Social Outbreak in Chile, and Its Association with the Effects Biological, Psychological, Social, and Quality of Life.

The World Health Organization has defined collective violence as the instrumental use of violence by people who identify themselves as members of a group against other individuals and have political, economic, or social objectives. In Chile, the "Social Outbreak" was used to describe an episode of collective violence, which began on October 18, 2019, triggered by a multitude of socioeconomic and political factors, with protests and mobilizations in the country's large and small cities; in central, commercial, and residential areas, that lasted for several months, affecting a large part of the population. The objective of the present study was to associate the social outbreak in Chile with its biological, psychological, and social effects on people's health and quality of life, as well as its characteristics in terms of exposure, proximity, type, and frequency. This was a cross-sectional study with non-probabilistic national-level sampling, conducted from 28 November 2019, to 3 March 2020. The instrument had four sections. A total of 2651 participants answered the survey; 70.8% were female, and the mean age was 35.2. The main disturbances perceived were protests (70.9%), alarm sounds (68.1%), shooting sounds (59.0%), and tear gas bombs (56.9%). When quantifying the magnitude of these associations, people who had a medium exposure have a higher probability (OR: 1.99, CI: 1.58; 2.50) of suffering three or more biological effects than people that have a low exposure, while people with higher exposition have a 4.09 times higher probability (CI: 3.11; 5.38). A similar pattern was observed regarding psychological effects, although social effects were primarily experienced by those with high exposure. Social networks, TV, and radio were the most used media among people who perceived a greater effect. People who lived, worked, or shopped near the disturbance's areas show a higher proportion negative effect.

Codetection of Plasmodium falciparum in Children Hospitalized With Dengue Fever in the Dominican Republic.

BACKGROUND: Cases of malaria and dengue in the Dominican Republic both spiked in 2019, but their rates of codetection are poorly characterized, especially in children. METHODS: We performed a prospective, observational study in January to December 2019 at the Hospital Infantil Robert Reid Cabral, in the Dominican Republic, enrolling hospitalized children with a clinical suspicion of dengue fever. Participants with a positive plasma dengue IgM antibodies were included in this study. Clinical and hospital data were abstracted, and dried blood spot samples were collected from participants and tested with quantitative polymerase chain reaction to detect the presence of Plasmodium falciparum DNA. RESULTS: A total of 429 children with serological evidence of acute dengue were included in this study, of whom 1.4% (n = 6/429) had codetection of dengue and malaria. There were no significant differences in fever duration or presence of vomiting, abdominal pain and rash between both groups. Children with dengue and malaria codetection were numerically more often admitted to the pediatric intensive care unit, despite no differences found in overall clinical severity. CONCLUSIONS: The codetection of malaria and dengue in children was overall uncommon in our Dominican Republic cohort despite the rise in cases in 2019 but may be associated with a more severe hospital course. Further epidemiological and cohort studies to characterize the risk of both pathogens as case numbers fluctuate will be important to better understand the dynamics of coinfections.

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder.

PURPOSE: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype but with limited neuroradiological data and insufficient evidence for causality of the variants. METHODS: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays and a zebrafish model. RESULTS: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. CONCLUSION: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity.

Consumo de lácteos y asociación con el exceso de peso en adultos chilenos / Dairy consumption and association with excess weight in chilean adults

Fundamentos: El objetivo de este estudio es asociar el consumo de lácteos con el índice de masa corporal (IMC) en adultos chilenos. Métodos: Estudio analítico transversal, se evaluaron adultos sanos de 18 años en adelante, en diferentes regiones del país. A los 2776 participantes se les aplicó una encuesta de hábitos alimentarios (frecuencia de consumo), encuesta de actividad física (cumple o no con 150 min /semana), de hábito tabáquico (consumo o no consumo) y se les realizaron mediciones antropométricas (peso y estatura). Resultados: Se observaron correlaciones negativas entre la frecuencia de consumo de lácteos con peso (p<0,001) e IMC (p<0,001). Al comparar el tercil de mayor consumo vs el tercil de menor consumo de lácteos, el grupo de mayor consumo presentaba un significativo menor peso e IMC y una mayor puntuación de alimentación, vs el tercil de menor consumo en <30 años (<0,001), pero no en los otros grupos etarios. Finalmente, la ingesta de lácteos se asociaba con menor peso, tanto en el modelo crudo, como en el modelo 1 (OR:0,623; IC95% 0,514-0,755), sin embargo, en el modelo 2 perdía esta asociación (OR:0,934; IC 95% 0,739- 1,181). Conclusiones: El tercil de mayor consumo de lácteos presenta un menor peso, IMC y mayor puntuación en alimentación saludable. Sin embargo, al realizar las asociaciones finales, el consumo de lácteos se muestra como un factor protector frente al exceso de peso solo en los primeros 2 modelos. (AU)

Background: The objective of this study is to associate dairy consumption with body mass index (BMI) in adults in Chile. Methods: Cross-sectional analytical study, the participants correspond to 2276 healthy adults of 18 years or older, in different regions. Each participant answers a survey which includes an eating habit questionnaire (consumption frequency), a physical activity questionnaire (complies or not with 150 min / week), and a smoking habit questionnaire (consumption or non-consumption). This data is complemented with direct measurement of weight and height. Results: Negative correlations were observed between the frequency of dairy consumption with weight (p<0.001) and BMI (p<0.001). When comparing the tertile with the highest vs. the tertile with the lowest consumption of dairy products, the group with the highest consumption has a significantly lower weight, BMI and higher food score than the tertile with the lowest consumption in those <30 years (<0.001), but not in the other age groups. Finally, dairy intake is associated with lower weight, both in the raw model and in model 1 (OR:0.623; CI95% 0.514-0.755), however, in model 2 this association is lost (OR:0.934 ; CI95% 0.739-1.181). Conclusions: The tertile with the highest consumption of dairy products has a lower weight, BMI and a higher score in healthy eating, however, when making the final associations, the consumption of dairy products is shown as a protective factor against excess weight only in the first 2 models. (AU)

The 2019-2020 Dengue Fever Epidemic: Genomic Markers Indicating Severity in Dominican Republic Children.

We performed an observational cohort study to assess associations between genetic factors of dengue fever (DF) severity in children in the Dominican Republic. A total of 488 participants had serologically confirmed DF. We replicated the association between the IFIH1 gene (rs1990760) and severe DF (n = 80/488, p = 0.006) and identified novel associations needing further investigation.

International Pediatric Multidisciplinary Management Using Telemedicine to Promote Equitable Care.

Objective: To evaluate the use of telemedicine as a collaboration tool between a pediatrician and subspecialists looking to address challenges, such as the lack of health care specialists, which are present in the Dominican Republic. Study design: During this 6-year study, 65 patients were evaluated by a medical team consisting of a local pediatrician and 17 subspecialists from a leading academic medical center in the Unites States. Patient's age ranged from 2 months to 16 years of age (mean 8 years old). The most common reasons for referral were masses or malignancies, vascular malformations, urogenital anomalies, stuttering, and cochlear implant programming. Results: A total of 39 out of 65 cases (60%) carried an initial diagnosis. Of the 65 cases, a change in medical management occurred in 92.31% of cases (60 cases). There was no change in medical diagnosis or treatment in 5 of 65 cases (8%). Conclusion: This protocol exhibited high patient satisfaction with the technology and platform and direct patient savings from transportation costs. It also demonstrated the importance of thorough diagnosis in providing appropriate treatment and solutions. Telemedicine use in comparable practices should be studied further to aid in the development of policies for the diagnosis and management of chronic illnesses that require referrals to subspecialists.

Effects of a Structured Multicomponent Physical Exercise Intervention on Quality of Life and Biopsychosocial Health among Chilean Older Adults from the Community with Controlled Multimorbidity: A Pre-Post Design.

Structured multicomponent physical exercise (PE) for older adults, with a combination of strength, aerobic, flexibility, and balance exercises, has been shown to have benefits for physical, cognitive, social, and metabolic functioning, as well as counteracting chronic pathologies and geriatric syndromes. However, little is known about the effect of these interventions in Chilean older adults. Our objective was to determine the effect of a structured multicomponent PE intervention on the quality of life (QoL) and biopsychosocial factors of community-living older adults. We conducted a pre-post intervention without control group, with a face-to-face structured multicomponent PE intervention (cardiovascular, strength/power, flexibility, static and dynamic balance, other psychomotor components, and education), based on FITT-VP principles (frequency, intensity, type, time, volume, and progression of exercise), at moderate intensity, 60 min per session, three times per week, and 12 weeks in duration, among 45 persons with an average age of 70.74 years. Participants were evaluated at the beginning and end of the intervention with different instruments of comprehensive gerontological assessment (CGA). Post intervention, participants (83.70% average attendance) significantly improved scores in QoL, biological and biopsychosocial frailty, sarcopenia, functionality in basic, instrumental, and advanced activities of daily living, dynamic balance, cognitive status and mood, systolic and diastolic blood pressure, weight, body mass index, strength and flexibility clinical tests of lower and upper extremity, aerobic capacity, agility, and tandem balance. The indication and prescription of structured multicomponent PE based on FITT-VP principles, as evaluated with the CGA, improved the QoL and biopsychosocial health of older adults. This intervention could serve as a pilot for RCTs or to improve PE programs or services for older adults under the auspices of existing public policy.

Granuloma eosinofílico cervical en el adolescente: reporte de un caso y revisión de la literatura / Cervical eosinophilic granuloma in adolescents: case report and literature review

INTRODUCCIÓN El granuloma eosinofílico (GE) es una patología infrecuente, sobre todo en adultos, que puede afectar la columna cervical. A pesar de la vasta literatura, esta enfermedad afecta principalmente a la población infantil, y no hay un consenso sobre el manejo en adultos. Con el objetivo de aportar conocimiento respecto a esta patología poco frecuente, se presenta un caso clínico de GE cervical en un paciente de 16 años, a quien se trató de manera conservadora, con buenos resultados y retorno completo a sus actividades. CASO CLÍNICO Un hombre de 16 años, seleccionado de rugby, consultó por dolor cervical axial persistente y nocturno de 6 semanas de evolución, sin trauma evidente. Al examen, destacó dolor a la compresión axial sin compromiso neurológico asociado. Los exámenes de tomografía computarizada (TC) y resonancia magnética (RM) revelaron lesión lítica en el cuerpo de C3 de características agresivas, de presentación monostótica en tomografía por emisión de positrones-tomografía computada (TEP-TC) compatible con tumor primario vertebral. Se decidió realizar biopsia percutánea bajo TC, para definir el diagnóstico y manejo adecuado, la cual fue compatible con células de Langerhans. Al no presentar clínica ni imagenología de inestabilidad ósea evidente o compromiso neurológico, se manejó con tratamiento conservador, inmovilización cervical, analgesia oral, y seguimiento estrecho. A los cuatro meses de evolución, se presentó con una TC con cambios reparativos del cuerpo vertebral y sin dolor, y logró retomar sus actividad habituales. CONCLUSIONES El diagnóstico de GE es infrecuente a esta edad, y se debe plantear entre diagnósticos diferenciales de lesiones líticas agresivas primarias vertebrales. Es necesario el uso de imágenes, y la biopsia vertebral es fundamental para confirmar el diagnóstico. Su manejo va a depender de la sintomatología, del compromiso de estructuras vecinas, y de la estabilidad de la vértebra afectada. El manejo conservador con seguimiento clínico e imagenológico es una opción viable.

INTRODUCTION Eosinophilic granuloma (EG) is a rare, tumor-like lesion, infrequently affecting the cervical spine, particularly in adults. Although vastly described in literature, this pathology mainly affects children, and there is still no consensus on its treatment in older patients. With the goal of contributing to increase the knowledge regarding this infrequent pathology, we present a case of a C3 eosinophilic granuloma in a 16-year-old patient, who was treated conservatively, with good results, including complete return to his previous activities. CLINICAL CASE a 16-year-old male, elite rugby player, presented with a history of persistent neck pain, mainly at night, with no previous trauma. Upon physical examination, he reported neck pain with axial compression of the head, without neurological impairment. Both computed tomography (CT) and magnetic resonance imaging (MRI) scan revealed an aggressive lytic lesion in the C3 vertebral body, a with monostotic presentation on positron emission tomography-computed tomography (PET-CT) compatible with a primary spine tumor. A CT-guided percutaneous biopsy was obtained to establish the diagnosis and provide the proper management. The results were compatible with Langerhans cells. As he presented no symptoms or imaging findings of evident bone instability, as well as no neurological impairment, the patient was treated conservatively, with a cervical brace, oral pain medication and close followup. A CT obtained after four months of treatment showed reparative changes of the C3 vertebral body; at this point, the patient reported no neck pain, so he was able to return to his previous activities. CONCLUSIONS Although an EG is rare at this age, it should be considered in the differential diagnosis of primary vertebral aggressive lytic lesions. Imaging and a vertebral biopsy are paramount to confirm the diagnosis. The treatment modality depends on the symptoms, the involvement of adjacent structures, and the stability of the affected vertebra. Conservative management including clinical and imaging followup is a viable option.

Social outbreak and its association with insomnia and daytime sleepiness in Chile.

Objectives: To associate the effects of the social outbreak with insomnia and daytime sleepiness according to the distance from the riots. Material and Methods: Cross-sectional analytical study; a non-probabilistic sampling was carried out at a national level. The Google Forms tool was used; a document was submitted using a national database. The instrument consisted of four sections: socio-demographic data, biopsychosocial symptoms, insomnia severity index (ISI), and the Epworth sleepiness scale (ESS). The data were analyzed using descriptive statistics and the zero-inflated negative binomial model. Results: Of a total of 2,532 surveyed people, 29% were male; 43% was younger than 30 years old. The 50% of the sample suffers from sleepiness and 71% shows some type of insomnia. The marginal effects of the zero-inflated negative binomial model show that women, people aged 51 or older, who are neither studying a healthcare degree nor working in the healthcare sector, that are exposed to 4 or more hours per day to the news and that live in areas near or very near the riots, have significantly higher ISI (marginal effect 1.356, SE 0.381, p-value 0.000) and ESS scores (marginal effect 0.693, SE 0.320, p-value 0.030). To live/work in rioting areas has the greater marginal effect compared to other determinants. Finally, neither employment status nor educational level are associated with significant effects in the aforementioned scales. Conclusion: The riots occurred during the social outbreak of October 2019 in Chile had an effect on insomnia and daytime sleepiness. Particularly, to live/work in rioting areas has the greater marginal effect compared to other determinants.

Efectos del ejercicio físico sobre la calidad de vida en personas mayores. Revisión de la literatura

RESUMEN El objetivo de esta revisión fue determinar cuál es la dosis óptima necesaria de ejercicio físico que debe realizar una persona mayor para generar efectos en la Calidad de Vida. Se realizó una búsqueda en bases de datos electrónicas entre 2015-2020. Como resultado, 9 de 33 artículos cumplieron con criterios de inclusión. La prescripción de ejercicio físico más utilizada en términos de FITT o FITT-VP fue: tipo, fuerza muscular a intensidad moderada a intensa, y/o ejercicio físico aeróbico a intensidad moderada; tiempo de sesión de 60 minutos; frecuencia 3 veces por semana; y tiempo de intervención mínimo 3 meses. En cuanto al volumen y progresión, la información fue limitada y justifica más estudios. Los efectos del ejercicio físico sobre la Calidad de Vida de las personas mayores se producirán cuando exista una programación basada como mínimo según FITT, se consideren los objetivos de la persona mayor, y la práctica sea regular.

ABSTRACT The objective of this review was to determine the optimal dose of physical exercise that an elderly person should perform to generate effects on Quality of Life. A search was carried out in electronic databases between 2015-2020. As a result, 9 of 33 articles met the inclusion criteria. The most used physical exercise prescription in terms of FITT or FITT-VP was: type, muscular strength at moderate to intense intensity, and / or aerobic physical exercise at moderate intensity; 60-minute session time; frequency 3 times a week; and intervention time at least 3 months. In terms of volume and progression, the information was limited and needs further studies. The effects of physical exercise on the Quality of Life of the elderly will occur when there is a schedule based at least according to FITT, the objectives of the elderly person are considered, and the practice is regular.

Prenatal Diagnosis of Fetal Lymphangioma: A Case Series.

Fetal lymphangioma is an uncommon congenital malformation that is mainly comprised of the subcutaneous tissue of the neck. This malformation can develop in other areas like the thoracic and axillary regions, though rarely. We report 6 consecutive cases of lymphatic malformation in a fetal center in Dominican Republic. In our case series fetal chest lymphangiomas were present in 2 fetuses. In addition, 2 cases of axillary lymphangiomas also involved the thoracic region. Adequate management by a multidiciplinary team is necessary to provide a better approach to delivery.

Nivel de Alfabetización en Salud entre Adultos Mayores Atendidos en Dos Centros Comunitarios de Rehabilitación / Level of Health Literacy among Older Adults Served in Two Community Rehabilitation Centers

Objetivos: Determinar el nivel de Alfabetización en Salud (AS) en población adulta mayor de 2 Centros Comunitarios de Rehabilitación del Norte de Chile. Configuración y Diseño: Estudio descriptivo transversal. Materiales y Métodos: Se aplicó el Cuestionario Short Assessment of Health Literacy for Spanish-Speaking Adults (SAHLSA-50), que evalúa alfabetización en Salud en Adultos Mayores (AM) atendidos en 2 Centros Comunitarios de Rehabilitación del Norte de Chile. Análisis Estadístico utilizado: Al comparar grupos que tenían variables normales se utilizó la prueba de T de Student, para 3 o más grupos se utilizó la prueba ANOVA. Para variables categóricas se utilizó la prueba de Chi-cuadrado. Resultados: Se entrevistaron a 221 adultos mayores. Edad promedio 72,7 ± 5,9 años, 70,7% a mujeres. El 79,5% de los adultos mayores presenta un adecuado AS. Las diferencias en el puntaje del cuestionario SAHLSA-50 se presentaron con la escolaridad de los participantes, es mayor el puntaje a mayor escolaridad (p<0,001), y en edad, los sujetos que presentaban menor edad (<75 años) presentaban significativamente mayor puntaje (p<0,05). Conclusiones: El Cuestionario SAHLSA-50 evidenció un buen nivel de AS, sin embargo, se observa una mejor AS en sujetos de menor escolaridad y de menor edad.(AU)

Aims: To determine the level of Health Literacy (SA) in the older adult population of 2 Community Rehabilitation Centers in the North of Chile. Settings and Design: descriptive and cross-sectional study. Methods and Material: The Short Assessment of Health Literacy for Spanish-Speaking Adults Questionnaire (SAHLSA-50) was applied, which assesses health literacy in MA attended in 2 Community Rehabilitation Centers in the North of Chile. Statistical analysis used: When comparing groups that had normal variables, the Student's t test was used, for 3 or more groups the ANOVA test was used. For categorical variables, the Chi-square test was used. Results: 221 older people were interviewed. Average age 72.7 ± 5.9 years, 70.7% women. 79.5% of the elderly have adequate SA. The differences in the score of the SAHLSA-50 questionnaire were presented with the schooling of the participants, the higher the score the higher the schooling (p <0.001), and in terms of age, the subjects who were younger (<75 years) had significantly higher score (p <0.05). Conclusions: The SAHLSA-50 questionnaire showed a good level of SA, however, a better SA is observed in subjects with less education and younger age.(AU)

Nitric oxide-targeted therapy inhibits stemness and increases the efficacy of tamoxifen in estrogen receptor-positive breast cancer cells.

Cancer stem cells (CSCs) are involved in the resistance of estrogen (ER)-positive breast tumors against endocrine therapy. On the other hand, nitric oxide (NO) plays a relevant role in CSC biology, although there are no studies addressing how this important signaling molecule may contribute to resistance to antihormonal therapy in ER+ breast cancer. Therefore, we explored whether targeting NO in ER+ breast cancer cells impacts CSC subpopulation and sensitivity to hormonal therapy with tamoxifen. NO was targeted in ER+ breast cancer cells by specific NO depletion and NOS2 silencing and mammosphere formation capacity, stem cell markers and tamoxifen sensitivity were analyzed. An orthotopic breast tumor model in mice was also performed to analyze the efficacy of NO-targeted therapy plus tamoxifen. Kaplan-Meier curves were made to analyze the association of NOS2 gene expression with survival of ER+ breast cancer patients treated with tamoxifen. Our results show that targeting NO inhibited mamosphere formation, CSC markers expression and increased the antitumoral efficacy of tamoxifen in ER+ breast cancer cells, whereas tamoxifen-resistant cells displayed higher expression levels of NOS2 and Notch-1 compared with parental cells. Notably, NO-targeted therapy plus tamoxifen was more effective than either treatment alone in an orthotopic breast tumor model in immunodeficient mice. Furthermore, low NOS2 expression was significantly associated with a higher metastasis-free survival in ER+ breast cancer patients treated with tamoxifen. In conclusion, our data support that NO-targeted therapy in ER+ breast cancer may contribute to increase the efficacy of antihormonal therapy avoiding the development of resistance to these treatments.

Relación entre Apoyo Social percibido, Severidad de Insomnio y Somnolencia Diurna en Adultos Mayores / Relationship between perceived Social Support, Severity of Insomnia and Daytime Sleepiness in Elderly

El apoyo social es un importante factor protector de la salud de los adultos mayores (AM). Asimismo, un buen dormir es fundamental para su bienestar y funcionalidad, siendo las alteraciones del sueño un importante problema de salud pública en este grupo etario. El objetivo del estudio fue determinar la relación entre apoyo social percibido, insomnio y somnolencia diurna en AM residentes en Chillán, Chile. Se realizó un estudio cuantitativo, no experimental, correlacional, de corte transversal. Se aplicó la versión chilena de la Escala de Apoyo Social Percibido (MOS), el Índice de severidad del insomnio (ISI), y la Escala de somnolencia diurna de Epworth a AM pertenecientes a agrupaciones comunitarias. Se entrevistaron a 202 AM de ambos sexos, de edad 72,3±6,2 años. Se presentaron correlaciones positivas entre escolaridad y severidad del insomnio (p<0,05) y entre severidad del insomnio y somnolencia (p<0,001), además, se encontraron correlaciones negativas entre severidad del insomnio y apoyo social percibido, tanto en forma global como por dimensiones (p<0,05). La dimensión "Interacción social positiva" se correlacionó también de forma negativa con la somnolencia diurna. Los AM participantes del estudio que presentaron un alto nivel de apoyo social presentaron una menor prevalencia y severidad del insomnio

Social support is an important protective factor for the health of elderly (E).Likewise, good sleep is fundamental for their well-being and functionality, being sleep disorder an important public health problem in this age group. The objective of this study was to determine the relationship between perceived social support, insomnia and daytime sleepiness in elderly residents of Chillán, Chile. A quantitative, non-experimental, correlational, cross-sectional study was carried out. The Chilean version of the Perceived Social Support Scale (MOS), the Index of severity of insomnia (ISI) and the Daytime Sleepiness Scale of Epworth was applied to elderly belonging to community groups. Two hundred two elderly of both sexes were interviewed, age 72.3 ± 6.2 years. There were positive correlations between schooling and severity of insomnia (p <0.05) and between severity of insomnia and somnolence (p< 0.001). In addition, there were negative correlations between severity of insomnia and perceived social support, both globally and by dimensions (p <0.05). The dimension "Positive social interaction" also correlates negatively with daytime sleepiness. The elderly participants of the study who presented a high level of social support had a lower prevalence and severity of insomnia

An international telemedicine program for diagnosis of genetic disorders: Partnership of pediatrician and geneticist.

There is a shortage of genetics providers worldwide and access is limited to large academic centers. Telemedicine programs can facilitate access to genetic services to patients living in remote locations. The goal of this study was to improve access to genetic services in the Dominican Republic by creating a partnership model between a pediatrician and geneticist. This approach has been used within the United States but not in the setting of two different countries, healthcare system, and cultures. Patients were referred to the Centro de Obstetricia y Ginecologia program if a syndromic or genetic etiology was suspected by their local provider. Pediatrician first evaluated all patients prior to telemedicine appointment to review family and medical history. All genetic visits were scheduled within 2 weeks of referral in collaboration with telehealth program at Cincinnati Children's Hospital Medical Center. A total of 66 individuals were evaluated during a period of 5 years. Fifty-seven individuals underwent genetic studies, and a molecular diagnosis was made in 39 individuals. Exome sequencing was the most common first line test when differential diagnosis was broad (n = 40). The most common inheritance was autosomal recessive in 15 individuals, followed by 13 individuals with autosomal dominant disorders, 7 individuals X-linked disorders, and 4 individuals with chromosomal abnormalities. This study provides data to support utility of geneticist and pediatrician partnership to provide outreach telemedicine diagnostics and management services for rare diseases in an international setting.

Association of Tumor Budding With Immune Evasion Pathways in Primary Colorectal Cancer and Patient-Derived Xenografts.

Tumor budding has been found to be of prognostic significance for several cancers, including colorectal cancer (CRC). Additionally, the molecular classification of CRC has led to the identification of different immune microenvironments linked to distinct prognosis and therapeutic response. However, the association between tumor budding and the different molecular subtypes of CRC and distinct immune profiles have not been fully elucidated. This study focused, firstly, on the validation of derived xenograft models (PDXs) for the evaluation of tumor budding and their human counterparts and, secondly, on the association between tumor budding and the immune tumor microenvironment by the analysis of gene expression signatures of immune checkpoints, Toll-like receptors (TLRs), and chemokine families. Clinical CRC samples with different grades of tumor budding and their corresponding PDXs were included in this study. Tumor budding grade was reliably reproduced in early passages of PDXs, and high-grade tumor budding was intimately related with a poor-prognosis CMS4 mesenchymal subtype. In addition, an upregulation of negative regulatory immune checkpoints (PDL1, TIM-3, NOX2, and IDO1), TLRs (TLR1, TLR3, TLR4, and TLR6), and chemokine receptors and ligands (CXCR2, CXCR4, CXCL1, CXCL2, CXCL6, and CXCL9) was detected in high-grade tumor budding in both human samples and their corresponding xenografts. Our data support a close link between high-grade tumor budding in CRC and a distinctive immune-suppressive microenvironment promoting tumor invasion, which may have a determinant role in the poor prognosis of the CMS4 mesenchymal subtype. In addition, our study demonstrates that PDX models may constitute a robust preclinical platform for the development of novel therapies directed against tumor budding in CRC.

Orthopedic surgery residents' perception of online education in their programs during the COVID-19 pandemic: should it be maintained after the crisis?

Background and purpose - During the COVID-19 pandemic, most of the teaching centers in Chile have shifted to online resources. We decided to do a survey on orthopedic residents regarding this type of education to assess for strengths and weaknesses of digital education in orthopedic programs.Methods - A survey was performed targeting 110 orthopedic residents belonging to different training programs around the country. 100 residents completed the survey.Results - 86% stated that their programs are using online education. When asked in detail, 86% had been involved in webinars, 28% had received online presentations, 12% had participated in online tests, and 7% had evaluated patients. Webinars were rated (1 = very unsatisfactory, 10 = very satisfactory) with a mean grade of 8.1 (1-10), online presentations 7.3 (1-10), online tests 3.8 (1-8), and online patient evaluations 2.9 (1-9). When asked if, after the end of the pandemic, they would continue using the online modalities, 82% would continue attending webinars, 72% would continue watching online presentations, 27% would continue performing online tests, and 33% of the residents would continue performing online evaluations of patients.Interpretation - Even though resident evaluation of online activities is positive, face-to-face theoretical activities are still valued as a necessary complement for orthopedic residency education.

Efectos del ejercicio físico sobre la calidad del sueño, insomnio y somnolencia diurna en personas mayores. Revisión de la literatura / Effects of physical exercise on sleep quality, insomnia, and daytime sleepiness in the elderly. A literature review

El transcurso del envejecimiento altera las etapas del sueño, y las personas mayores que consultan por este problema tienden a recibir tratamiento farmacológico, lo cual a largo plazo causa efectos secundarios y elevados costos en salud. En cambio, la práctica de ejercicio físico pudiese ser una alternativa, la cual tiene efectos multifactoriales, bajo costo y es accesible. Además estos beneficios podrían extrapolarse a la calidad del sueño. Por esto, el objetivo de esta revisión es determinar la dosificación de ejercicio físico a través del principio frecuencia, intensidad, tiempo y tipo de ejercicio y su efecto en la calidad de sueño, insomnio y somnolencia diurna en personas mayores. Esto generaría un cambio de paradigma en el tratamiento de los trastornos del sueño y ser una alternativa en el tratamiento de las personas mayores

The ageing process alters the stages of sleep, and the elderly that have this problem tend to be prescribed pharmacological treatment. This has long term side effects and results in increased health costs. On the other hand, frequent or regular physical exercise could be an overall superior alternative, due to its multifactorial effects. It is also less expensive, thus more affordable and accessible. Furthermore, these benefits could be extrapolated to the quality of sleep. Taking this into account the purpose of this paper is to establish the proper amount of physical exercise using the FITT (frequency, intensity, time, type of exercise) principle, and its effect on the quality of sleep, insomnia, and daytime sleepiness in the elderly. This could lead us to a paradigm shift in the treatment of sleep disorders, and also may constitute an alternative method for treating the elderly

[Effects of physical exercise on sleep quality, insomnia, and daytime sleepiness in the elderly. A literature review]. / Efectos del ejercicio físico sobre la calidad del sueño, insomnio y somnolencia diurna en personas mayores. Revisión de la literatura.

The ageing process alters the stages of sleep, and the elderly that have this problem tend to be prescribed pharmacological treatment. This has long term side effects and results in increased health costs. On the other hand, frequent or regular physical exercise could be an overall superior alternative, due to its multifactorial effects. It is also less expensive, thus more affordable and accessible. Furthermore, these benefits could be extrapolated to the quality of sleep. Taking this into account the purpose of this paper is to establish the proper amount of physical exercise using the FITT (frequency, intensity, time, type of exercise) principle, and its effect on the quality of sleep, insomnia, and daytime sleepiness in the elderly. This could lead us to a paradigm shift in the treatment of sleep disorders, and also may constitute an alternative method for treating the elderly.