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Jéssica Rodrigues Orlandin,1 Ingrid da Silva Gomes,1 Shamira de Fátima Sallum Leandro,1 Artur Fuertes Cagnim,1 Juliana Barbosa Casals,1 Adriano Bonfim Carregaro,1 Silvio Henrique Freitas,1 Luciana Cristina Machado,1 Maria Cristina Reis Castiglioni,2 Ana Liz Garcia Alves,2 Vânia Maria de Vasconcelos Machado,2 Carlos Eduardo Ambrósio1 1Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering (FZEA-USP), University of São Paulo, Pirassununga, São Paulo, Brazil; 2Department of Veterinary Medicine, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, BrazilCorrespondence: Carlos Eduardo Ambrósio Email ceambrosio@usp.brIntroduction: Intervertebral disc diseases (IVDD) represent the majority of neurological attendance and responsible for the most cases of paralysis in dogs. Treatments currently used do not show satisfactory results in patients with more severe and chronic neurological manifestations.Methods: To promote nerve and muscular recovery, as well as improve quality of life, we aimed to create a double-blind test method, associating spinal decompression surgery and allogeneic transplantation of amniotic membrane-derived stem cells (AMSCs) in dogs with chronic IVDD. Cells were characterized as fetal mesenchymal cells and safe for application. Eight animals completed the experiment: stem cell applications were made in four animals that had previously undergone an unsuccessful surgical procedure (“SC group”, n = 4); two animals were submitted to surgery, followed by applications of stem cells (“Surgery + SC”, n = 2); two other animals were submitted to surgery, followed by the application of saline solution (“Surgery + placebo”, n = 2). During the surgical procedure, a topical application was performed on the lesion and after fifteen and forty-five days another two applications were made via epidural. Animals were monitored biweekly and reassessed three months after surgery, by functional tests and magnetic resonance exams.Results: Some animals presented significant neurological improvement, such as the recovery of nociception and ability to remain on station. Despite the need further studies, until the present moment, cell therapy has been feasible and has no harmful effects on animals.Conclusion: The protocol of preclinical trial showed the association with decompressive surgery and cell transplantation in dogs with thoracolumbar IVDD proved feasible, and it was possible to observe neurological improvement after treatment. No tissue improvement through MRI was found. The double-blind test guaranteed reliability of the evaluations and results obtained that, even with a small sample size, generated satisfactory results for the animals and owners.Keywords: cell therapy, spinal cord injury, discopathy, amnion, regenerative medicine

Abstract Background Evidence suggests that semi-facial respirators provide protection against contamination in high-risk environments, although the COVID-19 pandemic called for greater protection and viral inactivation capacity. Thus, the aim of this study was to investigate the efficacy of a novel semi-facial respirator containing chitosan nanoparticles, compared with a conventional N95 respirator on the incidence of laboratory-confirmed SARS-CoV-2 in healthcare professionals. The secondary outcomes were influenza infection, usability and comfort. Methods Randomized controlled trial within a large public hospital (reference for COVID-19 patients) carried out between March 2021 and June 2023. We included 230 healthcare professionals exposed to SARS-Cov-2 and influenza, working in emergency departments, hospital wards, and intensive care units. Participants were assessed at baseline, after 10 days, and 21 days of follow-up. Researchers, participants, and outcome assessors were blinded to the allocated groups. Outcomes were analyzed by bivariate and multivariate comparisons using logistic regression. Crude (cOR) and adjusted odds ratios (aOR) were estimated, followed by 95% confidence intervals (CIs 95%). We adopted intention-to-treat (ITT) and complete-case (CC) analyses. Results Baseline characteristics were considered homogeneous between groups, and usability and comfort were reported as excellent in both groups. Non-significant differences were found for all outcomes, both in the ITT and CC analyses. The incidence of COVID-19 and influenza were, respectively, cOR: 0.96 [CI95%: 0.21–4.42] and cOR: 1.25 [CI95%: 0.34–4.62]; and aOR: 1.08 [CI95%: 0.21–5.47] and aOR: 1.11 [CI95%: 0.17–7.01]. Conclusions We found that the incidence of SARS-Cov-2 and influenza infections were similar between the new respirator compared to the conventional respirator. Furthermore, we observed that usability and comfort were similar and considered excellent for both respirators. Trial registration Clinicaltrials.gov (NCT04490200, 29/07/2020).

Introduction Chronic non-specific low back pain (CNLBP) is a major cause of disability resulting in high healthcare and lost productivity costs worldwide. Exercise therapy is the most prescribed treatment for CNLBP worldwide. Despite the benefits of exercise therapy, systematic reviews have highlighted the need for further high-quality evidence regarding their (cost-)effectiveness related to alternative treatments such as Pilates. Therefore, the aim was to investigate the cost-effectiveness of Pilates compared with home-based exercises for CNLBP.

Introdução Os estudos de avaliação econômica em saúde foram introduzidos na década de 60 e, nas últimas décadas, foram tidos como importantes ferramentas para o planejamento e gestão dos sistemas de saúde, no entanto a principal restrição dos estudos de avaliação econômica é a relação entre estimativas encontradas nos estudos e a tomada de decisão. Nos últimos anos, tem-se observado um notável avanço dos métodos em avaliação econômica, o que gera uma demanda constante de atualização por parte dos gestores e profissionais de saúde que utilizam a avaliação econômica no seu processo de trabalho. Portanto, destaca-se a importância de processos contínuos de capacitação dos tomadores de decisão sobre as diferentes abordagens metodológicas em AES, e a necessidade de fundamentação sobre sua aplicabilidade. O objetivo deste estudo foi elaborar um consenso, por meio de um painel de especialistas, quanto a um conjunto de conteúdos essenciais em avaliação econômica em saúde para a capacitação de profissionais de saúde e gestores. Métodos Trata-se de estudo Delphi para obter consenso sobre conteúdos essenciais em AES para a formação de gestores e profissionais de saúde em nível latu sensu. Vinte e um especialistas foram incluídos para avaliar conteúdos pertinentes à formação de profissionais da saúde e gestores, em AES. O painel de especialistas foi composto por profissionais da saúde, economia, docentes, pesquisadores e profissionais de NATS (Núcleos de Avaliação de Tecnologias em Saúde), com atuação prática e experiência em pesquisa na área de AES por pelo menos 3 anos. O painel foi implementado em três rodadas, sendo as duas primeiras relacionadas aos conteúdos de AES e a última referente à carga horária de cada módulo. Cada conteúdo foi apresentado em formato de afirmação, e os especialistas poderiam manifestar-se por meio de uma escala Likert de 5 pontos (variando de 1 – discordo plenamente a 5 – concordo plenamente). Foi utilizado um limiar igual ou superior a 70% de concordância para definir a concordância definitiva. Os itens com concordância entre >50% e

ABSTRACT: This study evaluated the sedation and the physiological effects produced by three doses of intranasal midazolam in green iguanas. Eight adult iguanas weighing 850 ± 165 grams, received each of five treatments: intramuscular midazolam 2 mg.kg-1 (IM), intranasally administered midazolam at doses of 2 mg.kg-1 (IN2), 3 mg.kg-1 (IN3) and 5 mg.kg-1 (IN5), and intramuscular saline (CON). The degree of sedation, heart rate, respiratory rate and body temperature were assessed from the baseline to 360 minutes post-administrations. The IM treatment induced mild to deep sedation from 10 (9 [8-12]) to 120 minutes (8 [3-9]). Sedation was not achieved in groups IN2 and IN3. When compared to the baseline, mild sedation was achieved in IN5 at 20 (5 [2-6]), 45 (5 [1-6]) and 90 minutes (5 [1-7]). There was a reduction in heart rate only in the IM group at 360 minutes (40 ± 15.1 bpm). Respiratory rate decreased to the baseline only in IN5, at 30 (12 [8-16] mpm) and 90 minutes (12 [8-24] mpm). No changes in body temperature were observed with any of the treatments during the evaluation period. Intranasally administered midazolam at a dose of 5 mg.kg-1, but not at 2 and 3 mg.kg-1, induced mild sedation in green iguanas. However, the effect exhibited a lower intensity and duration compared to the intramuscular dose of 2 mg.kg-1. Therefore, the administration of intranasal midazolam is not a reasonable option compared to the intramuscular route.

Introduction:Translational Health Research (THR) is a tool aimed at assisting in the transformation of basic and/or applied scientific research into a health technology ready for commercialization. The aim of this study is to present the translational pathway in wich our research group developed a Personal Protective Equipment (PPE) called VESTA® Facial Respirator with chitosan nanotechnology for protection against viruses, bacteria, and fungi. The aim of this study is to present the process of THR applied to a health technology research.Methods:The theoretical-methodological process of THR was applied to the Research and Development (R&D) of the respirator. This method is characterized by subsequent phases, as follow: T (0)—Concept, T (1) Pre-Clinical, T (2) Clinical, T (3) Industrial Scale Production, and T (4) Characterized by subsequent phases, as follow: Technological Evaluation.Results:Applying the THR process in the development and production of the Particulate Filtering Facepiece class 2 (PFF2) respirator with chitosan nanotechnology, University of Brasilia was able to transform the research idea into a respirator approved by the National Regulatory Agency for industrial-scale production within 24 months. The THR process is not a linear action; this flexibility allows essential activities for transforming research into a marketable product.Discussion:The integration among various stakeholders right from the genesis of research is a driving force for the effective utilization of results. The maturity of the country’s industrial sector is crucial for converting university research into a marketable product, and governments need to prioritize these products in healthcare system incorporations. The academic culture of scientific research needs to intensify the technological transfer phase of its inventions. Conclusion: In less than 24 months, the University of Brasilia translated research on a new PPE into the market by applying the THR method.

Abstract Background It is known that some sectors of hospitals have high bacteria and virus loads that can remain as aerosols in the air and represent a significant health threat for patients and mainly professionals that work in the place daily. Therefore, the need for a respirator able to improve the filtration barrier of N95 masks and even inactivating airborne virus and bacteria becomes apparent. Such a fact motivated the creation of a new N95 respirator which employs chitosan nanoparticles on its intermediate layer (SN95 + CNP). Results The average chitosan nanoparticle size obtained was 165.20 ± 35.00 nm, with a polydispersity index of 0.36 ± 0.03 and a zeta potential of 47.50 ± 1.70 mV. Mechanical tests demonstrate that the SN95 + CNP respirator is more resistant and meets the safety requisites of aerosol penetration, resistance to breath and flammability, presenting higher potential to filtrate microbial and viral particles when compared to conventional SN95 respirators. Furthermore, biological in vitro tests on bacteria, fungi and mammalian cell lines (HaCat, Vero E6 and CCL-81) corroborate the hypothesis that our SN95 + CNP respirator presents strong antimicrobial activity and is safe for human use. There was a reduction of 96.83% of the alphacoronavirus virus and 99% of H1N1 virus and MHV-3 betacoronavirus after 120 min of contact compared to the conventional respirator (SN95), demonstrating that SN95 + CNP have a relevant potential as personal protection equipment. Conclusions Due to chitosan nanotechnology, our novel N95 respirator presents improved mechanical, antimicrobial and antiviral characteristics.

Abstract Background Influenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza’s burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. Objective: The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza’s inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population. Methods We searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments. Findings We included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population. Conclusion Our findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.

Submitting late-term pregnant mares to anesthesia for non-obstetric surgery raises concerns about the survival of the mother and fetus. This study aimed to evaluate and describe transient maternal and fetal hemodynamic changes during general inhalation anesthesia in mares during the last month of gestation. Nine adult mares in the last month of gestation were subjected to general inhalation anesthesia and dorsal recumbency for 90 minutes. Trans-anesthetic vital parameters, arterial hemogasometry, cardiac output, pulmonary arterial pressure, central venous pressure, and fetal heart rates were assessed at defined intervals. During various timespans of the anesthetic procedure, the mares demonstrated an increase in heart rate, mean arterial pressure, and diastolic pressure as well as a decrease in temperature. Additionally, arterial hemogasometry indicated respiratory acidosis. No changes in cardiac output were observed; however, there was a reduction in pulmonary arterial and central venous pressures and stroke volume. Fetal heart rate was significantly decreased. General inhalation anesthesia in late term pregnancy in mares in a recumbent position implies in significant hemodynamic and metabolic changes. Up to 90 minutes those changes does not seem to affect negatively the maternal-fetus prognosis.

ObjectiveTo describe the profile of individuals with depression who received assistance at CAPS in Brazil between 2013 and 2019, focusing on their clinical and demographic characteristics, and to calculate the estimated coverage of CAPS across the national territory and its constituent federal units.MethodsDescriptive, ecological, time-series study with secondary data from national databases, referring to care provided at CAPS in the country for adults aged 18 years or over-diagnosed with depression (F32-32.9 and F33-F33.9). The estimated coverage of CAPS was calculated for 2013 and 2019 using registered and active services.ResultsThere was a 107% increase in the number of patients with depression receiving treatment at CAPS between 2013 and 2019. Women accounted for 77% of the patients, with the majority falling within the age range of 41 to 61years (49%). The predominant racial demographics were white (38%) and brown (34%). The diagnosis of depressive episodes was prevalent among 65% of the patients, and individual care was administrated to 75% of them. The presumed CAPS coverage was 71% in 2013 and increased to 87% in 2019 nationwide, although significant discrepancies were observed among different states.ConclusionProgress was evident in the implementation of CAPS across Brazil during the period spanning 2013 to 2019. Nonetheless, disparities persist among the federative units, and there remains an underutilization of group and family care within CAPS services.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15–T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15–T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p

Abstract BackgroundLow back pain is one of the main causes of disability worldwide. Individuals with chronic conditions have been widely affected by the COVID-19 pandemic. In this context, mobile health (mHealth) has become popular, mostly due to the widespread use of smartphones. Despite the considerable number of apps for low back pain available in app stores, the effectiveness of these technologies is not established, and there is a lack of evidence regarding the effectiveness of the isolated use of mobile apps in the self-management of low back pain. ObjectiveWe summarized the evidence on the effectiveness of mHealth interventions on pain and disability for individuals with chronic low back pain. MethodsWe conducted a systematic review and meta-analysis comparing mHealth to usual care or no intervention. The search terms used were related to low back pain and mHealth. Only randomized controlled trials were included. The primary outcomes were pain intensity and disability, and the secondary outcome was quality of life. Searches were carried out in the following databases, without date or language restriction: PubMed, Scopus, Embase, Physiotherapy Evidence Database (PEDro), the Cochrane Library, and OpenGrey, in addition to article references. The risk of bias was analyzed using the PEDro scale. Data were summarized descriptively and through meta-analysis (pain intensity and disability). In the meta-analysis, eligible studies were combined while considering clinical and methodological homogeneity. The certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria. ResultsA total of 5 randomized controlled trials were included, totaling 894 participants (447 allocated to the mHealth group and 445 to the usual care group), and they had similar methodological structure and interventions. Follow-up ranged from 6 weeks to 12 months. The studies did not demonstrate significant differences for pain intensity (mean difference −0.86, 95% CI −2.29 to 0.58; PP ConclusionsmHealth alone was no more effective than usual care or no treatment in improving pain intensity and disability in individuals with low back pain. Due to the biases found and the low certainty of evidence, the evidence remains inconclusive, and future quality clinical trials are needed.

In many infectious diseases, the pathogen-induced inflammatory response could result in protective immunity that should be regulated to prevent tissue damage and death. In fact, in Trypanosoma cruzi infection, the innate immune and the inflammatory response should be perfectly controlled to avoid significant lesions and death. Here, we investigate the role of Blimp-1 expression in T cells in resistance to T. cruzi infection. Therefore, using mice with Blimp-1 deficiency in T cells (CKO) we determined its role in the controlling parasites growth and lesions during the acute phase of infection. Infection of mice with Blimp-1 ablation in T cells resulted failure the cytotoxic CD8+ T cells and in marked Th1-mediated inflammation, high IFN-γ and TNF production, and activation of inflammatory monocyte. Interestingly, despite high nitric-oxide synthase activation (NOS-2), parasitemia and mortality in CKO mice were increased compared with infected WT mice. Furthermore, infected-CKO mice exhibited hepatic lesions characteristic of steatosis, with significant AST and ALT activity. Mechanistically, Blimp-1 signaling in T cells induces cytotoxic CD8+ T cell activation and restricts parasite replication. In contrast, Blimp-1 represses the Th1 response, leading to a decreased monocyte activation, less NOS-2 activation, and, consequently preventing hepatic damage and dysfunction. These data demonstrate that T. cruzi-induced disease is multifactorial and that the increased IFN-γ, NO production, and dysfunction of CD8+ T cells contribute to host death. These findings have important implications for the design of potential vaccines against Chagas disease.

Abstract One hundred and sixty-six cats from two animal shelters were subjected to enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence antibody test (IFAT), conventional polymerase chain reaction (cPCR), quantitative PCR (qPCR) and parasitological tests (PA) for the diagnosis of Leishmania spp. Among them, 15% (25/166), 53.6% (89/166), 3.6% (06/166) and 1.8% (03/166) were positive by ELISA, IFAT, both PCRs and PA, respectively. The sequencing of ITS-1 PCR amplicons revealed a 100% match with Leishmania infantum. After the Leishmania spp. survey, 12 cats were selected and divided into two groups for clinical, hematological, and biochemical analysis: six L. infantum positive cats (G1) and six Leishmania spp. negative cats (G2). All the cats were negative for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). A statistical analysis indicated significantly low platelet counts and significant hyperproteinemia associated with hypoalbuminemia in positive cats (p

Submitting late-term pregnant mares to anesthesia for non-obstetric surgery raises concerns about the survival of the mother and fetus. This study aimed to evaluate and describe transient maternal and fetal hemodynamic changes during general inhalation anesthesia in mares during the last month of gestation. Nine adult mares in the last month of gestation were subjected to general inhalation anesthesia and dorsal recumbency for 90 minutes. Trans-anesthetic vital parameters, arterial hemogasometry, cardiac output, pulmonary arterial pressure, central venous pressure, and fetal heart rates were assessed at defined intervals. During various timespans of the anesthetic procedure, the mares demonstrated an increase in heart rate, mean arterial pressure, and diastolic pressure as well as a decrease in temperature. Additionally, arterial hemogasometry indicated respiratory acidosis. No changes in cardiac output were observed; however, there was a reduction in pulmonary arterial and central venous pressures and stroke volume. Fetal heart rate was significantly decreased. General inhalation anesthesia in late term pregnancy in mares in a recumbent position implies in significant hemodynamic and metabolic changes. Up to 90 minutes those changes does not seem to affect negatively the maternal-fetus prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of a Pilates exercise program compared with home-based exercises in individuals with chronic non-specific low back pain. Design: A randomised controlled trial with a six-month follow-up. Setting: Rehabilitation clinic. Participants: One hundred and forty-five individuals (18–50 years of age) with low back pain for ≥ 12 consecutive weeks were enrolled and randomly allocated to either Pilates (n = 72) or home-based exercise groups (n = 73). Interventions: Method Pilates (Mat Pilates exercises using accessories) versus home-based exercise (postural exercises, muscle stretching and strengthening, and spine stabilisation/mobilisation), twice a week, for 6 weeks. Main measures: Assessments were performed at baseline, post-intervention, and six months follow-up. Outcomes were pain intensity, disability, and health-related quality of life. Results: At post-intervention, the Pilates group had significantly lower pain intensity (mean difference = −1.14; 95% CI −2.05; −0.23), less disability (mean difference = −6.7; 95% CI −11.3; −2.0), and higher health-related quality of life (mean difference = 0.102; 95% CI 0.054; 0151) compared to the home-based exercise group. At follow-up, the Pilates group had a significantly higher health-related quality of life (mean difference = 0.055; 95% CI 0.003; 0.106) compared with the home-based exercise group but there were no significant differences in pain and disability. A significant overall effect of Pilates compared to home-based exercise was found for disability (mean difference = −4.4; 95% CI −7.6; −1.1), and health-related quality of life (mean difference = 0.049; 95% CI 0.022; 0.076), but not for pain. Conclusion: Although Pilates was significantly superior to home exercise for pain and disability, the differences were not considered clinically relevant. However, Pilates did provide significant and clinically relevant differences in utility. [ABSTRACT FROM AUTHOR]

Introduction: Considering the prospects of increased prevalence and disability due to neck and low back pain, it is relevant to investigate the care processes adopted, to assist future public policies and decision-making for a better allocation of resources. Objective: the aim of this study was to estimate the costs arising from inpatient and outpatient care of individuals with Neck Pain (NP) and Low Back Pain (LBP) in Brazil, between 2010 and 2019. Methods: This is a cost-of-illness study from the perspective of the Brazilian public health system, based on health conditions with high prevalence (neck and low back pain). Data were presented descriptively using absolute and relative values. Results: Between 2010 and 2019, the health system spent more than $600 million (R$ 2.3 billion) to treat NP and LBP in adults, and LBP accounted for most of the expenses. Female had higher absolute expenses in inpatient care and in the outpatient system. Conclusion: Our study showed that the costs with NP and LBP in Brazil were considerable. Female patients had higher outpatient costs and male patients had higher hospitalization costs. Healthcare expenses were concentrated for individuals between 34 and 63 years of age. Plain Language Summary: This study focused on understanding how much it cost to treat neck pain (NP) and low back pain (LBP) in Brazil between 2010 and 2019, from the point of view of the public health system (i.e. Unified Health System – SUS). The idea was to find out how much money was spent and where. It turned out that the SUS spent, in total, more than US$600 million (R$2.3 billion) with LBP responsible for most of these expenses. Furthermore, we noted that women had higher outpatient care costs, while men had higher hospitalization costs. Those costs were more concentrated in people aged between 34 and 63 years. [ABSTRACT FROM AUTHOR]

Adenosine is an endogenously released purine nucleoside that signals through four widely expressed G protein-coupled receptors: A1, A2A, A2B, and A3. Of these, A2AR is recognized as mediating major adenosine anti-inflammatory activity. During cutaneous leishmaniasis, adenosine induces immunosuppression, which promotes the establishment of infection. Herein, we demonstrated that A2AR signaling is exploited by Leishmania infantum parasites, the etiologic agent that causes Visceral Leishmaniasis, to successfully colonize the vertebrate host. A2AR gene-deleted mice exhibited a well-developed cellular reaction with a strong Th1 immune response in the parasitized organs. An intense infiltration of activated neutrophils into the disease-target organs was observed in A2AR-/- mice. These cells were characterized by high expression of CXCR2 and CD69 on their cell surfaces and increased cxcl1 expression. Interestingly, this phenotype was mediated by IFN-γ on the basis that a neutralizing antibody specific to this cytokine prevented neutrophilic influx into parasitized organs. In evaluating the immunosuppressive effects, we identified a decreased number of CD4+ FOXP3+ T cells and reduced il10 expression in A2AR-/- infected mice. During ex vivo cell culture, A2AR-/- splenocytes produced smaller amounts of IL-10. In conclusion, we demonstrated that the A2AR signaling pathway is detrimental to development of Th1-type adaptive immunity and that this pathway could be associated with the regulatory process. In particular, it promotes parasite surveillance.

Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Among inflammatory cells, neutrophils are recruited to the site of Leishmania infection, and these cells may control parasite replication through oxidative or non-oxidative mechanisms. The recruitment, activation and functions of the neutrophils are coordinated by pro-inflammatory cytokines and chemokines during recognition of the parasite by pattern recognition receptors (PRRs). Here, we demonstrated that the Toll-like receptor 2 (TLR2) signaling pathway contributes to the development of the innate immune response during L. infantum infection. The protective mechanism is related to the appropriate recruitment of neutrophils to the inflammatory site. Neutrophil migration is coordinated by DCs that produce CXCL1 and provide a prototypal Th1 and Th17 environment when activated via TLR2. Furthermore, infected TLR2-/- mice failed to induce nitric oxide synthase (iNOS) expression in neutrophils but not in macrophages. In vitro, infected TLR2-/- neutrophils presented deficient iNOS expression, nitric oxide (NO) and TNF-α production, decreased expression of CD11b and reduced L. infantum uptake capacity. The non-responsive state of neutrophils is associated with increased amounts of IL-10. Taken together, these data clarify new mechanisms by which TLR2 functions in promoting the development of the adaptive immune response and effector mechanisms of neutrophils during L. infantum infection.

Objective: To describe the profile of individuals with depression who received assistance at CAPS in Brazil between 2013 and 2019, focusing on their clinical and demographic characteristics, and to calculate the estimated coverage of CAPS across the national territory and its constituent federal units. Methods: Descriptive, ecological, time-series study with secondary data from national databases, referring to care provided at CAPS in the country for adults aged 18 years or over-diagnosed with depression (F32-32.9 and F33-F33.9). The estimated coverage of CAPS was calculated for 2013 and 2019 using registered and active services. Results: There was a 107% increase in the number of patients with depression receiving treatment at CAPS between 2013 and 2019. Women accounted for 77% of the patients, with the majority falling within the age range of 41 to 61years (49%). The predominant racial demographics were white (38%) and brown (34%). The diagnosis of depressive episodes was prevalent among 65% of the patients, and individual care was administrated to 75% of them. The presumed CAPS coverage was 71% in 2013 and increased to 87% in 2019 nationwide, although significant discrepancies were observed among different states. Conclusion: Progress was evident in the implementation of CAPS across Brazil during the period spanning 2013 to 2019. Nonetheless, disparities persist among the federative units, and there remains an underutilization of group and family care within CAPS services. [ABSTRACT FROM AUTHOR]

ABSTRACT OBJECTIVE To estimate the direct costs due to hospital care for extremely, moderate, and late preterm newborns, from the perspective of a public hospital in 2018. The second objective was to investigate whether factors associated with birth and maternal conditions explain the costs and length of hospital stay. METHODS This is a cost-of-illness study, with data extracted from hospital admission authorization forms and medical records of a large public hospital in the Federal District, Brazil. The association of characteristics of preterm newborns and mothers with costs was estimated by linear regression with gamma distribution. In the analysis, the calculation of the parameters of the estimates (B), with a confidence interval of 95% (95%CI), was adopted. The uncertainty parameters were estimated by the 95% confidence interval and standard error using the Bootstrapping method, with 1,000 samples. Deterministic sensitivity analysis was performed, considering lower and upper limits of 95%CI in the variation of each cost component. RESULTS A total of 147 preterm newborns were included. We verified an average cost of BRL 1,120 for late preterm infants, BRL 6,688 for moderate preterm infants, and BRL 17,395 for extremely preterm infants. We also observed that factors associated with the cost were gestational age (B = -123.00; 95%CI: -241.60 to -4.50); hospitalization in neonatal ICU (B = 6,932.70; 95%CI: 5,309.40–8,556.00), and number of prenatal consultations (B = -227.70; 95%CI: -403.30 to -52.00). CONCLUSIONS We found a considerable direct cost resulting from the care of preterm newborns. Extreme prematurity showed a cost 15.5 times higher than late prematurity. We also verified that a greater number of prenatal consultations and gestational age were associated with a reduction in the costs of prematurity.

The relationship established between Leishmania infantum and the vertebrate host can lead to a self-healing infection or to the manifestation of visceral leishmaniasis, a chronic systemic infection associated with high rates of mortality. We hypothesized that regulatory cytokines, such as interleukin-27 (IL-27), play a role in susceptibility to L. infantum infection. IL-27 is a heterodimeric cytokine composed of IL-27p28 and EBi3 subunits which, when combined, bind to IL-27R, leading to STAT-1 and -3 activation, playing a role in the regulation of the immune response. We observed in this work that IL-27 regulates the Th1/Th17 profiles in a mouse model of visceral leishmaniasis (VL) caused by L. infantum We showed here that the pathogen recognition by endosomal Toll-like receptors triggers a type I interferon (IFN) response, which acts through the type I IFN receptor and interferon regulatory factor 1 to induce IL-27 production by macrophages. Furthermore, IL-27 plays a major regulatory role in vivo, because Ebi3(-/-) mice can efficiently control parasite replication despite reduced levels of IFN-γ compared to wild-type mice. On the other hand, the absence of Ebi3 leads to exacerbated IL-17A production in the infected organs as well as in a coculture system, suggesting a direct regulatory action of IL-27 during L. infantum infection. As a consequence of exacerbated IL-17A in Ebi3(-/-) mice, a greater neutrophil influx was observed in the target organs, playing a role in parasite control. Thus, this work unveiled the molecular steps of IL-27 production after L. infantum infection and demonstrated its regulatory role in the IL-17A-neutrophil axis.

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.

Cold-Water-Immersion (CWI) has been frequently used to accelerate muscle recovery and to improve performance after fatigue onset. In the present study, the aim was to investigate the effects of different CWI temperatures on neuromuscular activity on quadriceps after acute fatigue protocol. Thirty-six young athletes (16.9 ± 1.4 years-old; 72.1 ± 13.8 kg; 178.4 ± 7.2 cm) were divided into three groups: passive recovery group (PRG); CWI at 5 °C group (5G); and CWI at 10 °C group (10G). All participants performed a fatigue exercise protocol; afterwards, PRG performed a passive recovery (rest), while 5G and 10G were submitted to CWI by means of 5 °C and 10 °C temperatures during 10 min, respectively. Fatigue protocol was performed by knee extension at 40% of isometric peak force from maximal isometric voluntary contraction. Electromyography was used to evaluate neuromuscular performance. The passive recovery and CWI at 5 °C were associated with normalized isometric force and quadriceps activation amplitude from 15 until 120 min after exercise-induced fatigue (F = 7.169, p < 0.001). CWI at 5 °C and 10 °C showed higher muscle activation (F = 6.850, p < 0.001) and lower median frequency (MF) than passive recovery after 15 and 30 min of fatigue (F = 5.386, p < 0.001). For neuromuscular efficiency (NME) recovery, while PRG normalized NME values after 15 min, 5G and 10G exhibited these responses after 60 and 30 min (F = 4.330, p < 0.01), respectively. Passive recovery and CWI at 5 °C and 10 °C revealed similar effects in terms of recovery of muscle strength and NME, but ice interventions resulted in higher quadriceps activation recovery.