Abstract: Latin American countries are experiencing a significant increase in the reports of mistreatment that women experience while using the maternity healthcare services, a phenomenon acknowledged as “Obstetric Violence” (OV). The Latin American region is crucial for the recognition of OV, not only because the term OV was originated there, but also because of its particular response to the matter. The present Scoping Review aimed to identify and review the available evidence about the response of Latin American countries to OV. As a result, it was found, firstly, that the emergence of the concept of OV in Latin America demonstrated to be a transformative tool useful to raise awareness about the mistreatment women face when giving birth. This OV concept also positions this problematic as subset of gendered violence and as a type of structural violence, through which the need to address it systemically is highlighted. Secondly, the used categorization of OV appears to be the broadest and more inclusive typology, emphasizing that OV might stem from both intentional and unintentional actions of healthcare professionals, as well as from conditions within healthcare organizations. Moreover, the identified variables that influence the response to OV in Latin America were synthetized into a theoretical framework, which offers insight into how the problem has been addressed until now and subsequently, provides useful lessons for other countries seeking approaches to combat mistreatment of women during childbirth. Lastly, it was determined that, in order to address OV and allow the progression of public policies to become regionally available, a broadened view encompassing a human rights-based approach is necessary. This research allowed to conclude that OV is a multi-faceted and complex phenomenon whose solution requires a multidimensional and multidisciplinary approach. Furthermore, OV should be understood as more than a simple act of mistreatment, but rather be viewed as a set of socially constructed symbolic, and violent, meanings allowing different stakeholders to reframe the abuse and violence that women undergoing childbirth experience as natural, expected, and accepted, reinforcing specific gender dynamics not merely in maternity care but in society overall. Finally, the framework to tackle OV within the human rights approach developed by the author is expected to be advantageous for the development of further research, programs, and policies to prevent OV in Latin America and beyond.

Abstract: Mixed microbial cultures have become a preferred choice of biocatalyst for chain elongation systems due to their ability to convert complex substrates into medium chain carboxylates. However, the complexity of the effects of process parameters on the microbial metabolic networks is a drawback that makes the task of optimizing product selectivity challenging. Here, we studied the effects of small air contaminations on the microbial community dynamics and the product formation in anaerobic bioreactors fed with lactate, acetate and H2/CO2. Two stirred tank reactors and two bubble column reactors were operated with H2/CO2 gas recirculation for 139 and 116 days, respectively, at pH 6.0 and 32°C with a hydraulic retention time of 14 days. One reactor of each type had periods with air contamination (between 97 ± 28 and 474 ± 33 mL O2 L−1 d−1, lasting from 4 to 32 days), while the control reactors were kept anoxic. During air contamination, production of n-caproate and CH4 was strongly inhibited, whereas no clear effect on nbutyrate production was observed. In a period with detectable O2 concentrations that went up to 18%, facultative anaerobes of the genus Rummeliibacillus became predominant and only n-butyrate was produced. However, at low air contamination rates and with O2 below the detection level, Coriobacteriia and Actinobacteria gained a competitive advantage over Clostridia and Methanobacteria, and propionate production rates increased to 0.8–1.8 mmol L−1 d−1 depending on the reactor (control reactors 0.1–0.8 mmol L−1 d−1). Moreover, i-butyrate production was observed, but only when Methanobacteria abundances were low and, consequently, H2 availability was high. After air contamination stopped completely, production of n-caproate and CH4 recovered, with n-caproate production rates of 1.4–1.8 mmol L−1 d−1 (control 0.7–2.1 mmol L−1 d−1). The results underline the importance of keeping strictly anaerobic conditions in fermenters when consistent n-caproate production is the goal. Beyond that, micro-aeration should be further tested as a controllable process parameter to shape the reactor microbiome. When odd-chain carboxylates are desired, further studies can develop strategies for their targeted production by applying micro-aerobic conditions.

Abstract: Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. This platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets. Resumen: El botulismo es causado por una potente neurotoxina que bloquea la transmisión neuromuscular, provocando la muerte por asfixiamiento. Actualmente, las opciones de tratamiento son limitadas y no existe un antídoto. En este artículo aprovechamos las propiedades estructurales y de tráfico neuronal de un derivado atóxico de la neurotoxina botulínica (BoNT) para transportar un anticuerpo que bloquea la función al citosol neuronal, donde puede inhibir la toxicidad molecular del serotipo A de la BoNT (BoNT /A1). El tratamiento post-sintomático alivió los signos tóxicos del botulismo y rescató de la muerte a ratones, conejillos de indias y primates no humanos después de la exposición letal a BoNT / A1. Esta plataforma podría permitir la administración de anticuerpos y otros terapéuticos basados en proteínas a blancos intraneuronales que previamente eran inaccesibles.

Mutations in PCDH19 gene are associated with Early Infantile Epileptic Encephalopathy type 9 (EIEE-9), a very rare disorder characterized by early onset of seizures, intellectual disability and psychiatric comorbidities with an unusual form of X-linked inheritance in which only females and mosaic male patients are affected. Materials and Methods: We report three patients, one male and two females carrying PCDH19 variants (D233G, V589Cfs*8 and N1103K) found by Whole exome sequencing (WES). One is a novel missense mutation (N1103K) while the others had been previously reported in female affected patients. Although, there is the first time that variant V589Cfs*8 is reported in a male patient. We performed a complete phenotype evaluation of our cases and establish the pathogenicity of each variant by in silico and functional analysis accessing many aspects of Protocadherin-19 including subcellular localization and protein expression. Results: Two of the three variants are predicted to be deleterious to protein function. The variant D233G is predicted to affect the calcium binding site and avoids cadherin strands swapping compromising the cell adhesion activity and the structural stability of the protein. While, the variant V589Cfs*8 introduced a premature stop codon which led to the loss of the transmembrane domain of the protein as well as to the cytoplasmic domain, including all predicted nuclear localization signals, suggesting the variant might affect the subcellular localization of Pcdh-19. The last findings were corroborated by western blotting and immunolabelling comparing the protein localization in patient and control fibroblasts. Conclusions: Our findings enhance understanding of molecular functions of Protocadherin-19, as well as highlighting the importance of functional testing of variants that emerge from NGS studies. Resumen: Las mutaciones en el gen PCDH19 están asociadas con la encefalopatía epiléptica infantil temprana tipo 9 (EIEE-9), un trastorno muy raro caracterizado por la aparición temprana de convulsiones, discapacidad intelectual y comorbilidades psiquiátricas con una forma inusual de herencia ligada al cromosoma X en la que solo las mujeres y mosaico pacientes masculinos se ven afectados. Materiales y métodos: Reportamos tres pacientes, un hombre y dos mujeres con variantes en el gen PCDH19 (D233G, V589Cfs*8 y N1103K) encontrados por secuenciación de exoma completo (WES). Una es una nueva mutación sin sentido (N1103K) mientras que las otras habían sido reportadas previamente en pacientes femeninas afectadas. Aunque, es la primera vez que se informa la variante V589Cfs*8 en un paciente masculino. Realizamos una evaluación completa del fenotipo de nuestros casos y establecimos la patogenicidad de cada variante mediante análisis in silico y funcional accediendo a muchos aspectos de la Protocadherin-19, incluida la localización subcelular y la expresión de proteínas. Resultados: se predice que dos de las tres variantes son perjudiciales para la función de la proteína. La variante D233G afecta el sitio de unión al calcio y evita el intercambio de hebras de caderina que comprometen la actividad de adhesión celular y la estabilidad estructural de la proteína. Mientras que la variante V589Cfs*8 introdujo un codón de parada prematuro que condujo a la pérdida del dominio transmembrana de la proteína, así como al dominio citoplasmático, incluidas todas las señales de localización nuclear esperadas, lo que sugiere que la variante podría afectar la localización subcelular de la proteína. Los últimos hallazgos fueron corroborados por Western blot e inmunomarcaje comparando la localización de la proteína en fibroblastos de pacientes y controles. Conclusiones: Nuestros hallazgos mejoran la comprensión de las funciones moleculares de Protocadherin-19, así como resaltan la importancia de las pruebas funcionales de las variantes que surgen de los estudios de secuenciación de siguiente generación (NGS).

Abstract: The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.

Abstract: Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or Xlinked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Abstract: Objective: To investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping. Background: Zambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC). Methods: We evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task- shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics. Results: From 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurologi- cal diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills. Conclusions: Epilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substan- tially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.

Abstract: Objective: To investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping. Background: Zambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC). Methods: We evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task- shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics. Results: From 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurologi- cal diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills. Conclusions: Epilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substan- tially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.

Abstract: Functional Electrical Stimulation (FES) and robotic gait orthoses are rehabilitation technologies that help patients who have lost their normal gait function due to conditions such as spinal cord injury or stroke. FES promotes active muscle contractions that facilitate the rehabilitation process, while the Lokomat (an automated gait orthosis developed by Hocoma in collaboration with Balgrist University Hospital) provides passive limb movements that help to restore and increase mobility. The goal of this project was to combine both technologies in order to improve the beneficial effects that they provide individually. For that purpose, a control algorithm was developed for real-time Linux using an Iterative Learning Control approach in parallel with feedback control. The system was implemented on the ankle and knee joints. The ankle was controlled using a desired angle based on medical literature, while the knee was controlled using a reference force trajectory measured on subjects inside the Lokomat under high-effort conditions. As an alternative to force control on the knee, angle control was implemented for experiments in the lab. The controllers were tested on healthy subjects with and without the inclusion of voluntary movement. Based on these tests, we show the advantages and disadvantages of the control scheme and the physical setup, and give ideas for further improvement. Resumen: La estimulación eléctrica funcional (FES) y las ortesis de marcha robótica son tecnologías de rehabilitación que ayudan a los pacientes que han perdido su función de marcha normal debido a afecciones como una lesión de la médula espinal o un accidente cerebrovascular. FES promueve contracciones musculares activas que facilitan el proceso de rehabilitación, mientras que Lokomat (una órtesis de marcha automatizada desarrollada por Hocoma en colaboración con el Hospital Universitario Balgrist) proporciona movimientos pasivos de las extremidades que ayudan a restaurar y aumentar la movilidad. El objetivo de este proyecto fue combinar ambas tecnologías para mejorar los efectos beneficiosos que proporcionan individualmente. Para ello, se desarrolló un algoritmo de control para Linux en tiempo real utilizando un enfoque de control por aprendizaje iterativo en paralelo con el control de retroalimentación. El sistema se implementó en las articulaciones del tobillo y la rodilla. El tobillo se controló usando un ángulo deseado basado en la literatura médica, mientras que la rodilla se controló usando una trayectoria de fuerza de referencia medida en sujetos dentro del Lokomat bajo condiciones de alto esfuerzo. Como alternativa al control de fuerza en la rodilla, se implementó el control de ángulo para experimentos en el laboratorio. Los controladores se probaron en sujetos sanos con y sin la inclusión de movimiento voluntario. Con base en estas pruebas, mostramos las ventajas y desventajas del esquema de control y la configuración física, y brindamos ideas para mejoras adicionales.

Resumen: PREGUNTA DE ESTUDIO: ¿Cuáles son las opiniones de las mujeres sobre tener hijos, incluida la edad a la que quieren tenerlos y otras influencias como como la pandemia de la enfermedad por coronavirus 2019 (COVID-19)? RESPUESTA RESUMIDA: Las opiniones de las mujeres sobre tener hijos, a su edad preferida de 30 años, incluían su impulso maternal y sus preocupaciones. sobre su reloj biológico y estabilidad, mientras que el 19% dijo que COVID-19 había afectado sus puntos de vista. DISEÑO DEL ESTUDIO, TAMAÑO, DURACIÓN: Realizamos una encuesta anónima en línea de preguntas abiertas y de opción múltiple. los La encuesta estuvo activa durante 32 días, desde el 15 de mayo de 2020 hasta el 16 de junio de 2020, y se promocionó a través de las redes sociales. PARTICIPANTES/MATERIALES, ESCENARIO, MÉTODOS: Un total de 887 mujeres de 44 países participaron en la encuesta. Después de filtrar de las mujeres que no dieron su consentimiento, dieron respuestas en blanco o incompletas, y aquellas que no estaban en el Reino Unido, quedaron 411 respuestas. Desde los datos, se analizaron tres áreas de cuestionamiento: sus opiniones sobre tener hijos, la edad ideal a la que quieren tener hijos y los efectos de la pandemia de COVID-19. Los datos cualitativos fueron analizados por análisis temático. PRINCIPALES RESULTADOS Y EL PAPEL DEL AZAR: La edad media (§SD) de las mujeres que completaron la encuesta fue de 32,2 años. (§5.9), siendo mayoritariamente heterosexuales (90,8%) y 84,8% con estudios universitarios. Un tercio de las mujeres estaban casadas/en matrimonio pareja (37,7%) y 36,0% convivían. En relación a sus visiones sobre tener hijos, los principales temas identificados fueron: la urgencia, el tictac del reloj biológico, ¿por qué nadie nos enseñó esto?, la necesidad de estabilidad y equilibrio en su vida, presión para comenzar una familia y considerando otras maneras de tener una familia. Ante la pregunta 'En un mundo ideal, ¿a qué edad aproximadamente te gustaría tener tuvo o tiene hijos?’ se observó una distribución normal con una edad media de 29,9 (§3.3) años. Cuando se le preguntó ""¿Qué factores le han llevado decidir sobre esa edad en particular?’, la elección más frecuente fue ‘Estoy desarrollando mi carrera’. Tres temas surgieron de la cualitativa pregunta sobre por qué eligieron esa edad: la necesidad de estabilidad y equilibrio en su vida, la importancia de encontrar el momento adecuado y las experiencias de vida. La mayoría de las mujeres sintieron que la pandemia de COVID-19 no había afectado su decisión de tener hijos (72,3%), pero el 19,1% dijo tenía. Los comentarios cualitativos mostraron que tenían preocupaciones sobre la inestabilidad en su vida, como finanzas y carreras, y retrasos en la fertilidad. Tratamiento.