Search

Krister Lindmark,1 Kurt Boman,2 Mona Olofsson,2 Michael Törnblom,3 Aaron Levine,3 Anna Castelo-Branco,3 Raymond Schlienger,4 Sara Bruce Wirta,5 Jan Stålhammar,6 Gerhard Wikström7 1Department of Public Health and Clinical Medicine and Heart Centre, Umeå University Hospital, Umeå, Sweden; 2Research Unit, Medicine-Geriatric, Skellefteå County Hospital, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 3Real-World & Analytics Solutions, IQVIA, Solna, Sweden; 4Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland; 5Global RWE Cardio-Metabolics, Novartis Sweden AB, Stockholm, Sweden; 6Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 7Department for Medical Sciences, Uppsala University, Uppsala, Sweden Purpose: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden.Methods: Adults with incident HF (≥2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005–2013) and electronic medical records (cohort 2, 2010–2015; primary/secondary care patients from Uppsala and Västerbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed.Results: Baseline demographic and clinical characteristics were similar for cohort 1 (N=174,537) and 2 (N=8,702), with mean ages of 77.4 and 76.6 years, respectively; almost 30% of patients were aged ≥85 years. From 2010 to 2014, age-adjusted annual incidence rate of HF/1,000 inhabitants decreased (from 3.20 to 2.91, cohort 1; from 4.34 to 3.33, cohort 2), while age-adjusted prevalence increased (from 1.61% to 1.72% and from 2.15% to 2.18%, respectively). Age-adjusted 1-year all-cause and CVD-related mortality was higher in men than in women among patients in cohort 1 (all-cause mortality hazard ratio [HR] men vs women 1.07 [95% CI 1.06–1.09] and CVD-related mortality subdistribution HR for men vs women 1.04 [95% CI 1.02–1.07], respectively). While 83.5% of patients underwent N-terminal pro-B-type natriuretic peptide testing, only 36.4% of patients had an echocardiogram at the time of diagnosis, although this increased overtime. In the national prevalent HF population (patients with a diagnosis in 1997–2004 who survived into the analysis period; N=273,999), death from ischemic heart disease and myocardial infarction declined between 2005 and 2013, while death from HF and atrial fibrillation/flutter increased (P

Abstract Objective Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/− mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/− mice have altered seizure susceptibility at light and dark phases. Methods We assessed seizure susceptibility and progression in a Tsc2+/− mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non‐active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. Results We found increased seizure susceptibility in Tsc2+/− mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/− males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/− females were more susceptible during the dark and post‐ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. Significance The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC‐related epilepsy research. Plain Language Summary Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

Abstract Background The recent rise in the transmission of mosquito-borne diseases such as dengue virus (DENV), Zika (ZIKV), chikungunya (CHIKV), Oropouche (OROV), and West Nile (WNV) is a major concern for public health managers worldwide. Emerging technologies for automated remote mosquito classification can be supplemented to improve surveillance systems and provide valuable information regarding mosquito vector catches in real time. Methods We coupled an optical sensor to the entrance of a standard mosquito suction trap (BG-Mosquitaire) to record 9151 insect flights in two Brazilian cities: Rio de Janeiro and Brasilia. The traps and sensors remained in the field for approximately 1 year. A total of 1383 mosquito flights were recorded from the target species: Aedes aegypti and Culex quinquefasciatus. Mosquito classification was based on previous models developed and trained using European populations of Aedes albopictus and Culex pipiens. Results The VECTRACK sensor was able to discriminate the target mosquitoes (Aedes and Culex genera) from non-target insects with an accuracy of 99.8%. Considering only mosquito vectors, the classification between Aedes and Culex achieved an accuracy of 93.7%. The sex classification worked better for Cx. quinquefasciatus (accuracy: 95%; specificity: 95.3%) than for Ae. aegypti (accuracy: 92.1%; specificity: 88.4%). Conclusions The data reported herein show high accuracy, sensitivity, specificity and precision of an automated optical sensor in classifying target mosquito species, genus and sex. Similar results were obtained in two different Brazilian cities, suggesting high reliability of our findings. Surprisingly, the model developed for European populations of Ae. albopictus worked well for Brazilian Ae. aegypti populations, and the model developed and trained for Cx. pipiens was able to classify Brazilian Cx. quinquefasciatus populations. Our findings suggest this optical sensor can be integrated into mosquito surveillance methods and generate accurate automatic real-time monitoring of medically relevant mosquito species. Graphical Abstract

Stroke is the second leading cause of death and disability in Latin America; however, few epidemiological studies have been conducted in South America. An observational study was conducted to analyze trends in stroke mortality in South American (SA) countries. Age-standardized mortality rates and proportional mortality due to stroke in the populations of SA countries between 1990 and 2019 were assessed by extracting data from the Global Burden of Disease 2019 study. Joinpoint regression models were employed to identify trends in the annual percentage change in mortality rates for each segment. Considering the data collected over the 30 years that were studied, the age-standardized stroke mortality trend decreased in Argentina (−1.6%), Uruguay (−0.6%), Brazil (−0.5%), Guyana (−0.5%), and Bolivia (−0.4%), while Venezuela (+1.6%) and Suriname (+1.0%) showed an increasing trend. The proportional stroke mortality trend decreased in Argentina (−1.7%), Paraguay (−0.9%), Uruguay (−0.7%), Guyana (−0.7%), Brazil (−0.5%), and Chile (−0.5%), whereas Bolivia (+1.0%), Suriname (+0.6%), and Peru (+0.4%) exhibited an increasing trend. The trends in stroke mortality between 1990 and 2019 demonstrated considerable variability. While most SA countries experienced significant decreases in stroke mortality trends, Venezuela and Suriname showed increases in age-standardized mortality rates, and Bolivia, Suriname, and Peru exhibited increases in proportional mortality rates. No decreasing stroke mortality trend was observed in the segment after the last joinpoint, highlighting the need for improvement in prevention and treatment.

Abstract Background Knowing the prevalence of myopia at school age is essential to implement preventive measures and appropriate interventions, ensure access to vision care, promote a healthier educational environment and improve academic performance. The purpose of this study was to determine the prevalence of myopia and its associated sociodemographic risk factors, as well as to estimate the coverage of myopia correction among adolescents in center of Portugal. Methods This cross-sectional study evaluated 1115 adolescents from the 5th to the 9th year of school, with an average of 12.9 years (SD = 1.5) ranging from 10.0 to 18.0 years. Optometric evaluations were carried out in a school environment and consisted of the evaluation of distance visual acuity, assessed using a logarithmic visual acuity chart (ETDRS charts 1 and 2) at 4 m, and measured by refractive error with a pediatric autorefractometer (Plusoptix), by non-cycloplegic. Myopia was defined as spherical equivalent (SE ≤ -0.50 diopter (D)) and uncorrected visual acuity (UVA ≤ 95VAR). Adjusted logistic regression analysis was applied to investigate risk factors. Results We found a myopia rate of 21.5% and a high myopia rate of 1.4%. Higher school level and attendance at urban schools were associated with myopia, but no association was found with age or sex. Only 34.6% of myopic adolescents use the best optical correction and 26.4% do not use any type of optical correction. Conclusions Data on the prevalence of refractive problems in Portugal are scarce and heterogeneous. This study, although regional, provides a valuable contribution with a clear and reproducible methodology, following international guidelines and filling gaps in the existing literature. The results show that the rate of myopia in this age group is similar to reports from other European studies. The high rate of adolescents with uncorrected or under-corrected myopia in Portugal is a problem that deserves attention.

Abstract To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

The disparity between the sexes in stroke mortality has been demonstrated in people from different locations. The objective of this study was to analyze the disparity between sexes in stroke mortality in adults in the metropolitan area of Greater Vitoria between 2000 and 2021. Ecological time series design was conducted with a database of the Brazilian Health System Informatics Department. The annual percentage change and average annual percentage change were calculated through joinpoint regression. Pairwise comparisons using parallelism and coincidence tests were applied to compare temporal trends between men and women. Men had higher mortality rates in most years between 2000 and 2021. In contrast, women had higher proportional mortality values in all years evaluated from 2000 to 2021. The paired comparison revealed a disparity between the sexes in the proportional mortality time series (parallelism test: p = 0.003; coincidence test: p < 0.001). However, the time series of the mortality rates showed no disparity between the sexes (parallelism test: p = 0.114; coincidence test: p = 0.093). From 2000 to 2021, there was a disparity in proportional mortality from stroke between the sexes of the population in the metropolitan area of Greater Vitoria, Brazil. However, the time series of mortality rates between the sexes did not reveal any disparity in the study period.

Abstract Comprehending digital content written in natural language online is vital for many aspects of life, including learning, professional tasks, and decision-making. However, facing comprehension difficulties can have negative consequences for learning outcomes, critical thinking skills, decision-making, error rate, and productivity. This paper introduces an innovative approach to predict comprehension difficulties at the local content level (e.g., paragraphs). Using affordable wearable devices, we acquire physiological responses non-intrusively from the autonomous nervous system, specifically pulse rate variability, and electrodermal activity. Additionally, we integrate data from a cost-effective eye-tracker. Our machine learning algorithms identify ’hotspots’ within the content and regions corresponding to a high cognitive load. These hotspots represent real-time predictors of comprehension difficulties. By integrating physiological data with contextual information (such as the levels of experience of individuals), our approach achieves an accuracy of 72.11% ± 2.21, a precision of 0.77, a recall of 0.70, and an f1 score of 0.73. This study opens possibilities for developing intelligent, cognitive-aware interfaces. Such interfaces can provide immediate contextual support, mitigating comprehension challenges within content. Whether through translation, content generation, or content summarization using available Large Language Models, this approach has the potential to enhance language comprehension.

Abstract When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.

Urinary tract infections are defined as the presence of microorganisms in any part of the urinary system, with the exception of the distal urethra. A majority of them are uncomplicated infections that are resolved on an outpatient basis, with empirical therapy. The objectives of this work were to study the sociodemographic characteristics of patients, analyze associated strains and examine the response of the main microorganisms to antibiotics. A retrospective observational study of all positive urine cultures between 2018 and 2022 was carried out at an institution (8340 samples). Sociodemographic data were also collected. In total, 61.3% were women, with an average age of 63.4 years, and 43.2% were from the Emergency Department. A total of 13.5% were fitted, 56% of whom were women. Also, 95.9% were not taking any antibiotics, and among the individuals who were taking antibiotics, 50% were injected. Escherichia coli (53.5%) and Klebsiella pneumoniae (13.8%) are identified as the most prevalent strains. In the time periods analyzed, Escherichia coli decreased its resistance to 11 antibiotics and increased to 5 antibiotics, while Klebsiella pneumoniae decreased to 7 and increased to 7, with emphasis on the presence of 3 antibiotics with a resistance rate of 100% to all Klebsiella pneumoniae strains identified in 2022.

BackgroundFirefighters face stressful life-threatening events requiring fast decision-making. To better prepare for those situations, training is paramount, but errors in real-life training can be harmful. Virtual reality (VR) simulations provide the desired realism while enabling practice in a secure and controlled environment. Firefighters’ affective states are also crucial as they are a higher-risk group. ObjectiveTo assess the impact on affective states of 2 simulated immersive experiences in a sample of healthy firefighters (before, during, and after the simulation), we pursued a multivariate approach comprising cognitive performance, situational awareness, depression, anxiety, stress, number of previous adverse events experienced, posttraumatic stress disorder (PTSD) severity, and emotions. The efficacy and ecological validity of an innovative VR haptic system were also tested, exploring its impact on performance. MethodsIn collaboration with the Portuguese National Fire Service School, we exposed 22 healthy firefighters to 2 immersive scenarios using the FLAIM Trainer VR system (neutral and arousing scenarios) while recording physiological data in a quasi-experimental study. Baseline cognitive performance, depression, anxiety, stress, number of adverse events, and severity of PTSD symptoms were evaluated. Positive and negative affective states were measured before, between, and after each scenario. Situational awareness, sense of presence, ecological validity, engagement, and negative effects resulting from VR immersion were tested. ResultsBaseline positive affect score was high (mean 32.4, SD 7.2) and increased after the VR tasks (partial η2=0.52; Greenhouse-Geisser F1.82,32.78=19.73; P

O presente trabalho destina-se à investigação dos atos judiciais autoritários, sejam eles desligados das normas jurídicas vigentes, ou detentores de normas próprias. Inicialmente, busca-se verificar a existência de uma relação entre o Estado de Exceção e o recente fenômeno jurídico-político denominado lawfare, compreendido como o uso da lei como arma de guerra para destruição do adversário. Posto isso, examina-se o conceito de Estado de Exceção e sua relação com a democracia moderna, apontando casos emblemáticos. A partir disso, busca-se responder o seguinte questionamento: “O emprego manobras jurídico-legais atua efetivando o caráter substancialista da intervenção penal?”. Para responder ao problema de pesquisa, por meio de revisão bibliográfica, bem como análise documental, partiu-se da definição do fenômeno lawfare, passando pelo conceito de substancialismo penal a fim de compreender a aplicação de medidas de exceção em relação ao processo constitucional, na democracia brasileira. Por fim, chega-se a conclusão de que de que na democracia moderna a suspensão de direitos tem sido frequente principalmente em face daqueles que recebem a imagem de inimigo, indigno de proteção jurídica. Nota-se que tal abordagem é incompatível com um Estado Democrático de Direito.