Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease.

Background: Cerebral Cavernous Malformations (CCMs) are neurovascular abnormalities in the central nervous system (CNS) caused by loss of function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3) genes. One of the most common symptoms in CCM patients is associated with motor disability, weakness, seizures, stress, and anxiety, and the extent of the symptom or symptoms may be due to the location of the lesion within the CNS or whether multiple lesions are present. Previous studies have primarily focused on understanding the pathology of CCM using animal models. However, more research has yet to explore the potential impact of CCM lesions on behavioral deficits in animal models, including effects on short-term and long-term memory, motor coordination, and function. Methods: We used the accelerating RotaRod test to assess motor and coordination deficits. We also used the open field test to assess locomotor activity and pathology-related behavior and Pavlovian fear conditioning to assess short-and long-term memory deficits. Our behavioral studies were complemented by proteomics, histology, immunofluorescence, and imaging techniques. We found that neuroinflammation is crucial in behavioral deficits in male and female mice with neurovascular CCM lesions (Slco1c1-iCreERT2; Pdcd10 fl/fl ; Pdcd10 BECKO ). Results: Functional behavior tests in male and female Pdcd10 BECKO mice revealed that CCM lesions cause sudden motor coordination deficits associated with the manifestation of profound neuroinflammatory lesions. Our findings indicate that maturation of CCM lesions in Pdcd10 BECKO mice also experienced a significant change in short- and long-term memory compared to their littermate controls, Pdcd10 fl/fl mice. Proteomic experiments reveal that as CCM lesions mature, there is an increase in pathways associated with inflammation, coagulation, and angiogenesis, and a decrease in pathways associated with learning and plasticity. Therefore, our study shows that Pdcd10 BECKO mice display a wide range of behavioral deficits due to significant lesion formation in their central nervous system and that signaling pathways associated with neuroinflammation and learning impact behavioral outcomes. Conclusions: Our study found that CCM animal models exhibited behavioral impairments such as decreased motor coordination and amnesia. These impairments were associated with the maturation of CCM lesions that displayed a neuroinflammatory pattern.

Genetic variation in UGT1A1 is not associated with altered liver biochemical parameters in healthy volunteers participating in bioequivalence trials.

Introduction: Bioequivalence clinical trials are conducted in healthy volunteers whose blood tests should be within normal limits; individuals with Gilbert syndrome (GS) are excluded from these studies on suspicion of any liver disease, even if the change is clinically insignificant. GS is a benign genetic disorder characterized by elevated bilirubin levels, the primary cause of which is the presence of polymorphisms in UGT1A1 gene. In this work, subjects with UGT1A1 intermediate (IM) or poor (PM) metabolizer genotype-informed phenotypes were investigated to determine whether they have a higher incidence of liver disease or other biochemical parameters. Methods: The study population comprised 773 healthy volunteers who underwent biochemical analysis at baseline and at the end of the study which were genotyped for UGT1A1*80 (rs887829), as an indicator of UGT1A1*80+*28 (rs887829 and rs3064744), and UGT1A1*6 (rs4148323). Results: Bilirubin levels were higher in subjects IMs and PMs compared to normal metabolizers (NMs). Decreased uric acid levels was observed in PMs compared to NMs. No associations were observed in liver enzyme levels according to UGT1A1 phenotype. Discussion: Considering that there is no hepatic toxicity in subjects with UGT1A1 IM or PM phenotype, who are more likely to develop GS, this study suggests that they could be included in bioequivalence clinical trials as their biochemical parameters are not affected outside normal ranges.

Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling.

BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models. METHODS: We used genetic studies, RNA sequencing, spatial transcriptome, micro-computed tomography, fluorescence-activated cell sorting, multiplex immunofluorescence, coculture studies, and imaging techniques to reveal that sustained mild hypoxia via the CX3CR1-CX3CL1 (CX3C motif chemokine receptor 1/chemokine [CX3C motif] ligand 1) signaling pathway influences cell-specific neuroinflammatory interactions, contributing to heterogeneity in CCM severity. RESULTS: Histological and expression profiles of CCM neurovascular lesions (Slco1c1-iCreERT2;Pdcd10fl/fl; Pdcd10BECKO) in male and female mice found that sustained mild hypoxia (12% O2, 7 days) accelerates CCM disease. Our findings indicate that a small reduction in oxygen levels can significantly increase angiogenesis, neuroinflammation, and thrombosis in CCM disease by enhancing the interactions between endothelium, astrocytes, and immune cells. Our study indicates that the interactions between CX3CR1 and CX3CL1 are crucial in the maturation of CCM lesions and propensity to CCM immunothrombosis. In particular, this pathway regulates the recruitment and activation of microglia and other immune cells in CCM lesions, which leads to lesion growth and thrombosis. We found that human CX3CR1 variants are linked to lower lesion burden in familial CCMs, proving it is a genetic modifier in human disease and a potential marker for aggressiveness. Moreover, monoclonal blocking antibody against CX3CL1 or reducing 1 copy of the Cx3cr1 gene significantly reduces hypoxia-induced CCM immunothrombosis. CONCLUSIONS: Our study reveals that interactions between CX3CR1 and CX3CL1 can modify CCM neuropathology when lesions are accelerated by environmental hypoxia. Moreover, a hypoxic environment or hypoxia signaling caused by CCM disease influences the balance between neuroinflammation and neuroprotection mediated by CX3CR1-CX3CL1 signaling. These results establish CX3CR1 as a genetic marker for patient stratification and a potential predictor of CCM aggressiveness.

Real-time EEG-based emotion recognition for neurohumanities: perspectives from principal component analysis and tree-based algorithms.

Within the field of Humanities, there is a recognized need for educational innovation, as there are currently no reported tools available that enable individuals to interact with their environment to create an enhanced learning experience in the humanities (e.g., immersive spaces). This project proposes a solution to address this gap by integrating technology and promoting the development of teaching methodologies in the humanities, specifically by incorporating emotional monitoring during the learning process of humanistic context inside an immersive space. In order to achieve this goal, a real-time emotion recognition EEG-based system was developed to interpret and classify specific emotions. These emotions aligned with the early proposal by Descartes (Passions), including admiration, love, hate, desire, joy, and sadness. This system aims to integrate emotional data into the Neurohumanities Lab interactive platform, creating a comprehensive and immersive learning environment. This work developed a ML, real-time emotion recognition model that provided Valence, Arousal, and Dominance (VAD) estimations every 5 seconds. Using PCA, PSD, RF, and Extra-Trees, the best 8 channels and their respective best band powers were extracted; furthermore, multiple models were evaluated using shift-based data division and cross-validations. After assessing their performance, Extra-Trees achieved a general accuracy of 94%, higher than the reported in the literature (88% accuracy). The proposed model provided real-time predictions of VAD variables and was adapted to classify Descartes' six main passions. However, with the VAD values obtained, more than 15 emotions can be classified (reported in the VAD emotion mapping) and extend the range of this application.

A collaborative approach to develop indicators for quality of care for ST segment Elevation Myocardial Infarction in networks without coronary intervention: A position paper.

BACKGROUND: Data about performance measures (PM) in patients with ST segment Elevation Myocardial Infarction (STEMI) in low- and middle-income countries is really scarce. One of the reasons is the lack of appropriate measures for these scenarios where coronary intervention is not the standard treatment. OBJECTIVE: This study aimed to develop a set of PM and quality markers for patients with STEMI in these countries. METHODS: Two investigators systematically reviewed existing guidelines and scientific literature to identify potential PM by referring to documents searched through PubMed from 2010 through 2019, using terms "Myocardial Infarction", "STEMI", "quality indicator", and "performance measure". A modified Delphi technique, involving multidisciplinary panel interview, was used. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 5 (highest) during three rounds. All indicators that received a median score ≥4.5, in final round without significant disagreement were included as PM. RESULTS: Through the consensus-building process, 84 potential indicators were found, of which 10 were proposed as performance measures and 2 as quality metrics, as follows: Pre-Hospital Electrocardiogram; Patients with reperfusion therapy; Pre-hospital Reperfusion; Ischemic time less than 120 minutes; System delay time less than 90 minutes; In-hospital Mortality; Complete in-hospital Treatment; Complete in-hospital Treatment in patients with Heart Failure; 30 day-Re-admissions; 30 day-mortality; Patients with in-hospital stress test performed; and, Patients included in rehabilitation programs. CONCLUSION: This document provides the official set of PM of attention in ST segment Elevation Myocardial Infarction of the Cuban Society of Cardiology and Cuban National Group of Cardiology.

Variables de condición física predictivas de sintomatología depresiva en estudiantes universitarios de Cali, Colombia

Objetivo: Determinar las variables de condición física saludable predictoras de sintomatología depresiva en jóvenes universitarios. Método: Este estudio presenta un diseño observacional descriptivo de corte transversal con una fase multivariada, que utilizó el cuestionario autoadministrado BECK (BDI-2) con el objetivo de determinar sintomatología depresiva, en una muestra de 344 estudiantes universitarios entre 18 y 39 años, matriculados en cuatro diferentes universidades de la ciudad de Santiago de Cali, Colombia. La condición física relacionada con la salud se valoró a partir de la batería Alpha Fit Adultos; con los análisis correlacionales se construyó un modelo de regresión logística binario que pudiera establecer cuáles variables de condición física se asocian a una sintomatología depresiva en este tipo de población. Resultados: Correlaciones inversas y estadísticamente significativas fueron observadas entre el puntaje de depresión del inventario de Depresión de Beck-II, con los indicadores de condición física aeróbica r = -0,202, p=0,000; fuerza prensil media r =-0,113, p=0,036; salto alto r =-0,177, p=0,000; flexión de brazos r =-0,158, p=0,003; y test de figura en 8 r =-0,146, p=0,006). Universitarios con mayores niveles de sintomatología depresiva presentan un fenotipo de menor condición física, principalmente en el indicador de resistencia cardiorrespiratoria (ß=-0,059; p<0,004 Exp (B) 0,942). Conclusiones: Los resultados obtenidos en el presente estudio muestran que un fenotipo asociado a menor condición física cardiorrespiratoria se asocia con mayores niveles de sintomatología depresiva.

Objective: To determine healthy physical condition variables predictive of depressive symptomatology in young university students. Method: This study presents a cross-sectional descriptive observational design with a multivariate phase, which used the self-administered BECK questionnaire (BDI-2) to assess depressive symptomatology in a sample of 344 university students between 18 and 39 years of age, enrolled in four different universities in the city of Santiago de Cali, Colombia. Health-related physical fitness was assessed from the Alpha Fit Adult battery; with the correlational analyses, a binary logistic regression model was constructed to determine which physical fitness variables are associated with depressive symptomatology in this type of population. Results: Inverse and statistically significant correlations were observed between the Beck Depression Inventory-II depression score with aerobic fitness indicator r =0,202, p=0,000; mean prehensile strength r =0,113, p=0,036; high jump r =0,177, p=0,000; push-up r =0,158, p=0,003; and figure-8 test r =0,146, p=0,006). University students with higher levels of depressive symptomatology presented a lower physical fitness phenotype, mainly in the cardiorespiratory endurance indicator (ß=-0,059; p<0,004 Exp (B) 0,942). Conclusion: The results obtained in the present study show that a phenotype associated with lower cardiorespiratory fitness is associated with higher levels of depressive symptomatology.

Review of an international pilot project to adapt the Canadian Adult Obesity Clinical Practice Guideline.

Background: The evidence-based Canadian Adult Obesity Clinical Practice Guideline (CPG) released in August 2020 were developed through a systematic literature review and patient-oriented research process. This CPG is considered a paradigm shift for obesity care as it introduced a new obesity definition that is based on health not body size, incorporates lived experiences of people affected by obesity, and addresses the pervasive weight bias and stigma that patients face in healthcare systems. The purpose of this pilot project was to assess the feasibility of adapting the Canadian CPG in Chile and Ireland. Methods: An International Clinical Practice Guideline Adaptation Committee was established to oversee the project. The project was conducted through four interrelated phases: 1) planning and preparation; 2) pilot project application process; 3) adaptation; and 4) launch, dissemination, and implementation. Ireland used the GRADE-ADAPTE framework and Chile used the GRADE-ADOLOPMENT approach. Results: Chile and Ireland developed their adapted guidelines in one third of the time it took to develop the Canadian guidelines. In Ireland, 18 chapters, which underpin the 80 key recommendations, were contextually adapted. Chile adopted 18 chapters and 76 recommendations, adapted one recommendation, and developed 12 new recommendations.. Conclusion: The pilot project demonstrated it is feasible to adapt the Canadian CPG for use in other countries with different healthcare systems, languages, and cultural contexts, while retaining the Canadian CPG's key principles and values such as the treatment of obesity as a chronic disease, adoption of new clinical assessment approaches that go beyond anthropometric measurements, elimination of weight bias and stigma, shifting obesity care outcomes to improved health and well-being rather than weight loss alone, and the use of patient-centred, collaborative and shared-decision clinical care approaches.

Impact of Sex and Genetic Variation in Relevant Pharmacogenes on the Pharmacokinetics and Safety of Valsartan, Olmesartan and Hydrochlorothiazide.

Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters' genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, ß = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, ß = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.

Characteristics and outcomes of multisystem inflammatory syndrome in children: A multicenter, retrospective, observational cohort study in Mexico.

Introduction: Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. Methods: This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis (LCA) to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. Results: The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysms were found in 5.7% and 13.2% of the patients in whom coronary artery diameter was measured, respectively. Any cause in-hospital mortality was 5.4%. Hospitalization after ten days of symptoms was associated with coronary artery abnormalities (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0). Age ≥10 years (OR: 5.6, 95% CI: 1.4-2.04), severe underlying condition (OR: 9.3, 95% CI: 2.8-31.0), platelet count <150,000 /mm3 (OR: 4.2, 95% CI: 1.2-14.7), international normalized ratio >1.2 (OR: 3.8, 95% CI: 1.05-13.9), and serum ferritin concentration >1,500 mg/dl at admission (OR: 52, 95% CI: 5.9-463) were risk factors for death. Discussion: Mortality in patients with MIS-C was higher than reported in other series, probably because of a high rate of cases with serious underlying diseases.

A Glimpse into the Past: What Ancient Viral Genomes Reveal About Human History.

Humans have battled viruses for millennia. However, directly linking the symptomatology of disease outbreaks to specific viral pathogens was not possible until the twentieth century. With the advent of the genomic era and the development of advanced protocols for isolation, sequencing, and analysis of ancient nucleic acids from diverse human remains, the identification and characterization of ancient viruses became feasible. Recent studies have provided invaluable information about past epidemics and made it possible to examine assumptions and inferences on the origin and evolution of certain viral families. In parallel, the study of ancient viruses also uncovered their importance in the evolution of the human lineage and their key roles in shaping major events in human history. In this review, we describe the strategies used for the study of ancient viruses, along with their limitations, and provide a detailed account of what past viral infections have revealed about human history.

Ceftriaxone-Loaded Polymeric Microneedles, Dressings, and Microfibers for Wound Treatment.

The objective of this study was to create polymeric dressings, microfibers, and microneedles (MN) loaded with ceftriaxone, using PMVA (Poly (Methyl vinyl ether-alt-maleic acid), Kollicoat® 100P, and Kollicoat® Protect as polymers to treat diabetic wounds and accelerate their recovery. These formulations were optimized through a series of experiments and were subsequently subjected to physicochemical tests. The results of the characterization of the dressings, microfibers, and microneedles (PMVA and 100P) were, respectively, a bioadhesion of 281.34, 720, 720, 2487, and 510.5 gf; a post-humectation bioadhesion of 186.34, 831.5, 2380, and 630.5 gf, tear strength of 2200, 1233, 1562, and 385 gf, erythema of 358, 8.4, 227, and 188; transepidermal water loss (TEWL) of 2.6, 4.7, 1.9, and 5.2 g/h·m2; hydration of 76.1, 89.9, 73.5, and 83.5%; pH of 4.85, 5.40, 5.85, and 4.85; and drug release (Peppas kinetics release) of n: 0.53, n: 0.62, n: 0.62, and n: 0.66). In vitro studies were performed on Franz-type diffusion cells and indicated flux of 57.1, 145.4, 718.7, and 2.7 µg/cm2; permeation coefficient (Kp) of 13.2, 19.56, 42, and 0.00015 cm2/h; and time lag (tL) of 6.29, 17.61, 27. 49, and 22.3 h, respectively, in wounded skin. There was no passage of ceftriaxone from dressings and microfibers to healthy skin, but that was not the case for PMVA/100P and Kollicoat® 100P microneedles, which exhibited flux of 194 and 0.4 µg/cm2, Kp of 11.3 and 0.00002 cm2/h, and tL of 5.2 and 9.7 h, respectively. The healing time of the formulations in vivo (tests carried out using diabetic Wistar rats) was under 14 days. In summary, polymeric dressings, microfibers, and microneedles loaded with ceftriaxone were developed. These formulations have the potential to address the challenges associated with chronic wounds, such as diabetic foot, improving the outcomes.

Neurofibromatosis tipo 1 o enfermedad de Von Recklinghausen. Presentación de caso

La neurofibromatosis tipo I o enfermedad de Von Recklinghausen es una de las enfermedades genéticas que afectan el sistema nervioso, denominada así por su origen común embrionario. Es una enfermedad autosómica dominante, progresiva, de evolución impredecible, que afecta la piel y el sistema nervioso central y periférico. Se presenta el caso de una escolar, femenina, de siete años de edad que ingresó en el Hospital Pediátrico Paquito Gonzáles Cueto debido a la presencia de varias manchas en la piel color "café con leche". Se recogió como antecedente familiar la presencia de neurofibromatosis tipo 1 en la abuela y bisabuela materna, esta última ya fallecida por dicha causa. Al examen físico se constataron nódulos de Lisch en espesor del iris del ojo izquierdo. Los estudios de imágenes evidenciaron varias lesiones nodulares hiperintensas en T2 y FLAIR, a nivel de la cápsula interna y externa bilateral y ventricular izquierda, la mayor de 20 x 11 mm, así como imagen hipointensa a nivel del nervio óptico izquierdo, de 7 mm. Se diagnosticó como neurofibromatosis tipo I. Por ser una de las enfermedades menos estudiadas en nuestro medio se decidió la publicación de este caso.

Neurofibromatosis type I or Von Recklinghausen's disease is one of the genetic diseases that affect the nervous system, named for its common embryonic origin. It is an autosomal dominant, progressive disease with an unpredictable course that affects the skin and the central and peripheral nervous system. The case of a seven-year-old female schoolchild who was admitted to the Paquito Gonzáles Cueto Pediatric Hospital due to the presence of several "coffee-with-milk" spots on her skin is presented. The presence of type 1 neurofibromatosis in her maternal grandmother and great-grandmother, the latter already deceased from said cause, was collected as a family history. On physical examination, Lisch nodules were found in the thickness of the iris of the left eye. Imaging studies revealed several hyperintense nodular lesions on T2 and FLAIR, at the level of the internal and external bilateral and left ventricular capsule, the largest measuring 20 x 11 mm, as well as a hypointense image at the level of the left optic nerve, measuring 7 mm. It was diagnosed as neurofibromatosis type I. Because it is one of the least studied diseases in our environment, it was decided to publish this case.

Performance Measures in STEMI after COVID-19 Pandemic: Results from the RECUIMA Registry

Abstract Background To offer proper medical care to patients with ST-segment Elevation Acute Myocardial Infarction (STEMI) in low- and middle-income settings (LMIS) is challenging. However, it is not known if performance indicators have changed back after the epidemiological recovery. Objective to describe performance measures (PM) in patients with STEMI during and after the COVID-19 pandemic. Methods Observational study of patients with STEMI, from an LMIS, with analysis of PM suggested in the 2017 AHA-ACC Performance Measures for Adults with STEMI. COVID-19 period was determined from January 2020 to October 2021, and from November 2021 to February 2022 as the post-COVID-19 period. Baseline characteristics, treatments and selected PM were compared using the χ2 test or Mann-Whitney U test. All tests were two-sided, and statistical significance was considered as p-value <0.05. Coronary interventionism-related PM were not reported. Results Administration of thrombolysis decreased (71.2% vs 51.6% (p: 0.001)), while the delay time for its administration (Median (Interquartile Range)) increased considerably (30 min (16-60) to 45 min (35- 60) (p: 0.003)). Aspirin at admission was administered in each period at 92.9% vs 94.2% (p: 0.62); and at discharge to 97.8% vs 98.9% (p: 0.48). Beta-blockers, P2Y12 inhibitors, statins, and angiotensin-converting enzyme inhibitors in patients with heart failure were administered to 67.1% vs 85.1% (p: 0.01), 96.4% vs 84% (p: 0.001), 96.2 % vs 95.7% (p: 1), and 81.2% vs 94.3% (p: 0.14), respectively. Conclusion Despite this being a current period of epidemiological recovery, the COVID-19 pandemic continues to negatively impact the care of patients with STEMI.

Ozone Efficacy for the Disinfection of Ambulances Used to Transport Patients during the COVID-19 Pandemic in Peru.

We assessed the disinfection efficacy of an ozone generator prototype in ambulances used to transport patients with coronavirus disease (COVID-19). This research consisted of three stages: in vitro tests using microbial indicators, such as Candida albicans, Escherichia coli, Staphylococcus aureus and Salmonella phage, which were experimentally inoculated onto polystyrene crystal surfaces within a 23 m3 enclosure. They were then exposed to ozone at a 25 ppm concentration using the ozone generator (Tecnofood SAC) portable prototype, and the decimal reduction time (D) was estimated for each indicator. The second stage involved the experimental inoculation of the same microbial indicators on a variety of surfaces inside conventional ambulances. The third stage consisted of exploratory field testing in ambulances used to transport patients with suspected COVID-19. During the second and third stages, samples were collected by swabbing different surfaces before and after 25 ppm ozonisation for 30 min. Results suggested that ozone was most effective on Candida albicans (D = 2.65 min), followed by Escherichia coli (D = 3.14 min), Salmonella phage (D = 5.01 min) and Staphylococcus aureus (D = 5.40 min). Up to 5% of the microbes survived following ozonisation of conventional ambulances. Of the 126 surface samples collected from ambulances transporting patients with COVID-19, 7 were positive (5.6%) for SARS-related coronavirus as determined on reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Ozone exposure from the ozone generator prototype inside ambulances at a concentration of 25 ppm for 30 min can eliminate gram positive and negative bacteria, yeasts, and viruses.

[Ethiology, risk factors and Whole blood viscosity index in thromboembolic venous disease]. / Etiología, factores de riesgo e Índice de viscosidad sanguíneo total en enfermedad tromboembólica venosa.

Backround: Venous thromboembolic disease (VTED) is a frequent cause of hospitalization and mortality. Whole blood viscosity (WBV) participates in the pathogenesis of thrombosis. Objective: To identify the most frequent etiologies and their association with WBV index (WBVI) in hospitalized patients with VTED. Material and methods: Observational, cross-sectional, retrospective, analytical study, Group 1: cases (patients diagnosed with VTED) and Group 2: controls without thrombosis. Risk factors for VTED were described and WBVI was calculated from total proteins and hematocrit. Descriptive and inferential statistics were used with Chi-squared test, Fisher's exact test, Mann Whitney U test, bivariate and multivariate logistic regression analysis. Results: We included 146 patients and 148 controls, age 46.3 ±17.7 vs. 58 ± 18.2 years, of both sexes (female, 65.1%). The most frequent etiology was neoplastic (23.3%), followed by diseases with cardiovascular risk (17.8%). Independent risk factors for VTED were age, chronic kidney disease, presence of liver disease or solid neoplasia. WBVI was similar in patients with VTED as in those without thrombosis. We found an association of the presence of deep vein thrombosis and diseases with cardiovascular risk (p = 0.040). Conclusions: The presence of chronic kidney disease, liver disease, and solid neoplasia are independent risk factors for VTED. The WBVI is a simple and rapid diagnostic tool in the evaluation of patients with VTED.

Introducción: la enfermedad tromboembólica venosa (ETEV) es causa frecuente de hospitalización y mortalidad. La viscosidad sanguínea participa en la patogénesis de la trombosis. Objetivo: analizar los factores de riesgo y el índice de viscosidad sanguíneo total (IVTS) en pacientes con ETEV. Material y métodos: estudio observacional, transversal, retrospectivo, analítico. Grupo 1: casos (pacientes con diagnóstico de ETEV), y grupo 2: controles sin trombosis. Se describieron los factores de riesgo para ETEV y se calculó el IVTS a partir de proteínas totales y hematocrito. Se utilizó estadística descriptiva e inferencial con prueba de Chi cuadrada, prueba exacta de Fisher, U de Mann Whitney, análisis de regresión logística bivariado y multivariado. Resultados: incluimos 146 pacientes y 148 controles, edad 46.3 ± 17.7 frente a 58 ± 18.2 años, de ambos sexos, femenino (65.1%). La etiología más frecuente fue la neoplásica (23.3%), seguida de la enfermedad con riesgo cardiovascular (17.8%). Los factores de riesgo independientes para ETEV fueron: edad, enfermedad renal crónica, presencia de hepatopatía o neoplasia sólida. El IVTS fue similar en los pacientes con ETEV que en aquellos sin trombosis. Se encontró asociación de la presencia de trombosis venosa profunda y enfermedades con riesgo cardiovascular (p = 0.040). Conclusiones: la presencia de ERC, hepatopatía y neoplasia sólida son factores de riesgo independientes para ETEV. El IVTS es un instrumento diagnóstico sencillo y rápido en la evaluación de los pacientes con ETEV.

Definitions and factors associated with emergency physician productivity: a scoping review.

PURPOSE: There currently exists no standard productivity measure for emergency physicians. The objectives of this scoping review were to synthesize the literature to identify components of definitions and measurements of emergency physician productivity and to evaluate factors associated with productivity. METHODS: We searched Medline, Embase, CINAHL, and ProQuest One Business from inception to May 2022. We included all studies that reported on emergency physician productivity. We excluded studies that only reported departmental productivity, studies with non-emergency providers, review articles, case reports, and editorials. Data were extracted into predefined worksheets and a descriptive summary was presented. Quality analysis was performed with Newcastle-Ottawa Scale. RESULTS: After screening 5521 studies, 44 studies met full inclusion criteria. Components of the definition for emergency physician productivity included: number of patients managed, revenue generated, patient processing time, and a standardization factor. Most studies measured productivity using patients per hour, relative value units per hour, and provider-to-disposition time. The most studied factors influencing productivity included scribes, resident learners, electronic medical record implementation, and faculty teaching scores. CONCLUSION: Emergency physician productivity is heterogeneously defined, but includes common elements such as patient volume, complexity, and processing time. Commonly reported productivity metrics include patients per hour and relative value units that incorporate patient volume and complexity, respectively. The findings of this scoping review can guide ED physicians and administrators to measure the impact of QI initiatives, promote efficient patient care, and optimize physician staffing.

RéSUMé: OBJECTIF: Il n'existe actuellement aucune mesure de productivité standard pour les médecins urgentistes. L'objectif de cet examen de la portée était de synthétiser la littérature afin d'identifier les composantes des définitions et des mesures de la productivité des médecins urgentistes et d'évaluer les facteurs associés à la productivité. MéTHODES: Nous avons effectué des recherches dans Medline, Embase, CINAHL et ProQuest One Business depuis le début jusqu'à mai 2022. Nous avons inclus toutes les études portant sur la productivité des médecins urgentistes. Nous avons exclu les études qui ne faisaient état que de la productivité du service, les études portant sur des prestataires de soins non urgents, les articles de synthèse, les rapports de cas et les éditoriaux. Les données ont été extraites dans des feuilles de travail prédéfinies et un résumé descriptif a été présenté. L'analyse de la qualité a été réalisée à l'aide de l'échelle de Newcastle-Ottawa. RéSULTATS: Après la sélection de 5521 études, 44 études répondaient à tous les critères d'inclusion. Les éléments de la définition de la productivité des médecins urgentistes comprenaient : le nombre de patients pris en charge, les revenus générés, le temps de traitement des patients et un facteur de normalisation. La plupart des études ont mesuré la productivité en utilisant le nombre de patients par heure, les unités de valeur relative par heure et le temps de prise en charge par le prestataire. Les facteurs influençant la productivité les plus étudiés comprenaient les scribes, les apprenants résidents, la mise en œuvre du dossier médical électronique et les scores d'enseignement de la faculté. CONCLUSION: La productivité des médecins urgentistes est définie de manière hétérogène mais comprend des éléments communs tels que le volume de patients, la complexité et le temps de traitement. Les indicateurs de productivité couramment utilisés sont le nombre de patients par heure et les unités de valeur relative qui intègrent respectivement le volume et la complexité des patients. Les résultats de cette étude de la portée peuvent aider les médecins et les administrateurs des urgences à mesurer l'impact des initiatives d'amélioration de la qualité, à promouvoir l'efficacité des soins aux patients et à optimiser la dotation en personnel médical.

Genetic Variation in CYP2D6 and SLC22A1 Affects Amlodipine Pharmacokinetics and Safety.

Amlodipine is an antihypertensive drug with unknown pharmacogenetic biomarkers. This research is a candidate gene study that looked for associations between amlodipine pharmacokinetics and safety and pharmacogenes. Pharmacokinetic and safety data were taken from 160 volunteers from eight bioequivalence trials. In the exploratory step, 70 volunteers were genotyped for 44 polymorphisms in different pharmacogenes. CYP2D6 poor metabolizers (PMs) showed higher half-life (t1/2) (univariate p-value (puv) = 0.039, multivariate p-value (pmv) = 0.013, ß = -5.31, R2 = 0.176) compared to ultrarapid (UMs), normal (NMs) and intermediate metabolizers (IMs). SLC22A1 rs34059508 G/A genotype was associated with higher dose/weight-corrected area under the curve (AUC72/DW) (puv = 0.025; pmv = 0.026, ß = 578.90, R2 = 0.060) compared to the G/G genotype. In the confirmatory step, the cohort was increased to 160 volunteers, who were genotyped for CYP2D6, SLC22A1 and CYP3A4. In addition to the previous associations, CYP2D6 UMs showed a lower AUC72/DW (puv = 0.046, pmv = 0.049, ß = -68.80, R2 = 0.073) compared to NMs, IMs and PMs and the SLC22A1 rs34059508 G/A genotype was associated with thoracic pain (puv = 0.038) and dizziness (puv = 0.038, pmv = 0.014, log OR = 10.975). To our knowledge, this is the first work to report a strong relationship between amlodipine and CYP2D6 and SLC22A1. Further research is needed to gather more evidence before its application in clinical practice.

The Psychological Science Accelerator's COVID-19 rapid-response dataset.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.