Large conductance voltage-and calcium-activated K+ (BK) channel in health and disease.

Large Conductance Voltage- and Calcium-activated K+ (BK) channels are transmembrane pore-forming proteins that regulate cell excitability and are also expressed in non-excitable cells. They play a role in regulating vascular tone, neuronal excitability, neurotransmitter release, and muscle contraction. Dysfunction of the BK channel can lead to arterial hypertension, hearing disorders, epilepsy, and ataxia. Here, we provide an overview of BK channel functioning and the implications of its abnormal functioning in various diseases. Understanding the function of BK channels is crucial for comprehending the mechanisms involved in regulating vital physiological processes, both in normal and pathological conditions, controlled by BK. This understanding may lead to the development of therapeutic interventions to address BK channelopathies.

Complicaciones de la enfermedad de Parkinson relacionadas con la infección por SARS-CoV-2

El SARS-CoV-2 fue registrada en la ciudad de Wuhan-China, por primera vez en diciembre de 2019. El impacto de esta nueva patología en pacientes con Enfermedad de Parkinson fue negativo, por cuanto puso al descubierto el desarrollo de complicaciones graves posteriores a esta infección, Además, el virus puede afectar indirectamente el sistema nervioso central a través de la respuesta inflamatoria y la liberación de citocinas, lo que puede tener un impacto negativo en la función neuronal, conduciendo a una mayor afectación en la calidad de vida de estos pacientes. Objetivo. Describir las complicaciones de la Enfermedad de Parkinson relacionadas con la infección por SARS-CoV-2. Metodología. Se realizó una revisión sistemática, a través de una búsqueda en bases de datos. En donde se incluyeron estudios publicados entre 2019 y 2022, que cumplan criterios de inclusión y exclusión, e informen sobre las complicaciones en pacientes con enfermedad de Parkinson. Resultados. Se procedió a la lectura de texto completo de cada artículo, siendo excluidos 13 artículos, debido a que no cumplían totalmente con criterios de inclusión, presentaban otra temática o tenían una metodología poco clara, resultados 17 como resultado. Conclusión. Es importante reconocer que el COVID-19 es una enfermedad multifacética que afecta principalmente al sistema respiratorio, pero también puede tener impactos en otros sistemas del cuerpo, incluido el sistema nervioso. Si bien se ha observado que algunos pacientes con Parkinson experimentan un empeoramiento de los síntomas motores y no motores durante la infección por COVID-19, entre los síntomas que más mayor prevalencia de complicaciones presentaron se encuentran las alteraciones del sueño, alteraciones del estado de ánimo, bradicinesia, rigidez, temblor, alteraciones de la marcha.

SARS-CoV-2 was recorded in Wuhan City-China for the first time in December 2019. The impact of this new pathology in patients with Parkinson's Disease was negative, in that it uncovered the development of severe complications following this infection, in addition, the virus may indirectly affect the central nervous system through inflammatory response and cytokine release, which may have a negative impact on neuronal function, leading to further impairment in the quality of life of these patients. Objective. To describe the complications of Parkinson's disease related to SARS-CoV-2 infection. Methodology. A systematic review was carried out through a database search. We included studies published between 2019 and 2022 that met inclusion and exclusion criteria and reported on complications in patients with Parkinson's disease. Results. We proceeded to read the full text of each article, being excluded 13 articles, because they did not fully meet inclusion criteria, presented another subject or had an unclear methodology, 17 as a result. Conclusion. It is important to recognize that COVID-19 is a multifaceted disease that primarily affects the respiratory system, but can also have impacts on other body systems, including the nervous system. While it has been observed that some Parkinson's patients experience worsening of motor and non-motor symptoms during COVID-19 infection, among the symptoms with the highest prevalence of complications were sleep disturbances, mood disturbances, bradykinesia, rigidity, tremor, gait disturbances.

O SARS-CoV-2 foi registrado na cidade de Wuhan, na China, pela primeira vez em dezembro de 2019. O impacto dessa nova patologia em pacientes com doença de Parkinson foi negativo, pois revelou o desenvolvimento de complicações graves após essa infecção. Além disso, o vírus pode afetar indiretamente o sistema nervoso central por meio da resposta inflamatória e da liberação de citocinas, o que pode ter um impacto negativo na função neuronal, levando a um maior comprometimento da qualidade de vida desses pacientes. Objetivo. Descrever as complicações da doença de Parkinson relacionadas à infecção pelo SARS-CoV-2. Metodologia. Foi realizada uma revisão sistemática por meio de uma pesquisa em banco de dados. Foram incluídos estudos publicados entre 2019 e 2022 que atenderam aos critérios de inclusão e exclusão e relataram complicações em pacientes com doença de Parkinson. Resultados. Prosseguimos com a leitura do texto completo de cada artigo e excluímos 13 artigos porque eles não atendiam totalmente aos critérios de inclusão, apresentavam um tópico diferente ou tinham uma metodologia pouco clara, resultados 17 Conclusão. É importante reconhecer que a COVID-19 é uma doença multifacetada que afeta principalmente o sistema respiratório, mas também pode ter impactos em outros sistemas do corpo, incluindo o sistema nervoso. Embora alguns pacientes com Parkinson tenham apresentado piora dos sintomas motores e não motores durante a infecção por COVID-19, os sintomas com maior prevalência de complicações incluem distúrbios do sono, distúrbios do humor, bradicinesia, rigidez, tremor e distúrbios da marcha.

Atribuciones hacia la timidez y la soledad en niños y niñas de diferentes contextos sociales argentinos / Attributions towards shyness and unsociability in Argentinian children from different social contexts

Resumen Las atribuciones de los niños y las niñas hacia los comportamientos de retraimiento social suelen estar determinadas por el entorno sociocultural particular en el que se desarrollan e influyen en la forma en que reaccionan a las conductas de sus pares durante las interacciones sociales. El objetivo de este trabajo fue comparar dichas atribuciones hacia dos subtipos de retraimiento social (timidez y preferencia por la soledad) referidas por niños y niñas de tres contextos diferentes de Mendoza (Argentina): urbano, urbano-marginado y rural. Se llevó a cabo un estudio con 221 niños y niñas abordando jardines de infantes estatales de cada ámbito (urbano: . = 82, Mmeses= 62.33; urbano-marginado: . = 72, Mmeses= 60.47; rural: . = 67, Mmeses= 63.07). Los escolares fueron entrevistados individualmente con una serie de viñetas gráficas con personajes hipotéticos desplegando conductas sociables, tímidas, solitarias y agresivas frente a las cuales respondieron preguntas sobre sus atribuciones y percepciones en distintos aspectos. Las diferentes pruebas no paramétricas realizadas señalaron que el personaje tímido fue percibido con mayor motivación social y menor intencionalidad en su conducta que el personaje solitario en todos los grupos. No se encontraron diferencias entre los contextos en la atribución de consecuencias sociales negativas para estas conductas, aunque el grupo de escolares rurales reportó mayor preferencia afiliativa y compasión por el personaje tímido en comparación con el grupo urbano. Se discuten estos resultados considerando cómo las expectativas de socialización de cada contexto podrían influir en las percepciones de los escolares hacia el retraimiento social.

Abstract Children's attributions towards withdrawn behaviors are usually determined by the particular social milieu in which they develop and tend to influence their behaviors and reactions. The aim of this work was to compare the attributions towards two subtypes of social withdrawal (shyness and unsociability) referred by children from three different contexts in Mendoza, Argentina: urban, urban-marginalized and rural. Participants were 221 kindergarten children from these contexts (urban: n = 82, Mmonths = 62.33; urban-marginalized: n = 72, Mmonths = 60.47; rural: n = 67, Mmonths = 63.07). Children were individually interviewed with a series of graphic vignettes with hypothetical characters displaying shy and unsociable behaviors, and for comparison purposes were also assessed aggressive and socially competent behaviors. After each vignette, children were asked a series of questions designed to assess their attributions toward each behavior in six dimensions: intentionality, social motivation, affiliative preference, social status, negative impact and sympathy. The results of this study showed that young children in the three contexts were able to distinguish social withdrawal from other types of behaviors (i.e., aggressiveness and sociability). Overall, withdrawn behaviors received more positive attributions (greater affiliative preference, better social position and less negative impact) than aggressive behaviors, although they were also perceived negatively in relation to more socially competent behaviors (the latter were attributed greater affiliative preference and best position within the peer group). Furthermore, it was observed that children from the three contexts made clearly distinctions among the different forms of social withdrawal in terms of intentionality and social motivation. Specifically, they reported that compared with unsociable characters, shy ones are more socially motivated and less intentional in their behavior, evocating greater feelings of compassion. However, some peculiarities can be appreciated in each context. The results indicated that children in the urban group reported greater feelings of sympathy for the shy character in relation to the unsociable, which was not evidenced in the other groups. In addition, children from the rural sample showed a greater preference for interact with the hypothetical shy peer than with the unsociable character and this inclination was also greater when compared with the urban sample. Taken together, these results may suggest that different socialization norms and expectations would evoke different meanings and implications to the socially withdrawn manifestations. It might be possible that in urban contexts children's socialization expectations highlight extraversion and self-affirming behaviors which generate more empathetic reactions in front of passive or fearful manifestations as shyness. On the other hand, rural children may prefer peers who display shy behaviors possibly because it is in line with expectations of social cohesion and modesty that are value in this milieu. Nevertheless, no differences were found between shy and unsociable behaviors in any of the contexts in terms of social position and negative impact that they anticipated for the peer group. These results could provide some support for the idea that social withdrawal tends to be globally perceived as benign at an early age, and especially in the rural context, where it is a frequent and valued behavior. Although it is not possible with the limited variables included in this study to know which are the specific contextual aspects that affect some attributions and through what mechanisms they do so, these findings are an important starting point to continue deepening the socialization processes in urban, urban-marginalized and rural young children. This study is also one of the first to evaluate the knowledge and attributions of Argentinean children from different social context toward social withdrawal and provides new evidence on the differences in the cultural meaning and implications of withdrawn behaviors in early childhood.

A journey from molecule to physiology and in silico tools for drug discovery targeting the transient receptor potential vanilloid type 1 (TRPV1) channel.

The heat and capsaicin receptor TRPV1 channel is widely expressed in nerve terminals of dorsal root ganglia (DRGs) and trigeminal ganglia innervating the body and face, respectively, as well as in other tissues and organs including central nervous system. The TRPV1 channel is a versatile receptor that detects harmful heat, pain, and various internal and external ligands. Hence, it operates as a polymodal sensory channel. Many pathological conditions including neuroinflammation, cancer, psychiatric disorders, and pathological pain, are linked to the abnormal functioning of the TRPV1 in peripheral tissues. Intense biomedical research is underway to discover compounds that can modulate the channel and provide pain relief. The molecular mechanisms underlying temperature sensing remain largely unknown, although they are closely linked to pain transduction. Prolonged exposure to capsaicin generates analgesia, hence numerous capsaicin analogs have been developed to discover efficient analgesics for pain relief. The emergence of in silico tools offered significant techniques for molecular modeling and machine learning algorithms to indentify druggable sites in the channel and for repositioning of current drugs aimed at TRPV1. Here we recapitulate the physiological and pathophysiological functions of the TRPV1 channel, including structural models obtained through cryo-EM, pharmacological compounds tested on TRPV1, and the in silico tools for drug discovery and repositioning.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection†.

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement.

Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention.

INTRODUCTION: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women. METHODS: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women. Levels of knowledge were compared among groups. RESULTS: Of the 1,449 health professionals approached, 338 surveys were answered. 72% of professionals considered CMV a relevant problem. 47% of obstetricians and 28% of midwives (p ≤ 0.001) routinely informed pregnant women, and less than half knew the risk of fetal transmission. We observed significant differences in knowledge between obstetricians and midwives concerning the risks of recurrent infections, risk of transmission, and risk of severe infection (60.7% vs. 45.6%, p = 0.006 and 50.6% vs. 22.5%, p ≤ 0.001); and regarding maternal and neonatal symptoms and newborn sequelae (23% vs. 8.8%, p ≤ 0.001). Of the 700 women approached, we obtained a response rate of 72%. Only 23% had previously heard about CMV, 22% identified transmission routes, and 15% preventive measures. Compared to women without risk factors for CMV infection, women at greater risk had heard more about CMV (mothers of children <3 years: 36% vs. 20%, p < 0.001; occupational exposure: 43% vs. 20%, p ≤ 0.001) and had received more information (mothers of children <3 years: 18% vs. 9.5%, p ≤ 0.001; occupational exposure: 23% vs. 9.3%, p = 0.001). CONCLUSION: Health care professionals have limited knowledge about CMV and may fail to enforce preventive measures. While pregnant women have limited awareness about CMV infection, they recognize the need for information. Health campaigns should be promoted to enhance awareness about this perinatal infection.

Young Argentine Children's Attributions about Hypothetical Socially Withdrawn Peers.

This study assessed young children's attributions about different subtypes of hypothetical socially withdrawn peers. Participants were N = 114 (56% boys, Mage= 60.53 months, SD = 7.58) children attending urban public kindergartens in Mendoza, Argentina. Children were presented with vignettes describing hypothetical shy, unsociable, aggressive, and socially competent peers, and were asked a series of questions to assess their attributions toward each behavior. The results indicated that Argentine children characterized hypothetical unsociable peers as behaving with greater intentionality and lesser social motivations than shy children. No differences were found between the unsociable and shy hypothetical peers regarding the attributions of sympathy, affiliative preference, negative impact and social standing in the class. These findings provide some of the first evidence about Argentine children understanding of social withdrawal. Results are discussed in terms of the possible cultural meanings and implications of these behaviors.

Bisphosphonates Targeting Ion Channels and Musculoskeletal Effects.

Bisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line therapy in several bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. BPs target the farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their pain-relieving effects. Even so, molecular targets involved in these effects appear now largely elusive. Ion channels are emerging players in bone homeostasis. Nevertheless, the effects of BPs on these proteins have been poorly described. Here we reviewed the actions of BPs on ion channels in musculoskeletal cells. In particular, the TRPV1 channel is essential for osteoblastogenesis. Since it is involved in bone pain sensation, TRPV1 is a possible alternative target of BPs. Ion channels are emerging targets and anti-target for bisphosphonates. Zoledronic acid can be the first selective musculoskeletal and vascular KATP channel blocker targeting with high affinity the inward rectifier channels Kir6.1-SUR2B and Kir6.2-SUR2A. The action of this drug against the overactive mutants of KCNJ9-ABCC9 genes observed in the Cantu' Syndrome (CS) may improve the appropriate prescription in those CS patients affected by musculoskeletal disorders such as bone fracture and bone frailty.

Embarazo ectópico en cuerno rudimentario izquierdo de útero unicorne con embarazo de 15 semanas: reporte de un caso / Ectopic pregnancy in rudimentary left horn of unicorne uterus with pregnancy of 15 weeks: a case report

INTRODUCCIÓN: El embarazo ectópico en el cuerno rudimentario de un útero unicorne tiene una incidencia de 1 en 76.000 embarazos. La aproximación diagnóstica se realiza con la ecografía y como estudio complementario con la resonancia magnética. El diagnóstico temprano con tratamiento oportuno es fundamental para la prevención de la morbimortalidad materna asociada. El objetivo es describir el diagnóstico y el tratamiento temprano de un caso de embarazo ectópico de 15 semanas en cuerno rudimentario no comunicante de útero unicorne. CASO CLÍNICO: Mujer de 38 años con embarazo de 15 semanas, asintomática, que ingresa al servicio de urgencias referida desde el servicio de ecografía por sospecha de embarazo ectópico. Se realizan ecografía y resonancia magnética que muestran embarazo con feto único de 15 semanas en cuerno uterino izquierdo rodeado de miometrio, sin comunicación con la cavidad endometrial. Con impresión diagnóstica de embarazo ectópico cornual en paciente con malformación mülleriana, se realizó manejo quirúrgico que confirmó útero unicorne con embarazo ectópico en cuerno rudimentario no comunicante. CONCLUSIONES: El embarazo ectópico en un cuerno rudimentario de útero unicorne es infrecuente y presenta un alto riesgo de rotura, con aumento de la morbimortalidad obstétrica. El tratamiento estándar, al igual que la confirmación diagnóstica, es la escisión quirúrgica completa.

INTRODUCTION: Ectopic pregnancy in the rudimentary horn of a unicornuate uterus has an incidence of 1 in 76,000 pregnancies; the diagnostic approach is carried out with ultrasound and magnetic resonance imaging as a complementary study; Early diagnosis with timely treatment is essential for the prevention of associated maternal morbidity and mortality. The objective is to describe the early diagnosis and treatment of a case of 15-week ectopic pregnancy in a rudimentary non-communicating horn of the unicornuate uterus. CASE REPORT: A 38-year-old patient with an asymptomatic 15-week pregnancy was admitted to the emergency department, referred to the ultrasound service for suspected ectopic pregnancy. Ultrasound and magnetic resonance imaging were performed with pregnancy with a single fetus of 15 weeks in the left uterine horn surrounded by myometrium, without communication with the endometrial cavity. With a diagnostic impression of cornual ectopic pregnancy in a patient with a Müllerian malformation, a surgical management was performed where a unicornuate uterus with a rudimentary non-communicating ectopic horn was confirmed. CONCLUSIONS: Ectopic pregnancy in rudimentary horn of the unicornuate uterus is rare, it presents a high risk of rupture with increased obstetric morbidity and mortality. The standard treatment as well as the diagnostic confirmation is complete surgical excision.

Correction: Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress.

[This corrects the article DOI: 10.1371/journal.pone.0015658.].

Medication-related osteonecrosis of the jaw in cancer patients: Case series and review of the current literature.

Currently, a large proportion of cancer patients are treated with bone modifying agents (BMA). In this regard, the increase in the prescription of these drugs has lead to concerns in the increment of osteonecrosis of the jaws. This article describes four patients with BMA cancer treatments requested dental evaluation at our institution due to pain and swelling of the mandibular bone after tooth extraction, tooth loss, or unknown risk factor. Oral and radiographic evaluation reveals Medication-related osteonecrosis of the jaw (MRONJ) at different clinical stages according to the American Association of Oral and Maxillofacial Surgeons (AAOMS) classification. Some patients underwent abscess drainage, oral cleaning and antibiotic therapy with complete recovery. Follow-up showed treatment success in all patients. That is why we emphasize the importance of early establishment of appropriate treatment and emphasize the avoidance of dental procedures during BMA therapy.

En la actualidad, una gran cantidad de pacientes con cáncer son tratados con agentes modificadores óseos (AMO). En relación con esto, el aumento en la prescripción de estos fármacos ha generado preocupación por el incremento en la osteonecrosis de los maxilares. Este artículo describe cuatro casos de pacientes con cáncer, tratados con AMO, que acuden a nuestra institución debido a que padecen dolor e inflamación de la mandíbula, después de la extracción dental, así como pérdida de dientes con un factor de riesgo desconocido. La evaluación clínica y radiográfica evidenció osteonecrosis de los maxilares en diferentes etapas clínicas, según la clasificación de la Asociación Estadounidense de Cirujanos Orales y Maxilofaciales (AAOMS). Algunos de los pacientes fueron sometidos a drenaje de abscesos, limpieza bucal y antibioticoterapia con recuperación completa. El seguimiento clínico fue exitoso en todos los pacientes. Es por eso que hacemos énfasis en la importancia de establecer un tratamiento apropiado y evitar procedimientos dentales durante la terapia con AMO.

Eagle syndrome treated by a trans oral approach. Case report.

BACKGROUND: Eagle syndrome is an uncommon condition, characterized by alteration in the stylomastoid process and sometimes a complete calcification of the stylohyoid ligament. OBJECTIVE: To report the relevance of a timely diagnosis and treatment options. CASE REPORT: 53-year-old female, present symptoms, characterized by occipital headache and neck pain and dysphagia with one-year evolution, through studies Imaging and clinical, the diagnosis of eagle syndrome was obtained, which is treated by surgical transoral approach. CONCLUSIONS: Eagle syndrome consists of nonspecific clinical signs, so it is important to understand the diagnostic evaluation, and the variety of treatment options.

ANTECEDENTES: El síndrome de Eagle es una condición poco común caracterizada por una alteración en la apófisis estilomastoides o una calcificación completa del ligamento estilohioideo. OBJETIVO: Reportar la relevancia de un diagnóstico oportuno y las opciones de tratamiento. CASO CLÍNICO: Mujer de 53 años con síntomas de cefalea occipital, dolor cervical y disfagia con 1 año de evolución. Por medio de imagenología y la clínica se establece el diagnóstico de síndrome de Eagle, que fue tratado con un abordaje transoral. CONCLUSIONES: El síndrome de Eagle consta de signos clínicos inespecíficos, por lo que es importante comprender la evaluación diagnóstica y la variedad de opciones de tratamiento.

Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1.

Programmed cell death is regulated by the balance between activating and inhibitory signals. Here, we have identified RECS1 (responsive to centrifugal force and shear stress 1) [also known as TMBIM1 (transmembrane BAX inhibitor motif containing 1)] as a proapoptotic member of the TMBIM family. In contrast to other proteins of the TMBIM family, RECS1 expression induces cell death through the canonical mitochondrial apoptosis pathway. Unbiased screening indicated that RECS1 sensitizes cells to lysosomal perturbations. RECS1 localizes to lysosomes, where it regulates their acidification and calcium content, triggering lysosomal membrane permeabilization. Structural modeling and electrophysiological studies indicated that RECS1 is a pH-regulated calcium channel, an activity that is essential to trigger cell death. RECS1 also sensitizes whole animals to stress in vivo in Drosophila melanogaster and zebrafish models. Our results unveil an unanticipated function for RECS1 as a proapoptotic component of the TMBIM family that ignites cell death programs at lysosomes.

Physiological and affective responses to emoji faces: Effects on facial muscle activity, skin conductance, heart rate, and self-reported affect.

The objective of the present study was to evaluate emotional responses to emoji faces through physiological and self-report measures, and evaluate possible differences between men and women. One hundred participants (50 women) observed pictures of happy, neutral, and angry emoji faces, while activity of the zygomatic and corrugator muscles, skin conductance, and heart rate were measured. Self-report measures of emotional experience were also recorded. The results showed an increase in zygomatic muscle activity toward happy emoji faces. An increasing trend in corrugator muscle activity toward angry emoji faces was observed; however, this trend was only marginally significant. Happy emoji faces generated an increase in the skin conductance response. The emotional experience of the participants was also consistent with the emotions that were expressed by the emoji faces. No differences were found between sexes. Overall, the results suggest that emoji faces can especially induce pleasant affective states.

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.

Efficacy and Safety of Text Messages Targeting Adherence to Cardiovascular Medications in Secondary Prevention: TXT2HEART Colombia Randomized Controlled Trial.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide, with a prevalence of approximately 100 million patients. There is evidence that antiplatelet agents and antihypertensive medications could reduce the risk of new vascular events in this population; however, treatment adherence is very low. An SMS text messaging intervention was recently developed based on behavior change techniques to increase adherence to pharmacological treatment among patients with a history of ASCVD. OBJECTIVE: This study aims to evaluate the efficacy and safety of an SMS text messaging intervention to improve adherence to cardiovascular medications in patients with ASCVD. METHODS: A randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular events, such as acute myocardial infarction, unstable angina, cerebrovascular disease, or peripheral artery disease, in one center in Colombia was conducted. Patients randomized to the intervention arm were assigned to receive SMS text messages daily for the first 4 weeks, 5 SMS text messages on week 5, 3 SMS text messages each in weeks 6 and 7, and 1 SMS text message weekly from week 8 until week 52. In contrast, patients in the control arm received a monthly SMS text message reminding them of the next study appointment and the importance of the study, requesting information about changes in their phone number, and thanking them for participating in the study. The primary endpoint was the change in low-density lipoprotein cholesterol (LDL-C) levels, whereas the secondary endpoints were the changes in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure, medication adherence, cardiac and noncardiac mortality, and hospitalization. Linear regression analyses and bivariate tests were performed. RESULTS: Of the 930 randomized patients, 805 (86.5%) completed follow-up and were analyzed for the primary endpoint. There was no evidence that the intervention changed the primary outcome (LDL-C levels; P=.41) or any of the secondary outcomes evaluated (all P>.05). There was also no evidence that the intervention was associated with adverse events. CONCLUSIONS: In this study, there was no evidence that a behavior modification intervention delivered by SMS text messaging improved LDL-C levels, blood pressure levels, or adherence at 12 months. More research is needed to evaluate whether different SMS text messaging strategies, including personalized messages and different timings, are effective; future studies should include mixed methods to better understand why, for whom, and in which context (eg, health system or social environment) SMS text messaging interventions work (or not) to improve adherence in patients with ASCVD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03098186; https://clinicaltrials.gov/ct2/show/NCT03098186. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-028017.

Effects of Interleukin-1ß in Glycinergic Transmission at the Central Amygdala.

Interleukin-1ß (IL-1ß) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1ß is released by glial cells in regions associated with pain processing during neuropathic pain. It also has important roles in neuroinflammation and in regulating NMDA receptor activity required for learning and memory. The modulation of glycine-mediated inhibitory activity via IL-1ß may play a critical role in the perception of different levels of pain. The central nucleus of the amygdala (CeA) participates in receiving and processing pain information. Interestingly, this nucleus is enriched in the regulatory auxiliary glycine receptor (GlyR) ß subunit (ßGlyR); however, no studies have evaluated the effect of IL-1ß on glycinergic neurotransmission in the brain. Hence, we hypothesized that IL-1ß may modulate GlyR-mediated inhibitory activity via interactions with the ßGlyR subunit. Our results show that the application of IL-1ß (10 ng/ml) to CeA brain slices has a biphasic effect; transiently increases and then reduces sIPSC amplitude of CeA glycinergic currents. Additionally, we performed molecular docking, site-directed mutagenesis, and whole-cell voltage-clamp electrophysiological experiments in HEK cells transfected with GlyRs containing different GlyR subunits. These data indicate that IL-1ß modulates GlyR activity by establishing hydrogen bonds with at least one key amino acid residue located in the back of the loop C at the ECD domain of the ßGlyR subunit. The present results suggest that IL-1ß in the CeA controls glycinergic neurotransmission, possibly via interactions with the ßGlyR subunit. This effect could be relevant for understanding how IL-1ß released by glia modulates central processing of pain, learning and memory, and is involved in neuroinflammation.

Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the ß1 subunit.

Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary ß1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with ß1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the ß1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary ß1 subunit.

A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels.

In mammals, temperature-sensitive TRP channels make membrane conductance of cells extremely temperature dependent, allowing the detection of temperature ranging from noxious cold to noxious heat. We progressively deleted the distal carboxyl terminus domain (CTD) of the cold-activated melastatin receptor channel, TRPM8. We found that the enthalpy change associated with channel gating is proportional to the length of the CTD. Deletion of the last 36 amino acids of the CTD transforms TRPM8 into a reduced temperature-sensitivity channel (Q10 ∼4). Exposing the intracellular domain to a denaturing agent increases the energy required to open the channel indicating that cold drives channel gating by stabilizing the folded state of the CTD. Experiments in the presence of an osmoticant agent suggest that channel gating involves a change in solute-inaccessible volume in the CTD of ∼1,900 Å3 This volume matches the void space inside the coiled coil according to the cryogenic electron microscopy structure of TRPM8. The results indicate that a folding-unfolding reaction of a specialized temperature-sensitive structure is coupled to TRPM8 gating.