Clinical and genetic characterization of patients with eye diseases included in the Spanish Rare Diseases Patient Registry.

BACKGROUND: The low prevalence of rare diseases poses a significant challenge in advancing their understanding. This study aims to delineate the clinical and genetic characteristics of patients with rare eye diseases (RED) enrolled in the Spanish Rare Diseases Patient Registry. METHODS: A total of 864 patients from the registry database were included. Diseases were categorized into inherited retinal dystrophies (n=688); anterior segment diseases (n=48); congenital malformations (n=27); and syndromic diseases with ocular involvement including muscular (n=46), neurological (n=34), or metabolic (n=13); inflammatory diseases (n=4); and tumors (n=4). Data on visual acuity (VA) and/or visual field (VF), symptoms and signs, concurrent diseases in syndromic cases, age of onset and at diagnosis, affected genes, disability rating, inability to work and dependency grade recognition were collected. RESULTS: A mean diagnostic delay of 7 years from symptom onset was observed. Commonly reported symptoms included photophobia, night blindness, and progressive vision loss (≥57% of patients). Cataract was the most prevalent secondary disease (46%), with pseudophakia being the most common ocular surgery (26%). Hearing loss and cardiovascular diseases were the most prevalent concurrent systemic diseases (≥13%). Certificates of disability, incapacity for work, and dependency were held by 87%, 42%, and 19% of patients, respectively. Among the 719 patients with available VA data, 193 (27%) were blind, and 188 (26%) had moderate to severe visual impairment. Over half of the patients (54%) exhibited VF defects, and 216 (25%) had concentric contraction ≤5° or abolished VF. Most had genetic diseases with autosomal recessive (55%), autosomal dominant (30%), X-linked (9%), and mitochondrial (6%) patterns. One patient had mutations in both recessive USH2A and dominant RHO genes simultaneously. Of the 656 patients (75.7%) who underwent genetic testing, only 461 (70.3%) received a positive result (pathogenic or likely pathogenic mutations explaining the phenotype). We found 62 new gene variants related to RED not previously reported in databases of genetic variants related to specific phenotypes. CONCLUSIONS: This study delineates the clinical and genotypic profiles of RED in Spain. Genetic diseases, particularly retinal disorders, predominate, but a significant proportion of affected patients remain genetically undiagnosed, hindering potential gene therapy endeavors. Despite notable improvements in reducing diagnosis delays, it is still remarkable. RED frequently lead to disability and blindness among young populations.

Contemporary Parental Leave Policies and Practice Among Obstetrics and Gynecology Trainees and Faculty.

This article aims to describe contemporary parental leave among obstetrics and gynecology trainees and early-career faculty. Here, we present results of a survey that collected information about parental leave policies and contemporary practice, as well as beliefs about surgical and clinical experience for those who take leave. Faculty and trainees were equally well represented among respondents, with half of each group self-identifying as a parent. Most reported that childbearing trainees currently take 6 weeks or less of parental leave and believed that childbearing and nonchildbearing residents should be able to take 12 weeks of leave without extending training.

Transcriptomic signatures of classical monocytes reveal pro-inflammatory modules and heterogeneity in polyarticular juvenile idiopathic arthritis.

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.

Post-Treatment Displacement of Facial Soft Tissue Fillers-A Retrospective Ultrasound-based Investigation of 382 Zygomatic Regions.

BACKGROUND: Clinical and ultrasound experience has revealed that after soft tissue injections of the lateral cheek, the filler may displace from the zygoma to the caudal temporal area. OBJECTIVE: To obtain more data to provide insight into product distribution when soft tissue fillers are injected in the zygomatic region. METHODS: Two hundred patients were examined with facial ultrasound imaging of the zygomatic and temporal region. Inclusion criteria were simply a positive response on the screening questionnaire as to whether or not they had filler injections placed in their lateral cheek. Control injections were also performed to the zygomatic regions of a body donor and in 10 patients ultrasound-guided. RESULTS: A correlation was found between the layers in which filler was detected on the zygoma and where it was ultimately found in the temples. Four different redistribution patterns were observed: (1) migration of filler within the superficial muscular aponeurotic system (SMAS) on the zygoma into the superficial temporal fascia. Migration of filler from the lateral suborbicularis oculi fat to (2) the deep interfacial plane of the temple or (3) to the superficial temporal fat pad; (4) migration from the supraperiosteal layer of the zygoma to the superficial temporal fat pad. Body donor and patients: filler deposits injected on the zygoma were witnessed to shift during injection into the caudal part of the temple. CONCLUSION: Soft tissue filler aliquots may be redistributed into the temples after injections of the lateral side of the zygomatic arch. The displacement follows a distinct pattern depending on the initial layer of injection.

Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy.

Aging induces cardiac remodeling, resulting in an increase in the risk of suffering heart diseases, including heart failure. Collagen deposition increases with age and, together with sarcomeric changes in cardiomyocytes, may lead to ventricular stiffness. Multiphoton (MP) microscopy is a useful technique to visualize and detect variations in cardiac structures in a label free fashion. Here, we propose a method based on MP imaging (both two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) modalities) to explore and objectively quantify age-related structural differences in various components of cardiac tissues. Results in transmural porcine left ventricle (LV) sections reveal significant differences when comparing samples from young and old animals. Collagen and myosin SHG signals in old specimens are respectively 3.8x and >6-fold larger than in young ones. Differences in TPEF signals from cardiomyocyte were ∼3x. Moreover, the increased amount of collagen in old specimens results in a more organized pattern when compared to young LV tissues. Since changes in collagen and myosin are associated with cardiac dysfunction, the technique used herein might be a useful tool to accurately predict and measure changes associated with age-related myocardium fibrosis, tissue remodeling and sarcomeric alterations, with potential implications in preventing heart disease.

Risk factors associated with COVID-19 mortality in Mexico.

BACKGROUND: On December 31, 2019, one of the most serious pandemics in recent times made its appearance. Certain health conditions, such as obesity and diabetes mellitus, have been described to be related to COVID-19 unfavorable outcomes. OBJECTIVE: To identify factors associated with mortality in patients with COVID-19. MATERIAL AND METHODS: Retrospective cohort of 998,639 patients. Patient sociodemographic and clinical characteristics were analyzed, with survivors being compared with the deceased individuals. Cox proportional hazards model was used to identify variables predictive of COVID-19-associated mortality. RESULTS: Among the deceased patients, men accounted for 64.3%, and women, for 35.7%, with the difference being statistically significant. Subjects older than 80 years had a 13-fold higher risk of dying from COVID-19 (95% CI = 12,469, 13,586), while chronic kidney disease entailed a risk 1.5 times higher (95% CI = 1,341, 1,798), and diabetes mellitus involved a risk 1.25 times higher (95% CI = 1.238,1.276). CONCLUSIONS: Age, sex, diabetes mellitus and obesity were found to be predictors of COVID-19 mortality. Further research related to chronic obstructive pulmonary disease, cardiovascular diseases, smoking and pregnancy is suggested.

ANTECEDENTES: El 31 de diciembre de 2019, se inició una de las pandemias más graves de los últimos tiempos. Se ha descrito que ciertas condiciones de salud, como la obesidad y la diabetes mellitus, están relacionadas con desenlaces desfavorables por COVID-19. OBJETIVO: Identificar factores asociados a mortalidad en pacientes con COVID-19. MATERIAL Y MÉTODOS: Cohorte retrospectiva de 998 639 pacientes. Se analizaron las características sociodemográficas y clínicas de los pacientes, y se compararon supervivientes con fallecidos. Se utilizó el modelo de riesgos proporcionales de Cox para la identificación de variables predictivas de defunción por COVID-19. RESULTADOS: Entre los fallecidos, los hombres representaron 64.3 % y las mujeres 35.7 %, diferencia que resultó estadísticamente significativa. Las personas con más de 80 años presentaron un riesgo 13 veces mayor de morir por COVID-19 (IC 95 % = 12.469,13.586) y la enfermedad renal crónica, un riesgo de 1.5 (IC 95 % = 1.341, 1.798); la diabetes mellitus tuvo un riesgo de 1.25 (IC 95 % = 1.238,1.276). CONCLUSIONES: La edad, el sexo, la diabetes mellitus y la obesidad resultaron ser entidades predictivas de muerte por COVID-19. Se sugiere más investigación relacionada con enfermedad pulmonar obstructiva crónica, enfermedades cardiovasculares, tabaquismo y embarazo.

PGPB Consortium Formulation to Increase Fermentable Sugar in Agave tequilana Weber var. Blue: A Study in the Field.

Agave tequilana Weber var. Blue is used as the primary raw material in tequila production due to its fructans (inulin) content. This study evaluates the formulation of a plant-growth-promoting bacteria (PGPB) consortium (Pseudomonas sp. and Shimwellia sp.) to increase sugars in A. tequilana under field conditions. A total of three doses were tested: low (5 L ha-1), medium (10 L ha-1), and high (15 L ha-1), with a cellular density of 1 × 108 CFU mL-1 and one control treatment (without application). Total reducing sugars (TRS), inulin, sucrose, glucose, fructose, and plant growth were measured in agave plants aged 4-5 years at 0 (T0), 3 (T3), 6 (T6), and 12 (T12) months. Yield was recorded at T12. The TRS increased by 3%, and inulin by 5.3% in the high-dose treatment compared to the control at T12. Additionally, a low content of sucrose, glucose, and fructose (approximately 1%) was detected. At T12, the weight of agave heads increased by 31.2% in the medium dose and 22.3% in the high dose compared to the control. The high dose provided a higher inulin content. The A. tequilana plants were five years old and exhibited growth comparable to the standards for 6-7-year-old plants. This study demonstrates a sustainable strategy for tequila production, optimizing the use of natural resources and enhancing industry performance through increased sugar content and yield.

Macrophage proteomic analysis of covalent immobilization of hyaluronic acid and graphene oxide on CoCr alloy in a tribocorrosive environment.

In this work, a sequential covalent immobilization of graphene oxide (GO) and hyaluronic acid (HA) is performed to obtain a biocompatible wear-resistant nanocoating on the surface of the biomedical grade cobalt-chrome (CoCr) alloy. Nanocoated CoCr surfaces were characterized by Raman spectroscopy and electrochemical impedance spectroscopy (EIS) in 3 g/L HA electrolyte. Tribocorrosion tests of the nanocoated CoCr surfaces were carried out in a pin on flat tribometer. The biological response of covalently HA/GO biofunctionalized CoCr surfaces with and without wear-corrosion processes was studied through the analysis of the proteome of macrophages. Raman spectra revealed characteristic bands of GO and HA on the functionalized CoCr surfaces. The electrochemical response by EIS showed a stable and protective behavior over 23 days in the simulated biological environment. HA/GO covalently immobilized on CoCr alloy is able to protect the surface and reduce the wear volume released under tribocorrosion tests. Unsupervised classification analysis of the macrophage proteome via hierarchical clustering and principal component analysis (PCA) revealed that the covalent functionalization on CoCr enhances the macrophage biocompatibility in vitro. On the other hand, disruption of the HA/GO nanocoating by tribocorrosion processes induced a macrophage proteome which was differently clustered and was distantly located in the PCA space. In addition, tribocorrosion induced an increase in the percentage of upregulated and downregulated proteins in the macrophage proteome, revealing that disruption of the covalent nanocoating impacts the macrophage proteome. Although macrophage inflammation induced by tribocorrosion of HA/GO/CoCr surfaces is observed, it is ameliorated by the covalently grafting of HA, which provides immunomodulation by eliciting downregulations in characteristic pro-inflammatory signaling involved in inflammation and aseptic loosening of CoCr joint arthroplasties. Covalent HA/GO nanocoating on CoCr provides potential applications for in vivo joint prostheses led a reduced metal-induced inflammation and degradation by wear-corrosion.

The Role of Environmental Factors in Lyme Disease Transmission in the European Union: A Systematic Review.

BACKGROUND: Lyme disease (LD) is an emergent vector-borne disease caused by Borrelia spp. and transmitted through infected ticks, mainly Ixodes spp. Our objective was to determine meteorological and environmental factors associated with LD transmission in Europe and the effect of climate change on LD. MATERIALS AND METHODS: A systematic review following the PRISMA guidelines was performed. We selected studies on LD transmission in the European Union (EU) and the European Economic Area (EEA) published between 2000 and 2022. The protocol was registered in the PROSPERO database. RESULTS: We included 81 studies. The impact of environmental, meteorological or climate change factors on tick vectors was studied in 65 papers (80%), and the impact on human LD cases was studied in 16 papers (19%), whereas animal hosts were only addressed in one study (1%). A significant positive relationship was observed between temperature and precipitation and the epidemiology of LD, although contrasting results were found among studies. Other positive factors were humidity and the expansion of anthropized habitats. CONCLUSIONS: The epidemiology of LD seems to be related to climatic factors that are changing globally due to ongoing climate change. Unfortunately, the complete zoonotic cycle was not systematically analyzed. It is important to adopt a One Health approach to understand LD epidemiology.

Lead Levels in the Most Consumed Mexican Foods: First Monitoring Effort.

Globally, there is growing concern over the presence of lead (Pb) in foods because it is a heavy metal with several toxic effects on human health. However, monitoring studies have not been conducted in Mexico. In this study, we estimated the concentrations of Pb in the most consumed foods and identified those that exceeded the maximum limits (MLs) for Pb in foods established by the International Standards. Based on the Mexican National Health and Nutrition Survey, 103 foods and beverages were selected and purchased in Mexico City retail stores and markets. Samples were analyzed twice using atomic absorption spectrophotometry. Values above the limit of quantification (0.0025 mg/kg) were considered to be detected. The percentage of detected values was 18%. The highest concentration was found in infant rice cereal (1.005 mg/kg), whole wheat bread (0.447 mg/kg), pre-cooked rice (0.276 mg/kg), black pepper (0.239 mg/kg), and turmeric (0.176 mg/kg). Among the foods with detected Pb, the levels in infant rice cereal, whole wheat bread, pre-cooked rice, and soy infant formula exceeded the MLs. The food groups with the highest percentages of exceeded MLs were baby foods (18%) and cereals (11%). Monitoring the concentration of contaminants in foods is essential for implementing food safety policies and protecting consumer health.

Orthopedic Conditions and Interplay with Functional Abilities and MECP2 Variant Subtype in Rett Syndrome Patients.

PURPOSE: Rett syndrome (RTT) is a rare multi-systemic disorder primarily linked to mutations in MECP2 gene. This study aims to describe the prevalence of orthopedic conditions in RTT patients, and examine their intricate interplay with functional capabilities, and MECP2 variant subtypes. METHODS: Conducted as a cross-sectional retrospective observational study, the research encompassed 55 patients meeting clinical RTT criteria and holding MECP2 mutations. A review of clinical records was performed to gather demographic data, mutation subtypes, orthopedic conditions, management strategies, and assessments of function. RESULTS: Mean age of the participants was 10.22 ± 4.64 years (range, 2.9-19.41). Prevalence rates of orthopedic conditions were as follows: kyphoscoliosis 63.6%, hip displacement 14.6%, knee problems 40%, and foot deformities 75.5%. Significant relationship emerged between spinal (p < 0.01) and knee deformities (p < 0.01) with reduced motor function across various domains. Hip displacement significantly affected sitting ability (p = 0.002), and foot deformities impacted standing and walking capabilities (p = 0.049). Mutation clusters analysis revealed significant correlations with spinal (p = 0.022) and knee deformities (p = 0.002). Linear models highlighted the critical importance of mutation clusters, spine deformities, age, and hip management concerning functional variables. CONCLUSIONS: In this study, foot deformities were the most frequent orthopedic manifestation, followed by spinal, knee, and hip deformities; and unveiled their relationships with functional status and groups of mutations in RTT patients. LEVEL OF EVIDENCE: Level IV, Case series.

Targeting Trypanothione Metabolism in Trypanosomatids.

Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected Tropical Diseases affecting millions of people worldwide, mainly in vulnerable territories of tropical and subtropical areas. In general, current treatments against these diseases are old-fashioned, showing adverse effects and loss of efficacy due to misuse or overuse, thus leading to the emergence of resistance. For these reasons, searching for new antitrypanosomatid drugs has become an urgent necessity, and different metabolic pathways have been studied as potential drug targets against these parasites. Considering that trypanosomatids possess a unique redox pathway based on the trypanothione molecule absent in the mammalian host, the key enzymes involved in trypanothione metabolism, trypanothione reductase and trypanothione synthetase, have been studied in detail as druggable targets. In this review, we summarize some of the recent findings on the molecules inhibiting these two essential enzymes for Trypanosoma and Leishmania viability.

Low antiviral resistance in Influenza A and B viruses isolated in Mexico from 2010 to 2023.

The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods. A total of 255 isolates were assessed with the NAI assay, including Influenza A(H1N1)pdm09, A(H3N2) and Influenza B (IBV). Furthermore, 827 sequences contained in the GISAID platform were analyzed in search of relevant mutations.Overall, five isolates showed highly reduced inhibition or reduced inhibition to Oseltamivir, and two showed reduced inhibition to Zanamivir in the NAI assays. Additionally, five A(H1N1)pdm09 sequences from the GISAID possessed AA substitutions associated to reduced inhibition to Oseltamivir and none to Zanamivir. Oseltamivir resistant A(H1N1)pdm09 harbored the H275Y mutation. No genetic mutations were identified in Influenza A(H3N2) and IBV. Overall, these results show that in Mexico the rate of NAI resistance is low (0.6%), but it is essential to continue the Influenza surveillance in order to understand the drug susceptibility of circulating strains.

Toxoplasma gondii exposure in wildlife in Spain: Is there any predictable threat for humans and domestic animals?

Toxoplasmosis is a parasitic zoonosis of key importance in veterinary and public health. This article summarizes the available data (from 2000 to 2023) of exposition to Toxoplasma gondii in wildlife species in Spain based on a systematic bibliographic search, as well as further analysis of its potential relationship with environmental variables, biodiversity, anthropogenic impact on the habitat, and the reported human cases of toxoplasmosis. The overall seroprevalence of T. gondii in carnivorous mammals, birds, ungulate and lagomorph species in Spain was estimated at 69.3 %, 36.4 %, 18.4 %, and 16.2 %, respectively. Among the studies considered, great heterogeneity was observed both between and within taxonomic groups [Cohen's d > 0.8; X2 = 1039.10, df = 4 (p < 0.01) I2 = 97 %, r2 = 1.88, (p < 0.001)] and between and within bioregions [Cohen's d > 0.5; X2 = 368.59, df = 4 (p < 0.01)]. The results of a generalized linear model explaining T. gondii seroprevalence in wild animals suggest the influence of abiotic variables [wetland (p < 0.001), unvegetated (p < 0.001), isothermality (p < 0.001), and mean temperature during wettest quarter (p < 0.05)] and number of intermediate host species as positively associated with increased exposure of wildlife to T. gondii (p < 0.01). Toxoplasma gondii DNA was detected in both wild birds and wild mammals (range: 0.0-51.2 %) mainly from north-centre, northeast, and central-west of Spain. Regarding hospitalisation rates due to toxoplasmosis in humans, some abiotic variables [permanent crops (p < 0.05) and mean temperature during wettest quarter (p < 0.05)] showed a positive association. Despite certain limitations, this research evidences a substantial gap of knowledge on the implication of wildlife in the life cycle of T. gondii in Spain. This lack of knowledge is particularly evident in areas where the human-livestock-wildlife interface overlaps, preventing us from accurately determining its true distribution in different habitats, as well as its potential direct or indirect implications on public and veterinary health.

Determining the role of acculturative stress in predicting mental health service use among Latinx immigrants.

OBJECTIVES: Acculturative stress is an important factor that affects health for Latinx immigrants in the US, with multiple studies identifying a link between depression and acculturative stress in this population. However, far fewer studies have examined the specific role and relationship of acculturative stress on mental health service use in this population. Through the lens of Yang's 2016 Model of Immigrant Health Service Use, this study aimed to examine the role of acculturative stress in predicting mental health service use in a sample of Latinx immigrants in the Southeast US. DESIGN: We conducted a secondary data analysis from a longitudinal study of Latinx immigrant health (n = 391). RESULTS: Our study found that while total acculturative stress was not significantly associated with mental health service use in this sample, parenting stress was a significant predictor of mental health service use in the past six months when controlling for covariates (OR: 1.043, 95% CI [1.009, 1.078]). Additionally, important Predisposing and Need for Healthcare factors were significantly associated with mental health service use, specifically: males were less likely to utilize mental health services than females (OR: 0.401, 95% CI [0.166-0.968]), English language acculturation was positively associated with mental health service use (OR: 1.953, 95% CI [1.130, 3.377]), and depression was positively associated with mental health service use (OR: 1.107, 95% CI [1.027, 1.194]). CONCLUSION: These findings support the need for more culturally sensitive mental health services, and the need to develop strategies to engage males and less acculturated individuals in mental health services to promote health equity among Latinx immigrants.

Barriers and facilitators to vascular access point-of-care ultrasound in haemodialysis: An international survey of haemodialysis clinicians.

BACKGROUND: Utilising point-of-care ultrasound for assessment and cannulation of vascular access in people receiving haemodialysis has shown positive clinical results. Nonetheless, there is variation in how renal health care professionals worldwide embrace this method, and there's a lack of research on the factors that promote or hinder its adoption. OBJECTIVES: To explore regional differences, and barriers and facilitators, to the use of point-of-care ultrasound for assessment and cannulation of vascular access in haemodialysis. DESIGN: Exploratory descriptive cross-sectional web-based survey. PARTICIPANTS: Healthcare clinicians working in haemodialysis responsible for cannulation of arteriovenous fistula or grafts. RESULTS: The survey was completed by 645 health care clinicians from 38 countries. 75% to 93% of respondents from Australia/New Zealand, Canada, Europe and United Kingdom/Ireland reported access to ultrasound, compared to 26% (n = 43/167) from the United States respondent's reported lower levels of ultrasound training than other regions. Facilitators for using ultrasound were: the availability of ultrasound training (87%, n = 558), to reduce miscannulations (76%, n = 255/336) and to improve patient outcomes (73%, n = 246/336). Point-of-care ultrasound barriers were lack of access to ultrasound education (82%, n = 196/239), lack of ultrasound machines (33%, n = 212/645) or believing that ultrasound was someone else's role (38%, n = 29/86). CONCLUSIONS: This study revealed national and regional differences related to haemodialysis point-of-care ultrasound. Understanding the regions requiring more education and implementation of ultrasound and what motivates staff, or deters from using ultrasound, is crucial for effectiveness of future implementation and workplace change initiatives.

Light-Dependent Reactivity of Heavy Pnictogen Double Bonds.

The chemistry of light dipnictenes has been widely investigated in the last century with remarkable achievements especially for azobenzene derivatives. In contrast, distibenes and dibismuthenes are relatively rare and show very limited reactivity. Herein, we have designed a protocol using visible light to enhance the reactivity of heavy dipnictenes. Exploiting the distinctive π-π* transition, we have been able to isolate unique examples of dipnictene-cobalt complexes. The reactivity of the distibene complex was further exploited using red light in the presence of a diazoolefin to access an unusual four-membered bicyclo[1.1.0]butane analog, containing only a single carbon atom. These findings set the bases to a conceptually new strategy in heavy element double bonds chemistry where visible light is at the front seat of bond activation.

Efficacy of a transdiagnostic internet-based program for adolescents with emotional disorders: A randomized controlled trial.

OBJECTIVE: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) is a well-established transdiagnostic cognitive-behavioral therapy (T-CBT) intervention. The aim of the present study was to examine the efficacy of the program Learn to Manage your Emotions [Aprende a Manejar tus Emociones] (AMtE), a self-applied transdiagnostic internet-delivered program based on the Spanish version of the UP-A. This is the first transdiagnostic internet-based program designed for the treatment of emotional disorders in adolescents. METHOD: A sample of Spanish adolescents with a primary diagnosis of an anxiety and/or depressive disorder (n = 58; age range = 12-18 years; 78.3% girls; 90% Caucasian) were randomly allocated to receive AMtE (n = 28) or the UP-A via videocall (n = 30). Pre-treatment, post-treatment and 3-month follow-up data were collected using self-reports and clinician-rated measures of anxiety, depression, positive and negative affect, anxiety sensitivity and emotional avoidance. RESULTS: Based on generalized estimating equations (GEE) models, both intervention programs were effective in significantly reducing self-reported anxiety and depressive disorder symptoms and clinician-rated severity of anxiety and depression, as well as self-reported transdiagnostic outcome variables. CONCLUSIONS: Data provide empirical support for the efficacy of AMtE as a transdiagnostic online CBT treatment for anxiety and depressive disorders in adolescents. No marked nor consistent differences were observed between the UP-A and AMtE, highlighting the potential usefulness of the online self-administered AMtE program.

Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study.

INTRODUCTION: Owing to controversy information surrounds effect of glucocorticoids on the evolution of COVID-19, we evaluate the effects of outpatient glucocorticoid use on the severity and progression of COVID-19 and risk of infection and analyse the effect of window of exposure and dose. METHODS: We conducted a population-based case - control study, involving 4 substudies: (i) Hospitalisation; (ii) Mortality, using subjects hospitalised with a PCR + as cases and subjects without a PCR + as controls; (iii) Progression, including subjects with a PCR + (hospitalised versus non-hospitalised); and (iv) Susceptibility, with all subjects with a PCR + and subjects without a PCR + . Adjusted odds ratios (ORa) and their 95% confidence intervals (95% CI) were calculated. RESULTS: The outpatient glucocorticoid use was associated with an increased risk of hospitalisation (aOR 1.79; 95% CI 1.56-2.05), mortality (aOR 2.30; 95% CI 1.68-3.15), progression (aOR 1.69; 95% CI 1.43-2.00) and susceptibility (aOR 1.29, 95% CI 1.19-1.41). Furthermore, the effects was observed to be greater at higher doses and the closer that drug use approached the outcome date, with an almost fourfold increase in mortality among users in the previous month (aOR 3.85; 95% CI 2.63-5.62). CONCLUSIONS: According to the results of this real-world data study, outpatient glucocorticoid use should be considered in making decisions about intrahospital treatment.

Nutritional and Organoleptic Characteristics of Sausage Based on an Autochthonous Ecuatorian Fish, Old Blue (Andinoacara rivulatus).

The consumption of fisheries and aquaculture products has been increasing in recent decades, and it is necessary to strike a balance between production and sustainability in aquaculture; this is essential homework to support the demand for human food. This study aimed to investigate the sensory and nutritional characteristics of a sausage made from the fillet of the native fish Old Blue (Andinoacara rivulatus) to stimulate the local economy. A multifactorial A*B*C design was used, with Factor A being rearing systems (wild and farmed), Factor B being types of protein (quinoa meal and soybean meal), and Factor C being lipids of animal (pork fat) and vegetable (sunflower oil) origin. Highly significant differences were observed in all formulas, according to Tukey (p < 0.05). The highest protein percentage was with soybean flour at 11.24%, while quinoa flour had 10.80% of the product. In sensory characteristics, the best attributes were for texture in the mouth with a hedonic scale from 0 to 5, with 4.2 firmness being mostly acceptable, odor at 4.5, the aromatic attribute with the highest and best value, and color was the clearest at 4.3 acceptability. The flavor was 4.3, mostly more pleasant according to the tasters. The yield of farmed fillets was 23.16% compared to wild 13.89%, and the balance of sausage yield was 393 g with a yield of 76.33% of the total weight. Microbiological analysis of the sausage with the native species showed the absence of pathogenic microorganisms. A commercial shelf life of 30 days was also established for the sausage, demonstrating an added value through this processing, allowing its exploitation in areas further away from the fishing sites and, thus, a greater possibility of social development in the area.