Net Heart Rate for Estimating Oxygen Consumption in Active Adults.

The aim of this study was to verify the accuracy of predicting oxygen consumption (O2) in predominantly aerobic activities based on net heart rate (netHR), sex, and body mass index (BMI) in active adults. NetHR is the value of the difference between the resting HR (HRrest) and the average HR value obtained during a given session or period of physical activity. These activities must be continuous, submaximal, and of a stabilized intensity. The magnitude of the netHR depends mainly on the intensity of the exercise. The HR is measured in beats per minute (bpm). A total of 156 participants, 52 women and 104 men, between the ages of 18 and 81, had their netHR and net oxygen intake (netVO2) assessed. There were 79 participants in group 1 (prediction sample) (52 males and 27 females). There were 77 people in group 2 (validation sample) (52 males and 25 females). The results of the multiple linear regression showed that netVO2 (R2 = 85.2%, SEE = 3.38) could be significantly predicted by sex (p < 0.001), netHR (p < 0.001), and BMI (p < 0.001). The Bland-Altman plots satisfied the agreement requirements, and the comparison of the measured and estimated netVO2 revealed non-significant differences with a trivial effect size. We calculated the formula NetVO2 (mL/(kg·min)) = 16 + 3.67 (sex) + 0.27 (netHR) - 0.57 (BMI) to predict netVO2, where netVO2 is the amount of oxygen uptake (mL/(kg·min)) above the resting value, netHR is the heart rate (beats per minute) above the resting value measured during exercise, sex is equal to zero for women and one for men, and BMI is the body mass index. In addition, based on the knowledge of VO2, it was possible to estimate the energy expenditure from a particular training session, and to determine or prescribe the exercise intensity in MET (metabolic equivalent of task).

SARS-CoV-2 Spike protein triggers gut impairment since mucosal barrier to innermost layers: From basic science to clinical relevance.

Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl- secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context.

Influence of cigarette smoking on the Index of Cardiac Electrophysiological Balance in apparently healthy Angolans.

Background: Tobacco use accelerates atherosclerosis and is one of the predictors of death from ischemic heart disease, arrhythmias, heart failure, and sudden death. A new non-invasive parameter, the Index of Cardiac Electrophysiological Balance (iCEB) between depolarization and repolarization of the action potential, was considered a new biomarker for the identification of patients at increased arrhythmic risk. Objectives: We aimed to evaluate the iCEB in apparently healthy Angolans with habitual cigarette smoking compared to non-smokers. Subjects and methods: Data were obtained from the CardioBengo study, a cross-sectional community-based study in which a random sample of individuals aged between 15 and 84 years was selected. In total, 214 apparently healthy subjects, 102 smokers, and 112 non-smokers in the same age group were included in the final analysis. Results: The average age of the participants was 42.17 ± 13.04 years old and 26.6% of the sample was female. Smoking subjects had higher iCEB and corrected Index of Cardiac Electrophysiological Balance (iCEBc) values compared with non-smoking controls (4.39 vs. 4.25; p = 0.024, respectively), and (4.74 vs. 4.57; p = 0.030, respectively). Conclusions: In summary, iCEB and iCEBc were significantly higher in habitual smokers than in nonsmokers, which represents an increased risk of ventricular arrhythmogenesis in healthy habitual smokers. To the best of our knowledge, this is the first study performed in Africa to evaluate iCEB in smokers, making this type of study very important in low- and middle-income countries in the context of epidemiological transition.

Vasorelaxant effects of ellagitannins isolated from Cuphea carthagenensis.

Cuphea carthagenensis (Jacq.) J. F. Macbr. is a popular plant in Brazilian folk medicine owing to its hypotensive and central nervous system depressant effects. This study aimed to validate the hypotensive effect of the plant's aqueous extract (AE) in rats and examine the vascular actions of three hydrolyzable tannins, oenothein B, woodfordin C, and eucalbanin B, isolated from AE. Systolic blood pressure in unanesthetized rats was determined using the non-invasive tail-cuff method. Oral treatment of normotensive rats with 0.5 and 1.0 g/kg/day AE induced a dose-related hypotensive effect after 1 week. In rat aortic rings pre-contracted with noradrenaline, all ellagitannins (20 - 180 µM) induced a concentration-related vasorelaxation. This effect was blocked by either removing the endothelium or pre-incubating with NG-nitro-l-arginine methyl ester (10 µM), an inhibitor of nitric oxide (NO) synthase. In KCl-depolarized rat portal vein preparations, the investigated compounds did not affect significantly the maximal contractile responses and pD2 values of the concentration-response curves to CaCl2. Our results demonstrated the hypotensive effect of C. carthagenensis AE in unanesthetized rats. All isolated ellagitannins induced vasorelaxation in vitro via activating NO synthesis/NO release from endothelial cells, without altering the Ca2+ influx in vascular smooth muscle preparations. Considering the low oral bioavailability of ellagitannins, the determined in vitro actions of these compounds are unlikely to account for the hypotensive effect of AE in vivo. It remains to be determined the role of the bioactive ellagitannin-derived metabolites in the hypotensive effect observed after oral treatment of unanesthetized rats with the plant extract.

Effects of a 16-Week Training Program with a Pyramidal Intensity Distribution on Recreational Male Cyclists.

Different training intensity distributions (TIDs) have been proposed to improve cycling performance, especially for high-competition athletes. The objectives of this study were to analyze the effect of a 16-week pyramidal training intensity distribution on somatic and power variables in recreational cyclists and to explore the training zone with the greatest impact on performance improvement. The sample consisted of 14 male recreational cyclists aged 41.00 ± 7.29 years of age. A number of somatic variables were measured. During an incremental protocol, power at a 4 mMol·L-1 blood lactate concentration (P4), corresponding power to body mass ratio (P/W P4), and heart rate (HR P4) were also measured. Among the somatic variables, the percentage of fat mass showed the greatest improvement between moments (p < 0.001, d = 0.52). Both P4 (p < 0.001, d = 1.21) and P/W P4 (p < 0.001, d = 1.54) presented a significant increase between moments. The relative improvement in P4 (% P4) showed a significant correlation (Rs = 0.661, p = 0.038) and relationship (R2 = 0.61, p = 0.008) mainly with training zone Z2 (blood lactate levels ≥ 2 and <4 mMol·L-1). It seems that spending more time in Z2 promoted an improvement in both somatic and power variables in recreational cyclists.

Deep Learning-Assisted Single-Molecule Detection of Protein Post-translational Modifications with a Biological Nanopore.

Protein post-translational modifications (PTMs) play a crucial role in countless biological processes, profoundly modulating protein properties on both spatial and temporal scales. Protein PTMs have also emerged as reliable biomarkers for several diseases. However, only a handful of techniques are available to accurately measure their levels, capture their complexity at a single molecule level, and characterize their multifaceted roles in health and disease. Nanopore sensing provides high sensitivity for the detection of low-abundance proteins, holding the potential to impact single-molecule proteomics and PTM detection, in particular. Here, we demonstrate the ability of a biological nanopore, the pore-forming toxin aerolysin, to detect and distinguish α-synuclein-derived peptides bearing single or multiple PTMs, namely, phosphorylation, nitration, and oxidation occurring at different positions and in various combinations. The characteristic current signatures of the α-synuclein peptide and its PTM variants could be confidently identified by using a deep learning model for signal processing. We further demonstrate that this framework can quantify α-synuclein peptides at picomolar concentrations and detect the C-terminal peptides generated by digestion of full-length α-synuclein. Collectively, our work highlights the advantage of using nanopores as a tool for simultaneous detection of multiple PTMs and facilitates their use in biomarker discovery and diagnostics.

Correction: Wilson's Disease: A Prevalence Study in a Portuguese Population.

[This corrects the article DOI: 10.7759/cureus.43718.].

Public Support for Democracy in the United States Has Declined Generationally.

Support for democracy in the United States, once thought to be solid, has now been shown to be somewhat shaky. One of the most concerning aspects of this declining attachment to democracy is a marked age gap, with younger Americans less supportive of democracy than their older compatriots. Using age-period-cohort analysis of 12 national surveys collected between 1995 and 2019, we show that this age gap is largely a function of a long-term generational decline in support for democracy, with little evidence of an independent life-cycle effect apparent. The combination of generational decline without a positive and counterbalancing life-cycle effect offers a sober prognosis of how support for democracy in the United States might look in the future.

Characteristics of deaths by suicide in postmortem studies in Brazil: A systematic review and meta-analysis.

INTRODUCTION: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. METHODS: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. RESULTS: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05-43.32), previous suicide attempts in 23.92% (95% CI: 6.73-57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74-38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79-97.82), family history of suicidality in 21.33% (95% CI: 13.5-32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. CONCLUSION: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology.

Wilson's Disease: A Prevalence Study in a Portuguese Population.

Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies, specifically in Portugal, are scarce. Objectives This study aimed to evaluate the prevalence and incidence of WD and provide a description of its main clinical and laboratory features. Methods A retrospective study was carried out, with a search between 1995 and 2015, of all patients with a minimum follow-up of three months and birth confirmed in the northern region of Portugal, with an estimated population of 3,689,682 inhabitants. Database collection was based on the Portuguese National Health Service's clinical coding system, relying on clinical data from 13 northern Portuguese hospitals, liver biopsy histology results, and hospital prescription records. Clinical and biochemical correlations were statistically assessed using chi-square, Mann-Whitney U, Friedman, and Wilcoxon tests. Results Over the 20-year period, a prevalence of 1:37.000 and an incidence of one per million person-year was found. A total of 94 patients were analyzed, with a slight male predominance (53%), the majority with the onset of clinical manifestations in pediatric age (56%), with a median age at diagnosis of 16.6 years (interquartile range of 12.3-20,.8 years). Most patients presented with predominant liver disease (54.8%), with more than a third with cirrhosis; mixed hepatic and neurological manifestations in 17.9%; and mainly neurological symptoms in 10.7% of the patients. Neurological impairment was strongly associated with delayed development of the manifestations of the disease (p = 0.001) and also a higher detection of Kayser-Fleischer rings (p < 0.001), present in 27.0% of the patients. Regarding therapy, penicillamine has been the most widely used, with adverse reactions reported in 24.8%. At six and 12 months after initiation of therapy, a significant decrease in liver enzymes was found (ALT: p = 0.002; AST: p = 0.002, respectively), but no significant reduction was observed in urinary copper excretion. Conclusion This was one of the first studies regarding WD prevalence in a Portuguese population, contributing to a better understanding of the epidemiology, diagnosis, and management of WD in the northern region of Portugal. WD should be considered in any individual with unexplained hepatic or neurological manifestations, and initial symptoms may manifest at an early age, even in children less than five years old. A high percentage of patients were identified in the early stages of the disease by asymptomatic elevation of transaminases. Following copper chelation therapy, cytolysis markers appear to be more sensitive indicators of treatment response.

Acute Recovery after a Fatigue Protocol Using a Recovery Sports Legging: An Experimental Study.

Enhancing recovery is a fundamental component of high-performance sports training since it enables practitioners to potentiate physical performance and minimise the risk of injuries. Using a new sports legging embedded with an intelligent system for electrostimulation, localised heating and compression (completely embodied into the textile structures), we aimed to analyse acute recovery following a fatigue protocol. Surface electromyography- and torque-related variables were recorded on eight recreational athletes. A fatigue protocol conducted in an isokinetic dynamometer allowed us to examine isometric torque and consequent post-exercise acute recovery after using the sports legging. Regarding peak torque, no differences were found between post-fatigue and post-recovery assessments in any variable; however, pre-fatigue registered a 16% greater peak torque when compared with post-fatigue for localised heating and compression recovery methods. Our data are supported by recent meta-analyses indicating that individual recovery methods, such as localised heating, electrostimulation and compression, are not effective to recover from a fatiguing exercise. In fact, none of the recovery methods available through the sports legging tested was effective in acutely recovering the torque values produced isometrically.

The World of GPCR dimers - Mapping dopamine receptor D2 homodimers in different activation states and configuration arrangements.

G protein-coupled receptors (GPCRs) are known to dimerize, but the molecular and structural basis of GPCR dimers is not well understood. In this study, we developed a computational framework to generate models of symmetric and asymmetric GPCR dimers using different monomer activation states and identified their most likely interfaces with molecular details. We chose the dopamine receptor D2 (D2R) homodimer as a case study because of its biological relevance and the availability of structural information. Our results showed that transmembrane domains 4 and 5 (TM4 and TM5) are mostly found at the dimer interface of the D2R dimer and that these interfaces have a subset of key residues that are mostly nonpolar from TM4 and TM5, which was in line with experimental studies. In addition, TM2 and TM3 appear to be relevant for D2R dimers. In some cases, the inactive configuration is unaffected by the partnered protomer, whereas in others, the active protomer adopts the properties of an inactive receptor. Additionally, the ß-arrestin configuration displayed the properties of an active receptor in the absence of an agonist, suggesting that a switch to another meta-state during dimerization occurred. Our findings are consistent with the experimental data, and this method can be adapted to study heterodimers and potentially extended to include additional proteins such as G proteins or ß-arrestins. In summary, this approach provides insight into the impact of the conformational status of partnered protomers on the overall quaternary GPCR macromolecular structure and dynamics.

Water consumption assessment and classification in industrial buildings - The case study of Continental Advanced Antenna, Vila Real, Portugal.

Water abstraction for the industrial, domestic, and agricultural sectors increased from 0.67 trillion m3/year in the 1900s to 3.79 trillion m3/year in 2000, and it is expected to increase by 55 % in 2050 when the majority of the world's population will live in urban areas. Concerning the industrial sector, despite the efforts to a more sustainable use, water is still an essential and irreplaceable resource, and this situation tends to increase due to modern industrial installations that require large-scale and complex water distribution systems. Usually, industries consume a large volume of water, however due to more and severer regulations, it is necessary to propose strategies for the aid of water conservation. This article presents a methodology to analyse, classify and optimize water consumption in industrial installations, using a real case study located in Vila Real, Portugal. The daily water consumption per worker, the daily record of use of each type of device and the hourly usage pattern were analysed and a classification was achieved according to the ANQIP (National Association for Quality in Building Installations) calculator. The case study revealed a great opportunity of improvement in what concerns to water efficient use. Some measures to improve the efficiency of water use in the building were pointed out, such as the use of rainwater harvesting systems, the use of aerators and replacements of taps and faucets when possible. The methodology is expeditious and user-friendly, and easy to replicate in similar cases, however it reveals some difficulties (especially in the data collection process that is made by inquiry, once it is always dependent on the respondent sensibility and willingness).

Relative impact of diagnosis and clinical stage on response to electroconvulsive therapy: a retrospective cohort

Objectives: Electroconvulsive therapy (ECT) is commonly indicated for refractory psychiatric disorders. However, little research has compared response across diagnoses. Here, we aimed to evaluate the relative impact of diagnosis and clinical staging as response predictors in a cross-diagnostic sample. Methods: In a retrospective cohort of adult inpatients (n=287) who underwent at least six sessions of ECT, we investigated predictors of complete response (a clinical global impression of 1) to ECT. We use adjusted regression models to estimate the impact of clinical diagnosis and staging on complete response and dominance analysis to assess the relative importance of these predictors. Results: Those for whom a depressive episode was a primary indication for treatment were the most likely to have complete improvement, while those with psychosis were the least likely; clinical stage had a significant influence on outcome in all diagnoses. A diagnosis of psychosis was the strongest predictor of non-response. Conclusions: A diagnosis of psychosis (mainly schizophrenia) was the strongest predictor of non-response. We also found that clinical staging can aggregate information on ECT response that is independent of clinical diagnosis.

Artificial intelligence-coupled plasmonic infrared sensor for detection of structural protein biomarkers in neurodegenerative diseases.

Diagnosis of neurodegenerative disorders (NDDs) including Parkinson's disease and Alzheimer's disease is challenging owing to the lack of tools to detect preclinical biomarkers. The misfolding of proteins into oligomeric and fibrillar aggregates plays an important role in the development and progression of NDDs, thus underscoring the need for structural biomarker-based diagnostics. We developed an immunoassay-coupled nanoplasmonic infrared metasurface sensor that detects proteins linked to NDDs, such as alpha-synuclein, with specificity and differentiates the distinct structural species using their unique absorption signatures. We augmented the sensor with an artificial neural network enabling unprecedented quantitative prediction of oligomeric and fibrillar protein aggregates in their mixture. The microfluidic integrated sensor can retrieve time-resolved absorbance fingerprints in the presence of a complex biomatrix and is capable of multiplexing for the simultaneous monitoring of multiple pathology-associated biomarkers. Thus, our sensor is a promising candidate for the clinical diagnosis of NDDs, disease monitoring, and evaluation of novel therapies.

On suicidal ideation: the need for inductive methodologies to advance the field.

Recent scholarly investigation of suicidal ideation has been largely based on identifying associated factors and using ideation-to-action theories to explain its occurrence. However, this approach may not be sufficient, as many aspects of suicidal ideation fall beyond the reach of such conceptualizations. The overemphasis on explaining rather than understanding this phenomenon is a significant factor in this insufficiency. As such, it is argued that qualitative methods that use data to derive theories could offer a more nuanced understanding of suicidal ideation. By adopting bottom-up approaches, researchers can explore how individuals experience and understand suicidal ideation and how it relates to their lives and experiences. Furthermore, use of qualitative research methods could aid in development of more accurate and inclusive definitions that are more firmly grounded in data.

Prevalence of Type 2 Diabetes, Impaired Fasting Glucose, and Diabetes Risk in an Adult and Older North-Eastern Portuguese Population.

The aims of this study were (1) to evaluate the prevalence of type 2 diabetes (T2D) in a middle-aged north-eastern Portuguese population, (2) to analyze the prevalence of impaired fasting glucose (IFG), and (3) to assess the risk of T2D in this community-based sample. An exploratory, retrospective, and cross-sectional study was conducted from a total of 6570 individuals aged 18-102 years, among which 3865 were women (57.4 ± 18.1 years) and 2705 were men (60.0 ± 16.8 years). T2D diagnosis, IFG, and the diabetes risk score (low to very high risk) were assessed. The prevalence of T2D in this adult and an older north-eastern Portuguese population was 17.4%. A higher prevalence of T2D was reported in men (22.2%) than in women (14.0%); however, this was without significant differences (p = 0.086). Otherwise, the prevalence of T2D was significantly different among the age groups and increased with age (p < 0.001). Regarding IFG, a higher percentage of cases was observed in men (14.1%) than in women (8.4%) (p < 0.001). The risk of developing T2D in the next 10 years showed an association with sex and age group (p < 0.001) with a small-to-moderate effect (V = 0.1-0.3). Men and the elderly had the highest percentage of cases in the moderate-to-very high-risk bands. The current research confirmed a higher prevalence of T2D, IFG, and diabetes risk than previous Portuguese epidemiological reports. The results also suggest potential prediabetes cases, which should be carefully monitored. The current research adds evidence to the worldwide trend of the increasing prevalence of T2D and intermediate hyperglycemia (i.e., prediabetes).

Relative impact of diagnosis and clinical stage on response to electroconvulsive therapy: a retrospective cohort.

OBJECTIVE: Electroconvulsive therapy (ECT) is commonly indicated for refractory psychiatric disorders. However, response comparison across diagnoses is scantly investigated. Here, we aimed to evaluate the relative impact of diagnosis and clinical staging as response predictors in a cross-diagnostic sample. METHODS: We investigate, in a retrospective cohort of adult inpatients (N=287) who underwent at least six sessions of ECT, predictors of complete response (a clinical global impression of 1) to ECT. We use adjusted regression models to estimate the impact of clinical diagnosis and staging on complete response and dominance analysis to assess the relative importance of these predictors. RESULTS: Those with a depressive episode as a primary indication for treatment were more likely than all the other groups to have complete improvement, while those with psychosis were the least likely; clinical stage had a significant influence on outcome in all diagnoses. A diagnosis of psychosis stood as the strongest predictor of non-response. CONCLUSION: An indication of ECT for psychosis (mostly schizophrenia) had a dominant impact in our cohort, indicating a worse chance of response. We also demonstrate that clinical staging can aggregate information on response to electroconvulsive therapy that is independent of clinical diagnosis.

Real-World Populational-Based Quality of Life and Functional Status After Stroke.

OBJECTIVES: This study aimed to describe health-related quality of life (HRQoL) 3 months and 1 year after stroke, compare HRQoL between dependent (modified Rankin scale [mRS] 3-5) and independent (mRS 0-2) patients, and identify factors predictive of poor HRQoL. METHODS: Patients with a first ischemic stroke or intraparenchymal hemorrhage from the Joinville Stroke Registry were analyzed retrospectively. Using the 5-level version of the EuroQol-5D questionnaire, HRQoL was calculated for all patients 3 months and 1 year after stroke, stratified by mRS score (0-2 or 3-5). One-year HRQoL predictors were examined using univariate and multivariate analyses. RESULTS: Three months after a stroke, data from 884 patients were analyzed; 72.8% were categorized as mRS 0-2 and 27.2% as mRS 3-5, and the mean HRQoL was 0.670 ± 0.256. At 1-year follow-up, 705 patients were evaluated; 75% were classified as mRS 0-2 and 25% as mRS 3-5, and the mean HRQoL was 0.71 ± 0.249. An increase in HRQoL was observed between 3 months and 1 year (mean difference 0.024, P < .0001), both in patients with 3-month mRS 0-2 (0.013, P = .027) and mRS 3-5 (0.052, P < .0001). Increasing age, female sex, hypertension, diabetes, and a high mRS were associated with poor HRQoL at 1 year. CONCLUSIONS: This study described the HRQoL after a stroke in a Brazilian population. This analysis shows that the mRS was highly associated with HRQoL after stroke. Age, sex, diabetes, and hypertension were also associated with HRQoL, although not independently of mRS.