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Luma de O Comini,1 Laura C de Oliveira,1 Luiza D Borges,1 Heloísa H Dias,1 Clara R S Batistelli,1 Luciana S da Silva,2 Tiago R Moreira,3 Rodrigo G da Silva,4 Rosângela M M Cotta1 1Department of Nutrition and Health, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil; 2Medicine School, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil; 3Department of Nursing and Medicine, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil; 4Clinical Director of the Hemodialysis Service, São João Batista Hospital, Viçosa, Minas Gerais, BrasilCorrespondence: Luma de O CominiDepartment of Nutrition and Health, Federal University of Viçosa, Viçosa, Annex Building of the Biological Sciences Center II, University Campus, s/nº. Sala 101. Federal University of Viçosa, Viçosa, MG CEP: 36570-900, BrazilTel +55 31 3612-7538Fax +55 31 3612-5187Email lumacominiufv@gmail.comPurpose: To identify the associations between MetS and its components and chronic kidney disease (CKD) in a population with arterial hypertension (AH), or diabetes mellitus (DM) accompanied by the Primary Health Care (PHC).Patients and methods: A cross-sectional study with 788 individuals diagnosed with AH and/or DM followed by PHC of Viçosa, Brazil. Anthropometric, biochemical and clinical measures were performed for the diagnosis of MetS and CKD. MetS was identified using the NCEP-ATPIII criteria. CKD was identified by estimating the glomerular filtration rate using the CKD-EPI equation. Logistic regression models were used to estimate the chances of CKD associated with MetS and its components and specific combinations of components.Results: The prevalence of MetS reported in the population was 65.4%, that of hidden CKD was 15.4%. The prevalence of CKD among participants with MetS was 75.2%. The most prevalent component of MetS in the population was AH (96.7%). Elevated fasting blood glucose, central obesity, and reduced HDL-c were significantly associated with an increased chance of CKD (OR = 2.80, 95% CI 1.76–4.45, OR = 1.68, 95% CI, 05–2.71, OR = 1.61, CI 95% 1.03–2.50, respectively). For the multivariate adjustment, the participants with MetS were 2 times more likely to have CKD than those without MetS (OR = 2.07; 95% CI, 1.25–3.44). The combination of three components of MetS high blood pressure, abdominal obesity and elevated fasting blood glucose and the combination of four components of MetS high blood pressure, reduced HDL-c, high fasting blood glucose and abdominal obesity were associated with increased odds of CKD (OR = 2.67, CI 95% 1.70–4.20, OR = 2.50, CI 95% 1.55–4.02, respectively).Conclusion: MetS, as well as its individual or combined components were independently associated with CKD in the population with AH and/or DM accompanied by PHC.Keywords: high blood pressure, abdominal obesity, hypertriglyceridemia, fasting blood glucose, HDL-c, estimated glomerular filtration rate

Purpose: To analyze the correlation between pharyngeal residue and penetration/aspiration in post-stroke individuals., Methods: Cross-sectional, descriptive, retrospective, clinical study with 157 post-stroke individuals, 71 females and 86 males, aged 26 to 92 years (mean age: 67.2 years), all diagnosed by neurological assessment and imaging exams (computed tomography or magnetic resonance imaging), who underwent fiberoptic endoscopic evaluation of swallowing (FEES) in a rehabilitation center. They were served 5 mL of moderately thick liquid (level 3 in the International Dysphagia Diet Standardization Initiative [IDDSI]) in a spoon three times. Two expert raters in dysphagia assessed them with the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS) and Penetration Aspiration Scale (PAS). Their interrater sensitivity agreement was analyzed with the Kappa test, and Spearman's rank correlation (r) verified the correlation between pharyngeal residue and the PAS and calculated the effect size (r 2 )., Results: YPRSRS in vallecula was positively correlated with PAS (r = 0.43; r 2  = 0.18; p ≤ 0.000); YPRSRS in pyriform sinus, with PAS (r = 0.54; r 2  = 0.29; p ≤ 0.000); and YPRSRS in both vallecula/pyriform sinus with PAS (r = 0.57; r 2  = 0.32; p ≤ 0.000)., Conclusion: The severity of pharyngeal residue in post-stroke individuals with dysphagia is correlated with the level of penetration-aspiration., Competing Interests: Declarations Conflict of interest The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Detection before metastasis and efficient treatment of disease significantly improve patient survival and quality of life. However, limitations in diagnosis and postoperative surveillance are associated with low CRC detection and survival rates. Thus, this project aimed to evaluate the molecular profile of patients diagnosed with CRC, as molecular biomarkers constitute a new frontier for diagnosis, treatment and prognosis. Methods and Results: 42 patients were included in the study, predominantly male (59.5%), with a median age of 63 years (SD: 10.0; min: 41; max: 83). The majority of primary tumors were located in the rectum (38.1%), in the sigmoid (33.3%) and in the ascending (21.4%) colon. We evaluated the genes KRAS, NRAS, BRAF, EGFR and TP53 using Sanger sequencing. Somatic and germline mutations were found in the KRAS, EGFR and TP53 genes, with the most common somatic alteration being rs121913529 in KRAS. This variant was also strongly associated with alcoholism (p = 0.002). Furthermore, patients with somatic mutations in TP53 had significantly higher mortality compared to those with wild-type alleles (OR: 11.2; 95% CI 1.25-2.45). Conclusions: Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted., (© 2024. The Author(s).)

With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bonnetia is the most representative genus of the Pantepui woody flora and is among the groups with the greatest endemism in the local flora. The genus has 28 currently recognized species in tropical America, 26 of them endemic to the Pantepui. Here we describe Bonnetiaayangannensis from the summit of Mount Ayanganna tepui in Guyana, providing a morphological description, illustrations, distribution maps, characterization of micromorphology under scanning electron microscopy and leaf venation, comments comparing the new species with closely related species, and a key for the identification of the species of Bonnetia occurring in Guyana. With its restricted distribution threatened by climate change, Bonnetiaayangannensis is assessed in the conservation threat category of Critically Endangered. Its description raises the number of endemic species of Bonnetia in the Pantepui to 27., Competing Interests: The authors have declared that no competing interests exist., (Rafael G. Barbosa-Silva, Benjamin M. Torke, Pedro L. Viana.)

Purpose: To characterize the time structure of K1 kickboxing matches of Glory World Series (Glory) and to determine potential differences between winners and losers., Methods: Seventeen matches of Glory 2019 (17 first rounds, 13 second rounds, and 8 third rounds) were video-analyzed to quantify (1) the time expended in high- and low-intensity activity and pauses, (2) the number and pattern of attacks, and (3) the number of effective attacks. Fighters were professional male athletes (age 27.9 [2.7] y) of the middle-weight category (85 kg). The number and the pattern of attacks and the number of effective attacks were compared between winners and losers., Results: The mean times expended in high- and low-intensity activity and pauses were 234.6 (133.9) seconds, 97.4 (60.1) seconds, and 36.0 (19.9) seconds, respectively, resulting in an effort-to-pause ratio of ∼1.8:1. Compared with losers, winners presented (1) a greater number of attacks in the second round (P = .004) and entire match (P = .009), (2) a greater number of attacks containing 3 attacks in sequence in the second round (P = .001) and attacks containing >3 attacks in the third round (P = .049), and (3) a greater number of effective attacks in the second round (P = .011) and entire match (P = .008)., Conclusions: The findings of the present study indicate that K1 kickboxing in Glory matches presents a ∼1.8:1 effort-to-pause ratio and that winners perform more attacks, effective attacks, and attacks in sequence. These data provide useful insights to improve the training specificity of kickboxing athletes.

Long noncoding RNAs (lncRNAs) are versatile RNA molecules recently identified as key regulators of gene expression in response to environmental stress. Our primary focus in this study was to develop a robust computational pipeline for identifying structurally identical lncRNAs across replicates from publicly available bulk RNA-seq datasets. In order to demonstrate the effectiveness of the pipeline, we utilized the transcriptome of the thermophilic fungus Thermothelomyces thermophilus and assessed the expression pattern of lncRNAs in conjunction with Heat Shock Proteins (HSP), a well-known protein family critical for the cell's response to high temperatures. Our findings demonstrate that the identification of structurally identical transcripts among replicates in this thermophilic fungus ensures the reliability and accuracy of RNA studies, contributing to the validity of biological interpretations. Furthermore, the majority of lncRNAs exhibited a distinct expression pattern compared to HSPs. Our study contributes to advancing the understanding of the biological mechanisms comprising lncRNAs in thermophilic fungi., (© 2024. The Author(s).)

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds., 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 B.V. All rights reserved.)

The zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and dogs are reservoirs for this parasite. For the diagnosis of Leishmania at the species level in dogs in formalin-fixed, paraffin-embedded skin (FFPES) samples, colorimetric in situ hybridization (CISH) and quantitative real-time polymerase chain reaction (qPCR) are options, but their sensitivities are not well established. Therefore, the aim of this study was to determine the sensitivity of these two techniques in FFPES for the diagnosis of the L. infantum infection in dogs using culture as the reference standard. The FFPES of 48 dogs with cutaneous infection by L. infantum confirmed by culture and by multilocus enzyme electrophoresis were examined by CISH and qPCR using specific probes for L. infantum . The sensitivities of qPCR, CISH and their combination were, respectively, 77.0%, 58.0% and 83.3%. The sensitivities of qPCR in dogs with and without clinical signs were, respectively, 74.2% and 82.4%. The sensitivities of CISH in dogs with and without clinical signs were, respectively, 61.3% and 52.9%. The CISH and qPCR showed satisfactory sensitivities for the diagnosis of L. infantum in the FFPES of dogs, even in dogs without clinical signs, and their combination increases the sensitivity for this diagnosis.

Heavy-isotope substitution into enzymes slows down bond vibrations and may alter transition-state barrier crossing probability if this is coupled to fast protein motions. ATP phosphoribosyltransferase from Acinetobacter baumannii is a multi-protein complex where the regulatory protein HisZ allosterically enhances catalysis by the catalytic protein HisG S . This is accompanied by a shift in rate-limiting step from chemistry to product release. Here we report that isotope-labelling of HisG S has no effect on the nonactivated reaction, which involves negative activation heat capacity, while HisZ-activated HisG S catalytic rate decreases in a strictly mass-dependent fashion across five different HisG S masses, at low temperatures. Surprisingly, the effect is not linked to the chemical step, but to fast motions governing product release in the activated enzyme. Disruption of a specific enzyme-product interaction abolishes the isotope effects. Results highlight how altered protein mass perturbs allosterically modulated thermal motions relevant to the catalytic cycle beyond the chemical step., (© 2024. The Author(s).)

The human enzyme 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 (HsDNPH1) catalyses the hydrolysis of 5-hydroxymethyl-2'-deoxyuridine 5'-phosphate to generate 5-hydroxymethyluracil and 2-deoxyribose-5-phosphate via a covalent 5-phospho-2-deoxyribosylated enzyme intermediate. HsDNPH1 is a promising target for inhibitor development towards anticancer drugs. Here, site-directed mutagenesis of conserved active-site residues, followed by HPLC analysis of the reaction and steady-state kinetics are employed to reveal the importance of each of these residues in catalysis, and the reaction pH-dependence is perturbed by each mutation. Solvent deuterium isotope effects indicate no rate-limiting proton transfers. Crystal structures of D80N-HsDNPH1 in unliganded and substrate-bound states, and of unliganded D80A- and Y24F-HsDNPH1 offer atomic level insights into substrate binding and catalysis. The results reveal a network of hydrogen bonds involving the substrate and the E104-Y24-D80 catalytic triad and are consistent with a proposed mechanism whereby D80 is important for substrate positioning, for helping modulate E104 nucleophilicity, and as the general acid in the first half-reaction. Y24 positions E104 for catalysis and prevents a catalytically disruptive close contact between E104 and D80., (© 2024 Wiley‐VCH GmbH.)

Background: The COVID-19 pandemic has caused significant disruptions to everyday life and has had social, political, and financial consequences that will persist for years. Several initiatives with intensive use of technology were quickly developed in this scenario. However, technologies that enhance epidemiological surveillance in contexts with low testing capacity and healthcare resources are scarce. Therefore, this study aims to address this gap by developing a data science model that uses routinely generated healthcare encounter records to detect possible new outbreaks early in real-time., Methods: We defined an epidemiological indicator that is a proxy for suspected cases of COVID-19 using the health records of Emergency Care Unit (ECU) patients and text mining techniques. The open-field dataset comprises 2,760,862 medical records from nine ECUs, where each record has information about the patient's age, reported symptoms, and the time and date of admission. We also used a dataset where 1,026,804 cases of COVID-19 were officially confirmed. The records range from January 2020 to May 2022. Sample cross-correlation between two finite stochastic time series was used to evaluate the models., Results: For patients with age 18 years, we find time-lag () = 72 days and cross-correlation () ~ 0.82, = 25 days and ~ 0.93, and = 17 days and ~ 0.88 for the first, second, and third waves, respectively., Conclusions: In conclusion, the developed model can aid in the early detection of signs of possible new COVID-19 outbreaks, weeks before traditional surveillance systems, thereby anticipating in initiating preventive and control actions in public health with a higher likelihood of success., (© 2024. The Author(s).)

Resorption within cortices of long bones removes excess mass and damaged tissue and increases during periods of reduced mechanical loading. Returning to high-intensity exercise may place bones at risk of failure due to increased porosity caused by bone resorption. We used point-projection X-ray microscopy images of bone slices from highly loaded (metacarpal, tibia) and minimally loaded (rib) bones from 12 racehorses, 6 that died during a period of high-intensity exercise and 6 that had a period of intense exercise followed by at least 35 days of rest prior to death, and measured intracortical canal cross-sectional area (Ca.Ar) and number (N.Ca) to infer remodelling activity across sites and exercise groups. Large canals that are the consequence of bone resorption (Ca.Ar >0.04 mm 2 ) were 1.4× to 18.7× greater in number and area in the third metacarpal bone from rested than exercised animals (p = 0.005-0.008), but were similar in number and area in ribs from rested and exercised animals (p = 0.575-0.688). An intermediate relationship was present in the tibia, and when large canals and smaller canals that result from partial bony infilling (Ca.Ar >0.002 mm 2 ) were considered together. The mechanostat may override targeted remodelling during periods of high mechanical load by enhancing bone formation, reducing resorption and suppressing turnover. Both systems may work synergistically in rest periods to remove excess and damaged tissue., (© 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Nucleosides are ubiquitous to life and are required for the synthesis of DNA, RNA, and other molecules crucial for cell survival. Despite the notoriously difficult organic synthesis of nucleosides, 2'-deoxynucleoside analogues can interfere with natural DNA replication and repair and are successfully employed as anticancer, antiviral, and antimicrobial compounds. Nucleoside 2'-deoxyribosyltransferase (dNDT) enzymes catalyze transglycosylation via a covalent 2'-deoxyribosylated enzyme intermediate with retention of configuration, having applications in the biocatalytic synthesis of 2'-deoxynucleoside analogues in a single step. Here, we characterize the structure and function of a thermophilic dNDT, the protein from Chroococcidiopsis thermalis ( Ct NDT). We combined enzyme kinetics with structural and biophysical studies to dissect mechanistic features in the reaction coordinate, leading to product formation. Bell-shaped pH-rate profiles demonstrate activity in a broad pH range of 5.5-9.5, with two very distinct p K a values. A pronounced viscosity effect on the turnover rate indicates a diffusional step, likely product (nucleobase1) release, to be rate-limiting. Temperature studies revealed an extremely curved profile, suggesting a large negative activation heat capacity. We trapped a 2'-fluoro-2'-deoxyarabinosyl-enzyme intermediate by mass spectrometry and determined high-resolution structures of the protein in its unliganded, substrate-bound, ribosylated, 2'-difluoro-2'-deoxyribosylated, and in complex with probable transition-state analogues. We reveal key features underlying (2'-deoxy)ribonucleoside selection, as Ct NDT can also use ribonucleosides as substrates, albeit with a lower efficiency. Ribonucleosides are the building blocks of RNA and other key intracellular metabolites participating in energy and metabolism, expanding the scope of use of Ct NDT in biocatalysis., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The first step of histidine biosynthesis in Acinetobacter baumannii , the condensation of ATP and 5-phospho-α-d-ribosyl-1-pyrophosphate to produce N 1 -(5-phospho-β-d-ribosyl)-ATP (PRATP) and pyrophosphate, is catalyzed by the hetero-octameric enzyme ATP phosphoribosyltransferase, a promising target for antibiotic design. The catalytic subunit, HisG S , is allosterically activated upon binding of the regulatory subunit, HisZ, to form the hetero-octameric holoenzyme (ATPPRT), leading to a large increase in k cat . Here, we present the crystal structure of ATPPRT, along with kinetic investigations of the rate-limiting steps governing catalysis in the nonactivated (HisG S ) and activated (ATPPRT) forms of the enzyme. A pH-rate profile showed that maximum catalysis is achieved above pH 8.0. Surprisingly, at 25 °C, k cat is higher when ADP replaces ATP as substrate for ATPPRT but not for HisG S . The HisG S -catalyzed reaction is limited by the chemical step, as suggested by the enhancement of k cat when Mg 2+ was replaced by Mn 2+ , and by the lack of a pre-steady-state burst of product formation. Conversely, the ATPPRT-catalyzed reaction rate is determined by PRATP diffusion from the active site, as gleaned from a substantial solvent viscosity effect. A burst of product formation could be inferred from pre-steady-state kinetics, but the first turnover was too fast to be directly observed. Lowering the temperature to 5 °C allowed observation of the PRATP formation burst by ATPPRT. At this temperature, the single-turnover rate constant was significantly higher than k cat , providing additional evidence for a step after chemistry limiting catalysis by ATPPRT. This demonstrates allosteric activation by HisZ accelerates the chemical step.

Prosthechea jauana has been recognized as an orchid species endemic to the Venezuelan tepui. The first record of P. jauana in Brazil is presented here, also from a tepui in the Southern phytogeographical district of Pantepui in the Serra do Aracá, at the northern border of the Amazonas state. A detailed morphological description and images of the specimen are presented, as well as an updated distribution map, preliminary conservation status assessment, and taxonomic notes about the species. In addition, we provide species' distribution models for P. jauana based on current and future bioclimatic data. Future projections suggest that the geographic distribution of P. jauana will likely be severely affected, with ~79% of its suitable habitat being reduced by 2041-2060 and ~92% by 2061-2080. Prosthechea jauana could represent a flag species and an example of how climate change may affect the endemic Pantepui flora.

The objective of this study was to evaluate the availability of phosphorus (P) in a soil under no-tillage system after successive applications of liquid swine manure (LSM) doses in soil samples collected at different depths and to select the most appropriate chemical extractors. It was used soil with LSM applications for 19 years, using doses of 0, 25, 50, 75 and 100 m 3  ha -1 and mineral fertilization (350 kg ha -1 in formulation 02-20-18), evaluated at the following depths: 0-10, 10-20 and 20-40 cm. The extractors used were Mehlich-1, Mehlich-3, Prem, Olsen, Bray-1 and Resin. Successive fertilizations with LSM, especially with 100 m 3  ha -1 , increase the availability of P, especially in the 0-10 cm layer, as well adding P in the deeper layers evaluated (20-40 cm). The organic P content in relation to the total P ranged from 16 to 19 %. Bray-1, Olsen and Resin extractors are more efficient in extracting P in soil under no-tillage cultivation after successive fertilizations with liquid swine manure., Competing Interests: 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., (© 2023 Published by Elsevier Ltd.)

Introduction: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil., Methods: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves., Results: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves., Conclusions: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Samaan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study was performed to investigate the convergent validity, discriminative validity, and reliability of the Brazilian version of the low anterior resection syndrome (LARS) score in a population with low educational and socioeconomic levels., Methods: The LARS score was translated into the Portuguese language by forward- and back-translation procedures. In total, 127 patients from a public hospital in Brazil completed the questionnaires. The convergent validity was tested by comparing the LARS score with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core Module 30 (QLQ-C30) and with patients' self-reported quality of life. For the discriminative validity, we tested the ability of the score to differentiate among subgroups of patients regarding neoadjuvant radiotherapy, type of surgery, and tumor distance from the anal verge. The test-retest reliability was investigated in a subgroup of 36 patients who responded to the survey twice in 2 weeks., Results: The LARS score demonstrated a strong correlation with 5 of 6 items from the EORTC QLQ-C30 (P<0.05) and good concordance with patients' self-reported quality of life (95.3%), confirming the convergent validity. The score was able to discriminate between subgroups of patients with different clinical characteristics related to LARS (P<0.001). The agreement between the test and retest showed that 86.1% of the patients remained in the same LARS category, and there was no significant difference between the LARS score numerical values (P=0.80), indicating good reliability overall., Conclusion: The Brazilian version of the LARS score is a valid and reliable instrument to assess postoperative bowel function in a population with low educational and socioeconomic levels.

The enzyme 2'-deoxynucleoside 5'-phosphate N -hydrolase 1 (DNPH1) catalyzes the N -ribosidic bond cleavage of 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate to generate 2-deoxyribose 5-phosphate and 5-hydroxymethyluracil. DNPH1 accepts other 2'-deoxynucleoside 5'-monophosphates as slow-reacting substrates. DNPH1 inhibition is a promising strategy to overcome resistance to and potentiate anticancer poly(ADP-ribose) polymerase inhibitors. We solved the crystal structure of unliganded human DNPH1 and took advantage of the slow reactivity of 2'-deoxyuridine 5'-monophosphate (dUMP) as a substrate to obtain a crystal structure of the DNPH1:dUMP Michaelis complex. In both structures, the carboxylate group of the catalytic Glu residue, proposed to act as a nucleophile in covalent catalysis, forms an apparent low-barrier hydrogen bond with the hydroxyl group of a conserved Tyr residue. The crystal structures are supported by functional data, with liquid chromatography-mass spectrometry analysis showing that DNPH1 incubation with dUMP leads to slow yet complete hydrolysis of the substrate. A direct UV-vis absorbance-based assay allowed characterization of DNPH1 kinetics at low dUMP concentrations. A bell-shaped pH-rate profile indicated that acid-base catalysis is operational and that for maximum k cat / K M , two groups with an average p K a of 6.4 must be deprotonated, while two groups with an average p K a of 8.2 must be protonated. A modestly inverse solvent viscosity effect rules out diffusional processes involved in dUMP binding to and possibly uracil release from the enzyme as rate limiting to k cat / K M . Solvent deuterium isotope effects on k cat / K M and k cat were inverse and unity, respectively. A reaction mechanism for dUMP hydrolysis is proposed.

This study evaluated the drilling path (mm) and the dentin wear (mm 3 ) of two instruments used during guided endodontic access. Twenty mandibular incisors with calcified canals were selected using cone-beam computed tomography (CBCT) and fixed in articulated models. Preoperative CBCT scans were performed in combination with intraoral scanning, and the images were reconstructed in the Blue Sky Bio software for access planning and printing the guides. The access cavity was drilled with 1.0-mm-diameter bur (DSP) and 0.8-mm-diameter bur (Munce). Postoperative CBCT was performed, and the images obtained preoperative and postoperative were superimposed for the analyses. Data were analysed by a t-test and linear regression (α = 0.05). No difference was found in the drilling path (p = 0.422). However, the Munce bur had higher dentin wear than the DSP bur (p = 0.011). A positive linear correlation (R 2  = 0.859) was found between the factors., (© 2022 Australian Society of Endodontology Inc.)

Electroencephalography (EEG) is an exam widely adopted to monitor cerebral activities regarding external stimuli, and its signals compose a nonlinear dynamical system. There are many difficulties associated with EEG analysis. For example, noise can originate from different disorders, such as muscle or physiological activity. There are also artifacts that are related to undesirable signals during EEG recordings, and finally, nonlinearities can occur due to brain activity and its relationship with different brain regions. All these characteristics make data modeling a difficult task. Therefore, using a combined approach can be the best solution to obtain an efficient model for identifying neural data and developing reliable predictions. This paper proposes a new hybrid framework combining stacked generalization (STACK) ensemble learning and a differential-evolution-based algorithm called Adaptive Differential Evolution with an Optional External Archive (JADE) to perform nonlinear system identification. In the proposed framework, five base learners, namely, eXtreme Gradient Boosting, a Gaussian Process, Least Absolute Shrinkage and Selection Operator, a Multilayer Perceptron Neural Network, and Support Vector Regression with a radial basis function kernel, are trained. The predictions from all these base learners compose STACK's layer-0 and are adopted as inputs of the Cubist model, whose hyperparameters were obtained by JADE. The model was evaluated for decoding the electroencephalography signal response to wrist joint perturbations. The variance accounted for (VAF), root-mean-squared error (RMSE), and Friedman statistical test were used to validate the performance of the proposed model and compare its results with other methods in the literature, including the base learners. The JADE-STACK model outperforms the other models in terms of accuracy, being able to explain around, as an average of all participants, 94.50% and 67.50% (standard deviations of 1.53 and 7.44, respectively) of the data variability for one step ahead and three steps ahead, which makes it a suitable approach to dealing with nonlinear system identification. Also, the improvement over state-of-the-art methods ranges from 0.6% to 161% and 43.34% for one step ahead and three steps ahead, respectively. Therefore, the developed model can be viewed as an alternative and additional approach to well-established techniques for nonlinear system identification once it can achieve satisfactory results regarding the data variability explanation.

Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases., 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.)

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.

The components and the salivary flow have a direct influence on the composition of the oral microbiota of children and young people with oropharyngeal dysphagia, and studies have already demonstrated the excessive accumulation of supragingival dental calculus in individuals with enteral nutrition. This study aimed to compare the oral hygiene, biochemical, and microbiological aspects of the oral cavity of children and young people with neurological impairment and oropharyngeal dysphagia. Forty children and young people with neurological impairment and oropharyngeal dysphagia were enrolled and divided into two groups: group I, encompassing 20 participants fed via gastrostomy; and group II, encompassing 20 participants fed via the oral route. Oral hygiene and salivary pH and flow were assessed, and a polymerase chain reaction was performed to evaluate the messenger RNA expressions of Porphyromonas gingivalis , Tanerella forsythia , and Treponema denticola . In groups I and II, the mean Oral Hygiene Index-Simplified scores were 4 and 2, respectively, showing a significant difference; the mean Calculus Index scores were 2 and 0, respectively, showing a significant difference; and the mean pH was 7.5 and 6.0, respectively, showing a significant difference. Bacterial analysis indicated no association between the two groups. It can be concluded that children and young people who use gastrostomy had a poorer oral hygiene, greater dental calculus deposition, and higher salivary pH. The saliva of patients in both groups contained Porphyromonas gingivalis , Tanerella forsythia , and Treponema denticola .

The bifunctional enzyme phosphoribosyl-ATP pyrophosphohydrolase/phosphoribosyl-AMP cyclohydrolase (HisIE) catalyzes the second and third steps of histidine biosynthesis: pyrophosphohydrolysis of N 1 -(5-phospho-β-D-ribosyl)-ATP (PRATP) to N 1 -(5-phospho-β-D-ribosyl)-AMP (PRAMP) and pyrophosphate in the C-terminal HisE-like domain, and cyclohydrolysis of PRAMP to N -(5'-phospho-D-ribosylformimino)-5-amino-1-(5″-phospho-D-ribosyl)-4-imidazolecarboxamide (ProFAR) in the N-terminal HisI-like domain. Here we use UV-VIS spectroscopy and LC-MS to show Acinetobacter baumannii putative HisIE produces ProFAR from PRATP. Employing an assay to detect pyrophosphate and another to detect ProFAR, we established the pyrophosphohydrolase reaction rate is higher than the overall reaction rate. We produced a truncated version of the enzyme-containing only the C-terminal (HisE) domain. This truncated HisIE was catalytically active, which allowed the synthesis of PRAMP, the substrate for the cyclohydrolysis reaction. PRAMP was kinetically competent for HisIE-catalyzed ProFAR production, demonstrating PRAMP can bind the HisI-like domain from bulk water, and suggesting that the cyclohydrolase reaction is rate-limiting for the overall bifunctional enzyme. The overall k cat increased with increasing pH, while the solvent deuterium kinetic isotope effect decreased at more basic pH but was still large at pH 7.5. The lack of solvent viscosity effects on k cat and k cat / K M ruled out diffusional steps limiting the rates of substrate binding and product release. Rapid kinetics with excess PRATP demonstrated a lag time followed by a burst in ProFAR formation. These observations are consistent with a rate-limiting unimolecular step involving a proton transfer following adenine ring opening. We synthesized N 1 -(5-phospho-β-D-ribosyl)-ADP (PRADP), which could not be processed by HisIE. PRADP inhibited HisIE-catalyzed ProFAR formation from PRATP but not from PRAMP, suggesting that it binds to the phosphohydrolase active site while still permitting unobstructed access of PRAMP to the cyclohydrolase active site. The kinetics data are incompatible with a build-up of PRAMP in bulk solvent, indicating HisIE catalysis involves preferential channeling of PRAMP, albeit not via a protein tunnel., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Obesity is a pro-inflammatory disease critical for developing breast cancer (BC), which impacts the profiles of systemic inflammatory mediators and determinants of different disease clinical outcomes remains little explored., Methods: A total of 195 patients diagnosed with breast cancer were included. Aiming to exclude chemotherapy interference on circulating mediators, samples were collected at diagnosis, out of the treatment period. Patients were classified as normal weight (BMI up to 24.9 kg/m2) or overweight (BMI ≥25.0 kg/m2). Serum levels of IL-4, IL-12, hydroperoxides, and nitric oxide metabolites (NOx) were measured. Also, tumor expression of inducible nitric oxide synthase (iNOS), TGF-β1, CD4 + , and CD8 + lymphocytes were evaluated., Results: IL-4 levels were significantly increased in the overweight BC group (p = 0.0329), including patients with luminal B subtype (p = 0.0443), presence of lymph node metastases (p = 0.0115) and age of diagnosis below 50 years, (p = 0.0488). IL-12 levels were significantly increased in overweight BC patients with lymph node metastases (p = 0.0115). Hydroperoxides were increased in overweight BC patients (p = 0.0437), including those with tumors smaller than 2 cm (p = 0.05). NOx levels were also increased in overweight BC patients, including those with luminal B disorders (p = 0.0443), high-grade tumors (p = 0.0351) and lymph node metastases (p = 0.0155). The expression of iNOS (p < 0.001) and TCD4+ lymphocytes (p = 0.0378) was significantly investigated in tumor biopsies from overweight BC women., Conclusions: These data provide a picture of the influence of excess body weight on inflammatory mediators' systemic and tumoral profiles, especially in patients displaying poor outcome BC., Competing Interests: The authors have no conflict to declare., (© 2023 The Authors.)