Pollen-Food Allergy Syndrome: From Food Avoidance to Deciphering the Potential Cross-Reactivity between Pru p 3 and Ole e 7.

BACKGROUND: Cross-reactivity between nonspecific lipid transfer proteins could cause anaphylaxis, further influencing food avoidance and nutrient deficiencies. The one affecting olive pollen (Ole e 7) and peach (Pru p 3) may underlie a variety of pollen-food syndromes, though a deep molecular analysis is necessary. METHODS: Three Ole e 7-monosensitised patients (MON_OLE), three Pru p 3-monosensitised patients (MON_PRU) and three bisensitised patients (BI) were selected. For epitope mapping, both digested proteins were incubated with patient sera, and the captured IgE-bound peptides were characterised by LC-MS. RESULTS: The analysis revealed two Ole e 7 epitopes and the three Pru p 3 epitopes previously described. Interestingly, the "KSALALVGNKV" Ole e 7 peptide was recognised by MON_OLE, BI and MON_PRU patients. Conversely, all patients recognised the "ISASTNCATVK" Pru p 3 peptide. Although complete sequence alignment between both proteins revealed 32.6% identity, local alignment considering seven residue fragments showed 50 and 57% identity when comparing "ISASTNCATVK" with Ole e 7 and "KSALALVGNKV" with Pru p 3. CONCLUSIONS: This study mapped sIgE-Ole e 7-binding epitopes, paving the way for more precise diagnostic tools. Assuming non-significant sequence similarity, structural homology and shared key residues may underlie the potential cross-reactivity between Ole e 7 and Pru p 3 nsLTPs.

DNA damage and its association with early-life exposome: Gene-environment analysis in Colombian children under five years old.

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.

Caracterización epidemiológica de pacientes con síndrome posterior a resección anterior baja de recto y aproximación de su relación con aspectos demográficos, patológicos y quirúrgicos, en un centro de referencia en Medellín, entre 2016-2022 / Epidemiological characterization of patients with post-low anterior rectal resection syndrome and approximation of its relationship with demographic, pathological, and surgical aspects, in a referral center in Medellin, between 2016-2022

Introducción. El cáncer colorrectal es uno de los tipos de cáncer más comunes y mortales a nivel mundial. Aunque los avances médicos han mejorado el manejo, la cirugía sigue siendo fundamental. La resección anterior baja (RAB) de recto ha ganado relevancia, a pesar de que puede llevar al síndrome de resección anterior baja de recto (LARS, por sus siglas en inglés), afectando la calidad de vida. Métodos. Estudio de corte transversal con intención analítica en un centro de referencia en Medellín, Colombia. Los pacientes con cáncer de recto sometidos a RAB entre enero de 2016 y diciembre de 2022 completaron el cuestionario LARS para evaluar disfunción intestinal. Se evaluaron factores relacionados con la presencia de LARS por medio de un análisis bivariado. Resultados. De 234 pacientes elegibles, 110 (47 %) respondieron la encuesta, predominantemente mujeres (58,2 %). La edad promedio fue 62 años. Dos tercios de los pacientes recibieron neoadyuvancia y el 69 % requirieron ileostomía. La prevalencia de LARS fue 47,3 %. El 80,9 % llevaban más de 12 meses desde la cirugía o el cierre del estoma. Factores estadísticamente significativos asociados a LARS fueron edad mayor de 65 años (p=0,03), estadío patológico avanzado (p=0,02) y requerimiento de estoma (p=0,03). Conclusiones. El LARS afecta a casi la mitad de los pacientes en diferentes etapas posquirúrgicas. El LARS scorees una herramienta práctica para evaluar la función intestinal en el seguimiento del paciente. La prevalencia y los factores de riesgo identificados contribuyen a la comprensión del impacto de la cirugía conservadora del esfínter en la calidad de vida de los pacientes.

Introduction. Colorectal cancer is one of the most common and deadly types of cancer worldwide, with a high incidence of rectal cancer. Although medical advances have improved management, surgery remains crucial. Low anterior resection of the rectum (LAR) has gained significance, despite its potential to lead to low anterior resection syndrome (LARS), affecting quality of life. Methods. A cross-sectional study with analytical intent was conducted at a referral center in Medellín, Colombia. Patients with rectal cancer who underwent LAR between January 2016 and December 2022 completed the LARS questionnaire to assess intestinal dysfunction. Factors related to the presence of LARS were analyzed using bivariate analysis. Results. Of 234 eligible patients, 110 (47%) responded, predominantly women (58.2%). The average age was 62 years. Two-thirds of patients received neoadjuvant therapy and 69% required ileostomy. The prevalence of LARS was 47.3%. 80.9% had been more than 12 months post-surgery or stoma closure. Statistically significant factors associated with LARS included age over 65 years (p=0.03), advanced pathological stage (p=0.02), and stoma requirement (p=0.03). Conclusions. LARS affects almost half of the patients in various post-surgical stages. The LARS score is a practical tool for assessing intestinal function in patient follow-up. The prevalence and risk factors identified contribute to the understanding of the impact of sphincter-conserving surgery on patients' quality of life.

Incremento del riesgo hemorrágico en pacientes con fibrilación auricular y enfermedad renal crónica en hemodiálisis tratados con anticoagulantes. Serie de cuatro centros / Increased risk of bleeding in patients with atrial fibrillation and chronic kidney disease on hemodialysis treated with anticoagulants. A four center series

Resumen Objetivo: El objetivo de este estudio fue estimar si el uso de anticoagulantes se asociaba con una diferencia en la frecuencia de trombosis de cualquier sitio, hemorragia mayor y mortalidad en adultos con coexistencia de ambas patologías. Método: Se realizó un estudio de cohorte retrospectivo en cuatro centros de alta complejidad. Se incluyeron mayores de 18 años con ERC en hemodiálisis y FA no valvular, con indicación de anticoagulación (CHA2DS2VASc ≥ 2). El desenlace primario fue la ocurrencia de sangrado mayor, evento trombótico (accidente vascular cerebral, infarto agudo al miocardio o enfermedad tromboembólica venosa) o muerte. Se realizó ajuste por variables de confusión por regresión logística. Resultados: De los 158 pacientes incluidos, el 61% (n = 97) recibieron anticoagulante. El desenlace principal se encontró en el 84% de quienes recibieron anticoagulación y en el 70% de quienes no la recibieron (OR: 2.12, IC95%: 0.98-4.57; luego del ajuste OR: 2.13, IC95%: 1.04-4.36). De los desenlaces mayores se presentaron sangrado en el 52% vs. el 34% (OR: 2.03; IC95%: 1.05-3.93), trombosis en el 35% vs. el 34% (OR: 1.03; IC95%: 0.52-2.01) y muerte en el 46% vs. el 41% (OR: 1.25; IC95%: 0.65-2.38). Conclusiones: Los resultados de este estudio sugieren un incremento en el riesgo de sangrado en los pacientes con FA y ERC en hemodiálisis que reciben anticoagulación, sin disminución del riesgo de eventos trombóticos ni de muerte.

Abstract Objective: The aim of this study was to estimate whether the consumption of anticoagulants was associated with a difference in the frequency of thrombosis of any site, major bleeding and mortality, in adults with both diseases. Method: A retrospective cohort study was carried out in four high complexity centers. Patients older than 18 years with CKD on hemodialysis and non-valvular AF, with an indication for anticoagulation (CHA2DS2VASc ≥ 2), were included. The primary outcome was the occurrence of: major bleeding, thrombotic event (cerebrovascular accident, acute myocardial infarction or venous thromboembolic disease) or death. Adjustment for confounding variables was performed using logistic regression. Results: From 158 patients included, 61% (n = 97) received an anticoagulant. The main outcome was found in 84% of those who received anticoagulation and 70% of those who did not (OR: 2.12, 95%CI: 0.98-4.57; after the adjusted analysis OR: 2.13, 95%CI: 1.04-4.36). Separate outcomes were bleeding in 52% vs. 34% (OR: 2.03; 95%CI: 1.05-3.93), thrombosis in 35% vs. 34% (OR: 1.03; 95%CI: 0.52-2-01) and death in 46% vs. 41% (OR: 1.25; 95%CI: 0.65-2.38). Conclusions: The results of this study suggest an increased risk of bleeding in patients with AF and CKD on hemodialysis receiving anticoagulation, without a decrease in the risk of thrombotic events or all-cause mortality.

C57BL/6J offspring mice reared by a single-mother exhibit, compared to mice reared in a biparental parenting structure, distinct neural activation patterns and heightened ethanol-induced anxiolysis.

RATIONALE: Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition. OBJECTIVES: To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents. METHODS: Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence. RESULTS: Infant mice were sensitive to the stimulating effects of 2.0 g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis. CONCLUSIONS: These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

Functional assessment of children and adolescents with autism spectrum disorder in Argentina: ICF-ASD multicenter study. / Evaluación funcional de niños, niñas y adolescentes con diagnóstico de trastorno del espectro autista en Argentina: estudio multicéntrico TEA-CIFunciona.

Introduction. Autism spectrum disorder (ASD) is characterized by difficulties in social communication and repetitive and stereotyped behaviors. In addition to the diagnostic category, the activities performed by children and adolescents and their social involvement are the main aspects to be considered according to the International Classification of Functioning, Disability, and Health (ICF) proposed by the World Health Organization to describe health status. In a previous study, we developed the first version of a pediatric tool based on the ICF called ICF-ASD for the functional assessment of children and adolescents with ASD to capture functional characteristics adapted to our cultural setting. Our subsequent objective was to apply the ICF-ASD in a multicenter format to assess children and adolescents from different regions, review, and update it, and identify barriers and facilitators. Population and methods. The ICF-ASD version 1.0 was administered to children and adolescents younger than 16 years with a confirmed diagnosis of ASD (as per DSM-5 criteria), who were receiving follow-up at 5 children's health centers across Argentina. Results. Version 2.0 of the ICF-ASD was obtained, which included 34 categories (10 under body function, 15 under activities and participation, and 9 under environmental factors). A functional profile was developed for the whole sample (n = 308). Conclusions. The updated version of the ICF-ASD helps to standardize and systematize the collection of necessary data for an adequate follow-up of children and adolescents with ASD at a national level. It also allows to identify barriers to overcome and facilitators to be generalized.

Introducción. El trastorno del espectro autista (TEA) se caracteriza por dificultades de comunicación social y comportamientos repetitivos y estereotipados. Además de la categoría diagnóstica, las actividades que los niños, niñas y adolescentes (NNyA) pueden realizar y la participación social son los aspectos principales por considerar desde el marco de la Clasificación Internacional del Funcionamiento, la Discapacidad y la Salud (CIF), propuesta por la Organización Mundial de la Salud, para describir los estados de salud. En una investigación previa, elaboramos la primera versión de una herramienta pediátrica basada en la CIF llamada TEA-CIFunciona para evaluación funcional de NNyA con diagnóstico de TEA, que permitió captar características funcionales adaptadas a nuestro contexto cultural. Se propuso como objetivo posterior aplicar TEA-CIFunciona en formato multicéntrico para evaluar NNyA de diferentes regiones, revisar y actualizar la herramienta, e identificar barreras y facilitadores. Población y métodos. Se administró TEA-CIFunciona versión 1.0 a NNyA con diagnóstico confirmado de TEA (según criterios del DSM-5), menores de 16 años, en seguimiento en cinco centros de atención pediátrica del país. Resultados. Se obtuvo la versión 2.0 de TEA-CIFunciona con 34 categorías (10 funciones corporales, 15 actividades y participación, y 9 factores ambientales). Se elaboró el perfil funcional de la muestra completa (n = 308). Conclusiones. La versión actualizada de TEA-CIFunciona contribuye a estandarizar y a sistematizar la obtención de información necesaria para adecuar el seguimiento de los NNyA con TEA a nivel nacional. Además, permite identificar barreras por superar y facilitadores para generalizar.

Anesthetic Management of a Patient with Madelung's Disease Presenting with a Giant Cervical Lipoma: A Case Report.

Madelung's disease is characterized by the presence of multiple symmetric and nonencapsulated facial, neck, and upper trunk lipomas. Depending on the location and size of lipomas, there may be concerns for difficult airway management and cardiovascular collapse. We present the anesthetic management case of a patient with cervical and mediastinal lipomas who underwent elective cervical lipoma resection.

Impact of COVID-19 first wave on the mental health of healthcare workers in a Front-Line Spanish Tertiary Hospital: lessons learned.

Healthcare workers (HCWs) were at high risk of experiencing psychological distress during COVID-19 pandemic. The objective of this study was to evaluate the impact on HCWs' mental health in a Spanish hospital. Cross-sectional study of HCW, active between May and June 2020. A web-based survey assessed probable current mental disorders (major depressive disorder [PHQ-8 ≥ 10], generalized anxiety disorder [GAD-7 ≥ 10], panic attacks, post-traumatic stress disorder [PTSD; PLC-5 ≥ 7], or substance use disorder [CAGE-AID ≥ 2]). The Sheehan Disability Scale (SDS) was used to assess severe impairment and items taken from the modified self-report version of the Columbia Suicide Severity Rating Scale (C-SSRS) assessed suicidal thoughts and behaviors. A total of 870 HCWs completed the survey. Most frequent probable mental disorders were major depressive disorder (33.6%), generalized anxiety disorder (25.5%), panic attacks (26.9%), PTSD (27.2%), and substance use disorder (5.0%). Being female, having aged 18-29 years, being an auxiliary nurse, direct exposure to COVID-19-infected patients, and pre-pandemic lifetime mental disorders were positively associated with mental issues. Hospital HCWs presented a high prevalence of symptoms of mental disorders, especially depression, PTSD, panic attacks, and anxiety. Younger individuals and those with lifetime mental disorders have been more vulnerable to experiencing them.

Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

BACKGROUND: Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. METHODS: Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. RESULTS: SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. CONCLUSIONS: TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

The Showcases of Dental History - A time machine in miniature at the University of Puerto Rico: Part II - The Exhibits.

The University of Puerto Rico School of Dentistry was established in 1957. Over the years, it has played an important role in Puerto Rico's healthcare system. That legacy is displayed through the walls of the School of Dentistry. In Part 1, the evolution of 20-year-old dental museum-like showcases located in the lobby and the main hallway of the school were described along with important professions who impacted on this development. In this paper, we will describe in detail the items available at the museum.

Biofilm containing the Thymus serpyllum essential oil for rice and cherry tomato conservation.

Introduction: Fungal pathogens cause major yield losses in agriculture and reduce food quality and production worldwide. Purpose: To evaluate new safer alternatives to chemicals for disease management and preserve the shelf life of food, this research was conducted to: determine the chemical composition of the essential oils (EOs) of Thymus serpyllum and Thymus piperella chemotypes 1 and 2; investigate the antifungal potential of EOs in vitro against: Alternaria alternata, Bipolaris spicifera, Curvularia hawaiiensis, Fusarium oxysporum f. sp. lycopersici, Penicillium italicum, Botryotinia fuckeliana; evaluate a natural T. serpyllum extract biofilm to conserve rice grain and cherry tomatoes. Method: EOs were analyzed by GC-MS+GC-FID. EOs' antifungal activity was evaluated by dissolving Thymus extracts in PDA. Petri dishes were inoculated with disks of each fungus and incubated at 25°C for 7 days. Results: The T. serpyllum EO displayed the best Mycelial Growth Inhibition. The antifungal effect of the T. serpyllum EO biofilm was evaluated on rice caryopsis. Disinfected grains were dipped in a conidial suspension of each fungus and sprayed with EO (300 and 600 µg/mL) prepared in Tween 20. Grains were stored. The percentage of infected grains was recorded for 30 days. The T. serpyllum EO effect on cherry tomato conservation was evaluated in vivo. Wounded fruit were immersed in the T. serpyllum EO (300 and 400 µg/mL) and inoculated with Fusarium oxysporum f. sp. lycopersici. Fruit were evaluated for 7 and 14 days. Chemical profiles thymol/carvacrol for T. serpyllum, carvacrol for T. piperella Tp1 and thymol for T. piperella Tp2 were defined. The three evaluated EOs reduced all the studied phytopathogens' fungal growth. The T. serpyllum biofilm was effective with rice storage and against Fusarium oxysporum f. sp. lycopersici for extending the shelf life of tomatoes in warehouses and storing postharvest cherry tomatoes. Conclusion: We suggest applying these EOs as biofilms for safe food conservation to replace synthetic products.

Health service and psychotropic medication use for mental health conditions among healthcare workers active during the Spain Covid-19 Pandemic - A prospective cohort study using web-based surveys.

Little is known about healthcare workers' (HCW) use of healthcare services for mental disorders. This study presents data from a 16-month prospective cohort study of Spanish HCW (n = 4,809), recruited shortly after the COVID-19 pandemic onset, and assessed at four timepoints using web-based surveys. Use of health services among HCW with mental health conditions (i.e., those having a positive screen for mental disorders and/or suicidal thoughts and behaviours [STB]) was initially low (i.e., 18.2 %) but increased to 29.6 % at 16-month follow-up. Service use was positively associated with pre-pandemic mental health treatment (OR=1.99), a positive screen for major depressive disorder (OR=1.50), panic attacks (OR=1.74), suicidal thoughts and behaviours (OR=1.22), and experiencing severe role impairment (OR=1.33), and negatively associated with being female (OR = 0.69) and a higher daily number of work hours (OR=0.95). Around 30 % of HCW with mental health conditions used anxiolytics (benzodiazepines), especially medical doctors. Four out of ten HCW (39.0 %) with mental health conditions indicated a need for (additional) help, with most important barriers for service use being too ashamed, long waiting lists, and professional treatment not being available. Our findings delineate a clear mental health treatment gap among Spanish HCW.

[Increased risk of bleeding in patients with atrial fibrillation and chronic kidney disease on hemodialysis treated with anticoagulants. A four center serie]. / Incremento del riesgo hemorrágico en pacientes con fibrilación auricular y enfermedad renal crónica en hemodiálisis tratados con anticoagulantes. Serie de cuatro centros.

Background: Because the benefits and risks of anticoagulation are still unknown in patients with atrial fibrillation (AF) and with chronic kidney disease (CKD) on hemodialysis. Objective: The aim of this study was to estimate whether the consumption of anticoagulants was associated with a difference in the frequency of thrombosis of any site, major bleeding and mortality, in adults with both diseases. Method: A retrospective cohort study was carried out in four high complexity centers. Patients older than 18 years with CKD on hemodialysis and non-valvular AF, with an indication for anticoagulation (CHA2DS-2VASc ≥ 2), were included. The primary outcome was the occurrence of: major bleeding, thrombotic event (cerebrovascular accident, acute myocardial infarction or venous thromboembolic disease) or death. Adjustment for confounding variables was performed using logistic regression. Results: From 158 patients included, 61% (n = 97) received an anticoagulant. The main outcome was found in 84% of those who received anticoagulation and 70% of those who did not (OR: 2.12, 95%CI: 0.98-4.57; after the adjusted analysis OR: 2.13, 95%CI: 1.04-4.36). Separate outcomes were bleeding in 52% vs. 34% (OR: 2.03; 95%CI: 1.05-3.93), thrombosis in 35% vs. 34% (OR: 1.03; 95%CI: 0.52-2-01) and death in 46% vs 41% (OR: 1.25; 95%CI: 0.65-2.38). Conclusions: The results of this study suggest an increased risk of bleeding in patients with AF and CKD on hemodialysis receiving anticoagulation, without a decrease in the risk of thrombotic events or all-cause mortality.

Antecedentes: Puesto que se desconocen el beneficio y los riesgos de la anticoagulación en pacientes con fibrilación auricular (FA) y enfermedad renal crónica (ERC) terminal en hemodiálisis. Objetivo: El objetivo de este estudio fue estimar si el uso de anticoagulantes se asociaba con una diferencia en la frecuencia de trombosis de cualquier sitio, hemorragia mayor y mortalidad en adultos con coexistencia de ambas patologías. Método: Se realizó un estudio de cohorte retrospectivo en cuatro centros de alta complejidad. Se incluyeron mayores de 18 años con ERC en hemodiálisis y FA no valvular, con indicación de anticoagulación (CHA2DS2VASc ≥ 2). El desenlace primario fue la ocurrencia de sangrado mayor, evento trombótico (accidente vascular cerebral, infarto agudo al miocardio o enfermedad tromboembólica venosa) o muerte. Se realizó ajuste por variables de confusión por regresión logística. Resultados: De los 158 pacientes incluidos, el 61% (n = 97) recibieron anticoagulante. El desenlace principal se encontró en el 84% de quienes recibieron anticoagulación y en el 70% de quienes no la recibieron (OR: 2.12, IC95%: 0.98-4.57; luego del ajuste OR: 2.13, IC95%: 1.04-4.36). De los desenlaces mayores se presentaron sangrado en el 52% vs. el 34% (OR: 2.03; IC95%: 1.05-3.93), trombosis en el 35% vs. el 34% (OR: 1.03; IC95%: 0.52-2.01) y muerte en el 46% vs. el 41% (OR: 1.25; IC95%: 0.65-2.38). Conclusiones: Los resultados de este estudio sugieren un incremento en el riesgo de sangrado en los pacientes con FA y ERC en hemodiálisis que reciben anticoagulación, sin disminución del riesgo de eventos trombóticos ni de muerte.

Hybrid Cardiac Rehabilitation Program in a Low-Resource Setting: A Randomized Clinical Trial.

Importance: While effective, cardiovascular rehabilitation (CR) as traditionally delivered is not well implemented in lower-resource settings. Objective: To test the noninferiority of hybrid CR compared with traditional CR in terms of cardiovascular events. Design, Setting, and Participants: This pragmatic, multicenter, parallel arm, open-label randomized clinical trial (the Hybrid Cardiac Rehabilitation Trial [HYCARET]) with blinded outcome assessment was conducted at 6 referral centers in Chile. Adults aged 18 years or older who had a cardiovascular event or procedure, no contraindications to exercise, and access to a mobile telephone were eligible and recruited between April 1, 2019, and March 15, 2020, with follow-up until July 29, 2021. Interventions: Participants were randomized 1:1 in permuted blocks to the experimental arm, which received 10 center-based supervised exercise sessions plus counseling in 4 to 6 weeks and then were supported at home via telephone calls and text messages through weeks 8 to 12, or the control arm, which received the standard CR of 18 to 22 sessions with exercises and education in 8 to 12 weeks. Main Outcomes and Measures: The primary outcome was cardiovascular events or mortality. Secondary outcomes were quality of life, return to work, and lifestyle behaviors measured with validated questionnaires; muscle strength and functional capacity, measured through physical tests; and program adherence and exercise-related adverse events, assessed using checklists. Results: A total of 191 participants were included (mean [SD] age, 58.74 [9.80] years; 145 [75.92%] male); 93 were assigned to hybrid CR and 98 to standard CR. At 1 year, events had occurred in 5 unique participants in the hybrid CR group (5.38%) and 9 in the standard CR group (9.18%). In the intention-to-treat analysis, the hybrid CR group had 3.80% (95% CI, -11.13% to 3.52%) fewer cardiovascular events than the standard CR group, and relative risk was 0.59 (95% CI, 0.20-1.68) for the primary outcome. In the per-protocol analysis at different levels of adherence to the intervention, all 95% CIs crossed the noninferiority boundary (eg, 20% adherence: absolute risk difference, -0.35% [95% CI, -7.56% to 6.85%]; 80% adherence: absolute risk difference, 3.30% [95% CI, -3.70% to 10.31%]). No between-group differences were found for secondary outcomes except adherence to supervised CR sessions (79.14% [736 of 930 supervised sessions] in the hybrid CR group vs 61.46% [1201 of 1954 sessions] in the standard CR group). Conclusions and Relevance: The results suggest that a hybrid CR program is noninferior to standard center-based CR in a low-resource setting, primarily in terms of recurrent cardiovascular events and potentially in terms of intermediate outcomes. Hybrid CR may induce superior adherence to supervised exercise. Clinical factors and patient preferences should inform CR model allocation. Trial Registration: ClinicalTrials.gov Identifier: NCT03881150.

Effects of Memantine on the Auditory Steady-State and Harmonic Responses to 40 Hz Stimulation Across Species.

BACKGROUND: Click trains elicit an auditory steady-state response (ASSR) at the driving frequency (1F) and its integer multiple frequencies (2F, 3F, etc.) called harmonics; we call this harmonic response the steady-state harmonic response (SSHR). We describe the 40 Hz ASSR (1F) and 80 Hz SSHR (2F) in humans and rats and their sensitivity to the uncompetitive NMDA antagonist memantine. METHODS: In humans (healthy control participants, n = 25; patients with schizophrenia, n = 28), electroencephalography was recorded after placebo or 20 mg memantine in a within-participant crossover design. ASSR used 1 ms, 85-dB clicks presented in 250 40/s 500-ms trains. In freely moving rats (n = 9), electroencephalography was acquired after memantine (0, 0.3, 1, 3 mg/kg) in a within-participant crossover design; 65-dB click trains used 5-mV monophasic, 1-ms square waves (40/s). RESULTS: Across species, ASSR at 1F generated greater evoked power (EP) than the 2F SSHR. 1F > 2F intertrial coherence (ITC) was also detected in humans, but the opposite relationship (ITC: 2F > 1F) was seen in rats. EP and ITC at 1F were deficient in patients and were enhanced by memantine across species. EP and ITC at 2F were deficient in patients. Measures at 2F were generally insensitive to memantine across species, although in humans the ITC harmonic ratio (1F:2F) was modestly enhanced by memantine, and in rats, both the EP and ITC harmonic ratios were significantly enhanced by memantine. CONCLUSIONS: ASSR and SSHR are robust, nonredundant electroencephalography signals that are suitable for cross-species analyses that reveal potentially meaningful differences across species, diagnoses, and drugs.

Development of Low-Cost IoT System for Monitoring Piezometric Level and Temperature of Groundwater.

Rural communities in Mexico and other countries with limited economic resources require a low-cost measurement system for the piezometric level and temperature of groundwater for their sustainable management, since anthropogenic action (pumping extractions), natural recharge and climate change phenomena affect the behavior of piezometric levels in the aquifer and its sustainability is at risk. Decrease in the piezometric level under a balanced level promotes salt intrusion from ocean water to the aquifer, salinizing and deteriorating the water quality for agriculture and other activities; and a decrease in water level under the pumps or well drilling depth could deprive communities of water. Water temperature monitoring is essential to determine electric conductivity and dissolved salt content in groundwater. Using IoT technology, a device was developed that monitors both variables inside the well, and the ambient temperature and atmospheric pressure outside the well. The measurements are made in real time, with sampling every second and sending data to a dedicated server every 15 min so that the visualization can be accessed through a device with Internet access. The time series of the variables measured inside and outside the well were obtained over a period of three months in the rural community of Agua Blanca, Guasave, Sinaloa, Mexico. Through these records, a progressive temporary drawdown of the piezometric level is observed, as well as the frequency of pumping. This low-cost IoT system shows potential use in hydrological processes of interest such as the separation of regional and local flow, drawdown rates and recognition of geohydrological parameters.

CT-Guided vs. Navigational Bronchoscopic Biopsies for Solitary Pulmonary Nodules: A Single-Institution Retrospective Comparison.

OBJECTIVE: Lung cancer is the second most common cause of death by cancer. Multiple modalities can be used to obtain a tissue sample from a pulmonary nodule. We aimed to compare the yield and adverse events related to transthoracic needle aspiration (TTNA) and Electromagnetic Navigation Biopsy (ENB) at our institution. METHODS: This was a single-center retrospective study in which all patients referred for evaluation of a pulmonary lesion over 5 years (1 January 2013 to 31 December 2018) were identified. Our primary outcome was to compare the accuracy of TTNA to that of ENB in establishing the diagnosis of pulmonary lesions. Secondary outcomes included the evaluation of the adverse events and the sensitivity, specificity, positive, and negative predictive value of each modality. RESULTS: A total of 1006 patients were analyzed. The mean age of patients in the TTNA and the ENB group was 67.2 ± 11.2 years and 68.3 ± 9.2 years respectively. Local anesthesia was predominantly used for TTNA and moderate sedation was more commonly used in the ENB group. We found ENB to have an accuracy of 57.1%, with a sensitivity of 40.0%, a specificity of 100.0%, a positive predictive value of 100.0%, and a negative predictive value of 40.0%. As for the TTNA, the accuracy was 75.9%, with a sensitivity of 77.5%, a specificity of 61.5%, a positive predictive value of 95.0%, and a negative predictive value of 22.5%. The rate of clinically significant complications was higher in the TTNA group (8.2%) as compared to the ENB group (4.7%) with a p-value < 0.001. CONCLUSION: TTNA was superior to ENB-guided biopsy for the diagnostic evaluation of lung nodules. However, the complication rate was much higher in the TTNA group as compared to the ENB group.

A direct interaction between CPF and RNA Pol II links RNA 3' end processing to transcription.

Transcription termination by RNA polymerase II (RNA Pol II) is linked to RNA 3' end processing by the cleavage and polyadenylation factor (CPF or CPSF). CPF contains endonuclease, poly(A) polymerase, and protein phosphatase activities, which cleave and polyadenylate pre-mRNAs and dephosphorylate RNA Pol II to control transcription. Exactly how the RNA 3' end processing machinery is coupled to transcription remains unclear. Here, we combine in vitro reconstitution, structural studies, and genome-wide analyses to show that yeast CPF physically and functionally interacts with RNA Pol II. Surprisingly, CPF-mediated dephosphorylation promotes the formation of an RNA Pol II stalk-to-stalk homodimer in vitro. This dimer is compatible with transcription but not with the binding of transcription elongation factors. Disruption of the dimerization interface in cells causes transcription defects, including altered RNA Pol II abundance on protein-coding genes, tRNA genes, and intergenic regions. We hypothesize that RNA Pol II dimerization may provide a mechanistic basis for the allosteric model of transcription termination.

Nanomechanical Sensing for Mass Flow Control in Nanowire-Based Open Nanofluidic Systems.

Open nanofluidic systems, where liquids flow along the outer surface of nanoscale structures, provide otherwise unfeasible capabilities for extremely miniaturized liquid handling applications. A critical step toward fully functional applications is to obtain quantitative mass flow control. We demonstrate the application of nanomechanical sensing for this purpose by integrating voltage-driven liquid flow along nanowire open channels with mass detection based on flexural resonators. This approach is validated by assembling the nanowires with microcantilever resonators, enabling high-precision control of larger flows, and by using the nanowires as resonators themselves, allowing extremely small liquid volume handling. Both implementations are demonstrated by characterizing voltage-driven flow of ionic liquids along the surface of the nanowires. We find a voltage range where mass flow rate follows a nonlinear monotonic increase, establishing a steady flow regime for which we show mass flow control at rates from below 1 ag/s to above 100 fg/s and precise liquid handling down to the zeptoliter scale. The observed behavior of mass flow rate is consistent with a voltage-induced transition from static wetting to dynamic spreading as the mechanism underlying liquid transport along the nanowires.

Longitudinal study of patients with discrepant results in CLIFT and a solid-phase dsDNA antibody assay: does a gold standard dsDNA assay exist?

OBJECTIVE: Antidouble-stranded DNA (dsDNA) antibodies are essential for diagnosis and follow-up of systemic lupus erythematous (SLE). To ensure the best diagnostic approach, most healthcare laboratories opt for a combination of highly sensitive methods, such as solid-phase immunoassays, and highly specific methods, such as the Crithidia luciliae indirect immunofluorescence test (CLIFT). Even so, discordant results are common, thus hindering the diagnostic process. Therefore, this study aimed to characterise a cohort of patients with discrepant results for a dsDNA fluorescence enzyme immunoassay (FEIA) and CLIFT during 2016-2018 and to follow patients up until December 2021. METHODS: We performed an observational, longitudinal and retrospective study on 417 samples from 257 patients who had been referred for suspected connective tissue diseases or followed up after diagnosis. All of them were positive for antinuclear antibodies (ANAs) using an indirect immunofluorescence assay (IFA) on Hep-2 cells, the entry criterion in our laboratory, and positive for FEIA dsDNA. Samples were then tested with CLIFT according to our routine protocol, which includes CLIFT testing after FEIA dsDNA results ≥10 UI/ml. After the assessment of data quality, the final analysis was based on 222 patients. RESULTS: Eighty-three patients (37.4%) had positive results in both tests and met the diagnostic criteria for SLE. However, 139 patients (62.6%) had discrepant results (FEIA+, CLIFT-). Of these, 58 patients (41.7%) had a diagnosis of SLE, with 47 (33.8%) having been previously diagnosed and under treatment. The remaining 11 patients (7.9%) had a new diagnosis of SLE, which was made up within 4 years of the initial screening. A total of 81 of the 139 patients (57.5%) with discrepant results did not meet lupus criteria during the follow-up period. CONCLUSIONS: The study showed that CLIFT could be negative in both treated and newly diagnosed SLE, thus underlining the importance of follow-up of dsDNA-positive results using solid-phase tests. Therefore, quantitative tests such as FEIA could add value to the diagnosis and management of patients with suspected SLE.