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Natalia Horstmann Risso,1 Cheila Denise Ottonelli Stopiglia,2 Marília Teresa Oliveira,1 Sandra Elisa Haas,2 Tamara Ramos Maciel,2 Natália Reginatto Lazzari,3 Edilson Luis Kelmer,3 Jorge Abrão Pinto Vilela,3 Diego Vilibaldo Beckmann1 1Postgraduate Program in Animal Sciences, Federal University of Pampa (UNIPAMPA), Uruguaiana, Brazil; 2Postgraduate Program in Pharmaceutical Sciences, Federal University of Pampa (UNIPAMPA), Uruguaiana, RS, Brazil; 3Veterinary Medicine Course, Federal University of Pampa (UNIPAMPA), Uruguaiana, BrazilCorrespondence: Diego Vilibaldo BeckmannBR 472 - Km 585, Campus UNIPAMPA-Uruguaiana, Uruguaiana, RS 97501-970, BrazilTel +55 55999725509Fax +55 5539110204Email diegobeckmann@unipampa.edu.brIntroduction: Nanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v).Methods: The NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal–Wallis test was used between groups and inside the same group, at different sample times and the Mann–Whitney test was performed when difference was detected.Results: The NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤ 0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p< 0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤ 0.05).Conclusion: Both in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.Keywords: antisepsis, cutaneous microbiota, nanoformulation, nanotechnology

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Helicobacter pylori is a bacterium that is present in the stomach of about 50% of the global population and is associated with several gastric disorders, including cancer. Natural products with antimicrobial activity have been tested against H. pylori, among them Trichilia catigua (catuaba), which is widely distributed in Brazil. This study aimed to evaluate extracts of T. catigua bark against H. pylori via determination of the minimum inhibitory and bactericidal concentrations (MIC and MBC); evaluation of virulence factors by real-time PCR, synergism with standard antimicrobials and morphology by scanning electron microscopy and simulations of the mechanism of action by molecular docking. The ethyl acetate fraction provided the best results, with an MIC 50 of 250 μg/mL and a 42.34% reduction in urease activity, along with reduced expression of the CagA and VacA genes, which encode for the main virulence factors. This fraction presented synergistic activity with clarithromycin, reducing the MIC of the drug by four-fold. Docking simulations suggested that the extracts inhibit fatty acid synthesis by the FAS-II system, causing damage to the cell membrane. Therefore, T. catigua extracts have potential as an adjuvant to treatment and are promising for the development of new anti-H. pylori drugs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

The respiratory chain alternative enzymes (AEs) NDX and AOX from the tunicate Ciona intestinalis (Ascidiacea) have been xenotopically expressed and characterized in human cells in culture and in the model organisms Drosophila melanogaster and mouse, with the purpose of developing bypass therapies to combat mitochondrial diseases in human patients with defective complexes I and III/IV, respectively. The fact that the genes coding for NDX and AOX have been lost from genomes of evolutionarily successful animal groups, such as vertebrates and insects, led us to investigate if the composition of the respiratory chain of Ciona and other tunicates differs significantly from that of humans and Drosophila, to accommodate the natural presence of AEs. We have failed to identify in tunicate genomes fifteen orthologous genes that code for subunits of the respiratory chain complexes; all of these putatively missing subunits are peripheral to complexes I, III and IV in mammals, and many are important for complex-complex interaction in supercomplexes (SCs), such as NDUFA11, UQCR11 and COX7A. Modeling of all respiratory chain subunit polypeptides of Ciona indicates significant structural divergence that is consistent with the lack of these fifteen clear orthologous subunits. We also provide evidence using Ciona AOX expressed in Drosophila that this AE cannot access the coenzyme Q pool reduced by complex I, but it is readily available to oxidize coenzyme Q molecules reduced by glycerophosphate oxidase, a mitochondrial inner membrane-bound dehydrogenase that is not involved in SCs. Altogether, our results suggest that Ciona AEs might have evolved in a mitochondrial inner membrane environment much different from that of mammals and insects, possibly without SCs; this correlates with the preferential functional interaction between these AEs and non-SC dehydrogenases in heterologous mammalian and insect systems. We discuss the implications of these findings for the applicability of Ciona AEs in human bypass therapies and for our understanding of the evolution of animal respiratory chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Water buffalo (Bubalus bubalis) farming is increasing in many regions of the world due to the species' ability to thrive in environments where bovine cattle would struggle. Despite water buffaloes being known for their resistance to diseases, there is a lack of data about the diversity of the microbiome of the species. In this study, we examined the virome diversity in palatine tonsils collected from animals from the island of Marajó, northern Pará state, Brazil, which harbors the largest bubaline flock in the country. Tonsil fragments from 60 clinically healthy bubalines were randomly selected from a sample of 293 animals. The samples were purified, extracted, and randomly amplified with phi29 DNA polymerase. After amplification, the products were purified and sequenced. Circular DNA viruses were predominant in the tonsils' virome. Sequences of genome segments representative of members of the genera Alphapolyomavirus (including a previously unreported bubaline polyomavirus genome) and Gemycircularvirus were identified, along with other not yet classified circular virus genomes. As the animals were clinically healthy at the time of sampling, such viruses likely constitute part of the normal tonsillar virome of water buffaloes inhabiting the Ilha do Marajó biome., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Aim: In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (Salvator merianae) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy., Methods: We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements., Results: During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white)., Conclusion: The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity., (© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Herpesviruses are significant pathogens of ruminants. In water buffaloes ( Bubalus bubalis ), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils ( n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present.

Objective: To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs., Methods: This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022., Results: The main strengths reported by countries were health workers' commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level., Conclusions: Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties' interests, the lack of information systems and difficulty in accessing vaccines and vaccine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes' strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises., Competing Interests: Conflicts of interest. None declared.

The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic β-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic β-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Alves Abrantes et al.)

Background: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent., Methodology/principal Findings: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR., Conclusions/significance: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drosophila melanogaster is undoubtedly one of the most useful model organisms in biology. Initially used in solidifying the principles of heredity, and establishing the basic concepts of population genetics and of the synthetic theory of evolution, it can currently offer scientists much more: the possibility of investigating a plethora of cellular and biological mechanisms, from development and function of the immune system to animal neurogenesis, tumorigenesis and beyond. Extensive resources are available for the community of Drosophila researchers worldwide, including an ever-growing number of mutant, transgenic and genomically-edited lines currently carried by stock centers in North America, Europe and Asia. Here, we provide evidence for the importance of stock centers in sustaining the substantial increase in the output of Drosophila research worldwide in recent decades. We also discuss the challenges that Brazilian Drosophila scientists face to keep their research projects internationally competitive, and argue that difficulties in importing fly lines from international stock centers have significantly stalled the progression of all Drosophila research areas in the country. Establishing a local stock center might be the first step towards building a strong local Drosophila community that will likely contribute to all areas of life sciences research.

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including β-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. β-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, β-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, β-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of β-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a β-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Hybrid naphthalenediimide/zinc phosphonate materials (NDI/Zn) were prepared by mixing solutions of N , N '-bis(2-phosphonoethyl)-1,4,5,8-naphthalenediimide (PNDI) and zinc nitrate, resulting in the precipitation of the desired compounds. Samples precipitated from water and N , N -dimethylformamide (DMF) were produced. The obtained samples had the expected elemental composition, and the presence of naphthalenediimides (NDI) was ascertained by infrared and UV-visible spectroscopy. All the samples were crystalline, according to powder X-ray diffraction. Nitrogen adsorption isotherms showed the presence of porosity in the NDI/Zn samples. Mesopores with a diameter = 4.1 nm were present in the sample from DMF, with total pore volume reaching 0.13 cm 3 /g., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients., Material and Methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction., Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p  = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p  = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p  = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p  = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed., Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients., 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., (© 2023 Soeiro, Bossa, César, Leal, Garcia, Fonseca, Nakamura, Guimarães, Soeiro, Serrano, Soares, Mueller, Mebazaa, Fernandes, Nomura, Rochitte and de Oliveira.)

The Analytic Hierarchy Process (AHP) is a multi-criteria decision support method and is widely applied in many areas. The original AHP method proposed by Thomas L. Saaty in the 1970s requires (n²-n)/2 comparisons. The number of required comparisons can make using this method challenging for maintaining consistent judgments in problems involving many criteria and/or alternatives. Furthermore, the available software is platform-dependent and generally does not support group decision-making. In this paper, we present software for AHP that demands n-1 comparisons. Additionally, the software supports group decision-making using individual aggregation of priorities with arithmetic and geometric means. The system is available at http://ahpweb.net/ and is accessible from any internet-connected device. It currently has more than 100 users and dozens of decision problems in various areas.•The original AHP formulation requires (n²-n)/2 comparisons per cluster which makes it difficult to make consistent judgments.•AHP avaliable software does not enable group decision making.•The proposed system AHP-WEB fills these gaps. The method demands n-1 comparisons per cluster without any inconsistency and allows group decision making on a web system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: The diagnostic ultrasound-guided high mechanical index impulses during an intravenous microbubble infusion (sonothrombolysis) improve myocardial perfusion in acute ST segment elevation myocardial infarction, but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling is unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics., Methods: One hundred patients (59 ± 10 years; 34% women) were randomized to receive either high mechanical index impulses plus percutaneous coronary intervention (PCI) (therapy group) or PCI only (control group) (n = 50 in each group). Diastolic dysfunction grade and LA mechanics were assessed immediately before and after PCI and at 48 to 72 hours, 1 month, and 6 months of follow-up. Diastolic dysfunction grades were classified as grades I, II, and III. The LA mechanics was obtained by two-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS)., Results: As follow-up time progressed, increased DD grade was observed more frequently in the control group than in the therapy group at 1 month and 6 months of follow-up (all P < .05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48 to 72 hours, 24.0% ± 7.3% in the therapy group versus 19.6% ± 7.2% in the control group, P = .005; at 1 month, 25.3% ± 6.3% in the therapy group versus 21.5% ± 8.3% in the control group, P = .020; and at 6 months, 26.2% ± 8.7% in the therapy group versus 21.6% ± 8.5% in the control group, P = .015. The therapy group was less likely to experience LA remodeling (odds ratio, 2.91 [1.10-7.73]; P = .03). LA-GLS was the sole predictor of LA remodeling (odds ratio, 0.79 [0.67-0.94]; P = .006)., Conclusion: Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Psychobiotics are probiotics that have the characteristics of modulating central nervous system (CNS) functions or reconciled actions by the gut-brain axis (GBA) through neural, humoral and metabolic pathways to improve gastrointestinal activity as well as anxiolytic and even antidepressant abilities. The aim of this work was to evaluate the effect of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the gut microbiota of mildly anxious adults using SHIME ® . The protocol included a one-week control period and two weeks of treatment with L. helveticus R0052 and B. longum R0175. Ammonia (NH4+), short chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), cytokines and microbiota composition were determined. Probiotic strains decreased significantly throughout the gastric phase. The highest survival rates were exhibited by L. helveticus R0052 (81.58%; 77.22%) after the gastric and intestinal phase when compared to B. longum (68.80%; 64.64%). At the genus level, a taxonomic assignment performed in the ascending colon in the SHIME ® model showed that probiotics (7 and 14 days) significantly ( p < 0.005) increased the abundance of Lactobacillus and Olsenella and significantly decreased Lachnospira and Escheria-Shigella . The probiotic treatment (7 and 14 days) decreased ( p < 0.001) NH 4 + production when compared to the control period. For SCFAs, we observed after probiotic treatment (14 days) an increase ( p < 0.001) in acetic acid production and total SCFAs when compared to the control period. Probiotic treatment increased ( p < 0.001) the secretion of anti-inflammatory (IL-6 and IL-10) and decreased ( p < 0.001) pro-inflammatory cytokines (TNF-alpha) when compared to the control period. The gut-brain axis plays an important role in the gut microbiota, producing SCFAs and GABA, stimulating the production of anti-anxiety homeostasis. The signature of the microbiota in anxiety disorders provides a promising direction for the prevention of mental illness and opens a new perspective for using the psychobiotic as a main actor of therapeutic targets.

Ribosomally expressed proteins perform multiple, versatile, and specialized tasks throughout Nature. In modern times, chemically modified proteins, including improved hormones, enzymes, and antibody-drug-conjugates have become available and have found advanced industrial and pharmaceutical applications. Chemical modification of proteins is used to introduce new functionalities, improve stability or drugability. Undertaking chemical reactions with proteins without compromising their native function is still a core challenge as proteins are large conformation dependent multifunctional molecules. Methods for functionalization ideally should be chemo-selective, site-selective, and undertaken under biocompatible conditions in aqueous buffer to prevent denaturation of the protein. Here the present challenges in the field are discussed and methods for modification of the 20 encoded amino acids as well as the N -/ C -termini and protein backbone are presented. For each amino acid, common and traditional modification methods are presented first, followed by more recent ones.

The application of various density functional approximations (DFAs) and an emphasis on popular methods without any consensus have prevailed in computational studies dedicated to carbocations. More importantly, an extensive and rigorous benchmark investigation on density functionals for the class is still lacking. To close this gap, we present a comprehensive benchmark study of quantum chemical methods on a series of classical and nonclassical carbocations, the CARBO33 dataset. We evaluate a total of 107 DFT methods from all rungs giving particular attention to double hybrid density functionals as the potential of the class has been largely undermined in the context of carbocations. To support our findings, DLPNO-CCSD(T) at the complete basis set (CBS) limit and W1-F12 are used as reference methods. Our results indicate that the composite CBS-QB3 method performs poorly and should not be adopted for target energies. Oftentimes, the tested DFAs of a lower rung perform better than several DFAs in a higher rung of Perdew's "Jacob's ladder". Nonetheless, double hybrids DSD-PBEP86-NL and ωB97X-2-D3(BJ) stand out by showing the overall best performance. Among the hybrids evaluated, about half of them show mean absolute deviation (MAD) below 1.1 kcal mol -1 , including the popular hybrids M06-2X and mPW1PW91. In this family, MN15-D3(BJ) performs particularly well (MAD = 0.77 kcal mol -1 ) displaying reliable results across various tests. Highly popular B3LYP exhibited one of the worst performances (MAD = 4.74 kcal mol -1 ), and we do not recommend its application to carbocations. We also assess the 24 general-purpose basis sets of single- up to quadruple-ζ quality. The best compromise between accuracy and computational cost is achieved with cc-pVTZ followed by def2-TZVP. Computations on larger structures of general interest, including terpene carbocations, are also presented for selected DFT methods confirming general trends in the results.

All 37 mitochondrial DNA (mtDNA)-encoded genes involved with oxidative phosphorylation and intramitochondrial protein synthesis, and several nuclear-encoded genes involved with mtDNA replication, transcription, repair and recombination are conserved between the fruit fly Drosophila melanogaster and mammals. This, in addition to its easy genetic tractability, has made Drosophila a useful model for our understanding of animal mtDNA maintenance and human mtDNA diseases. However, there are key differences between the Drosophila and mammalian systems that feature the diversity of mtDNA maintenance processes inside animal cells. Here, we review what is known about mtDNA maintenance in Drosophila, highlighting areas for which more research is warranted and providing a perspective preliminary in silico and in vivo analyses of the tissue specificity of mtDNA maintenance processes in this model organism. Our results suggest new roles (or the lack thereof) for well-known maintenance proteins, such as the helicase Twinkle and the accessory subunit of DNA polymerase γ, and for other Drosophila gene products that may even aid in shedding light on mtDNA maintenance in other animals. We hope to provide the reader some interesting paths that can be taken to help our community show how Drosophila may impact future mtDNA maintenance research., (© 2022 The Author(s).)

Background: Facial palsy (FP) is defined as an injury of the seventh cranial nerve pair, partial or total, which can be classified as central or peripheral. Proprioceptive neuromuscular facilitation (PNF) is primarily used in the functional recovery of upper and lower limb conditions, however the technique has also been used for FP., Objective: To analyze the effect of PNF in the treatment of dysfunctions in FP., Methods: Ten databases including BVS, CENTRAL Cochrane, CINAHL, PEDro, PubMed, Scielo, ScienceDirect, SCOPUS, Web of Science, and Google Scholar were comprehensively searched for dates prior to April 2021. Randomized controlled trials of PNF in individuals with dysfunctions caused by facial paralysis were eligible. Outcomes measures were recovery rate and clinical recovery, both measured by using the House Brackmann Scale. Recovery time was measured in days and synkinesis assessed with the Synkinesis Assessment Questionnaire., Results: A total of 184 patients were included. In general, the included studies have low methodological quality. None of the five studies used PNF as the sole intervention. In all of the included studies PNF was used in combination with other interventions. Our findings show very low evidence that PNF is more effective than minimal intervention for treating FP., Conclusion: We conclude that given the limited number of studies included and the low methodological quality presented, recommendations based on these studies should be interpreted with caution. The effects of PNF on facial paralysis are not clear., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Sulphur-selective conjugate addition reactions play a central role in synthetic chemistry and chemical biology. A general tool for conjugate addition reactions should provide high selectivity in the presence of competing nucleophilic functional groups, namely nitrogen nucleophiles. We report CO 2 -mediated chemoselective S -Michael addition reactions where CO 2 can reversibly control the reaction pHs, thus providing practical reaction conditions. The increased chemoselectivity for sulphur-alkylation products was ascribed to CO 2 as a temporary and traceless protecting group for nitrogen nucleophiles, while CO 2 efficiently provide higher conversion and selectivity sulphur nucleophiles on peptides and human serum albumin (HSA) with various electrophiles. This method offers simple reaction conditions for cysteine modification reactions when high chemoselectivity is required.

Chagas disease is a life-threatening illness caused by the parasite Trypanosoma cruzi . The diagnosis of the acute form of the disease is performed by trained microscopists who detect parasites in blood smear samples. Since this method requires a dedicated high-resolution camera system attached to the microscope, the diagnostic method is more expensive and often prohibitive for low-income settings. Here, we present a machine learning approach based on a random forest (RF) algorithm for the detection and counting of T. cruzi trypomastigotes in mobile phone images. We analyzed micrographs of blood smear samples that were acquired using a mobile device camera capable of capturing images in a resolution of 12 megapixels. We extracted a set of features that describe morphometric parameters (geometry and curvature), as well as color, and texture measurements of 1,314 parasites. The features were divided into train and test sets (4:1) and classified using the RF algorithm. The values of precision, sensitivity, and area under the receiver operating characteristic (ROC) curve of the proposed method were 87.6%, 90.5%, and 0.942, respectively. Automating image analysis acquired with a mobile device is a viable alternative for reducing costs and gaining efficiency in the use of the optical microscope., Competing Interests: Helder I. Nakaya is an Academic Editor for PeerJ., (©2022 Morais et al.)

Background: Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk., Objective: To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients., Methods: A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05., Results: Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%)., Conclusion: CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

Objective: To investigate the association between the severity of periodontitis (exposure) and dyslipidemia (outcome)., Methods: This was a cross-sectional study of users of public health services. Periodontitis was defined using the Center for Disease Prevention and Control and the American Academy of Periodontology criteria. Lipid evaluation used data on systemic biomarkers. Dyslipidemia diagnosis was based on the Guidelines of total cardiovascular risk of the World Health Organization. Weight, height, waist circumference, and blood pressure were measured, and socioeconomic-demographic, lifestyle behavior factors, general and oral health conditions of the participants were collected. Hierarchical and logistic regression analyzes were used to determine the association between the exposures and the outcome. Odds Ratios, unadjusted and adjusted, and 95% confidence intervals were estimated., Results: Of 1,011 individuals examined, 75.17% had dyslipidemia, and 84.17% had periodontitis, 0.2% with mild, 48.56% moderate, and 35.41% severe disease. The association between periodontitis and dyslipidemia was maintained through hierarchical analysis and in the multiple regression modeling, showing that the occurrences of dyslipidemia in the group with periodontitis, and its moderate and severe levels, were, respectively, 14%, 30%, and 16% higher compared with those without periodontitis., Conclusions: The results showed a positive association between moderate and severe periodontitis and dyslipidemia., (© 2021 Wiley Periodicals LLC.)

Background: Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI., Methods and Results: We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System (Zoll Circulation Inc™, San Jose, CA, USA). The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Afterwards, the EHT protocol was successfully validated in a trial randomizing 50 patients for 18 minutes cooling before coronary recanalization at the target temperature of 32 ± 1.0 ∘C or PCI-only. A total of 35 patients underwent ETH (85.7% [30/35] in 90 ± 15 minutes), without delays in the mean door-to-balloon time for primary PCI when compared to 15 control group patients (92.1 minutes versus 87 minutes, respectively; p = 0.509)., Conclusions: Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI., Clinicaltrials: gov: NCT02664194., Competing Interests: Michael Dae is a consultant for ZOLL Circulation Inc (San Jose, CA, USA). None of the other authors have conflicts of interest related to this article., (© 2022 The Author(s). Published by IMR Press.)

This study aimed to identify meal and snack patterns in Brazilian schoolchildren and assess their stability over 3 years. This is a repeated cross-sectional study carried out in 2013, 2014 and 2015 with 6353 schoolchildren aged 7-12 years from public schools in Florianópolis, Brazil. Previous-day food consumption data for six pre-defined meals (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) were collected using the validated Web-CAAFE (Food Consumption and Physical Activity of Schoolchildren) questionnaire. Latent class analysis was performed to derive meal and snack patterns. The stability of patterns was analysed using multinomial logistic regression, and the probability of belonging to a meal pattern was calculated for each year. Three patterns were identified for breakfast and four patterns for a mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack. Most meal and snack patterns were stable over the 3-year evaluation period. In the total sample, for a mid-afternoon snack, there was an increase in the probability of the children belonging to the 'Fruits and porridge' pattern (14.5%, 95% CI 12%-17% in 2015 vs. 9.2%, 95% CI 6.8%-11.7% in 2013) and a reduction in the 'Ultra-processed' pattern (42.5%, 95% CI 39.4%-45.6% in 2015 vs. 51.3%, 95% CI 46.5%-56.1% in 2013). These results appear to be in line with the recommendations of the Brazilian Dietary Guidelines and regional policies to increase the intake of healthy foods and limit that of ultra-processed, high fat, sugar and salt foods., (© 2022 British Nutrition Foundation.)

Cyclic peptides are promising next-generation therapeutics with improved biological stability and activity. A catalyst-free stapling method for cysteine-containing peptides has been developed that enables fine-tuning of the macrocycle by using the appropriate regioisomers of fluorobenzene linkers. Stapling was performed on the unprotected linear peptide or, more conveniently, directly on-resin after peptide synthesis. NMR spectroscopy and circular dichroism studies demonstrate that the type of stapling can tune the secondary structures of the peptides. The method was applied to a set of potential agonists for melanocortin receptors, generating a library of macrocyclic potent ligands with ortho, meta or para relationships between the thioethers. Their small but significant differences in potency and efficacy demonstrate how the method allows facile fine-tuning of macrocyclic peptides towards biological targets from the same linear precursor., (© 2021 Wiley-VCH GmbH.)

A benchmark density functional theory (DFT) study of 1 H NMR chemical shifts for data sets comprising 200 chemical shifts, including complex natural products, has been carried out to assess the performance of DFT methods. Two new benchmark data sets, NMRH33 and NMRH148, have been established. The meta-GGA revTPSS performs remarkably well against the NMRH33 benchmark set (mean absolute deviation (MAD), 0.10 ppm; maximum deviation (max), 0.26 ppm) with the smallest MAD of all evaluated functionals. The best-performing double-hybrid density functional (DHDF), revDSD-BLYP (MAD, 0.16 ppm; max, 0.35 ppm), performs similarly to hybrid-GGA methods (e.g., mPW1PW91/6-311G(d) (MAD, 0.15 ppm; max, 0.36 ppm)), but at a considerably higher computational cost. The results indicate that currently available double-hybrid DFT methods offer no benefit over GGA (including hybrid and meta) functionals in the calculation of 1 H NMR chemical shifts.

The COVID-19 pandemic prompted the FDA to authorize a new nucleoside analogue, remdesivir, for emergency use in affected individuals. We examined the effects of its active metabolite, remdesivir triphosphate (RTP), on the activity of the replicative mitochondrial DNA polymerase, Pol γ. We found that while RTP is not incorporated by Pol γ into a nascent DNA strand, it remains associated with the enzyme impeding its synthetic activity and stimulating exonucleolysis. In spite of that, we found no evidence for deleterious effects of remdesivir treatment on the integrity of the mitochondrial genome in human cells in culture., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

The usefulness of Drosophila as a model organism for the study of human diseases, behaviors and basic biology is unquestionable. Although practical, Drosophila research lacks popularity in developing countries, possibly due to the misinformed idea that establishing a lab and performing relevant experiments with such tiny insects is difficult and requires expensive, specialized apparatuses. Here, we describe how to build an affordable flylab to quantitatively analyze a myriad of behavioral parameters in D. melanogaster, by 3D-printing many of the necessary pieces of equipment. We provide protocols to build in-house vial racks, courtship arenas, apparatuses for locomotor assays, etc., to be used for general fly maintenance and to perform behavioral experiments using adult flies and larvae. We also provide protocols on how to use more sophisticated systems, such as a high resolution oxygraph, to measure mitochondrial oxygen consumption in larval samples, and show its association with behavioral changes in the larvae upon the xenotopic expression of the mitochondrial alternative oxidase (AOX). AOX increases larval activity and mitochondrial leak respiration, and accelerates development at low temperatures, which is consistent with a thermogenic role for the enzyme. We hope these protocols will inspire researchers, especially from developing countries, to use Drosophila to easily combine behavior and mitochondrial metabolism data, which may lead to information on genes and/or environmental conditions that may also regulate human physiology and disease states.

Background: Chronic Chagas disease (CChD), one of the infectious parasitic diseases with the greatest social and economic impact upon a large part of the American continent, has distinct clinical manifestations in humans (cardiac, digestive, or mixed clinical forms). The mechanisms underlying the development of the most common and ominous clinical form, the chronic Chagas cardiomyopathy (CCC) have not been completely elucidated, despite the fact that a high intensity of parasite persistence in the myocardium is deemed responsible for an untoward evolution of the disease. The present study aimed to assess the parasite load CCC and its relation to left ventricular ejection fraction (LVEF), a definite prognostic marker in patients with CCC. Methods: Patients with CCC were clinically evaluated using 12-lead-electrocardiogram, echocardiogram, chest X-ray. Peripheral blood sampling (5 ml of venous blood in guanidine/EDTA) was collected from each patient for subsequent DNA extraction and the quantification of the parasite load using real-time PCR. Results: One-hundred and eighty-one patients with CCC were evaluated. A total of 140 (77.3%) had preserved left ventricular ejection fraction (of ≥40%), and 41 individuals had LV dysfunction (LVEF of <40%). A wide variation in parasite load was observed with a, mean of 1.3460 ± 2.0593 (0.01 to 12.3830) par. Eq./mL. The mean ± SD of the parasite load was 0.6768 ± 0.9874 par. Eq./mL and 3.6312 ± 2.9414 par. Eq./mL in the patients with LVEF ≥ 40% and <40%, respectively. Conclusion: The blood parasite load is highly variable and seems to be directly related to the reduction of LVEF, an important prognostic factor in CCC patients., 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 © 2021 de Oliveira, Schmidt, da Silva, Donadi, da Silva and Marin-Neto.)

Endovascular Therapeutic hypothermia (ETH) reduces the damage caused by postischemia reperfusion injury syndrome in cardiopulmonary arrest and has already established its role in patients with sudden death; however, its role in ST-segment elevation myocardial infarction (STEMI) remains controversial. The objectives of this study were to investigate the safety, feasibility, and 30-day efficacy of rapid induction of therapeutic hypothermia as adjunctive therapy to percutaneous coronary intervention (PCI) in patients with anterior and inferior STEMIs. This was a prospective, controlled, randomized, two-arm, prospective, interventional study of patients admitted to the emergency department within 6 hours of angina onset, with anterior or inferior STEMI eligible for PCI. Subjects were randomized to the hypothermia group (primary PCI+ETH) or to the control group (primary PCI) at a 4:1 ratio. The ETH was induced by 1 L cold saline (1-4°C) associated with the Proteus™ System, by cooling for at least 18 minutes before coronary reperfusion with a target temperature of 32°C ± 1°C. Maintenance of ETH was conducted for 1-3 hours, and active reheating was done at a rate of 1°C/h for 4 hours. Primary safety outcomes were the feasibility of ETH in the absence of (1) door-to-balloon (DTB) delay; (2) major adverse cardiac events (MACE) within 30 days after randomization. The primary outcomes of effectiveness were infarct size (IS) and left ventricular ejection fraction (LVEF) at 30 days. An as-treated statistical analysis was performed. Fifty patients were included: 35 (70%) randomized to the hypothermia group and 15 (30%) to the control group. The mean age was 58 ± 12 years; 78% were men; and associated diseases were 60% hypertension, 42% diabetes, and 72% dyslipidemia. The compromised myocardial wall was anterior in 38% and inferior in 62%, and the culprit vessels were left anterior descending artery (LAD) (40%), right coronary artery (38%), and left circumflex (18%). All 35 patients who attempted ETH (100%) had successful cooling, with a mean endovascular coronary reperfusion temperature of 33.1°C ± 0.9°C. The mean ischemic time was 375 ± 89.4 minutes in the hypothermia group and 359.5 ± 99.4 minutes in the control group. The mean DTB was 92.1 ± 20.5 minutes in the hypothermia group and 87 ± 24.4 minutes in the control group. The absolute difference of 5.1 minutes was not statistically significant ( p  = 0.509). The MACE rates were similar between both groups (21.7% vs. 20% respectively, p  = 0.237). In the comparison between the hypothermia and control groups, no statistically significant differences were observed at 30 days between mean IS (13.9% ± 8% vs. 13.8% ± 10.8%, respectively, p  = 0.801) and mean final LVEF (43.3% ± 11.2% vs. 48.3 ± 10.9%, respectively; p  = 0.194). Hypothermia as an adjunctive therapy to primary PCI in STEMI is feasible and can be implemented without delay in coronary reperfusion. Hypothermia was safe regarding the incidence of MACE at 30 days. However, there was a higher incidence of arrhythmia and in-hospital infection in the hypothermia group, with no increase in mortality. Regarding efficacy, there was no difference in IS or LVEF at 30 days that would suggest additional myocardial protection with ETH. ClinicalTrials.gov: NCT02664194.

Key Points: The costs associated with immune and thermal responses may exceed the benefits to the host during severe inflammation. In this case, regulated hypothermia instead of fever can occur in rodents as a beneficial strategy to conserve energy for vital functions with consequent tissue protection and hypoxia prevention. We tested the hypothesis that this phenomenon is not exclusive to mammals, but extends to the other endothermic group, birds. A decrease in metabolic rate without any failure in mitochondrial respiration, nor oxygen delivery, is the main evidence supporting the regulated nature of endotoxin-induced hypothermia in chicks. Thermolytic mechanisms such as tachypnea and cutaneous vasodilatation can also be recruited to facilitate body temperature decrease under lipopolysaccharide treatment, especially in the cold. Our findings bring a new perspective for evolutionary medicine studies on energy trade-off in host defence because regulated hypothermia may be a phenomenon spread among vertebrates facing a severe immune challenge., Abstract: A switch from fever to regulated hypothermia can occur in mammals under circumstances of reduced physiological fitness (e.g. sepsis) to direct energy to defend vital systems. Birds in which the cost to resist a pathogen is additive to the highest metabolic rate and body temperature (T b ) among vertebrates may also benefit from regulated hypothermia during systemic inflammation. Here, we show that the decrease in T b observed during an immune challenge in birds is a regulated hypothermia, and not a result of metabolic failure. We investigated O 2 consumption (thermogenesis index), ventilation (respiratory heat loss), skin temperature (sensible heat loss) and muscle mitochondrial respiration (thermogenic tissue) during T b fall in chicken chicks challenged with endotoxin [lipopolysaccharide (LPS)]. Chicks injected with LPS were also tested regarding the capacity to raise O 2 consumption to meet an increased demand driven by 2,4-dinitrophenol. LPS decreased T b and the metabolic rate of chicks without affecting muscle uncoupled, coupled and non-coupled mitochondrial respiration. LPS-challenged chicks were indeed capable of increasing metabolic rate in response to 2,4-dinitrophenol, indicating no O 2 delivery limitation. Additionally, chicks did not attempt to prevent T b from falling during hypothermia but, instead, activated cutaneous and respiratory thermolytic mechanisms, providing an additional cooling force. These data provide the first evidence of the regulated nature of the hypothermic response to endotoxin in birds. Therefore, it changes the current understanding of bird's thermoregulation during severe inflammation, indicating that regulated hypothermia is either a convergent trait for endotherms or a conserved response among vertebrates, which adds a new perspective for evolutionary medicine research., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)