Placebo-controlled efficacy of 5-HT3 antagonists for postoperative nausea and vomiting prophylaxis in supratentorial craniotomies: A systematic review and comparative meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common and distressing complications following neurosurgical procedures, affecting up to 73 % of patients undergoing craniotomy. Therefore, we aimed to assess the placebo-controlled efficacy of 5-HT3 antagonists to prevent PONV following supratentorial craniotomies. METHODS: We searched Medline, Web of Science, and Embase databases following PRISMA guidelines for RCTs comparing the outcomes of prophylactic use of 5-HT3 antagonists with placebo to prevent PONV following supratentorial craniotomy. We pooled odds ratios (OR) with 95 % confidence intervals with a random-effects model. I2 statistics was used to assess heterogeneity. RESULTS: Five RCTs, comprising 347 patients, of which 145 received a placebo, were included. The analysis identified a lower likelihood of early postoperative vomiting in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.24-0.91, p<0.05; I2=7 %), a lower likelihood of vomit within the 24-h period in 5-HT3 antagonists group (OR=0.27; 95 % CI: 0.15-0.48, p<0.01; I2=40 %), a lower likelihood of nausea within the 24-h period in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.28-0.72, p<0.01; I2=34 %), and a lower likelihood of rescue interventions in 5-HT3 antagonists group (OR = 0.18; 95 % CI: 0.10-0.34; I2 = 0 %. Subgroup analyses focusing on ondansetron also identified a lower likelihood of nausea and vomiting within the 24-h period in the 5-HT3 antagonist group. CONCLUSION: This systematic review and meta-analysis identified that 5-HT3 antagonists are effective in preventing PONV in the postoperative period following supratentorial craniotomy when compared to placebo. Our findings provide synthesized and robust evidence derived from randomized studies to support the use of 5-HT3 antagonists in clinical practice.

[The impact of the COVID-19 pandemic on the incidence of sexual violence against children and adolescents in the home environment in Brazil]. / Impacto da pandemia de COVID-19 na incidência de violência sexual domiciliar contra crianças e adolescentes no Brasil.

The scope of this article is to identify the impact of the COVID-19 pandemic on the incidence of sexual violence against children and adolescents in the home environment in Brazil. It involves an ecological time-series study using joinpoint regression based on data from the Notifiable Diseases Information System from 2009 to 2021. The relative frequency and crude incidence rates of sexual violence occurring in the home against the population group aged 0 to 19 years were analyzed, estimating the annual percentage change (APC) and average annual percentage change (AAPC), with a 95% confidence interval. The relative frequency of the problem was higher in 2020 (69.8%) and 2021 (71.7%), with an increase of 3.1% (p = 0.001) in 2017-2021. Girls were more affected, with rates rising in 2009-2012 (APC = 44.4; p = 0.010) and 2015-2019 (APC = 16.6; p=0.017) but falling in 2019-2021 (APC= -17.7; p = 0.042). All age groups showed a significant increase until 2019, and a reduction after this year for 5-9 years (APC = -18.6; p = 0.016), 10-14 years (APC = -14.1; p = 0.040) and 15-19 years (APC = -18.4; p = 0.021). The reduction in the incidence rates of this type of violence may have been influenced by the context of social isolation during the COVID-19 pandemic, which led to the underreporting of cases.

O objetivo do artigo é identificar o impacto da pandemia de COVID-19 na incidência de violência sexual de crianças e adolescentes no ambiente domiciliar no Brasil. Estudo ecológico de série temporal utilizando regressão joinpoint a partir de dados do Sistema de Informação de Agravos de Notificação, período 2009-2021. Analisaram-se frequência relativa e taxas brutas de incidência de violência sexual ocorrida na residência contra a população de 0 a 19 anos, estimando-se variação percentual anual (APC) e variação percentual anual média (AAPC), com intervalo de confiança de 95%. A frequência relativa do agravo obteve maiores valores em 2020 (69,8%) e 2021 (71,7%), com aumento de 3,1% (p = 0,001) em 2017-2021. As meninas foram mais atingidas, com elevação das taxas em 2009-2012 (APC = 44,4; p = 0,010) e 2015-2019 (APC = 16,6; p = 0,017), porém queda em 2019-2021 (APC = -17,7; p = 0,042). Todas as faixas etárias apresentaram aumento significativo até 2019, e redução após esse ano para 5-9 anos (APC = -18,6; p = 0,016), 10-14 anos (APC = -14,1; p = 0,040) e 15-19 anos (APC = -18,4; p = 0,021). A redução nas taxas de incidência desse tipo de violência pode ter sofrido influência do contexto de isolamento social na pandemia de COVID-19, que levou à subnotificação dos casos.

In Silico Approach to Model Heat Distribution of Magnetic Hyperthermia in the Tumoral and Healthy Vascular Network Using Tumor-on-a-Chip to Evaluate Effective Therapy.

Glioblastoma multiforme (GBM) is the most severe form of brain cancer in adults, characterized by its complex vascular network that contributes to resistance to conventional therapies. Thermal therapies, such as magnetic hyperthermia (MHT), emerge as promising alternatives, using heat to selectively target tumor cells while minimizing damage to healthy tissues. The organ-on-a-chip can replicate this complex vascular network of GBM, allowing for detailed investigations of heat dissipation in MHT, while computational simulations refine treatment parameters. In this in silico study, tumor-on-a-chip models were used to optimize MHT therapy by comparing heat dissipation in normal and abnormal vascular networks, considering geometries, flow rates, and concentrations of magnetic nanoparticles (MNPs). In the high vascular complexity model, the maximum velocity was 19 times lower than in the normal vasculature model and 4 times lower than in the low-complexity tumor model, highlighting the influence of vascular complexity on velocity and temperature distribution. The MHT simulation showed greater heat intensity in the central region, with a flow rate of 1 µL/min and 0.5 mg/mL of MNPs being the best conditions to achieve the therapeutic temperature. The complex vasculature model had the lowest heat dissipation, reaching 44.15 °C, compared to 42.01 °C in the low-complexity model and 37.80 °C in the normal model. These results show that greater vascular complexity improves heat retention, making it essential to consider this heterogeneity to optimize MHT treatment. Therefore, for an efficient MHT process, it is necessary to simulate ideal blood flow and MNP conditions to ensure heat retention at the tumor site, considering its irregular vascularization and heat dissipation for effective destruction.

Effects of Cryolipolysis on the Conversion of White Adipose Tissue: Pilot Study.

INTRODUCTION: Cryolipolysis (CLL) is a widely employed noninvasive procedure for body fat reduction. It operates by inducing cooling, leading to the crystallization of cytoplasmic lipids, loss of cellular integrity, and apoptosis/necrosis of adipocytes, accompanied by local inflammation. Ongoing discussions revolve around CLL's potential to transform white adipocytes into brown adipocytes, potentially yielding more significant effects compared to alternative procedures. OBJECTIVE: Thus, this randomized, blinded clinical study aimed to investigate the effects of CLL on adipose tissue and elucidate the mechanisms involved in its application and capacity for adipocyte conversion. METHODOLOGY: Tissue samples from six patients were assessed at intervals of 45, 60, and 90 days following the application of the CLL protocol during abdominoplasty surgeries. RESULTS: The samples underwent immunohistochemical analyses targeting various markers, revealing higher expression of PPAR-gamma, PPAR-alpha, and UCP-1 markers in CLL-treated samples. CONCLUSION: Therefore, the present study suggests that CLL has the ability to intervene in adipocyte conversion.

The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.

INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.

Is it possible to replace eCG by GnRH in the hormonal protocol for timed artificial insemination in ewes during the breeding season?

Hormonal protocols based on progestogens and equine chorionic gonadotrophin (eCG) are efficient for estrus and ovulation synchronization in ewes. Although eCG is indispensable during seasonal anestrus, it may not be necessary during the breeding season. Thus, we tested the hypothesis that GnRH is effective in replacing eCG during the breeding season allowing satisfactory ovulation rate, luteal function and conception rates after timed artificial insemination (TAI). Ewes (n = 134) with a minimum body condition score of 2.5 (0-5 scale) were treated with intravaginal devices (IVD) containing 60 mg of medroxyprogesterone acetate (MPA) for seven days and received 0.26 mg of sodium cloprostenol at the time of IVD removal. In Exp. 1, at IVD removal, ewes (n = 29) were allocated to three groups: eCG (200 IU at IVD removal; n = 10); eCG+GnRH (200 IU eCG at IVD removal and 4 µg of buserelin 36 h later; n = 10); or GnRH (buserelin 36 h after IVD removal; n = 9). Blood samples were collected 2, 6 and 12 days after TAI moment (54 h after IVD removal), for progesterone (P4) analysis. In Exp 2, the ewes were allocated to eCG (n = 10) or GnRH (n = 10) groups, as above described, and ovulation moment was evaluated 54, 66 and 78 h after IVD removal. In Exp 3, TAI was performed in ewes from eCG (n = 45) and GnRH (n = 40) groups using 100 × 106 motile spermatozoa from a pool of semen collected from four rams. In Exp. 1, based on P4 levels, we confirmed that all the ewes ovulated (29/29) and there was no significant effect of group (P = 0.89) or group x day (P = 0.18) on P4 concentration, being observed a significant effect of day (P = 0.0001). In Exp. 2, the maximum DF diameter (P = 0.26) and ovulation moment (P = 0.69) did not differ between groups. In Exp. 3, pregnancy rate was significantly lower (P = 0.02) in GnRH (22.5 %; 9/40) compared to eCG (46.7 %; 21/45). The results indicate that, although ovulation and luteal function were not altered after eCG, eCG+GnRH or GnRH treatment, GnRH alone before TAI cannot be used to replace eCG treatment during the breeding season.

Exploring the diversity and functional profile of microbial communities of Brazilian soils with high salinity and oil contamination.

Environmental pollution associated with the petroleum industry is a major problem worldwide. Microbial degradation is extremely important whether in the extractive process or in bioremediation of contaminants. Assessing the local microbiota and its potential for degradation is crucial for implementing effective bioremediation strategies. Herein, contaminated soil samples of onshore oil fields from a semiarid region in the Northeast of Brazil were investigated using metagenomics and metataxonomics. These soils exhibited hydrocarbon contamination and high salinity indices, while a control sample was collected from an uncontaminated area. The shotgun analysis revealed the predominance of Actinomycetota and Pseudomonadota, while 16S rRNA gene amplicon analysis of the samples showed Actinomycetota, Bacillota, and Pseudomonadota as the most abundant. The Archaea domain phylotypes were assigned to Thermoproteota and Methanobacteriota. Functional analysis and metabolic profile of the soil microbiomes exhibited a broader metabolic repertoire in the uncontaminated soil, while degradation pathways and surfactant biosynthesis presented higher values in the contaminated soils, where degradation pathways of xenobiotic and aromatic compounds were also present. Biosurfactant synthetic pathways were abundant, with predominance of lipopeptides. The present work uncovers several microbial drivers of oil degradation and mechanisms of adaptation to high salinity, which are pivotal traits for sustainable soil recovery strategies.

Cross-Mapping the Portuguese Nursing Ontology with ICNP, SNOMED CT and NANDA-I.

EHR Interoperability is crucial to obtain a set of benefits. This can be achieved by using data standards, like ontologies. The Portuguese Nursing Ontology (NursingOntos) is a reference model describing a set of nursing concepts and their relationships, to represent nursing knowledge in the Electronic Health Records (EHR). The purpose of this work was to define a set of correspondences between Nursing Ontology concepts of NursingOntos and other terminologies, which have the same or similar meaning. In this project, we are using the ISO/TR12300:2016 standard on the principles of mapping between terminological systems. Regarding the domain of "airway clearance", we can say that Portuguese Nursing Ontology has a good level of mapping with other terminologies. In conclusion, we can say that Portuguese Nursing Ontology can be used in EHR with the purpose of a global digitalization of health.

Effects of magnification on restorative dental preparation performance: a scoping review and level of evidence mapping.

OBJECTIVE: This scoping review aimed to identify and describe the available evidence on the effect of magnifying devices (loupe or microscope) on the performance of restorative dental preparations. MATERIALS AND METHODS: This study was conducted according to the PRISMA-ScR guidelines for scoping reviews and registered on the INPLASY database. An electronic search was performed in four databases and Grey literature for articles published until November 2023. Eligibility criteria were determined using the PICOS strategy and comprised studies that evaluated the performance of magnification devices for restorative dental preparations. A bibliographic mapping of the evidence was conducted. RESULTS: Sixteen studies met the inclusion criteria. Most of the studies (n = 12) compared the performance of dental preparations using magnification loupes vs. no magnification. The magnification for loupes and microscopes ranged from 2.5x to 4.0x and 6.4x to 10x, respectively. The use of magnifying loupes improved the performance of restorative preparations in 66.6% of the evaluated studies. However, when the magnifications were compared, the greater magnification provided by microscopes did not improve preparation performance compared to magnification loupes. Regarding the place of publication, the American continent concentrates the most significant number of evidence. CONCLUSIONS: Although evidence for magnification improving the performance of dental preparations has increased over the last decade, basically only in vitro studies (most of which have taken place in the Americas) have been reported in the literature. The evidence suggests that magnification significantly improves restorative preparation performance when compared to non-magnification. However, higher magnifications (e.g., microscopes) do not appear to improve tooth preparation performance compared with lower magnification devices (e.g., magnification loupes). CLINICAL RELEVANCE: Available evidence supports that using magnification can improve the performance of restored tooth preparations. However, high magnifications have no advantages over lower magnifications.

Estudo das prescrições de psicotrópicos dispensados em uma farmácia básica do sertão paraibano / Study of psychotropic prescriptions dispensed in a basic pharmacy in the hinterland of Paraíba

O uso indiscriminado de psicotrópicos tem importância econômica, social e requer atenção dos profissionais de saúde. Nessa perspectiva, a pesquisa tem como objetivo avaliar a prescrição e o perfil de utilização de psicotrópicos na Farmácia Básica do município de Catolé do Rocha/PB. O presente estudo é transversal, quantitativo do tipo descritivo. A coleta de dados foi realizada por meio de questionários aplicados no período de abril a maio de 2021. Foram entrevistados 200 usuários, selecionados com base em critérios de inclusão e exclusão. Os resultados apontaram a prevalência do sexo feminino (63,0%), casados (53,5%), residentes da zona urbana (70,5%), baixa escolaridade (56,5%) e aposentados (44,5%). Em suma, as prescrições eram obtidas em UBS (81,0%) por queixas de ansiedade (24,0%) e insônia (23,5%). Observou-se maior frequência de prescrição para clonazepam (18,6%) e alprazolam (15,9%), ambos considerados MPI. Estes foram prescritos principalmente por clínicos gerais (71,8%). Assim, evidencia-se a importância do farmacêutico na APS, tanto na sensibilização dos prescritores com relação à escolha e prescrição adequada destes medicamentos quanto na orientação dos pacientes com vistas à promoção do uso racional de psicotrópicos.

The use of psychotropic drugs has economic and social importance and requires attention from health professionals. he objective of this research was to evaluate the prescription and the profile of use of psychotropic drugs in the Basic Pharmacy in the municipality of Catolé do Rocha/PB. This is a cross-sectional, quantitative, descriptive study. Data collection was carried out through questionnaires applied from April to May 2021. Two hundred users were interviewed, selected based on inclusion and exclusion criteria. The results showed a prevalence of females (63.0%), married (53.5%), residing in the urban area (70.5%), with low education (56.5%), and retired (44.5%). The prescriptions were obtained at the Basic Health Unit (81.0%) for complaints of anxiety (24.0%) and insomnia (23.5%). We observed a higher frequency of prescriptions for clonazepam (18.6%) and alprazolam (15.9%), both considered potential inappropriate drugs. These were mainly prescribed by general practitioners (71.8%). Thus, the importance of pharmacists in Primary Health Care is evident both to increase the awareness among prescribers regarding the choice and proper prescription of medications and to guide patients with a view to promoting the rational use of psychotropic drugs.

Inter-software reliability and agreement for follicular and luteal morphometric and echotextural ultrasonographic parameters in beef cattle.

This study aimed to compare the inter-software and inter-observer reliability and agreement for the assessment of follicular and luteal morphometry and echotexture parameters in beef crossbreed females (3/8 Bos taurus indicus and 5/8 Bos taurus taurus). B-mode and color Doppler ultrasonographic ovarian images were obtained at specific time points of estradiol-progesterone-based protocols for timed artificial insemination (TAI). Sonograms were analyzed by two observers using a licensed (IASP1) and an open access (IASP2) software package. A total of 292 snap-shot sonograms were analyzed for morphometric parameters and 504 for echotexture parameters. inter-software reliability was judged moderate to excellent (ICC or CCC=0.73-0.98), whereas inter-observer reliability for morphometric parameters was deemed good to excellent (ICC or CCC=0.82-0.98). A small percentage (up to 10.95 %) of measured parameters fell outside the limits of inter-software and inter-observer agreement. For echotexture parameters, inter-software reliability varied widely (ICC or CCC=0.16-0.95) based on the size of regions of interest (ROI), while inter-observer reliability ranged from moderate to excellent (ICC or CCC= 0.71-0.97). The highest inter-software reliability for pixel value and heterogeneity value was observed for the corpus luteum (ICCs=0.81-0.95; P>0.05), followed by the peripheral follicular antrum (ICCs=0.75-0.78; P<0.05). However, lower reliability was determined for the follicular wall (ICCs=0.08-0.33; P<0.0001) and perifollicular stroma (ICCs=0.16-0.46; P<0.05). In conclusion, both software packages showed high reproducibility for morphometric measurements, while echotexture measurements were more challenging to replicate based on ROI sizes. Caution is advised when selecting ROI sizes for echotexture measurements in bovine ovaries.

Temporal patterns of food consumption and their association with cardiovascular risk in rotating shift workers.

OBJECTIVE: We aimed to evaluate the association of temporal patterns of food consumption with cardiovascular disease (CVD) risk. METHODS: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Data on food consumption was collected using a 24 h recall, applied by trained interviewers. The variables for temporal patterns of food consumption were: eating window, eating at night, number of meals and omission of breakfast. CVD-risk was measured by calculating the Framingham coronary heart disease risk score (FCRS), and classified as low risk or intermediate to high risk. Descriptive, univariate and multivariate logistic regression analyses examined the association between variables related to temporal patterns of food consumption and CVD-risk. RESULTS: The study assessed 208 workers, the majority with 20-34 years (45.1%), non-white (77.2%), and 5 years or more in shift work (76.0%). Most participants had a feeding window exceeding 12 h (63.9%), consumed meals until 10 p.m. (68.1%), had five or more meals per day (54.8%), and did not skip breakfast (86.5%). Regarding CVD-risk, 43.8% of the participants were classified with intermediate to high risk for CVD. In the multivariate model, a feeding window (OR: 2.32; 95%CI: 1.01-5.35), eating after 10 p.m. (OR: 3.31; 95%CI: 1.01-11.0), and skipping breakfast (OR: 2.58; 95%CI: 1.07-6.19) increased the likelihood of intermediate to high CVD-risk. Conversely, having five or more meals per day decreased the odds (OR: 0.27; 95%CI: 0.08-0.92). CONCLUSION: Eating window longer than 12 h, eating after 10 p.m., less than four meals a day and omission of breakfast, are associated with cardiovascular risk in shift workers.

Algorithm-Based Linearly Graded Compositions of GeSn on GaAs (001) via Molecular Beam Epitaxy.

The growth of high-composition GeSn films in the future will likely be guided by algorithms. In this study, we show how a logarithmic-based algorithm can be used to obtain high-quality GeSn compositions up to 16% on GaAs (001) substrates via molecular beam epitaxy. Herein, we use composition targeting and logarithmic Sn cell temperature control to achieve linearly graded pseudomorph Ge1-xSnx compositions up to 10% before partial relaxation of the structure and a continued gradient up to 16% GeSn. In this report, we use X-ray diffraction, simulation, secondary ion mass spectrometry, and atomic force microscopy to analyze and demonstrate some of the possible growths that can be produced with the enclosed algorithm. This methodology of growth is a major step forward in the field of GeSn development and the first ever demonstration of algorithmically driven, linearly graded GeSn films.

A subiculum-hypothalamic pathway functions in dynamic threat detection and memory updating.

Animals need to detect threats, initiate defensive responses, and, in parallel, remember where the threat occurred to avoid the possibility of re-encountering it. By probing animals capable of detecting and avoiding a shock-related threatening location, we were able to reveal a septo-hippocampal-hypothalamic circuit that is also engaged in ethological threats, including predatory and social threats. Photometry analysis focusing on the dorsal premammillary nucleus (PMd), a critical interface of this circuit, showed that in freely tested animals, the nucleus appears ideal to work as a threat detector to sense dynamic changes under threatening conditions as the animal approaches and avoids the threatening source. We also found that PMd chemogenetic silencing impaired defensive responses by causing a failure of threat detection rather than a direct influence on any behavioral responses and, at the same time, updated fear memory to a low-threat condition. Optogenetic silencing of the main PMd targets, namely the periaqueductal gray and anterior medial thalamus, showed that the projection to the periaqueductal gray influences both defensive responses and, to a lesser degree, contextual memory, whereas the projection to the anterior medial thalamus has a stronger influence on memory processes. Our results are important for understanding how animals deal with the threat imminence continuum, revealing a circuit that is engaged in threat detection and that, at the same time, serves to update the memory process to accommodate changes under threatening conditions.

Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies.

OBJECTIVE: To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. METHODS: Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. RESULTS: Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. CONCLUSION: Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.

Evaluation of polymersome permeability as a fundamental aspect towards the development of artificial cells and nanofactories.

Polymersomes are synthetic vesicles with potential use in healthcare, chemical transformations in confined environment (nanofactories), and in the construction of artificial cells and organelles. In this framework, one of the most important features of such supramolecular structures is the permeability behavior allowing for selective control of mass exchange between the inner and outer compartments. The use of biological and synthetic nanopores in this regard is the most common strategy to impart permeability nevertheless, this typically requires fairly complex strategies to enable porosity. Yet, investigations concerning the permeability of polymer vesicles to different analytes still requires further exploration and, taking these considerations into account, we have detailed investigated the permeability behavior of a variety of polymersomes with regard to different analytes (water, protons, and rhodamine B) which were selected as models for solvents, ions, and small molecules. Polymersomes based on hydrophilic blocks of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) or PEO (poly(ethylene oxide)) linked to the non-responsive blocks poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA) or poly(methyl methacrylate) (PMMA), or to the stimuli pH-responsive block poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) have been investigated. Interestingly, the produced PEO-based vesicles are notably larger than the ones produced using PHPMA-containing block copolymers. The experimental results reveal that all the vesicles are inherently permeable to some extent with permeability behavior following exponential profiles. Nevertheless, polymersomes based on PMMA as the hydrophobic component were demonstrated to be the least permeable to the small molecule rhodamine B as well as to water. The synthetic vesicles based on the pH-responsive PDPA block exhibited restrictive and notably slow proton permeability as attributed to partial chain protonation upon acidification of the medium. The dye permeability was evidenced to be much slower than ion or solvent diffusion, and in the case of pH-responsive assemblies, it was demonstrated to also depend on the ionic strength of the environment. These findings are understood to be highly relevant towards polymer selection for the production of synthetic vesicles with selective and time-dependent permeability, and it may thus contribute in advancing biomimicry and nanomedicine.

Flavonoids isolated from Vismia macrophylla Kunth against resistant bacteria.

The antimicrobial activity of Vismia macrophylla extract is reported in the literature; however, little is known about the presence of phenolic compounds and their antimicrobial activity in this species. This study aimed to isolate phenolic compounds with antimicrobial action from the leaves of V. macrophylla. The ethanolic extract (VmL-Et) was submitted to sephadex column separation, and some fractions were submitted to derivatization with BSTFA and analysed by GC-MS. This study indicated the presence of the catechin, osajaxanthone, quercetin, quercitrin, and glucodistylin. Of these, osajaxanthone, quercetin, quercitrin, and glucodistylin were isolated and identified by spectroscopic techniques. VmL-Et, quercetin, quercitrin, glucodistylin, and maslinic acid, were tested against the Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis. The results showed broad spectrum action of the extract Vm-Et, glucodistylin and quercitrin. The species V. macrophylla occurring in the Brazilian biome showed potential for obtaining phenolic compounds that can help combat microbial resistance.

Development of Ac2-26 Mesoporous Microparticle System as a Potential Therapeutic Agent for Inflammatory Bowel Diseases.

Introduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology. Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut. Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 µg; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis. Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results. Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non-invasive IBD therapy.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.