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Currently, no treatments available for Parkinson’s disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson’s Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.

Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease.Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD.Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society—Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial Registration: NCT03100149.

Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.

Abstract Background Gluconacetobacter diazotrophicus Pal5 is an endophytic diazotrophic bacterium that lives in association with sugarcane plants. It has important biotechnological features such as nitrogen fixation, plant growth promotion, sugar metabolism pathways, secretion of organic acids, synthesis of auxin and the occurrence of bacteriocins. Results Gluconacetobacter diazotrophicus Pal5 is the third diazotrophic endophytic bacterium to be completely sequenced. Its genome is composed of a 3.9 Mb chromosome and 2 plasmids of 16.6 and 38.8 kb, respectively. We annotated 3,938 coding sequences which reveal several characteristics related to the endophytic lifestyle such as nitrogen fixation, plant growth promotion, sugar metabolism, transport systems, synthesis of auxin and the occurrence of bacteriocins. Genomic analysis identified a core component of 894 genes shared with phylogenetically related bacteria. Gene clusters for gum-like polysaccharide biosynthesis, tad pilus, quorum sensing, for modulation of plant growth by indole acetic acid and mechanisms involved in tolerance to acidic conditions were identified and may be related to the sugarcane endophytic and plant-growth promoting traits of G. diazotrophicus. An accessory component of at least 851 genes distributed in genome islands was identified, and was most likely acquired by horizontal gene transfer. This portion of the genome has likely contributed to adaptation to the plant habitat. Conclusion The genome data offer an important resource of information that can be used to manipulate plant/bacterium interactions with the aim of improving sugarcane crop production and other biotechnological applications.

Bruna Lallo da Silva,1 Marina Paiva Abuçafy,1 Eloisa Berbel Manaia,1 João Augusto Oshiro Junior,1 Bruna Galdorfini Chiari-Andréo,1,2 Rosemeire CL R Pietro,1 Leila Aparecida Chiavacci1 1Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil; 2Department of Biological and Health Sciences, Universidade De Araraquara, UNIARA, Araraquara, SP, BrazilCorrespondence: Leila Aparecida ChiavacciDepartment of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara Jaú, km 1 – s/n Campos Ville, Araraquara, SP, BrazilTel +55 16 33016966Fax +55 16 33016900Email leila@fcfar.unesp.brAbstract: The inappropriate use of antimicrobials has resulted in the selection of resistant strains. Thus, a great number of studies have focused on the investigation of new antimicrobial agents. The use of zinc oxide nanoparticles (ZnO NPs) to optimise the fight against microbial resistance has been receiving increased attention due to the non-specific activity of inorganic antimicrobial agents. The small particle size and the high surface area of ZnO NPs can enhance antimicrobial activity, causing an improvement in surface reactivity. In addition, surface modifiers covering ZnO NPs can play a role in mediating antimicrobial activity since the surface properties of nanomaterials alter their interactions with cells; this may interfere with the antimicrobial effect of ZnO NPs. The possibility of using surface modifiers with groups toxic to microorganisms can improve the antimicrobial activity of ZnO NPs. Understanding the exact toxicity mechanisms is crucial to elucidating the antimicrobial activity of ZnO NPs in bacteria and fungi. Therefore, this review aims to describe the mechanisms of ZnO NPs toxicity against fungi and bacteria and how the different structural and physical-chemical characteristics of ZnO NPs can interfere in their antimicrobial activity.Keywords: nanoparticles, zinc oxide, antimicrobial activity, toxicity mechanisms

Eloísa Berbel Manaia,1 Marina Paiva Abuçafy,1 Bruna Galdorfini Chiari-Andréo,1,2 Bruna Lallo Silva,1 João Augusto Oshiro Junior,1 Leila Aparecida Chiavacci1 1Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil, 2Department of Biological and Health Sciences, Centro Universitário de Araraquara, UNIARA, Araraquara, SP, Brazil Abstract: Pharmaceutical design has enabled important advances in the prevention, treatment, and diagnosis of diseases. The use of nanotechnology to optimize the delivery of drugs and diagnostic molecules is increasingly receiving attention due to the enhanced efficiency provided by these systems. Understanding the structures of nanocarriers is crucial in elucidating their physical and chemical properties, which greatly influence their behavior in the body at both the molecular and systemic levels. This review was conducted to describe the principles and characteristics of techniques commonly used to elucidate the structures of nanocarriers, with consideration of their size, morphology, surface charge, porosity, crystalline arrangement, and phase. These techniques include X-ray diffraction, small-angle X-ray scattering, dynamic light scattering, zeta potential, polarized light microscopy, transmission electron microscopy, scanning electron microcopy, and porosimetry. Moreover, we describe some of the commonly used nanocarriers (liquid crystals, metal–organic frameworks, silica nanospheres, liposomes, solid lipid nanoparticles, and micelles) and the main aspects of their structures. Keywords: nanoparticles, drug delivery, physicochemical properties, controlled drug release

Mariana R Sato,1 João A Oshiro Junior,1 Rachel TA Machado,1 Paula C de Souza,2 Débora L Campos,2 Fernando R Pavan,2 Patricia B da Silva,1,* Marlus Chorilli1,* 1Department of Drugs and Medicines, Faculdade de Ciências Farmacêuticas, UNESP – Univ Estadual Paulista, Campus Araraquara, Araraquara, SP, Brazil; 2Department of Biological Sciences, Faculdade de Ciências Farmacêuticas, UNESP – Univ Estadual Paulista, Campus Araraquara, Araraquara, SP, Brazil *These authors contributed equally to this work Abstract: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1–F6), and 0.50% cetyltrimethylammonium bromide (F7–F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis. Keywords: tuberculosis, M. tuberculosis, nanostructured lipid carriers, copper(II) complex, in vitro activity, in vivo acute toxicity assay

In spite of the large experience acquired in the last 50 years with the surgical treatment of the Chagasic megacolon, the use of colorectal video laparoscopic surgery brought some controversy in several aspects of the treatment that already had been considered as re- solved. One of the basic aspects to the establishment of the colorectal video laparoscopic surgery is to maintain the same procedure of the conventional surgery, since the results obtained in this operation were considered as curative. Constipation is only a symptom of a multisymptomatic disease, and the surgical treatment of acquired megacolon must be considered as definitive in the cure of this symptom; recurrence of the constipation or dilatation after a short period of time must be considered deleterious to the patient. Based in 41 years of experience with the Duhamel procedure in the treatment of 912 patients with acquired megacolon, the authors propose to apply the same technique in the surgical laparoscopic approach of acquired megacolon, including the same colon-recto-anal anas- tomosis. The results obtained in 56 patients operated on by laparoscopic approach showed the same curative results, but with lower morbidity. Resumo: Apesar da vasta experiência adquirida nos últimos 50 anos com o tratamento cirúrgico do megacolo adquirido, a introdução da cirurgia laparoscópica voltou a trazer controvérsia para alguns pontos anteriormente considerados como esclarecidos. Uma das regras básicas para a introdução da videolaparoscopia no tratamento das enfermidades colorretais tem sido a de se manter a técnica original utilizada em cirurgias pela via convencional, desde que os resultados observados na mesma conduzam à cura dos sintomas ou da enfermidade causal. Em especial, no referente ao tratamento cirúrgico do megacolo adquirido a proposta de um tratamento cirúrgico deve ter em mente que diferentemente do que ocorre com a cirurgia para tratamento de outras enfermidades, benignas ou malignas, neste caso não se almeja o tratamento causal da enfermidade, mas essencialmente a cura da manifestação de um de seus sintomas. É, pois, realmente importante que se considere um tratamento que não venha a resultar em bons resultados por apenas um curto espaço de tempo, mas que possibilite ao paciente livrar-se definitivamente de um sintoma, visto que é possível que em curto espaço de tempo ele venha a necessitar tratar outra manifestação sintoma- tológica (cardíaca ou esofágica) da enfermidade causal. Baseados na experiência adquirida nos últimos 50 anos (912 pacientes) com a técnica de Duhamel, em que o ponto importante é a realização de uma ampla anastomose da parede anterior do cólon abaixado à parede posterior (mucosa) do reto, ao mesmo tempo em que se anastomosa a parede posterior do cólon abaixado ao canal anal, são analisados os resultados obtidos com esta mesma técnica realizada por laparoscopia. Esta mesma incisão no canal anal serve para a retirada do seg- mento cólico ressecado, sem necessidade de laparotomia auxiliar. Os resultados observa- dos em 56 pacientes quanto à cura da obstipação são similares aos registrados na cirurgia convencional, porém com um menor índice de morbidade, seja intra ou pós-operatória. Keywords: Obstipation Constipation Acquired megacolon Laparoscopy Duhamel surgery Mechanic colon-recto-anal anastomosis, Palavras-chave: Obstipação Constipação Megacolo adquirido Laparoscopia Cirurgia de Duhamel Anastomose cólon-reto-anal mecânica

Entre 1978-1996, un total de 287 pacientes con adenocarcinoma rectal fueron tratados con radioterapia. El mismo protocolo fue utilizado en todos los pacientes: dosis total de 400cGy; dosis diaria de 200cGy; durante un período de 4 semanas y cirugía 10 días después. Un análisis de los resultados demostró que la irradiación aplicada en el preoperatorio disminuyó el número de células carcinomatosas, cambiando significativamente el porcentaje de Broders, al mismo tiempo que redujo la incidencia de recidiva local (3,48%) y la mortalidad secundaria a la misma (2,43%)

Nicotine (NIC) detection is vital for monitoring its presence in various environments, including tobacco products, electronic cigarettes, and clinical samples; NIC's widespread use and health implications necessitate precise and reliable detection methods as it is linked to diseases such as lung cancer and vascular disorders. In this study, we developed and characterized Au tadpole-like nanostructures immobilized onto titanium oxide (TiO 2 ) to provide a cost-effective and sensitive NIC detection material. The comprehensive characterization of the composite used transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), showing the robustness of the synthesis. Moreover, this material is unique due to its customized design, which combines structural features with functional capabilities, as demonstrated by the study's results. Electrochemical impedance spectroscopy (EIS) demonstrated significant enhancements in sensor performance, including improved charge transfer resistance, double-layer capacitance, and pseudocapacitance. Square wave voltammetry (SWV), performed under optimized conditions, demonstrated two linear ranges: 1.99-108.9 μmol L -1 and 159.3-900.8 μmol L -1 , with limits of detection (LOD) and quantification (LOQ) of 0.149 and 0.497 μmol L -1 , respectively. This novel electrochemical method demonstrated high accuracy in determining NIC levels in electronic cigarettes and simulated clinical samples, with a recovery range of 99.95 %-110.1 %. Furthermore, a comparative study using molecular absorption spectrometry confirmed the sensor's performance, employing a t-test for statistical validation. Thus, the Au-TiO 2 material advances the field of electrochemical detection and provides an effective tool for NIC monitoring, with significant potential for public health guidelines., 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 © 2025 Elsevier B.V. All rights reserved.)

This study evaluated the role of temperature and fine particulate matter in hospitalizations of children living in Cuiabá-MT, obtained from DATASUS, between 01/01/2016 and 12/31/2018. Daily concentrations of the pollutant fine particulate matter were estimated using the CAMS mathematical model, made available by CPTEC. Diagnoses of tracheitis and laryngitis, pneumonia, bronchitis, bronchiolitis and asthma were included. INMET provided data on maximum and minimum temperatures and relative humidity. Statistical analysis was performed with three generalized additive Poisson regression models, one of which only included the minimum temperature, another including the pollutant and the last with an interaction variable. There were 1,612 hospitalizations in the period; in the multivariate model, associations were identified between minimum temperature and hospitalizations in lags 1 to 5; the effect of increasing the minimum temperature by 4°C resulted in an increase in the risk of hospitalizations by 18%; 15.2% of hospitalizations are attributed to this increase and an excess of approximately US$ 68,000.00 in expenses for the health system during the period evaluated. In addition to the known effects of exposure to pollutants on health, it was possible to identify that an increase in the minimum daily temperature can cause damage to children's health.

Background: Consistent monitoring of PrEP adherence with accurate measurement tools at point-of-care could greatly contribute to reaching adolescents with poor adherence. We aimed to assess the performance of indirect adherence measures to oral PrEP among adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW)., Methods: PrEP15-19 is a prospective, multicenter, PrEP demonstration cohort study that includes AMSM and ATGW aged 15-19 in three Brazilian cities. A diagnostic accuracy study was conducted using tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots as the reference standard, along with three index tests: medication possession ratio (MPR), pill count, and self-report. We calculated the area under the curve (AUC) for protective TFV-DP levels (≥800 fmol/punch) and sensitivity (SE) and specificity (SP) for established cutoff points., Results: We included 302 samples from 188 participants. Most of participants were AMSM (78.7%), aged 18-19 years (80.3%), and non-whites (72.9%). The AUC was 0.59 for MPR, 0.69 for pill count, and 0.75 for self-report. When combining MPR and self-report, the AUC increased to 0.77. Sensitivity was high for the cutoff points identified by the Youden index, 80% for MPR, 92% for self-report, and 97% for pill count. However, specificities were low 40%, 46%, and 38%, respectively., Conclusions: Indirect measures were able to discriminate adolescents with good adherence. However, their performance in identifying those with low adherence might be limited, suggesting that it is necessary to initiate adherence interventions when there is no evidence of perfect adherence. Combining measures can provide wider information on adherence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zeballos 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.)

Background: The population is aging rapidly worldwide, impacting public health, with countries in the Global South, such as Brazil, aging faster than developed nations. The 24-hour movement behavior is crucial for healthy aging, but its relationship with the neighborhood built environment is underresearched, especially for older adults. The EpiMove Study uses accelerometers and GPS to investigate the relationships between 24-hour movement behavior, community mobility and the neighborhood built environment for healthy aging in older Brazilian adults., Methods: The EpiMove Study is a representative cross-sectional study of older adults aged 60 years and older from an urban area in the southern region of Brazil. It consists of two phases. Phase 1 involves conducting home interviews to gather subjective measures of the neighborhood built environment and physical activity. Phase 2 involves delivering devices to participants' homes and collecting objective data on 24-hour movement behavior via wrist-worn wGT3X-BT ActiGraph accelerometers and community-based active transportation via hip-mounted GPS Qstarz-1000XT devices. The data are collected simultaneously over seven consecutive days, along with the participants' reasons for adhering to the study protocol., Discussion: The EpiMove study will provide a better understanding of the relationships between the perceived neighborhood environment and 24-hour movement behaviors and community-based active transportation among older adults, with a particular focus on whether environmental factors influence these behaviors, which are crucial for healthy aging. The results from the EpiMove study could offer essential evidence for developing public policies and urban interventions that support healthier and more equitable environments for aging populations, particularly in rapidly urbanizing regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zorzi 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.)

The study aimed to evaluate the in vitro anthelminthic and antimicrobial activity of silver nanoparticles (AgNPs) against Dactylogyrus minutus and Aeromonas hydrophila, pathogens of Cyprinus carpio Koi. Gill arches of the fish were removed and placed into six-well plates containing 10 mL of tank water with varying concentrations of AgNPs: 100, 400, 500, 600, and 800 mg/L, along with control groups using tank water and distilled water. Each group was tested in triplicate. Parasites were observed every 10 min for 300 min (5 h) using a stereomicroscope, and mortality rates were recorded. Anthelminthic efficacy was calculated at the end of the tests. For the in vitro antimicrobial test, the Minimum Inhibitory Concentration (MIC) of AgNPs was determined by adding 100 μL of Poor Broth (PB) culture medium to all 96 wells of a microplate. The first well was filled with 100 μL of AgNPs, followed by serial dilutions (1:2 ratio). Subsequently, 50 μL of A. hydrophila (1 × 10 7  CFU/mL) was added to all wells and incubated for 24 h at 28 °C. Results showed that 800 mg/L of AgNPs achieved 87% anthelminthic efficacy within 300 min, while 100 mg/L achieved 47% efficacy. The MIC showed bacterial growth inhibition at 125 mg/mL. Despite the 87% efficacy against parasites within 300 min, AgNPs did not reach 100% efficacy quickly, limiting their potential use in ornamental fish farming. Further studies are needed to assess the toxicity of AgNPs in fish., 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 Inc. All rights reserved.)

Background/Objectives: Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB's effects on the heart are unclear. Therefore, we investigated the potential cardioprotective or arrhythmogenic effects of MB in an animal model of CIR. To this end, 12-16-week-old male Wistar rats were divided into four experimental groups: (a) rats subjected to SHAM surgery with no ischemia; (b) rats subjected to CIR and treated with a vehicle (SS + CIR); and (c) rats subjected to CIR and treated with 2 mg/kg i.v. MB before ischemia (MB + ISQ) or (d) after ischemia but before reperfusion (ISQ + MB). An ECG analysis was used to evaluate the incidence of ventricular arrhythmias (VAs), atrioventricular blocks (AVBs), and lethality (LET) resulting from CIR. After CIR, rat hearts were removed for histopathological analysis and lipid hydroperoxide (LH) measurements. Results: The incidence of VA, AVB, and LET was significantly increased in the MB + ISQ group (VA = 100%; AVB = 100%; LET = 100%) but significantly reduced in the ISQ + MB group (VA = 42.8%; AVB = 28.5%; LET = 21.4%) compared with the SS + CIR group (VA = 85.7%; AVB = 71.4%; LET = 64.2%). LH concentration was significantly reduced in both MB-treated groups, but myocardial injuries were increased only in the MB + ISQ group when compared with the SS + CIR group. Conclusions: These results indicate that MB produces a biphasic effect on CIR, with cardiotoxic effects when administered before cardiac ischemia and cardioprotective effects when administered after ischemia but before cardiac reperfusion.

Melatonin (MLT) is a hormone that can stimulate bone formation and inhibit bone resorption, among other functions. Aim: To evaluate the effect on new bone formation of MLT applied locally to critical defects created in the calvaria of rats, compared to the effect of Bio-Oss® xenogeneic bone substitute (BO), by analyzing histomorphometry, microtomography and gene expression. Materials and Method: Two critical defects (5.0 mm in diameter) were created in the calvaria of 36 adults male Wistar rats. The rats were divided randomly into two groups: a test group, in which one of the defects was filled with MLT, and the other with MLT with Bio-Oss® (MLTBO), and a control group, in which one of the defects was filled only with the clot (C), and the other with BO. The rats were euthanized 30 days after surgery. Samples of the calvaria containing the critical defects were collected for analysis by histomorphometry, microtomography, and the expression of the genes for type I collagen (COL-I), osteopontin (OPN) and bone morphogenetic protein 2 (BMP-2). Results: A qualitative improvement was observed in bone healing when MLT was used, though there was no statistical difference in the quantification of newly formed bone (p>0.05). Micro-CT showed that bone volume was significantly smaller in absence of BO (p=0.006). Bone trabeculae thickness (p=0.590) and number (p=0.150) were not significantly affected by MLT. Regarding the expression of the genes COL-I, OPN and BMP-2, no significant differences were observed between the MLT, BO and MLTBO groups. Conclusion: Topical application of MLT resulted in a qualitative improvement in bone healing, although it did not affect bone formation quantitatively. In the absence of BO, less bone volume and less bone trabecular thickness were observed., Competing Interests: The authors declare no potential conflicts of interest regarding this research or the authorship and/or publication of this article, (SAIO.)

The effects on the structure, valence state and morphological properties of FeCo-containing SnO 2 nanostructured solids were investigated. The physicochemical features were tuned by distinct synthesis routes e.g., sol-gel, coprecipitation and nanocasting, to apply them as catalysts in the glycerol valorization to cyclic acetals. Based on Mössbauer and XPS spectroscopy results, all nanosized FeCoSn solids have Fe-based phases, which contain Co and Sn included in the structure, and well-dispersed Fe 3+ and Fe 2+ surface active sites. Raman, FTIR and EPR spectroscopies measurements of the spent solids demonstrated structural stability for the sol-gel based solid, which is indeed responsible for the highest catalytic performance, among the nanocasted and coprecipitated counterparts. Morphological and elemental analyses illustrated distinct morphologies and composition on solid surface, depending on the synthesis route. The Fe/Co and Fe/Sn surface ratios are closely related to the catalytic performance. The improved glycerol conversion and selectivities of the solid obtained by sol-gel method was ascribed to the leaching resistance and the Sn action as a structural promoter., 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.)

This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with Annona muricata concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.

Mesenchymal stem cells can differentiate into specific cell lineages in the tissue repair process. Photobiomodulation with laser and LED is used to treat several comorbidities, can interfere in cell proliferation and viability, in addition to promoting responses related to the physical parameters adopted. Evaluate and compare the effects of laser and LED on mesenchymal cells, with different energy doses and different wavelengths, in addition to viability and wound closure. Mesenchymal stem cells derived from human adipocytes were irradiated with laser (energy of 0.5 J, 2 J and 4 J, wavelength of 660 nm and 830 nm), and LED (energy of 0.5 J, 2 J and 4 J, where lengths are 630 nm and 850 nm). The wound closure process was evaluated through monitoring the reduction of the lesion area in vitro. Viability was determined by analysis with Hoechst and Propidium Iodide markers, and quantification of viable and non-viable cells respectively Data distributions were analyzed using the Shapiro-Wilk test. Homogeneity was analyzed using Levene's test. The comparison between the parameters used was analyzed using the Two-way ANOVA test. The T test was applied to data relating to viability and lesion area. For LED photobiomodulation, only the 630 nm wavelength obtained a significant result in 24, 48 and 72 h (p = 0,027; p = 0,024; p = 0,009). The results related to the in vitro wound closure test indicate that both photobiomodulation with laser and LED demonstrated significant results considering the time it takes to approach the edges (p < 0.05). Considering the in vitro experimental conditions of the study, it is possible to conclude that the physical parameters of photobiomodulation, such as energy and wavelength, with laser or LED in mesenchymal stem cells, can play a potential role in cell viability and wound closure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Simvastatin (SIM) is widely prescribed to treat hyperlipidemia, despite its limitations, such as a short half-life and low oral bioavailability. To overcome these drawbacks, the development of a controlled-release formulation is desirable. This study aims to develop a microparticulate system based on cellulose acetate (ACT) obtained from Agave sisalana Perrine to promote a controlled SIM release. SIM-loaded microparticles (SMP) were prepared using the solvent emulsification-evaporation method. Several parameters were evaluated, including particle size, surface charge, morphology, encapsulation efficiency, thermochemical characteristics, crystallinity, and in vitro release profile. ACT exhibited favorable flow properties after acetylation, with a degree of substitution values superior to 2.5, as confirmed by both the chemical route and H-NMR, indicating the formation of cellulose triacetate. The obtained SMP were spherical with an average size ranging from 1842 to 1857 nm, a zeta potential of -4.45 mV, and a high SIM incorporation efficiency (98%). Thermal and XRD analyses revealed that SIM was homogeneously dispersed into the polymeric matrix in its amorphous state. In vitro studies using dialysis bags revealed that the controlled SIM release from microparticles was higher under simulated intestinal conditions and followed the Higuchi kinetic model. Our results suggest that ACT-based microparticles are a promising system for SIM delivery, which can improve its bioavailability, and result in better patient compliance.

Background: As new and improved antigen-detecting rapid diagnostic tests for SARS-CoV-2 infection (Ag-RDT) continue to be developed, assessing their diagnostic performance is necessary to increase test options with accurate and rapid diagnostic capacity especially in resource-constrained settings. This study aimed to assess the performance of two Ag-RDTs in a population-based study., Methods: We conducted a diagnostic accuracy study in neighborhoods with high socioeconomic vulnerability in Salvador-Brazil, including individuals aged ≥12 years old who attended primary health services, between July and December 2022, with COVID-19 symptoms or who had been in contact with a confirmed case. Two Ag-RDTs were compared in parallel using reverse transcription polymerase chain reaction (RT-PCR) as reference standard, the PanbioTM COVID-19 Ag test (Abbott®) and Immuno-Rapid COVID-19 Ag (WAMA Diagnostic®). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated., Results: For the Abbott test the sensitivity was 52.7% (95% CI: 44.3% - 61.0%), specificity 100% (95% CI: 98.7% - 100%), PPV 100% (95% CI: 95.4% - 100%) and NPV 80.4% (95% CI: 75.9% - 84.4%). For the WAMA test, the sensitivity was 53.4% (95% CI: 45.0% - 61.6%), specificity 100% (95% CI: 98.7% - 100%), PPV 100% (95% CI: 95.4% - 100%) and NPV 80.7% (95% CI: 76.2% - 84.6%). Sensitivity for the group with Cycle Threshold (CT) <24 was 82.3% (95%CI: 72.1-90.0, n = 83) for PanbioTM COVID-19 Ag test and 87.3% (95%CI: 77.9-93.8, n = 83) for Immuno-Rapid COVID-19 Ag test., Conclusion: Sensitivity for both Ag-RDT was lower than reported by manufacturers. In the stratified analysis, sensitivity was higher among those with lower CT values <24. Specificity was high for both rapid antigen tests. Both Ag-RDT showed to be useful for rapid diagnostic of potential cases of COVID-19. Negative results must be assessed carefully according to clinical and epidemiological information., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zeballos 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.)

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4 + STAT4 and CD4 + CD25 + Foxp3 + cells as well as the production of CD4 + IFN- γ and CD4 + CD25 + IL-10 in the lung after PBM therapy in a COPD mice model., Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% ( p < 0.05)., Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells., Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brito, Herculano, de Alvarenga-Nascimento, Estefano-Alves, Duran, Marcos, Silva Junior, Chavantes, Zamuner, Aimbire, Lladó-Pelfort, Gubern, Fàbrega, da Palma and Ligeiro de Oliveira.)

Snakes in the family Elapidae largely produce venoms rich in three-finger toxins (3FTx) that bind to the α 1 subunit of nicotinic acetylcholine receptors (nAChRs), impeding ion channel activity. These neurotoxins immobilize the prey by disrupting muscle contraction. Coral snakes of the genus Micrurus are specialist predators who produce many 3FTx, making them an interesting system for examining the coevolution of these toxins and their targets in prey animals. We used a bio-layer interferometry technique to measure the binding interaction between 15 Micrurus venoms and 12 taxon-specific mimotopes designed to resemble the orthosteric binding region of the muscular nAChR subunit. We found that Micrurus venoms vary greatly in their potency on this assay and that this variation follows phylogenetic patterns rather than previously reported patterns of venom composition. The long-tailed Micrurus tend to have greater binding to nAChR orthosteric sites than their short-tailed relatives and we conclude this is the likely ancestral state. The repeated loss of this activity may be due to the evolution of 3FTx that bind to other regions of the nAChR. We also observed variations in the potency of the venoms depending on the taxon of the target mimotope. Rather than a pattern of prey-specificity, we found that mimotopes modeled after snake nAChRs are less susceptible to Micrurus venoms and that this resistance is partly due to a characteristic tryptophan → serine mutation within the orthosteric site in all snake mimotopes. This resistance may be part of a Red Queen arms race between coral snakes and their prey., (© 2024. The Author(s).)

Background: Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated., Methodology/principal Findings: C2C12 myoblast cells were exposed to BjsuV (12.5 μg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кβ, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-β, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-β, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP., Conclusion/significance: These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Silva 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.)

Among the species described within the Onchocercidae family, Dirofilaria immitis is regarded as the most common worldwide, causing severe and often fatal conditions in dogs, cats, and occasionally humans. Dirofilaria spp. are vectored by mosquitoes, simulids, and culicoids, with their epidemiology dependent on the geographical distribution of competent vectors. Eight species of Dirofilaria have been reported so far in Brazil, of which six parasitize non-human primates, deer, procyonids, and marsupials. Here, we investigated the occurrence of Onchocercidae in wild felids (i.e., Panthera onca, Puma concolor, Herpailurus yagouaroundi, Leopardus geoffroyi, Leopardus guttulus, Leopardus pardalis, Leopardus wiedii, Leopardus munoai) from different locations in Brazil. Overall, 82 samples (n = 63 blood; n = 19 tissues) were molecularly screened for cytochrome c oxidase subunit-1 (cox1) gene. Four (i.e., 4.8%) wild felid samples were positive, and at BLAST analysis, the obtained sequences showed varying percentage of nucleotide identity with the genera Brugia (i.e., 87-88%), Setaria (i.e., 89%), and D. immitis (i.e., 94.4%). Phylogenetic analyses clustered sequences obtained into three distinct clades, one with D. immitis and the remaining two with other Onchocercidae spp. Data herein obtained highlight the need for a more comprehensive understanding of the diversity and biology of Onchocercidae in South America in order to assess the potential impact that these species may have for domestic and wild animals, as well as humans., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three-phase induction motors are widely used in various industrial sectors and are responsible for a significant portion of the total electrical energy consumed. To ensure their efficient operation, it is necessary to apply control systems with specific algorithms able to estimate rotation speed accurately and with an adequate response time. However, the angular speed sensors used in induction motors are generally expensive and unreliable, and they may be unsuitable for use in hostile environments. This paper presents an algorithm for speed estimation in three-phase induction motors using the chaotic variable of maximum density. The technique used in this work analyzes the current signals from the motor power supply without invasive sensors on its structure. The results show that speed estimation is achieved with a response time lower than that obtained by classical techniques based on the Fourier Transform. This technique allows for the provision of motor shaft speed values when operated under variable load.

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by Candida albicans treatment's efficacy. This study aimed to develop ureasil-polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 µg/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 µg/mL, while that of CUR decreased eight-fold to 32 µg/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO/MCZ and U-PEO/CUR/MCZ ovules showed the greatest zones of inhibition (≥18 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.

Trypanosoma evansi is a widespread and neglected zoonotic parasite that affects domestic and wild animals, causing a disease commonly known as "surra." The Brazilian Pantanal wetland is recognized as an enzootic area for this protozoan, yet recognizing the importance of reservoir hosts also in order to prevent zoonotic outbreaks. This study aimed to assess the occurrence of T. evansi in jaguars (Panthera onca) from the Brazilian Pantanal wetland and explore associated clinical and hematological manifestations. A total of 42 animals were screened by PCR and sequenced for species identification when positive. Trypanosoma evansi was detected in six free-ranging jaguars (six positive animals of 42 captures and 16 recaptures), representing the first molecular evidence of such infection in this animal species. Our findings suggest that jaguars may act as reservoir hosts of T. evansi in the Brazilian Pantanal wetland. The better understanding of the role of wildlife in the epidemiology of T. evansi is also of importance to future reintroduction and translocation programs toward wildlife conservation efforts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer is the third most common cancer and the second in cases of cancer-related death. Polytherapy generates many adverse effects, leading the patient to give up. Nanotechnology has been studied in recent years to circumvent limitations. Groups composed of polymeric, lipid, and inorganic nanoparticles are the most purpose. Thus, the objective of this work is to bring information on how nanosystems can improve the chemotherapeutic treatment for colorectal cancer. Therefore, a search in journals such as "LILACS", "SciELO" and "PubMed/Medline" was performed, resulting in 25,000 articles found when applied the search engines "nanoparticle," "colorectal cancer," "malignant neoplasms," and "chemotherapy." After inclusion and exclusion factors, 24 articles remained, which were used as the basis for this integrative review. The results reveal that, regardless of the choice of matrix, nanoparticles showed an increase in bioavailability of the active, increasing the half-life by up to 13 times, modified release, as well as a significant reduction in tumor size, with cell viability up to 20% lower than the free drug tested, in different colorectal cancer cell lines, such as HCT-116, HT-29, and CaCo-2. However, more in vivo and clinical studies need to be performed, regardless of the formulation of its matrix, aiming at a higher rate of safety for patients and stability of the formulations, as well as knowledge of detailed indices of its pharmacokinetics and pharmacodynamics, seeking to avoid further damage to the recipient organism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nematode species of the genus Dracunculus (Spirurida: Dracunculoidea) infect tissues and body cavities of reptiles, domestic and wild carnivores, and humans. The definitive hosts acquire the infection by ingesting intermediate (i.e., cyclopoid copepod) or paratenic (i.e., amphibians and fishes) hosts. Here we report the jaguar (Panthera onca) as a potential new host for Dracunculus sp. The nematode was collected from an ulcerated cutaneous nodule on the left anterior limb of a female jaguar in the municipality of Miranda, Mato Grosso do Sul state, Brazil. Based on the morphology of first stage larvae collected from a small fragment of the uterus of the adult nematode, the species was identified as Dracunculus sp. Reichard, 1759. Additionally, the morphological identification was molecularly confirmed by sequencing the cox1 gene. This report advocates for further investigations into the transmission cycle of this parasite in the Brazilian Pantanal wetland, considering the role of wildlife hosts and the zoonotic potential of Dracunculus species in that area., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a case of high-grade undifferentiated pleomorphic sarcoma in a free-living white-eared opossum (Didelphis albiventris) in Central Brazil. Grossly, it appeared as a soft yellow mass, approximately 8 cm in diameter, with an irregular, adherent and ulcerated surface, which extended from the proximal epiphysis of the femur to the proximal third of the tibia and fibula. The mass invaded the medullary cavity and had a necrotic centre. Multiple nodular metastases (0.5-1.5 cm) were present in the liver, lungs and spleen. Histologically, the neoplasm was characterized by pleomorphic cells with indistinct boundaries, many multinucleated cells, necrosis and tissue invasion. There was intense cytoplasmic immunolabelling of neoplastic cells for vimentin and moderate cytoplasmic and nuclear labelling for human muscle actin, human smooth muscle actin and lysozyme. Immunolabelling for Iba1, CD18, CD1A, cytokeratin AE1/AE3, glial fibrillary acidic protein and desmin was negative. To our knowledge, this is the first report of an undifferentiated pleomorphic sarcoma in this species., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

COVID-19 has emerged as a global pandemic leading to an increase in hospitalization and intensive care unit (ICU) admissions worldwide. Due to severe acute respiratory distress syndrome (ARDS), many patients require prone positioning, which is associated with increased pressure ulcer/injury (PU/PI) incidence. COVID-19 pathophysiology may favor the occurrence of PU/PI due to hypoxemia, inflammatory status, and vasculopathy. This study aimed to compare the incidence of PU/PI in ICU patients before and during the COVID-19 pandemic. A retrospective cohort study was conducted at a university hospital in Brazil. Data from the medical charts of every adult patient admitted to ICU from March to July 2019 and the same period in 2020 were collected. The group from 2019 included 408 patients admitted due to multiple causes, and the group from 2020 included 229 patients admitted due to COVID-19 infection. The incidence of PU/PI was significantly higher in patients admitted in 2020 compared to 2019 (62,5 vs. 33,8%, respectively). Also, PU/PI location and severity have been different between groups, with the patients with COVID-19 (2020 group) more exposed to stage 3, 4, and non-stageable lesions, as well as more PU/PI on face skin and other less common locations. In conclusion, the COVID-19 pandemic has highlighted a higher PU/PI incidence. ICU patients were older during the pandemic, had higher body mass index and comorbidities, and needed more invasive medical devices and pronation. The occurrence of PU/PI was also associated with prolonged hospitalization and mortality., Competing Interests: Declaration of Competing Interest All authors have nothing to disclose, and they have no conflict of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission., Study Design: Retrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017., Results: Evaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20-4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05-1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93-10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07-6.93), relapse (RR:10.27; 95%CI:3.08-34.28) and death due to GTN (RR:3.62; 95%CI:1.51-8.67)., Conclusions: The distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Research suggests that increased voting among adults is associated with improved child health. Despite the benefits of voting, the United States has low voter turnout compared with peer nations. Turnout is especially low among marginalized people in the United States. Voter registration is essential for increasing voter turnout, and registration efforts have been successfully carried out in clinical settings. Working with a nonprofit called Vot-ER, we advocated for nonpartisan voter registration efforts in pediatric settings nationwide preceding the November 2020 US elections. We describe lessons learned from these efforts. Using data obtained from Vot-ER, we also provide the first estimates of participation in a national voter registration campaign in pediatric settings. There was widespread engagement in voter registration efforts among pediatricians in 2020. Many lessons were learned from these efforts, including the benefits of advanced planning because registration deadlines can be up to 1 month in advance of Election Day. Obtaining buy-in from numerous stakeholders (e.g., health center leadership, public relations teams) supports widespread staff participation. Also important is to consider the tradeoffs between active voter registration (in which staff can broach the topic of voting with patients and families) and passive efforts (in which voting is discussed only if patients or families inquire about it). These and other lessons can inform future voter registration efforts in diverse pediatric settings across the country., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans , whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans -induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG)., Methods: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated., Results: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans ( p < 0.001) by 1.2 log 10 for Hy.NLC-HG/PDT and 1.9 log 10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group., Conclusions: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

Objective: To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment., Methods: Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board., Results: Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab., Conclusion: Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Snakes of the Philodryadini tribe are included in the Dipsadidae family, which is a diverse group of rear-fanged snakes widespread in different ecological conditions, including habitats and diet. However, little is known about the composition and effects of their venoms despite their relevance for understanding the evolution of these snakes or even their impact on the occasional cases of human envenoming. In this study, we integrated venom gland transcriptomics, venom proteomics and functional assays to characterize the venoms from eight species of the Philodryadini tribe, which includes the genus Philodryas , Chlorosoma and Xenoxybelis . The most abundant components identified in the venoms were snake venom metalloproteinases (SVMPs), cysteine-rich secretory proteins (CRISPs), C-type lectins (CTLs), snake endogenous matrix metalloproteinases type 9 (seMMP-9) and snake venom serinoproteinases (SVSPs). These protein families showed a variable expression profile in each genus. SVMPs were the most abundant components in Philodryas , while seMMP-9 and CRISPs were the most expressed in Chlorosoma and Xenoxybelis , respectively. Lineage-specific differences in venom composition were also observed among Philodryas species, whereas P. olfersii presented the highest amount of SVSPs and P. agassizii was the only species to express significant amounts of 3FTx. The variability observed in venom composition was confirmed by the venom functional assays. Philodryas species presented the highest SVMP activity, whereas Chlorosoma species showed higher levels of gelatin activity, which may correlate to the seMMP-9 enzymes. The variability observed in the composition of these venoms may be related to the tribe phylogeny and influenced by their diets. In the presented study, we expanded the set of venomics studies of the Philodryadini tribe, which paves new roads for further studies on the evolution and ecology of Dipsadidae snakes.

Introduction: The beneficial effects of physical exercise on functional capacity and inflammatory response are well-known in cardiovascular diseases; however, studies on sickle cell disease (SCD) are limited. It was hypothesized that physical exercise may exert a favorable effect on the inflammatory response of SCD patients, contributing to an improved quality of life. This study aimed to evaluate the effect of a regular physical exercise program on the anti-inflammatory responses in SCD patients., Methods: A non-randomized clinical trial was conducted in adult SCD patients. The patients were divided into two groups: 1-Exercise Group, which received a physical exercise program three times a week for 8 weeks, and; 2-Control Group, with routine physical activities. All patients underwent the following procedures initially and after eight weeks of protocol: clinical evaluation, physical evaluation, laboratory evaluation, quality of life evaluation, and echocardiographic evaluation., Statistical Analysis: Comparisons between groups were made using Student's t -test, Mann-Whitney test, chi-square test, or Fisher's exact test. Spearman's correlation coefficient was calculated. The significance level was set at p < 0.05., Results: There was no significant difference in inflammatory response between the Control and Exercise Groups. The Exercise Group showed an improvement in peak VO 2 values ( p < 0.001), an increase in the distance walked ( p < 0.001), an improvement in the limitation domain due to the physical aspects of the 36-Item Short Form Health Survey (SF-36) quality of life questionnaire ( p = 0.022), and an increase in physical activity related to leisure ( p < 0.001) and walking ( p = 0.024) in the International Physical Activity Questionnaire (IPAQ). There was a negative correlation between IL-6 values and distance walked on the treadmill (correlation coefficient -0.444, p = 0.020) and the estimated peak VO 2 values (correlation coefficient -0.480; p = 0.013) in SCD patients in both groups., Conclusions: The aerobic exercise program did not change the inflammatory response profile of SCD patients, nor did it show unfavorable effects on the parameters evaluated, and patients with lower functional capacity were those with the highest levels of IL-6.

Nanofibers have shown promising clinical results in the process of tissue regeneration since they provide a similar structure to the extracellular matrix of different tissues, high surface-to-volume ratio and porosity, flexibility, and gas permeation, offering topographical features that stimulate cell adhesion and proliferation. Electrospinning is one of the most used techniques for manufacturing nanomaterials due to its simplicity and low cost. In this review, we highlight the use of nanofibers produced with polyvinyl alcohol and polymeric associations (PVA/blends) as a matrix for release capable of modifying the pharmacokinetic profile of different active ingredients in the regeneration of connective, epithelial, muscular, and nervous tissues. Articles were selected by three independent reviewers by analyzing the databases, such as Web of Science, PubMed, Science Direct, and Google Scholar (last 10 years). Descriptors used were "nanofibers", "poly (vinyl alcohol)", "muscle tissue", "connective tissue", "epithelial tissue", and "neural tissue engineering". The guiding question was: How do different compositions of polyvinyl alcohol polymeric nanofibers modify the pharmacokinetics of active ingredients in different tissue regeneration processes? The results demonstrated the versatility of the production of PVA nanofibers by solution blow technique with different actives (lipo/hydrophilic) and with pore sizes varying between 60 and 450 nm depending on the polymers used in the mixture, which influences the drug release that can be controlled for hours or days. The tissue regeneration showed better cellular organization and greater cell proliferation compared to the treatment with the control group, regardless of the tissue analyzed. We highlight that, among all blends, the combinations PVA/PCL and PVA/CS showed good compatibility and slow degradation, indicating their use in prolonged times of biodegradation, thus benefiting tissue regeneration in bone and cartilage connective tissues, acting as a physical barrier that results in guided regeneration, and preventing the invasion of cells from other tissues with increased proliferation rate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Importance: Infant mortality in the United States is highest among peer nations; it is also inequitable, with the highest rates among Black infants. The association between tax policy and infant mortality is not well understood., Objective: To examine the association between state-level tax policy and state-level infant mortality in the US., Design, Setting, and Participants: This state-level, population-based cross-sectional study investigated the association between tax policy and infant mortality in the US from 1996 through 2019. All US infant births and deaths were included, with data obtained from the National Center for Health Statistics. Data were analyzed from November 28, 2021, to July 9, 2022., Exposures: State-level tax policy was operationalized as tax revenue per capita and tax progressivity. The Suits index was used to measure tax progressivity, with higher progressivity indicating increased tax rates for wealthier individuals., Main Outcomes and Measures: The association between tax policy and infant mortality rates was analyzed using a multivariable, negative binomial, generalized estimating equations model. Since 6 years of tax progressivity data were available (1995, 2002, 2009, 2012, 2014, and 2018), 300 state-years were included. Adjusted incidence rate ratios (aIRRs) were calculated controlling for year, state-level demographic variables, federal transfer revenue, and other revenue. Secondary analyses were conducted for racial and ethnic subgroups., Results: There were 148 336 infant deaths in the US from 1996 through 2019, including 27 861 Hispanic infants, 1882 non-Hispanic American Indian or Alaska Native infants, 5792 non-Hispanic Asian or Pacific Islander infants, 41 560 non-Hispanic Black infants, and 68 666 non-Hispanic White infants. The overall infant mortality rate was 6.29 deaths per 1000 live births. Each $1000 increase in tax revenue per capita was associated with a 2.6% decrease in the infant mortality rate (aIRR, 0.97; 95% CI, 0.95-0.99). An increase of 0.10 in the Suits index (ie, increased tax progressivity) was associated with a 4.6% decrease in the infant mortality rate (aIRR, 0.95; 95% CI, 0.91-0.99). Increased tax progressivity was associated with decreased non-Hispanic White infant mortality (aIRR, 0.95; 95% CI, 0.91-0.99), and increased tax revenue was associated with increased non-Hispanic Black infant mortality (aIRR, 1.04; 95% CI, 1.01-1.08)., Conclusions and Relevance: In this cross-sectional study, an increase in tax revenue and the Suits index of tax progressivity were both associated with decreased infant mortality. These associations varied by race and ethnicity. Tax policy is an important, modifiable social determinant of health that may influence state-level infant mortality.

Background: Streptococcus mutans and Candida albicans can colonize the teeth, the oral cavity as biofilm and can cause oral infections. Thus, strategies to prevent and control oral biofilms are requested. The present study aims the development and characterization of methylene blue (MB)-loaded polymeric micelles for antimicrobial photodynamic therapy (aPDT) against Streptococcus mutans and Candida albicans biofilms METHODS: MB-loaded polymeric micelles were produced and characterized by particle size, polydispersity index, morphology, zeta potential, stability, MB release profile, and antimicrobial effect against S. mutans and C. albicans biofilms., Results: MB-loaded polymeric micelles showed a reduced particle size, moderate polydisperse profile, spherical and neutral shape, which demonstrated to be promising features to allow micelles penetration into biofilms. Antimicrobial effect against bacterial and yeast biofilms was demonstrated once MB was irradiated by light under 660 nm (aPDT). Furthermore, MB-loaded polymeric micelles showed significant inhibition of S. mutans and C. albicans biofilms. Furthermore, the treatment with MB-micelles incubated with high pre-incubation times (15 and 30 min) were more effective than 5 min. It can be explained by the time required for this nanosystem to penetrate the innermost layer of biofilms and release MB for aPDT., Conclusion: MB-loaded polymeric micelles can effectively decrease the bacteria and yeast viability and it may cause positive impacts in the clinical practice. Thus, the developed formulation showed potential in the treatment to remove oral biofilms, but clinical studies are needed to confirm its potential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC)., Study Design: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020., Results: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC., Conclusions: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID-19 pandemic., Design: Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross-sectional analysis, with application of a questionnaire., Setting: Six Brazilian Reference Centres on gestational trophoblastic disease., Population: 2662 patients with MP/postmolar GTN treated from March-December/2015-2020 were retrospectively evaluated and 528 of these patients answered a questionnaire., Methods: Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross-sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID-19 pandemic compared with previous years., Main Outcome Measures: The incidence of MP/postmolar GTN., Results: Compared with the last 5 pre-pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID-19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be >10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90-3.29, P < 0.001), have a pre-evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38-2.28, P < 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01-3.43, P = 0.047) when compared with 2015-2019., Conclusions: Although the incidence of MP/postmolar GTN remained stable during the COVID-19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN., (© 2022 John Wiley & Sons Ltd.)