Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil.

Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Hypertensive disorders of pregnancy and long-term maternal cardiovascular risk: Bridging epidemiological knowledge into personalized postpartum care and follow-up.

Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD.

Oxidative stress induction by essential oil from Piper alatipetiolatum (Piperaceae) triggers lethality in the larvae of Culex quinquefasciatus (Diptera: Culicidae).

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.

Father's Absence in the Mongolian gerbil (Meriones unguiculatus) is associated with alterations in paternal behavior, T, cort, presence of ERα, and AR in mPOA/ BNST.

Testosterone (T), estrogen receptor alpha (ERα), and androgen receptor (AR) play a significant role in the regulation of paternal behavior. We determined the effects of deprivation of paternal care on alterations in paternal behavior, T concentrations in plasma, and the presence of ERα and AR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB), as well as the corticosterone (CORT) concentrations in plasma caused by deprivation of paternal care in the Mongolian gerbil (Meriones unguiculatus). Twenty pairs of gerbils were formed; the pups were deprived of paternal care (DPC) in 10 pairs. In another 10 pairs, the pups received paternal care (PC). Ten males raised in DPC condition and 10 males raised in PC conditions were mated with virgin females. When they became fathers, each DPC male and PC male was subjected to tests of paternal behavior on day three postpartum. Blood samples were obtained to quantify T and CORT concentrations, and the brains were removed for ERα and AR immunohistochemistry analyses. DPC males gave less care to their pups than PC males, and they had significantly lower T concentrations and levels of ERα and AR in the mPOA and BNST than PC males. DPC males also had higher CORT concentrations than PC males. These results suggest that in the Mongolian gerbil father's absence causes a decrease in paternal care in the offspring, which is associated with alterations in the neuroendocrine mechanisms that regulate it.

The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling.

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.

Sickle cell disease and increased adverse maternal and perinatal outcomes in different genotypes.

BACKGROUND: Sickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established. METHODS: A retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sß) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available. RESULTS: Sixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sß (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sß (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings CONCLUSION: SCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

Pain management effectiveness in advanced cancer: palliative care unit inpatient study.

OBJECTIVES: The aim of this study is to evaluate pain management adequacy based on the Pain Management Index (PMI), and its association with the Brief Pain Inventory (BPI) in advanced cancer inpatients to a palliative care unit. METHODS: This is a quantitative study concerning advanced cancer inpatients in a specialised palliative care unit between June 2021 and February 2022. The BPI was applied, and analgesia was observed on the first (D1), third (D3) and seventh (D7) day of hospitalisation. Adequate analgesia was considered when PMI≥0. RESULTS: A total of 104 patients were evaluated on D1, 68 on D3 and 45 on D7, with a mean age of 53.6 years (SD±14.1), most of them female (65.4%), with the most frequent primary tumour site located in the gastrointestinal tract (22.1%). The observed analgesia was adequate (PMI≥0) in 52.9% of all patients on D1, 95.6% on D3 and 100% on D7 (p value=0.012). The number of patients with moderate to severe pain interference in general activities (p value 0.012), mood (p value 0.014), walking ability (p value 0.047), normal work (p value 0.038) and pleasure of living (p value 0.025) decreased during hospitalisation. CONCLUSIONS: Pain is a prevalent and impacting symptom in patients undergoing palliative care. Thus, objective analgesic adequacy assessments in specialised services are required. These findings reinforce the importance of effective pain control and corroborate the importance of employing objective tools in evaluating medical services and improving quality of life of patients.

Chemical Characterization and Biological Properties Assessment of Euphorbia resinifera and Euphorbia officinarum Moroccan Propolis.

Although the plants of the genus Euphorbia are largely exploited by therapists in Morocco, the composition and antibacterial activities of propolis from these plants are still unknown. To address this gap, this study aimed to characterize the pollen type, the volatile compounds, and the phenolic and mineral profiles of three Euphorbia propolis samples collected in Morocco and evaluate their antimicrobial activities. The minimum inhibitory concentration of the propolis samples was determined by the microdilution method, and the anti-adherence activity was evaluated by the crystal violet assay. The examination of anti-quorum-sensing proprieties was performed using the biosensor Chromobacterium violaceum CV026. Pollen analysis revealed that Euphorbia resinifera pollen dominated in the P1 sample (58%), while E. officinarum pollen dominated in the P2 and P3 samples (44%). The volatile compounds were primarily composed of monoterpene hydrocarbons, constituting 35% in P1 and 31% in P2, with α-pinene being the major component in both cases, at 16% in P1 and 15% in P2. Calcium (Ca) was the predominant mineral element in both E. resinifera (P1) and E. officinarum (P2 and P3) propolis samples. Higher levels of phenols, flavonoids and dihydroflavonoids were detected in the E. officinarum P2 sample. The minimum inhibitory concentration (MIC) value ranged from 50 to 450 µL/mL against Gram-positive and Gram-negative bacteria. Euphorbia propolis displayed the ability to inhibit quorum sensing in the biosensor C. violaceum CV026 and disrupted bacterial biofilm formation, including that of resistant bacterial pathogens. In summary, the current study evidences the potential use of E. officinarum propolis (P2 and P3) to combat important features of resistant pathogenic bacteria, such as quorum sensing and biofilm formation.

Epigenetic remodeling to improve the efficacy of immunotherapy in human glioblastoma: pre-clinical evidence for development of new immunotherapy approaches.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM. Thus, manipulating the tumor epigenome can be considered a therapeutic opportunity in GBM. METHODS: Microarray transcriptional and methylation profiles, followed by gene set enrichment and IPA analyses, were performed to study the differences in the constitutive expression profiles of GBM vs MM-BM cells, compared to the extracranial MM cells and to investigate the modulatory effects of the DNA hypomethylating agent (DHA) guadecitabine among the different tumor cells. The prognostic relevance of DHA-modulated genes was tested by Cox analysis in a TCGA GBM patients' cohort. RESULTS: The most striking differences between GBM and MM-BM cells were found to be the enrichment of biological processes associated with tumor growth, invasion, and extravasation with the inhibition of MHC class II antigen processing/presentation in GBM cells. Treatment with guadecitabine reduced these biological differences, shaping GBM cells towards a more immunogenic phenotype. Indeed, in GBM cells, promoter hypomethylation by guadecitabine led to the up-regulation of genes mainly associated with activation, proliferation, and migration of T and B cells and with MHC class II antigen processing/presentation. Among DHA-modulated genes in GBM, 7.6% showed a significant prognostic relevance. Moreover, a large set of immune-related upstream-regulators (URs) were commonly modulated by DHA in GBM, MM-BM, and MM cells: DHA-activated URs enriched for biological processes mainly involved in the regulation of cytokines and chemokines production, inflammatory response, and in Type I/II/III IFN-mediated signaling; conversely, DHA-inhibited URs were involved in metabolic and proliferative pathways. CONCLUSIONS: Epigenetic remodeling by guadecitabine represents a promising strategy to increase the efficacy of cancer immunotherapy of GBM, supporting the rationale to develop new epigenetic-based immunotherapeutic approaches for the treatment of this still highly deadly disease.

Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions.

BACKGROUND: Osteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is due to a combination of factors, although the pivotal mechanisms underlying the disease are still obscure. Moreover, current treatments are still poorly effective, and patients experience a painful and degenerative disease course. METHODS: We used an integrative approach that led us to extract a consensus signature from a meta-analysis of three different OA cohorts. We performed a network-based drug prioritization to detect the most relevant drugs targeting these genes and validated in vitro the most promising candidates. We also proposed a risk score based on a minimal set of genes to predict the OA clinical stage from RNA-Seq data. RESULTS: We derived a consensus signature of 44 genes that we validated on an independent dataset. Using network analysis, we identified Resveratrol, Tenoxicam, Benzbromarone, Pirinixic Acid, and Mesalazine as putative drugs of interest for therapeutics in OA for anti-inflammatory properties. We also derived a list of seven gene-targets validated with functional RT-qPCR assays, confirming the in silico predictions. Finally, we identified a predictive subset of genes composed of DNER, TNFSF11, THBS3, LOXL3, TSPAN2, DYSF, ASPN and HTRA1 to compute the patient's risk score. We validated this risk score on an independent dataset with a high AUC (0.875) and compared it with the same approach computed using the entire consensus signature (AUC 0.922). CONCLUSIONS: The consensus signature highlights crucial mechanisms for disease progression. Moreover, these genes were associated with several candidate drugs that could represent potential innovative therapeutics. Furthermore, the patient's risk scores can be used in clinical settings.

Nature-based solutions for coastal risk management in the Mediterranean basin: A literature review.

The Mediterranean basin is one of the most vulnerable regions worldwide due to its population density, the concentration of economic activities along the coasts and borderline climatic balance. It is identified as one of the most critical erosion hotspots in Europe, mainly due to the degradation of coastal areas, overexploitation and unsustainable practices affecting beach tourism, agriculture and fishing. The region is also affected by other phenomena such as storms and floods, which are exacerbated by climate change. To mitigate and adapt to these environmental and climatic changes, Nature based Solutions (NbSs) are considered a promising step-forward. However, despite their global recognition in both research and policy, few scientific papers and documents on the state of NbSs implementation for coastal risk management in the Mediterranean exist. This paper aims to provide an understanding of the status of NbS adoption for coastal risk management in the Mediterranean through a literature review. Out of 162 scientific papers and documents, only 23 were found to be relevant to the study. Through the definition and support of an innovative matrix-based approach, the analysis of the state of adoption of NbSs have been performed. Despite the limited information on the state of the adoption of NbSs for coastal risk management in the Mediterranean due to the low numbers of scientific research and documents available, some key considerations have been revealed.

Relación entre cognición y ciertos biomarcadores sanguíneosen función de factores de riesgo vascular / Relationship between cognition and certain blood biomarkers as a functionof vascular risk factors

Introducción: En años reciente se señalado que trastor-nos como la obesidad, la diabetes mellitus tipo 2 (DMT-II) es-tán asociados a deterioro cognitivo. Una posibilidad para com-prender la relación entre la cognición y estos trastornos sonlos biomarcadores en sangre. Objetivo: El objetivo de esta investigación fue determinarla relación de la hemoglobina glucosilada (HbA1c) y lípidoscon el desempeño cognitivo de pacientes que están expues-tos varios factores de riesgo vascular en comparación con pa-cientes que tienen menos factores de riesgo. Metodología: Se llevó a cabo un muestreo no probabilís-tico por conveniencia. Se consideraron a adultos de ambossexos que tuvieran una edad mayor a 18 años y que conta-ran con algún factor de riesgo como un estilo de vida seden-tario y/o diagnóstico de DMT-II, hipertensión u obesidad. Losparticipantes (n=28) fueron evaluados mediante EvaluaciónCognitiva Montreal (MoCA) y tareas para evaluar memoria detrabajo verbal y visoespacial (Dspan y Mspan). Asimismo, sedeterminaron los niveles de hemoglobina glicosilada (HbA1c),colesterol (HDL y LDL) y triglicéridos (TG). Resultados: Se encontró que los niveles elevados deHbA1c y TG se asociaron con una menor puntuación en laprueba MoCA, mientras que los niveles elevados de HDL seasociaron con mejor desempeño cognitivo en dicha prueba.Al dividir a la muestra en función de la cantidad de factoresde riesgo vascular a los que han sido expuestos se encon-tró que a mayor presencia de factores de riesgo la relaciónde la HbA1c y TG con un menor desempeño cognitivo esmás fuerte. Conclusión: Se concluye que la relación entre biomarca-dores y funciones cerebrales es fuerte y dependiente de lacantidad de factores de riesgo vascular a los que están ex-puestos los pacientes.(AU)

Introduction: In recent years it has been reported thatdisorders such as obesity and type 2 diabetes mellitus (T2DM)are associated with cognitive impairment. One possibility tounderstand the relationship between cognition and these dis-orders is blood biomarkers. Objective: The aim of this research was to determine therelationship of glycosylated hemoglobin (HbA1c) and lipidswith cognitive performance in patients who are exposed tovarious vascular risk factors compared with patients who havefewer risk factors. Methodology: Non-probability convenience sampling wasperformed. Adults of both sexes who were older than 18 years of age and who had some risk factor such as a sedentarylifestyle and/or diagnosis of T2DM, hypertension, or obesitywere considered. Participants (n=28) were assessed byMontreal Cognitive Assessment (MoCA) and tasks to evaluateverbal and visuospatial working memory (Dspan and Mspan).Glycosylated hemoglobin (HbA1c), cholesterol (HDL and LDL)and triglycerides (TG) levels were also determined. Results: It was found that elevated HbA1c and TG levelswere associated with a lower score on the MoCA test, whileelevated HDL levels were associated with better cognitive per-formance on the MoCA test. When the sample was divided ac-cording to the number of vascular risk factors to which theyhad been exposed, it was found that the greater the presenceof risk factors the stronger the relationship of HbA1c and TGwith poorer cognitive performance. Conclusion: We conclude that the relationship betweenbiomarkers and brain function is strong and dependent on thenumber of vascular risk factors to which patients are exposed.(AU)

In vitro evaluation of the susceptibility of bacterial biofilms to hecogenin acetate.

Biofilms are a bacterial resistance strategy through which microorganisms organize themselves in the form of a colony fixed to a surface that is protected by a polymer matrix. Infectious diseases that result in biofilm formation have been considered a relevant public health problem due to the potential to increase patient morbidity and mortality, in addition to increasing the burden on health services. Such pathologies are treated with the use of antimicrobial drugs, the indiscriminate use of which has contributed to the process of bacterial resistance, demanding the need to invest in new alternatives to combat them. Based on this, the present work aimed to evaluate the anti-biofilm formation and eradication capacity of Hecogenin Acetate, a steroidal sapogenin of natural origin with important antibacterial properties. For this, we used strains of Streptococcus mutans INCQS 00,446 (ATCC 25,175), Enterococcus faecalis INCQS 00,018 (ATCC 14,506), Staphylococcus epidermidis INCQS 00,016 (ATCC 12,228), Staphylococcus aureus ATCC 25,923, Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 259,223. The formation, formation inhibition and treatment assays were carried out in microdilution plates and revealed using the crystal violet method. Readings were carried out using absorbance at wavelengths of 492 nm. All tests were performed in triplicate and statistical analyzes were performed using Graphpad Prism v.5.0 software. It was observed that the bacterial strains used have a relevant capacity for biofilm formation, with the Gram positive ones identified in the present study as the best former. In the results of the analyzes with bacterial biofilm, it was identified that Hecogenin Acetate had a relevant antibiofilm capacity, and could therefore serve as a basis for further research into the development of new antimicrobial drugs.

Blood and cerebellar abundance of ATXN3 splice variants in spinocerebellar ataxia type 3/Machado-Joseph disease.

Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is a heritable proteinopathy disorder, whose causative gene, ATXN3, undergoes alternative splicing. Ataxin-3 protein isoforms differ in their toxicity, suggesting that certain ATXN3 splice variants may be crucial in driving the selective toxicity in SCA3. Using RNA-seq datasets we identified and determined the abundance of annotated ATXN3 transcripts in blood (n = 60) and cerebellum (n = 12) of SCA3 subjects and controls. The reference transcript (ATXN3-251), translating into an ataxin-3 isoform harbouring three ubiquitin-interacting motifs (UIMs), showed the highest abundance in blood, while the most abundant transcript in the cerebellum (ATXN3-208) was of unclear function. Noteworthy, two of the four transcripts that encode full-length ataxin-3 isoforms but differ in the C-terminus were strongly related with tissue expression specificity: ATXN3-251 (3UIM) was expressed in blood 50-fold more than in the cerebellum, whereas ATXN3-214 (2UIM) was expressed in the cerebellum 20-fold more than in the blood. These findings shed light on ATXN3 alternative splicing, aiding in the comprehension of SCA3 pathogenesis and providing guidance in the design of future ATXN3 mRNA-lowering therapies.

Prostaglandin E2/Leukotriene B4 balance and viral load in distinct clinical stages of COVID-19: A cross-sectional study.

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Quality of Life and Hormonal Impairment in Pediatric Patients With Craniopharyngiomas.

INTRODUCTION: Craniopharyngiomas (CP) are tumors in the sellar region that, despite a high survival rate, are associated with significant morbidity, including hypothalamic, hormonal, and visual dysfunction. This study aimed to assess the quality of life (QoL) in pediatric patients with CP and to evaluate its relationship with various factors, with a focus on the impact of endocrine dysfunction. METHODS: In this observational cross-sectional study, patients with CP aged between 0 and 18 years, currently followed up in a tertiary hospital by a multidisciplinary team, were included. QoL was assessed using the validated PEDS-QL4.0 questionnaire, which was administered to parents. This tool estimates Global QoL (QoL-G), further divided into Physical (QoL-P) and Psychosocial (QoL-PS) dimensions, including Emotional (QoL-Em), Social (QoL-S), and School (QoL-Sc) aspects. In Portugal, the estimated average QoL-G is 79.8, QoL-P is 83.5, and QoL-PS is 78.2. Variables studied included gender, current and diagnostic age, follow-up time, presence of hydrocephalus, hypothalamic involvement, type of resection (total or subtotal), radiotherapy, visual impairment, hormonal deficits, and therapy. RESULTS: The study included 11 patients with a median age of 15.2 years (interquartile ratio (IQR), 9.7-17.9 years) and a mean age at diagnosis of 9.3±4.1 years. Of these patients, 54.5% were male, and 36.4% were obese. Subtotal resection was performed in 72.7% of cases. Hydrocephalus was present in 54.5% of the patients, hypothalamic involvement in 63.7%, radiotherapy was received by 81.8%, and visual impairment was noted in 54.5%. All patients presented with at least one hormonal deficit. The average QoL-G was 69.9±22.5, with QoL-P at 66.9±30.0 and QoL-PS at 70.9±21.4. A worse QoL-S was associated with female gender (p=0.030) and subtotal resection (p=0.048). Worse QoL-G, QoL-P, QoL-Em, and QoL-PS were linked to hypothalamic involvement (p values 0.008, 0.025, 0.015, and 0.009, respectively). Irradiated patients had worse QoL-G (p=0.006). Treatment with sexual hormones enhanced QoL-Global (p=0.035) and QoL-Emotional (p=0.020), while treatment for adrenal insufficiency and diabetes insipidus improved QoL-Emotional (p=0.021 and p=0.013). No significant associations with visual deficit or obesity were found. CONCLUSIONS: Pediatric patients with CP appear to have poorer QoL-G, QoL-P, and QoL-PS compared to the healthy Portuguese population. However, the small sample size limits statistically significant associations with many of these variables. Predictors of worse QoL include female gender, hypothalamic involvement, subtotal resection, and radiotherapy. The results may be biased due to the small sample size, questionnaire administration to parents, and possible inadequacy of the questionnaire for the studied population. There is a need for a more suitable tool to enable a more precise assessment of QoL in these patients.

[Sociodemographic characteristics associated with underweight and overweight in adults aged 50 years and over (ELSI-Brasil): differences between sexes]. / Características sociodemográficas associadas ao baixo peso e ao excesso de peso em adultos com 50 anos ou mais (ELSI-Brasil): diferenças entre sexos.

The objective were to describe the prevalence of underweight and overweight, assessed by body mass index (BMI), stratified by sex and age group, and to analyze the sociodemographic characteristics associated with BMI in older women and men. This is a cross-sectional analysis of 8,974 participants aged ≥ 50 years from the baseline of the Brazilian Longitudinal Study of Aging (ELSI-Brasil, 2015-2016). BMI was classified as underweight, eutrophy, and overweight according to the participant's age. A multinomial logistic regression model was used, considering the sociodemographic characteristics of women and men. The results showed a higher prevalence of overweight in women compared to men (64.1% vs. 57.3%). In both sexes, the prevalence of underweight was higher in the longest-lived individuals, while overweight was lower. In women, the chance of underweight was higher than the chance of eutrophy in those who were single/widowed/divorced (OR = 1.95; 95%CI: 1.42-2.66) and in those living in rural areas (OR = 1.58; 95%CI: 1.01-2.49), while the chance of being overweight was lower than the chance of being eutrophy in those living in rural areas (OR = 0.78; 95%CI: 0.62-0.97) and in all geographic macro-regions related to the South Region. For men, the chance of being overweight was lower than the chance of being eutrophy among single/widowed/divorced individuals (OR = 0.58; 95%CI: 0.48-0.69). The richest had a lower chance of being underweight (OR = 0.59; 95%CI: 0.38-0.90), as well as a higher chance of being overweight (OR = 1.52; 95%CI: 1.20-1.92). In conclusion, the sociodemographic characteristics associated with BMI differed between the sexes.

Os objetivos foram descrever a prevalência de baixo peso e excesso de peso, avaliados pelo índice de massa corporal (IMC), estratificada por sexo e faixa etária, e analisar as características sociodemográficas associadas ao IMC em mulheres e homens mais velhos. Trata-se de uma análise transversal de 8.974 participantes com ≥ 50 anos da linha de base do Estudo Longitudinal da Saúde dos Idosos Brasileiros (ELSI-Brasil, 2015-16). O IMC foi classificado em baixo peso, eutrofia e excesso de peso de acordo com a idade do participante. Foi utilizado modelo de regressão logística multinominal, considerando-se as características sociodemográficas de mulheres e homens. Os resultados evidenciaram maior prevalência de excesso de peso nas mulheres em comparação aos homens (64,1% vs. 57,3%). Em ambos os sexos, a prevalência de baixo peso foi maior nos mais longevos, enquanto que o excesso de peso foi menor. Nas mulheres, a chance de baixo peso foi maior do que a chance de eutrofia naquelas solteiras/viúvas/divorciadas (OR = 1,95; IC95%: 1,42-2,66) e nas residentes na área rural (OR = 1,58; IC95%: 1,01-2,49), ao passo que a chance de excesso de peso foi menor do que a chance de eutrofia nas residentes na área rural (OR = 0,78; IC95%: 0,62-0,97) e em todas as macrorregiões geográficas relativas à Região Sul. Para os homens, a chance de excesso de peso foi menor do que a chance de eutrofia entre solteiros/viúvos/divorciados (OR = 0,58; IC95%: 0,48-0,69). Os mais ricos apresentaram menor chance de baixo peso (OR = 0,59; IC95%: 0,38-0,90), bem como maior chance de excesso de peso (OR = 1,52; IC95%: 1,20-1,92). Em conclusão, as características sociodemográficas associadas ao IMC diferiram entre os sexos.

Los objetivos fueron describir la prevalencia de bajo peso y sobrepeso, evaluados a través del índice de masa corporal (IMC), estratificada por sexo y grupo de edad, y analizar las características sociodemográficas asociadas al IMC en mujeres y hombres mayores. Se trata de un análisis transversal de 8.974 participantes con ≥ 50 años de la línea de base del Estudio Longitudinal Brasileño sobre el Envejecimiento (ELSI-Brasil, 2015-2016). Se clasificó el IMC en bajo peso, eutrofia y sobrepeso conforme la edad del participante. Se utilizó el modelo de regresión logística multinomial, teniendo en cuenta las características sociodemográficas de mujeres y hombres. Los resultados evidenciaron una prevalencia más alta de sobrepeso en las mujeres en comparación con los hombres (64,1% vs. 57,3%). En ambos sexos, la prevalencia de bajo peso fue más alta en los grupos de mayor edad, mientras que la prevalencia del sobrepeso fue menor. La chance de bajo peso fue más alta que la chance de eutrofia en las mujeres solteras/viudas/divorciadas (OR = 1,95; IC95%: 1,42-2,66) y en las que viven en el área rural (OR = 1,58; IC95%: 1,01-2,49), mientras que la chance de sobrepeso fue menor que la chance de eutrofia en las que viven en el área rural (OR = 0,78; IC95%: 0,62-0,97) y en todas las macrorregiones geográficas relacionadas a la región Sur. La chance de sobrepeso fue menor que la chance de eutrofia entre los hombres solteros/viudos/divorciados (OR = 0,58; IC95%: 0,48-0,69). Los más ricos presentaron una chance menor de bajo peso (OR = 0,59; IC95%: 0,38-0,90), así como una chance más alta de sobrepeso (OR = 1,52; IC95%: 1,20-1,92). En conclusión, las características sociodemográficas asociadas al IMC difirieron entre los sexos.

Pesticide water variability and prioritization: The first steps towards improving water management strategies in irrigation hydro-agriculture areas.

The presence of pesticides in aquatic ecosystems poses significant risks to non-target organisms, necessitating monitoring and environmental risk assessment. This study aimed to evaluate the dynamics and environmental risk of pesticides in a hydro-agricultural area with intensive agricultural practices, in the Mediterranean region (South of Portugal). Seasonality and location influenced pesticide numbers and concentrations, with the highest levels observed during the dry season. Triazines, phenylureas, and organophosphates were the predominant pesticide classes, with terbuthylazine, bentazone, terbutryn, diazinon, and metolachlor exhibiting the highest detection frequencies (68 % to 72 %). Notably, 44 % of the quantified pesticides are no longer authorized in Portugal, with 33 % posing a high environmental risk. Some insecticides, including imidacloprid, methiocarb, and malathion, were occasionally detected at concentrations that posed high risks to the aquatic ecosystem (RQ ≥ 1). Irgarol, an algicide used in irrigation canals, presented a high risk in 91 % of the analysed samples. The study's distribution profile of pesticides revealed a significant transportation of these compounds from reservoirs to irrigation hydrants, establishing them as a secondary source of crop and environmental contamination. Additionally, the assessment of spatial distribution and environmental risk allowed for the identification of specific pollutants in different locations, prioritizing them based on their ecotoxicological risk to aquatic ecosystems. These findings reinforce the importance of implementing management measures at the level of hydro-agricultural areas, helping to stop the cycle of pesticide contamination. Only this type of strategy will make it possible to protect water quality, biodiversity and the health of citizens, contributing to the European Union's objectives of improving the condition of freshwater bodies and promoting the sustainable use of pesticides.