. Oligodendrocyte dysfunction and/or dysmyelination can contribute to a range of neurodegenerative diseases and neuropsychiatric disorders such as Multiple Sclerosis (MS), Leukodystrophy (LD), Schizophrenia (SCZ), and Autism Spectrum Disorder (ASD). Common characteristics identified across these disorders were either an inability of oligodendrocytes to remyelinate after degeneration or defects in oligodendrocyte development and maturation. Unfortunately, the causal mechanisms of oligodendrocyte dysfunction are still uncertain, and therapeutic targets remain elusive. Many studies rely on the use of animal models to identify the molecular and cellular mechanisms behind these disorders, however, such studies face species-specific challenges and therefore lack translatability. The use of human induced pluripotent stem cells (hiPSCs) to model neurological diseases is becoming a powerful new tool, improving our understanding of pathophysiology and capacity to explore therapeutic targets. Here, we focus on the application of hiPSC-derived oligodendrocyte model systems to model disorders caused by oligodendrocyte dysregulation.

Cancer Incidence in Merida, Mexico 2015-2018: First Report from the Population-based Cancer Registry.

BACKGROUND: Cancer registries are essential for monitoring cancer burden and patterns, and document changes in time for cancer control. Hereby, we present the first results of four years of the Merida population-based cancer registry in Mexico. METHODS: The registry collects data on all new cancers diagnosed since 2015 using both active and passive methods including a total of 104 information sources. Definitions and coding follow international standards. Using CanReg5 software, age-standardized incidence rates (ASR/100,000 person years) were computed by direct method using the world standard population. RESULTS: A total of 5684 new cancer cases were registered during 2015-2018, 2321 in males and 3363 in females corresponding to age-adjusted incidence rates (ASR per 100,000) of 128.5, and 153.1, respectively. Most frequent cancers among males were prostate cancer (ASR 29.8), lymphomas (ASR 10.9) and colorectal cancer (ASR 9.7) while among females it was breast cancer (ASR 49.3), cervical cancer (ASR 17.5) and corpus uteri (ASR 11.5). Childhood cancers (0-14 year) represented 2.9% of all cancers, with leukemias accounting for 52% of the new cases. Overall, 87.6% of new cases were microscopically verified. CONCLUSIONS: The data reported provide information on the cancer profile in Merida. Prostate and breast cancer are the main incident cancers. Cervical cancers present high rates among women, while lymphomas and liver cancer data merit further exploration. Efforts to support the Merida cancer registry as well as other registries in Mexico need to be pursued in order to have locally recorded data to support cancer control measures.

Donar leche humana salva vidas: percepciones de mujeres donantes y receptoras de leche en un banco de leche humana en Colombia / A doação de leite humano salva vidas: conhecimentos de mulheres dadoras e receptoras de leite num banco de leite humano na Colômbia / Donating human milk saves lives: insights from women donors and recipients of milk at a human milk bank in Colombia

Objective: To learn about the experiences of women who are milk donors and users of thehuman milk bank, who are mothers of pre-term infants, low birth weight infants and sick newbornshospitalized in a neonatal intensive care unit (NICU). Method Descriptive, qualitative, micro ethnographic study following the method proposed by James Spradley, focused semi-structured interviews were conducted with 10 human milk donor/receiver mothers. Results: six categories wereestablished: human milk for humans, motivation and maintenance of human milk donation, recognition of Human Milk Banks (HMLB) as a suitable place for donation, donating human milk requires commitment and technique, feelings of women donors and recipients, barriers to donation,from these categories emerged the central category "Donating human milk saves lives" ConclusionsDonating and receiving human milk is an experience in which biological, cultural, emotional and political aspects are linked. Women demand social recognition of the work of Human Milk Banksin the promotion, protection, support of breastfeeding, nutrition and protection of premature and sick newborns in neonatal units. (AU)

Objetivo: conocer las experiencias de las mujeres donantes de leche y usuarias receptoras del banco de leche humana, que son madres de recién nacidos pre-término, recién nacidos debajo peso y recién nacidos enfermos hospitalizados en una unidad de cuidado intensivo neonatal(UCIN). Método Estudio descriptivo, de tipo cualitativo, micro etnográfico siguiendo el métodopropuesto por James Spradley, se realizaron entrevistas semiestructuradas focalizadas a 10 madresdonantes/receptoras de leche humana. Resultados: seis categorías fueron establecidas: leche de humanos para humanos, motivación y mantenimiento de la donación de leche humana, reconocer losBancos de Leche Humana (BLH) como un lugar idóneo para la donación, donar leche humana exigecompromiso y técnica, sentimientos de las mujeres donantes y receptoras, barreras para la donación,de estas categorías emergió la categoría central “Donar leche humana salva vidas” ConclusionesDonar y recibir leche humana es una experiencia en la cual se vinculan aspectos biológicos, culturales, emocionales y políticos. Las mujeres reclaman el reconocimiento social, a la labor de los Bancosde Leche Humana en la promoción, protección, apoyo a la lactancia materna, la nutrición y protección de los prematuros y recién nacidos enfermos en las unidades neonatales. (AU)

Objectivo: Conhecer as experiências de mulheres dadoras de leite e utilizadorasdo banco de leite humano, mães de bebés pré-termo, bebés de baixo peso ao nascer e recém-nascidos doentes hospitalizados numa unidade de cuidados intensivos neonatais(UCIN). Método Estudo descritivo, qualitativo, microecnográfico seguindo o método proposto por James Spradley, foram realizadas entrevistas semi-estruturadas com 10 mãesdoadoras/receptoras de leite humano. Resultados: foram estabelecidas seis categorias:leite humano para consumo humano, motivação e manutenção da doação de leite humano, reconhecimento dos Bancos de Leite Humano (HMLB) como local adequado paraa doação, a doação de leite humano requer empenho e técnica, sentimentos das mulheresdadoras e receptoras, obstáculos à doação, destas categorias surgiu a categoria central"Doar leite humano salva vidas" Conclusões Doar e receber leite humano é uma experiência em que os aspectos biológicos, culturais, emocionais e políticos estão ligados. As mulheres exigem o reconhecimento social do trabalho dos Bancos de Leite Humano na promoção, protecção, apoio à amamentação, nutrição e protecção de recém-nascidos prematuros e doentes em unidades neonatais. (AU)

Serological Evidence of Exposure to Saint Louis Encephalitis and West Nile Viruses in Horses of Rio de Janeiro, Brazil.

Infections with arboviruses are reported worldwide. Saint Louis encephalitis (SLEV) and West Nile (WNV) viruses are closely related flaviviruses affecting humans and animals. SLEV has been sporadically detected in humans, and corresponding antibodies have been frequently detected in horses throughout Brazil. WNV was first reported in western Brazil over a decade ago, has been associated with neurological disorders in humans and equines and its prevalence is increasing nationwide. Herein, we investigated by molecular and serological methods the presence of SLEV and WNV in equines from Rio de Janeiro. A total of 435 serum samples were collected from healthy horses and tested for specific neutralizing antibodies by plaque reduction neutralization test (PRNT90). Additionally, samples (serum, cerebrospinal fluid, central nervous system tissue) from 72 horses, including horses with neurological disorders resulting in a fatal outcome or horses which had contact with them, were tested by real-time reverse transcription-polymerase chain reaction (RT-qPCR) for both viruses. Adopting the criterion of four-fold antibody titer difference, 165 horses (38%) presented neutralizing antibodies for flaviviruses, 89 (20.4%) for SLEV and five (1.1%) for WNV. No evidence of SLEV and WNV infection was detected by RT-qPCR and, thus, such infection could not be confirmed in the additional samples. Our findings indicate horses of Rio de Janeiro were exposed to SLEV and WNV, contributing to the current knowledge on the distribution of these viruses in Brazil.

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.

Revealing the Impact of Mitochondrial Fitness During Early Neural Development Using Human Brain Organoids.

Mitochondrial homeostasis -including function, morphology, and inter-organelle communication- provides guidance to the intrinsic developmental programs of corticogenesis, while also being responsive to environmental and intercellular signals. Two- and three-dimensional platforms have become useful tools to interrogate the capacity of cells to generate neuronal and glia progeny in a background of metabolic dysregulation, but the mechanistic underpinnings underlying the role of mitochondria during human neurogenesis remain unexplored. Here we provide a concise overview of cortical development and the use of pluripotent stem cell models that have contributed to our understanding of mitochondrial and metabolic regulation of early human brain development. We finally discuss the effects of mitochondrial fitness dysregulation seen under stress conditions such as metabolic dysregulation, absence of developmental apoptosis, and hypoxia; and the avenues of research that can be explored with the use of brain organoids.

A Randomized Controlled Trial to Increase Cancer Screening and Reduce Depression Among Low-Income Women.

Low-income women of color receive fewer cancer screenings and have higher rates of depression, which can interfere with cancer screening participation. This study assessed the comparative effectiveness of two interventions for improving colorectal, breast, and cervical cancer screening participation and reducing depression among underserved women in Bronx, NY, with depression. This comparative effectiveness randomized controlled trial (RCT) with assessments at study entry, 6, and 12 months utilized an intent-to-treat statistical approach. Eligible women were aged 50 to 64, screened positive for depression, and were overdue for ≥ 1 cancer screening (colorectal, breast, and/or cervical). Participants were randomized to a collaborative depression care plus cancer screening intervention (CCI + PCM) or cancer screening intervention alone (PCM). Interventions were telephone-based, available in English or Spanish, delivered over 12 months, and facilitated by a skilled care manager. Cancer screening data were extracted from electronic health records. Depression was measured with a validated self-report instrument (PHQ-9). Seven hundred fifty seven women consented and were randomized (CCI + PCM, n = 378; PCM, n = 379). Analyses revealed statistically significant increases in up-to-date status for all three cancer screenings; depression improved in both intervention groups. There were no statistically significant differences between the interventions in improving cancer screening rates or reducing depression. CCI and PCM both improved breast, cervical, and colorectal cancer screening and depression in clinical settings in underserved communities; however, neither intervention showed an advantage in outcomes. Decisions about which approach to implement may depend on the nature of the practice and alignment of the interventions with other ongoing priorities and resources.

Oligodendrocytes depend on MCL-1 to prevent spontaneous apoptosis and white matter degeneration.

Neurologic disorders often disproportionately affect specific brain regions, and different apoptotic mechanisms may contribute to white matter pathology in leukodystrophies or gray matter pathology in poliodystrophies. We previously showed that neural progenitors that generate cerebellar gray matter depend on the anti-apoptotic protein BCL-xL. Conditional deletion of Bcl-xL in these progenitors produces spontaneous apoptosis and cerebellar hypoplasia, while similar conditional deletion of Mcl-1 produces no phenotype. Here we show that, in contrast, postnatal oligodendrocytes depend on MCL-1. We found that brain-wide Mcl-1 deletion caused apoptosis specifically in mature oligodendrocytes while sparing astrocytes and oligodendrocyte precursors, resulting in impaired myelination and progressive white matter degeneration. Disabling apoptosis through co-deletion of Bax or Bak rescued white matter degeneration, implicating the intrinsic apoptotic pathway in Mcl-1-dependence. Bax and Bak co-deletions rescued different aspects of the Mcl-1-deleted phenotype, demonstrating their discrete roles in white matter stability. MCL-1 protein abundance was reduced in eif2b5-mutant mouse model of the leukodystrophy vanishing white matter disease (VWMD), suggesting the potential for MCL-1 deficiency to contribute to clinical neurologic disease. Our data show that oligodendrocytes require MCL-1 to suppress apoptosis, implicate MCL-1 deficiency in white matter pathology, and suggest apoptosis inhibition as a leukodystrophy therapy.

Relación entre actividad física y calidad de vida en adolescentes durante la pandemia por la COVID-19

RESUMEN Introducción: La pandemia por la COVID-19 ha generado distanciamiento social, lo cual provoca disminución de la práctica de actividad física y menor calidad de vida relacionada con la salud. Objetivo: Relacionar el nivel de actividad física con la calidad de vida relacionada con la salud, en adolescentes, durante el confinamiento por la COVID-19. Métodos: Estudio transversal que evaluó 184 estudiantes (61,4 % mujeres) con una edad media de 13,97 + 1,69 años, residentes en la región del Maule, Chile. Se emplearon dos encuestas de autoaplicación, la versión corta del Cuestionario Internacional de Actividad Física y la versión validada en población chilena, del KIDDO-KINDL. Resultados: Se presentó correlación directa y significativa entre el tiempo total de actividad física leve con la autoestima (p= 0,043) y, entre el tiempo total sentado con el bienestar emocional (p= 0,025), autoestima (p= 0,014), escuela (p= 0,031) y puntaje total de calidad de vida (p= 0,006) para el total de la muestra. Solo las mujeres presentaron correlación (p< 0,05) entre el tiempo total sentado con la familia, escuela y puntaje total de calidad de vida. Además, se encontraron diferencias significativas (p< 0,05) en el tiempo total de actividad física moderada, escuela y puntaje total de calidad de vida a favor de los hombres. Conclusión: Existe relación entre el tiempo total de actividad física con la autoestima y, entre el tiempo total sentado con el bienestar emocional, autoestima, escuela y puntaje total de calidad de vida en adolescentes durante el confinamiento por la COVID-19.

ABSTRACT Introduction: The COVID-19 pandemic has generated social distancing, causing a decrease in the practice of physical activity and a lower health-related quality of life. Objective: To relate the level of physical activity with health-related quality of life in youth, during COVID-19 lockdown. Methods: Cross-sectional study that evaluated 184 students (61,4 % female) with a mean age of 13,97 + 1,69 years, residing in the Maule region, Chile. Two self-application surveys were applied, with the short version of the International Physical Activity Questionnaire and the valid version in the Chilean population of the KIDDO-KINDL. Results: There was a direct and significant correlation between the total time of mild physical activity with self-esteem (p= 0,043) and, between the total sitting time with emotional well-being (p= 0,025), self-esteem (p= 0,014), school (p= 0,031), and total quality of life score (p= 0,006) for the total sample. Only females showed a correlation (p< 0,05) between total time sitting with family, school, and total quality of life score. In addition, significant differences (p< 0,05) were found in the total time of moderate physical activity, school, and total quality of life score in favor of males. Conclusion: There is a relationship between the total time of physical activity with self-esteem and between the total sitting time with emotional well-being, self-esteem, school, and total quality of life score in youth during COVID-19 lockdown.