Search

Gustavo R Mota,1 Mário Antônio de Moura Simim,2 Izabela Aparecida dos Santos,1 Jeffer Eidi Sasaki,1 Moacir Marocolo3 1Human Performance and Sport Research Group, Department of Sport Sciences, Institute of Health Sciences, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil; 2Research Group in Biodynamic Human Movement, Institute of Physical Education and Sports, Federal University of Ceará, Fortaleza, CE, Brazil; 3Physiology and Human Performance Research Group, Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora, MG, BrazilCorrespondence: Gustavo R MotaHuman Performance and Sport Research Group, Department of Sport Sciences/Institute of Health Sciences, Federal University of Triângulo Mineiro, Av. Tutunas, 490 Uberaba/MG, Uberaba 38061-500, BrazilTel +55 34 3700-6633Email grmotta@gmail.comAbstract: This systematic review investigated the effects of wearing below-knee compression stockings (CS) on exercise performance (or sports activity) and associated physiological and perceived indicators. We searched articles on PubMed using the following terms: “graduated compression stockings”; “compression stockings”; “graduated compression socks”; “compression socks” combined with “performance”, “athletes”, “exercise”, “exercise performance”, “fatigue”, “sports” and “recovery”, resulting in 1067 papers. After checking for inclusion criteria (e.g., original studies, healthy subjects, performance analysis), 21 studies were selected and analyzed. We conclude that wearing CS during exercise improved performance in a small number of studies. However, wearing CS could benefit muscle function indicators and perceived muscle soreness during the recovery period. Future research should investigate the chronic effect of CS on Sports Medicine and athletic performance.Keywords: ergogenic aid, fatigue, sports, medicine, prevention, soccer, running

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy., Methods: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial comparing a QFR-based with an FFR-based diagnostic strategy for patients with intermediate coronary stenosis. Enrolment was performed in 34 centres across 11 European countries. Patients aged 18 years or older with either chronic coronary syndrome or stabilised acute coronary syndrome, and with at least one intermediate non-culprit stenosis (40-90% diameter stenosis by visual estimate; referred to here as a study lesion), were randomly assigned (1:1) to the QFR-guided or the FFR-guided group. Randomisation was done using a concealed web-based system and was stratified by diabetes and presence of a left anterior descending coronary artery study lesion. The primary endpoint was a composite of death, myocardial infarction, and unplanned revascularisation at 12 months. The predefined non-inferiority margin was 3·4% and the primary analysis was performed in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03729739) and long-term follow-up is ongoing., Findings: Between Nov 6, 2018, and July 21, 2023, 2000 patients were enrolled and randomly assigned to the QFR-guided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67·3 years (IQR 59·9-74·7); 1538 (76·9%) patients were male and 462 (23·1%) were female. Median follow-up time was 365 days (IQR 365-365). At 12 months, a primary endpoint event had occurred in 67 (6·7%) patients in the QFR group, and in 41 (4·2%) patients in the FFR group (hazard ratio 1·63 [95% CI 1·11-2·41]). The event proportion difference was 2·5% (90% two-sided CI 0·9-4·2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3·4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1·8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1·0%) patients in the QFR group and seven (0·7%) in the FFR group. One patient in the QFR group died in relation to the index procedure., Interpretation: The results of the FAVOR III Europe trial do not support the use of QFR if FFR is available to guide revascularisation decisions in patients with intermediate coronary stenosis. This finding could have implications for current clinical guidelines recommending QFR for this purpose., Funding: Medis Medical Imaging Systems and Aarhus University., Competing Interests: Declaration of interests BKA reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. GCam reports institutional research grants from SMT, Medis Medical Imaging, Abbott Vascular, GADA, Siemens, and GE Healthcare outside the present work. TR reports consultant and proctoring honoraria from Boston Scientific, EPS Vascular, and Cardirad. BES is supported by the H H Sheikh Khalifa bin Hamad Al-Thani Research Programme; has received research grants to the institution from Boston Scientific, the B Braun Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, Edwards Lifesciences, the Iten-Kohaut Foundation, and the OPO Foundation; has received consulting and speaker fees from Abbott Vascular, Abiomed, and Boston Scientific; and received free licences for the QFR application from Medis Medical Imaging during the trial. LDS reports consulting fees from Abbott Vascular, Boston Scientific, and Philips outside the submitted work. JE reports serving as a speaker or advisory board member for Abbott, Boston Scientific, Medis Medical Imaging, and Philips. RL-P received a free licence for the QFR software from Medis Medical Imaging during the trial. UL reports research grants to the institution from Abbott, Amgen, Bayer, and Novartis. RSD reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. HM-R reports consultancy fees from Medis Medical Imaging and speaker fees from Philips and Abbott. LK received free licences for the QFR application from Medis Medical Imaging during the trial. JA reports teaching grants from Biotronik and Medis Medical Imaging. YSA reports consulting fees from Boston Scientific and Shockwave. TL served as a Medis technical and research support consultant in Haga Hospital (The Hague, Netherlands) and performed beta testing of software from Medis Medical Imaging, neither of which was study related, and received a free licence for the QFR application from Medis Medical Imaging during the trial. KL received free licences for the QFR application from Medis Medical Imaging during the trial; speaker fees and travel support from BMS and Boston Scientific; speaker fees from DGK; and served as an advisory board member for BMS. GCas received a free licence for the QFR application from Medis Medical Imaging during the trial. SB reports institutional research grants from Medis Medical Imaging, SMT, Abbott, Siemens, Insight Lifetech, and Amgen; free licences for the QFR application from Medis Medical Imaging during the trial; speaker's fee from SMT, Medis Medical Imaging, Abbott, and Siemens; and advisory board activities for Siemens. NTO reports institutional research grants from Abbott and from Shockwave. RS reports an institutional research grant from Abbott; institutional research contract with Medis Medical Imaging; and speaker and consultation fees from Abbott and Fondazione Menarini. EHC reports institutional research grants from Abbott, Biosensors, Meril, and Medis Medical Imaging; and speaker fees from Abbott and EPS. NRH reports Institutional research grants from Abbott, B Braun, Biosensors, Boston Scientific, and Medis Medical Imaging; and speaker fees from Abbott and EPS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV., Methods: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action., Results: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV., Conclusions: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Aims: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients., Methods and Results: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status., Conclusion: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status., Clinical Trial Registration: ClinicalTrials.gov NCT03772743., Competing Interests: Conflict of interest: G.Cam. received research grants and personal fees from ABBOTT VASCULAR, personal fees from MENARINI, personal fees from AMGEN, personal fees from SANOFI, outside the submitted work. S.B. received personal fees from ABBOTT VASCULAR, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV- firefly and MAYV- nanoluc , respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV- firefly and three rounds for MAYV- nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV- nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase., 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI)., Objective: To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease., Design, Setting, and Participants: This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document., Interventions: Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy., Main Outcomes and Measures: The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5., Results: Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points., Conclusions and Relevance: HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI., Trial Registration: ClinicalTrials.gov Identifier: NCT03772743.

Background: patients with atrial fibrillation (AF) under treatment with chronic oral anticoagulation (OAC) often require coronary angiography with or without percutaneous coronary intervention (PCI). Deciding the management of OAC during this periprocedural period requires balancing the risks of hemorrhage and thrombotic complications. Guidelines recommend an uninterrupted strategy in patients receiving Vitamin-K Antagonists (VKA). However, for patients undergoing coronary angiography or PCI while on direct oral anticoagulants (DOACs), withdrawal 12-24 h prior to the procedure is still recommended. This is based on expert opinions given the lack of evidence. Therefore, whether DOAC discontinuation prior to trans-radial coronary procedures should be the strategy of choice is a matter of debate and solid evidence is needed to guide clinical decision making., Methods: The DOAC-NOSTOP study is a prospective, single-arm, open-label study evaluating the safety of DOACs continuation in 200 patients undergoing transradial percutaneous coronary procedures. DOAC treatment will not be interrupted throughout the periprocedural period. Primary outcome will be Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 events, assessed at a 30-day follow-up., Conclusions: The DOAC-NOSTOP is the first study prospectively assessing the risk of bleeding with uninterrupted DOAC in patients undergoing trans-radial percutaneous coronary procedures., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [Ru II (L)(NO 2 )(tpy)]PF 6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [Ru II (L)(NO 2 )(tpy)] + were evaluated. The K a values for the HSA-[Ru II (bdq)(NO 2 )(tpy)] + is 10 times bigger than HSA-[Ru II (bd)(NO 2 )(tpy)] + . The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [Ru II (bdq)(NO 2 )(tpy)] + is found close to the Trp-241 residue, while the [Ru II (bd)(NO 2 )(tpy)] + complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (K b ) and ethidium bromide replacement (K SV and K app ) showed weak interaction in the system fs-DNA-[Ru II (bdq)(NO)(tpy)] + . Furthermore, fs-DNA-[Ru II (bd)(NO 2 )(tpy)] + and fs-DNA-[Ru II (bd)(NO)(tpy)] 3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[Ru II (bd)(NO 2 )(tpy)] + and fs-DNA-[Ru II (bd)(NO)(tpy)] 3+ , suggest semi-intercalative accompanied by major groove binding interaction modes. The [Ru II (bd)(NO 2 )(tpy)] + and [Ru II (bd)(NO)(tpy)] 3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Mayaro virus (MAYV) is an arbovirus with emerging potential, though with a limited understanding of its epidemiology and evolution due to the lack of studies and surveillance. Here, we investigated 71 MAYV genome sequences from the Americas available at GenBank and characterized the phylogenetic relationship among virus strains. A phylogenetic analysis showed that sequences were grouped according to the genotypes L, D, and N. Genotype D sequences were closely related to sequences collected in adjacent years and from their respective countries, suggesting that isolates may have originated from circulating lineages. The coalescent analysis demonstrated similar results, indicating the continuous circulation of the virus between countries as well. An unidentified sequence from the USA was grouped with genotype D, suggesting the insertion of this genotype in the country. Furthermore, the recombination analysis detected homologous and three heterologous hybrids which presented an insertion into the nsP3 protein. Amino acid substitutions among sequences indicated selective pressure sites, suggesting viral adaptability. This also impacted the binding affinity between the E1-E2 protein complex and the Mxra8 receptor, associated with MAYV entry into human cells. These results provide information for a better understanding of genotypes circulating in the Americas.

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl 2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI 50 of 10.5 μM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 μM., (© 2023 Wiley-VCH GmbH.)

Background: The performance of latest iteration transcatheter aortic valve replacement platforms in patients with small aortic anatomy remains underexplored., Objectives: The aim of this study was to evaluate effectiveness and performance between the self-expanding (SE) Evolut PRO and PRO+ and the balloon-expandable (BE) SAPIEN ULTRA in patients with small aortic annuli., Methods: Data from the OPERA-TAVI (Comparative Analysis of Evolut PRO vs. SAPIEN 3 ULTRA Valves for Transfemoral Transcatheter Aortic Valve Implantation) registry were used, with 1:1 propensity score matching. Primary endpoints included 1-year effectiveness composite (all-cause mortality, disabling stroke, or heart failure hospitalization) and 30-day device-related (hemodynamic structural valve dysfunction and nonstructural valve dysfunction) outcomes., Results: Among 3,516 patients, 251 matched pairs with aortic annular area <430 mm 2 were assessed. The 1-year primary effectiveness outcome did not differ significantly between cohorts (SE 10.8% vs BE 11.2%; P = 0.91). The 30-day device-oriented composite outcome was more favorable in the Evolut PRO group (SE 4.8% vs BE 10.4%; P = 0.027). Notably, SE valve recipients showed higher rates of disabling stroke (SE 4.0% vs BE 0.0%; P < 0.01) and paravalvular leaks (mild or greater: SE 48.5% vs BE 18.6% [P < 0.001]; moderate: SE 4.5% vs BE 1.2% [P = 0.070]). The BE group had higher rates of prosthesis-patient mismatch (moderate or greater: SE 16.0% vs BE 47.1% [P < 0.001]; severe: SE 1.3% vs BE 5.7% [P = 0.197]) and more patients with residual mean gradients >20 mm Hg (SE 1.0% vs BE 13.5%; P < 0.001)., Conclusions: In patients with small aortic annuli, transcatheter aortic valve replacement with latest iteration devices is safe. SE platforms are associated with more favorable device performance in terms of hemodynamic structural and nonstructural dysfunction. Randomized data are needed to validate these findings and guide informed device selection., Competing Interests: Funding Support and Author Disclosures Dr Scotti has served as a consultant for Edwards Lifesciences and NeoChord. Dr Pilgrim has received research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and has received speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Meier has received an institutional grant from Edwards Lifesciences. Dr Barbanti is a consultant for Boston Scientifics, Edwards Lifesciences, and Medtronic. Dr Latib has served on advisory boards for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord, VDyne, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Wearable resistance (WR) and weighted vests (WV) can be used in almost all training conditions to enhance sprint performance; however, positioning and additional mass are different in WV and WR strategies, affecting performance and kinematics differently. We aimed to systematically review the literature, searching for intervention studies that reported the acute or chronic kinematic and performance impact of WV and WR and comparing them. We analyzed Pubmed, Embase, Scopus, and SPORTDiscuss databases for longitudinal and cross-over studies investigating sprint performance or kinematics using an inverse-variance with a random-effect method for meta-analysis. After the eligibility assessment, 25 studies were included in the meta-analysis. Cross-over WR and WV studies found significantly higher sprint times and higher ground contact times (CT) compared to unloaded (UL) conditions. However, WR presented a lower step frequency (SF) compared to UL, whereas WV presented a lower step length (SL). Only one study investigated the chronic adaptations for WR, indicating a superiority of the WR group on sprint time compared to the control group. However, no difference was found chronically for WV regarding sprint time, CT, and flight time (FT). Our findings suggest that using WV and WR in field sports demonstrates overload sprint gesture through kinematic changes, however, WR can be more suitable for SF-reliant athletes and WV for SL-reliant athletes. Although promising for chronic performance improvement, coaches and athletes should carefully consider WV and WR use since there is no supporting evidence that WV or WR will impact sprint performance, CT, and FT., (© 2024. The Author(s).)

Evidence regarding sex-related differences in response to transcatheter aortic valve implantation according to the valve type is lacking. This study sought to evaluate the impact of sex on the treatment effect of Evolut-PRO/PRO+ (PRO) or Sapien 3 Ultra (ULTRA) devices on clinical outcomes. Comparative Analysis of Evolut PRO vs Sapien 3 Ultra Valves for Transfemoral Transcatheter Aortic Valve Implantation (OPERA-TAVI) is a multicenter multinational registry including patients undergoing latest-iteration PRO or ULTRA implantation. Overall, 1174 out of 1897 patients were matched based on valve type and compared according to sex, while 470 males and 630 females were matched and compared according to valve type. Thirty-day and 1-year outcomes were evaluated. In both PRO and ULTRA group, males had a higher comorbidity burden, while females had smaller aortic root. Both 30-day (device success [DS], early safety outcome, permanent pacemaker implantation [PPI], patient-prosthesis mismatch [PPM], paravalvular regurgitation [PVR], bleedings, vascular complications, and all-cause death) and 1-year outcomes (all-cause death, stroke and heart failure hospitalization) did not differ according to sex in both valve groups. However, male sex decreased the likelihood of 30-day DS with ULTRA versus PRO (p for interaction 0.047). A higher risk of 30-day PPI and 1-year stroke, and a lower risk of PPM was observed in PRO versus ULTRA, regardless of sex. In conclusion, sex did not modify the treatment effect of PRO versus ULTRA on clinical outcomes, with the exception of 30-day DS that was decreased in males (versus females) receiving ULTRA (versus PRO)., (Copyright © 2024. Published by Elsevier Inc.)

We investigated whether the application of photobiomodulation therapy (PBMT) immediately after a standardized warm-up (WU + PBMT) or traditional PBMT (no pre-warming) would influence performance in intermittent testing and intensity variables. In a counterbalanced randomized crossover design, twelve female futsal players (mean age: 23.9 ± 3.8 years) attended four sessions. Each session involved either a standardized warm-up or maintaining seated rest for five minutes. Subsequently, PBMT or placebo (with the PBMT device turned off) was applied, followed by the YoYo Intermittent Recovery Level 1 test (YYIR1) during which we assessed heart rate, rating of perceived exertion, and blood lactate levels. The performance in YYIIR1 was superior ( p  = 0.02) in the WU + PBMT condition (440.0 ± 59.0 m) compared to the WU + Placebo (353.3 ± 94.7 m), and placebo alone (no warm-up) (325.0 ± 67.2 m). We conclude that a combination of a specific warm-up before PBMT application improves high-intensity intermittent performance in amateur female futsal players without affecting intensity variables., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Santos, Lemos, Puggina and Mota.)

Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro . To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV endonuclease, which possibly limits the interaction of viral RNA with other proteins. Therefore, our results suggest a dual mechanism of antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of antiviral drugs could be developed based on the selective optimization of molecules., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mauricio Lacerda Nogueira reports financial support was provided by The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics., (© 2023 The Author(s).)

The genus Mammarenavirus belonging to the family Arenaviridae encompasses pathogenic viral species capable of triggering severe diseases in humans, causing concern for the health system due to the high fatality rate associated with them. Currently, there is a dearth of specific therapies against pathogens of the genus. Natural products isolated from plants have impacted the development of drugs against several diseases. The Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) database offers several natural compounds with antimicrobial activities that can be used in the development of new antiviral drugs. In this context, here we modeled the arenavirus L protein, multifunctional machinery essential for the viral replicative cycle, making this enzyme a potential candidate for targeting the development of antivirals against genus pathogens. Using the modeled L protein, a virtual screening was performed, which suggested eleven molecules from the NuBBE database that binds to the active site of the L protein, which was promising in the in silico predictions of absorption and toxicity analysis. The NuBBE 1642 molecule proved to be the best candidate for four of the five species evaluated, acting as a possible broad-spectrum molecule. Additionally, our results showed that the L protein is highly conserved among species of the genus, as well as presenting close phylogenetic relationships between many of the species studied, strengthening its candidacy as a therapeutic target. The data presented here demonstrate that some NuBBE molecules are potential ligands for the L protein of arenaviruses, which may help to contain possible outbreaks.Communicated by Ramaswamy H. Sarma.

Chikungunya virus (CHIKV) belongs to the Alphavirus genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. Initial screening showed that all three peptides inhibited the CHIKV replication cycle in baby hamster kidney fibroblast cells (BHK-21) and human hepatocarcinoma epithelial cells (Huh-7). GA-Hecate and its analog PSSct1905 were the most active, demonstrating suppression of viral infection by more than 91%. The analog PSSct1905 exhibited a protective effect in cells against CHIKV infection. We also observed that the analogs PSSct1905 and PSSct1910 affected CHIKV entry into both cell lines, inhibiting viral attachment and internalization. Finally, all tested compounds presented antiviral activity on the post-entry steps of CHIKV infection in all cells evaluated. In conclusion, this study highlights the potential of the peptide GA-Hecate and its analogs as novel anti-CHIKV compounds targeting different stages of the viral replication cycle, warranting the development of GA-Hecate-based compounds with broad antiviral activity.

Enteroviruses are pathogens responsible for several diseases, being enterovirus A71 (EVA71) the second leading cause of hand, foot, and mouth disease (HFMD), especially in Asia-Pacific countries. HFMD is mostly common in infants and children, with mild symptoms. However, the disease can result in severe nervous system disorders in children as well as in immunosuppressed adults. The virus is highly contagious, and its transmission occurs via fecal-oral, oropharyngeal secretions, and fomites. The EVA71 burdens the healthy systems and economies around the world, however, up to date, there is no antiviral approved to treat infected individuals and the existent vaccines are not available or approved to be used worldwide. In this context, an extensive literature research was conducted to describe and summarize the recent advances in natural and/or synthetic compounds with antiviral activity against EVA71. The summarized data presented here might simply encourage the future studies in EVA71 antiviral development, by encouraging further research encompassing these compounds or even the application of the techniques and technologies to improve or produce new antiviral molecules., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated the associations between total and regional body composition with performance in the special judo fitness test (SJFT), as well as strength and power tests (countermovement vertical jump-CMJ, squat jump-SJ, plyometric push-up-PPU, and force push-up-FPU). Twenty-three high-level judo athletes participated in this study. Initially, they underwent dual-energy X-ray absorptiometry, after which they performed the CMJ, SJ, PPU, and FPU tests. On another day, the SJFT was carried out. Correlations were tested using Pearson's test. The performance in the SJFT was correlated with the total and arm %fat mass (r = -0.759), torso fat mass (r = -0.802), torso %fat mass (r = -0.822) and in the lower limb regions with the leg fat mass (r = -0.803) and leg %fat (r = -0.745). In the strength and power tests, there were also negative correlations observed between regional fat and performance. There was a negative correlation between the percentage of total fat and performance in the SJFT (r = -0.824), SJ (r = -0.750), CMJ (r = -0.742), PPU (r = -0.609), and FPU (r = -0.736). Fat, both total fat and regional fat in the arms, torso, and legs, is strongly correlated with a poor performance in the SJFT and poor strength and power.

The objective was to optimize the phenolic compounds extraction from cocoa shells using the simplex-centroid design with a mixture of solvents (water, methanol, and acetone) as its components, to prove the presence of these compounds and antioxidant activity. Also, the development of dairy products, such as milk beverages and dairy desserts, with bioactive compounds, through the replacement of cocoa powder by cocoa shell was studied and evaluated sensorially. The extraction optimization indicated that a solvent with 56.44% water, 23.77% methanol, and 19.80% acetone are ideal for maximizing the phenolic compounds. In addition, the cocoa shell showed a high antioxidant activity by the methods β-carotene/linoleic acid, FRAP, and phosphomolybdenum complex. The Check-All-That-Apply, Cochran's Q test, contingency analysis, and hierarchical cluster analysis allowed description characteristics of the dairy products and showed sensory differences between formulations with 100% cocoa shell and others. Both dairy products had good sensory acceptance in all attributes evaluated (appearance, flavor, texture, and overall impression), and their scores did not differ statistically by Tukey's test ( p  > 0.05). Thus, the cocoa shell is shown as an alternative substitute ingredient to be used in the dairy industry., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Enterovirus A71 (EVA71) belongs to the Picornaviridae family and is the main etiological agent of hand, foot, and mouth disease (HFMD). There is no approved antiviral against EVA71, and therefore the search for novel anti-EVA71 therapeutics is essential. In this context, the antiviral activity of proteins isolated from snake venoms has been reported against a range of viruses. Here, the proteins CM10 and CM14 isolated from Bothrops moojeni, and Crotamin and PLA2 CB isolated from Crotalus durissus terrificus were investigated for their antiviral activity against EVA71 infection. CM14 and Crotamin possessed a selective index (SI) of 170.8 and 120.4, respectively, while CM10 and PLA2 CB had an SI of 67.4 and 12.5, respectively. CM14 inhibited all steps of viral replication (protective effect: 76 %; virucidal: 99 %; and post-entry: 99 %). Similarly, Crotamin inhibited up to 99 % of three steps. In contrast, CM10 and PLA2 CB impaired one or two steps of EVA71 replication, respectively. Further dose-response assays using increasing titres of EVA71 were performed and CM14 and Crotamin retained functionality with high concentrations of EVA71 (up to 1000 TCID 50 ). These data demonstrate that proteins isolated from snake venom are potent inhibitors of EVA71 and could be used as scaffolds for future development of novel antivirals., 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.)

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I) 2 K [(KKYRYHLKPF) 2 K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I) 2 K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I) 2 K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I) 2 K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV.

Mayaro virus (MAYV), first isolated in 1954 in Trinidad and Tobago islands, is the causative agent of Mayaro fever, a disease characterized by fever, rashes, headaches, myalgia, and arthralgia. The infection can progress to a chronic condition in over 50% of cases, with persistent arthralgia, which can lead to the disability of the infected individuals. MAYV is mainly transmitted through the bite of the female Haemagogus spp. mosquito genus. However, studies demonstrate that Aedes aegypti is also a vector, contributing to the spread of MAYV beyond endemic areas, given the vast geographical distribution of the mosquito. Besides, the similarity of antigenic sites with other Alphavirus complicates the diagnoses of MAYV, contributing to underreporting of the disease. Nowadays, there are no antiviral drugs available to treat infected patients, being the clinical management based on analgesics and non-steroidal anti-inflammatory drugs. In this context, this review aims to summarize compounds that have demonstrated antiviral activity against MAYV in vitro, as well as discuss the potentiality of viral proteins as targets for the development of antiviral drugs against MAYV. Finally, through rationalization of the data presented herein, we wish to encourage further research encompassing these compounds as potential anti-MAYV drug candidates., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research findings in natural sciences need to be comparable and reproducible to effectively improve our understanding of ecological and behavioural patterns. In this sense, knowledge frontiers in biodiversity studies are directly tied to taxonomic research, especially in species-rich tropical regions. Here we analysed the taxonomic information available in 470 studies on Brazilian ant diversity published in the last 50 years. We aimed to quantify the proportion of studies that provide enough data to validate taxonomic identification, explore the frequency of studies that properly acknowledge their taxonomic background, and investigate the primary resources for ant identification in Brazil. We found that most studies on Brazilian ant diversity (73.6%) explicitly stated the methods used to identify their specimens. However, the proportion of papers that provide complete data for the repository institutions and vouchered specimens is vanishingly small (5.8%). Additionally, only 40.0% of the studies consistently presented taxon authorities and years of description, rarely referencing taxonomic publications correctly. In turn, the number of specialists and institutions consulted for ant identification in Brazil has increased in the last years, along with the number of studies that explicitly provide their taxonomic procedures for ant identification. Our findings highlight a shift between generations regarding the recognition of taxonomy as fundamental science, deepening our understanding of biodiversity., (© 2023 The Authors.)

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [Co III (L 1 ) 2 ]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication). Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV-nanoluciferase in the presence of the compound, showing that [Co III (L 1 ) 2 ]Cl inhibited CHIKV infection with the selective index of 3.26. [Co III (L 1 ) 2 ]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [Co III (L 1 ) 2 ]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [Co III (L 1 ) 2 ]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [Co III (L 1 ) 2 ]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects., (© 2022. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Zika virus is the etiologic agent of Zika fever, and has been previously associated with cases of microcephaly, drawing the attention of the health authorities worldwide. However, no vaccine or antiviral are currently available. Phospholipases A 2 (PLA 2 ) isolated from snake venoms have demonstrated antiviral activity against several viruses. Here we demonstrated the anti-ZIKV activity of bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 h, when virus titers were evaluated. BthTX-I and II presented strong dose-dependent inhibition of ZIKV, with a SI of 149.1 and 1.44 × 10 5 , respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards post-entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with DII and DIII domains from ZIKV Envelope protein. Our findings show that these PLA 2 s could be used as useful templates for the development of future antiviral candidate drugs against Zika fever., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis., Methods: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies., Conclusions: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072)., Competing Interests: Conflict of interest R Nuis: nothing to declare. E van Belle: nothing to declare. R Teles: nothing to declare. D Blackman: nothing to declare. V Veulemans: received consulting fees, travel expenses, or study honoraria from Medtronic, Edwards Lifesciences, and Boston Scientific. I Amat Santos: proctor for Medtronic, Boston Scientific, Meril Life, and Products&Features. T Pilgrim: nothing to declare. G Tarantini: consulting fees, travel expenses, or study honoraria from Medtronic, Edwards Lifesciences, and gada. F Saia: advisory Board and Lecture Fees from Abbott, Medtronic, Edwards. I Iakovou: nothing to declare. J Mascherbauer: consulting fees, travel expenses, unrestricted grants from Medtronic,. Edwards Lifesciences, Boston Scientific, Abbott. F Vincent: nothing to declare. M Geleijnse: nothing to declare. J Sathananthan: consultant to Edwards, Medtronic and Boston scientific. D Wood: nothing to declare. R Makkar: nothing to declare. N Van Mieghem: received research grants from Edwards, Medtronic and Boston scientific., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The emergence and rapid spread outside of monkeypox virus (MPXV) to non-endemic areas has led to another global health emergency in the midst of the COVID-19 pandemic. The scientific community has sought to rapidly develop in vitro and in vivo models that could be applied in research with MPXV. In vitro models include two-dimensional (2D) cultures of immortalized cell lines or primary cells and three-dimensional (3D) cultures. In vitro models are considered cost-effective and can be done in highly controlled conditions; however, they do not always resemble physiological conditions. In this way, several in vivo models are being characterized to meet the growing demand for new studies related to MPXV. In this review, we summarize the main MPXV models that have already been developed and discuss how they can contribute to advance the understanding of its pathogenesis, replication, and transmission, as well as identifying antivirals to treat infected patients., Competing Interests: The authors declare no conflict of interest., (© 2022.)

The Chikungunya virus (CHIKV) causes Chikungunya fever, a disease characterized by symptoms such as arthralgia/polyarthralgia. Currently, there are no antivirals approved against CHIKV, emphasizing the need to develop novel therapies. The imidazonaphthyridine compound (RO8191), an interferon-α (IFN-α) agonist, was reported as a potent inhibitor of HCV. Here RO8191 was investigated for its potential to inhibit CHIKV replication in vitro. RO8191 inhibited CHIKV infection in BHK-21 and Vero-E6 cells with a selectivity index (SI) of 12.3 and 37.3, respectively. Additionally, RO8191 was capable to protect cells against CHIKV infection, inhibit entry by virucidal activity, and strongly impair post-entry steps of viral replication. An effect of RO8191 on CHIKV replication was demonstrated in BHK-21 through type-1 IFN production mechanism and in Vero-E6 cells which has a defective type-1 IFN production, also suggesting a type-1 IFN independent mode of action. Molecular docking calculations demonstrated interactions of RO8191 with the CHIKV E proteins, corroborated by the ATR-FTIR assay, and with non-structural proteins, supported by the CHIKV-subgenomic replicon cells assay., 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 © 2022. Published by Elsevier B.V.)

We aimed to evaluate the effect of 4 weeks of plyometric training (PT), performed in the pre-competitive period, on the vertical jump performance of professional volleyball athletes. We recruited 17 professional female volleyball players (age: 19 ± 3 years; weight: 67.2 ± 5.50 kg; height: 1.81 ± 0.22 m; body fat: 14.4 ± 2.12%; squat 1RM test: 75.5 ± 7.82 kg; training time experience: 6.2 ± 3.4 years) to participate in four weeks of training and assessments. They were divided into an experimental group (EG = 9) and a control group (CG = 8). Both groups were submitted to friendly matches, technical, tactical and resistance training (4 weeks/˜9 sessions per week), and internal load monitoring was carried out. The EG performed PT twice a week. At the beginning and end of the four weeks, jump tests were performed. The main findings are: 1) PT when incorporated into the pre-competitive period can induce greater improvements in jumping performance (EG = 28.93 ± 3.24 cm to 31.67 ± 3.39 cm; CG = 27.91 ± 4.64 cm to 28.97 ± 4.58 cm; when comparing the percentage delta, we found a difference between groups with ES of 1.04 and P = 0.02); 2) this result is observed when the training load is similar between groups and increases over the weeks, respecting the linear progression principle. Therefore, including plyometric training in the preparatory period for volleyball, with low monotony and training strain increment, is an effective strategy for further CMJ performance improvement., Competing Interests: The experimental work conforms to the highest standards of safety and ethics, and to the laws of the country in which the work took place. The authors state that there is no conflict of interest., (Copyright © Biology of Sport 2023.)

Co-amorphization is a promising approach to stabilize drugs in the amorphous form. Olanzapine, a poorly water-soluble drug was used in this study. Sulfonic acids (saccharin, cyclamic acid and acesulfame), free and in salt forms, were used as co-formers and compared with carboxylic acids commonly used in the preparation of co-amorphous systems. Several manufacturing techniques were tested, and the co-amorphous systems characterized by differential scanning calorimetry, X-ray powder diffraction, thermogravimetry and Fourier-transform infrared spectroscopy. Free sulfonic acids produced co-amorphous systems with the drug, unlike their salts. Spectroscopy data suggests the formation of salts between olanzapine and the sulfonic acids, used as co-formers. The co-amorphous system produced with saccharin by solvent evaporation, showed the most notable solubility enhancement (145 times). The stability of amorphous and co-amorphous olanzapine systems was assessed upon exposure to stress conditions during storage. Amorphized olanzapine readily reconverted back to the crystalline form while sulfonic acids:olanzapine co-amorphous were stable for up to 24 weeks in low/medium humidity conditions (11-75% RH). Results highlight the potential advantages offered by sulfonic acids as co-formers to produce stable and more soluble co-amorphous olanzapine., 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 © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Although the past epidemic of Zika virus (ZIKV) resulted in severe neurological consequences for infected infants and adults, there are still no approved drugs to treat ZIKV infection. In this study, we applied computational approaches to screen an in-house database of 77 natural and semi-synthetic compounds against ZIKV NS5 RNA-dependent RNA-polymerase (NS5 RdRp), an essential protein for viral RNA elongation during the replication process. For this purpose, we integrated computational approaches such as binding-site conservation, chemical space analysis and molecular docking. As a result, we prioritized nine virtual hits for experimental evaluation. Enzymatic assays confirmed that pedalitin and quercetin inhibited ZIKV NS5 RdRp with IC 50 values of 4.1 and 0.5 µM, respectively. Moreover, pedalitin also displayed antiviral activity on ZIKV infection with an EC 50 of 19.28 µM cell-based assays, with low toxicity in Vero cells (CC 50 = 83.66 µM) and selectivity index of 4.34. These results demonstrate the potential of the natural compounds pedalitin and quercetin as candidates for structural optimization studies towards the discovery of new anti-ZIKV drug candidates.

The search for gold-standard materials for bone regeneration is still a challenge in reconstruction surgery. The ratio between hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) in biphasic calcium phosphate ceramics (BCPs) is one of the most important factors in osteoinduction promotion and controlled biodegradability, configurating what is currently considered as a possible gold standard material for bone substitution in reconstructive surgery. Exploring the natural genesis of the HAp and β-TCP phases in fishbones during their postnatal growth, this study developed a biphasic bioceramic obtained from the calcination of Nile tilapia (Oreochromis niloticus) bones as a function of their ages. The natural genesis dynamics of the structural evolution of the β-TCP and HAp phases were characterized by physicochemical methods, taking into account of the age of the fish and the material processing conditions. Thermal analysis (TGA / DTA) showed complete removal of the organic matter and transitions associated with the transformation of carbonated hydroxyapatite (CDHA) to HAp and β-TCP phases. After calcination at 900 °C, the material was characterized by: X-ray diffraction (XRD) and refinement by the Rietveld method; Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR-ATR); Raman spectroscopy; Scanning Electron Microscopy (SEM) and Flame Atomic Absorption Spectroscopy (FAAS). The analysis allowed identification and quantitative estimate of the variations of the HAp and β-TCP phases in the formation of the BCPs. The results showed that the decrease in β-TCP against the increase in the HAp phases is symmetrical to the dynamics of the natural genesis of these phases, surprisingly maintaining the balanced phase proportion even when bones of young fishes were used. The microstructure analysis confirms the observed transformation. In addition, in vivo tests demonstrated the osteoinductive potential of BCP scaffolds implanted in an ectopic site, and their remarkable regenerative functionality, as bone graft, was demonstrated in alveolar bone after tooth extraction. MTT cytotoxicity assay for BCP samples for MC3T3-E1 pre-osteoblasts and L929 fibroblasts cells showed viability equal or higher than 100%. A logistic empirical model is presented to explain the three stages of HAp natural formation with fish age and it is also compared to the fish size evolution., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Biomaterials that effectively act in biological systems, as in treatment and healing of damaged or lost tissues, must be able to mimic the properties of the body's natural tissues in its various aspects (chemical, physical, mechanical and surface). These characteristics influence cell adhesion and proliferation and are crucial for the success of the treatment for which a biomaterial will be required. In this context, the electrospinning process has gained prominence in obtaining fibers of micro- and nanometric sizes from polymeric solutions aiming to produce scaffolds for tissue engineering. In this manuscript, poly(vinylidene fluoride) (PVDF) was used as a polymeric matrix for the manufacture of piezoelectric scaffolds, exploring the formation of the β-PVDF piezoelectric phase. Micro- and nanometric hydroxyapatite (HA) particles were incorporated as a dispersed phase in this matrix, aiming to produce multifunctional composite membranes also with bioactive properties. The results show that it is possible to produce membranes containing micro- and nanofibers of the composite by the electrospinning process. The HA particles show good dispersion in the polymer matrix and predominance of β-PVDF phase. Also, the composite showed apatite growth on its surface after 21 days of immersion in simulated body fluid (SBF). Tests performed on human fibroblasts culture revealed that the electrospun membranes have low cytotoxicity attesting that the composite shows great potential to be used in biomedical applications as bone substitutions and wound healing.

Introduction: Rheumatoid arthritis (RA) composite disease activity indices have become handy tools in daily clinical practice and crucial in defining remission or low disease activity, the main target of the RA treatment. However, there is no definition of the best index to assess disease activity in clinical practice., Objectives: To compare the residual activity among the indices with the ACR/EULAR remission criteria (Boolean method) to identify the most feasible for assessing remission in daily practice, also considering correlation and concordance, sensibility, and specificity., Patients and Methods: We selected 1116 patients with established RA from the real-life rheumatoid arthritis study database-REAL. The composite disease activity indices-DAS28-ESR, DAS28-CRP, SDAI, and CDAI-and their components were compared to the Boolean method to identify residual activity using binomial regression. The indices were analyzed for correlation and agreement using the Spearman index and weighted kappa. The chi-square test evaluated sensibility and specificity for remission based on the Boolean method., Results: DAS28-CRP overestimated remission and confirmed higher residual activity than SDAI and CDAI. The indices showed good correlation and agreement, with a better relationship between SDAI and CDAI (k:0,88). CDAI and SDAI showed higher sensitivity and specificity for remission based on the Boolean method. CDAI was performed in 99% of patients, while DAS28 and SDAI were completed in approximately 85%., Conclusions: Although all composite indices of activity can be used in clinical practice and showed good agreement, CDAI and SDAI have better performance in evaluating remission based on the Boolean method, showing less residual activity and higher sensibility and specificity. In addition, CDAI seems to be more feasible for disease activity evaluation in daily clinical practice, especially in developing countries., Competing Interests: The authors have declared that no competing interests exist.

Herein a systematic series of four [AuLL']n+ n = 0, +1 complexes, where L = 1,3-bis(mesityl)imidazole-2-ylidene (IMes), or triphenylphosphine (PPh3), and L' = chloride, or 4-dimethylaminopyridine (DMAP), had their in vitro antiviral activity assessed against Chikungunya virus (CHIKV). The PPh3 derivatives inhibited viral replication by 99%, whereas the IMes derivatives about 50%. The lipophilicity of the PPh3 derivatives is higher than the IMes-bearing compounds, which can be related to their more prominent antiviral activities. The dissociation of DMAP is faster than chloride in solution for both IMes and PPh3 derivatives; however, it does not significantly affect their in vitro activities, showing a higher dependence on the nature of L rather than L' towards their antiviral effects. All complexes bind to N-acetyl-L-cysteine, with the Ph3P-bearing complexes coordinating at a faster rate to this amino acid. The binding constants to bovine serum albumin are in the order of 104, slightly higher for the DMAP complexes in both PPh3 and IMes derivatives. Mechanistic investigations of the PPh3 complexes showed a ubiquitous protective effect of the compounds in the pretreatment, early stages, and post-entry assays. The most significant inhibition was observed in post-entry activity, in which the complexes blocked viral replication in 99%, followed by up to 95% inhibition of the early stages of infection. Pretreatment assays showed a 92% and 80% replication decrease for the chloride and DMAP derivatives, respectively. dsRNA binding assays showed a significant interaction of the compounds with dsRNA, an essential biomolecule to viral replication., (© The Author(s) 2022. Published by Oxford University Press.)

SARS-CoV-2 is the etiological agent of COVID-19, which represents a global health emergency that was rapidly declared a pandemic by the World Health Organization. Currently, there is a dearth of effective targeted therapies against viruses. Natural products isolated from traditional herbal plants have had a huge impact on drug development aimed at various diseases. Lapachol is a 1,4- naphthoquinone compound that has been demonstrated to have therapeutic effects against several diseases. SARS-CoV-2 non-structural proteins (nsps) play an important role in the viral replication cycle. Nsp9 seems to play a key role in transcription of the RNA genome of SARS-CoV-2. Virtual screening by docking and molecular dynamics suggests that lapachol derivatives can interact with Nsp9 from SARS-CoV-2. Complexes of lapachol derivatives V, VI, VIII, IX, and XI with the Nsp9 RNA binding site were subjected to molecular dynamics assays, to assess the stability of the complexes via RMSD. All complexes were stable over the course of 100 ns dynamics assays. Analyses of the hydrogen bonds in the complexes showed that lapachol derivatives VI and IX demonstrated strongest binding, with a stable or increasing number of hydrogen bonds over time. Our results demonstrate that Nsp9 from SARS-CoV-2 could be an important target in prospecting for ligands with antiviral potential. In addition, we showed that lapachol derivatives are potential ligands for SARS-CoV-2 Nsp9.Communicated by Ramaswamy H. Sarma.

Background: Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV). To date there is no antiviral treatment against this infection or licensed vaccine to prevent it. Our study aims to evaluate whether (-)-cassine (1) and (-)-spectaline (2), the main alkaloids of Senna spectabilis, display anti-CHIKV activity. Both compounds have been described to be biologically active against neglected tropical diseases, including malaria, leishmaniasis, and schistosomiasis, which emphasizes that these molecules could be repurposed for chikungunya fever treatment., Methods: The structures of the isolated compounds 1 and 2 were identified by NMR and HRESIMS analyses, and their antiviral activity against CHIKV was assessed by a dose-response assay employing BHK-21 cells and CHIKV-nanoluc, a recombinant virus carrying the nanoluciferase gene reporter., Results: Compound 1 presented CC 50 of 126.5 µM and EC 50 of 14.9 µM, while compound 2 presented CC 50 of 91.9 µM and EC 50 of 8.3 µM. The calculated selectivity index (SI) was 8.5 for 1 and 11.3 for 2., Conclusion: The data presented herein show that compounds 1 and 2 have potential for being repurposed as anti-CHIKV drug. Our promising in vitro results encourage further in vitro and in vivo assays. This is the first description of the antiviral activity of compounds 1 and 2 against CHIKV infection, which can impact the development of antiviral drug candidates against chikungunya fever, which sometimes can be debilitating., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection., (© 2022. The Author(s).)

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.

Most of the patients infected with Chikungunya virus (CHIKV) develop chronic manifestations characterized by pain and deformity in joints, impacting their quality of life. The aminoadamantanes, in their turn, have been exploited due to their biological activities, with amantadine and memantine recently described with anti-CHIKV activities. Here we evaluated the antiviral activity of rimantadine hydrochloride (rtdH), a well-known antiviral agent against influenza A, its platinum complex (Pt-rtd), and the precursor cis-[PtCl 2 (dmso) 2 ], against CHIKV infection in vitro. The rtdH demonstrated significant antiviral activity in all stages of CHIKV replication (29% in pre-treatment; 57% in early stages of infection; 60% in post-entry stages). The Pt-rtd complex protected the cells against infection in 92%, inhibited 100% of viral entry, mainly by a virucidal effect, and impaired 60% of post-entry stages. Alternatively, cis-[PtCl 2 (dmso) 2 ] impaired viral entry in 100% and post-entry steps in 60%, but had no effect in protecting cells when administered prior to CHIKV infection. Collectively, the obtained data demonstrated that rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, with the strongest effect observed to Pt-rtd complex, which reduced up to 100% of CHIKV infection. Moreover, molecular docking analysis and infrared spectroscopy data (ATR-FTIR) suggest an interaction of Pt-rtd with CHIKV glycoproteins, potentially related to the mechanism of inhibition of viral entry by Pt-rtd. Through a migration retardation assay, it was also shown that Pt-rtd and cis-[PtCl 2 (dmso) 2 ] interacted with the dsRNA in 87% and 100%, respectively. The obtained results highlight the repurposing potential of rtdH as an anti-CHIKV drug, as well as the synthesis of promising platinum(II) metallodrugs with potential application for the treatment of CHIKV infections. Importance Chikungunya fever is a disease that can result in persistent symptoms due to the chronic infection process. Infected patients can develop physical disability, resulting and high costs to the health system and significant impacts on the quality of life of affected individuals. Additionally, there are no licensed vaccines or antivirals against the Chikungunya virus (CHIKV) and the virus is easily transmitted due to the abundance of viable vectors in epidemic regions. In this context, our study highlights the repurposing potential of the commercial drug rimantadine hydrochloride (rtdH) as an antiviral agent for the treatment of CHIKV infections. Moreover, our data demonstrated that a platinum(II)-rimantadine metallodrug (Pt-rtd) poses as a potent anti-CHIKV molecule with potential application for the treatment of Chikungunya fever. Altogether, rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, reducing up to 100% of CHIKV infection in vitro., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ants, an ecologically successful and numerically dominant group of animals, play key ecological roles as soil engineers, predators, nutrient recyclers, and regulators of plant growth and reproduction in most terrestrial ecosystems. Further, ants are widely used as bioindicators of the ecological impact of land use. We gathered information of ant species in the Atlantic Forest of South America. The ATLANTIC ANTS data set, which is part of the ATLANTIC SERIES data papers, is a compilation of ant records from collections (18,713 records), unpublished data (29,651 records), and published sources (106,910 records; 1,059 references), including papers, theses, dissertations, and book chapters published from 1886 to 2020. In total, the data set contains 153,818 ant records from 7,636 study locations in the Atlantic Forest, representing 10 subfamilies, 99 genera, 1,114 ant species identified with updated taxonomic certainty, and 2,235 morphospecies codes. Our data set reflects the heterogeneity in ant records, which include ants sampled at the beginning of the taxonomic history of myrmecology (the 19th and 20th centuries) and more recent ant surveys designed to address specific questions in ecology and biology. The data set can be used by researchers to develop strategies to deal with different macroecological and region-wide questions, focusing on assemblages, species occurrences, and distribution patterns. Furthermore, the data can be used to assess the consequences of changes in land use in the Atlantic Forest on different ecological processes. No copyright restrictions apply to the use of this data set, but we request that authors cite this data paper when using these data in publications or teaching events., (© 2021 The Authors. Ecology © 2021 The Ecological Society of America.)

Polyvinylidene fluoride - hydroxyapatite composite filaments were processed by twin-screw extrusion at different processing angular velocities and characterized by scanning electron and atomic force microscopies, differential scanning calorimetry and tensile tests. Polymer-ceramic composites with a 0-3 connectivity were successfully obtained. Regardless of the used processing parameters, all composite filaments present very similar melting (∼152°C) and solidification (∼139°C) points and elastic moduli (∼1.0 GPa) for hydroxyapatite as dispersed phase in the composite with concentrations up to 25 wt%, indicating that they are adequate for twin-screw extrusion and 3D printing. However, the yield strength (∼29 MPa), ultimate tensile strength (∼36 MPa) and tensile point (∼29 MPa) parameters are similar only for hydroxyapatite concentrations up to 15 wt%, once higher concentrations of hydroxyapatite as dispersed phase result in fragile samples (∼50% lower for each studied property)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Since the beginning of the SARS-CoV-2 spread in Brazil, few studies have been published analysing the variability of viral genome. Herein, we described the dynamic of SARS-CoV-2 strains circulating in Brazil from May to September 2020, to better understand viral changes that may affect the ongoing pandemic. Our data demonstrate that some of the mutations identified are currently observed in variants of interest and variants of concern, and emphasize the importance of studying previous periods in order to comprehend the emergence of new variants. From 720 SARS-CoV-2 genome sequences, we found few sites under positive selection pressure, such as the D614G (98.5 %) in the spike, that has replaced the old variant; the V1167F in the spike (41 %), identified in the P.2 variant that emerged from Brazil during the period of analysis; and I292T (39 %) in the N protein. There were a few alterations in the UTRs, which was expected, however, our data suggest that the emergence of new variants was not influenced by mutations in UTR regions, since it maintained its conformational structure in most analysed sequences. In phylogenetic analysis, the spread of SARS-CoV-2 from the large urban centres to the countryside during these months could be explained by the flexibilization of social isolation measures and also could be associated with possible new waves of infection. These results allow a better understanding of SARS-CoV-2 strains that have circulated in Brazil, and thus, with relevant infomation, provide the potential viral changes that may have affected and/or contributed to the current and future scenario of the COVID-19 pandemic.

The 2015/16 Zika virus (ZIKV) epidemic led to almost 1 million confirmed cases in 84 countries and was associated to the development of congenital microcephaly and Guillain-Barré syndrome. More recently, a ZIKV African lineage was identified in Brazil raising concerns about a future outbreak. The long-term consequences of viral infection emphasizes the need for the development of effective anti-ZIKV drugs. In this study, we developed and characterized a ZIKV replicon cell line for the screening of viral replication inhibitors. The replicon system was developed by engineering the IRES-Neo cassette into the 3' UTR terminus of the ZIKV Rluc DNA construct. After in vitro transcription, replicon RNA was used to transfect BHK-21 cells, that were selected with G418, thus generating the BHK-21-RepZIKV&#95;IRES-Neo cell line. Through this replicon-based cell system, we identified two molecules with potent anti-ZIKV activities, an imidazonaphthyridine and a riminophenazine, both from the MMV/DNDi Pandemic Response Box library of 400 drug-like compounds. The imidazonaphthyridine, known as RO8191, showed remarkable selectivity against ZIKV, while the riminophenazine, the antibiotic Clofazimine, could act as a non-nucleoside analog inhibitor of viral RNA-dependent RNA polymerase (RdRp), as evidenced both in vitro and in silico. The data showed herein supports the use of replicon-based assays in high-throughput screening format as a biosafe and reliable tool for antiviral drug discovery., (Copyright © 2021 Elsevier B.V. All rights reserved.)