Test-retest reliability of Latin American Group for Maturity (GDLAM) protocol in older women.

Functional autonomy (FA) is a critical factor in determining the quality of life of older adults (OA), especially in the case of older women (OW), as they face a decline in FA in their later years of life. FA should be assessed early, using valid, reliable, and low-cost tests. This study evaluated the test-retest reliability of GDLAM and GDLAM autonomy index (GI) in OW. Thirty-nine OW (71.2 ± 6.50 years) participated in the study. A repeated measures design was used to compare the interday test-retest reliability of the five GDLAM tests (seconds) and the GI (points). The five tests represent activities of daily living, such as dressing or wandering around the house, while the GI provides a weighting of the results of the five tests. The analysis consisted of the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). A CV ≤ 10% and an ICC ≥ 0.80 were considered acceptable reliability, whereas a CV ≤ 5% and an ICC ≥ 0.90 were considered high reliability. The outcome of the five tests, represented by the GI, showed high interday test-retest reliability (CV = 6.00% and ICC = 0.91). The results of this study demonstrate that the five tests of the GDLAM protocol and the GI have high interday test-retest reliability and good interday reproducibility. From a practical point of view, the GDLAM protocol allows the assessment of FA of community-dwelling OW, providing background for early diagnosis and, with it, the possibility of developing an individualized physical exercise prescription.

NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing.

BACKGROUND: Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions. In this work, we report the development of a single-nucleus RNA sequencing (snRNA-seq) approach with targeted islet cell enrichment for endocrine-population focused transcriptomic profiling using frozen archival pancreatic tissues without islet isolation. RESULTS: We cross-compared five nuclei isolation protocols and selected the citric acid method as the best strategy to isolate nuclei with high RNA integrity and low cytoplasmic contamination from frozen archival human pancreata. We innovated fluorescence-activated nuclei sorting based on the positive signal of NKX2-2 antibody to enrich nuclei of the endocrine population from the entire nuclei pool of the pancreas. Our sample preparation procedure generated high-quality single-nucleus gene-expression libraries while preserving the endocrine population diversity. In comparison with single-cell RNA sequencing (scRNA-seq) library generated with live cells from freshly isolated human islets, the snRNA-seq library displayed comparable endocrine cellular composition and cell type signature gene expression. However, between these two types of libraries, differential enrichments of transcripts belonging to different functional classes could be observed. CONCLUSIONS: Our work fills a technological gap and helps to unleash frozen archival pancreatic tissues for molecular profiling targeting the endocrine population. This study opens doors to retrospective mappings of endocrine cell dynamics in pancreatic tissues of complex histopathology. We expect that our protocol is applicable to enrich nuclei for transcriptomics studies from various populations in different types of frozen archival tissues.

Histopathological Clues of Enhanced Inflammation in the Placental Tissue of Women with Chronic Venous Disease in Lower Limbs during Pregnancy.

It is estimated that approximately one in three women develop chronic venous disease (CVD) during pregnancy, a broad spectrum of morphofunctional disorders affecting the venous system in different regions of the body, including the lower limbs. A growing body of evidence supports the diverse maternofetal consequences derived from this condition, with the placenta being an organ particularly affected. Among other consequences, having CVD during pregnancy has been associated with systemic inflammation and altered cytokines and chemokine profiles in the maternal and fetal serum related to this condition. In the present work, we aimed to analyze if these inflammatory changes also occurred in the placental tissue of women with CVD, exploring by immunohistochemistry and real-time PCR (RT-qPCR) gene and protein expression of critical inflammatory markers like allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A, and IL-18. Our results demonstrate an enhanced tissue expression of AIF-1, IL-12A, and IL-18, accompanied by a decrease in IL-10 in the placentas of women who had undergone CVD during pregnancy. Overall, our results suggest a possible pathophysiological role of inflammation in the placental tissue of women with CVD during pregnancy, although the precise consequences of this feature remain to be deeply analyzed.

Percepción de los médicos frente al consumo de vino tinto y la salud cardiovascular / Doctors’ perception of red wine consumption and cardiovascular health

Introducción: El consumo de vino tinto se ha relacionado históricamente con una reducción de riesgo cardiovascular, con una evidencia científica en ocasiones controvertida. Método: Se ha realizado una encuesta vía WhatsApp con fecha 01/09/22 a una cohorte de médicos de la provincia de Málaga sobre los posibles hábitos de consumo de vino tinto saludables, diferenciando: nunca, 3-4 copas semanales, 5-6 copas semanales y una copa diaria. Resultados: Contestaron 184 facultativos, con una media de edad de 35 años ± 11,1, de los cuales 84 (45,6%) fueron mujeres, distribuidos en diferentes especialidades. La mayoritaria fue medicina interna con 52 (28,2%). La opción más elegida fue la d (59,2%), seguida de la a (21,2%), la c (14,7%) y la b (5%). Conclusiones: Más de la mitad de los médicos encuestados recomendaron nulo consumo y solo el 20% indicaron que una copa diaria podría ser saludable en sujetos no abstemios. (AU)

Introduction: The consumption of red wine has historically been associated with a reduction in cardiovascular risk, with sometimes controversial scientific evidence. Method: A survey was carried out via whatsapp dated 09/01/22 to a cohort of doctors from the province of Malaga, asking about possible healthy red wine consumption habits, differentiating: never, 3-4 glasses per week, 5 -6 weekly drinks and one daily drink. Results: A total of 184 physicians answered, with a mean age of 35 years ± 11.1, of which 84 (45.6%) were women, distributed in different specialties, the majority being internal medicine with 52 (28.2%). The most frequently chosen option was D (59.2%), followed by A (21.2%), C (14.7%) and B (5%). Conclusions: More than half of the doctors surveyed recommended zero consumption, and only 20% indicated that a daily drink could be healthy in non-drinkers. (AU)

Comparación de las expectativas académicas de universitarios colombianos de primer año según el nivel de escolaridad de los padres

Introducción: Las expectativas académicas representan aquello que los estudiantes esperan alcanzar durante su formación y son un factor predictivo del desempeño académico y social. Estas expectativas académicas son moldeadas por los padres, luego la educación de estos es una variable importante en el desarrollo académico de los hijos. Si bien los progenitores proyectan sus anhelos sobre sus hijos, los motivan a tener altos niveles de aspiración y son los responsables de crear ambientes intelectualmente más estimulantes; el objetivo de este estudio fue identificar las diferencias en las expectativas académicas de una muestra de estudiantes, según el nivel de escolaridad de sus padres. Método: Esta investigación contó con la participación de 261 estudiantes colombianos universitarios quienes están cursando su primer año de pregrado, entre los 16 y 54 años (media=21,9). Para este estudio se utilizó el Cuestionario de percepciones académicas-expectativas (CPA-E; Deaño et al., 2015); se obtuvieron los puntajes de cada participante, junto con sus datos sociodemográficos que estipulaban el nivel de escolaridad de los padres, y se llevaron a cabo los análisis descriptivos de cada grupo, y los análisis de varianza unidireccional (ANOVA). Resultados: Las expectativas académicas de los estudiantes con ambos padres sin educación superior (media = 189.176), se encuentran por debajo de la media, siendo significativamente diferentes a los puntajes de expectativas académicas de individuos con uno (media = 202.050) o ambos padres con estudios superiores (media = 204.286, p < 0,001). Discusión: Se demuestra la relevancia y necesidad del acceso a la educación para la mayoría de la población colombiana, entendiendo que este es un factor influyente en las expectativas académicas de una persona, y que debe tenerse un acompañamiento diferencial a los estudiantes con padres sin formación profesional.

Introduction: Academic expectations represent what students hope to achieve during their training and are a predictor of academic and social performance. These academic expectations are shaped by the parents, therefore their education is an important variable in the academic development of the children. Although parents project their aspirations on their children, motivate them to have high levels of aspiration and are responsible for creating more intellectually stimulating environments, the objective of this study was to identify the differences in the academic expectations of a sample of students, according to the level of education of their parents. Method: This research had the participation of 261 Colombian university students who are studying their first year of undergraduate, between the ages of 16 and 54 (mean = 21,9). For this study, the Academic Perceptions-Expectations Questionnaire (CPA-E; Deaño et al., 2015), was used, the scores of each participant were obtained, together with their sociodemographic data stipulating the parents' level of education, and descriptive data and one-way variance (ANOVA) analyzes were done. Results: The academic expectations of students with both parents without higher education (mean= 189.176), are below the average, being significantly different from the academic expectations scores of individuals with one (mean= 202.050) or both parents with higher education (mean= 204.286, p < 0,001). Discussion: The relevance and need of access to education for most of the Colombian population is demonstrated, understanding that this is an influential factor in the academic expectations of a person, and that there must be differential support for students with parents without training professional.

Interlaminar endoscopic uniportal approach for implantation of a paddle lead larger than 10 mm for spinal cord stimulation: illustrative case.

BACKGROUND: The authors aim to describe a new technique for implantation of a spinal cord stimulation paddle lead sized over 10 mm through an endoscopic uniportal approach. A new endoscopic cannula was developed for the passage of a paddle lead width between 10 and 13 mm. The distal portion of the cannula was designed with a larger opening, providing better visibility of the anterior portion of the adjacent structures, thus allowing a panoramic view of the electrode passage. An electrode was implanted in an 11-mm paddle. OBSERVATIONS: After searching PubMed, Cochrane, and Lilacs databases, the authors found no mention of the implantation of a paddle electrode with a width greater than 10 mm. The implantation of a paddle electrode less than 10 mm wide is possible via endoscopic access using 10-mm working channels. However, for electrodes with a width greater than 10 mm, access via endoscopy is impossible, since the working channel is only 10 mm. LESSONS: The authors concluded that it is possible to pass electrodes safely and effectively with a paddle width between 10 and 13 mm using spinal endoscopy via uniportal interlaminar access. However, it is necessary to expand studies to elucidate this technique of endoscopic implantation of electrodes for neurostimulation.

Radiation dose reduction and image quality evaluation for lateral lumbar spine projection.

Purpose: Optimization studies in digital radiology help to reduce the radiological risk to patients and maximize the benefits associated with their clinical purpose. The aim of this study was to assess the optimization of lateral lumbar spine projection via a combination of exposure parameters adjustments and additional filtration using a sectional anthropomorphic phantom. Materials and methods: We evaluated the effects of peak voltage, tube loading, and low-cost filters made of copper, titanium, brass, and nickel on both the perceived and physical quality of 125 radiographs obtained in a computer radiography system. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) with their Figure of Merit (FOM), based on the entrance surface air kerma with backscatter (ESAK), was used to assess physical image quality. Results: The standard image had a perceived image quality, SNR, FOMSNR, CNR, FOMCNR and ESAK of 3.4, 22.3, 386.4, 23.6, 433.7 and 1.28 mGy, respectively. Copper (90.3% purity) and titanium (95.0% purity) filters reduced ESAK by an average of 60% without compromising diagnostic quality, while brass and nickel filters increased dose under the conditions of the study. Conclusions: Our findings show that optimizing lumbar spine projection can reduce radiation dose without compromising image quality. Low-cost copper and titanium filters can be valuable in resource-limited settings. Further research can explore additional strategies for radiological optimization.

Doctors' perception of red wine consumption and cardiovascular health. / Percepción de los médicos frente al consumo de vino tinto y la salud cardiovascular.

INTRODUCTION: The consumption of red wine has historically been associated with a reduction in cardiovascular risk, with sometimes controversial scientific evidence. METHOD: A survey was carried out via whatsapp dated 09/01/22 to a cohort of doctors from the province of Malaga, asking about possible healthy red wine consumption habits, differentiating: never, 3-4 glasses per week, 5 -6 weekly drinks and one daily drink. RESULTS: A total of 184 physicians answered, with a mean age of 35 years ± 11.1, of which 84 (45.6%) were women, distributed in different specialties, the majority being internal medicine with 52 (28.2%). The most frequently chosen option was D (59.2%), followed by A (21.2%), C (14.7%) and B (5%). CONCLUSIONS: More than half of the doctors surveyed recommended zero consumption, and only 20% indicated that a daily drink could be healthy in non-drinkers.

Design and rationale of behavioral nudges for diabetes prevention (BEGIN): A pragmatic, cluster randomized trial of text messaging and a decision aid intervention for primary care patients with prediabetes.

BACKGROUND: Among 96 million U.S. adults with prediabetes, adoption of evidence-based treatment to prevent diabetes remains low. Primary care represents an essential venue for preventing diabetes, yet providers in this setting have limited time to address prevention. This highlights the need for low-touch interventions that promote diabetes prevention and are not delivered by primary care providers. Text messaging and decision aids displaying disease risk and treatment information have improved outcomes in prior research. However, these approaches have not been definitively studied for managing prediabetes. METHODS: The Behavioral Nudges for Diabetes Prevention (BEGIN) trial is a pragmatic, cluster randomized trial testing the effectiveness of text messaging about diabetes prevention and a prediabetes decision aid. These interventions are being studied in 8 primary care clinics using a 2 × 2 factorial design, in which pairs of clinics are randomized in a 1:1:1:1 ratio to receive usual care, text messaging alone, prediabetes decision aid alone, or both interventions. A total of 656 patients are recruited to participate, receive the study interventions, and contribute data at baseline and 12 months. The primary outcome is 12-month weight change, and the secondary outcome is adoption of evidence-based treatment to prevent diabetes. Change in hemoglobin A1c is an exploratory outcome that will be assessed among participants with available values. CONCLUSION: Findings from the BEGIN trial will provide evidence about the effectiveness of two novel, low-touch interventions focused on diabetes prevention in primary care, where patients are diagnosed with prediabetes and there is little prior research. TRIAL REGISTRY: NCT04869917.

Adherence to antiretroviral therapy and viral suppression: Analysis of three periods between 2011 and 2017 at an HIV-AIDS center, Brazil.

The increased effectiveness of antiretroviral therapy (ART) in the last 30 years is a scientific landmark, and viral suppression is directly associated with treatment adherence. The aim of this study was to compare the results of ART adherence and viral load suppression with the evolution of the protocols and other associated factors, in people living with HIV. A panel analysis of three descriptive longitudinal studies investigating ART adherence and viral load suppression was conducted in people with HIV treated at a drug dispensing unit in the Federal District. The studies were carried out during periods of 2011, 2013, and 2017, coinciding with the three different recommended treatment schemes for the country. Adherence was assessed using drug dispensing records. Viral load data were obtained from the Ministry of Health's Laboratory Examination Information System. Analysis of the data of 522 individuals in the three periods showed sociodemographic differences such as a decline in the percentage of women (from 33% in period 1 to 4% in period 3) and an increase in the percentage of young people. ART adherence was higher in period 2 (tenofovir/lamivudine/efavirenz scheme). Viral load suppression was greater in period 3 (tenofovir/lamivudine/dolutegravir scheme). The relative detectable viral load risk was nearly two-fold higher (RR 1.83) in people living with HIV with less than 80% adherence when compared to those above 80%. With respect to the different schemes recommended in Brazil during the periods studied, ART containing dolutegravir was the most effective in achieving viral load suppression. By contrast, there was better ART adherence in the daily combined fixed dose consisting of tenofovir/lamivudine/efavirenz in tablet form. Adherence to ART above 80% seemed to be enough to promote an effective treatment in therapeutic schemes including efavirenz or dolutegravir.

Role of lipoprotein lipase activity measurement in the diagnosis of familial chylomicronemia syndrome.

BACKGROUND: Activity assays for lipoprotein lipase (LPL) are not standardised for use in clinical settings. OBJECTIVE: This study sought to define and validate a cut-off points based on a ROC curve for the diagnosis of patients with familial chylomicronemia syndrome (FCS). We also evaluated the role of LPL activity in a comprehensive FCS diagnostic workflow. METHODS: A derivation cohort (including an FCS group (n = 9), a multifactorial chylomicronemia syndrome (MCS) group (n = 11)), and an external validation cohort (including an FCS group (n = 5), a MCS group (n = 23) and a normo-triglyceridemic (NTG) group (n = 14)), were studied. FCS patients were previously diagnosed by the presence of biallelic pathogenic genetic variants in the LPL and GPIHBP1 genes. LPL activity was also measured. Clinical and anthropometric data were recorded, and serum lipids and lipoproteins were measured. Sensitivity, specificity and cut-offs for LPL activity were obtained from a ROC curve and externally validated. RESULTS: All post-heparin plasma LPL activity in the FCS patients were below 25.1 mU/mL, that was cut-off with best performance. There was no overlap in the LPL activity distributions between the FCS and MCS groups, conversely to the FCS and NTG groups. CONCLUSION: We conclude that, in addition to genetic testing, LPL activity in subjects with severe hypertriglyceridemia is a reliable criterium in the diagnosis of FCS when using a cut-off of 25.1 mU/mL (25% of the mean LPL activity in the validation MCS group). We do not recommend the NTG patient based cut-off values due to low sensitivity.

Prevalence of Oestrus ovis in small ruminants from the eastern Iberian Peninsula. A long-term study.

Oestrus ovis is an obligate parasite that causes myiasis in domestic ruminants, being commonly found in the Mediterranean area. From 2009 to 2019 a total of 3476 heads of culling sheep and goats from the Mediterranean coast of Spain were examined for the presence of O. ovis. The total prevalence was 56.3%, significantly higher in sheep than in goats (61.2% and 43%, respectively). Differences were found in the mean annual prevalence, with the highest value being registered in 2018 (61.7%) and the lowest in 2012 (50.3%). Autumn, for sheep, and winter, for goats, were the seasons with the highest number of infested specimens. Temperature, but not rainfall, was found to be associated with prevalence (p < 0.05). Most L1 were found in the anatomic region I (septum, meatus, and ventral conchae), while L2 and L3 were mainly located in regions II (nasopharynx, ethmoid labyrinth, and dorsal conchae), and III (sinuses). The overall intensity was 12.8 larvae per head, significantly higher in sheep (13.3) than in goats (3.5). Our results confirm the high prevalence of O. ovis in sheep and goats in this geographic area over the last decade, with the trend increasing in recent years in association with higher mean temperatures.

DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy.

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.

Are birds more afraid in urban parks or cemeteries? A Latin American study contrasts with results from Europe.

The escape behaviour, measured as flight initiation distance (FID; the distance at which individuals take flight when approached by a potential predator, usually a human in the study systems), is a measure widely used to study fearfulness and risk-taking in animals. Previous studies have shown significant differences in the escape behaviour of birds inhabiting cemeteries and urban parks in European cities, where birds seem to be shyer in the latter. We collected a regional dataset of the FID of birds inhabiting cemeteries and parks across Latin America in peri-urban, suburban and urban parks and cemeteries. FIDs were recorded for eighty-one bird species. Mean species-specific FIDs ranged from 1.9 to 19.7 m for species with at least two observations (fifty-seven species). Using Bayesian regression modelling and controlling for the phylogenetic relatedness of the FID among bird species and city and country, we found that, in contrast to a recent publication from Europe, birds escape earlier in cemeteries than parks in the studied Latin American cities. FIDs were also significantly shorter in urban areas than in peri-urban areas and in areas with higher human density. Our results indicate that some idiosyncratic patterns in animal fearfulness towards humans may emerge among different geographic regions, highlighting difficulties with scaling up and application of regional findings to other ecosystems and world regions. Such differences could be associated with intrinsic differences between the pool of bird species from temperate European and mostly tropical Latin American cities, characterized by different evolutionary histories, but also with differences in the historical process of urbanization.

Neuronal and astrocytic tetraploidy is increased in drug-resistant epilepsy.

AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.

Captive Breeding and Trichomonas gallinae Alter the Oral Microbiome of Bonelli's Eagle Chicks.

Bonelli's eagle (Aquila fasciata) is an endangered raptor species in Europe, and trichomonosis is one of the menaces affecting chicks at nest. In this paper, we attempt to describe the oral microbiome of Bonelli's eagle nestlings and evaluate the influence of several factors, such as captivity breeding, Trichomonas gallinae infection, and the presence of lesions at the oropharynx. The core oral microbiome of Bonelli's eagle is composed of Firmicutes, Bacteroidota, Fusobacteria and Proteobacteria as the most abundant phyla, and Megamonas and Bacteroides as the most abundant genera. None of the factors analysed showed a significant influence on alfa diversity, but beta diversity was affected for some of them. Captivity breeding exerted a high influence on the composition of the oral microbiome, with significant differences in the four most abundant phyla, with a relative increase of Proteobacteria and a decrease of the other three phyla in comparison with chicks bred at nest. Some genera were more abundant in captivity bred chicks, such as Escherichia-Shigella, Enterococcus, Lactobacillus, Corynebacterium, Clostridium and Staphylococcus, while Bacteroides, Oceanivirga, Peptostreptococcus, Gemella, Veillonella, Mycoplasma, Suttonella, Alloscardovia, Varibaculum and Campylobacter were more abundant in nest raised chicks. T. gallinae infection slightly influenced the composition of the microbiome, but chicks displaying trichomonosis lesions had a higher relative abundance of Bacteroides and Gemella, being the last one an opportunistic pathogen of abscess complications in humans. Raptor's microbiomes are scarcely studied. This is the first study on the factors that influence the oral microbiome of Bonelli's eagle.

Alteraciones oftalmológicas en pacientes con COVID-19 / Ophthalmologic Alterations in Patients with COVID-19

Introducción: Las alteraciones oftalmológicas asociadas al SARS-CoV-2 se pueden clasificar como efectos directos del virus, por reacción inmunológica o por la vacunación. Objetivo: Describir las alteraciones oftalmológicas en pacientes con COVID-19. Métodos: Se presenta una serie de casos con diagnóstico clínico y serológico de COVID-19 en el curso de la enfermedad, posterior a esta o por la vacunación. Fueron estudiados 7 casos (4 mujeres y 3 hombres), que acudieron de forma consecutiva a la consulta de Neuroftalmología del Hospital "Hermanos Ameijeiras" (HHA), remitidos por especialistas que evalúan el protocolo de casos "Pos-COVID-19" en esta institución con las siguientes alteraciones: neurorretinitis (NR), papilitis (P), uveítis y papilitis (U-P), membrana epirretiniana (MER) y parálisis facial periférica (PFP), en el periodo de agosto a noviembre de 2021. Resultados: La edad promedio fue de 44 años. La NR, P y MER unilateral predominaron en la serie estudiada. La etiología inmunológica fue la más frecuente. Los síntomas y signos referidos por los pacientes fueron: disminución visual y déficit en la visión de los colores. Los resultados terapéuticos no fueron satisfactorios en los casos 1 y 6, con un tiempo de evolución prolongado, desde el inicio de los síntomas hasta el diagnóstico y tratamiento con esteroides y vitaminas del complejo B. Conclusiones: Existe una asociación entre las enfermedades oftalmológicas encontradas en pacientes jóvenes con antecedentes de padecer la COVID-19 o relacionado con la vacunación. La efectividad terapéutica estuvo condicionada por el tiempo de evolución de la enfermedad(AU)

Introduction: Ophthalmologic alterations associated with SARS-CoV-2 can be classified as direct effects of the virus, by immunologic reaction or by vaccination. Objective: To describe the ophthalmologic alterations in patients with COVID-19. Methods: A series of cases with clinical and serologic diagnosis of COVID-19 during the course of the disease, after the disease or after vaccination is presented. Seven cases were studied (4 women and 3 men), who consecutively attended the Neurophthalmology Consultation of the "Hermanos Ameijeiras" Hospital (HHA), referred by specialists who evaluate the "Post-COVID-19" case protocol in this institution with the following alterations: neuroretinitis (NR), papillitis (P), uveitis and papillitis (U-P), epiretinal membrane (MER) and peripheral facial palsy (PFP), in the period from August to November 2021. Results: The average age was 44 years. NR, P and unilateral MER predominated in the series studied. Immunologic etiology was the most frequent. The symptoms and signs referred by the patients were visual impairment and color vision deficit. Therapeutic results were not satisfactory in cases 1 and 6, with a prolonged evolution time, from the onset of symptoms to diagnosis and treatment with steroids and B-complex vitamins. Conclusions: There is an association between the ophthalmologic diseases found in young patients with a history of suffering from COVID-19 or related to vaccination. Therapeutic effectiveness was conditioned by the time of evolution of the disease(AU)

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

INTRODUCTION: Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice. OBJECTIVE: To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication. METHODS: Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available. RESULTS: 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy. CONCLUSION: The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.

Sex Differences in the Molecular Programs of Pancreatic Cells Contribute to the Differential Risks of Type 2 Diabetes.

Epidemiology studies demonstrate that women are at a significantly lower risk of developing type 2 diabetes (T2D) compared to men. However, the molecular basis of this risk difference is not well understood. In this study, we examined the sex differences in the genetic programs of pancreatic endocrine cells. We combined pancreas perifusion data and single-cell genomic data from our laboratory and from publicly available data sets to investigate multiple axes of the sex differences in the human pancreas at the single-cell type and single-cell level. We systematically compared female and male islet secretion function, gene expression program, and regulatory principles of pancreatic endocrine cells. The perifusion data indicate that female endocrine cells have a higher secretion capacity than male endocrine cells. Single-cell RNA-sequencing analysis suggests that endocrine cells in male controls have molecular signatures that resemble T2D. In addition, we identified genomic elements associated with genome-wide association study T2D loci to have differential accessibility between female and male delta cells. These genomic elements may play a sex-specific causal role in the pathogenesis of T2D. We provide molecular mechanisms that explain the differential risk of T2D between women and men. Knowledge gained from our study will accelerate the development of diagnostics and therapeutics in sex-aware precision medicine for diabetes.