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Izo Helber,1 Claudia Maria Rodrigues Alves,1 Stela Maris Grespan,1 Eduardo CA Veiga,2 Pedro IM Moraes,1 José Marconi Souza,1 Adriano H Barbosa,1 Iran Gonçalves Jr,1 Francisco AH Fonseca,1 Antônio Carlos C Carvalho1,†, Adriano Caixeta1,3 1Department of Medicine, Discipline of Cardiology, Escola Paulista de Medicina, Universidade Federal São Paulo, São Paulo, Brazil; 2Department of Gynecology and Obstetrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 3Department of Cardiology, Hospital Israelita Albert Einstein, São Paulo, Brazil†Dr Antonio Carlos De Camargo Carvalho passed away on January 8, 2019Correspondence: Adriano CaixetaEscola Paulista de Medicina, Universidade Federal São Paulo, Av. Napoleão de Barros, 715, São Paulo, CEP: 04024002, BrazilTel +55 11- 5576-4000Email adriano.caixeta@einstein.br Twitter @adrianocaixetaBackground: There is little research in the efficacy and safety of a pharmaco-invasive strategy (PIS) in patients ≥ 75 years versus < 75 years of age. We aimed to evaluate and compare the influence of advanced age on the risk of death and major adverse cardiac events (MACE) in patients undergoing PIS.Methods: Between January 2010 and November 2016, 14 municipal emergency rooms in São Paulo, Brazil, used full-dose tenecteplase to treat patients with STEMI as part of a pharmaco-invasive strategy for a local network implementation.Results: A total of 1852 patients undergoing PIS were evaluated, of which 160 (9%) were ≥ 75 years of age. Compared to patients < 75 years, those ≥ 75 years were more often female, had lower body mass index, higher rates of hypertension; higher incidence of hypothyroidism, chronic renal failure, prior stroke, and diabetes. Compared to patients < 75 years of age, in-hospital MACE and mortality were higher in patients with ≥ 75 years (6.5% versus 19.4%; p< 0.001; and 4.0% versus 18.2%; p< 0.001, respectively). Patients ≥ 75 years had higher rates of in-hospital major bleeding (2.7% versus 5.6%; p=0.04) and higher incidence of cardiogenic shock (7.0% versus 19.6%; p< 0.001). By multivariable analysis, age ≥ 75 years was independent predictor of MACE (OR 3.57, 95% CI 1.72 to 7.42, p=0.001) and death (OR 2.07, 95% CI 1.12– 3.82, p=0.020).Conclusion: In patients with ST-segment elevation myocardial infarction undergoing PIS, age ≥ 75 years was an independent factor that entailed a 3.5-fold higher MACE and 2-fold higher mortality rate compared to patients < 75 years of age.Keywords: acute myocardial infarction, elderly, fibrinolysis, primary percutaneous coronary intervention, pharmaco-invasive strategy

Background and Purpose Huntington's disease ( HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. We have previously demonstrated that the cell signalling of the metabotropic glutamate receptor 5 ( mGluR5) is altered in a mouse model of HD. Although mGluR5-dependent protective pathways are more activated in HD neurons, intracellular Ca2+ release is also more pronounced, which could contribute to excitotoxicity. In the present study, we aim to investigate whether mGluR5 positive allosteric modulators ( PAMs) could activate protective pathways without triggering high levels of Ca2+ release and be neuroprotective in HD. Experimental Approach We performed a neuronal cell death assay to determine which drugs are neuroprotective, Western blot and Ca2+ release experiments to investigate the molecular mechanisms involved in this neuroprotection, and object recognition task to determine whether the tested drugs could ameliorate HD memory deficit. Key Results We find that mGluR5 PAMs can protect striatal neurons from the excitotoxic neuronal cell death promoted by elevated concentrations of glutamate and NMDA. mGluR5 PAMs are capable of activating Akt without triggering increased intracellular Ca2+ concentration ([Ca2+]i); and Akt blockage leads to loss of PAM-mediated neuroprotection. Importantly, PAMs' potential as drugs that may be used to treat neurodegenerative diseases is highlighted by the neuroprotection exerted by mGluR5 PAMs on striatal neurons from a mouse model of HD, BACHD. Moreover, mGluR5 PAMs can activate neuroprotective pathways more robustly in BACHD mice and ameliorate HD memory deficit. Conclusions and Implications mGluR5 PAMs are potential drugs that may be used to treat neurodegenerative diseases, especially HD. [ABSTRACT FROM AUTHOR]

Background: Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause-of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of São Paulo, Brazil, between 1985 and 2007.Methods: We analyzed mortality data from the São Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant.Results: Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age- and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 ± 20.81 years for DM and 54.24 ± 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03).Conclusions: Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM. [ABSTRACT FROM AUTHOR]

Background: Cerebral Cavernous Malformations (CCM) is a genetic disease characterized by vascular abnormalities in the brain and spinal cord, affecting 0.4-0.5 % of the population. We identified two novel pathogenic mutations, CCM1/KRIT1 c.811delT (p.Trp271GlyfsTer5) and CCM2/MGC4607 c.613&#95;614insGG p.Glu205GlyfsTer31), which disrupt crucial protein domains and potentially alter disease progression., Objective: The study aims to comprehensively analyze a Brazilian cohort of CCM patients, integrating genetic, clinical, and structural aspects. Specifically, we sought to identify novel mutations within the CCM complex, and explore their potential impact on disease progression., Methods: We conducted a detailed examination of neuroradiological and clinical features in both symptomatic and asymptomatic CCM patients, performing genetic analyses through sequencing of the CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes In silico structural predictions were carried out using PolyPhen-2, SIFT, and Human Genomics Community tools. Protein-protein interactions and docking analyses were explored using the STRING database., Results: Genetic analysis identifies 6 pathogenic mutations, 4 likely pathogenic, 1 variants of uncertain significance, and 7 unclassified mutations, including the novel mutations in CCM1 c.811delT and CCM2 c.613&#95;614insGG. In silico structural analysis revealed significant alterations in protein structure, supporting their pathogenicity. Protein-protein interaction analysis indicated nuanced impacts on cellular processes. Clinically, we observed a broad spectrum of symptoms, including seizures and focal neurological deficits. However, no statistically significant differences were found in lesion burden, age of first symptom onset, or sex between the identified CCM1/KRIT1 and CCM2/MGC4607 mutations among all patients studied., Conclusion: This study enhances the understanding of CCM by linking clinical variability, genetic mutations, and structural effects. The identification of these novel mutations opens new avenues for research and potential therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that all authors agreed with the final manuscript, that they do not have any conflict of interest and there is no financial/personal interest of beliefs that could affect this research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Frazão 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.)

Temporal lobe epilepsy (TLE) is a prevalent form of epilepsy originating in the temporal lobes. A common pathological feature is hippocampal sclerosis (HS), characterized by the loss of neuronal cells, which is associated with the typical temporal mesial lobe epilepsy (MTLE). In this study, we aimed to analyze gray matter alterations in patients with MTLE with right and left hemisphere HS using voxel-based morphometry and compare them with control groups. A meta-analysis was performed based on the guidelines contained in the Protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the MEDLINE database, with the keywords: "gray matter" AND "temporal lobe epilepsy " AND ("hippocampal sclerosis" OR "hippocampal abnormalities") AND ("voxel-based morphometry" OR "VBM" OR "voxel-wise"). Of the 14 articles included in the review, 8 were added by the method, in which the meta-analysis was performed. Our results indicate that in the right hemisphere, the hippocampus, caudate nucleus, parahippocampal gyrus, thalamus, dorsalis medial nucleus, insula, and right claustrum were most commonly implicated. In the left hemisphere, a significant pattern of gray matter loss was observed in the putamen, lentiform nucleus, uncus, Brodmann areas 20 and 23, cingulate gyrus, caudate nucleus, cerebellum, and cuneus compared to healthy controls.Our study highlights distinct patterns of gray matter alteration in MLTE-HS and suggests that these regions may contribute to changes in verbal memory and visuospatial impairment based on their anatomical and hemispheric locations. Our findings can be potentially helpful for future diagnostic markers, therapeutic targets, and insights into disease progression, better understanding of these findings., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Familial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research., Objective: This study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population., Methods: This retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes., Results: A total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68 % were symptomatic, with 30 % having CASH and 36 % experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17 % had a new CASH event, 20 % had seizures without CASH, and 60 % remained asymptomatic. The bleeding rate was 1.02 % per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001)., Conclusion: This study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs., 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. Published by Elsevier Inc.)

Tuberculosis (TB) remains an impactful infectious disease, leading to millions of deaths every year. Mycobacterium tuberculosis causes the formation of granulomas, which will determine, through the host-pathogen relationship, if the infection will remain latent or evolve into active disease. Early TB diagnosis is life-saving, especially among immunocompromised individuals, and leads to proper treatment, preventing transmission. This review addresses different approaches to diagnosing TB, from traditional methods such as sputum smear microscopy to more advanced molecular techniques. Integrating these techniques, such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), has significantly improved the sensitivity and specificity of M. tuberculosis identification. Additionally, exploring novel biomarkers and applying artificial intelligence in radiological imaging contribute to more accurate and rapid diagnosis. Furthermore, we discuss the challenges of existing diagnostic methods, including limitations in resource-limited settings and the emergence of drug-resistant strains. While the primary focus of this review is on TB diagnosis, we also briefly explore the challenges and strategies for diagnosing non-tuberculous mycobacteria (NTM). In conclusion, this review provides an overview of the current landscape of TB diagnostics, emphasizing the need for ongoing research and innovation. As the field evolves, it is crucial to ensure that these advancements are accessible and applicable in diverse healthcare settings to effectively combat tuberculosis worldwide.

There may be an increased risk of metabolic disorders, such as rumen acidosis, in cattle fed high-concentrate diets, particularly those from Bos taurus indicus genotypes, which have shown to be more sensitive to ruminal acidification. Therefore, this study aimed to estimate (co)variance components and identify genomic regions and pathways associated with ruminal acidosis in feedlot Nellore cattle fed high-concentrate diets. It was utilized a dataset containing a total of 642 Nellore bulls that were genotyped from seven feedlot nutrition studies. The GGP Indicus 35k panel was used with the single step genome-wide association study methodology in which the effects of the markers were obtained from the genomic values estimated by the GBLUP model. A bivariate model to estimate genetic correlations between the economically important traits and indicator traits for acidosis was used. The traits evaluated in this study that were nutritionally related to rumen acidosis included average daily gain (ADG), final body weight, time spent eating (TSE), time spent ruminating, rumenitis score (RUM), rumen absorptive surface area (ASA), rumen keratinized layer thickness (KER) and hot carcass weight (HCW). The identified candidate genes were mainly involved in the negative or non-regulation of the apoptotic process, salivary secretion, and transmembrane transport. The genetic correlation between HCW and ASA was low positive (0.27 ± 0.23), and between ADG and ASA was high moderate (0.58 ± 0.59). A positive genetic correlation between RUM and all performance traits was observed, and TSE correlated negatively with HCW (-0.33 ± 0.21), ASA (-0.75 ± 0.48), and KER (-0.40 ± 0.27). The genetic association between economically important traits and indicator traits for acidosis suggested that Nellore cattle may be more sensitive to acidosis in feedlot systems., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objective: The biological behavior of Cerebral Cavernous Malformation (CCM) is still controversial, lacking a clear-cut signature for a mechanistic explanation of lesion aggressiveness. In this study, we evaluated the predictive capacity of genetic variants concerning the aggressive behavior of CCM and their implications in biological processes., Methods: We genotyped the variants in VDR rs7975232 , VDR rs731236 , VDR rs11568820 , PTPN2 rs72872125 and FCGR2A rs1801274 genes using TaqMan Genotyping Assays in a cohort study with 103 patients, 42 of whom had close follow-up visits for 4 years, focusing on 2 main aspects of the disease: (1) symptomatic events, which included both intracranial bleeding or epilepsy, and (2) the onset of symptoms. The genotypes were correlated with the levels of several cytokines quantified in peripheral blood, measured using the x-MAP method., Results: We report a novel observation that the PTPN2 rs72872125 CT and the VDR rs7975232 CC genotype were independently associated with an asymptomatic phenotype. Additionally, PTPN2 rs72872125 CC genotype and serum level of GM-CSF could predict a diagnostic association with symptomatic phenotype in CCM patients, while the FCGR2A rs1801274 GG genotype could predict a symptomatic event during follow-up. The study also found a correlation between VDR r s731236 AA and VDR rs11568820 CC genotype to the time to the first symptomatic event., Conclusions: These genetic markers could pave the way for precision medicine strategies for CCM, enhancing patient outcomes by enabling customized therapeutic approaches., 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.)

Candida tropicalis is regarded as an opportunistic pathogen, causing diseases ranging from superficial infections to life-threatening disseminated infections. The ability of this yeast to form biofilms and develop resistance to antifungals represents a significant therapeutic challenge. Herein, the effect of geraniol (GER), alone and combined with fluconazole (FLZ), was evaluated in the planktonic and sessile cells of azole-resistant C. tropicalis . GER showed a time-dependent fungicidal effect on the planktonic cells, impairing the cell membrane integrity. Additionally, GER inhibited the rhodamine 6G efflux, and the molecular docking analyzes supported the binding affinity of GER to the C. tropicalis Cdr1 protein. GER exhibited a synergism with FLZ against the planktonic and sessile cells, inhibiting the adhesion of the yeast cells and the viability of the 48-h biofilms formed on abiotic surfaces. C. tropicalis biofilms treated with GER, alone or combined with FLZ, displayed morphological and ultrastructural alterations, including a decrease in the stacking layers and the presence of wilted cells. Moreover, neither GER alone nor combined with FLZ caused toxicity, and both treatments prolonged the survival of the Galleria mellonella larvae infected with azole-resistant C. tropicalis . These findings indicate that the combination of GER and FLZ may be a promising strategy to control azole-resistant C. tropicalis infections.

Central nervous system (CNS) involvement in autoimmune rheumatic diseases represents a significant challenge for clinicians across all specialties. While most reviews on the subject focus on neurological manifestations within a specific rheumatic disease, few descriptions shift from neurological clinical syndromes to achieve rheumatological diagnoses. This narrative review aims to synthesize current knowledge on the diagnosis and management of CNS manifestations occurring in the most prevalent rheumatic conditions in adults. We searched the MEDLINE database using the terms "central nervous system", "rheumatic diseases", "systemic lupus erythematosus", "rheumatoid arthritis", "Sjögren syndrome", and "vasculitis". The search strategy included review articles from 2019 to 2024, published in English, Spanish, or Portuguese. We explored the pathophysiological mechanisms linking autoimmunity to CNS pathology, emphasizing the role of syndromic reasoning, autoantibody profiles, and imaging modalities as tools for diagnosis and determination of inflammatory activity. The review also discusses differential diagnoses through a stepwise approach to neurological syndromes, summarized in diagnostic flowcharts, and presents updated treatment options. Although our approach is primarily semiology-based, the complexity of the subject invites future endeavors involving new technologies, such as functional MRI, MR spectroscopy, and nuclear medicine.

Plastic and reconstructive surgeons continually evolve their surgical strategies with the aim of achieving the optimal patient outcome. Numerous well-known frameworks intended to guide reconstructive planning have been introduced and are entrenched in plastic surgery education, but are limited in their scope due to their procedure-based construct. Here, we introduce the hierarchy of reconstructive needs: a problem-based reconstructive framework that shifts operative planning to the specific needs of the defect and goals for restoration of normality while allowing for further innovation and evolution beyond our existing surgical capabilities., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: Minimally invasive surgery (MIS) is the standard approach for the staging and treatment of early-stage endometrial cancer (EC) and often includes use of a uterine manipulator. Uterine perforation is a known risk in this setting, and the impact of perforation and tumor spillage on cancer recurrence is largely unknown. The aim of this study was to assess the association between uterine perforation and/or tumor spillage at the time of MIS for low-grade, early-stage EC on disease recurrence., Methods: A retrospective single-center cohort study was conducted including patients who underwent MIS for management of low-grade and early-stage EC with use of a uterine manipulator. Rates of disease recurrence were compared between patients with and without documented uterine perforation and/or tumor spillage at the time of surgery. Statistical significance was defined as p < 0.05., Results: 408 patients with low-grade and early-stage EC were identified from the tumor registry and included in the study. Uterine perforation and/or tumor spillage was documented in 5.9 % (24/408) of cases. Recurrent disease was noted in 8.1 % (33/408) of the entire cohort. Most patients had isolated local recurrence (23/33; 69.7 %), while 9.1 % (3/33) had distant recurrence and 21.2 % (7/33) had both local and distant recurrence. There was no association between uterine perforation and/or tumor spillage and recurrence rates (p = 0.67). The trend in disease free survival was shorter among patients with these complications., Conclusions: Our analysis did not demonstrate a statistically significant difference in disease recurrence rates among patients with early-stage, low-grade EC based on uterine perforation and/or tumor spillage at the time of surgery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

» The purpose of this article was to review the multidisciplinary, team-based approach necessary for the optimal management of patients with limb loss undergoing osseointegration surgery.» In this study, we describe the interdisciplinary process of screening, counseling, and surgical and rehabilitation considerations with an emphasis on principles rather than specific implants or techniques.» Integrated perioperative management and long-term surveillance are crucial to ensure the best possible outcomes.» We hope this model will service as an implant-agnostic guide to others seeking to development an osseointegration center of excellence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B115)., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Upper extremity limb loss profoundly impacts a patient's quality of life and well-being and carries a significant societal cost. Although osseointegration allows the attachment of the prosthesis directly to the bone, it is a relatively recent development as an alternative to conventional socket prostheses. The objective of this review was to identify reports on osseointegrated prosthetic embodiment for transhumeral amputations and assess the implant systems used, postoperative outcomes, and complications., Methods: A systematic review following PRISMA and AMSTAR guidelines assessed functional outcomes, implant longevity and retention, activities of daily living, and complications associated with osseointegrated prostheses in transhumeral amputees., Results: The literature search yielded 794 articles, with eight of these articles (retrospective analyses and case series) meeting the inclusion criteria. Myoelectric systems equipped with Osseointegrated Prostheses for the Rehabilitation of Amputees implants have been commonly used as transhumeral osseointegration systems. The transhumeral osseointegrated prostheses offered considerable improvements in functional outcomes, with participants demonstrating enhanced range of motion and improved performance of activities compared with traditional socket-based prostheses. One study demonstrated the advantage of an osseointegrated implant as a bidirectional gateway for signal transmission, enabling intuitive control of a bionic hand., Conclusions: Osseointegrated prostheses hold the potential to significantly improve the quality of life for individuals with transhumeral amputations. Continued research and clinical expansion are expected to lead to the realization of enhanced efficacy and safety in this technique, accompanied by cost reductions over time as a result of improved efficiencies and advancements in device design., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Antimicrobial peptides are an emerging class of antibiotics that present a series of advantageous characteristics such as wide structural variety, broad spectrum of activity, and low propensity to select for resistance. They are found in all classes of life as defense molecules. A group of peptides derived from the protein Bothropstoxin-I has been previously studied as an alternative treatment against multi-drug-resistant bacteria. The peptide p-BthTX-I (sequence: KKYRYHLKPFCKK) and its homodimer, linked by disulfide oxidation through the residues of Cys11 and the serum degradation product [sequence: (KKYRYHLKPFC) 2 ], were evaluated and showed similar antimicrobial activity. In this study, we synthesized an analogue of p-BthTX-I that uses the strategy of Fmoc-Lys(Fmoc)-OH in the C-terminal region for dimerization and tryptophan for all aromatic amino acids to provide better membrane interactions. This analogue, named p-BthW, displayed potent antibacterial activity at lower concentrations and maintained the same hemolytic levels as the original molecule. Our assessment revealed that p-BthW has a quick in vitro bactericidal action and prolonged post-antibiotic effect, comparable to the action of polymyxin B. The mode of action of p-BthW seems to rely not only on membrane depolarization but also on necrosis-like effects, especially in Gram-negative bacteria. Overall, the remarkable results regarding the propensity to develop resistance reaffirmed the great potential of the developed molecule., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

We aimed to investigate the effectiveness of physical training as a protective strategy to mitigate alveolar bone damage and blood antioxidant defense caused by ethanol (EtOH) consumption in a binge-drinking pattern. Male Wistar rats aged approximately 90 days were divided into four groups: control, training, EtOH, and training + EtOH. The physical training protocol was conducted on a treadmill for four consecutive weeks, while the animals in the EtOH group were administered EtOH via orogastric gavage for three consecutive days each week, following the binge drink pattern. After the training period, blood and mandibles were collected for plasma oxidative biochemistry analysis, and the alveolar bone was subjected to physicochemical composition analysis, tissue evaluation, and microtomography evaluation. Our results showed that EtOH induced oxidative stress and physical exercise promoted the recovery of antioxidant action. Physical training minimized the damage to the mineral/matrix composition of the alveolar bone due to EtOH consumption and increased the density of osteocytes in the trained group treated with EtOH than in those exposed only to EtOH. Furthermore, physical training reduced damage to the alveolar bone caused by EtOH consumption. Our findings suggest that physical training can serve as an effective strategy to reduce systemic enzymatic oxidative response damage and alleviate alveolar bone damage resulting from alcohol consumption. Further investigations are warranted to elucidate the underlying mechanisms and explore, in addition to physical training, the potential effects of other activities with varying intensities on managing alcohol-induced bone 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: to understand health and education professionals' perceptions regarding children's learning difficulties in public schools., Methods: qualitative research, of the participatory action type, linked to Paulo Freire's Research Itinerary. Forty-five professionals participated, through interviews and a Virtual Culture Circle. The analysis was developed through careful reading, reflection and interpretation of highlighted topics., Results: professionals discussed the (in)visibility of learning difficulties, strategies and resources in the educational sector and the search for solutions in the health sector. It was found that the production of complaints related to school learning is attributed predominantly as an individual problem of children or their family, exempting the educational institution from this process., Final Considerations: greater investment in professional training and development policies is urgently needed to facilitate coordination between sectors, with a view to overcoming outdated pedagogical and health models.

The peanut thrips, Enneothrips enigmaticus (Thysanoptera: Thrypidae), is an important pest of the peanut (Arachis hypogaea) in South America. Due to concerns about the environment and human health induced by the extensive use of pesticides in the management control of pests, environmentally and friendlier tactics must be targeted. Thus, this study investigates, for the first time, the behavior of Xylocoris sordidus (Hemiptera: Anthocoridae) as a biological control agent for E. enigmaticus. The methodology included no-choice tests to assess whether the predation rate varies according to the developmental stage of the prey, as well as the predator's developmental stage with the highest predation capacity. Additionally, an analysis of the functional response of adult and 5th instar nymphs of X. sordidus exposed to different densities of E. enigmaticus nymphs (1, 2, 4, 8, 16, and 32) was conducted. The results confirm the predation of peanut thrips by X. sordidus, with a higher predation rate in the nymphal stages of the prey. There was no difference in predation capacity between predator nymphs and adults, and exhibiting a type II functional response. Therefore, the potential of X. sordidus as a biological control agent for E. enigmaticus is confirmed, showing the importance of adopting measures to preserve this predator in peanut crops., (© 2024. Sociedade Entomológica do Brasil.)

Cerebral cavernous malformation (CCM) is a vascular disease that affects the central nervous system, which familial form is due to autosomal dominant mutations in the genes KRIT1(CCM1), MGC4607(CCM2), and PDCD10(CCM3). Patients affected by the PDCD10 mutations usually have the onset of symptoms at an early age and a more aggressive phenotype. The aim of this study is to investigate the molecular mechanism involved with CCM3 disease pathogenesis. Herein, we report two typical cases of CCM3 phenotype and compare the clinical and neuroradiological findings with five patients with a familial form of KRIT1 or CCM2 mutations and six patients with a sporadic form. In addition, we evaluated the PDCD10 gene expression by qPCR and developed a bioinformatic pipeline to understand the structural changes of mutations. The two CCM3 patients had an early onset of symptoms and a high lesion burden. Furthermore, the sequencing showed that Patient 1 had a frameshift mutation in c.222delT; p.(Asn75Thrfs*14) that leads to lacking the last 124 C-terminal amino acids on its primary structure and Patient 2 had a variant on the splicing site region c.475-2A > G. The mRNA expression was fourfold lower in both patients with PDCD10 mutation. Using in silico analysis, we identify that the frameshift mutation transcript lacks the C-terminal FAT-homology domain compared to the wild-type PDCD10 and preserves the N-terminal dimerization domain. The two patients studied here allow estimating the potential impact of mutations in clinical interpretation as well as support to better understand the mechanism and pathogenesis of CCM3., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)