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The Paranaguá Estuarine System (PES) plays a crucial ecological and economic role in the coastal zone of Brazil, containing significant remaining portions of the Atlantic rainforest, which is considered a World Heritage Site (WHS) by UNESCO. At the same time, the PES accommodates the largest bulk grain port terminal and is the leader in container handling in Latin America. In this study, we combined elemental, isotopic, and molecular markers (n-alkanes and n-alkanols) with a comprehensive sample set of surface sediments to understand and distinguish the primary sources of sedimentary organic matter (OM) and evaluate the environmental quality of a WHS under human pressure. The C/N ratio and δ 13 C ranged from 4.98 to 17.9 and - 27.15 to - 22.88‰, respectively. These results suggest that the primary bulk OM origin is the terrigenous contribution from river inputs. The total long-chain n-alkanes and n-alkanols results ranged from 0.29 to 12.3 µg g -1 and 0.19 and 998.1 µg g -1 , respectively, and the n-alkanes diagnostic indices (e.g. CPI and TAR) agree with elementary and isotopic proxies. The river contribution, together with tidal currents, dominates the local hydrodynamics. However, the estuarine mouth region and northern sector are strongly influenced by marine-sourced OM. It was also observed that the low-energy estuarine hydrodynamics controls the OM deposition in Antonina Bay, which favours the deposition of fine sediments. In Paranaguá Bay, due to a mixing zone with the intrusion of fresh and marine waters, there are sites of preferential accumulation of OM caused by fine particles' flocculation. This geochemical mapping of sedimentary OM composition may provide important insights into future scenarios of environmental changes and may be applied to track the deposition and accumulation of anthropogenic residues from the continental basin and port activities., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: All authors have reviewed the manuscript thoroughly and consented to the publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The effectiveness of indirect Intravascular laser irradiation of blood (ILIB) is not fully understood. In this study, we provided a novel experiment that employs metabolomics to investigate the effects of ILIB in women. Twenty-eight volunteers underwent indirect ILIB and had their plasma collected before and after this procedure. The ILIB was applied at the radial artery for 30 min, using low-power photobiomodulation (660 nm), and a power output of 0.1 W. Plasma samples were extracted and analyzed using liquid chromatography-high-resolution mass spectrometry in an untargeted approach. Partial Least Squares Discriminant Analysis revealed 151 molecules with the Variable In Projection score of ≥ 1. From these, 26 were identified. After checking for molecules related to dietary intake, fasting, medication, or part of the human exposome, 15 were affected by ILIB. The abundances of Estradiol 17b-glucuronide 3-sulfate, CAR 14:3, PI 22:6/PGJ2, and CAR 12:1 significantly increased by ILIB, while AcylGlcADG 62:9, Tyrosyl-Glutamine, and CDP-DG 22:3/PGF1 had the contrary effect. ILIB was shown to modulate molecules from different chemical classes, although its impact on plasma metaboloma was minimal. Further research is warranted to fully elucidate the implications of these findings across various metabolic pathways, thus advancing the science surrounding ILIB., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was conducted by the Helsinki criteria and approved by the Ethics Committee of São Francisco University (Approval Number: 63939422.2.0000.5514). Patient consent: All patients consented to participate in the study, providing their approval for this purpose., (© 2024. The Author(s).)

Background: We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice., Research Design and Methods: A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c)., Results: Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline ( p  = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i ( p  = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint ( p  < 0.0001), with a higher percentage of patients achieving ≥ 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores ( p  = 0.004 and p  = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint ( p  = 0.010 and p  = 0.002, respectively)., Conclusions: Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.

Background: Effective infection prevention and control (IPC) was central to keeping healthcare workers (HCWs) safe during the COVID-19 pandemic. However, as the pandemic continued, the maintenance of high-quality IPC practices waned, placing HCWs at increased risk of infection. A COVID-19 Safety Officer (SO) program was piloted by the United States Agency for International Development (USAID)-funded Reaching Impact, Saturation and Epidemic Control (RISE) project across two health facilities in Ethiopia, which trained clinical and non-clinical HCWs on IPC protocols to promote safe practices in patient care areas. We sought to evaluate the implementation and effectiveness of the SO program in improving IPC practices within the clinical setting., Methods: This is a post-implementation evaluation of the SO program, implemented in two hospitals in Ethiopia between May 2022 and December 2022. Participants completed a 4-day course on COVID-19 epidemiology, IPC, safety communication, and learning theory as a part of the Training of Trainers component ( n = 23), and were posted in clinical wards to provide staff training and support to maintain IPC protocols. The program was evaluated at 6 months using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Effectiveness was measured using direct observation of IPC practices across intervention sites. Implementation outcomes were measured using surveys and qualitative interviews to capture training cascade, knowledge, comfort, acceptability, and maintenance., Results: Participants were able to cascade training to an additional 167 clinical (67.6%) and 80 non-clinical (32.3%) staff across both sites. Direct observation of clinical staff at 6 months showed that 95% (59/62) wore at least a surgical mask with patients and were compliant with masking and/or distancing protocol. Clinical interviews revealed that SOs contributed to increased perceived comfort with screening and isolation procedures and environmental cleaning procedures., Conclusion: The SO training program was widely adopted, and effective in improving the implementation and comfort of maintaining IPC practices in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Woldeamanuel, Thumba, Gabul, Ahmed, Mekonnen, Tarekegn, Nhanala, Kent, Ashengo, Wu, Dagoye, Curless, Fisseha, Ayalew, Gebremichael and Hansoti.)

Introduction: Obesity aligned with quadriceps muscle weakness contributes to the high incidence of knee osteoarthritis (KOA), which is prevalent in women. Although molecular signatures of KOA have been suggested, the association between biopsychosocial responses and the plasma metabolomic profile in overweight/ obese women with KOA remains in its early stages of investigation. This study aims to associate the plasma metabolome with biopsychosocial parameters of overweight/obese women diagnosed with KOA., Methods: Twenty-eight overweight/obese women (Control-n = 14; KOA-n = 14) underwent two visits to the laboratory. Functional tests and questionnaires assessing biopsychosocial parameters were administered during the first visit. After 48 h, the participants returned to the laboratory for blood collection. Specific to the KOA condition, the Numerical Pain Rating Scale (NPRS), Tampa Scale for Kinesiophobia (TSK), and Knee injury and Osteoarthritis Outcome Score (KOOS) were applied., Results: Thirteen molecules were different between groups, and four correlated with KOA's biopsychosocial parameters. DG 22:4-2OH and gamma-Glutamylvaline were inversely associated with KOSS leisure and TSK score, respectively. LysoPE 18:0 and LysoPE 20:5 were positively associated with KOSS symptoms and TSK score, respectively., Discussion: While the correlations of LysoPE 18:0 and gamma-Glutamylvaline are supported by existing literature, this is not the case for DG 22:4-2OH and LysoPE 20:5. Further studies are recommended to better elucidate these correlations before dismissing their potential involvement in the biopsychosocial factors of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lisboa, Benevento, Kaneko, Bertolucci, Rosini Silva, Sardim, Ruiz, dos Reis, Porcari and Messias.)

Staphylococcal protein-A affinity chromatography has been optimized for antibody purification, achieving a current capacity of up to 90 mg/ml in packed bed. The morphology of the particles, the number of antibodies bound per ligand and the spatial arrangement of the ligands were assessed by in-situ Small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) combined with measurement of adsorption isotherms. We employed SAXS measurements to probe the nanoscale structure of the chromatographic resin. From scanning electron microcopy, the morphology and area of the beads were obtained. The adsorption isotherm revealed a bi-Langmuirian behavior where the association constant varied with the critical bulk concentration, indicating multilayer adsorption. Determining the antibody-ligand stoichiometry was crucial for understanding the adsorption mechanism, which was estimated to be 4 at lower concentrations and 4.5 at higher concentrations, suggestive of reversible protein-protein interactions. The same results were reached from the in-situ small angle X-ray scattering measurements. A stoichiometry of 6 cannot be achieved since the two protein A monomers are anchored to the stationary phase and thus sterically hindered. Normalization through ellipsoids facilitated SAXS analysis, enabling the determination of distances between ligands and antibody-ligand complexes. Density fluctuations were examined by subtracting the elliptical fit, providing insights into ligand density distribution. The dense ligand packing of TOYOPEARL® AF-rProtein A HC was confirmed, making further increases in ligand density impractical. Additionally, SAXS analysis revealed structural rearrangements of the antibody-ligand complex with increasing antibody surface load, suggesting reversible association of antibodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This is a cross-sectional study, aimed to develop and cross-validate a fat-free mass (FFM) predictive equation using single-frequency bioelectrical impedance (BIA), considering the predicted age at peak height velocity (PHV) as a variable. Additionally, the study aims to test the FFM-BIA obtained using a previous predictive equation that used skeletal maturity as a variable., Method: The participants (n = 169 male adolescent athletes) were randomly divided into two groups: development of a new predictive equation (n = 113), and cross-validation (n = 56). The concordance test between the FFM values obtained by Koury et al. predictive equation and DXA data was determined (n = 169). Bioelectrical data was obtained using a single-frequency analyzer., Results: Among the models tested, the new predictive equation has resistance index (height2/resistance) and predictive age at PHV as variables and presented R2 = 0.918. The frequency of maturity status using skeletal maturity and PHV diagnosis was inadequate (Kappa = 0.4257; 95%CI = 0.298-0.553). Bland-Altman plots and concordance correlation coefficient showed substantial concordance between the FFM-DXA values (48.8 ± 11.2 kg) and the new predictive equation (CCC = 0.960). The results showed that the new equation performed better than the equation developed by Koury et al. (CCC = 0.901)., Conclusions: Our results show that it is feasible to predict FFM in male adolescent athletes using predictive age at PHV, with moderate concordance. The calculation of FFM using more economical and less complex variables is viable and should be further explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America., Methods: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated., Results: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months., Conclusions: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database., Methods: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up., Results: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods., Conclusion: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Background: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations., Aim: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care., Method: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland-Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison., Results: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations., Conclusion: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average., (© 2023. The Author(s).)

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), has shown demonstrated benefits for renal and cardiovascular outcomes in large clinical trials. However, short-term concerns regarding its impact on renal function and electrolyte balance exist. This study aimed to evaluate the short-term effects of dapagliflozin on renal function and electrolyte balance in patients newly prescribed the medication. A retrospective analysis of 246 patients who initiated dapagliflozin therapy was conducted. Serum creatinine, sodium, and potassium levels were measured at baseline (before dapagliflozin) and 5-8 days after initiation (endpoint). A Wilcoxon signed-rank test, Pearson's chi-square test, and Fischer's exact test were used for the data analysis. Glycemia and sodium levels were significantly higher at the baseline compared to the endpoint ( p < 0.001). Conversely, creatinine and potassium levels were significantly higher at the endpoint than at the baseline ( p < 0.001). The prevalence of hyponatremia and hyperkalemia were increased at the endpoint (17.5% vs. 10.2% and 16.7% vs. 8.9%, respectively). Although not statistically significant, a trend towards increased hyponatremia with the co-administration of furosemide was observed ( p = 0.089). No significant association was found between potassium-sparing medications ( p > 0.05) and hyperkalemia, except for angiotensin receptor blockers ( p = 0.017). The combination of dapagliflozin and furosemide significantly increased the risk of acute kidney injury (AKI) at the endpoint ( p = 0.006). Age, gender, and chronic kidney disease status did not significantly influence the occurrence of AKI, hyponatremia, or hyperkalemia ( p > 0.05). These findings emphasize the importance of the close monitoring of renal function and electrolyte balance, particularly in the early stages of dapagliflozin therapy, especially in patients receiving diuretics or renin-angiotensin-aldosterone system inhibitors.

Polychlorinated biphenyls (PCBs) and dichloro-diphenyl-trichloroethane (DDT) were evaluated in water and sediments from the Espírito Santo Inner Shelf (ESIS), Brazil, three years after the Fundão dam failure (FDF). We discuss the levels, sources, fate, and current environmental risks of these contaminants on temporal and spatial scales. In addition, the associated coastal dispersion patterns, water-sediment exchange trends, and environmental alterations were also discussed. Low contributions and no environmental risks were verified for PCBs after FDF. However, the low concentrations and frequency of occurrence in the samples did not allow for further reliable conclusions regarding the source of this contaminant. In contrast, hazard risk has been detected for DDTs in water and sediments. In sediments, there were a significant increase in level (up to 13.42 ng g -1 ; outlier = 369.6 ng g -1 ), inventory (maximum = 35.98 ng cm -2 ) and mean total mass (21.1 ± 39.4 kg) of DDTs after FDF. The integrated assessment of the spatial distribution in water and sediment suggests that DDTs was released from the Doce River, travelled south by the water column, and returned to the mouth region by northward sediment transport, where it accumulated. However, intense rainfall increased the input of DDTs to the ESIS and may have also altered its spatial distribution. Fugacity fraction analysis (ƒƒ) indicated a net flux of DDTs from water to sediment, suggesting that vertical sinking was an important transport process in this area. Finally, the findings indicate that FDF contributed to DDTs input on ESIS by remobilizing contaminated past sediments and soils from the Doce River drainage basin. This contribution is expected to continue since a large amount of tailings is still stored in the river basin and estuary. These results highlight the importance of assessing the indirect impacts of large-scale land disasters on marine environments, and may be helpful in future interpretations of additional local trends and global inventories of legacy pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Different questionnaires assess self-reported medication adherence and others quantify aspects of patients attitudes towards medication, but not together in a single instrument. Gathering these two aspects in a single instrument could reduce patients survey burden., Aim: The aim of this study was to develop the Medication Adherence Universal Questionnaire (MAUQ) using the Maastricht Utrecht Adherence in Hypertension short version (MUAH-16) factorial structure as the hypothesized model., Method: A multistep process started with the modification of the MUAH-16 to obtain the MAUQ. Patients using at least one antihypertensive medicine were recruited. The two questionnaires, the MUAH-16 and MAUQ, were applied. A confirmatory factor analysis (CFA) was performed using the initial MUAH-16 s-order 4-factor model. An additional bifactor model with four uncorrelated factors and an overall score was tested. The comparative fit index (CFI), root mean square error of approximation (RMSEA) with confidence intervals (CIs), and standardized root mean squared residual (SRMR) were used to assess both models., Results: A sample of 300 hypertensive patients completed the instruments. The CFA with the second-order 4-factor solution resulted in similar results for the MUAH-16 and MAUQ: CFIs of 0.934 and 0.930, RMSEAs of 0.043 [CI 0.030-0.056] and 0.045 [CI 0.031-0.057] and SRMRs of 0.060 and 0.061, respectively. The CFA with the bifactor model showed slightly better results for both the MUAH-16 and MAUQ: CFIs of 0.974 and 0.976, RMSEAs of 0.030 [CI 0.005-0.046] and 0.028 [CI 0.001-0.044], and SRMRs of 0.043 and 0.044, respectively., Conclusion: CFA demonstrated that the MAUQ presented a better fit to both models than the MUAH-16, obtaining a robust universal free instrument to assess medicine-taking behaviour and four medicine beliefs components., (© 2023. The Author(s).)

Delivering electroconvulsive therapy (ECT) during the reconsolidation of traumatic memories may enhance the treatment efficacy in posttraumatic stress disorder (PTSD). To test this, 14 patients with severe and refractory PTSD were randomly allocated to receive ECT sessions either after retrieving the traumatic (n=8) or a neutral (n=6) memory. We found that delivering ECT after retrieving the traumatic memory enhanced the improvement of PTSD symptoms and the reduction of subjective reactivity to the traumatic memory. Reduction in anxiety and mood symptoms and physiological reactivity to the traumatic memory were observed in the sample as a whole regardless of memory retrieval., Competing Interests: Declaration of Competing Interest All other authors report no biomedical financial interests or potential conflicts of interest. This study was funded by the São Paulo Research Agency (FAPESP), Brazil, grant #2014/04810–0 to Felipe Corchs., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) were analysed in the sediments of one of the most well-preserved estuaries in South Brazil, the Paranaguá Estuarine System (PES), using several source apportionment tools. The ∑PAH ranged from < DL to 125.6 ng g -1 dw (dry weight) (average 29.9 ± 26.1 ng g -1 dw), and the lowest levels detected were similar to those found in other protected areas of the world. In general, the PAH concentrations indicated excellent environmental quality for the entire estuary. Principal component analysis indicated that fine sediments and total organic carbon were the main factors controlling PAH concentrations in the PES. Multiple PAH sources were identified in the study area; biomass burning and fossil fuel combustion predominated but considerable amounts of petrogenic residues were also observed. We identified evidence of a contribution from an adjacent watershed resulting from the construction of interconnections between large rivers and from years of intense deforestation in the local Atlantic Forest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before. Outcome variables were analyzed using Pearson's Chi-Square, Fisher's exact test, and linear regression test. In total, 420 patients were randomly selected (48.6% male and 51.4% female). Patients with family support showed a lower incidence of high glycemia at admission ( p = 0.016). Higher blood creatinine levels were associated with higher blood glycemia ( p = 0.005), and hyperuricemia (HU) ( p = 0.001), as well as HU, was associated with a higher incidence of acute cardiovascular diseases (ACD) ( p = 0.007). Hemoglobin levels are lower with age ( p = 0.0001), creatinine ( p = 0.009), and female gender ( p = 0.03). The lower the AST/ALT ratio, the higher the glycemia at admission ( p < 0.0001). Obese patients with ( p = 0.021) or without ( p = 0.027) concomitant dyslipidemia had a higher incidence of ACD. Insulin ( p = 0.003) and glucagon-like peptide-1 agonists (GLP1 RA) ( p = 0.023) were associated with a higher incidence of decompensated heart failure, while sulfonylureas ( p = 0.009), metformin-associated with dipeptidyl peptidase-4 inhibitors (DPP4i) ( p = 0.029) or to a sulfonylurea ( p = 0.003) with a lower incidence. Metformin, in monotherapy or associated with DPP4i, was associated with a lower incidence of acute kidney injury ( p = 0.017) or acute chronic kidney injury ( p = 0.014). SGLT2i monotherapy ( p = 0.0003), associated with metformin ( p = 0.026) or with DPP4i ( p = 0.007), as well as insulin and sulfonylurea association ( p = 0.026), were associated with hydroelectrolytic disorders, unlike GLP1 RA ( p = 0.017), DPP4i associated with insulin ( p = 0.034) or with a GLP1 RA ( p = 0.003). Insulin was mainly used by autonomous and institutionalized patients ( p = 0.0008), while metformin ( p = 0.003) and GLP1 RA ( p < 0.0001) were used by autonomous patients. Sulfonylureas were mostly used by male patients ( p = 0.027), while SGLT2 ( p = 0.0004) and GLP1 RA ( p < 0.0001) were mostly used by patients within the age group 65-85 years. Sulfonylureas ( p = 0.008), insulin associated with metformin ( p = 0.040) or with a sulfonylurea ( p = 0.048), as well as DPP4i and sulfonylurea association ( p = 0.031), were associated with higher blood glycemia. T2DM patients are characterized by great heterogeneity from a clinical point of view presenting with several associated comorbidities, so the pharmacotherapeutic approach must consider all aspects that may affect disease progression.

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings.

Bothrops snake envenomation is characterized by severe local manifestations such as pain, edema, inflammation, hemorrhage, and myonecrosis. Furthermore, it is described that venom from juvenile and adult snakes may have differences in their composition that can lead to differences in the evolution of the clinical manifestation of the victim. Photobiomodulation (PBM) has been shown to be an effective adjuvant therapy to serum therapy to reduce the local effects induced by bothropic snake venom. This study evaluated the effect of PBM on the local reaction, after Bothrops alternatus snake venom (BaV) injection, in its juvenile (BaJV) and adult (BaAV) stages. Balb/C mice were injected with the juvenile or adult venoms of BaV or saline solution (control group). PBM at a wavelength of 660 nm, 100 mW, 0.33 W/cm 2 , 40 s, and a 0.028 cm 2 beam was applied transcutaneous to a single point with a radiant exposure of 4 J/cm 2 , 30 min after venom injection. Edema, inflammatory infiltrate, hyperalgesia, and myonecrosis were analyzed. Both venoms induced significant edema and myonecrosis in the gastrocnemius muscle. Hyperalgesia in the mice paw and a prominent leukocyte infiltrate into the peritoneum were also observed. PBM significantly reduced all evaluated parameters. In conclusion, PBM treatment was effective in reducing the local effects induced by B. alternatus venom at different stages of snake development and could be a useful tool as an adjuvant treatment for bothropic envenomation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amanda Cabral David reports financial support was provided by Fundação de Amparo a Pesquisa do Estado de São Paulo - FAPESP., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The present study aimed to identify associations between extremes in body weight status (underweight and excess body weight) before a COVID-19 diagnosis and clinical outcomes in patients infected with SARS coronavirus type 2., Methods: A multicenter cohort study was conducted in eight different states in northeastern Brazil. Demographic, clinical (previous diagnosis of comorbidities), and anthropometric (self-reported weight and height) data about individuals who tested positive for COVID-19 were collected. Outcomes included hospitalization, mechanical ventilation, and death. Multivariable logistic regression models, adjusted based on age, sex and previous comorbidities, were used to assess the effects of extremes in body weight status on clinical outcomes., Results: A total of 1308 individuals were assessed (33.6% were elderly individuals). The univariable analyses showed that only hospitalization was more often observed among underweight (3.2% versus 1.2%) and overweight (68.1% versus 63.3%) individuals. In turn, cardiovascular diseases were more often observed in all clinical outcomes (hospitalization: 19.7% versus 4.8%; mechanical ventilation: 19.9% versus 13.5%; death: 21.8% versus 14.1%). Based on the multivariable analysis, body weight status was not associated with risk of hospitalization (underweight: odds ratio [OR]: 1.10; 95% confidence interval [CI] 95%, 0.50-2.41 and excess body weight: OR: 0.81; 95 CI, 0.57-1.14), mechanical ventilation (underweight: OR: 0.92; 95% CI, 0.52-1.62 and excess weight: OR: 0.90; 95% CI, 0.67-1.19), and death (underweight: OR: 0.61; 95% CI, 0.31-1.20 and excess body weight: OR 0.88; 95% CI, 0.63-1.23)., Conclusions: Being underweight and excess body weight were not independently associated with clinical outcomes in patients with COVID-19 in the herein analyzed cohort. This finding indicates that the association between these variables may be confounded by both age and comorbidities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The survival of children with acute lymphoblastic leukemia (ALL) has improved due to changes in the treatment and the disease diagnosis. A significant advance was the incorporation of asparaginase. However, hypersensitivity reactions are a common cause of early discontinuation of this drug., Aim: The proposed study aims to evaluate early interruptions and the influence of the number of asparaginase doses effectively administered on the prognosis of patients with ALL., Methods and Results: An observational cohort study was carried out, with retrospective data collection, in medical records. The prognostic variables indicated in the protocol applied were used, and the principal outcomes were 5 years event-free survival (EFS) and 5 years of overall survival (OS) probability. Statistical analyzes were performed using SPPS 20.0 and R. In Cox's proportional hazards model for EFS and OS, variables of prognostic importance (n = 126 children) were: high-risk group (HGR), by the protocol classification, and less than 10 doses of asparaginase. The increased risk of events and death in HGR, who did less than 10 doses, was 3.6 and 7 times, respectively. The study did not show statistical significance for the number of asparaginase doses in patients who were not at high risk., Conclusions: We demonstrated that the early interruption of asparaginase treatment could negatively impact the prognosis of patients with ALL, especially HGR, reinforcing the need for careful diagnosis of reactions and the availability of alternative types of asparaginase., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objectives: To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D., Methods: We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group)., Results: The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several miRNAs were related to metabolic derangements, inflammatory pathways, and several other autoimmune diseases. Pathway analysis of putative DEM targets revealed an enrichment in pathways related to metabolic syndrome, inflammatory response, apoptosis and insulin signaling pathways, metabolic derangements, and decreased immunomodulation. One of the miRNAs' gene targets was DYRK2 (dual-specificity tyrosine-phosphorylation-regulated kinase 2), which is an autoantigen targeted by an antibody in T1D. ROC curve analysis showed hsa-miR-16 and hsa-miR-200a-3p with AUCs greater than for glucose levels, with discriminating power for T1D prediction greater than glucose levels. Conclusions/Interpretation. Our data suggests a potential influence of DEMs on disease progression from the initial autoimmune lesion up to severe beta cell dysfunction and the role of miRNAs hsa-miR-16 and hsa-miR-200a-3p as biomarkers of T1D progression., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Aritania Sousa Santos et al.)

Background: The Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking., Methods: Cellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus., Results: Fifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4 + T cell responses (including circulating follicular helper (cTfh, CD45RA - CXCR5 + ) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4 + T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period., Conclusions: CoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year., Funding: Fundação Butantan, Instituto Butantan and São Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.

Introduction and Objectives: Patient knowledge about hypertension is an important patient-related determinant for poor blood pressure control and is a target for more effective interventions. We aimed to evaluate hypertensive patients' knowledge and awareness about hypertension and its influence on their beliefs about their medication and their adherence to antihypertensive therapy., Methods: A cross-sectional study was conducted among adult patients attending one of the participating pharmacies and taking at least one antihypertensive drug. Data on personal and family history were collected, and Portuguese versions of the Hypertension Knowledge Test (HKT), Beliefs about Medicines Questionnaire (BMQ), and short version of the Maastricht Utrecht Adherence in Hypertension questionnaire (MUAH-16) were administered., Results: A total of 240 patients were enrolled. The mean number of antihypertensive drugs used was 1.62±0.99, with 15.4% of patients treated with three or more drugs. More than 80% of patients knew the blood pressure therapeutic goals and identified overweight, sedentary lifestyle, and salt as risk factors for hypertension. Conversely, the majority of the patients were not aware of the asymptomatic characteristics of hypertension and believed that antihypertensive treatment had to be used for a limited time duration. Negative and significant correlations were found between the HKT and negative attitudes toward medication, but no association was found with positive attitudes., Conclusions: Hypertensive patients had good knowledge of hypertension risk factors but not of antihypertensive treatment. Increasing patient knowledge about hypertension may possibly reduce negative attitudes toward medication but will probably have no impact on positive attitudes., (Copyright © 2021 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To assess testicular volumes and sexual maturation in patients with testicular torsion., Methods: A retrospective analysis of consecutively treated patients with testicular torsion between 2016 and 2018. Age, pubic hair staging (Tanner), and by ultrasonography, volume of the unaffected testis (in cubic centimeters) were evaluated either immediately before surgery or at the first postoperative visit. Patients with previous testicular disease, such as cryptorchidism, or with no records of testicular volume were excluded. The analysis included descriptive statistics and Bayesian regression., Results: We treated 149 patients during the study period, and 141 (94.6%, median age 17.3 years) met the inclusion criteria. Median testicular volume was 13.0cm3 (interquartile range of 10.5-15.2), with similar right and left volumes (12.9cm3versus 13.3cm3; p=0.94). Sixty-five (46.1%) patients were Tanner stage IV, 17 (12.1%) stage III, and 59 (41.8%) stage V., Conclusion: In this study, we were able to estimate volumes of testicular torsion, which aggregated around late puberty values (13.0cm3 for the whole dataset, 12.2cm3 for patients <25 years), suggesting that testicular hypermobility, due to congenital anatomical abnormalities, remains quiescent until the organ reaches a critical volume, after which torsion becomes possible. These findings provide a tentative explanation for the disease's age distribution.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain., Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days., Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed., Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia., Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219., Competing Interests: CM was employeed by AAC&T Research Consulting LTDA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rocco, Silva, Cruz, Tierno, Rabello, Junior, Haag, de Ávila, da Silva, Mamede, Buchele, Barbosa, Cabral, Junqueira, Araújo-Filho, da Costa, Alvarenga, Moura, Carajeleascow, de Oliveira, Silva, Soares, Fernandes, Fonseca, Camargos, Reis, Franchini, Luiz, Morais, Sverdloff, Martins, Felix, Mattos-Silva, Nogueira, Caldeira, Pelosi and Lapa-e-Silva.)

Background: Therapy management in patients suffering from mental health disorders is complex and the risks derived from changes or interruptions of treatment should not be ignored. Medication reconciliation in psychiatry may reduce medication errors and promote patient safety during transitions of care., Objective: To identify the influence of complementary information sources in the construction of the best possible medication history, and to ascertain the potential clinical impact of discrepancies identified in a medication reconciliation service., Methods: An observational study was conducted in an acute mental hospital unit, with a further validation in an internal medicine unit. Adult patients taking at least one medicine admitted in the unit were included. Patients/caregivers were interviewed upon admission and the information gathered was compared with hospital medical and shared electronic medical records. Once the best possible medication history was gathered, therapeutic information was reconciled against the prescription on admission to identify discrepancies. Potential clinical impact of medication errors was classified using the International Safety Classification., Results: During the study period, 148 patients were admitted, 50.7% females, mean age 54.6 years (SD=16.3). Collaboration of a caregiver was a needed in 74% of the interviews. In total, 1,147 drugs were considered to obtain patients' best possible medication history. After reconciliation, 560 clinically sound intentional discrepancies were identified and 359 discrepancies required further clarification from prescribers: 84.12% "drug omission", 5.57% "drug substitution", 6.96% "dose change", and 3.34% "dosage frequency change". Potential clinical impact of these medication discrepancies was classified as: 95 mild, 100 moderate, and 29 severe medication errors., Conclusion: About 1 in three intentional discrepancies observed in a pharmacists-led medication reconciliation service required further clarification from prescribers, being 80% of them unintentional discrepancies. Results highlight the importance of the caregiver as source of information for the psychiatric patient, the relevance of analyzing shared electronic health records until 6 months before, and the need to use hospital medical records efficiently. Additionally, 29 discrepancies were classified as errors with potentially severe clinical impact. A medication reconciliation service is concluded to be feasible and necessary in a mental health unit., Competing Interests: CONFLICT OF INTEREST The authors declare they have no conflicts of interest., (Copyright: © Pharmacy Practice.)

The pharmaceutical industry is currently trying to develop new bioactive compounds to inactivate both enveloped and non-enveloped viruses for therapeutic purposes. Consequently, microalgal and macroalgal bioactive compounds are being explored by pharmaceutical, as well as biotechnology and food industries. In this review, we show how compounds produced by algae include important candidates for viral control applications. We discuss their mechanisms of action and activity against enveloped and non-enveloped viruses, including those causing infections by enteric, parenteral, and respiratory routes. Indeed, algal products have potential in human and animal medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Reis, Cadamuro, Cabral, Thaís da Silva, Rodríguez-Lázaro and Fongaro.)

The Doce River mouth (DRM) was severely impacted by the rupture of the Fundão Dam in 2015, considered the greatest Brazilian environmental tragedy in terms of tailings volume released (>40 million m 3 ) and traveled distance (~600 km until the Atlantic Ocean). Environmental monitoring has been performed since then, but background levels are scarce or absent to Persistent Organic Pollutants (POPs), making impact assessments difficult. In the current study, we presented the baseline levels, inventories, and risk assessment of the POPs polychlorinated biphenyl (PCBs) and organochlorinated pesticides (OCPs), in surface sediment of the DRM. Samples were collected in December 2010 and July 2011, i.e., four years before the Fundão dam failure. The total PCBs and the OCPs (Aldrin, HCHs, and Chlordanes) were detected in both sampling campaigns, with levels up to 9.50 and 1.64, 0.28, and 0.63 ng g -1 , respectively. The decrease of the Doce River flow was the main factor contributing to seasonal variations in the spatial distribution, and to a slight decline in the levels and frequency of the analyzed POPs in sediments collected in the dry season (July 2011). Environmental risk assessment, inventories, and total mass results suggest a low potential of PCBs and OCPs accumulation before the dam failure. This is the first POPs assessment in the study area that helped identify some unexpected impacts of the Fundão dam failure and contributed to the understanding of POPs cycles in the Southern Atlantic, data that are still scarce in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: We investigated the clinical course and outcomes of patients submitted to cardiovascular surgery in Brazil and who had developed symptoms/signs of coronavirus disease 2019 (COVID-19) in the perioperative period., Methods: A retrospective multicenter study including 104 patients who were allocated in three groups according to time of positive real time reverse transcriptase-polymerase chain reaction (RT-PCR) for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2): group 1, patients who underwent cardiac surgery > 10 days after positive RT-PCR; group 2, patients with a positive RT-PCR within 10 days before or after surgery; group 3, patients who presented positive RT-PCR > 10 days after surgery. The primary outcome was mortality and secondary outcomes were postoperative complications, intensive care unit (ICU) length of stay, and postoperative days of hospitalization., Results: The three groups were similar with respect to age, the European System of Cardiac Operative Risk Evaluation score, and comorbidities, except hypertension. Postoperative complications and death were significantly higher in groups 2 and 3 than in group 1, and no significant difference between groups 2 and 3 was seen. Group 2 showed a high prevalence of surgery performed as an urgent procedure. Although no significant differences were observed in ICU length of stay, total postoperative hospitalization time was significantly higher in group 3 than in groups 1 and 2., Conclusion: COVID-19 affecting the postoperative period of patients who underwent cardiovascular surgery is associated with a higher rate of morbidity and mortality. Delaying procedures in RT-PCR-positive patients may help reduce risks of perioperative complications and death.

Background: In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.7. Based on initial data from the UK and later data from other countries, this variant was estimated to have a transmission fitness advantage of around 40-80 % (Volz et al., 2021; Leung et al., 2021; Davies et al., 2021)., Aim: This study aims to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time based on data from Switzerland., Methods: We generated whole genome sequences from 11.8 % of all confirmed SARS-CoV-2 cases in Switzerland between 14 December 2020 and 11 March 2021. Based on these data, we determine the daily frequency of the B.1.1.7 variant and quantify the variant's transmission fitness advantage on a national and a regional scale., Results: We estimate B.1.1.7 had a transmission fitness advantage of 43-52 % compared to the other variants circulating in Switzerland during the study period. Further, we estimate B.1.1.7 had a reproductive number above 1 from 01 January 2021 until the end of the study period, compared to below 1 for the other variants. Specifically, we estimate the reproductive number for B.1.1.7 was 1.24 [1.07-1.41] from 01 January until 17 January 2021 and 1.18 [1.06-1.30] from 18 January until 01 March 2021 based on the whole genome sequencing data. From 10 March to 16 March 2021, once B.1.1.7 was dominant, we estimate the reproductive number was 1.14 [1.00-1.26] based on all confirmed cases. For reference, Switzerland applied more non-pharmaceutical interventions to combat SARS-CoV-2 on 18 January 2021 and lifted some measures again on 01 March 2021., Conclusion: The observed increase in B.1.1.7 frequency in Switzerland during the study period is as expected based on observations in the UK. In absolute numbers, B.1.1.7 increased exponentially with an estimated doubling time of around 2-3.5 weeks. To monitor the ongoing spread of B.1.1.7, our plots are available online., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Meta-analyses have demonstrated that isometric handgrip training (IHT) decreases blood pressure in hypertensive individuals. Nonetheless, most studies were conducted in laboratory settings and its effects in real-world settings remain unclear., Objective: To analyze the effects of IHT on office and ambulatory blood pressure in hypertensive patients attended within primary healthcare., Design and Setting: Randomized controlled trial conducted in primary healthcare units within the Family Health Program, Petrolina, Pernambuco, Brazil., Methods: 63 hypertensive patients (30-79 years old; 70% female) were randomly allocated into IHT or control groups. IHT was performed three times per week (4 x 2 minutes at 30% of maximal voluntary contraction, one-minute rest between bouts, alternating the hands). Before and after the 12-week training period, office and ambulatory blood pressure and heart rate variability were obtained. The significance level was set at P < 0.05 (two-tailed testing) for all analyses., Results: IHT significantly decreased office systolic blood pressure (IHT: 129 ± 4 versus 121 ± 3 mmHg, P < 0.05; control: 126 ± 4 versus 126 ± 3 mmHg, P > 0.05), whereas there was no effect on diastolic blood pressure (IHT: 83 ± 3 versus 79 ± 2 mmHg, P > 0.05; control: 81 ± 3 versus 77 ± 3 mmHg, P > 0.05). Heart rate variability and ambulatory blood pressure were not altered by the interventions (P > 0.05 for all)., Conclusion: IHT reduced office systolic blood pressure in hypertensive patients attended within primary care. However, there were effects regarding diastolic blood pressure, ambulatory blood pressure or heart rate variability., Clinicaltrials.gov Identifier: NCT03216317.

Mitochondrial ATP-sensitive potassium channels (mitoKATP) locate in the inner mitochondrial membrane and possess protective cellular properties. mitoKATP opening-induced cardioprotection (using the pharmacological agent diazoxide) is preventable by antagonists, such as glibenclamide. However, the mechanisms of action of these drugs and how mitoKATP respond to them are poorly understood. Here, we show data that reinforce the existence of a mitochondrial sulfonylurea receptor (mitoSUR) as part of the mitoKATP. We also show how diazoxide and glibenclamide compete for the same binding site in mitoSUR. A glibenclamide analog that lacks its cyclohexylurea portion (IMP-A) loses its ability to inhibit diazoxide-induced swelling. These results suggest that the cyclohexylureia portion of glibenclamide is indispensable for mitoKATP inhibition. Moreover, IMP-A did not suppress diazoxide-induced preconditioning (EC50 10.66 μM) in a rat model of a cardiac ischemia/reperfusion. Importantly, glibenclamide inhibited both diazoxide-induced cardioprotection (IC50 86 nM). We suggest that IMP-A must be used with caution since we found this drug possesses significant inhibitory effects on mitochondrial respiration. We characterized the binding of glibenclamide and diazoxide using a molecular simulation (docking) approach. Using the molecular structure of the ATP binding protein ABCB8 (pointed by others as the mitoSUR) we demonstrate that glibenclamide competitively inhibits diazoxide actions. This was reinforced (pharmacologically) in a competitive antagonism test. Taken together, these results bring valuable and novel insights into the pharmacological/biochemical aspects of mitokATP activation and cardioprotection. This study may lead to the discovery of novel therapeutic strategies that may impact ischemia-reperfusion injury., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Interactions of biomolecules with inorganic oxide surfaces such as silica in aqueous solutions are of profound interest in various research fields, including chemistry, biotechnology, and medicine. While there is a general understanding of the dominating electrostatic interactions, the binding mechanism is still not fully understood. Here, chromatographic zonal elution and flow microcalorimetry experiments were combined with molecular dynamic simulations to describe the interaction of different capped amino acids with the silica surface. We demonstrate that ion pairing is the dominant electrostatic interaction. Surprisingly, the interaction strength is more dependent on the repulsive carboxy group than on the attracting amino group. These findings are essential for conducting experimental and simulative studies on amino acids when transferring the results to biomolecule-surface interactions.

Objective:  To evaluate whether performing preoperative urodynamic study influences postoperative urinary symptoms of women with stress urinary incontinence that underwent transobturator sling., Methods:  Retrospective analysis of patients treated for stress urinary incontinence by transobturator sling from August 2011 to October 2018. Predictor variables included preoperative urodynamic study, age, incontinence severity, body mass index, preoperative storage symptoms and previous anti-urinary incontinence procedure. Outcome variables were postoperative subjective continence status, storage symptoms and complications. Logistic regression after propensity score was employed to compare outcomes between patients who underwent or not pre-operative urodynamic study., Results:  The present study included 88 patients with an average follow-up of 269 days. Most patients ( n =  52; 59.1%) described storage symptoms other than stress urinary incontinence, and 38 patients (43.2%) underwent preoperative urodynamic studies. Logistic regression after propensity score did not reveal an association between urinary continence outcomes and performance of preoperative urodynamic study (odds ratio 0.57; confidence interval [CI]: 0.11-2.49). Among women that did not undergo urodynamic study, there was a subjective improvement in urinary incontinence in 92% of the cases versus 87% in those that underwent urodynamic study ( p  = 0.461). Furthermore, postoperative storage symptoms were similar between women who did not undergo urodynamic study and those who underwent urodynamic study, 13.2% versus 18.4%, respectively ( p  = 0.753)., Conclusion:  Preoperative urodynamic study had no impact on urinary incontinence cure outcomes as well as on urinary storage symptoms after the transobturator sling in women with stress urinary incontinence., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background Several anticholinergic scales and equations to evaluate the anticholinergic burden have been previously created. Association of these instruments with the anticholinergic outcomes are usually estimated by means of hypothesis contrast tests, which ignore the size of the association effect. Objective To evaluate the effect size of the associations between the scores on cumulative anticholinergic burden instruments with peripheral or central anticholinergic adverse outcomes in older patients. Setting Internal medicine ward of a Tertiary University Hospital. Methods A case-control study was conducted in patients over 65 years who were admitted to two internal medicine wards of a Portuguese university hospital. The Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden scale and Drug Burden Index were used to calculate the patients' anticholinergic burden. Peripheral (dry mouth-swab technique; dry eye-Schirmer test) and central (falls and cognitive impairment-Mini-Mental State Examination) anticholinergic adverse outcomes were investigated. The Barthel Index was used to assess overall physical functionality. The Mann-Whitney test was used to evaluate probabilistic differences in the anticholinergic scores between case and control individuals. To establish the effect size of the associations, the area under the curve of the receiver operating characteristics curve was calculated. Main outcome measure Anticholinergic adverse effects. Results A total of 250 patients (mean age 81.67 years, standard deviation 7.768; 50% females) were included. In total, 148 patients (59.2%) presented with dry mouth, 85 (34%) with dry eye, 141 (56.4%) with impaired functionality, 44 (17.6%) with a history of falls and 219 (87.6%) with cognitive impairment. Significant differences (p < 0.05) were obtained for the majority of the associations between Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden and Drug Burden Index and adverse effects. Conversely, the effect sizes of these associations ranged from "fail" (area under the curve 0.5 to 0.6) to "fair" (area under the curve 0.7 to 0.8). Conclusion Although significant differences in the scores of anticholinergic burden instruments and adverse outcomes may exist, the effect sizes of these associations ranged from 'fail' to 'fair', which limits their utility in preventing anticholinergic adverse outcomes with medication review interventions.

Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30 mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10 mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H 2 O 2 , and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4 days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H 2 O 2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H 2 O 2 . We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.

The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To estimate statewide presentation delay, misdiagnosis rate, inter-hospital transfer times and testicular salvage for testicular torsion patients treated in our state's public health system., Patients and Methods: Case series of consecutive testicular torsion patients treated in our state's public health system between 2012-2018. Predictors included presentation delay (time from symptoms to first medical assessment), facilitie's level-of-care (primary, secondary, tertiary), first diagnosis (torsion, epididymitis, other), Doppler-enhanced ultrasound request (Doppler-US) and inter-hospital transfer times, with surgical organ salvage as the main response. We used Bayesian regression to estimate the effect of first examining facilitie's level-of-care, first diagnosis, and Doppler-US on transfer time., Results: 505 patients were included, most (298, 59%) with presentation delay >6 hours. Misdiagnosis at first examining facility raised transfer time from median 2.8 to 23.4 (epididymitis) and 37.9 hours (other) and lowered testicular salvage rates from 60.3% (torsion) to 10.7% (epididymitis) and 18.3% (other). Doppler-US had negligible effects on transfer time once controlling for misdiagnosis in the regression model. Although organ salvage in patients presenting before 6 hours at the tertiary facility was high (94.6%, and about 20% lower for those presenting at lower levels-of-care), the overall salvage rate was more modest (46%)., Conclusion: Our low overall testicular salvage rates originated from a large proportion of late presentations combined with long transfer times caused by frequent misdiagnoses. Our results indicate that efforts to improve salvage rates should aim at enhancing population-wide disease awareness and continuously updating physicians working at primary and secondary levels-of-care about scrotal emergencies., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Some patients with clinically diagnosed penile fracture actually have a false fracture (no tunica albuginea tear found at surgery). Although previous reports indicate that these patients often do not report hearing a snapping sound (henceforth sound) at injury, there are no studies of the sound's role in this differential diagnosis. To assess if the sound's absence increased the likelihood of intraoperatively diagnosing a false fracture, we retrospectively analyzed 65 consecutive clinically diagnosed penile fracture patients between January 2008 and December 2017, using surgical diagnosis of penile fracture as outcome variable and sound as main predictor, including as covariates age, presentation delay, immediate detumescence after injury, and whether injury occurred during sexual intercourse. Fifty-six patients had penile fracture (86.2%), and most (40, 71.4%) reported the sound, whereas two of the nine patients with false fracture reported the sound (22.2%, p = 0.007, Fisher's exact test). Bayesian logistic regression revealed that the sound was associated with surgical diagnosis of penile fracture (relative odds ratio = 4.25), and the probability of penile fracture fell from 92 to 74% when the sound was not reported among patients injured during intercourse experiencing immediate detumescence. This study followed PROCESS (Preferred Reporting of Case Series in Surgery) guidelines.

Sedimentary sterols and linear alkylbenzenes associated with allochthonous organic matter (AOM) inputs were studied in surface sediments along the Tubarão riverbed, South Brazil. These markers were analysed in terms of concentrations, diagnostic ratios and by using multivariate analyses to identify the main organic matter sources. It was necessary to integrate all these factors to distinguish the sources and determine sewage contamination. Phytosterols predominated over faecal sterols, but the contributions of livestock waste along the river (determined in 50% of the sites) were confirmed by the fingerprint analysis. Raw sewage contamination was verified at one site, according to the increased levels of sewage molecular markers and confirmed by the multivariate analyses and diagnostic ratios calibrated to this region. A possible synergistic effect between inorganic nanoparticles from coal mine waste and organic contaminants related to AOM input was suggested and should not be ignored since both activities severely contribute to the environmental changes in much of this fluvial-estuarine gradient from the South Atlantic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)