AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.

This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the DMPK gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in DMPK. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myotube area across CTG expansions. Unexpectedly, the treatment also reduced DMPK transcripts and ribonuclear foci. A leading antimiR reversed 68% of dysregulated genes. This study highlights the potential of antimiRs to treat various DM1 forms across a range of repeat sizes and genetic backgrounds by mitigating MBNL1 sequestration and enhancing protein synthesis.

Duodenal Pseudolipomatosis. Literature review and case report of a very unusual finding.

Pseudolipomatosis (PL) is a rare, benign, iatrogenic condition first described in colorectal mucosa. This condition is thought to arise from gas penetration into the mucosa due to mechanical or chemical injury during endoscopy. Despite these associations and its characteristic appearence, the definitive pathogenesis remains unclear and it continues to be underrecognized by some pathologists and endoscopists, which is crucial to avoid any further unnecessary treatments. Immunohistochemistry techniques play a role in differentiating PL from similar conditions such as cystic intestinal pneumatosis, intestinal lipomatosis, or lymphangiectasia. A 70-year-old man with a family history of colon adenocarcinoma was diagnosed with duodenal pseudolipomatosis after a routine endoscopic assessment. To the best of our knowledge, there have been only two reports of PL diagnosed in the duodenum. A review of over 500 duodenal biopsies at our centre revealed that no other instances were identified, emphasizing the unusual occurrence of this particular location.

Transcriptomic Analysis Reveals the Heterogeneous Role of Conducting Films Upon Electrical Stimulation.

Central nervous system (CNS) injuries and neurodegenerative diseases have markedly poor prognoses and can result in permanent dysfunction due to the general inability of CNS neurons to regenerate. Differentiation of transplanted stem cells has emerged as a therapeutic avenue to regenerate tissue architecture in damaged areas. Electrical stimulation is a promising approach for directing the differentiation outcomes and pattern of outgrowth of transplanted stem cells, however traditional inorganic bio-electrodes can induce adverse effects such as inflammation. This study demonstrates the implementation of two organic thin films, a polymer/reduced graphene oxide nanocomposite (P(rGO)) and PEDOT:PSS, that have favorable properties for implementation as conductive materials for electrical stimulation, as well as an inorganic indium tin oxide (ITO) conductive film. Transcriptomic analysis reveals that electrical stimulation improves neuronal differentiation of SH-SY5Y cells on all three films, with the greatest effect for P(rGO). Unique material- and electrical stimuli-mediated effects are observed, associated with differentiation, cell-substrate adhesion, and translation. The work demonstrates that P(rGO) and PEDOT:PSS are highly promising organic materials for the development of biocompatible, conductive scaffolds that will enhance electrically-aided stem cell therapeutics for CNS injuries and neurodegenerative diseases.

Comprehensive Nutritional and Functional Characterization of Novel Mycoprotein Derived from the Bioconversion of Durvillaea spp.

This study aimed, for the first time, to determine the nutritional composition, beta-glucan and ergosterol contents, phenolic compound composition, and biological and functional activities of a novel mycoprotein produced through a bioconversion process of Durvillaea spp., a brown seaweed. An untargeted metabolomics approach was employed to screen metabolites and annotate molecules with nutraceutical properties. Two products, each representing a distinct consortia of co-cultured fungi, named Myco 1 and Myco 2, were analysed in this study. These consortia demonstrated superior properties compared to those of Durvillaea spp., showing significant increases in total protein (~238%), amino acids (~219%), and ß-D-glucans (~112%). The protein contains all essential amino acids, a low fatty acid content, and exhibits high antioxidant activity (21.5-25.5 µmol TE/g). Additionally, Myco 2 exhibited the highest anti-alpha-glucosidase activity (IC50 = 16.5 mg/mL), and Myco 1 exhibited notable anti-lipase activity (IC50 = 10.5 mg/mL). Among the 69 top differentially abundant metabolites screened, 8 nutraceutical compounds were present in relatively high concentrations among the identified mycoproteins. The proteins and polysaccharides in the mycoprotein may play a crucial role in the formation and stabilization of emulsions, identifying it as a potent bioemulsifier. In conclusion, the bioconversion of Durvillaea spp. results in a mycoprotein with high-quality protein, significant nutritional and functional value, and prebiotic and nutraceutical potential due to the production of unique bioactive compounds.

Abernethy syndrome as a cause of liver transplantation.

Congenital portosystemic shunts are rare abnormalities in which blood flow from the liver is diverted to the systemic circulation. We would like to present the case of a 48-year-old male, during his neurological follow-up he was diagnosed with a congenital intrahepatic portosystemic shunt. Embolization of the portosystemic communicating veins was attempted on two occasions, but without success. Due to the poor clinical course, the patient was presented to our transplant committee and a liver transplant was decided upon.

Toward biomanufacturing of next-generation bacterial nanocellulose (BNC)-based materials with tailored properties: A review on genetic engineering approaches.

Bacterial nanocellulose (BNC) is a biopolymer that is drawing significant attention for a wide range of applications thanks to its unique structure and excellent properties, such as high purity, mechanical strength, high water holding capacity and biocompatibility. Nevertheless, the biomanufacturing of BNC is hindered due to its low yield, the instability of microbial strains and cost limitations that prevent it from being mass-produced on a large scale. Various approaches have been developed to address these problems by genetically modifying strains and to produce BNC-based biomaterials with added value. These works are summarized and discussed in the present article, which include the overexpression and knockout of genes related and not related with the nanocellulose biosynthetic operon, the application of synthetic biology approaches and CRISPR/Cas techniques to modulate BNC biosynthesis. Further discussion is provided on functionalized BNC-based biomaterials with tailored properties that are incorporated in-vivo during its biosynthesis using genetically modified strains either in single or co-culture systems (in-vivo manufacturing). This novel strategy holds potential to open the road toward cost-effective production processes and to find novel applications in a variety of technology and industrial fields.

LC-HRMS and GC-MS Profiling of Urine Free Cortisol, Cortisone, 6Β-, and 18-Hydroxycortisol for the Evaluation of Glucocorticoid and Mineralocorticoid Disorders.

INTRODUCTION: Urine free cortisol measurements are routinely performed to evaluate hypercortisolism. Despite their analytical inaccuracy, immunoassay-based methods are frequently used. Advances in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) facilitate the incorporation of powerful diagnostic tools into clinical laboratories. In addition to its high analytical specificity and simultaneous analysis of different metabolites, accurate mass measurement allows for untargeted compound identification, which may help to identify clinically relevant metabolites or drugs. METHODS: The present study aimed to validate a simple routine LC-HRMS method to quantify cortisol, cortisone, 6ß-hydroxycortisol, and 18-hydroxycortisol simultaneously in human urine. Additionally, the study also validated a GC-MS method for the same steroids, evaluated their cross-reactivity with commercial cortisol immunoassays, and quantified the 24 h urine excretion in patients under clinical suspicion or follow-up for hypercortisolism. RESULTS: The LC-HRMS method involved liquid-liquid extraction using dichloromethane, micro-LC for chromatographic separation and detection using the accurate masses of the steroids, and simultaneous high-resolution full scan acquisition. The method presented acceptable linearity, precision, and accuracy. Significant interference from 6ß-hydroxycortisol and cortisone was demonstrated in the cortisol immunoassays, which impacted their reliability in the follow-up of patients with hypercortisolism and significant changes in these cortisol metabolites (i.e., due to drug-induced changes in CYP3A4 activity). CONCLUSION: A rapid and accurate routine LC-HRMS method was validated, which is useful for the evaluation of hypercortisolism and other disorders of glucocorticoid and mineralocorticoid metabolism.

Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico.

Chronic liver disease is a global health issue. Patients with chronic liver disease require a fresh approach that focuses on the genetic and environmental factors that contribute to disease initiation and progression. Emerging knowledge in the fields of Genomic Medicine and Genomic Nutrition demonstrates differences between countries in terms of genetics and lifestyle risk factors such as diet, physical activity, and mental health in chronic liver disease, which serves as the foundation for the implementation of Personalized Medicine and Nutrition (PerMed-Nut) strategies. Most of the world's populations have descended from various ethnic groupings. Mexico's population has a tripartite ancestral background, consisting of Amerindian, European, and African lineages, which is common across Latin America's regional countries. The purpose of this review is to discuss the genetic and environmental components that could be incorporated into a PerMed-Nut model for metabolic-associated liver disease, viral hepatitis B and C, and hepatocellular carcinoma in Mexico. Additionally, the implementation of the PerMed-Nut approach will require updated medicine and nutrition education curricula. Training and equipping future health professionals and researchers with new clinical and investigative abilities focused on preventing liver illnesses in the field of genomic hepatology globally is a vision that clinicians and nutritionists should be concerned about.

Selective Isolation and Identification of Microorganisms with Dual Capabilities: Leather Biodegradation and Heavy Metal Resistance for Industrial Applications.

Tanning, crucial for leather production, relies heavily on chromium yet poses risks due to chromium's oxidative conversion, leading to significant wastewater and solid waste generation. Physico-chemical methods are typically used for heavy metal removal, but they have drawbacks, prompting interest in eco-friendly biological remediation techniques like biosorption, bioaccumulation, and biotransformation. The EU Directive (2018/850) mandates alternatives to landfilling or incineration for industrial textile waste management, highlighting the importance of environmentally conscious practices for leather products' end-of-life management, with composting being the most researched and viable option. This study aimed to isolate microorganisms from tannery wastewater and identify those responsible for different types of tanned leather biodegradation. Bacterial shifts during leather biodegradation were observed using a leather biodegradation assay (ISO 20136) with tannery and municipal wastewater as the inoculum. Over 10,000 bacterial species were identified in all analysed samples, with 7 bacterial strains isolated from tannery wastewaters. Identification of bacterial genera like Acinetobacter, Brevundimonas, and Mycolicibacterium provides insights into potential microbial candidates for enhancing leather biodegradability, wastewater treatment, and heavy metal bioremediation in industrial applications.

Elranatamab treatment in a multiple myeloma patient undergoing renal dialysis.

We present the case of a dialyzed patient with relapsed IgA and lambda free light chain multiple myeloma treated with elranatamab. Despite end-stage renal impairment, the treatment with anti-B cell maturation antigen (BCMA)xCD3 bispecific antibody proved to be feasible, without unexpected side effects. Increased attention to infectious risk is crucial for these doubly fragile patients.

Effectiveness of family metacognitive training in mothers with psychosis and their adolescent children: a multicenter study protocol.

Background: More than half of women with psychosis take care of their children despite the difficulties caused by the disease. Additionally, these kids have a higher risk of developing a mental health disorder. However, no interventions have been developed to meet these needs. Metacognitive Training (MCT) is a psychological intervention that has demonstrated its efficacy in improving cognitive insight, symptom management and social cognition in people with first-episode psychosis (FEP). Additionally, MCT has shown better results in women than men with FEP. This study aims to adapt and evaluate the efficacy of MCT-F in mothers and adolescent children in an online group context with the main purpose of improving family relationships, cognitive awareness and symptoms in women with psychosis and increase their children's knowledge of the disease and their functioning. As secondary objectives, it also aims to evaluate improvements in metacognition, social cognition, symptoms, protective factors and self-perception of stigma. Materials and methods: A quasi-experimental design with participants acting as their own control will be carried out. Forty-eight mothers with psychosis and their adolescent children (between 12 and 20 years old) recruited from a total of 11 adult mental health care centers will receive MCT-F. Participants will be evaluated 11 weeks before the intervention (T1), at baseline (T2), and post-intervention (T3) with a cognitive insight scale, as a primary outcome. Measures of metacognitive and social cognition, symptoms, cognitive functioning, family and social functioning, protective factors (self-esteem, resilience, and coping strategies) and self-perceived stigma will be addressed as secondary outcomes. Assessment will also address trauma and attachment in mothers and, lastly, the feasibility and acceptability of MCT-F in both participant groups. Discussion: This will be the first investigation of the efficacy, acceptability, and viability of the implementation of MCT-F. The results of this study may have clinical implications, contributing to improving mothers' with psychosis and adolescents' functioning and better understanding of the disease, in addition to the possible protective and preventive effect in adolescents, who are known to be at higher risk of developing severe mental disorders.Clinical trial registration:https://clinicaltrials.gov/, identifier [NCT05358457].

Síndrome visual informático en pacientes menores de 35 años

Introducción: El síndrome visual informático o fatiga visual digital es una enfermedad causada por el cansancio ocular que provoca el pasar mucho tiempo frente a una pantalla. Objetivo: Diagnosticar el síndrome visual informático en pacientes menores de 35 años atendidos en la consulta de refracción. Métodos: Se realizó un estudio descriptivo prospectivo y transversal de pacientes atendidos en la consulta de refracción del Policlínico Especialidades del Hospital Provincial Docente Clínicoquirúrgico Saturnino Lora, durante el periodo de abril a junio de 2022. Resultados: Predominaron los pacientes en las edades comprendidas entre 26 y 35 años y del sexo femenino; los síntomas más frecuentes fueron el cansancio visual, ardor ocular, sensación de ojo seco, visión borrosa de cerca, ojo rojo y el dolor de cabeza después del esfuerzo visual. Los dispositivos digitales más usados fueron el celular y la computadora con un tiempo de uso de una a tres horas, destacándose este último con un tiempo superior a 4 horas. Los defectos refractivos constituyeron la principal causa de limitaciones visuales. Los pacientes con síndrome visual informático y alguna ametropía sin corrección fueron los que mayor cantidad de síntomas tuvieron, seguidos de los pacientes corregidos inadecuadamente. Conclusiones: Este síndrome afecta en gran medida a la población más joven. El adecuado interrogatorio y la incorporación de los procedimientos correctos en el estudio optométrico diario permitió el diagnóstico de tal síndrome en los pacientes atendidos y la corrección óptica pertinente.

Introduction: Digital visual syndrome or digital visual fatigue is a disease caused by the ocular fatigue provoked by spending much time in front of a screen. Objective: To diagnose the digital visual syndrome in patients under 35 years assisted in the refraction service. Methods: A prospective descriptive and cross-sectional study of patients assisted in the refraction service of the Specialties Polyclinic in Saturnino Lora Teaching Clinical Surgical Provincial Hospital, was carried out from April to June, 2022. Results: There was a prevalence of patients aged 26 and 35 and female sex; the most frequent symptoms were visual fatigue, ocular burning, dry eye sensation, closely blurred vision, red eye and headache after visual effort. The most used digital devices were the cellphone and the computer with a time of use from one to three hours, with emphasis in the last one with more than 4 hours. The refractive defects constituted the main cause of visual limitations. The patients with digital visual syndrome and some type of ametropia without correction were those with more symptoms, followed by the patients inadequately corrected. Conclusions: This syndrome affects the youngest population to a great extent. The appropriate interrogation and the incorporation of correct procedures in the daily optometric study allowed the diagnosis of such a syndrome in the assisted patients and the pertinent optic correction.

Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.

Metabolic syndrome in systemic lupus erythematosus patients under Mediterranean diet / Síndrome metabólico en pacientes con lupus eritematoso sistémico con patrón de dieta mediterránea

Background and aims: Metabolic syndrome (MetS) is a chronic proinflammatory and prothrombotic condition that exacerbates insulin resistance, oxidative damage, and cardiovascular risk, being more prevalent in patients with systemic lupus erythematosus (SLE), a chronic multisystemic autoimmune disorder. This study aim was to determine the prevalence of MetS and associations with SLE clinical characteristics, cardiovascular risk and dietary pattern in a population of Spanish SLE patients. Design and methods: Cross-sectional study of 293 patients was conducted (90.4% females; mean age 46.8 (12.94)). The diagnosis of MetS was established based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III. SLE Disease Activity Index (SLEDAI-2K) and SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Med Diet adherence was assessed through a 14 items questionnaire on food consumption frequency and habits. Results: MetS was present in 15% SLE patients. Triglycerides, high-density lipoprotein cholesterol, systolic blood pressure and waist circumference were significantly increased (p<0.001) in the group of MetS patients. Patients with MetS showed significantly increased SDI damage index (1.70 (1.69) vs 0.88 (1.12), p<0.001) and complement C3 level (118.70 (32.67) vs 107.55 (26.82), p=0.011). No significant differences were observed according to Med Diet adherence level. Conclusion: We observed a lower prevalence of MetS in SLE than that reported in previous studies, which may be a result of the good level of adherence to the MedDiet in our study sample. Additionally, MetS was associated with higher SDI and complement C3 levels but no with medication use.(AU)

Antecedentes y objetivos: El síndrome metabólico (SM) es una condición crónica proinflamatoria y protrombótica que exacerba resistencia a insulina, daño oxidativo y riesgo cardiovascular, más prevalente en pacientes con lupus eritematoso sistémico (LES) y trastorno autoinmune multisistémico crónico. El objetivo del estudio fue determinar la prevalencia de SM y asociación con características clínicas del LES, riesgo cardiovascular y patrón dietético en pacientes españoles con LES. Diseño y métodos: Estudio transversal, 293 pacientes (90,4% mujeres; edad media 46,85 [12,94]). Diagnóstico de SM según criterios National Cholesterol Education Program Adult Treatment Panel III. Se utilizó el Índice de Actividad de la Enfermedad del LES (SLEDAI-2K) e Índice de Daño del LES para evaluar actividad de la enfermedad y el daño relacionado con la enfermedad. Adherencia a la dieta mediterránea (DM) se evaluó mediante un cuestionario de 14 ítems sobre frecuencia y hábitos de consumo de alimentos. Resultados: El 15% de los pacientes con LES presentaron SM. Encontramos triglicéridos, colesterol de lipoproteínas de alta densidad, presión arterial sistólica y perímetro cintura significativamente elevados (p<0,001) en pacientes con SM. Pacientes con SM mostraron índice de daño SDI (1,70 [1,69] vs. 0,88 [1,12]; p<0,001) y nivel de complemento C3 (118,70 [32,67] vs. 107,55 [26,82]; p=0,011) significativamente elevados. No diferencias significativas según el nivel de adherencia a la DM. Conclusiones: Observamos menor prevalencia de SM en pacientes con LES que la descrita en estudios previos, podría deberse a la buena adherencia a la DM en nuestra muestra. El SM se asoció con mayores niveles de SDI y complemento C3, no con el uso de medicación.(AU)

Impact of SARS-COV-2 Infection on Maternal, Obstetric and Neonatal Outcomes in a Cohort of Vaccinated Women: A Pilot Study.

We aimed to investigate the impact of COVID-19 infection on maternal characteristics and obstetric and neonatal outcomes in a cohort of women in labor previously vaccinated who tested positive for SARS-CoV-2 infection, compared to aged-matched healthy controls. A retrospective case-control study was conducted among 66 women in labor. Clinical data were obtained from medical records. The attendance rates at childbirth and parenting classes, as well as the implementation of a birth plan, were significantly lower in the COVID-19 infection group (6.1% vs. 48.5%, <0.001; 6.1% vs. 33.3%, p = .005, respectively). Women with COVID-19 had a higher prevalence of prolonged postpartum hospital stay (33.3% vs. 9.1%, p = .016), and significantly higher prevalence of spontaneous preterm birth (27.3% vs. 1.09%, p = .006). Breastfeeding within the first 24 hr was also lower in women with COVID-19 (72.7% vs. 97.0%, p = .006). Maternal characteristics and neonatal outcomes are influenced by COVID-19 infection in vaccinated women. Complications include spontaneous preterm birth, prolonged postpartum hospital stay, and lack of breastfeeding within the first 24 hr. Childbirth education, parenting classes and implementing a birth plan may be associated with a decreased risk of COVID-19 infection.

Ultrasound screening for abdominal aortic aneurysm in primary care. / Utilidad de la ecografía en el cribado del aneurisma de aorta abdominal en atención primaria.

INTRODUCTION: Abdominal aortic aneurysm (AAA) constitutes a pathology with high mortality. There is currently no screening program implemented in primary care in Spain. OBJECTIVES: To evaluate the usefulness of ultrasound in the detection of AAA in the at-risk population in primary care. Secondarily, to identify subjects whose vascular risk (VR) should be reclassified and to determine whether AAA is associated with the presence of carotid plaque and other risk factors. MATERIAL AND METHODS: Cross-sectional, descriptive, multicenter, national, descriptive study in primary care. SUBJECTS: A consecutive selection of hypertensive males aged between 65 and 75 who are either smokers or former smokers, or individuals over the age of 50 of both sexes with a family history of AAA. MEASUREMENTS: Diameter of abdominal aorta and iliac arteries; detection of abdominal aortic and carotid atherosclerotic plaque. VR was calculated at the beginning and after testing (SCORE). RESULTS: One hundred and fifty patients were analyzed (age: 68.3±5 years; 89.3% male). Baseline RV was high/very high in 55.3%. AAA was detected in 12 patients (8%; 95% CI: 4-12); aortic ectasia in 13 (8.7%); abdominal aortic plaque in 44% and carotid plaque in 62% of the participants. VR was reclassified in 50% of subjects. The detection of AAA or ectasia was associated with the presence of carotid plaque, current smoking and lipoprotein(a), p<0.01. CONCLUSIONS: The prevalence of AAA in patients with VR is high. Ultrasound in primary care allows detection of AAA and subclinical atherosclerosis and consequently reclassification of the VR, demonstrating its utility in screening for AAA in the at-risk population.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk.

Genome-wide association studies (GWAS) have revealed the polygenic nature of treatment-resistant schizophrenia TRS. Gene expression imputation allowed the translation of GWAS results into regulatory mechanisms and the construction of gene expression (GReX) risk scores (GReX-RS).  In the present study we computed GReX-RS from the largest GWAS of TRS to assess its association with clinical features. We perform transcriptome imputation in the largest GWAS of TRS to find GReX associated with TRS using brain tissues. Then, for each tissue, we constructed a GReX-RS of the identified genes in a sample of 254 genotyped first episode of psychosis (FEP) patients to test its association with clinical phenotypes, including clinical symptomatology, global functioning and cognitive performance. Our analysis provides evidence that the polygenic basis of TRS includes genetic variants that modulate the expression of certain genes in certain brain areas (substantia nigra, hippocampus, amygdala and frontal cortex), which at the same time are related to clinical features in FEP patients, mainly persistence of negative symptoms and cognitive alterations in sustained attention, which have also been suggested as clinical predictors of TRS. Our results provide a clinical explanation of the polygenic architecture of TRS and give more insight into the biological mechanisms underlying TRS.

Association between perfectionism, personality traits and probable sleep bruxism in Spanish schoolchildren: A case-control study.

BACKGROUND: The aetiology of Sleep bruxism includes specific personality traits, related to perfectionism. AIM: To investigate the relationship between probable sleep bruxism (PSB) and personality traits in children and their parents, determining whether children with PSB and their parents are more perfectionists. DESIGN: This case-control study included 104 children aged 8-9 years, 52 cases and 52 controls. A clinical examination was performed on the children who completed the Big Five Personality Questionnaire (BFQ-NA) and the Child Perfectionism Inventory. Parents completed a bruxism diagnostic questionnaire according to the AASM criteria, BFQ and Frost multidimensional perfectionism scale questionnaires. t-Tests for independent samples and multivariate logistic regression models were used for statistical analysis. RESULTS: A significant relationship between PSB and a self-demanding personality (OR = 1.11, p = .01), restless sleep (OR = 4.41, p = .004), and a family history of clenching and grinding teeth (OR = 3.07, p = .0006) was found in a binary logistic regression model. When adjusted, only restless sleep showed a significant relationship with PSB (p = .03, OR 3.32, 95% CI 1.13-9.81). CONCLUSION: Children whose parents reported as clenching or grinding their teeth while asleep in the previous 6 months, and who were found to have abnormal dental wear, had significantly more nightmares, sleep disruption, daytime sleepiness, family history of bruxism, and tended to be more perfectionist.

Factors related to the development of high antibody titres against SARS-CoV-2 in convalescent plasma donors from the ConPlas-19 trial.

BACKGROUND AND OBJECTIVES: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. MATERIALS AND METHODS: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. RESULTS: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). CONCLUSION: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.