Pharmacological and molecular mechanisms of miRNA-based therapies for targeting cardiovascular dysfunction.

Advances in understanding gene expression regulation through epigenetic mechanisms have contributed to elucidating the regulatory mechanisms of noncoding RNAs as pharmacological targets in several diseases. MicroRNAs (miRs) are a class of evolutionarily conserved, short, noncoding RNAs regulating in a concerted manner gene expression at the post-transcriptional level by targeting specific sequences of the 3'-untranslated region of mRNA. Conversely, mechanisms of cardiovascular disease (CVD) remain largely elusive due to their life-course origins, multifactorial pathophysiology, and co-morbidities. In this regard, CVD treatment with conventional medications results in therapeutic failure due to progressive resistance to monotherapy, which overlooks the multiple factors involved, and reduced adherence to poly-pharmacology approaches. Consequently, considering its role in regulating complete gene pathways, miR-based drugs have appreciably progressed into preclinical and clinical testing. This review summarizes the current knowledge about the mechanisms of miRs in cardiovascular disease, focusing specifically on describing how clinical chemistry and physics have improved the stability of the miR molecule. In addition, a comprehensive review of the main miRs involved in cardiovascular disease and the clinical trials in which these molecules are used as active pharmacological molecules is provided.

Obesogenic Diet in Mice Leads to Inflammation and Oxidative Stress in the Mother in Association with Sex-Specific Changes in Fetal Development, Inflammatory Markers and Placental Transcriptome.

BACKGROUND: Obesity during pregnancy is related to adverse maternal and neonatal outcomes. Factors involved in these outcomes may include increased maternal insulin resistance, inflammation, oxidative stress, and nutrient mishandling. The placenta is the primary determinant of fetal outcomes, and its function can be impacted by maternal obesity. The aim of this study on mice was to determine the effect of obesity on maternal lipid handling, inflammatory and redox state, and placental oxidative stress, inflammatory signaling, and gene expression relative to female and male fetal growth. METHODS: Female mice were fed control or obesogenic high-fat/high-sugar diet (HFHS) from 9 weeks prior to, and during, pregnancy. On day 18.5 of pregnancy, maternal plasma, and liver, placenta, and fetal serum were collected to examine the immune and redox states. The placental labyrinth zone (Lz) was dissected for RNA-sequencing analysis of gene expression changes. RESULTS: the HFHS diet induced, in the dams, hepatic steatosis, oxidative stress (reduced catalase, elevated protein oxidation) and the activation of pro-inflammatory pathways (p38-MAPK), along with imbalanced circulating cytokine concentrations (increased IL-6 and decreased IL-5 and IL-17A). HFHS fetuses were asymmetrically growth-restricted, showing sex-specific changes in circulating cytokines (GM-CSF, TNF-α, IL-6 and IFN-γ). The morphology of the placenta Lz was modified by an HFHS diet, in association with sex-specific alterations in the expression of genes and proteins implicated in oxidative stress, inflammation, and stress signaling. Placental gene expression changes were comparable to that seen in models of intrauterine inflammation and were related to a transcriptional network involving transcription factors, LYL1 and PLAG1. CONCLUSION: This study shows that fetal growth restriction with maternal obesity is related to elevated oxidative stress, inflammatory pathways, and sex-specific placental changes. Our data are important, given the marked consequences and the rising rates of obesity worldwide.

Aprendizaje en investigación clínica: experiencia de enseñanza híbrida con estudiantes de medicina / Learning in Clinical Research: Hybrid Teaching Experience with Medical Students

Introducción: la pandemia de COVID-19 indujo un cambio en nuestro sistema de salud y de educación. Los programas formativos también tuvieron que adaptarse y exigieron un cambio rápido. Objetivos: describir una experiencia educativa de enseñanza virtual/híbrida en investigación clínica, entre docentes del Servicio de Clínica de un hospital universitario y estudiantes de Medicina de una institución privada, que participaron del Programa ESIN (EStudiantes en INvestigación). Metodología: los contenidos y las estrategias educativas incluyeron las clases teóricas audiograbadas o videograbadas (asincrónicas y autoadministradas), el aprendizaje basado en proyectos, los talleres prácticos (encuentros sincrónicos virtuales y grupales), mediante la adopción de modelos de aprendizaje como el aula invertida, y la tutoría individual entre docente-estudiante. Los datos se recopilaron mediante la observación en contextos académicos, y basándonos en elementos de encuestas anónimas de satisfacción, previo consentimiento informado de los participantes. Resultados: participaron 14 estudiantes, 6 durante el año 2021 y 8 durante 2022. Todas mujeres y estudiantes de medicina (50% de cuarto año, 35% de sexto año y 15% de quinto año). Las técnicas implementadas favorecieron la participación y promovieron el aprendizaje activo, basado en proyectos. Mencionaron aspectos positivos como el enfoque académico práctico, la disponibilidad del equipo docente para atender cualquier duda, el tiempo y el entusiasmo por enseñar y fomentar la participación. Los videos teóricos resultaron útiles como herramientas de repaso, y los encuentros grupales fueron especialmente valorados, si bien los encuentros individuales fueron destacados como ayuda y apoyo previo a los congresos científicos. En general, manifestaron que fue una experiencia enriquecedora que demostró que se puede lograr lo que se creía imposible. Todas participaron activamente de al menos un congreso científico, y el 50% resultó coautora de una publicación académica. Conclusión: los estudiantes asumieron compromisos y responsabilidades, e incorporaron competencias y habilidades en la implementación y en la difusión de los proyectos. Esta experiencia educativa facilitó que el tiempo de clase pudiera optimizarse para intercambio, discusión y dudas. Los recursos producidos, las actividades desarrolladas y los contenidos abordados quedan disponibles a nivel institución. (AU)

Introduction: the COVID-19 pandemic brought about a change in our health and education system. Training programs also had to adapt and required rapid change. Objectives: to describe an educational experience of virtual/hybrid teaching in clinical research between teachers of the Clinical Service of a university hospital and medical students of a private institution who participated in the ESIN Program (Students in Research). Methodology: the contents and educational strategies included audio or videotaped lectures (asynchronous and self-administered), project-based learning, practical workshops (virtual and group synchronous meetings) by adopting learning models such as the inverted classroom, and individual tutoring between teacher and student. We gathered the data through observation in academic contexts and based on elements of anonymous satisfaction surveys, with prior informed consent of participants. Results: fourteen students participated, six in 2021 and eight in 2022. All were women and medical students (50% fourth year, 35% sixth year, and 15% fifth year). The techniques implemented favored participation and promoted active, project-based learning. They mentioned positive aspects such as the practical academic approach, the availability of the teaching team for any doubts, the time and enthusiasm for teaching, and encouraging participation. The theory videos were a valuable review tool, and team meetings received high praise even if the one-on-one meetings received much attention as help and support before the scientific congresses. In general, they stated that it was an enriching experience that showed that you can achieve what you thought impossible. All of them actively participated in at least one scientific congress, and 50% were co-authors of an academic publication. Conclusion: the students assumed commitments and responsibilities and incorporated competencies and skills in project implementation and dissemination. This educational experience helped to optimize class time for exchange, discussion, and doubts. The resources produced, the activities developed, and the contents addressed are now available at the institutional level. (AU)

El autocuidado de salud en adolescentes del interior argentino.

Introduction: Adolescent health is currently undergoing a serious deterioration. The aim of this study was to identify the self-care practices in adolescents between 15 and 18 years of age attending secondary schools in four departments of the interior of the province of La Rioja, Argentina. Methodology: descriptive cross-sectional and analytical study; data collected between October and November 2022 by non-probabilistic convenience sampling, with analysis of absolute and relative frequencies, multivariate logistic regression analysis and Odds ratio with 95% CI statistical significance of p= ˂0.05. Exploratory factor analysis (EFA) using the Principal Components method as extraction and the Orthogonal Varimax method as rotation. Analysis software, SPSS version 26. Results: There are discordances between the self-perception of health care and the practice carried out by the adolescents. Gender disparity in self-care is identified. The factors that increase self-care are the use of digital health applications, annual or shorter medical check-ups, and maintaining positive thinking habits. The main concern in relation to self-care among adolescents was the consumption of alcoholic beverages.

Introducción: La salud adolescente transcurre por un grave deterioro en la actualidad. El objetivo de este trabajo fue identificar las prácticas de autocuidado de salud en adolescentes escolarizados entre 15 y 18 años que asisten a escuelas secundarias de cuatro departamentos del interior de la provincia de La Rioja, Argentina. Metodología: estudio descriptivo transversal y analítico; datos relevados entre octubre y noviembre 2022 por muestreo no probabilístico por conveniencia, con análisis de frecuencias absolutas, relativas, análisis multivariado de regresión logística y Odds ratio con IC 95% significancia estadística de p= ˂0,05. Análisis factorial exploratorio (AFE) aplicando como extracción, el método de Componentes principales y como rotación el método Ortogonal Varimax. Software de análisis, SPSS versión 26. Resultados: Existen discordancias entre la auto-percepción del cuidado de salud y la práctica del cuidado. Se identifican disparidades del autocuidado según el género. Los factores que incrementan el autocuidado son el uso de aplicaciones digitales en salud, los controles médicos anuales o en menor tiempo, el mantener hábitos de pensamientos positivos. La principal preocupación de los adolescentes en relación al autocuidado de salud fue el consumo de bebidas con contenido etílico.

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs.

PIEZO1 is a mechanosensitive cation channel implicated in shear stress-mediated endothelial-dependent vasorelaxation. Since altered shear stress patterns induce a pro-inflammatory endothelial environment, we analyzed transcriptional profiles of human endothelial cells to determine the effect of altered shear stress patterns and subsequent prooxidant and inflammatory conditions on PIEZO1 and mechanosensitive-related genes (MRG). In silico analyses were validated in vitro by assessing PIEZO1 transcript levels in both the umbilical artery (HUAEC) and vein (HUVEC) endothelium. Transcriptional profiling showed that PIEZO1 and some MRG associated with the inflammatory response were upregulated in response to high (15 dyn/cm2) and extremely high shear stress (30 dyn/cm2) in HUVEC. Changes in PIEZO1 and inflammatory MRG were paralleled by p65 but not KLF or YAP1 transcription factors. Similarly, PIEZO1 transcript levels were upregulated by TNF-alpha (TNF-α) in diverse endothelial cell types, and pre-treatment with agents that prevent p65 translocation to the nucleus abolished PIEZO1 induction. ChIP-seq analysis revealed that p65 bonded to the PIEZO1 promoter region, an effect increased by the stimulation with TNF-α. Altogether this data showed that NF-kappa B activation via p65 signaling regulates PIEZO1 expression, providing a new molecular link for prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.

Evidence of Electron Heating by Alpha Particles in JET Deuterium-Tritium Plasmas.

The fusion-born alpha particle heating in magnetically confined fusion machines is a high priority subject for studies. The self-heating of thermonuclear fusion plasma by alpha particles was observed in recent deuterium-tritium (D-T) experiments on the joint European torus. This observation was possible by conducting so-called "afterglow" experiments where transient high fusion yield was achieved with neutral beam injection as the only external heating source, and then termination of the heating at peak performance. This allowed the first direct evidence for electron heating of plasmas by fusion-born alphas to be obtained. Interpretive transport modeling of the relevant D-T and reference deuterium discharges is consistent with the alpha particle heating observation.

Maternal obesity and high leptin levels prime pro-inflammatory pathways in human cord blood leukocytes.

INTRODUCTION: Maternal obesity alters the immune function in the offspring. We hypothesize that maternal obesity and pro-inflammatory pathways induce leptin-related genes in neonatal monocytes, whereby high leptin levels enhance their inflammatory response. METHODS: Transcriptional profiles of cord blood leukocytes (CBL) in basal and pro-inflammatory conditions were studied to determine differentially expressed genes (DEG). The DNA methylation profile of CB monocytes (CBM) of neonates born to control BMI mothers and women with obesity was assayed to identify differentially methylated probes (DMP). CBM-derived macrophages were cultured with or without leptin (10-100 ng/ml) and then stimulated with lipopolysaccharide (LPS, 100 ng/ml) and interferon-gamma (20 ng/ml) to assess the induction of TNF-α and IL-10 transcripts. RESULTS: CBL from pregnancies with obesity (CBL-Ob) showed 12,183 DEG, affecting 49 out of 78 from the leptin pathway. Control CBM exposed to LPS showed 45 leptin-related DEG, an effect prevented by the co-exposure to LPS and IL-10. Conversely, CBM-Ob showed 5279 DMP enriched in insulin- and leptin-related genes, and Lasso regression of leptin-related DMP showed high predictive value for plasma leptin levels (r2 = 0.9897) and maternal BMI categories (AUC = 1). Chronic exposure to leptin increased TNF-α and decreased IL-10 levels in control BMI samples but not in Ob-CBM. Enhanced TNF-α induction after proinflammatory stimulation was observed in leptin-treated control BMI samples. DISCUSSION: Obesity in pregnancy is associated with a distinctive expression and DNA methylation profile of leptin-related genes in cord blood monocytes, meanwhile, leptin enhances the expression of pro-inflammatory cytokines upon stimulation with M1-skewing agents.

Scaling Up Latent Tuberculosis Infection Testing and Treatment for Non-US Born Patients in a Federally Qualified Community Health Center.

In the United States (US), tuberculosis elimination strategies include scaling up latent tuberculosis infection (LTBI) diagnosis and treatment for persons at risk of progression to tuberculosis disease. The Massachusetts Department of Public Health partnered with Lynn Community Health Center to provide care to patients with LTBI who were born outside the US. The electronic health record was modified to facilitate collection of data elements for public health assessment of the LTBI care cascade. Among health center patients born outside the US, testing for tuberculosis infection increased by over 190%. From October 1, 2016 to March 21, 2019, 8827 patients were screened and 1368 (15.5%) were diagnosed with LTBI. Using the electronic health record, we documented treatment completion for 645/1368 (47.1%) patients. The greatest drop-offs occurred between testing for TB infection and clinical evaluation after a positive test (24.3%) and between the recommendation for LTBI treatment and completion of a treatment course (22.8%). Tuberculosis care delivery was embedded in the primary care medical home, bringing patient-centered care to those at high risk for loss to follow up. The partnership between public health and the community health center promoted quality improvement.

Altered placental ion channel gene expression in preeclamptic high-altitude pregnancies.

High-altitude (>2,500 m) residence increases the risk of pregnancy vascular disorders such as fetal growth restriction and preeclampsia, each characterized by impaired placental function. Genetic attributes of highland ancestry confer relative protection against vascular disorders of pregnancy at high altitudes. Although ion channels have been implicated in placental function regulation, neither their expression in high-altitude placentas nor their relationship to high-altitude preeclampsia has been determined. Here, we measured the expression of 26 ion-channel genes in placentas from preeclampsia cases and normotensive controls in La Paz, Bolivia (3,850 m). In addition, we correlated gene transcription to maternal and infant ancestry proportions. Gene expression was assessed by PCR, genetic ancestry evaluated by ADMIXTURE, and ion channel proteins localized by immunofluorescence. In preeclamptic placentas, 11 genes were downregulated (ABCC9, ATP2A2, CACNA1C, KCNE1, KCNJ8, KCNK3, KCNMA1, KCNQ1, KCNQ4, PKD2, and TRPV6) and two were upregulated (KCNQ3 and SCNN1G). KCNE1 expression was positively correlated with high-altitude Amerindian ancestry and negatively correlated with non-high altitude. SCNN1G was negatively correlated with African ancestry, despite minimal African admixture. Most ion channels were localized in syncytiotrophoblasts (Cav1.2, TRPP2, TRPV6, and Kv7.1), whereas expression of Kv7.4 was primarily in microvillous membranes, Kir6.1 in chorionic plate and fetal vessels, and MinK in stromal cells. Our findings suggest a role for differential placental ion channel expression in the development of preeclampsia. Functional studies are needed to determine processes affected by these ion channels in the placenta and whether therapies directed at modulating their activity could influence the onset or severity of preeclampsia.

Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2 Variant.

Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent. However, a missense variant in RANBP2 has been identified in some families with recurrent ANE (OMIM # 608033), also named autosomal dominant ANE (ADANE). Clinical manifestation, clinical course, and brain MRI imaging findings of six affected members of two distinct families with ADANE were described. Sequencing revealed heterozygous c.1754C > T variant in RANBP2 (p.Thr585Met) in affected and asymptomatic family members. Only few ADANE families have been reported and it is the first description in South America. Differential diagnosis of Leigh disease and acute disseminated encephalomyelitis is discussed. Our report reinforces incomplete penetrance of ADANE and intrafamilial phenotypic variability of outcome.

A Cross-Sectional, Retrospective, and Comparative Study between Delirium and Non-Delirium Psychiatric Disorders in a Psychogeriatric Inpatient Population Referred to Consultation-Liaison Psychiatry Unit.

Background and objectives: Delirium is the most prevalent psychiatric disorder in inpatient older people. Its presence is associated with higher rates of institutionalization, functional disability and mortality. This study aims to evaluate delirium in a hospitalized psychogeriatric population, focusing on which factors predict the appearance of delirium, the impact it generates and the diagnostic concordance between non-psychiatric physicians and psychiatrists. Material and methods: This is an observational, cross-sectional, retrospective, and comparative study. We obtained data from a sample of 1017 patients (≥65 years) admitted to general hospital and referred from different services to the consultation-liaison psychiatry (CLP) unit. Logistic regression was performed using delirium as the dependent variable. To estimate the concordance of the diagnoses, the Kappa coefficient was used. To assess the impact of delirium, an ordinal regression, Wilcoxon median test and Fisher's test were performed. Results: Delirium is associated with a higher number of visits, OR 3.04 (95% CI 2.38-3.88), longer length of stay and mortality, OR 2.07 (95% CI, 1.05 to 4.10). The model to predict delirium shows that being >75 years old has an OR of 2.1 (95% CI, 1.59-2.79), physical disability has an OR of 1.66 (95% CI, 1.25-2.20), history of delirium has an OR of 10.56 (95% CI, 5.26-21.18) and no use of benzodiazepines has an OR of 4.24 (95% CI, 2.92-6.14). The concordance between the referring physician's psychiatric diagnosis and the psychiatrist CLP unit showed a kappa of 0.30. When analysing depression and delirium, the concordance showed Kappa = 0.46. Conclusions: Delirium is a highly prevalent psychiatric disorder, but it is still underdiagnosed, with low diagnostic concordance between non-psychiatric doctors and psychiatrists from CLP units. There are multiple risk factors associated with the appearance of delirium, which must be managed to reduce its appearance.

Developmental Ultrasound Characteristics in Guinea Pigs: Similarities with Human Pregnancy.

BACKGROUND: Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. METHODS: Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. RESULTS: Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. CONCLUSIONS: BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy.

Effect of aquatic resistance interval training and dietary education program on physical and psychological health in older women: Randomized controlled trial.

Due to demographic changes, the world's population is progressively aging. The physiological deterioration of the older adult may lead to reduced balance capacity and increased risk of falls, among others, due to the prevalence of degenerative diseases. Physical exercise can be effective in reducing the risk of disease and slowing functional decline in older people. The aim of the research is to test the effects of aquatic resistance training and dietary education on health indicators, strength, balance, functional autonomy, perception of satisfaction with life. Thirty-four participants aged 69 ± 4 years were randomly assigned into two groups: experimental (aquatic resistance interval training) and control group (no intervention). The intervention consisted of resistance training in an aquatic environment carried out for 14 weeks (three sessions per week: 60 min each). All variables were analyzed twice; pre - post intervention. Aquatic resistance training has positive effects on strength (p < 0.001), functional self-sufficiency (p < 0.001) and aerobic capacity (p < 0.001), however, no significant differences were observed in the perception of satisfaction with life and balance. Research results suggest that older women who engage in regular, scheduled aquatic resistance training have greater autonomy in performing activities of daily living, agility, gait control, and body composition variables (lower fat compartment and greater muscle mass).

Transcriptional and Epigenomic Markers of the Arterial-Venous and Micro/Macro-Vascular Endothelial Heterogeneity within the Umbilical-Placental Bed.

Umbilical and placental vessels and endothelial cells (EC) are common models to study placental function and vascular programming. Arterio-venous differences are present in the umbilical endothelium; however, the heterogeneity of small placental vessels and the expression of potential micro- vs. macro-vascular (MMV) markers are poorly described. Here, we performed a meta-analysis of transcriptomic and DNA methylation data from placental and umbilical EC. Expression and methylation profiles were compared using hierarchical clustering, dimensionality reduction (i.e., tSNE, MDS, and PHATE), and enrichment analysis to determine the occurrence of arterio-venous (AVH) and micro-macro heterogeneity (MMH). CpG sites correlated with gene expression of transcriptional markers of MMH and AVH were selected by Lasso regression and used for EC discrimination. General transcriptional profile resulted in clear segregation of EC by their specific origin. MM and AVH grouping were also observed when microvascular markers were applied. Altogether, this meta-analysis provides cogent evidence regarding the transcriptional and epigenomic profiles that differentiate among EC, proposing novel markers to define phenotypes based on MM levels.

Relationship between Anthropometric Measures and Anxiety Perception in Soccer Players.

In the sports context, it has been corroborated that the physical demands of presenting an "ideal" body configuration have been associated with different psychological variables, such as self-esteem, anxiety and personality dimensions, such as perfectionism. Specifically, there is evidence that anthropometric measures may be closely related to psychological indicators. A total of 33 male soccer players (18.12 ± 1.24 years) participated in the investigation. Anthropometric assessments were carried out following the ISAK standards for the restricted profile. All of them completed the Competitive Trait Anxiety Inventory (CTAI-2D) in its Spanish version. The percent fat was calculated using Withers (density) and Siri equations. The ∑7 skinfolds were used to calculate this. After statistical analysis, significant mean differences were observed in the somatic anxiety dimension (valence) and a medium-large effect size. Regarding correlations, the significantly negative relationship between self-confidence (intentionality) and somatic anxiety (valence) was noteworthy. The relationship between psychological variables and anthropometric measurements was corroborated, showing the need for interdisciplinary work between psychologists and nutritionists who do not ignore the physical health and psychological well-being of the soccer player.

Comparative Performance of Different Respiratory Test Parameters for Detection of Early Respiratory Insufficiency in Patients With ALS.

BACKGROUND AND OBJECTIVES: To compare the performance of different respiratory function testing parameters in a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic. METHODS: Demographics, clinical data, and respiratory testing parameters were abstracted from the medical records of patients who attended a multidisciplinary ALS clinic from 2008 to 2016. We compared the performance of the 3 primary respiratory test parameters used by Medicare for the initiation of noninvasive ventilation (NIV) (forced vital capacity [FVC] < 50% predicted, maximum inspiratory pressure [MIP] < 60 cm H2O, and abnormal overnight pulse oximetry [OvOx]) on how they related to several clinically relevant attributes. RESULTS: Four hundred seventy-six patients were identified who underwent at least 1 respiratory test. Abnormalities of OvOx, MIP, and FVC occurred at a median of 1.6, 1.5, and 3.8 years from disease onset, respectively (p < 0.00001). Patients with bulbar-onset ALS exhibited earlier abnormalities in MIP and FVC than in spinal-onset ALS (p < 0.005). The median survival after an abnormal OvOx, MIP, or FVC test was 1.4, 1.4, and 0.9 years, respectively (p < 0.0001). Using the ALS Functional Rating Score respiratory subscales, at the time of reported respiratory symptoms there were abnormalities in OvOx (60%), MIP (69%), and FVC (19%). Conversely, when respiratory parameter abnormalities preceded reported respiratory symptoms, this occurred with frequencies in OvOx (79%), MIP (42%), or FVC (24%). Four hundred forty-three patients (93.1%) developed at least 1 abnormal respiratory measure meeting Medicare criteria for NIV consideration, but fewer than 50% in our cohort demonstrated NIV use. Improved survival in subjects using NIV was statistically significant in patients with bulbar-onset ALS. DISCUSSION: Abnormalities in OvOx and MIP perform better than FVC at early detection of neuromuscular respiratory weakness in ALS. Initiation of NIV in patients with respiratory insufficiency may improve the overall survival in ALS. In the setting of the COVID-19 pandemic, FVC and MIP have not been routinely performed because of infectious aerosol generation. OvOx, which we now routinely mail to patients' homes, has been used exclusively during the COVID-19 pandemic and allows for continued remote monitoring of the respiratory status of patients with ALS. CLASSIFICATION OF EVIDENCE: This cohort study provides Class III evidence that in people with ALS, OvOx and MIP are valuable respiratory parameters for the detection of early respiratory insufficiency.

Clinical Efficacy and Safety of Fanhdi®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. METHODS: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. RESULTS: Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. CONCLUSIONS: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.

Three-state majority-vote model on small-world networks.

In this work, we study the opinion dynamics of the three-state majority-vote model on small-world networks of social interactions. In the majority-vote dynamics, an individual adopts the opinion of the majority of its neighbors with probability 1-q, and a different opinion with chance q, where q stands for the noise parameter. The noise q acts as a social temperature, inducing dissent among individual opinions. With probability p, we rewire the connections of the two-dimensional square lattice network, allowing long-range interactions in the society, thus yielding the small-world property present in many different real-world systems. We investigate the degree distribution, average clustering coefficient and average shortest path length to characterize the topology of the rewired networks of social interactions. By employing Monte Carlo simulations, we investigate the second-order phase transition of the three-state majority-vote dynamics, and obtain the critical noise [Formula: see text], as well as the standard critical exponents [Formula: see text], [Formula: see text], and [Formula: see text] for several values of the rewiring probability p. We conclude that the rewiring of the lattice enhances the social order in the system and drives the model to different universality classes from that of the three-state majority-vote model in two-dimensional square lattices.

Pulmonary Cystic Disease Associated With COVID 19 Pneumonia: An Emerging Atypical Manifestation.

Chest tomography has played an essential role during the coronavirus disease 2019 (COVID-19) pandemic since it has allowed to suspect and diagnose the disease early and to assess the severity of lung involvement, predict the disease's course, and detect the complications associated with it. Certain chest CT findings have been reported in more than 70% of reverse transcription polymerase chain reaction (RT-PCR) test-proven COVID-19 cases, including ground-glass opacities, vascular enlargement, bilateral abnormalities, lower lobe involvement, and posterior predilection. In COVID-19-endemic regions, observing these chest CT findings should raise the suspicion of a possible COVID-19 diagnosis. Rare reported CT findings in RT-PCR test-proven COVID-19 cases include pleural effusion, lymphadenopathy, tree-in-bud sign, central lesion distribution, pericardial effusion, and cavitating lung lesions. The observation of one or more of these findings suggests an alternative diagnosis, although COVID-19 cannot be excluded from the differential diagnosis. Here, we report an interesting case of a patient with no relevant history presenting a COVID-19 infection which, as a complication, presented cystic lesions; we discuss its etiology briefly.