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Larissa Franciny de Souza,1 Jaquelini Betta Canever,1 Bruno de Souza Moreira,2 Ana Lúcia Danielewicz,1 Núbia Carelli Pereira de Avelar1 1Laboratory of Aging, Resources and Rheumatology, Department of Health Sciences, Federal University of Santa Catarina, Araranguá, Santa Catarina, Brazil; 2René Rachou Institute, Oswaldo Cruz Foundation (Fiocruz Minas), Belo Horizonte, Minas Gerais, BrazilCorrespondence: Bruno de Souza MoreiraRené Rachou Institute, Oswaldo Cruz Foundation (Fiocruz Minas), Augusto de Lima Avenue 1715, Barro Preto, Belo Horizonte, Minas Gerais, 30190-002, Brazil, Tel +55 31 3349-7707, Email brunosouzamoreira@gmail.comBackground/Objective: Fear of falling (FoF) and frailty are common problems in older adults. FoF can lead to self-imposed restriction of activities and then further decline in physical capacities that predispose older adults to frailty. Evaluating the association of these two geriatric syndromes may be the first step for understanding their complex relationship and might ultimately lead to establishing therapeutic goals and guiding treatments for older adults with frailty. This systematic review was conducted to provide evidence regarding the association between FoF and frailty.Methods: All the articles that provided information on the association between FoF and frailty were selected from PubMed, Scopus, CINAHL, and EMBASE in search of relevant papers. Articles reporting information on the association between FoF (exposure) and frailty (outcome), with older adults (age ≥ 60 years) living in the community (ie, living either at home or in places of residence that do not provide nursing care or rehabilitation) were included. Only original articles with observational design (cross-sectional or longitudinal/cohort) were included. The methodological quality of included articles was evaluated independently by the two assessors through the Newcastle-Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) critical appraisal checklist for longitudinal and cross-sectional studies, respectively.Results: The initial searches found 4,342 articles, of which 10 articles were included in this review: 7 cross-sectional and 2 longitudinal studies, and 1 study with cross-sectional and longitudinal analyses. The total sample was composed of 6,294 community-dwelling older adults (61.8% women). Among the longitudinal studies, adjusted odds ratios ranged from 1.18 (95% CI = 1.02; 1.36) to 9.87 (95% CI = 5.22; 18.68), while the adjusted odds ratios of the cross-sectional studies ranged from 1.04 (95% CI = 1.02; 1.07) to 7.16 (95% CI = 2.34; 21.89).Conclusion: FoF increases the risk of frailty in community-dwelling older adults. The knowledge of this association is of utmost importance in clinical practice, since it can help health professionals in the development of rehabilitation, prevention, and health promotion protocols. In addition, these findings can contribute to the development of public health policies and actions aimed at reducing the FoF and consequently the frailty.Prospero: CRD42021276775.Keywords: fear of falling, frailty, older adults, systematic review, geriatric syndromes

RATIONALE: Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related to alterations in the bombesin/gastrin-releasing peptide (GRP) receptor pathways. OBJECTIVES: To determine the effects of a selective GRP receptor antagonist, RC-3095, on cytokine release from macrophages and its in vivo effects in the cecal ligation and puncture (CLP) model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. METHODS: We determined the effects of RC-3095 in the CLP model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. In addition, we determined the effects of RC-3095 on tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and nitric oxide release from activated macrophages. MEASUREMENTS AND MAIN RESULTS: The GRP antagonist attenuated LPS- or CLP-induced TNF-alpha, IL-1beta, and nitric oxide release in cultured macrophages and decreased the mRNA levels of inducible nitric oxide synthase. The administration of RC-3095 (0.3 mg/kg) 6 h after sepsis induction improved survival in the CLP model, and diminished lung damage after intratracheal instillation of LPS. These effects were associated with attenuation on the circulating TNF-alpha and IL-1beta levels and decreased myeloperoxidase activity in several organs. CONCLUSIONS: We report that a selective GRP receptor antagonist attenuates the release of proinflammatory cytokines in vitro and in vivo and improves survival in 'established' sepsis. These are consistent with the involvement of a new inflammatory pathway relevant to the development of sepsis. [ABSTRACT FROM AUTHOR]

Purpose: Seat tilting wheelchair features can increase the comfort and safety of the user. Although many power wheelchairs have tilting mechanisms, they are often designed with a specific wheelchair model in mind. In this study, a design process for seat tilting mechanisms that can be applied to most rear-wheel drive wheelchair models is developed., Methodology: Equations were developed to describe the geometrical and load constraints that were used to size the electric actuator that powers the system and define its position. Finally, the equations were used to create the seat tilting mechanism of a prototype wheelchair, which was then tested., Results: The equations yielded coherent results which showed that advantageous actuator positions from a load minimization perspective usually require dimensions that cannot be found in commercial actuators. Also, there are positions in which the load increases exponentially, which should be avoided. The tests showed that the system was able to function properly on the prototype wheelchair and that the actuator position affected the time taken for the actuator to execute different parts of the tilting movement., Conclusions: The design process presented here was successful and modelled by general equations that can be applied to most front-wheel drive wheelchairs. It presents a low-cost option for the design of seat tilting systems, which can increase their accessibility.

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1β levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

Oxidative stress during in vitro of ovarian tissues has adverse effects on follicle survival. α-pinene is a monoterpenoid molecule with antioxidant activity that has great potential to maintain cell survival in vitro. This study investigated the effect of α-pinene (1.25, 2.5, 5.0, 10.0, or 20.0 μg/mL) on primordial follicle growth and morphology, as well as on stromal cells and collagen fibers in bovine ovarian slices cultured for six days. The effect of α-pinene on transcripts of catalase ( CAT ), superoxide dismutase ( SOD ), peroxiredoxin 6 ( PRDX6 ), glutathione peroxidase ( GPX1 ), and nuclear factor erythroid 2-related factor 2 ( NRF2 ) was investigated by real-time PCR. The tissues were processed for histological analysis to evaluate follicular growth, morphology, stromal cell density, and collagen fibers. The results showed that 2.5, 5.0, or 10.0 µg/mL α-pinene increased the percentages of normal follicles but did not influence follicular growth. The α-pinene (10.0 µg/mL) kept the stromal cell density and collagen levels in cultured bovine ovarian tissue like uncultured tissues. Ovarian tissues cultured in control medium had reduced expression of mRNA for NRF2 , SOD , CAT , GPX1, and PRDX6 , but α-pinene (10.0 µg/mL) increased mRNA levels for NRF2 and PRDX6 . In conclusion, 10.0 µg/mL α-pinene improves the follicular survival, preserves stromal cell density and collagen levels, and increases transcripts of NRF2 and PRDX6 after in vitro culture of bovine ovarian tissue.

Plant growth promoting bacteria (PGPB) have been used as integrative inputs to minimize the use of chemical fertilizers. However, a holistic comprehension about PGPB-plant-microbiome interactions is still incipient. Furthermore, the interaction among PGPB and the holobiont (host-microbiome association) represent a new frontier to plant breeding programs. We aimed to characterize maize bulk soil and rhizosphere microbiomes in irradiated soil (IS) and a native soil (NS) microbial community gradient (dilution-to-extinction) with Azospirillum brasilense Ab-V5, a PGPB commercial inoculant. Our hypothesis was that plant growth promotion efficiency is a result of PGPB niche occupation and persistence according to the holobiont conditions. The effects of Ab-V5 and NS microbial communities were evaluated in microcosms by a combined approach of microbiomics (species-specific qPCR, 16S rRNA metataxonomics and metagenomics) and plant phenomics (conventional and high-throughput methods). Our results revealed a weak maize growth promoting effect of Ab-V5 inoculation in undiluted NS, contrasting the positive effects of NS dilutions 10 -3 , 10 -6 , 10 -9 and IS with Ab-V5. Alpha diversity in NS + Ab-V5 soil samples was higher than in all other treatments in a time course of 25 days after sowing (DAS). At 15 DAS, alpha diversity indexes were different between NS and IS, but similar in all NS dilutions in rhizospheric samples. These differences were not persistent at 25 DAS, demonstrating a stabilization process in the rhizobiomes. In NS 10 -3 +Ab-V5 and NS 10 -6 Ab-V5, Ab-V5 persisted in the maize rhizosphere until 15 DAS in higher abundances compared to NS. In NS + Ab-V5, abundance of six taxa were positively correlated with response to (a)biotic stresses in plant-soil interface. Genes involved in bacterial metabolism of riboses and amino acids, and cresol degradation were abundant on NS 10 -3 + Ab-V5, indicating that these pathways can contribute to plant growth promotion and might be a result of Ab-V5 performance as a microbial recruiter of beneficial functions to the plant. Our results demonstrated the effects of holobiont on Ab-V5 performance. The meta-omics integration supported by plant phenomics opens new perspectives to better understanding of inoculants-holobiont interaction and for developing better strategies for optimization in the use of microbial products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferrarezi, Defant, de Souza, Azevedo, Hungria and Quecine.)

Riparian buffer systems (RBS) are a common agroforestry practice that involves maintaining a forested boundary adjacent to water bodies to protect the aquatic ecosystems in agricultural landscapes. While RBS have potential for carbon sequestration, they also can be sources of methane emissions. Our study site at Washington Creek in Southern Ontario, includes a rehabilitated tree buffer (RH), a grassed buffer (GRB), an undisturbed deciduous forest (UNF), an undisturbed coniferous forest (CF), and an adjacent agricultural field (AGR). The objective of this study was to assess the diversity and activity of CH 4 cycling microbial communities in soils sampled during hot moments of methane fluxes (July 04 and August 15). We used qPCR and high-throughput amplicon sequencing from both DNA and cDNA to target methanogen and methanotroph communities. Methanogens, including the archaeal genera Methanosaeta, Methanosarcina, Methanomassiliicoccus, and Methanoreggula, were abundant in all RBSs, but they were significantly more active in UNF soils, where CH 4 emissions were highest. Methylocystis was the most prevalent taxon among methanotrophs in all the riparian sites, except for AGR soils where the methanotrophs community was composed primarily of members of rice paddy clusters (RPCs and RPC-1) and upland soil clusters (TUSC and USCα). The main factors influencing the composition and assembly of methane-cycling microbiomes were soil carbon and moisture content. We concluded that the differences in CH 4 fluxes observed between RBSs were primarily caused by differences in the presence and activity of methanogens, which were influenced by total soil carbon and water content. Overall, this study emphasizes the importance of understanding the microbial drivers of CH 4 fluxes in RBSs in order to maximize RBS environmental benefits., 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. Published by Elsevier B.V.)

Livestock is an important part of many countries gross domestic product, and sanitary control impacts herd management costs. To contribute to incorporating new technologies into this economic chain, this work presents a mobile application for decision assistance to treatment against parasitic infection by Haemonchus contortus in small ruminants. Based on the Android system, the proposed software is a semi-automated computer-aided procedure to assist Famacha© pre-trained farmers in applying anthelmintic treatment. It mimics the two-class decision procedure performed by the veterinarian with the help of the Famacha© card. The embedded cell phone camera was employed to acquire an image from the ocular conjunctival mucosa, classifying the animal as healthy or anemic. Two machine-learning strategies were assessed, resulting in an accuracy of 83 % for a neural network and 87 % for a support vector machine (SVM). The SVM classifier was embedded into the app and made available for evaluation. This work is particularly interesting to small property owners from regions with difficult access or restrictions on obtaining continuous post-training technical guidance to use the Famacha© method effectively., 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.)

Objective: Chronic Ankle Instability (CAI) or Functional Ankle Instability (FAI) is a condition characterized by laxity and mechanical instability in the ankle joint. This instability interferes with the activities and physical-functional parameters of athletes, which leads to repetitive ankle sprains. The current systematic review was carried out to identify the effects of whole-body vibration exercise (WBVE) in athletes with CAI., Methods: We conducted electronic searches in Pubmed, the Cochrane Library, Embase, Web of Science, Scopus, Science Direct, Allied Health Literature (CINAHL) and Academic Search Premier (ASP) (EBSCO) databases on 26 February 2022. Registers were identified, and studies were selected for inclusion according to the eligibility criteria. The methodological quality was assessed by the Physiotherapy Evidence Database (PEDro) scale., Results: Seven studies were included with a mean methodological quality score of 5.85, considered 'regular' quality on the PEDro scale. WBVE interventions in athletes with CAI showed that this exercise contributes to a better response on parameters of neuromuscular performance, muscle strength and consequently in balance and postural control, variables that are for the management of CAI., Conclusion: WBVE interventions in sports modalities promote physiological responses that may lead to positive effects in several parameters. The protocols proposed in each modality can be carried out in practice and are considered effective additional exercise and training methods beyond traditional types of training for athletes. However, more studies are needed on athletes with this condition, with specific protocols, to highlight the possible physiological and physical-functional responses. Protocol study registration: PROSPERO (CRD42020204434).

Introduction: Fear of falling (FOF) is a prevalent condition among older adults and several variables have been pointed out as risk factors., Objectives: To identify the cut-off point on waist circumference (WC), capable of discriminating between older adults with and without FOF, and to test the association between WC and FOF., Methods: A cross-sectional observational study was carried out with older adults of both sexes from Balneário Arroio do Silva, Brazil. We used Receiver Operating Characteristic (ROC) curves to determine the cut-off point on WC and logistic regression adjusted for potential confounding variables to test the association., Results: Older women with WC >93.5 cm [area under the curve: 0.61 (95%CI 0.53; 0.68)] had 3.30 (95%CI 1.53; 7.14) greater chances of having FOF compared with older women with WC ≤93.5 cm. WC was not able to discriminate FOF in older men., Conclusion: WC values >93.5 cm are associated with higher chances of FOF in older women., Competing Interests: Declarations of Competing Interest The authors declare that they did not have any competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

(1) Background: Metabolic syndrome (MSy) is defined by a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increase the risk of cardiovascular disease. This systematic review with meta-analysis was conducted to assess the effects of whole-body vibration exercise (WBVE) in metabolic syndrome (MSy) individuals. (2) Methods: An electronic search in Pubmed, Embase, Scopus, Web of Science, ScienceDirect, PEDro, and CINAHL databases in December 2022 was performed. Data regarding the included studies were extracted. The level of evidence, the methodological quality, and the risk of bias of each selected publication were individually evaluated. (3) Results: Eight studies were included in the systematic review and four studies in the meta-analysis, with a mean methodological quality score on the Physiotherapy Evidence Database (PEDro scale) of 5.6, considered "fair" quality. The qualitative results suggested positive effects of the systemic vibration therapy in relevant outcomes, such as quality of life, functionality, pain level, trunk flexibility, cardiovascular responses (blood pressure and heart rate), neuromuscular activation, range of motion of the knees, rating of perceived exertion, and body composition. The quantitative results, with weighted mean differences, standard mean differences, and 95% confidence intervals (CIs), were calculated. Conclusions: WBVE may be an alternative capable of interfering with physical-mainly for flexibility with weighted mean differences (1.70; 95% CI 0.15, 3.25; n = 39)-functional, psychosocial, neuromuscular, emotional parameters, and consequently contribute to improvements in metabolic health and reduce the cardiovascular risk factor in MSy individuals. Nevertheless, further additional studies are required to understand the long-term effects of WBVE on MSy and its complications in a better way. Protocol study registration was as follows: PROSPERO (CRD 42020187319).

COVID-19 has probably contributed as a risk factor for sleep disturbance. Actigraphy has been used to evaluate sleep complaints in self-isolated populations and frontline doctors during the COVID-19 pandemic. This systematic review aims to summarize the impact of the COVID-19 pandemic on sleep through wrist actigraphy, estimating sleep latency, total sleep time, awakening-after-sleep onset, and sleep efficiency. Searches were conducted of observational studies on the PubMed, Embase, Scopus, Web of Science, and PEDro databases from 1 December 2019 to 31 December 2022. Ninety articles were found, and given the eligibility criteria, fifteen were selected. Six studies were classified by the National Health and Medical Research Council as evidence level IV, two studies as level III-3, and seven studies as level III-2. According to the ACROBAT-NRSI instrument, three studies were classified as having a "serious" risk of bias, two as having "critical" risk, four as having "moderate" risk, and six as having "low" risk. In the selected publications, various populations were evaluated via actigraphy during the COVID-19 pandemic, with reports of "poor" sleep quality. Actigraphy may be a relevant tool to assess individual day-night rhythms and provide recommendations under enduring pandemic conditions. Moreover, as actigraphy presents objective data for sleep evaluations, it is suggested that this method be used in similar pandemics and that actigraphy be included as part of the sleep hygiene strategy.

Purpose: Chronic kidney disease (CKD) is a clinical condition that promotes a decline in the overall health status of individuals affected, including parameters physical, functional, and psychosocial. This systematic review was conducted to assess effects of whole-body vibration exercise (WBVE) in individuals with CKD., Materials and Methods: It was conducted electronic searches in Pubmed, Embase, Scopus, Web of Science databases on May 2021. Records were identified and irrelevant studies were excluded based in eligibility criteria., Results: Five studies were included with a mean methodological quality score of 9, considered high quality in PEDRo scale. The studies have shown that the WBVE intervention, when applied low intensity was well tolerated, and no adverse effects; was able to improve the motor performance and strength in frail people, which could benefit the prevention of falls events. However, did not improve the quality of life, and the heart rate variability; and not altered cardiorespiratory parameters., Conclusions: WBVE intervention promotes a better response in parameters of the motor performance and muscular strength, and interaction bone-muscle. Nevertheless, more studies are needed with this intervention to improve physiological responses, and to understand your recommendation to prevent and reduce the complications and symptoms of the CKD, promoting an active life to these patients., Protocol Study Registration: PROSPERO (CRD42020203295).IMPLICATIONS FOR REHABILITATIONChronic kidney disease (CKD) is a clinical condition that promotes a decline in the overall health status of individuals affected, including parameters physical, functional, and psychosocial.WBVE program possibility, of good acceptance, efficient as well tolerated by physically deconditioned patients who present difficulty to perform any type of exercise.WBVE protocol can promote changes in the patient with CKD lifestyle and benefits for this population because is an exercise without fatigue, impact, stress, or discomfort.

We show that homogeneous and nonhomogeneous states of the one-dimensional self-gravitating sheets models have different ergodic properties. The former are nonergodic and the one-particle distribution function has a zero collision term if a proper limit is taken for the periodic boundary conditions. As a consequence, homogeneous states of the sheets model are nonergodic and do not relax to the equilibrium state, while nonhomogeneous states are ergodic in a time window of the order of the relaxation time to equilibrium, as similarly observed in other systems with a long range interaction.

We evaluated the co-occurrence of archaeal taxonomic groups and soil physicochemical characteristics in relation to the structuring of the archaeal community in Amazonian soil under different land use systems. Soil samples were collected in primary forest (PF), secondary forest (SF), agricultural systems (AG) and cattle pastures (PA). Archaeal community composition was revealed based on high-throughput amplicon sequencing of the 16S rRNA gene. The results revealed co-occurrence of archaeal classes, with two groups formed: Thaumarchaeota classes, including South Africa Gold Mine-Group 1 (SAGMG-1), Crenarchaeotic group (SCG) and Crenarchaeota candidate division YNPFFA, with predominance in PF and SF; and Bathyarchaeota_unclassified, Methanomicrobia and Methanobacteria (Euryarchaeota) with the FHMa11 terrestrial group, with predominance in PA. The number of co-occurrences between groups was lower in SF, AG and PA (approximately 30%) than in PF. The qPCR analysis revealed that PF also had the largest number of archaeal representatives. Soil texture may be a limiting factor of interactions between groups since the most representative groups, SAGMG-1 and the SCG (over 20% in all sites), were positively associated with coarse sand, the soil factor most correlated with the groups (33% of the total). These results suggest that interactions between archaeal classes belonging to different phyla may be dependent on the number of individuals in the soil environment. In this context, differences in soil physical structure among the land use systems can reduce the representatives of key groups and consequently the co-occurrence of Archaea, which could compromise the natural dynamics of this complex environment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Screening for probable and confirmed sarcopenia using sociodemographic and anthropometric indicators can be a practical, cheap, and effective strategy to identify and treat older people susceptible to this condition., Objectives: To identify cutoff points for sociodemographic and anthropometric variables in screening probable and confirmed sarcopenia in community-dwelling older adults., Design and Setting: This was a cross-sectional study of community-dwelling older adults in Araranguá, Santa Catarina, Brazil., Methods: Sociodemographic (age, education) and anthropometric (weight, height, body mass index [BMI], waist circumference [WC], and dominant calf circumference [DCC]) factors were considered as predictors. The outcomes were probable sarcopenia (reduction in muscle strength assessed by time ≥ 15 s in the five-time sit-to-stand test) and confirmed sarcopenia (reduction in strength and muscle mass). Receiver operating characteristic curve analysis was used to analyze the ability to track sociodemographic and anthropometric variables for sarcopenia., Results: In 308 older adults, WC > 91 cm in women and age > 69 years in men were useful in screening for probable sarcopenia. The variables age, weight, BMI, WC, and DCC can be used to screen for sarcopenia in older women and men., Conclusion: Sociodemographic and anthropometric variables are simple and accessible tools for sarcopenia screening in older adults.

In this work, we implement models that are able to describe complex rheological behaviour (such as shear-banding and elastoviscoplasticity) in the HiGTree/HiGFlow system, which is a recently developed Computational Fluid Dynamics (CFD) software that can simulate Newtonian, Generalised-Newtonian and viscoelastic flows using finite differences in hierarchical grids. The system uses a moving least squares (MLS) meshless interpolation technique, allowing for more complex mesh configurations while still keeping the overall order of accuracy. The selected models are the Vasquez-Cook-McKinley (VCM) model for shear-banding micellar solutions and the Saramito model for viscoelastic fluids with yield stress. Development of solvers and numerical simulations of inertial flows of these models in 2D channels and planar-contraction 4:1 are carried out in the HiGTree/HiGFlow system. Our results are compared with those predicted by two other methodologies: the OpenFOAM-based software RheoTool that uses the Finite-Volume-Method and an in-house code that uses the Vorticity-Velocity-Formulation ( VVF ). We found an excellent agreement between the numerical results obtained by these three different methods. A mesh convergence analysis using uniform and refined meshes is also carried out, where we show that great convergence results in tree-based grids are obtained thanks to the finite difference method and the meshless interpolation scheme used by the HiGFlow software . More importantly, we show that our methodology implemented in the HiGTreee/HiGFlow system can successfully reproduce rheological behaviour of high interest by the rheology community, such as non-monotonic flow curves of micellar solutions and plug-flow velocity profiles of yield-stress viscoelastic fluids.

Sedentary activities, such as watching television and using the computer, are frequent conditions in older adults and can be associated with sarcopenia. The objectives of this study were: (a) to establish sedentary behavior (SB) cutoff values for screening probable sarcopenia in community-dwelling older adults and (b) to verify the association between SB and probable sarcopenia according to the established cutoff point. This was a cross-sectional study including 1,165 community residents in Florianopolis/SC. SB was assessed using the International Physical Activity Questionnaire. The outcome was probable sarcopenia (assessed by time ≥ 15 s in the Five times sit-to-stand test). The cut-off points found for SB were time > 120 min/day [AUC: 0.54 (95%CI: 0.51; 0.57)] watching TV or video/DVD and ≤ 20 min/day [AUC: 0.59 (95%CI: 0.56;0.62)] using computer/internet. Older adults with SB had 1.30 (95% CI: 1.01; 1.66) and 1.46 (95% CI: 1.08; 1.96) greater chances of having sarcopenia, respectively., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification of some compounds such as phenolics, to determine their antioxidant and antimicrobial action. This study aims at botanical identification, physicochemical analyses, and the determination of total polyphenols, chromatographic profile and antiradical and antimicrobial activity of honey from different regions of Minas Gerais. Seven different samples were analyzed for the presence of pollen, and color determination. The physicochemical analyses performed were total acidity, moisture, HMF, reducing sugar, and apparent sucrose. The compound profile was determined by UHPLC/MS, the determination of total phenolics and antiradical activity (DPPH method) were performed by spectrophotometry, and minimum inhibitory and bacterial concentrations were determined for cariogenic bacteria. All honey samples met the quality standards required by international legislation, twenty compounds were detected as the main ones, the polyfloral honey was the only honey that inhibited all of the bacteria tested. Sample M6 (Coffee) was the one with the highest amount of total polyphenols, while the lowest was M4 (Cipó-uva). Regarding the antioxidant activity, M5 (Velame) had the best result and M4 (Cipó-uva) was the one that least inhibited oxidation. Of the polyfloral honeys, there was not as high a concentration of phenolic compounds as in the others. Coffee, Aroeira, Velame and Polyfloral have the best anti-radical actions. Betônica, Aroeira, Cipó-uva and Pequi inhibited only some bacteria. The best bacterial inhibition results are from Polyfloral.

Hypnosis presents an auxiliary adjunct in medical, dental, physiotherapeutic, and other clinical fields. This narrative review verified the effect of hypnosis in the control of pain and anxiety in dentistry. It presents the importance and effectiveness of hypnosis to aid dental procedures. It´s use in dentistry allows a wide range of applications such as sedation, analgesia, anesthesia, and hemostasis to facilitate treatment and improve the experience of dental care for dental patients. A discussion about the regulation of hypnosis in dentistry in Brazil, the attributions of dentists qualified in hypnosis, as well as the benefits of application based on evidence of hypnosis in dentistry, and the need for certification by hypnosis practitioners due to the possible risks inherent to the use of hypnosis are presented. Hypnosis is useful in the management of pain and anxiety in dentistry, when the dental practitioner is adequately experienced in this modality and the patients are carefully selected.

The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host's immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease.

Hepatitis B is considered an important public health problem worldwide because it is a chronic infection with a risk factor for cirrhosis and cellular hepatocellular carcinoma. In Brazil, the Rondônia State ranks first in the Northern region regarding the number of deaths due to hepatitis B. In the Amazon basin, genotype F is considered specific to the Americas identified in native populations. But few data on HBV genotyping and phylogenetic analysis are available. The objective of this study was to evaluate the genotypes and subgenotypes of the hepatitis B virus in indigenous people chronic carriers residing in cities of Guajará Mirim and Nova Mamoré in state of Rondônia/Brazil, on the border with Bolivia. A fragment of 417 bp (S gene) was amplified by PCR and submitted to nucleotide sequencing. The genotypes and subgenotypes of the HBV strains were determined through phylogenetic inference using genomic sequences from 197 representatives of the genotypes (A-H). Of the 41 chronic hepatitis B patients enrolled in this study, 27 were HBV-DNA positive. Of the 27 DNA-HBV positives, 39% (17/41) had individual HBV infection and 27% (10/41) were coinfected with HDV. The frequency of genotypes was 40.7% (11/27) for genotype D (HBV-D), 33.3% (9/27) for genotype F (HBV-F) and 25.9% (7/27) for genotype A (HBV-A) with circulating subgenotypes F2, F4, D2, D3, A1, and A2. We characterized the genotypes and subgenotypes of HBV circulating among in indigenous in the State of Rondônia shows for the first time the HBV/D genotype whit greater frequency circulating in nativos of state Rondônia. In conclusion, our findings showed a diversity of HBV genotypes, which is also found in other Brazilian geographical regions., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

We classify the main variants of the SARS-CoV-2 virus representing a given biological sequence coded as a symbolic digital sequence and by its evolution by a cellular automata with a properly chosen rule. The spike protein, common to all variants of the SARS-CoV-2 virus, is then by the picture of the cellular automaton evolution yielding a visible representation of important features of the protein. We use information theory Hamming distance between different stages of the evolution of the cellular automaton for seven variants relative to the original Wuhan/China virus. We show that our approach allows to classify and group variants with common ancestors and same mutations. Although being a simpler method, it can be used as an alternative for building phylogenetic trees., (© 2022. The Author(s).)

Iron is an essential component for metabolic processes, including oxygen transport within hemoglobin, tricarboxylic acid (TCA) cycle activity, and mitochondrial energy transformation. Iron deficiency can thus lead to metabolic dysfunction and eventually result in iron deficiency anemia (IDA), which affects approximately 1.5 billion people worldwide. Using a rat model of IDA induced by phlebotomy, we studied the effects of IDA on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the liver. Furthermore, we evaluated whether the mitochondrial function evaluated by high-resolution respirometry in PBMCs reflects corresponding alterations in the liver. Surprisingly, mitochondrial respiratory capacity was increased in PBMCs from rats with IDA compared to the controls. In contrast, mitochondrial respiration remained unaffected in livers from IDA rats. Of note, citrate synthase activity indicated an increased mitochondrial density in PBMCs, whereas it remained unchanged in the liver, partly explaining the different responses of mitochondrial respiration in PBMCs and the liver. Taken together, these results indicate that mitochondrial function determined in PBMCs cannot serve as a valid surrogate for respiration in the liver. Metabolic adaptions to iron deficiency resulted in different metabolic reprogramming in the blood cells and liver tissue.

Background: Sarcopenia has a high prevalence in older adults and is associated with chronic aggravations to health, so therefore it is important to identify older adults who are affected by sarcopenia in order to establish preventative strategies or early interventions., Objective: To estimate the prevalence of probable sarcopenia and verify its association with cognitive impairment, fear of falling, depressive symptoms and health self-perception in community-dwelling older adults., Methods: A cross-sectional study with simple random sampling including 306 older adults of both genders. The outcome variable was probable sarcopenia evaluated by the Five times sit-to-stand test (5XSST) considering probable sarcopenia when the measured time was > 15 seconds, following the recommendation of the European Working Group on Sarcopenia in Older People. The predictor variables were cognitive impairment, fear of falling, depressive symptoms and self-perception of health. Multivariate Logistic Regression was performed to verify associations between the variables., Results: The prevalence of probable sarcopenia was 50.00%. The older adults had significantly higher chances of presenting probable sarcopenia when displaying cognitive impairment (OR 2.49; 95%CI 1.46-4.24), fear of falls (OR 4.23; 95%CI 2.51-7.12), depressive symptoms (OR 2.20; 95%CI 1.32-3.67), poor (OR 2.48; 95%CI 1.19-5.16) and fair self-perception of health (OR 2.11; 95%CI 1.22-3.63) when compared to those who did not have the same conditions., Conclusion: The prevalence of probable sarcopenia in this study was 50.00%, and was associated with the presence of depressive symptoms, cognitive impairment, fear of falls and negative self-perception of health.

This study was carried out with the objective of determining the antioxidant properties and quantification of total phenolics and flavonoids in relation to quercetin and rutin in some of the monofloral honeys produced in Minas Gerais (Brazil). In this study, 15 monofloral honey samples were obtained from different geographic regions of Minas Gerias, Brazil. The honeys were obtained from Cooperative of Beekeepers and Family Farmers of Northern Minas. To determine the antioxidant properties of honey samples, the test methods of total phenolic content, flavonoids (rutin and quercetin) and DPPH were used. As a result of the analysis of phenolic and flavonoid contents, the samples with the best results were A1-Aroeira and A4-Assa peixe. In antioxidant activity, the honey with the best EC50 results was A6-Aroeira. Differences between the antioxidant activities of the honey samples were found significantly (p< 0.01)., Competing Interests: The authors have declared that no competing interests exist.

Objective: To verify the factors associated with risk, perception, and knowledge of falls; and pain among older adults., Method: A cross-sectional study carried out in the Emergency Service of a teaching hospital in the city of São Paulo between September 2019 and March 2020. We selected 197 older adults aged 65 and over, who were not disoriented or confused, of both genders. The instruments Awareness Questionnaire on the Risk of Falls, Morse Fall Scale and Numerical Pain Scales were applied. Mann-Whitney and Kruskal-Wallis tests were used., Results: Interviewees with a high risk of falls in older adults (p = 0.0041); those with a support network had a lower perception and knowledge about the risk of falls (p = 0.0025) and lower percentage of severe pain (p = 0.0033)., Conclusion: Factors associated with risk, perception and knowledge of falls and pain among older adults were age, family income, number of dependents, caregiver, support network, hypertension, impaired walking, antihypertensive medication, lipid-lowering medication, level of education, comorbidities and religion.

Multiple non-aggregatory functions of human platelets (PLT) are widely acknowledged, yet their functional examination is limited mainly due to a lack of standardized isolation and analytic methods. Platelet apheresis (PA) is an established clinical method for PLT isolation aiming at the treatment of bleeding diathesis in severe thrombocytopenia. On the other hand, density gradient centrifugation (DC) is an isolation method applied in research for the analysis of the mitochondrial metabolic profile of oxidative phosphorylation (OXPHOS) in PLT obtained from small samples of human blood. We studied PLT obtained from 29 healthy donors by high-resolution respirometry for comparison of PA and DC isolates. ROUTINE respiration and electron transfer capacity of living PLT isolated by PA were significantly higher than in the DC group, whereas plasma membrane permeabilization resulted in a 57% decrease of succinate oxidation in PA compared to DC. These differences were eliminated after washing the PA platelets with phosphate buffer containing 10 mmol·L -1 ethylene glycol-bis (2-aminoethyl ether)- N , N , N ', N '-tetra-acetic acid, suggesting that several components, particularly Ca 2+ and fuel substrates, were carried over into the respiratory assay from the serum in PA. A simple washing step was sufficient to enable functional mitochondrial analysis in subsamples obtained from PA. The combination of the standard clinical PA isolation procedure with PLT quality control and routine mitochondrial OXPHOS diagnostics meets an acute clinical demand in biomedical research of patients suffering from thrombocytopenia and metabolic diseases.

The actions in Occupational Health developed by Primary Health Care teams in a medium-sized municipality were assessed in a cross-sectional analytical study. A questionnaire consisting of 35 questions, divided up into four sections and answered by 289 health professionals, was used. The results were analyzed according to the distribution of absolute and relative frequencies using the chi-square test with a significance level of 0.05. The results revealed that activities developed in the area, as well as the epidemiological profile of the working population living in the area of coverage, are acknowledged as being productive, however interventions based on this diagnosis were not identified. It was observed that, among the professionals, more frequently it is the physician who identifies the epidemiological profile of the workers, while the nurse takes the lead role in the surveillance of diseases and in the technical-pedagogical support for the development of actions in Occupational Health. Based on the findings, it was observed that teams find it difficult to incorporate actions in Occupational Health in the planning of daily activities in their praxis, suggesting the need for professional qualification and pedagogical and institutional technical support from the specialized units.

Human blood cells may offer a minimally invasive strategy to study systemic alterations of mitochondrial function. Here we tested the reliability of a protocol designed to study mitochondrial respiratory control in human platelets (PLTs) in field studies, using high-resolution respirometry (HRR). Several factors may trigger PLT aggregation during the assay, altering the homogeneity of the cell suspension and distorting the number of cells added to the two chambers (A, B) of the Oroboros Oxygraph-2k (O2k). Thus, inter-chamber variability (∆ ab ) was calculated by normalizing oxygen consumption to chamber volume ( J O 2 ) or to a specific respiratory control state (flux control ratio, FCR ) as a reliable parameter of experimental quality. The method's reliability was tested by comparing the ∆ ab of laboratory-performed experiments (LAB, N = 9) to those of an ultramarathon field study (three sampling time-points: before competition (PRE, N = 7), immediately after (POST, N = 10) and 24 h after competition (REC; N = 10)). Our results show that ∆ ab &nbsp; J O 2 changed PRE-POST, but also for LAB-POST and LAB-REC, while all ∆ ab FCR remained unchanged. Thus, we conclude that our method is reliable for assessing PLT mitochondrial function in LAB and field studies and after systemic stress conditions.

Our aim with this study was to evaluate the consumption, performance, quantitative characteristics of carcasses, biochemical profile, plasma levels of ghrelin and leptin, expression of the receptor for ghrelin (GHS-R1a) in the hypothalamus and duodenum, and the number of goblet cells in the duodenum of calves subjected to milk volume restriction and supplemented with 2-hydroxy-4-(methylthio)butanoic acid (HMTBa). We used 21 Holstein mixed-breed calves, aged between 3 and 15 d with an average weight of 36.8 kg, and housed in pens with troughs for hay, concentrate, and water. The study included two consecutive experimental periods (first period [P1] and second period [P2]) of 21 d each, with 7 d of adaptation to the diet and facilities. The calves were distributed in a completely randomized design in three treatments with seven repetitions. 1) Control: 6 liters of milk/d during P1 and 6 liters of milk/day during P2; 2) RES (milk restriction): 3 liters of milk/day during P1 and 6 liters of milk/day during P2; and 3) RES + HMTBa: 3 liters of milk/day during P1 and 6 liters of milk/day during P2 + 3.3 g of HMTBa/day in both periods. HMTBa was supplied in milk, and the amount of concentrated ration and hay provided and leftovers were recorded daily to estimate dry matter (DM) and crude protein consumption. Mean daily weight gain (DWG), final weight (FW), and feed conversion (FC) were obtained at the beginning and at the end of each 21-d period. Plasma concentrations of ghrelin and leptin, triglycerides, total protein, urea, lactate, creatinine, alkaline phosphatase, and cholesterol were measured for P1 and P2 at the end of each 21-d period. At the end of P2, animals were slaughtered; sections of the duodenum were collected to evaluate the expression of GHS-R1a and quantity of goblet cells; hypothalamus was used to evaluate the expression of GHS-R1a; rumen was used to evaluate the thickness of epithelium and keratin and the density, height, and width of ruminal papillae. In P1, total DM consumption, FW, DWG, glucose, and triglycerides were lower in the RES and RES + HMTBa groups (P < 0.001). In P2, there was an improvement in the FC of the RES + HMTBa group (compared with Control and RES groups) and a lower urea concentration in the RES group (compared with Control and RES + HMTBa groups) (P < 0.001). No differences were observed among groups regarding hormonal concentrations, histological parameters, and GHS-R1a expression in the duodenum and hypothalamus. Therefore, milk restriction combined with HMTBa supplementation promoted greater compensatory gain by a mechanism independent of changes in GHS-R1a expression and hormone levels of ghrelin and leptin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

In many countries, there is an interest in determining the location of the women with the highest breast density. This investigation is important for optimize screening for breast cancer for women with dense breasts as other imaging modalities since 2D mammography is not very efficient on this type of breast. The objective of this study was to evaluate the variations in breast density in Brazilian women of different regions of Brazil. The mammographic images were taken from four regions of Brazil. The images, in the cranial caudal (CC) projection, were separated into intervals of compressed breast thickness (CBT) and patient age and were analysed by the software VolparaDensity, where volumetric breast density (VBD) calculations were performed. For each interval, null hypothesis tests for the mean difference between the VBD from the four regions of Brazil were performed. The paired tests indicated that there was a significant difference in the VBD of the women in the different regions of Brazil, with variations from 11.05% to 36.73%. Higher VBD was observed for women living in the Southeast region, followed by the Midwest, Northeast, and North regions. The Brazilian IBGE data show that the most urbanised region in Brazil is the Southeast, which coincides with the second highest rate of breast cancer in Brazil, according to the Brazilian National Cancer Institute (INCA). It is also known that breast cancer is strongly related to breast density; therefore, the results of this work support the data presented by federal agencies demonstrating that women living in the most urbanised region of Brazil (e.g., Southeast) present the highest breast density., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

The Amazon rainforest is a biodiversity hotspot and large terrestrial carbon sink threatened by agricultural conversion. Rainforest-to-pasture conversion stimulates the release of methane, a potent greenhouse gas. The biotic methane cycle is driven by microorganisms; therefore, this study focused on active methane-cycling microorganisms and their functions across land-use types. We collected intact soil cores from three land use types (primary rainforest, pasture, and secondary rainforest) of two geographically distinct areas of the Brazilian Amazon (Santarém, Pará and Ariquemes, Rondônia) and performed DNA stable-isotope probing coupled with metagenomics to identify the active methanotrophs and methanogens. At both locations, we observed a significant change in the composition of the isotope-labeled methane-cycling microbial community across land use types, specifically an increase in the abundance and diversity of active methanogens in pastures. We conclude that a significant increase in the abundance and activity of methanogens in pasture soils could drive increased soil methane emissions. Furthermore, we found that secondary rainforests had decreased methanogenic activity similar to primary rainforests, and thus a potential to recover as methane sinks, making it conceivable for forest restoration to offset greenhouse gas emissions in the tropics. These findings are critical for informing land management practices and global tropical rainforest conservation.

SARS-CoV-2 has spread rapidly around the world, with Brazil currently considered an epicenter of the pandemic. The Northern region has the second highest incidence coefficient, as well as the third highest mortality rate in the country. This study aimed to investigate information about the evolutionary history of epidemic spread and genetic aspects of strains isolated on the Western Amazon, in the State of Rondônia, Brazil. It was possible to detect a total of 22 mutations. Some of these alterations may possibly be related to effects on transmissibility, the fidelity of RNA replication, the ability of cancer patients to respond to infection, beyond a mutation that emerged after the introduction of SARS-CoV-2 in Rondônia. At least two events of introduction were detected, corresponding to the B.1 and B.1.1 European lineages. An introduction was observed possibly through Argentina, where strains originated that circulated in the Minas Gerais and Ceará Brazilian states, prior to Rondônia (B.1.), as well as through the Minas Gerais state and the Federal District, which gave rise to strains that spread to Rondônia, from the capital to more rural parts of the state (B.1.1.). The findings show the need to monitor the genetic epidemiology of COVID-19, in order to surveil the virus's evolution, dispersion and diversity.

Background: Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat., Methods: The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy., Results: Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin.  Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells., Conclusion: Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs.

Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 12 weeks. After that, metabolic, and neurochemical alterations were evaluated, focusing on neurotransmitters, and antioxidant defenses. Behavioral parameters related to motor activity, memory, anxiety, and depression were also evaluated. Mice consuming FRU diet displayed increased water, and caloric intake, resulting in weight gain, which was partially compensated due to decreased food pellet intake. FRU fed animals displayed increased plasma glucose, and cholesterol levels, which was not observed in overnight-fasted animals. Superoxide dismutase (SOD), and catalase (CAT) activities were markedly decreased in the prefrontal cortex of animals receiving FRU diet, while glutathione peroxidase (GPx) slightly increased. Liver (lower GPx), striatum (higher SOD and lower CAT), and hippocampus (no changes) were less impacted. No changes were observed in glutathione reductase, and thioredoxin reductase activities, two ancillary enzymes for peroxide detoxification. FRU intake did not alter serotonin, dopamine, and norepinephrine levels in the hippocampus, prefrontal cortex, and striatum. No significant alterations were observed in working, and short-term spatial memory; and in anxiety- and depressive-like behaviors in animals treated with FRU. Increased locomotor activity was observed in FRU-fed middle-aged mice, as evaluated in the open field, elevated plus-maze, Y maze, and object location tasks. Overall, these results demonstrate that high FRU consumption can disturb antioxidant defenses, and increase locomotor activity in middle-aged mice, open the opportunity for further studies to address the underlying mechanisms related to these findings.

Introduction: This work aims to develop a biomathematical transmission model of COVID-19, in the State of Sergipe, Brazil, to estimate the distribution of cases over time and project the impact on the spread of the epidemic outbreak due to interventions and control measures over the local population., Methods: This is an epidemiological mathematical modeling study conducted to analyze the dynamics of the accumulated cases of COVID-19, which used a logistic growth model that adds a term of withdrawal of individuals as a control measure. Three possible COVID-19 propagation scenarios were simulated based on three different rates of withdrawal of individuals. They were adjusted with real data of the infected and measures of control over the population., Results: The lockdown would be the best scenario, with a lower incidence of infected people, when compared to the other measures. The number of infected people would grow slowly over the months, and the number of symptomatic individuals in this scenario would be 40,265 cases. We noticed that the State of Sergipe is still in the initial stage of the disease in the scenarios. It was possible to observe that the peak of cases and the equilibrium, in the current situation of social isolation, will occur when reaching the new support capacity, at the end of August in approximately 1,171,353 infected individuals., Conclusions: We established that lockdown is the intervention with the highest ability to mitigate the spread of the virus among the population.

Peroxiredoxin 2 (Prdx2) and other typical 2-Cys Prdxs function as homodimers in which hydrogen peroxide oxidizes each active site cysteine to a sulfenic acid which then condenses with the resolving cysteine on the alternate chain. Previous kinetic studies have considered both sites as equally reactive. Here we have studied Prdx2 using a combination of non-reducing SDS-PAGE to separate reduced monomers and dimers with one and two disulfide bonds, and stopped flow analysis of tryptophan fluorescence, to investigate whether there is cooperativity between the sites. We have observed positive cooperativity when H 2 O 2 is added as a bolus and oxidation of the second site occurs while the first site is present as a sulfenic acid. Modelling of this reaction showed that the second site reacts 2.2 ± 0.1 times faster. In contrast, when H 2 O 2 was generated slowly and the first active site condensed to a disulfide before the second site reacted, no cooperativity was evident. Conversion of the sulfenic acid to the disulfide showed negative cooperativity, with modelling of the exponential rise in tryptophan fluorescence yielding a rate constant of 0.75 ± 0.08 s -1 when the alternate active site was present as a sulfenic acid and 2.29 ± 0.08-fold lower when it was a disulfide. No difference in the rate of hyperoxidation at the two sites was detected. Our findings imply that oxidation of one active site affects the conformation of the second site and influences which intermediate forms of the protein are favored under different cellular conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)