Insights into the function and regulation of the calcium-activated chloride channel TMEM16A.

The TMEM16A channel, a member of the TMEM16 protein family comprising chloride (Cl-) channels and lipid scramblases, is activated by the free intracellular Ca2+ increments produced by inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release after GqPCRs or Ca2+ entry through cationic channels. It is a ubiquitous transmembrane protein that participates in multiple physiological functions essential to mammals' lives. TMEM16A structure contains two identical 10-segment monomers joined at their transmembrane segment 10. Each monomer harbours one independent hourglass-shaped pore gated by Ca2+ ligation to an orthosteric site adjacent to the pore and controlled by two gates. The orthosteric site is created by assembling negatively charged glutamate side chains near the pore´s cytosolic end. When empty, this site generates an electrostatic barrier that controls channel rectification. In addition, an isoleucine-triad forms a hydrophobic gate at the boundary of the cytosolic vestibule and the inner side of the neck. When the cytosolic Ca2+ rises, one or two Ca2+ ions bind to the orthosteric site in a voltage (V)-dependent manner, thus neutralising the electrostatic barrier and triggering an allosteric gating mechanism propagating via transmembrane segment 6 to the hydrophobic gate. These coordinated events lead to pore opening, allowing the Cl- flux to ensure the physiological response. The Ca2+-dependent function of TMEM16A is highly regulated. Anions with higher permeability than Cl- facilitate V dependence by increasing the Ca2+ sensitivity, intracellular protons can replace Ca2+ and induce channel opening, and phosphatidylinositol 4,5-bisphosphate bound to four cytosolic sites likely maintains Ca2+ sensitivity. Additional regulation is afforded by cytosolic proteins, most likely by phosphorylation and protein-protein interaction mechanisms.

2-Cys peroxiredoxins contribute to thylakoid lipid unsaturation by affecting ω-3 fatty acid desaturase 8.

Fatty acid unsaturation levels affect chloroplast function and plant acclimation to environmental cues. However, the regulatory mechanism(s) controlling fatty acid unsaturation in thylakoid lipids is poorly understood. Here, we have investigated the connection between chloroplast redox homeostasis and lipid metabolism by focusing on 2-Cys peroxiredoxins (Prxs), which play a central role in balancing the redox state within the organelle. The chloroplast redox network relies on NADPH-dependent thioredoxin reductase C (NTRC), which controls the redox balance of 2-Cys Prxs to maintain the reductive activity of redox-regulated enzymes. Our results show that Arabidopsis (Arabidopsis thaliana) mutants deficient in 2-Cys Prxs contain decreased levels of trienoic fatty acids, mainly in chloroplast lipids, indicating that these enzymes contribute to thylakoid membrane lipids unsaturation. This function of 2-Cys Prxs is independent of NTRC, the main reductant of these enzymes, hence 2-Cys Prxs operates beyond the classic chloroplast regulatory redox system. Moreover, the effect of 2-Cys Prxs on lipid metabolism is primarily exerted through the prokaryotic pathway of glycerolipid biosynthesis and fatty acid desaturase 8 (FAD8). While 2-Cys Prxs and FAD8 interact in leaf membranes as components of a large protein complex, the levels of FAD8 were markedly decreased when FAD8 is overexpressed in 2-Cys Prxs-deficient mutant backgrounds. These findings reveal a function for 2-Cys Prxs, possibly acting as a scaffold protein, affecting the unsaturation degree of chloroplast membranes.

Plastid 2-Cys peroxiredoxins are essential for embryogenesis in Arabidopsis.

The redox couple formed by NADPH-dependent thioredoxin reductase C (NTRC) and 2-Cys peroxiredoxins (Prxs) allows fine-tuning chloroplast performance in response to light intensity changes. Accordingly, the Arabidopsis 2cpab mutant lacking 2-Cys Prxs shows growth inhibition and sensitivity to light stress. However, this mutant also shows defective post-germinative growth, suggesting a relevant role of plastid redox systems in seed development, which is so far unknown. To address this issue, we first analyzed the pattern of expression of NTRC and 2-Cys Prxs in developing seeds. Transgenic lines expressing GFP fusions of these proteins showed their expression in developing embryos, which was low at the globular stage and increased at heart and torpedo stages, coincident with embryo chloroplast differentiation, and confirmed the plastid localization of these enzymes. The 2cpab mutant produced white and abortive seeds, which contained lower and altered composition of fatty acids, thus showing the relevance of 2-Cys Prxs in embryogenesis. Most embryos of white and abortive seeds of the 2cpab mutant were arrested at heart and torpedo stages of embryogenesis suggesting an essential function of 2-Cys Prxs in embryo chloroplast differentiation. This phenotype was not recovered by a mutant version of 2-Cys Prx A replacing the peroxidatic Cys by Ser. Neither the lack nor the overexpression of NTRC had any effect on seed development indicating that the function of 2-Cys Prxs at these early stages of development is independent of NTRC, in clear contrast with the operation of these regulatory redox systems in leaves chloroplasts.

La inclusión en diferentes realidades educativas: voces de profesionales / Inclusion in Different Educational Realities: Voices of Professionals

Ante el debate surgido a partir de la nueva ley de educación en España sobre las modalidades de escolarización, el presente artículo pretende sumergirse en el ámbito de la inclusión educativa, exponiendo lo que sucede dentro de las aulas en relación con la educación del alumnado denominado con Necesidades Educativas Especiales. Para ello, este trabajo se adentra en la realidad de cinco centros educativos que ofrecen diferentes modalidades de escolarización con el objetivo de conocer, según la valoración de sus profesionales, cuáles son las barreras que impiden el éxito educativo o hacia dónde debemos de dirigir las futuras acciones si queremos alcanzar la inclusión. La investigación se realiza con un método cualitativo, siguiendo un diseño emergente que busca la heterogeneidad de los participantes, y empleando entrevistas semiestructuradas en profundidad que permiten acercarse a la realidad tal como la interpretan sus agentes. La información recabada en las entrevistas se ha analizado siguiendo el modelo inductivo (codificación, categorización, descripción y valoración) con el apoyo del software profesional QDA ATLAS.ti.8. Los resultados hallados inciden en la necesidad de mayor coordinación y formación docente, pero, sobre todo, insisten en las barreras culturales y administrativas para poder mejorar la inclusión real en los centros educativos. (AU)

In view of the debate that has arisen from the new education law in Spain on the modalities of schooling, this article aims to dive into the field of educational inclusion, exposing what happens inside the classroom in relation to the education of students with Special Educational Needs. This work delves into the reality of five educational centres that offer different types of schooling with the aim of finding out, according to the voices of their professionals, what are the barriers that prevent educational success. The research is carried out using a qualitative method, following an emergent design that seeks the heterogeneity of the sample, using semi-structured in-depth interviews that allow us to approach the reality as interpreted by its agents. The information collected in the interviews has been analysed following the inductive model (coding, categorisation, description and assessment) with the support of the professional software QDA ATLAS.ti.8. The results found stress the need for greater coordination and teacher training, but, above all, they insist on cultural and administrative barriers in order to improve real inclusion in educational centres. (AU)

Workloads of Different Soccer-Specific Drills in Professional Players.

Soccer is a predominantly tactical sport and, therefore, tactical training has become the most widely used strategy to improve players' performance. The objective of the present study was to assess the workload of soccer-specific drills in professional players over a two-season period in an established context. GPS technology was used to record the data. One hundred and thirty-two (n = 132) soccer-specific drills were studied and grouped by categories. The individual demands of each task were related to the individual competitive profile of each player. The level of physical demand was significantly different in relation to the specific soccer drills analysed. Total distance covered, high-speed running, and the total number of high accelerations and decelerations were significantly higher in competition than in drills used for training sessions (p < .001). The Large-Sided Games (LSG), Big-Position Games (BPG) and Position Games (PG) showed higher maximum running speed values than the rest of the exercises (p < .01). The sum of high accelerations and decelerations values was greater in the Small-Sided Games (SSG) than in BPG (p < .001), Small-Position Games (SPG) (p < .001) and Physical-Technical Circuits (PTC) (p < .001). Significant differences were observed in the exercises analysed according to the player's position. The current findings provide a detailed description of conditional demands placed on soccer players in different soccer-specific drills during training sessions, in a professional soccer context and according to their playing position, which may be helpful in the development of individualized training programs in other contexts.

Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).

Various human tissues express the calcium-activated chloride channel Anoctamin 1 (ANO1), also known as TMEM16A. ANO1 allows the passive chloride flux that controls different physiological functions ranging from muscle contraction, fluid and hormone secretion, gastrointestinal motility, and electrical excitability. Overexpression of ANO1 is associated with pathological conditions such as hypertension and cancer. The molecular cloning of ANO1 has led to a surge in structural, functional, and physiological studies of the channel in several tissues. ANO1 is a homodimer channel harboring two pores - one in each monomer - that work independently. Each pore is activated by voltage-dependent binding of two intracellular calcium ions to a high-affinity-binding site. In addition, the binding of phosphatidylinositol 4,5-bisphosphate to sites scattered throughout the cytosolic side of the protein aids the calcium activation process. Furthermore, many pharmacological studies have established ANO1 as a target of promising compounds that could treat several illnesses. This chapter describes our current understanding of the physiological roles of ANO1 and its regulation under physiological conditions as well as new pharmacological compounds with potential therapeutic applications.

Triclosan is a KCNQ3 potassium channel activator.

KCNQ channels participate in the physiology of several cell types. In neurons of the central nervous system, the primary subunits are KCNQ2, 3, and 5. Activation of these channels silence the neurons, limiting action potential duration and preventing high-frequency action potential burst. Loss-of-function mutations of the KCNQ channels are associated with a wide spectrum of phenotypes characterized by hyperexcitability. Hence, pharmacological activation of these channels is an attractive strategy to treat epilepsy and other hyperexcitability conditions as are the evolution of stroke and traumatic brain injury. In this work we show that triclosan, a bactericide widely used in personal care products, activates the KCNQ3 channels but not the KCNQ2. Triclosan induces a voltage shift in the activation, increases the conductance, and slows the closing of the channel. The response is independent of PIP2. Molecular docking simulations together with site-directed mutagenesis suggest that the putative binding site is in the voltage sensor domain. Our results indicate that triclosan is a new activator for KCNQ channels.

Refranes que matan: hacia la concienciación social desde el aula / Raising social awareness in the classroom: Spanish proverbs that kill

Este trabajo surge de mi ponencia en el Congreso Anual de la Asociación de Lenguas Modernasde los Estados Unidos (MLA) el 9 de enero del 2019, en Chicago, Illinois. Aborda la función didácticade dichos y refranes como auténticas cápsulas culturales en el contexto del español médico,campo de primera necesidad en los Estados Unidos. El papel protagonístico de la lengua en lacultura (y viceversa) —condensado en máximas que hacen eco de una conciencia colectiva—, amenudo transmite altas dosis de machismo que, abierta o solapadamente, alimenta el engranajeinstitucionalizado de la violencia contra la mujer y contra el colectivo LGTBIQ+. Por ello, este breverecorrido por tonos disonantes nos hablará de creencias culturales opresivas que aún repercutenen la salud y en el bienestar de la mujer y de otras personas también históricamente vulneradas.El objetivo de esta experiencia de aprendizaje (mía y nuestra) es que la voz que escuchemosnos llame a examinar junto con nuestro alumnado ideas heredadas que —lejos de dar vida yesperanza— enferman y matan. Así posibilitaremos el cambio individual y social en pro de la salud y de los derechos humanos. (AU)

Part of this work was presented by the author on January 9, 2019, at the MLA (ModernLanguage Association) Annual Convention in Chicago, Illinois. It addresses the didactic role ofSpanish sayings and proverbs as authentic cultural capsules in the context of medical Spanish,a necessary field in the United States. The leading role of language in culture (and vice versa),synthesized within maxims echoing a collective consciousness, frequently conveys high levels ofsexism. It is male chauvinism that, openly or covertly, feeds the institutionalized mechanism ofviolence against women and against the LGBTQIA+ community. Thus, this short journey throughdissonant tones will talk to us about oppressive cultural beliefs that still impact women’s healthand the health of others whose rights have also been historically violated. The objective of thislearning experience (mine and yours) is that the voice that we hear will call us and our studentsto examine inherited ideas so remote from life and hope, that they sicken and kill. In so doing,we will be empowering individual and social change towards improved health and the defense of human rights. (AU)

Assistive Technology Use and Provision During COVID-19: Results From a Rapid Global Survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19. Objective: The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. METHODS: This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis. RESULTS: Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic. CONCLUSION: COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations.

Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis.

Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.

Evidence of Paraoxonases 1, 2, and 3 Expression in Human Ovarian Granulosa Cells.

Increasing evidence suggests that the antioxidant paraoxonase proteins, PON1, PON2, and PON3, have a role in reproduction and may be synthesized by ovarian cells. The aim of this work was to investigate whether human ovarian granulosa cells (GC) express paraoxonases 1, 2, and 3 (PON1, PON2, and PON3) at both the transcriptional and protein levels. Cells were purified from follicle samples of women undergoing ovarian stimulation at oocyte retrieval. We analyzed mRNA by polymerase chain reaction using specific primers for the different variants and quantified the proteins by Western blot using commercially available human recombinant PON proteins as standards. The protein subcellular distribution was determined by immunofluorescence and confocal microscopy and the cell cycles by flow cytometry. Thymidine was used for cellular synchronization at G1/S. Human hepatoma HepG2 and immortalized granulosa COV434 cell lines were used to optimize methodologies. mRNAs from PON1, the two variants of PON2, and PON3 were detected in GC. The cells actively secreted PON1 and PON3, as evidenced by the protein detection in the incubation medium. PON1 and PON3 were mainly distributed in the cytoplasm and notably in the nucleus, while PON2 colocalized with mitochondria. Subcellular nucleo-cytoplasmic distribution of PON1 was associated with the cell cycle. This is the first evidence describing the presence of mRNAs and proteins of the three members of the PON family in human ovarian GC. This study provides the basis of further research to understand the role of these proteins in GC, which will contribute to a better understanding of the reproduction process.

The Effect of Weekly Training Load across a Competitive Microcycle on Contextual Variables in Professional Soccer.

Analysis of the key performance variables in soccer is one of the most continuous and attractive research topics. Using global positioning devices (GPS), the primary aim of this study was to highlight the physiological response of a professional soccer team across competitive microcycles in-season according to the most influential contextual performance variables. Determining the training load (TL), a work ratio was established between all recorded data within the training sessions and the competitive profile (CP). Each microcycle was classified in accordance with the contextual variables: opponent level (high, medium, low), match location (home and away) and score (win, draw, lose). Results revealed that the team were significantly more successful (games won) in competitive games against high-level opponents and when played at home. Cumulative microcycle/weekly training load (WTL) was significantly lower when the team won. In addition to the opponent level and the match location, WTL could condition the athlete's performance in the competition. Competitive performance responses are the main source of information for the planning of training programs. The results of this study could be used as a reference to structure TL and WTL according to contextual variables in the competition. This study, which is the first of its kind, revealed that WTL effects the performance of the players in the competition.

Nutrition education on obesity and diabetes to medical students.

It is important for medical students to understand the relationship between nutrition, obesity, and diabetes to educate their patients in the future. However, medical training does not always include nutritional education. An experiential learning project was incorporated into the medical school curriculum as an effort to implement nutrition in the physiology course. First-year medical students (n = 140) received lectures on the regulation of blood glucose levels and their relationship to carbohydrates with different glycemic indexes (GI), obesity, and diabetes. Lectures were followed by a laboratory exercise where students calculated their body mass index (BMI), percentage body fat, and percentage muscle using a Bioelectrical Impedance Commercial Scale. While 63% of students had normal BMI, 31% were overweight or obese and 5% were underweight. A subgroup of 54 students tested different types of breakfasts with varying GI and provided blood samples at 0, 30, 60, 90, and 120 min. Their glucose responses were plotted based on the breakfast GI. Pre- and posttests were conducted to assess the teaching intervention where the Wilcoxon signed ranks test indicated that posttest ranks were significantly higher than pretest ranks (Z = -6.6, P < 0.001), suggesting the intervention was beneficial to students.

Variación de la tasa de infecciones asociadas a la atención sanitaria en neonatos / Variation in the rate of healthcare-associated infections in neonates

En el neonato las infecciones asociadas a la atención sanitaria son causas de aumento de morbilidad, mortalidad y una estancia hospitalaria prolongada. El Hospital Nacional San Juan de Dios de San Miguel, reportó una tasa de estas infecciones de 3,1 %, entre el 2008 al 2013. Objetivo. Describir la disminución de la tasa de infecciones asociadas a la atención sanitaria en la unidad de cuidado intensivos neonatal y servicio de neonatología en el hospital nacional San Juan de Dios de San Miguel con las medidas preventivas mejoradas. Metodología. Se realizó un estudio transversal descriptivo en las unidades de cuidados intensivos y neonatología entre 2014 y 2019. Se valoró la tasa anual, que identifica los casos de la vigilancia de infecciones asociadas a atención sanitaria en neonatos ingresados posterior a la intervención, que consistió en mejorar las medidas preventivas dirigidas al usuario, personal de salud y al entorno. Resultados. La tasa promedio de infecciones en ambos servicios presentó una variación, de 3,1 % de 2008-2013 a 1,6 % de 2014-2019 (p<0,3). Conclusiones. Las acciones de mejora en la prevención de infecciones asociadas a atención sanitaria, planificadas sobre sus causas y en coordinación con los tomadores de decisiones, influyen efectivamente en la incidencia de casos

In the neonate, infections associated with health care are causes of increased morbidity, mortality, and prolonged hospital stay. The San Juan de Dios National Hospital in San Miguel, reported a rate of these infections of 3.1%, between 2008 and 2013. Objective. Describe the decrease in the rate of infections associated with health care in the neonatal intensive care unit and neonatology service at the San Juan de Dios national hospital in San Miguel with improved preventive measures. Methodology. A descriptive cross-sectional study was carried out in the intensive care and neonatology units between 2014 and 2019. The annual rate was assessed, which identifies the cases of surveillance of infections associated with health care in neonates admitted after the intervention, which consisted of improving preventive measures aimed at the user, health personnel and the environment. Results. The average rate of infections in both services varied, from 3.1% from 2008-2013 to 1.6% from 2014-2019 (p <0.3). Conclusions. Actions to improve the prevention of healthcare-associated infections, planned on their causes and in coordination with decision makers, effectively influence the incidence of cases

In silico analysis of the association of hsa-miR-16 expression and cell survival in MDA-MB-231 breast cancer cells subjected to photodynamic therapy.

BACKGROUND: Breast cancer is the most common malignancy effecting women, and the triple-negative breast cancer (TNBC) subtype is particularly aggressive. This study aimed to evaluate the differential expression pattern of microRNAs (miRNAs) between untreated MDA-MB-231 cells (TNBC cell model) and those that survived photodynamic therapy (PDT) to gain insights into cell survival mechanisms. METHODS: Two PDT cycles were applied to MDA-MB-231 cells, using δ-aminolevulinic acid (ALA) followed by laser light at 635 nm. RNA was obtained from cells surviving PDT and untreated cells. The miRNAs expression profile was analyzed to detect the differences between the two groups. The potential target network of hsa-miR-16 was examined in silico with the integrative database Ingenuity® Pathway Analysis software. RESULTS: After the first and second PDT cycles, 17.8% and 49.6% of the MDA-MB-231 cells were viable. Microarray profiling of miRNAs showed decreased hsa-miR-16 expression (p < 0.05) in MDA-MB-231 cells surviving PDT when compared to the control cells. The predicted downstream targets of hsa-miR-16 were: 1) tumor suppressor protein 53; 2) molecules related to the cell cycle, such as cyclin D1, D3, and E1, and checkpoint kinase 1; 3) cell proliferation molecules, including fibroblast growth factor 1, 2 and 7 and fibroblast growth factor receptor 1; and 4) apoptosis-related molecules, consisting of BCL-2, B-cell leukemia/lymphoma 2, caspase 3, and cytochrome c. CONCLUSIONS: The differential expression of hsa-miR-16 between untreated MDA-MB-231 cells and those surviving PDT has not been previously reported. There was a lower expression of hsa-miR-16 in treated cells, which probably altered its downstream target network. In silico analysis predicted, a network related to the cell cycle, proliferation and apoptosis. These results are congruent with previous descriptions of hsa-miR-16 as a tumor suppressor and suggest that the treated population has increased their capacity to survive.

Preliminary steps of the development of a Minimum Uniform Dataset applicable to the international wheelchair sector.

Assistive products outcomes are needed globally to inform policy, practice, and drive investment. The International Society of Wheelchair Professionals developed a Minimum Uniform Dataset (MUD) for wheelchair services worldwide with the intent to gather data that is comparable globally. The MUD was developed with the participation of members from around the globe and its feasibility piloted at 3 sites. Three versions of the MUD are now available-a short form with 29 data points (available in English, Spanish, and French) and a standard version with 38 data points in English. Future work is to validate and complete the translation cycles followed by promoting the use of the MUD globally so that the data can be leveraged to inform policy, practice and direct investments.

Regulation of the Ca2+-activated chloride channel Anoctamin-1 (TMEM16A) by Ca2+-induced interaction with FKBP12 and calcineurin.

Chloride fluxes through the calcium-gated chloride channel Anoctamin-1 (TMEM16A) control blood pressure, secretion of saliva, mucin, insulin, and melatonin, gastrointestinal motility, sperm capacitation and motility, and pain sensation. Calcium activates a myriad of regulatory proteins but how these proteins affect TMEM16A activity is unresolved. Here we show by co-immunoprecipitation that increasing intracellular calcium with ionomycin or by activating sphingosine-1-phosphate receptors, induces coupling of calcium/calmodulin-dependent phosphatase calcineurin and prolyl isomerase FK506-binding protein 12 (FKBP12) to TMEM16A in HEK-293 cells. Application of drugs that target either calcineurin (cyclosporine A) or FKBP12 (tacrolimus known as FK506 and sirolimus known as rapamycin) caused a decrease in TMEM16A activity. In addition, FK506 and BAPTA-AM prevented co-immunoprecipitation between FKBP12 and TMEM16A. FK506 rendered the channel insensitive to cyclosporine A without altering its apparent calcium sensitivity whereas zero intracellular calcium blocked the effect of FK506. Rapamycin decreased TMEM16A activity in cells pre-treated with cyclosporine A or FK506. These results suggest the formation of a TMEM16A-FKBP12-calcineurin complex that regulates channel function. We conclude that upon a cytosolic calcium increase the TMEM16A-FKPB12-calcineurin trimers are assembled. Such hetero-oligomerization enhances TMEM16A channel activity but is not mandatory for activation by calcium.

Factors that influence the use of community assets by people with physical disabilities: results of participatory mapping in Envigado, Colombia.

BACKGROUND: Disability is an evolving concept that results from the complex interaction between a person with an impairment and the context in which he/she lives. There is limited understanding on the types, access and use of community assets valuable for people with disabilities, and the role of contextual factors in Colombia. Our goal with this work was to identify the factors at the levels of the socio-ecological framework, and their interaction, that influence the use of community assets among people with physical disabilities and community stakeholders in Envigado, Colombia. METHODS: Using participatory mapping, a community based participatory approach, we carried out an assessment of community assets identified by people with disabilities and rehabilitation professionals. In-depth interviews (n = 32) informed the design of two participatory mapping activities, one among people with disabilities (n = 5) and a second with rehabilitation professionals (n = 4). Results were presented in a community forum to receive feedback on the findings. RESULTS: Main findings indicate a chain of contextual factors that limit access and use of assets stemming from the personal (e.g. financial resources, inaccessible housing), interpersonal level (e.g. lack of a personal assistance or aid), and community levels (e.g. lack of accessible public transportation and inaccessible buildings). In most cases these barriers are heightened by system level barriers (e.g. lack of effective enforcement of the legal framework). CONCLUSIONS: Identifying these contextual factors, and their interactions, calls for stronger enforcement of the existing legal framework through articulated work between different stakeholders, so that people with disabilities can enjoy community assets.

Undergraduate physiotherapy students' basic wheelchair provision knowledge: a pilot study in two universities in Colombia.

Purpose: Access to an appropriate wheelchair is a human right. Only between 5-15% of people who need a wheelchair have access to one. One of the key barriers to access is the lack of appropriately trained rehabilitation professionals. The objective of this study was to evaluate basic manual wheelchair provision knowledge in final-year physiotherapy undergraduate students in two programs in Colombia.Materials and methods: Students took the International Society of Wheelchair Professionals Wheelchair Service Provision - Basic Test which was administered online and in Spanish. The minimum score to pass the test is 70%; it assesses seven domains: Assessment; Prescription; Products; Fitting; User training; Follow-up, maintenance, and repairs; and Process.Results and conclusions: One-hundred sixteen students took the test and no one passed the test. The highest median domain scores were in Assessment and Process while the lowest were in Fitting and Products. The limitations of this study include that this sample does not represent all physiotherapy programmes or students in Colombia, there may be potential errors in the Spanish translation of the outcome measure, and students encountered Internet connectivity issues during the test that may have impacted their scores. Immediate interventions are required to improve teaching and students' learning outcomes related to basic manual wheelchair provision in these two programs. This study may serve as a foundation for future regional or national studies that assess the situation of wheelchair provision training in rehabilitation programs that will inform improvement actions. This manuscript is also available in Spanish as Supplemental Material.Implications for rehabilitationThis study indicates that students' current knowledge on basic appropriate manual wheelchair provision from two physiotherapy programs in Colombia is insufficient. Students' knowledge does not align with the minimum guidelines recommended for wheelchair service provision by the World Health Organization.Objectively identifying the gap in knowledge in rehabilitation trainees (i.e., physiotherapy students) is a strategy to promote the inclusion of assistive technology related content in formal academic training.The need to include formal training of appropriate wheelchair provision persists and without this training, people with disabilities who require a wheelchair for mobility will continue to face barriers to full participation in society.

Personas con discapacidad, salud laboral y capacidades en las leyes del 2011-2020 / People with disabilities, occupational health and capacities in laws from 2011-2020 / Pessoas com deficiência, saúde do trabalhador e capacidades nas leis de 2011-2020

Objetivo: Identificar los conceptos de capacidades en las leyes relacionadas con la salud laboral para las personas con discapacidad en Colombia entre el 2011 y 2019. Materiales y método: Cualitativo con un enfoque metodológico es el hermenéutico-comprensivo a través de un análisis de contenido. Resultados: El estudio evidenció algunos conceptos de capacidades relacionados con las posibilidades que tienen las personas con discapacidad de elegir funcionamientos valiosos para su vida sin embargo las normas siguen presentando vacíos en cuanto a la definición de capacidad y una orientación hacia los funcionamientos que no permiten a las personas con discapacidad desarrollar sus capacidades. Conclusiones: Desde la perspectiva de la salud pública, son claras las desigualdades que pretenden solucionar las normas, pero puede afirmarse que, desde lo legislativo, las capacidades son abordadas desde conceptos muy generales y con elementos básicos respecto al desarrollo de capacidades de las personas con discapacidad y por lo tanto la posibilidad de evitar la discriminación de esta población en los entornos laborales sigue siendo un reto de cara a la práctica y la inclusión social

Objective: Identify the concepts of capacities in laws related to occupational health for people with disabilities in Colombia, between 2011 and 2020. Materials and methods: Qualitative study with hermeneutic-comprehensive methodological approach through the analysis of the content. The tracking of information was made through the annual reports from the Congress of Colombia found in digital archives denominated gazettes, issued between 2011- 2020. Law 361 of 1997, which regulates the reinforced labor stability was also included. For the processing of information, the 8th version of the program Atlas/Ti was used. The categories for analysis that were considered were: health, work, employment, labor disability, and capacities. Results: The study showed some capacity concepts related to the possibilities of people with disabilities of choosing valuable functions for their life: however, laws keep presenting voids regarding the definition of capacity and an orientation towards working operations that do not allow people with disabilities to develop their skills. Conclusions: From the public health standpoint, the inequalities that the laws pretend to solve are clear; but it can be claimed, from a legislative perspective, that the capacities are addressed from very general concepts and with basic elements. On the other hand, regarding the development of skills in people with disabilities and the possibility of avoiding discrimination for this population in work environments, it remains a challenge for practice and social inclusion.

Objetivo: Identificar os conceitos de capacidades nas leis relacionadas com a saúde do trabalhador para as pessoas com deficiência na Colômbia, entre 2011 e 2020. Métodos: Estudo qualitativo com metodologia hermenêutico-compreensiva na análise de conteúdo. A procura da informação realizou-se através dos anais do Congresso da República que repousam em arquivos digitais nomeados "gacetas", produzidos desde 2011 a 2020. Para o processamento da informação empregou-se o software Atlas/Ti, versão 8. As categorias na análise foram: saúde, trabalho, emprego, deficiência laboral e capacidades. Resultados: O estudo evidenciou alguns conceitos de capacidades relacionados com as possibilidades que tem as pessoas com deficiência de escolher funcionamentos de valor para as suas vidas; entretanto, as normas continuam apresentando vazios na definição de capacidade e à orientação aos funcionamentos, impedindo que às pessoas com deficiência desenvolver as suas capacidades. Conclusões: Na perspectiva de saúde pública, são claras as desigualdades que pretendem solucionar com as normas, porém desde a legislação, as capacidades são definidas com conceitos superficiais e básicos. Por outro lado, em relação com desenvolvimento de capacidades nas pessoas com deficiência e a possibilidade de evitar a discriminação e preconceito no ambiente de trabalho, continua sendo um desafio de cara à prática e à inclusão social.