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Fabricio Beltrame,1,2 Bianca Nascimento-Carlos,3 Jaqueline S da Silva,1,3 Rodolfo Couto Maia,4 Tadeu Lima Montagnoli,3,4 Eliezer J Barreiro3,4 ,† Gisele Zapata-Sudo1– 4 1Programa de Pós-Graduação em Medicina (Cardiologia), Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Instituto do Coração Edson Saad, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 3Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 4Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil†Professor Eliezer Barreiro passed away on April 8, 2024Correspondence: Gisele Zapata-Sudo, Universidade Federal do Rio de Janeiro, Instituto do Coração Edson Saad, Faculdade de Medicina, Centro de Ciências da Saúde, Bloco J, Sala 11, Rio de Janeiro, RJ, 21941-902, Brasil, Tel/Fax +55-21-39386505, Email gsudo@icb.ufrj.br; gzsudo@gmail.comBackground and Purpose: Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI.Methods: AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis.Results: MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%.Conclusion: Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.Keywords: cardiac remodeling, inflammation, myocardial infarction, adenosine receptors

Priscila R Oliveira1, Adriana P Paula1, Karine Dal-Paz1, Cassia S Felix1, Flavia Rossi2, Jorge S Silva1, Ana Lucia M Lima11Orthopaedics and Traumatology Department, 2Pathology Department, University of São Paulo, São Paulo, BrazilIntroduction: In recent decades, antimicrobial resistance has become a public health problem, particularly in cases of healthcare-associated infections. Interaction between antibiotic consumption and resistance development is of particular interest regarding Gram-negative bacilli, whose growing resistance has represented a great challenge.Objective: Assess the impact of restriction of cefepime use on antimicrobial susceptibility among the Gram-negative bacilli (GNB) most frequently involved in healthcare-associated infections (HAI).Methods: Data relating to hospital occupancy and mortality rates, incidence of HAI, incidence of GNB as causative agents of HAI, antimicrobial consumption at the hospital and antimicrobial susceptibility of GNB related to HAI were compared between two periods: a 24-month period preceding restriction of cefepime use and a 24-month period subsequent to this restriction.Results: There was a significant drop in cefepime consumption after its restriction. Susceptibility of Acinetobacter baumanii improved relating to gentamicin, but it worsened in relation to imipenem, subsequent to this restriction. For Pseudomonas aeruginosa, there was no change in antimicrobial susceptibility. For Klebsiella pneumoniae and Enterobacter spp, there were improvements in susceptibility relating to ciprofloxacin.Conclusion: Restriction of cefepime use had a positive impact on K. pneumoniae and Enterobacter spp, given that after this restriction, their susceptibilities to ciprofloxacin improved. However, for A. baumanii, the impact was negative, given the worsening of susceptibility to imipenem.Keywords: ecological studies, cross infection, drug resistance, microbial, Gram-negative bacilli, cefepime

Larissa do Nascimento Pereira,1 Maycon Sousa Pegorari,2– 4 Lislei Jorge Patrizzi,2,3 Isabel Aparecida Porcatti de Walsh,2,3 Caroline de Fátima Ribeiro Silva,1 Juliana de Souza da Silva,4 Areolino Pena Matos,1,4 Ana Carolina Pereira Nunes Pinto,1,5– 7 Daniela Gonçalves Ohara2 1Department of Biological and Health Sciences, Federal University of Amapá, Macapá, AP, Brazil; 2Department of Applied Physiotherapy, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil; 3Postgraduate Program in Physical Therapy, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil; 4Postgraduate Program in Health Sciences, Federal University of Amapá, Macapá, AP, Brazil; 5Iberoamerican Cochrane Centre - Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 6Cochrane Brazil, Center for Evidence-Based Health Studies and Health Technology Assessment, Sao Paulo, Brazil; 7Department of Medicine, Evidence-Based Health Post-Graduation Program, Federal University of São Paulo, Sao Paulo, BrazilCorrespondence: Maycon Sousa Pegorari, Department of Applied Physiotherapy, Federal University of Triângulo Mineiro, Boulevard Frei Paulino, n° 30, Abadia, Uberaba, Minas Gerais, 38025-180, Brazil, Email mayconpegorari@yahoo.com.br; maycon.pegorari@uftm.edu.brPurpose: Impaired respiratory muscle strength has been associated with some geriatric syndromes. However, no studies have previously evaluated the relationship between respiratory muscle strength and dynapenic abdominal obesity. This study aimed to analyze whether there is an association between respiratory muscle strength and abdominal obesity, dynapenia and dynapenic abdominal obesity (DAO) in community-dwelling older adults.Patients and Methods: Cross-sectional study conducted with community-dwelling older adults (n=382 / 70.03 ± 7.3 years) from Macapá, Amapá, Brazil. Respiratory muscle strength was assessed by measuring maximal inspiratory and expiratory pressures (MIP and MEP, respectively), using an analog manovacuometry. DAO was defined as the combination of dynapenia (grip strength < 26 kgf for men and < 16 kgf for women) and abdominal obesity (abdominal circumference > 102 cm for men and > 88 cm for women). We performed descriptive and inferential statistical analyses using the student’s t-test for independent and related samples and linear regression model.Results: Older adults with abdominal obesity, dynapenia, and DAO presented lower mean values (obtained and obtained versus predicted; except abdominal obesity versus MIP) for maximal respiratory pressures compared to individuals without these conditions. However, the adjusted analysis only indicated an association between MIP and the following conditions: dynapenia (MIP - β =− 0.171; p< 0.001), abdominal obesity (MIP - β=0.102; p=0.042), and DAO (MIP - β=− 0.101; p=0.028).Conclusion: Older adults with abdominal obesity, dynapenia, and DAO showed impaired maximal respiratory pressures. The results of the adjusted analysis indicate that inspiratory muscle strength may require greater attention by health professionals aiming at preventing respiratory complications and improving respiratory health care in older people with these conditions.Keywords: respiratory muscles, muscle strength, respiratory function tests, obesity, abdominal, aged

Marcio Carneiro Vieira,1,2 Fernanda Bezerra de Mello Monte,3 Bruno Eduardo Dematte,3 Tadeu Lima Montagnoli,3 Guilherme Carneiro Montes,3 Jaqueline Soares da Silva,3 Rosalia Mendez-Otero,4 Margarete Manhães Trachez,3 Roberto Takashi Sudo,1,3 Gisele Zapata-Sudo1,3 1Programa de Pós-graduação em Ciências Cirúrgicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 2Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 3Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; 4Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio De Janeiro, 21941-902, BrazilCorrespondence: Gisele Zapata-SudoInstituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, BrazilTel +55 21 3938 6505Email gsudo@icb.ufrj.brIntroduction: New therapeutic alternatives for pain relief include the use of phosphodiesterase-5 (PDE5) inhibitors, which could prevent the transmission of painful stimuli by neuron hyperpolarization via nitric oxide (NO)/cyclic 3ʹ,5ʹ-guanosine monophosphate (cGMP) pathway. The present work investigated the antinociceptive activity of a new PDE5 inhibitor, lodenafil carbonate, in inflammatory and neuropathic pain models.Methods and Results: Although no effect was detected on neurogenic phase of formalin test in mice, oral administration of lodenafil carbonate dose-dependently reduced reactivity in the inflammatory phase (200.6 ± 39.1 to 81.9 ± 18.8 s at 10 μmol/kg, p= 0.0172) and this effect was totally blocked by NO synthase inhibitor, L-Nω-nitroarginine methyl ester (L-NAME). Lodenafil carbonate (10 μmol/kg p.o.) significantly reduced nociceptive response as demonstrated by increased paw withdrawal latency to thermal stimulus (from 6.8 ± 0.7 to 10.6 ± 1.3 s, p= 0.0006) and paw withdrawal threshold to compressive force (from 188.0 ± 14.0 to 252.5 ± 5.3 g, p< 0.0001) in carrageenan-induced paw inflammation model. In a spinal nerve ligation-induced neuropathic pain, oral lodenafil carbonate (10 μmol/kg) also reversed thermal hyperalgesia and mechanical allodynia by increasing paw withdrawal latency from 17.9 ± 1.5 to 22.8 ± 1.9 s (p= 0.0062) and paw withdrawal threshold from 26.0 ± 2.8 to 41.4 ± 2.9 g (p= 0.0196). These effects were reinforced by the reduced GFAP (3.4 ± 0.5 to 1.4 ± 0.3%, p= 0.0253) and TNF-alpha (1.1 ± 0.1 to 0.4 ± 0.1%, p= 0.0111) stained area densities as detected by immunofluorescence in ipsilateral dorsal horns.Conclusion: Lodenafil carbonate demonstrates important analgesic activity by promoting presynaptic hyperpolarization and preventing neuroplastic changes, which may perpetuate chronic pain, thus representing a potential treatment for neuropathic pain.Keywords: neuropathic pain, inflammatory pain, phosphodiesterase 5 inhibitor, lodenafil carbonate, spinal cord, GFAP

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected co

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumor-initiating cells in stage I and II breast cancer. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.Experimental Approach: Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-alpha. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.Key Results: Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-alpha, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-alpha antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-alpha production, which were inhibited by reparixin or anti-TNF-alpha treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-alpha upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-alpha or anti-LIX/CXCL5.Conclusion and Implications: Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-alpha, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). MATERIAL AND METHODS: The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. RESULTS: No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. CONCLUSION: Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome. [ABSTRACT FROM AUTHOR]

Objective: To discuss why clinical information systems are failing.Method: Subjectively analyzing the development of clinical IT systems during the last decades.Results and Conclusions: The challenge is to anticipate what information clinicians need and then deliver it in a way that is tailored for their unique views. Clinicians need workstations that offer the highest level possible of user-determined flexibility and customization. We envision and outline a so-called point of care work station, automatically scaling to the display, hardware capacity, operating system, applications (local or distributed) the user needs and across diverse health IT systems. [ABSTRACT FROM AUTHOR]

Endogenous regulatory T (T(reg)) cells are involved in the control of infections, including Leishmania infection in mice. Leishmania viannia braziliensis is the main etiologic agent of cutaneous leishmaniasis (CL) in Brazil, and it is also responsible for the more severe mucocutaneous form. Here, we investigated the possible involvement of T(reg) cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional T(reg) cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of T(reg) cells--such as CD25, cytotoxic T lymphocyte-associated antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor--and are able to produce large amounts of interleukin-10 and transforming growth factor- beta . Furthermore, CD4(+)CD25(+) T cells derived from the skin lesions of 4 of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin-induced proliferative T cell responses of allogeneic peripheral-blood mononuclear cells (PBMCs) from healthy control subjects at a ratio of 1 T(reg) cell to 10 allogeneic PBMCs. These findings suggest that functional T(reg) cells accumulate at sites of Leishmania infection in humans and possibly contribute to the local control of effector T cell functions. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Robotic liver transplantation represents a cutting-edge technique that may surpass traditional open surgery. Nonetheless, it introduces unique anesthetic challenges, including extended pneumoperitoneum, restricted patient access, and a risk of undetected blood loss. This article describes an anesthetic approach and patient outcomes for the first four total robotic liver transplants performed at a tertiary university hospital in Portugal, along with inaugural procedures of their kind in Europe. We retrospectively analyzed surgical and anesthetic data from four patients who underwent total robotic liver transplantation from February to April 2024. Data encompassed clinical profile, preoperative assessment, surgical and anesthesia details, postoperative course, and outcomes. Patients' age ranged from 51 to 69 years. Their cirrhosis was primarily due to alcohol use, hepatitis C virus infection, hepatocellular carcinoma, or nonalcoholic steatohepatitis. General anesthesia was administered. Hemodynamic monitoring and goal-directed fluid therapy were conducted using a PiCCO system. Blood loss varied from 1,000 to 5,000 mL. Blood products were transfused as needed. All donor livers underwent hypothermic oxygenated machine perfusion before transplantation. After surgery, two patients were immediately extubated, while two required extended ventilation. Hospital stays ranged from 10 to 40 days. The 30-day survival rate was 100%. This initial case series affirmed the feasibility and safety of total robotic liver transplantation for carefully selected patients, yielding favorable short-term results. Anesthetic management can rely on proactive strategies, acute situational awareness, and effective multidisciplinary collaboration.

Background: The rapid spread and increase of chikungunya (CHIKV) and dengue (DENV) cases in Brazilian regions in 2023 has raised concerns about the impact of arboviruses on public health. Epidemiological and genomic surveillance was performed to estimate the introduction and spread of CHIKV and DENV in Brazil., Methods: This study obtained results from the Hermes Pardini (HP), a private medical laboratory, and the Health Department of Minas Gerais state (SES-MG). We investigated the positivity rates of CHIKV and DENV by analyzing the results of 139,457 samples tested for CHIKV (44,029 in 2022 and 95,428 in 2023) and 491,528 samples tested for DENV (163,674 in 2022 and 327,854 in 2023) across the five representative geographical regions of Brazil. Genome sequencing was performed on 80 CHIKV and 153 DENV samples that had been positive for RT-PCR tests., Results: In our sampling, the data from CHIKV tests indicated that the Northeast region had the highest regional positivity rate in 2022 (58.1%). However, in 2023, the Southeast region recorded the highest positivity rate (40.5%). With regard to DENV, the South region exhibited the highest regional positivity rate in both 2022 (40.8%) and 2023 (22.7%), followed by the Southeast region in both years (34.8% in 2022; 21.4% in 2023). During the first 30 epidemiological weeks of 2023 in the state of Minas Gerais (MG), there was a 5.8-fold increase in CHIKV cases and a 3.5-fold increase in DENV compared to the same period in 2022. Analysis of 151 new DENV-1 and 80 CHIKV genomes revealed the presence of three main clusters of CHIKV and circulation of several DENV lineages in MG. All CHIKV clades are closely related to genomes from previous Brazilian outbreaks in the Northeast, suggesting importation events from this region to MG. We detected the RNA of both viruses in approximately 12.75% of the confirmed positive cases, suggesting an increase of co-infection with DENV and CHIKV during the period of analysis., Conclusions: These high rates of re-emergence and co-infection with both arboviruses provide useful data for implementing control measures of Aedes vectors and the urgent implementation of public health politics to reduce the numbers of CHIKV and DENV cases in the country., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Research Ethics Committee (CAAE- 33202820.7.1001.5348). Consent for publication: There is no consent for publication for this paper. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Nitric oxide (NO) holds promise for wound healing due to its antimicrobial properties and role in promoting vasodilation and tissue regeneration. The local delivery of NO to target cells or organs offers significant potential in numerous biomedical applications, especially when NO donors are integrated into nontoxic viscous matrices. This study presents the development of robust cellulose nanofibril (CNF) hydrogels designed to control the release of nitric oxide (NO) generated in situ from a NO-donor molecule ( S -nitrosoglutathione, GSNO) obtained from the nitrosation of its precursor molecule glutathione (GSH). CNF, efficiently isolated from sugar cane bagasse, exhibited a high aspect ratio and excellent colloidal stability in water. Although depletion forces could be observed upon the addition of GSH, this effect did not significantly alter the morphology of the CNF network at low GSH concentrations (<20 mM). Ionic cross-linking with Ca 2+ resulted in nontoxic and robust hydrogels (elastic moduli ranging from 300 to 3000 Pa) at low CNF solid content. The release rate of NO from GSNO decreased in CNF from 1.61 to 0.40 mmol. L -1 ·h -1 when the nanofibril content raised from 0.3 to 1.0 wt %. The stabilization effect monitored for 16 h was assigned to hydrogel mesh size, which was easily tailored by modifying the concentration of CNF in the initial suspension. These results highlight the potential of CNF-based hydrogels in biomedical applications requiring a precise NO delivery.

Objectives: This systematic review aimed to determine whether bioactive resin materials can prevent secondary caries or enhance the longevity of direct posterior restorations., Data Sources: The protocol was registered in PROSPERO (CRD42024561179). The review followed PRISMA guidelines, utilizing a PICO framework. Studies were identified through searches in six databases (PubMed, Scopus, Cochrane, Embase, Scielo, Web of Science) up to May 2024., Study Selection: Two independent reviewers applied inclusion criteria, selecting randomized clinical trials evaluating bioactive resin composites in restorative dentistry. Data were extracted into pre-designed forms, and article quality was assessed using the CONSORT, RoB 2, and GRADE tools. Meta-analyses focused on secondary caries incidence and restoration longevity using USPHS and FDI criteria., Results: Of 1,565 articles identified, 10 met the inclusion criteria. These studies, conducted in five countries, included 411 participants with follow-up periods ranging from 1 to 8 years. Materials evaluated included ACTIVA™ BioACTIVE, Giomer, and Cention N. Meta-analysis found no statistically significant differences between bioactive and conventional resin composites in preventing secondary caries or reducing retention loss (p > 0.05), the two primary outcomes considered in this review for assessing restoration longevity. Subgroup analysis showed no differences between follow-up periods., Conclusions: Bioactive materials demonstrated similar clinical performance to conventional composites in preventing secondary caries and retaining restorations, offering no additional benefit in enhancing the longevity of direct posterior restorations., Clinical Significance: This review provides evidence that bioactive resin materials offer no significant clinical advantage over traditional composites, guiding (or informing) clinicians in (or about) material selection for restorative treatments., 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 Ltd. All rights reserved.)

Background: Most of the investigations related to inflammasome activation during HIV infection have focused on the receptor NLRP3 and innate immune cells such as monocytes/macrophages. However, during the past years, inflammasome activation has also been explored in lymphocytes, and novel sensors, other than the NLRP3, have been shown to play a role in the biology of these cells. Here, we hypothesized that NLRP1 may be involved in CD4+ T cell dysregulation in people living with HIV (PLWH), therefore contributing to chronic inflammation and to the pathogenesis of non-HIV-associated diseases., Methods: The activation of NLRP1 in CD4+ T cells was assessed ex-vivo and in-vitro by the meaning of anti-CD3/anti-CD28 and Talabostat/Val-boroPro (VbP) response., Results: Our results showed that the NLRP1 inflammasome was activated in PLWH CD4+ T cells, and that the stimulation of CD4+ T cells resulted in increased response to anti-CD3/anti-CD28 and VbP. Functional variants in NLRP1 significantly affected the level of inflammatory dysregulation of CD4+ T cells, therefore explaining at least in part the association with CD4+ T-mediated diseases., Conclusion: PLWH CD4+ T cells are more prone to IL-1β release and pyroptosis, therefore contributing to chronic inflammation.

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare non-infectious inflammatory musculoskeletal disease where imaging plays a key diagnostic role. Vertebral and mandibular lesions are frequent manifestations, meaning their awareness is crucial for the neuroradiologist to avoid delays in diagnosis and treatment., Objective: Characterize vertebral and mandibular CNO lesions on imaging to assist practicing neuroradiologists in better identifying this disease., Materials and Methods: Retrospective review of all CNO patients of our pediatric center, including only patients with vertebral or mandibular lesions. All imaging exams were analyzed to record lesion characteristics., Results: We included 13 patients (six male). The mean age of onset was 12.3 years. Ten patients had only vertebral lesions, two had only mandibular lesions, and one had both. For patients with vertebral lesions, the median number of levels affected was three, 81.8% had multiple levels affected, 90.0% had dorsal spine lesions, 72.7% had platyspondyly, and 81.8% had inflammatory changes. All vertebral lesions had at least partial resolution of inflammatory findings, the mean time of lesion activity was 2.5 years, and recurrence occurred in 27.3%. Three patients had sacral lesions, all with sacroiliitis. In patients with mandibular lesions, all had unilateral lesions involving the mandibular ramus, all had hyperostosis, periosteal reaction, bone edema, and soft tissue inflammation, all had partial resolution on follow-up, and one had recurrence., Conclusion: CNO vertebral lesions are not rare, are often multiple, predominantly affect dorsal levels, and most result in vertebral height loss. Resolution of vertebral inflammatory lesions is frequent, but so is recurrence. Sacral lesions may be present and result in sacroiliitis. The mandible may be a site of unifocal disease, typically affecting the ramus, with prominent bony changes and soft tissue inflammation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We report a case of Burkholderia mallei causing glanders in a 73-year-old patient from the Northeast Region of Brazil. The patient was hospitalized with severe pneumonia. PCR and genomic sequencing confirmed B. mallei in pleural drainage. Genotyping revealed a novel genotype, emphasizing the need for genetic surveillance in zoonotic infections.

In recent years, natural polysaccharides (PSs) have attracted increasing interest because of their remarkable biological properties and potential in various areas, such as medicine, and food. This study aimed to present a detailed review of the evidence on the therapeutic potential of PSs for the treatment of gastrointestinal diseases. The main evidence was correlated with their chemical composition, mechanism of action and therapeutic effect. The main results showed that the action can be attributed to their ability to suppress excessive inflammatory responses, regulating the expression of cytokines and interleukins, reducing intestinal inflammation and promoting wound healing. Furthermore, we discussed how PSs help in the repair of the intestinal mucosa and related these effects with the composition of monosaccharides. A detailed analysis was performed on the ability of PSs to modulate the intestinal microbiota, promoting the growth of beneficial bacteria and suppressing inflammatory bacteria, in addition to its probiotic action with production of short-chain fatty acids. All this evidence was also taken into a broader context, in which the main challenges in processing PSs were considered and strategies to circumvent them were pointed out. Therefore, this review sought to demonstrate the great potential and viability of PSs as innovative and effective therapeutic agents., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Homocysteine (Hcy) is produced through methionine transmethylation. Elevated Hcy levels are termed Hyperhomocysteinemia (HHcy) and represent a risk factor for neurodegenerative conditions such as Alzheimer's disease. This study aimed to explore the impact of mild HHcy and the neuroprotective effects of ibuprofen and rivastigmine via immunohistochemical analysis of glial markers (Iba-1 and GFAP). Additionally, we assessed levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), chemokine ligand 5 (CCL5/RANTES), CX3C chemokine ligand 1 (CX3CL1), and the NGF/p75NTR/tropomyosin kinase B (TrkB) pathway in the hippocampus of adult rats. Mild chronic HHcy was induced chemically in Wistar rats by subcutaneous administration of Hcy (4 mg/kg body weight) twice daily for 30 days. Rivastigmine (0.5 mg/kg) and ibuprofen (40 mg/kg) were administered intraperitoneally once daily. Results revealed elevated levels of CCL5/RANTES and reduced levels of VEGF, EGF, and TrkB in the hippocampus of HHcy-exposed rats. Rivastigmine mitigated the neurotoxic effects of HHcy by increasing TrkB and VEGF levels. Conversely, ibuprofen attenuated CCL5/RANTES levels against the neurotoxicity of HHcy, significantly reducing this chemokine's levels. HHcy-induced neurochemical impairment in the hippocampus may jeopardize neurogenesis, synapse formation, axonal transport, and inflammatory balance, leading to neurodegeneration. Treatments with rivastigmine and ibuprofen alleviated some of these detrimental effects. Reversing HHcy-induced damage through these compounds could serve as a potential neuroprotective strategy against brain damage., 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.)

Objective: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services., Methods: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview., Results: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources., Conclusions: Fear about their child's well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD., (© 2024 Wiley Periodicals LLC.)

Purpose: The association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia., Methods: The WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses., Results: MDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype., Conclusion: The findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The emergence of new SARS-CoV-2 variants of concern associated with waning immunity induced by natural infection or vaccines currently in use suggests that the COVID-19 pandemic will become endemic. Investing in new booster vaccines using different platforms is a promising way to enhance protection and keep the disease under control. Here, we evaluated the immunogenicity, efficacy, and safety of the SpiN-Tec vaccine, based on a chimeric recombinant protein (SpiN) adjuvanted with CTVad1 (MF59-based adjuvant), aiming at boosting immunity against variants of concern of SARS-CoV-2. Immunization of K18-hACE-2 transgenic mice and hamsters induced high antibody titers and cellular immune response to the SpiN protein as well as to its components, RBD and N proteins. Importantly in a heterologous prime/boost protocol with a COVID-19 vaccine approved for emergency use (ChAdOx1), SpiN-Tec enhanced the level of circulation neutralizing antibodies (nAb). In addition to protection against the Wuhan isolate, protection against the Delta and Omicron variants was also observed as shown by reduced viral load and lung pathology. Toxicity and safety tests performed in rats demonstrated that the SpiN-Tec vaccine was safe and, based on these results, the SpiN-Tec phase I/II clinical trial was approved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ricardo Tostes Gazzinelli reports financial support was provided by Rede Virus from the Ministry of Science, Technology and Innovation. Ricardo Tostes Gazzinelli reports financial support was provided by National Council for Scientific and Technological Development. Ricardo Tostes Gazzinelli reports financial support was provided by National Institute of Science and Technology of Vaccines. Ricardo Tostes Gazzinelli reports financial support was provided by State of São Paulo Research Foundation. Ricardo Tostes Gazzinelli reports financial support was provided by Ministry of Education. Ricardo Tostes Gazzinelli reports financial support was provided by Oswaldo Cruz Foundation. Ricardo Tostes Gazzinelli reports financial support was provided by Belo Horizonte City Council. Ricardo Tostes Gazzinelli reports financial support was provided by Parliamentary Amendment of State and Federal Representatives from Minas Gerais. Ricardo Tostes Gazzinelli has patent #BR1020210095733 issued to Licensee. If there are other authors, they 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To describe the trends in antibiotic prescribing by dental practitioners and to investigate the relationship between these trends and some factors of public oral health services in Minas Gerais (MG), Brazil., Methods: This was a time-series analysis of antibiotics prescribed by dental practitioners between January 2011 and December 2021. The outcome variables were number of defined daily doses (DDD) and DDD/1000 population/year in a sample of cities in MG. Covariates were public oral healthcare factors, such as coverage, estimates of dental procedures, and frequency of dental pain. Linear time-series regression models were used to examine trends and the influence of covariates on antibiotic prescribing., Results: Overall, the number of prescriptions increased by 334.69% between 2011 and 2021, with amoxicillin being the most commonly prescribed drug (78.53%). The number of DDD for all antibiotics increased from 17,147.13 to 77,346.67 and the average DDD/1000 inhabitants/year was 126.66 (SD: 130.28). The linear time-series regression model showed that for each one-year increase, the average log DDD/1000 inhabitants increased by 0.35 (standard error = 0.07, p < 0.001). No covariates were found to be associated with the outcome., Conclusions: In Minas Gerais, Brazil, a significant upward trend was observed in the number of prescriptions and the number of DDD of antibiotics prescribed by dental practitioners. No influence of factors related to public oral healthcare services on the outcome was observed, thereby emphasizing the need for further research on factors influencing medication use in dental practice., (© 2024 American Association of Public Health Dentistry.)

Spinal cord injury (SCI) is one of the most serious conditions of the central nervous system, causing motor and sensory deficits that lead to a significant impairment in the quality of life. Previous studies have indicated that inosine can promote regeneration after SCI. Here we investigated the effects of inosine on the behavioral and morphological recovery after a compressive injury. Adult female C57BL/6 mice were subjected to laminectomy and spinal cord compression using a vascular clip. Inosine or saline injections were administered intraperitoneally, with the first dose performed 24 h after injury and daily for 7 days after injury. The mice were evaluated using Basso Mouse Scale (BMS), locomotor rating scale, and pinprick test for 8 weeks. At the end, the animals were anesthetized and euthanized, and the spinal cords were collected for morphological evaluation. Inosine-treated animals presented better results in the immunostaining for oligodendrocytes and in the number of myelinated fibers through semithin sections compared to saline-treated animals, showing that there was a greater preservation of the white matter. Analysis of the immunoreactivity of astrocytes and evaluation of the inflammatory profile with macrophage labeling revealed that the animals of the inosine group had a lower immunoreactivity when compared to control, which suggests a reduction of the glial scar and less inflammation, respectively, leading to a more favorable microenvironment for spinal cord regeneration. Indeed, inosine-treated animals scored higher on the BMS scale and presented better results on the pinprick test, indicating that the treatment contributed to motor and sensory recovery. After the animals were sacrificed, we obtained the electroneuromyography, where the inosine group showed a greater amplitude of the compound muscle action potential. These results indicate that inosine contributed to the regeneration process in the spinal cord of mice submitted to compressive injury and should be further investigated as a candidate for SCI therapy., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)