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Ethnopharmacological Relevance: Plectranthus ornatus is a medicinal plant originally from Africa but adapted to Brazil's climate conditions. It is recognized for its therapeutic properties, particularly for treating liver and stomach diseases, gastritis control, heartburn, and hangover. Therefore, studies on its chemical composition and pharmacological evaluation are important for the safe use of the plant., Aim of the Study: To investigate the chemical composition and pharmacological activity of leaf decoction of P. ornatus., Materials and Methods: The lyophilized herbal decoction from P. ornatus leaves was extracted with MeOH (methodology A), and CHCl 3 and n-BuOH (methodology B). The compounds were isolated using chromatographic techniques. Their structures were determined using spectroscopic methods ( 1 H and 13 C NMR, IR, and HRESIMS) and comparison with published data. The lyophilized herbal decoctions DPO A (decoction from methodology A) and DPO B (methodology B), and compounds 8, 9, 15, and 16 (4, 20, and 40 mg/kg) were evaluated for their toxicity, anti-nociceptive, and anti-inflammatory effects in experimental adult zebrafish (Danio rerio) models., Results: The present study focused on the CHCl 3 and MeOH soluble fractions from the lyophilized leaf decoction leading to the isolation of five new diterpenes (1, 4-7) and two new glucuronide flavonoid derivatives (2 and 3). In addition, four diterpenes (14-17), two glucuronide flavonoid derivatives (10 and 11), three phenolics (8, 12, and 13), and one disaccharide (9) previously reported were also isolated. In zebrafish essays, all samples showed no toxicity and exhibited an anti-nociceptive effect in at least one of the tested doses: 9, 15, 16, and DPO B (4 mg/kg), 8 (20 mg/kg), and DPO A (40 mg/kg). Moreover, the compounds 15 (4, 20, and 40 mg/kg) and 16 (4, 20, and 40 mg/kg) exhibited anti-inflammatory effects., Conclusion: The lyophilized decoctions (DPO A and DPO B) including the compounds 8, 9, 15, and 16 exhibited significant anti-nociceptive effects in adult zebrafish and showed no toxicity. Since pain can be a symptom of liver, stomach, and gastrointestinal disorders, and all the samples proved to be non-toxic, the herbal decoction of P. ornatus leaf could be considered a potential therapeutic option in pain management, supporting the ethnopharmacological use of the plant., 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.)

The progression of periodontal disease (PD) involves the action of oxidative stress mediators. Antioxidant agents may potentially attenuate the development of this condition. Thus, we aimed to evaluate the effects of different doses of humic acid (HA), extracted from biomass vermicomposting, on redox status and parameters related to PD progression in rats. Fifty-four adult male Wistar rats were distributed into six experimental groups (control; PD; PD + 40 mg/kg of HA; PD + 80 mg/kg of HA; PD + 160 mg/kg of HA; PD + 320 mg/kg of HA). HA was administered by gavage for 28 days, and PD was induced by ligature on the mandibular first molars on the 14th day of treatment. After euthanasia, alveolar bone loss, oxidative stress in the gum and erythrocytes, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were analyzed. Animals treated with HA showed less bone loss at the dose of 80 mg/kg compared to the untreated PD group (p < 0.05). Animals treated with HA at doses higher than 80 mg/kg showed improvements in local and systemic redox status parameters (total antioxidant activity, thiobarbituric reactive substances, carbonyl derivatives, and superoxide dismutase) compared to the PD group (p < 0.05). Treatment with HA reduced serum levels of creatinine (at doses of 80 and 160 mg/kg) and AST (at doses of 40 and 80 mg/kg) compared to the PD group (p < 0.05). HA treatment attenuated alveolar bone loss and improved local and systemic oxidative stress parameters in ligature-induced PD rats., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The expansion of human activities in northern Colombia has increased human-snake encounters, particularly with venomous Porthidium lansbergii lansbergii . Given the limited knowledge of systemic envenomation effects and previous studies focusing only on early murine symptoms, this investigation aimed to describe the time-course physiopathology of P. lansbergii lansbergii envenomation following intramuscular injection in vivo ., Methods: Venom was inoculated in the gastrocnemius muscles of Swiss Webster mice, and blood, urine, and tissue samples were taken at different times to evaluate lethality and biochemical markers of renal function and oxidative stress., Results: This study reports the first intramuscular LD 50 for P. lansbergii lansbergii venom at 24.83 mg/Kg. Administering 80% of this LD 50 induced early signs of renal injury, evidenced by urinary biomarkers over 24 h. The antioxidant activity was found at low levels in kidney tissue throughout the evaluated time post-envenomation. Malondialdehyde activity increased at the earliest point, while proinflammatory activity increased later. Urine metabolomics revealed elevated taurine and allantoin in the envenomed groups., Discussion: Compensatory mechanisms in response to oxidative stress and tissue damage induced by the venom were evident in the envenomed mice over the evaluated time. However, histological analysis revealed evidence of pro-inflammatory processes occurring only at early times. Metabolomic analyses of urine samples identified taurine as a potential early biomarker of elevated oxidative stress and protein and creatinine levels., Conclusions: P. lansbergii lansbergii venom induces alterations in murine renal tissue, affecting urinary biomarkers of kidney function within hours post-envenomation. Delayed proinflammatory effects may suggest an antioxidant imbalance in the envenomed mice, with unknown long-term effects. Further research on the role of oxidative stress and inflammation in renal structure and function following envenomation is necessary, emphasizing the need for prompt clinical management., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chitosan (CS) is a promising polymeric biomaterial for use in scaffolds for in vitro skin models and wound dressings, owing to its non-antigenic and antimicrobial properties. However, CS often exhibits insufficient physicochemical properties, mechanical strength, and bioactivity, limiting its efficacy in demanding applications. To address these challenges, cotton cellulose nanofibers (CNFs) represent a promising nanomaterial for enhancing CS-based scaffolds in tissue engineering. CNF offers superior stiffness, and mechanical properties that enhance cellular adhesion and proliferation, both crucial for effective tissue regeneration and healing. This study aimed to develop and characterize a scaffold combining cotton CNF and CS, focusing on its cytocompatibility with human fibroblasts and keratinocytes. The cotton CNF/CS scaffold was fabricated using the casting technique, and its physicochemical properties and cellular compatibility were assessed in vitro . The results demonstrated that incorporating cotton CNF significantly enhanced the stability of the CS matrix. The CS scaffold with 1000 μg ml -1 of cotton CNF exhibited increased roughness and reduced rupture strain compared to the pure CS scaffold. The cotton CNF/CS scaffold effectively promoted the adhesion, viability, proliferation, migration, and collagen synthesis of skin cells. Notably, increased cell viability was observed in human fibroblasts cultured on scaffolds with higher concentrations of cotton CNF (100 and 1000 μg ml -1 ). Based on the findings, the cotton CNF/CS scaffold demonstrates enhanced physicochemical properties and bioactivity, making it a promising candidate for the development of in vitro human skin models and wound healing dressings., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objectives: to analyze the factors associated with maternal well-being during childbirth among postpartum women in Minas Gerais., Methods: a cross-sectional study nested within a cohort was conducted with postpartum women in a municipality of Minas Gerais. The Maternal Well-being in Childbirth Scale 2 was used. The prevalence of maternal well-being during childbirth was estimated. The magnitude of the association between maternal distress and care practices was estimated using the Prevalence Ratio (PR), applying Poisson regression., Results: a total of 183 postpartum women aged between 15 and 46 years participated, with 26.2%, 27.9%, and 45.9% reporting excellent, adequate, and poor well-being during childbirth care, respectively. Maternal distress was more prevalent among women who underwent cesarean sections (PR = 1.60) and those who did not receive breastfeeding information (PR = 1.59)., Conclusions: a high prevalence of maternal distress during childbirth was observed, associated with cesarean delivery and the lack of breastfeeding information.

Background/aim: Lung cancer accounts for the largest percentage of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. Gefitinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown marked efficacy in NSCLC patients with an EGFR mutation. However, gefitinib resistance because of ABCG2 polymorphisms such as rs2231142(421C > A) might limit its clinical use., Patients and Methods: This meta-analysis followed the PRISMA guidelines and investigated the impact of the ABCG2 rs2231142 variant on gefitinib treatment outcomes in patients with NSCLC, using the PECOS model for study selection., Results: A total of 585 NSCLC patients treated with gefitinib were assessed for the association between genetic variants of the ABC transporter genes, specifically the ABCG2 C421A polymorphism, and clinical outcomes. No association was found between the ABCG2 C421A polymorphism and response to gefitinib chemotherapy (p=0.653; I2=0%). Similarly, no correlation was observed with gefitinib-induced skin rash (p=0.161177; I 2 =0%), diarrhea (p=0.064441), hepatotoxicity (p=0.210916; I 2 =0%), or interstitial pneumonia (p=0.138937)., Conclusion: The ABCG2 rs2231142 polymorphism plays a significant role in the clinical outcomes of patients with EGFR-mutated NSCLC treated with gefitinib, warranting further investigation to clarify its impact on treatment efficacy and patient safety., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background & Aims: Gender-affirming hormone therapy (GAHT) is essential for transgender individuals seeking body modifications. For transfeminine people assigned male at birth, GAHT typically involves a combination of antiandrogens and estrogens. Despite its importance, the scientific literature presents inconsistencies regarding the effects of these hormones on nutritional status, body composition, and biochemical markers. This study aims to evaluate the impact of estradiol enanthate and dihydroxyprogesterone acetophenide (E2EN/DHPA) hormonal treatment, in conjunction with resistive physical exercise, on body composition and metabolic profiles., Methods: Twenty-eight male rats were divided into three groups: MO (control group, n = 8), receiving sesame oil vehicle; MH (n = 11), receiving E2EN/DHPA; and MEH (n = 9), receiving E2EN/DHPA along with physical exercise. The hormonal treatment was administered every ten days for two months, while the exercise regimen involved stair climbing with progressively increasing weights, performed five times weekly for seven weeks. Evaluated parameters included body mass index (BMI), body composition (fat and lean mass), bone mineral density (BMD), and lipid profile (triglycerides, HDL-C, LDL-C)., Results: The rats that received E2EN/DHPA showed significant changes in body composition and BMI, regardless of exercise. The MH group had increased body fat, while both the MH and MEH groups had decreased bone area and mineral content. However, BMD remained the same across all groups. Elevated triglyceride levels were observed, and the MEH group also had reduced LDL-C levels. HDL-C levels did not show significant variation., Conclusion: The study's findings show similarities to changes seen in transfeminine individuals undergoing GAHT with estrogen and antiandrogens. These changes include decreased muscle mass, increased body fat, preserved bone mineral density, and elevated triglycerides. The study also found that resistance exercise positively impacted lipid profiles, particularly in reducing LDL-C. These results highlight the need for further research and comparative trials on hormone therapy regimens., Competing Interests: Declaration of competing interest The authors declare no commercial or financial affiliations that could be construed as a potential conflict of interest affecting the research presented in this paper., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM 817 , which selectively activates the chloride-permeable channel PSAM 4 -GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM 817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM 817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM 4 -GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy., (© 2024. The Author(s).)

Myracrodruon urundeuva , popularly known as 'aroeira-do-sertão', a large tree, with a tall trunk. Belonging to the Anacardiaceae family, it occurs in the 'caatinga' and dry forests of Brazil, from Ceará to the states of Paraná and Mato Grosso do Sul. The present study aimed to analyse the whitening and antioxidant activities of the aqueous extract of the leaves of Myracrodruon urundeuva (AELMU). Inhibition of the tyrosinase enzyme, as well as its copper chelating capacity and antioxidant effect were evaluated. The AELMU (at 2000 µg/mL) showed excellent inhibitory action (83.76%) on tyrosinase by chelating the copper ion while kojic acid at the same concentration inhibited 97.81%. Moreover, the extract displayed important antioxidant activity (inhibited 76,46% of the 2,2-diphenyl-1-picrylhydrazyl radical - DPPH; 49,59% of thiobarbituric acid reactive substances and 51,07% of the hydroxyl radical). Thus, the extract under study is promising for use in cosmetics, given its multifactorial action.

Background: This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software., Methods: This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis., Results: There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy., Conclusions: Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Maternal-foetal transmission of Chagas disease (CD) affects newborns worldwide. Although Benznidazole and Nifurtimox therapies are the standard treatments, their use during pregnancy is contra-indicated. The effectiveness of trypanocidal medications in preventing congenital Chagas Disease (cCD) in the offsprings of women diagnosed with CD was highly suggested by other studies., Methods: We performed a systematic review and meta-analysis of studies evaluating the effectiveness of treatment for CD in women of childbearing age and reporting frequencies of cCD in their children. PubMed, Scopus, Web of Science, Cochrane Library, and LILACS databases were systematically searched. Statistical analysis was performed using Rstudio 4.2 using DerSimonian and Laird random-effects models. Heterogeneity was examined with the Cochran Q test and I2 statistics. A p-value of <0.05 was considered statistically significant., Results: Six studies were included, comprising 744 children, of whom 286 (38.4%) were born from women previously treated with Benznidazole or Nifurtimox, trypanocidal agents. The primary outcome of the proportion of children who were seropositive for cCD, confirmed by serology, was signigicantly lower among women who were previously treated with no congenital transmission registered (OR 0.05; 95% Cl 0.01-0.27; p = 0.000432; I2 = 0%). In women previously treated with trypanocidal drugs, the pooled prevalence of cCD was 0.0% (95% Cl 0-0.91%; I2 = 0%), our meta-analysis confirms the excellent effectiveness of this treatment. The prevalence of adverse events in women previously treated with antitrypanocidal therapies was 14.01% (95% CI 1.87-26.14%; I2 = 80%), Benznidazole had a higher incidence of side effects than Nifurtimox (76% vs 24%)., Conclusion: The use of trypanocidal therapy in women at reproductive age with CD is an effective strategy for the prevention of cCD, with a complete elimination of congenital transmission of Trypanosoma cruzi in treated vs untreated infected women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moraes 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: In soccer, most studies evaluate metabolic profile changes in male athletes, often using data from a single match. Given the current landscape of women's soccer and the effects of biological sex on the physiological response and adaptation to exercise, more studies targeting female athletes and analyzing pre- and post-game moments throughout the season are necessary., Objectives: To describe the metabolomics profile of female soccer athletes from an elite team in Brazil. The study observed the separation of groups in three pre- and post-game moments and identified the discriminating metabolites., Methods: The study included 14 female soccer athletes. Urine samples were collected and analyzed using Nuclear Magnetic Resonance in pre-game and immediate post-game moments over three national championship games. The metabolomics data were then used to generate OPLS-DA and VIP plots., Results: Forty-three metabolites were identified in the samples. OPLS-DA analyses demonstrated a progressive separation between pre-post conditions, as supported by an increasing Q 2 value (0.534, 0.625, and 0.899 for games 1, 2 and 3, respectively) and the first component value (20.2% and 19.1% in games 1 and 2 vs. 29.9% in game 3). Eight out of the fifteen most discriminating metabolites appeared consistently across the three games: glycine, formate, citrate, 3-hydroxyvalerate, glycolic acid, trimethylamine, urea, and dimethylglycine., Conclusion: The main difference between the three games was the increasing separation between groups throughout the championship. Since the higher VIP-scores metabolites are linked to energy and protein metabolism, this separation may be attributed several factors, one being the accumulation of fatigue., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To investigate the effects of high-intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes., Materials and Methods: Forty-eight Wistar rats were divided into four groups: non-trained (NT); non-trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed., Results: PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p < .05), while HIIT attenuated these changes (p < .05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]-α, interleukin [IL]-10, TNF-α/IL-10 and IL-1β/IL-10 ratios, p < .05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p < .05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p < .05)., Conclusions: HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The understanding of how central metabolism and fermentation pathways regulate antimicrobial susceptibility in the anaerobic pathogen Bacteroides fragilis is still incomplete. Our study reveals that B. fragilis encodes two iron-dependent, redox-sensitive regulatory pirin protein genes, pir1 and pir2. The mRNA expression of these genes increases when exposed to oxygen and during growth in iron-limiting conditions. These proteins, Pir1 and Pir2, influence the production of short-chain fatty acids and modify the susceptibility to metronidazole and amixicile, a new inhibitor of pyruvate: ferredoxin oxidoreductase in anaerobes. We have demonstrated that Pir1 and Pir2 interact directly with this oxidoreductase, as confirmed by two-hybrid system assays. Furthermore, structural analysis using AlphaFold2 predicts that Pir1 and Pir2 interact stably with several central metabolism enzymes, including the 2-ketoglutarate:ferredoxin oxidoreductases Kor1AB and Kor2CDAEBG. We used a series of metabolic mutants and electron transport chain inhibitors to demonstrate the extensive impact of bacterial metabolism on metronidazole and amixicile susceptibility. We also show that amixicile is an effective antimicrobial against B. fragilis in an experimental model of intra-abdominal infection. Our investigation led to the discovery that the kor2AEBG genes are essential for growth and have dual functions, including the formation of 2-ketoglutarate via the reverse TCA cycle. However, the metabolic activity that bypasses the function of Kor2AEBG following the addition of phospholipids or fatty acids remains undefined. Overall, our study provides new insights into the central metabolism of B. fragilis and its regulation by pirin proteins, which could be exploited for the development of new narrow-spectrum antimicrobials in the future., (© 2024 The Author(s). MicrobiologyOpen published by John Wiley & Sons Ltd.)

The persistence of symptoms for more than three months following infection with severe acute respiratory syndrome coronavirus 2 is referred to as "Long COVID". To gain a deeper understanding of the etiology and long-term progression of symptoms, this study aims to analyze the prevalence of Long COVID and its associated factors in a cohort of Brazilian adults and elders, twelve months after hospital discharge. An observational, prospective, and follow-up study was performed with a cohort of adults and older adults diagnosed with COVID-19 in 2020 in the State of Paraná, Brazil. Twelve months after hospital discharge, patients answered a phone questionnaire about the persistence of symptoms after three levels of exposure to COVID-19's acute phase (ambulatory, medical ward, and intensive care unit). According to the characteristics of participants, the prevalence of Long COVID-19 was calculated, and logistic regression analyses were conducted. We analyzed data from 1822 participants (980 adults [≥18-<60 years] and 842 older people [≥60 years]) across three exposure levels. The overall Long COVID prevalence was 64.2%. Long COVID was observed in 646 adults (55%; of which 326 were women) and 523 older people (45%; of which 284 were women). Females had a higher prevalence of long-term symptoms (52%) compared with men. The most common post-COVID-19 conditions in the 12-month follow-up were neurological (49.8%), followed by musculoskeletal (35.1%) and persistent respiratory symptoms (26.5%). Male individuals were less likely to develop Long COVID (aOR = 0.50). Other determinants were also considered risky, such as the presence of comorbidities (aOR = 1.41). Being an adult and having been hospitalized was associated with the development of Long COVID. The risk of developing Long COVID was twice as high for ward patients (aOR = 2.53) and three times as high for ICU patients (aOR = 3.56) when compared to non-hospitalized patients. Presenting clinical manifestations of digestive (aOR = 1.56), endocrine (aOR = 2.14), cutaneous (aOR = 2.51), musculoskeletal (aOR = 2.76) and psychological systems (aOR = 1.66) made adults more likely to develop Long COVID. Long COVID was present in a large proportion of people affected by the SARS-CoV-2 infection. Presence of Long COVID symptoms displayed a dose-response relationship with the level of disease exposure, with a greater prevalence of symptoms associated with the severe form in the acute period.

Drug delivery selectivity is a challenge for cancer treatment. A hybrid pegylated pH-sensitive liposome-extracellular vesicle isolated from human breast cancer cell MDA-MB-231 was developed to investigate its in vitro activity against breast cancer cells of different molecular profiles to overcome this inconvenience. The hybrid nanosystem was produced by film hydration, and doxorubicin (DOX) was encapsulated in this system using the ammonium sulfate gradient method. The characterization of this hybrid nanosystem revealed a mean diameter of 140.20 ± 2.70 nm, a polydispersity index of 0.102 ± 0.033, an encapsulation efficiency of doxorubicin of 88.9% ± 2.4, and a great storage stability for 90 days at 4 °C. The fusion of extracellular vesicles with liposomes was confirmed by nanoflow cytometry using PE-conjugated human anti-CD63. This hybrid nanosystem demonstrated cytotoxicity against human breast cancer cell lines with different molecular subtypes, enhanced anti-migration properties, and exhibited similar cellular uptake to the free DOX treatment. Preliminary acute toxicity assessments using Balb/C female mice indicated a median lethal dose of 15-17.5 mg/kg, with no evidence of splenic, liver, heart, bone marrow, and renal damage at a dose of 15 mg/kg. These findings suggest the hybrid formulation as a versatile nanocarrier for the treatment of various breast cancer subtypes.

Zika virus (ZIKV) outbreak caused one of the most significant medical emergencies in the Americas due to associated microcephaly in newborns. To evaluate the impact of ZIKV infection on neuronal cells over time, we retrieved gene expression data from several ZIKV-infected samples obtained at different time point post-infection (pi). Differential gene expression analysis was applied at each time point, with more differentially expressed genes (DEG) identified at 72h pi. There were 5 DEGs (PLA2G2F, TMEM71, PKD1L2, UBD, and TNFAIP3 genes) across all timepoints, which clearly distinguished between infected and healthy samples. The highest expression levels of all five genes were identified at 72h pi. Taken together, our results indicate that ZIKV infection greatly impacts human neural cells at early times of infection, with peak perturbation observed at 72h pi. Our analysis revealed that all five DEGs, in samples of ZIKV-infected human neural stem cells, remained highly upregulated across the timepoints evaluated. Moreover, despite the pronounced inflammatory host response observed throughout infection, the impact of ZIKV is variable over time. Finally, the five DEGs identified herein play prominent roles in infection, and could serve to guide future investigations into virus-host interaction, as well as constitute targets for therapeutic drug development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodrigues 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.)

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes 1-6 ; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Aspidosperma nitidum Benth (Apocynaceae) is a tree found in Brazil especially in the Amazonia region, known as "carapanaúba", being used by indigenous and cabloco population in folk medicine in the treatment of malaria, leprosy, rheumatism, cancer, diabetes and inflammatory disorders. However, there are no scientific reports, up to now, to evidence its popular use as anti-inflammatory and healing agent., Aim of the Study: This study aimed to isolate indole alkaloids, as well as investigate the safety, anti-inflammatory and healing properties of hydroethanol extract from the stem barks of Aspidosperma nitidum Benth (An)., Material and Methods: The compounds were isolated using diverse chromatographic methodologies and the structures were determined by extensive spectroscopic analyses. The safety was evaluated in vitro through 3-methyl-[4-5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using murine fibroblast (3T3) and monkey kidney (Vero E6) cell lines and by the hemolytic assay, as well as, in vivo, through acute toxicity model, which the mice received a single dose of 2000 mg/kg of An, by intra-gastric (i.g.) route, and behavioral, hematological and biochemical parameters were evaluated. The anti-edematogenic effect was monitored through carrageenan-induced paw edema model, in which the rodents were treated with 50, 100 and 200 mg/kg of An by i. g., the percentage of edema (0-4 h), myeloperoxidase (MPO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) levels were quantified. The anti-inflammatory activity was demonstrated through the zymosan-air-pouch model, in which the animals were treated with 50, 100 and 200 mg/kg of An by i. g, and the leukocytes number, MPO, total protein and cytokines levels were determined. In addition, the healing potential was evaluated through a skin wound model, in which the mice received 50, 100 and 200 mg/mL of An in wound area, and the wound skins were photographed and the area calculated., Results: In total, five compounds were isolated in the An, being a new 8,9-dinorneolignan glucoside and four known indole alkaloids. The MTT and hemolytic assays, in all concentrations of the extract, demonstrated not be cytotoxic. Acute toxicity model also evidenced no sign of toxicity or significant changes on the behavior, biochemical and hematological parameters after use of the extract. In the edematogenic model, the An reduced significantly the percentage of edema, as well as, the MPO and pro-inflammatory cytokines levels. The same form, An revealed to be efficient in decreasing the leukocytes migration (mainly polymorphonuclears), total proteins, MPO and cytokines concentrations in the zymosan-air-pouch assay. Moreover, the An revealed a healing effect, reducing the area of the skin wound., Conclusion: Ours results evidence in the first time, the anti-inflammatory and healing property of An, justifying its use in traditional medicine. Moreover, include cytotoxicity in vitro and acute toxicity in vivo tests, which indicate the safety of use of the extract., 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: Several studies point to antibacterial properties and beneficial effects of honey on scar tissue formation, which is a low-cost and easy-to-use option. This study aimed to compare honey versus a placebo for cicatrization and pain control of obstetric wounds, and determine if one is superior to the other, in terms of efficacy, through a meta-analysis., Methods: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent investigators identified randomized controlled trials (RCTs) comparing honey and a placebo for obstetric wounds. The primary outcomes were wound healing and pain control., Results: Five randomized controlled trials and 353 patients were included, of whom, 177 (50.1%) were treated with honey. Differences were not found in the final wound healing between the honey and placebo groups (MD -0.34; 95% CI -1.13, 0.44; p = 0.39); however, there was a decrease in pain levels in the middle of the treatment (SMD -0.54; 95% CI 0.83 to 0.25, p = 0.03), reduction in the use of pain medication (ORR 0.26; 95% CI 0.08, 0.86; p = 0.03), increase in personal satisfaction in women who underwent the intervention (ORR 0.81; 95% CI 0.65, 0.98), and reduction in complications., Conclusion: According to the study results, honey treatments showed greater efficiency and provided benefits to the patients by accelerating wound healing and decreasing reported pain.

Aims and Objectives: This paper aims to: (a) determine the personal, sociodemographic, clinical, behavioural, and social characteristics of older Brazilians with clinical evidence of long COVID; (b) evaluate perceived quality of life and determine its association with personal, sociodemographic, behavioural, clinical and social variables; and (c) assess significant predictors of high perceived QoL., Background: Given the inherent vulnerabilities of the ageing process, the older people are an at-risk group for both contagion of SARS-CoV-2 and the perpetuation of residual symptoms after infection, the so-called long COVID or post-COVID syndrome., Design: A cross-sectional survey design using the STROBE checklist., Methods: Brazilian older people with long COVID syndrome (n = 403) completed a phone survey measuring personal, sociodemographic, behavioural, clinical, and social characteristics, and perceived Quality of Life (QoL). Data were collected from June 2021-March 2022. A multiple linear regression model was performed to identify salient variables associated with high perceived QoL., Results: The mean age of participants was 67.7 ± 6.6 years old. The results of the multivariate regression model showed that race, home ownership, daily screen time, musculoskeletal and anxiety symptoms, and work situation were the significant predictors of QoL among COVID-19 survivors., Conclusions: Knowledge about the persistence of physical, emotional, and social symptoms of COVID-19 can help nurses and other healthcare providers to improve the management of survivors, bringing benefits to the whole society., Relevance to Clinical Practice: Given the novelty of long-COVID and its heterogeneous trajectory, interventions focusing on the repercussions and requirements unique to more vulnerable older persons should be developed and these aspects should be included in public health recommendations and policymakers' concerns., Patient or Public Contribution: No patient or public contribution was required to design, to outcome measures or undertake this research. Patients/members of the public contributed only to the data collection., (© 2023 John Wiley & Sons Ltd.)

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

Ethnopharmacological Relevance: Egletes viscosa (L.) (macela) is a native wild herb that can be found in different states of northeastern Brazil. The infusions of its flower buds are traditionally used for the treatment of gastrointestinal disorders. E. viscosa possesses two chemotypes (named A and B), distinguishable by the composition of the essential oil from the flower buds. Although there are previous studies of the gastroprotective effect of the isolated constituents of E. viscosa, its infusions have not been investigated yet., Aim of the Study: The present study aimed to evaluate and compare the chemical composition and the gastroprotective effect of flower bud infusions of E. viscosa from chemotype A (EVCA) and chemotype B (EVCB)., Materials and Methods: Sixteen infusions were brewed with flower buds according to the traditional preparation mode and were analyzed through a UPLC-QTOF-MS/MS based metabolomic approach for determination of their metabolic fingerprints and quantification of bioactive compounds. Afterward, these data were analyzed by chemometric methods (OPLS-DA) for discrimination of the two chemotypes. Additionally, infusions of EVCA and EVCB (50, 100 and 200 mg/kg, p.o.) were evaluated on gastric ulcers induced by absolute ethanol (96%, 0.2 mL, p.o.) in mice. To elucidate the gastroprotective mechanisms, the effect of EVCA and EVCB on gastric acid secretion and gastric wall mucus was determined and the role of TRPV1 channels, prostaglandins, nitric oxide and K ATP channels were assessed. Moreover, the oxidative stress-related parameters and the histological aspects of the stomach tissue were analyzed., Results: The chemotypes can be discriminated from each other using UPLC-QTOF-MS/MS chemical fingerprints. Both chemotypes presented similar chemical compositions, consisting basically of caffeic acid derivatives, flavonoids and diterpenes. The quantification of bioactive compounds demonstrated that chemotype A possesses more ternatin, tanabalin and centipedic than chemotype B. EVCA and EVCB (50, 100 and 200 mg/kg, p.o.) significantly decreased the severity of ethanol-induced gastric lesions, as shown by a reduction in histological alterations and leucocyte infiltration in gastric tissue. The gastroprotective mechanism of both infusions involves an antioxidant effect, maintenance of gastric mucus and reduction gastric secretion. Stimulation of endogenous prostaglandins and nitric oxide release, activation of TRPV1 channels, and K ATP channels are also involved in the gastroprotection of the infusions., Conclusion: The gastroprotective effect of EVCA and EVCB was equivalent and mediated through antioxidant and antisecretory actions, including the activation of TRPV1 receptors, stimulation of endogenous prostaglandins and nitric oxide, and opening of K ATP channels. The presence of caffeic acid derivatives, flavonoids and diterpenes in both infusions is involved in mediating this protective effect. Our findings support the traditional use of infusions of E. viscosa for gastric disorders regardless of the chemotype., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Identify the one-year survival rate and major complications in patients submitted to pneumonectomy for infectious disease., Methods: Retrospective data from all cases of infectious disease pneumonectomy over the past 10 years were collected from two reference centers. The authors analyzed: patient demographics, etiology, laterality, bronchial stump treatment, presence of previous pulmonary resection, postoperative complications in the first 30 days, the treatment used in pleural complications, and one-year survival rate., Results: 56 procedures were performed. The average age was 44 years, with female predominance (55%). 29 cases were operated on the left side (51%) and the most frequent etiology was post-tuberculosis (51.8%). The overall incidence of complications was 28.6% and the most common was empyema (19.2%). Among empyema cases, 36.3% required pleurostomy, 27.3% required pleuroscopy and 36.3% underwent thoracoplasty for treatment. Bronchial stump fistula was observed in 10.7% of cases. From all cases, 16.1% were completion pneumonectomies and 62.5% of these had some complication, a significantly higher incidence than patients without previous surgery (p = 0.0187). 30-day in-hospital mortality was (7.1%) with 52 cases (92.9%) and 1-year survival. The causes of death were massive postoperative bleeding (1 case) and sepsis (3 cases)., Conclusions: Pneumonectomy for benign disease is a high-risk procedure performed for a variety of indications. While morbidity is often significant, once the perioperative risk has passed, the one-year survival rate can be very satisfying in selected patients with benign disease., 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.)

Bile salt hydrolase (BSH) in Bacteroides is considered a potential drug target for obesity-related metabolic diseases, but its involvement in colon tumorigenesis has not been explored. BSH-expressing Bacteroides is found at high abundance in the stools of colorectal cancer (CRC) patients  with overweight and in the feces of a high-fat diet (HFD)-induced CRC mouse model. Colonization of B. fragilis 638R, a strain with low BSH activity, overexpressing a recombinant bsh gene from B. fragilis NCTC9343 strain, results in increased unconjugated bile acids in the colon and accelerated progression of CRC under HFD treatment. In the presence of high BSH activity, the resultant elevation of unconjugated deoxycholic acid and lithocholic acid activates the G-protein-coupled bile acid receptor, resulting in increased β-catenin-regulated chemokine (C-C motif) ligand 28 (CCL28) expression in colon tumors. Activation of the β-catenin/CCL28 axis leads to elevated intra-tumoral immunosuppressive CD25 + FOXP3 + T reg cells. Blockade of the β-catenin/CCL28 axis releases the immunosuppression to enhance the intra-tumoral anti-tumor response, which decreases CRC progression under HFD treatment. Pharmacological inhibition of BSH reduces HFD-accelerated CRC progression, coincident with suppression of the β-catenin/CCL28 pathway. These findings provide insights into the pro-carcinogenetic role of Bacteroides in obesity-related CRC progression and characterize BSH as a potential target for CRC prevention and treatment., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment.

The suspension of social activities combined with health insecurity, uncertainty and fear of COVID-19 may influence physical activity practice. We aimed to investigate the relationship between the fear of COVID-19 and anxiety on physical activity patterns during the pandemic period. This cross-sectional study was performed in a sample of 520 Brazilian participants recruited by online sampling and snowball method. We assessed demographic variables, health perceptions, anxiety, fear of COVID-19 and physical activity characteristics. Both fear scores and anxiety were higher in woman (p < 0.0001). We observed a remarkable reduction in the frequency and intensity of physical activity and a modification in the exercise practice environment (from gym or sports centers to home-based physical activity) (p < 0.05). Sedentary (sitting) behavior increased during pandemic both in the weekdays and in the weekend (p < 0.0001). Participants who have never been infected were more prone of being classified in higher levels for physical activity (OR: 1.916, CI = 1.043-3.521) versus those who were previously infected (p = 0.05). Participants with a low or moderate level of physical activity before the pandemic presented lower chances of being classified as high physical activity level during the pandemic in comparison to those with high level before pandemic (p < 0.001). The Fear of Covid-19 score was negatively associated with the physical activity level (the higher the fear, the lower the level of physical activity); that is, for every increase in scale score, the odds of vigorous physical activity decreased 3%. In conclusion, fear of COVID-19 and previous contact with the virus negatively influenced physical activity practice.

Objectives: Bacteroides fragilis is an anaerobic bacterium that is commonly found in the human gut microbiota and an opportunistic pathogen in extra-intestinal infections. B. fragilis displays a robust response to oxidative stress which allows for survival in oxygenated tissues such as the peritoneal cavity and lead to the formation of abscesses. In this study, we investigated the synergy of the oxidative stress response regulators OxyR and BmoR in the ability of B. fragilis to resist oxidative damage and to survive in extra-intestinal infection., Methods: A ΔbmoR ΔoxyR double mutant B. fragilis strain was constructed, and its oxidative stress response was compared to parental and single mutant strains in phenotypical assays and gene expression analysis. The pathogenic potential in an in vivo mouse model of abscess formation was also evaluated., Results: Expression analysis showed a coordinated control of thioredoxin C (trxC) gene expression by BmoR and OxyR during oxygen exposure, with upregulation of trxC in the bmoR mutant strain (4.9-fold increase), downregulation in the oxyR mutant (2.5-fold decrease), and an intermediate level of deregulation (2-fold increase) in the double mutant strain compared to the parent strain. Expression analysis during oxidative stress conditions also showed that BmoR is a major repressor of the CoA-disulfide reductase gene (upregulated 47-fold in the bmoR mutant) while OxyR plays a minor repression role in this gene (upregulated 2.5-fold in the oxyR mutant). Exposure to atmospheric oxygen for up to 72 h revealed that the deletion of bmoR alone had no significant effect in in vitro survival phenotype assays, though it partially abolishes the OxyR sensitivity phenotype in the bmoR/oxyR double mutant strain compared to oxyR mutant. In vivo assays showed that bmoR and oxyR mutants were significantly impaired in the formation and development of abscesses compared to the parent strain in an experimental intra-abdominal infection mouse model., Conclusion: Although the full extent of genes whose expression are modulated by BmoR and OxyR is yet to be defined, we present evidence that these regulators have overlapping functions in B. fragilis response to oxidative stress and ability to form abscess in extra-intestinal tissues., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Withajardins, uncommon modified withanolide-type steroids, have been isolated exclusively from plants of the Solanaceae family so far. Two undescribed withajardins and the known tuboanosigenin were isolated from the hexane/EtOAc 1:1 extract from Athenaea velutina leaves. Their structures were established by an extensive analysis of 1D and 2D-NMR and HRMS data. The absolute configuration was determined by X-ray diffraction (withajardin L and tuboanosigenin) and circular dichroism (CD) analyses (withajardin M). The anti-inflammatory activity of compounds was evaluated through the inhibition of the lipopolysaccharide (LPS)-induced nitric oxide (NO), TNF-α, and IL-6 release in RAW264.7 cells. The cell viability effects to RAW 264.7 cells showed IC 50 values of 74.4-354.4 μM. The compounds attenuated LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 in RAW264.7 cells., 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 © 2022 Elsevier Ltd. All rights reserved.)

Exosome-liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.

Objective: To analyze the user embracement records of the Family Health Strategy (FHS) teams in a city in the North of Minas Gerais, Brazil., Methods: This was a cross-sectional and descriptive study based on secondary data. We analyzed FHS nurse and pharmacist service user embracement records for the period from March 2019 to February 2020. The total number of user embracement records and total number of records per service user were calculated according to the codes used by the International Classification of Primary Care (ICPC-2)., Results: A total of 20,513 user embracement records were identified, the majority for female health service users (63.5%), those aged between 20 and 59 years (52.5%) and related to the ICPC-2 Procedure chapter (18.5%). User embracement activities were carried out for only 31.1% of the population resident in the FHS territories., Conclusion: Having knowledge about user embracement in the FHS and the main reasons for it highlights the importance of interventions targeting prevalent groups, in addition to contributing to the organization of health care.

Introduction: Since 2020, the world has been going through a viral pandemic with a high morbidity and mortality rate along with the potential to evolve from an acute infection to post-acute and long-COVID, which is still in the process of elucidation. Diagnostic and prognostic research is essential to understand the complexity of factors and contexts involving the illness's process. This protocol introduces a study strategy to analyse predictors, sequelae, and repercussions of COVID-19 in adults and older adults with different disease severities in the State of Paraná, Brazil., Methods and Analysis: A mixed-methods sequential explanatory design. The quantitative data will be conducted by an ambispective cohort study, which will explore the manifestations of COVID-19 for 18 months, with nearly 3000 participants with confirmed diagnoses of COVID-19 (reverse transcription-PCR test) between March and December of 2020, retrieved from national disease reporting databases, over 18 years old, living in a Brazilian State (Paraná) and who survived the viral infection after being discharged from a health service. Data collection will be conducted through telephone interviews, at two different occasions: the first will be a recall 12 months after the acute phase as a retrospective follow-up, and the second will be another prospective interview, with data of the following 6 months. For the qualitative step, Grounded Theory will be used; participants will be selected from the cohort population. The first sample group will be composed of people who were discharged from the intensive care unit, and other sample groups will be composed according to theoretical saturation. The qualitative data will follow the temporal design and classification of the disease provided for in the cohort., Ethics and Dissemination: Ethics approval was granted by the State University of Maringá, under opinion number: 4 165 272 and CAAE: 34787020.0.0000.0104 on 21 July 2020, and Hospital do Trabalhador (Worker's Hospital), which is accountable for the Health Department of the State of Paraná, under opinion number: 4 214 589 and CAAE: 34787020.0.3001.5225 on 15 August 2020. The participants will verbally consent to the research, their consent will be recorded, and the informed consent form will be sent by mail or email. Outcomes will be widely disseminated through peer-reviewed manuscripts, conference presentations, media and reports to related authorities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Empyema is a complication of talc-pleurodesis that may lead to further surgical intervention and death. Therefore, the present study's objective was to identify the risk factors for the development of post-pleurodesis empyema after talc slurry pleurodesis in order to better select patients for this procedure and minimize its morbidity., Methods: Patients with malignant pleural effusion who underwent talc slurry pleurodesis at the present institution from January 2018 to January 2020 were retrospectively analyzed. Post-pleurodesis empyema was defined as pleural infection up to 30 days after pleurodesis. Using Cox regression analysis, significant prognostic factors for the development of empyema were examined., Results: Of the 86 patients identified for inclusion in the study, 62 were women (72%). Their mean age was 56.3±12.6 years. The median pleural drainage time was 9 days, and 20 patients (23.3%) developed empyema. In the univariate analysis, both drainage time (p = 0.038) and the use of antibiotics prior to pleurodesis (p < 0.001) were risk factors for pleural empyema. Multivariate analysis also identified the use of antibiotics as an independent risk factor (Odds Ratio [OR] 9.81; 95% Confidence Interval [95% CI] 2.87‒33.54). Although the pulmonary expansion was not associated with empyema in the multivariate analysis, patients with less than 50% pulmonary expansion had a 4.5-times increased risk of empyema (95% CI 0.90‒22.86; p = 0.067), and patients with 50‒70% pulmonary expansion had a 3.8-times increased risk of empyema (95% CI 0.98‒15; p = 0.053) after pleurodesis., Conclusion: The study suggests that antibiotic therapy prior to talc slurry pleurodesis may increase the risk of developing empyema. Furthermore, pleurodesis should be considered with caution in patients with long-duration chest tube placement and incomplete lung expansion., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Ethnopharmacological Relevance: Harpalyce brasiliana Benth (Leguminosae) is a shrub endemic to Brazil, popularly known as "snake's root." This species is used in folk medicine for the treatment of inflammation and snakebites. However, up to now there is no scientific research to justify its popular use. The study aimed to characterize the phytochemical profile of the hydroethanol extract from the roots of H. brasiliana (Hb), to evaluate its antioxidant and anti-inflammatory potential, as well as to investigate its cytotoxicity and acute toxicity., Materials and Methods: The extract was obtained by maceration method using a solution of ethanol:water (70: 30, v/v). The phytochemical profile was obtained by liquid chromatography coupled to mass spectrometry. The cytotoxicity of extract (31-2000 μg/mL) was evaluated in vitro, by the 3-methyl-[4-5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method using murine macrophage and fibroblast cell lines (RAW 247.6 and 3T3, respectively) and by the hemolytic assay. For the in vivo acute toxicity, the extract (2000 mg/kg) was administered and after 14 days the weight (body and organs) and hematological and biochemical parameters were analyzed. Chemical free radical scavenging effect of the extract (125-2000 μg/mL) was investigated through diphenylpicryl hydrazine reduction, total antioxidant capacity, reducing power, hydroxyl radical scavenging, and iron and copper chelating assays. In vitro anti-inflammatory effect of the extract (125, 500, and 2000 μg/mL) was demonstrated through of nitric oxide (NO) analyzed in lipopolysaccharides stimulated RAW 264.7 cells. In vivo anti-inflammatory activities were evaluated in carrageenan-induced paw edema and zymosan-air-pouch models, with gavage administration (post-treatment) of extract at 100, 200, and 400 mg/kg. For the first animal model, the anti-edematogenic activity and myeloperoxidase (MPO) levels were investigated, while in the zymosan-air-pouch model the leukocyte number, MPO, total protein and pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels were quantified. In addition, the oxidative parameters such as malondialdehyde (MDA) and reduced glutathione (GSH) were determined., Results: The phytochemical profile revealed the presence of 20 compounds, mainly prenylated and geranylated pterocarpans. The extract demonstrated no cytotoxicity in erythrocytes, macrophages and fibroblasts cells at the tested concentrations, as well as no sign of toxicity and mortality or significant alterations on the hematological and biochemical parameters in the acute toxicity model. The extract was also able to neutralize chemical free radicals, with copper and iron chelating effect. For the NO dosage, the extract evidenced the reduction of expression of NO after the administration of the extract (500 and 2000 μg/mL). The edematogenic model revealed a decrease in paw edema and MPO level, while the zymosan-air-pouch model evidenced a reduction of leukocyte number (especially of polymorphornuclears), MPO production, and total protein and cytokine levels, and demonstrated the antioxidant effect through a decrease in MDA and increase in GSH parameters., Conclusion: This approach demonstrates for the first time that Hb is not cytotoxic, has low acute toxicity, and possesses antioxidant and anti-inflammatory properties in preclinical analyses, corroborating its popular use., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM)., Objective: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis., Methods: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms., Results: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05)., Conclusion: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients., (© 2022. The Author(s).)

Mineral coal extraction in Santa Catarina State (Brazil) Carboniferous Basin has degraded the local ecosystem, restricting the use of its areas. One of the biggest environmental impacts in the mining areas is the uncontrolled disposal of waste and sterile mining with high concentrations of pyrite, which in the presence of air and water is oxidized promoting the formation of acid mine drainage (AMD). These contaminants can be leached into water resources, restrict the use of water and soil, and cause threats to fauna and flora. This study aimed to characterize these areas as to the content of Cd, Pb, Ni and Zn metals in the tailings and waste resulting from coal mining and to survey the species of ferns and lycophytes present. Wastes and tailing samples and specimens of ferns and lycophytes were collected in 23 landfills in six municipalities in the region and in four underlying areas used as controls. Chemical and physical analyses (pH in water and pH in KCl, Ca, Mg, P, K, Na, Mn, Fe, Al, clay and OM contents) were carried out and the total contents of heavy metals Cd, Pb, Ni and Zn were determined. Sampling of ferns and lycophytes was carried out by walking. The levels of heavy metals, Cd, Ni and Zn, were below the prevention concentrations established by CONAMA Resolution 420/2009. Pb levels were above prevention values in four landfills. Sixteen species of ferns and one lycophyte were found, with hemicryptophytes the most frequent and helophytes the most adapted to the environment. Of the species found, Pteridium esculentum (G. Forst.) Cockayne, Pityrogramma calomelanos (L.) Link and Telmatoblechnum serrulatum (Rich.) Perrie, DJ Ohlsen & Brownsey demonstrated resistance to degraded and contaminated environments with Pb, which may constitute an alternative for project monitoring and environmental recovery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the spatial correlation between confirmed cases of covid-19 and the intensive care unit beds exclusive to the disease in municipalities of Paraná., Methods: This is an epidemiological study of ecological type which used data from the Epidemiological Report provided by the Department of Health of Paraná on the confirmed cases of covid-19 from March 12, 2020, to January 18, 2021. The number of intensive care beds exclusive to covid-19 in each municipality of Paraná was obtained by the Cadastro Nacional de Estabelecimentos de Saúde (CNES - National Registry of Health Establishments), provided online by the Departamento de Informática do Sistema Único de Saúde (Datasus - Informatics Department of the Brazilian Unified Health System). The Bivariate Moran's Index (local and global) was used to analyze the intensive care bed variable and spatial correlation, with a 5% significance level. LISA Map was used to identify critical and transition areas., Results: In the analyzed period, we found 499,777 confirmed cases of covid-19 and 1,029 intensive care beds exclusive to the disease in Paraná. We identified a positive spatial autocorrelation between the confirmed cases of covid-19 (0.404-p ≤ 0.001) and intensive care beds exclusive to the disease (0.085-p ≤ 0.001) and disparities between the regions of Paraná., Conclusion: Spatial analysis indicated that confirmed cases of covid-19 are related to the distribution of intensive care beds exclusive to the disease in Paraná, allowing us to find priority areas of care in the state regarding the dissemination and control of the disease.

Background: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in T1DM patients has not yet been clarified. Our study evaluated the effects of high-dose VD supplementation on HRQoL in T1DM., Methods: We performed a prospective study with 64 patients receiving cholecalciferol (4000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks, as part of a research protocol. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS)., Results: There was an improvement in global EQ-5D index, and analysing specifically the EQ-5D domains, we observed an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p < 0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control and insulin doses. We found correlations between final albuminuria and the dimensions: mobility (r = 0.6; p < 0.01), personal care (r = 0.7; p < 0.01), pain and discomfort (r = 0.6; p < 0.01) and habitual activities (r = 0.6; p < 0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL., Conclusion: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context., Trial Registration: (ISRCTN32601947), 03/06/2017 retrospectively registered., (© 2022. The Author(s).)

The opportunistic, anaerobic pathogen and commensal of the human large intestinal tract, Bacteroides fragilis strain 638R, contains six predicted TonB proteins, termed TonB1-6, four ExbBs orthologs, ExbB1-4, and five ExbDs orthologs, ExbD1-5. The inner membrane TonB/ExbB/ExbD complex harvests energy from the proton motive force (Δp), and the TonB C-terminal domain interacts with and transduces energy to outer membrane TonB-dependent transporters (TBDTs). However, TonB's role in activating nearly one hundred TBDTs for nutrient acquisition in B. fragilis during intestinal colonization and extraintestinal infection has not been established. In this study, we show that growth was abolished in the ΔtonB3 mutant when heme, vitamin B 12 , Fe(III)-ferrichrome, starch, mucin-glycans, or N-linked glycans were used as a substrate for growth in vitro . Genetic complementation of the ΔtonB3 mutant with the tonB3 gene restored growth on these substrates. The ΔtonB1 , ΔtonB2 , ΔtonB4, ΔtonB5, and ΔtonB6 single mutants did not show a growth defect. This indicates that there was no functional compensation for the lack of TonB3, and it demonstrates that TonB3, alone, drives the TBDTs involved in the transport of essential nutrients. The ΔtonB3 mutant had a severe growth defect in a mouse model of intestinal colonization compared to the parent strain. This intestinal growth defect was enhanced in the ΔtonB3 ΔtonB6 double mutant strain, which completely lost its ability to colonize the mouse intestinal tract compared to the parent strain. The ΔtonB1 , ΔtonB2 , ΔtonB4, and ΔtonB5 mutants did not significantly affect intestinal colonization. Moreover, the survival of the ΔtonB3 mutant strain was completely eradicated in a rat model of intra-abdominal infection. Taken together, these findings show that TonB3 was essential for survival in vivo . The genetic organization of tonB1 , tonB2 , tonB4, tonB5, and tonB6 gene orthologs indicates that they may interact with periplasmic and nonreceptor outer membrane proteins, but the physiological relevance of this has not been defined. Because anaerobic fermentation metabolism yields a lower Δp than aerobic respiration and B. fragilis has a reduced redox state in its periplasmic space-in contrast to an oxidative environment in aerobes-it remains to be determined if the diverse system of TonB/ExbB/ExbD orthologs encoded by B. fragilis have an increased sensitivity to PMF (relative to aerobic bacteria) to allow for the harvesting of energy under anaerobic conditions.

Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.

Objective: to characterize surgical hospitalizations, length of stay, cost and mortality, according to the legal nature (public and private) of the hospital institution linked to the Unified Health System (Sistema Único de Saúde, SUS). Method: a descriptive study, of the survey type, with retrospective data collection (2008 to 2017) and a quantitative approach. The dependent variables surgical hospitalizations in Brazil, costs, length of stay and mortality and the independent variables regime/legal nature (public and private) were obtained from the Informatics Department of the Unified Health System. The Mann-Whitney test was used for analysis., Results: the average number of hospitalizations through the Unified Health System was 4,214,083 hospitalizations/year, 53.5% occurred in private hired hospitals and 46.5% in public hospitals (p=0.001). The financial transfer was greater for the private sector (60.6%) against 39.4% for the public (p=0.001). The average stay was 4.5 days in the public hospital and 3.1 days in its private counterpart (p<0.001). Mortality was higher in the public (1.8%) than in the private hospital (1.4%) (p<0.001)., Conclusion: there was predominance of surgical hospitalizations through the Unified Health System in private hospitals with greater financial transfer to this sector, to the detriment of the public. The diverse evidence produced contributes to the debate and actions to avoid budgetary asphyxiation in the public sector in favor of the private sector.

This study aimed to analyze the influence of COVID-19 social distancing on the dietary pattern of university students in the Northeast of Brazil and associated factors. This is a cross-sectional study of 955 students from four universities carried out via a web survey containing social, economic, demographic, and health information. A food frequency questionnaire was used to evaluate diet. Weight and dietary alterations were reported. Exploratory factor analysis and multivariate logistic regression were used as statistical analyses. The mean age was 26 and 53.7% of the students observed an increase in their weight. Four dietary patterns were identified: (1) a predominantly in natura pattern, (2) a pattern of processed and ultra-processed foods, (3) a protein-based pattern, and (4) an infusion-based pattern. It was observed that students having a darker skin colour (OR 1.8; CI 95% 1.3-2.6) and 19-29 years old and not being a health course student (OR 1.5; CI 95% 1.1-2.1) were associated with greater adhesion to the in natura pattern. Not engaging in physical activity was statistically associated with not adhering (OR 0.5; CI 95% 0.4-0.7) to that pattern. The university students who saw an alteration in their weight during the social distancing period studied presented a greater probability of consuming the processed and ultra-processed foods pattern (OR 1.8; CI 95% 1.2-2.6), while the men (OR 0.7; CI 95% 0.4-0.9) and those not engaging in physical activity (OR 0.7; CI 95% 0.5-0.9) presented less adhesion to that pattern. These findings indicate that social isolation affected the dietary intake of university students, with adhesion to mixed dietary patterns in terms of health. The adhesion to the pattern of processed and ultra-processed foods identified may affect the students' health, especially the occurrence of excess weight and obesity., (Copyright © 2021. Published by Elsevier Ltd.)

As part of our efforts to develop sustainable drugs for Alzheimer's disease (AD), we have been focusing on the inexpensive and largely available cashew nut shell liquid (CNSL) as a starting material for the identification of new acetylcholinesterase (AChE) inhibitors. Herein, we decided to investigate whether cardanol, a phenolic CNSL component, could serve as a scaffold for improved compounds with concomitant anti-amyloid and antioxidant activities. Ten new derivatives, carrying the intact phenolic function and an aminomethyl functionality, were synthesized and first tested for their inhibitory potencies towards AChE and butyrylcholinesterase (BChE). 5 and 11 were found to inhibit human BChE at a single-digit micromolar concentration. Transmission electron microscopy revealed the potential of five derivatives to modulate Aβ aggregation, including 5 and 11 . In HORAC assays, 5 and 11 performed similarly to standard antioxidant ferulic acid as hydroxyl scavenging agents. Furthermore, in in vitro studies in neuronal cell cultures, 5 and 11 were found to effectively inhibit reactive oxygen species production at a 10 μM concentration. They also showed a favorable initial ADME/Tox profile. Overall, these results suggest that CNSL is a promising raw material for the development of potential disease-modifying treatments for AD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Since more than 40 years liposomes have being extensively studied for their potential as carriers of anticancer drugs. The basic principle behind their use for cancer treatment consists on the idea that they can take advantage of the leaky vasculature and poor lymphatic drainage present at the tumor tissue, passively accumulating in this region. Aiming to further improve their efficacy, different strategies have been employed such as PEGlation, which enables longer circulation times, or the attachment of ligands to liposomal surface for active targeting of cancer cells. A great challenge for drug delivery to cancer treatment now, is the possibility to trigger release from nanosystems at the tumor site, providing efficacious levels of drug in the tumor. Different strategies have been proposed to exploit the outer and inner tumor environment for triggering drug release from liposomes and are the focus of this review., 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 © 2021 Franco, Gomes, Roque and Oliveira.)

Background: Solid Dispersions (SDs) have been extensively used to increase the dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets., Objective: This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed., Methods: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as a carrier, according to a 2 3 factorial design. The formulation variables were gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed., Results: SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil- HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release, while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time., Conclusion: SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Clinical Background: Chronic kidney disease (CKD) is a condition that causes important limitations to patients' lives. The limitations imposed as a result of the disease end up hampering the exercise of citizenship by individuals, including work and daily activities. Epidemiology: The prevalence of CKD in Brazil, India, Nigeria, Portugal, and South Africa is, respectively, 5.8-25.2, 13-17.2, 7.8-23.5, 6.1-20.7, and 6.4-17.3%, and is higher among the most disadvantaged populations. Challenges: The present study intends to make an intersection between health sciences, considering the reality faced by the patient with CKD, and the legal perspectives regarding the protective dimension of the right to healthcare and the access of these individuals to a better quality of life. Despite differences in size, population, and human development, there are some similarities among countries in the normative approach regarding the right to healthcare of patients with CKD. The study was developed based on an analysis carried out by legal scholars and specialists from Brazil, India, Portugal, South Africa, and Nigeria. Not only the texts of constitutions and laws were examined, but also how courts interpret and apply them. It was identified that the impact of kidney disease is also associated with human development issues. Adequate access to renal replacement therapy is not always found in the countries examined as well as to kidney transplants. It was observed that the constitutional protection of the right to healthcare is present in some constitutions such as those of Brazil, Portugal, and South Africa. Specific legislation that regulates access to medicines, dialysis, and kidney transplantation was analyzed. Financial aid and right to social assistance and social insurance benefits guaranteed by law are found only in some countries. However, for legal provisions to become effective, it is still necessary to overcome sociocultural and budgetary issues. Prevention and Treatment: Public policies directed to CKD patients, ensuring access to information, preventive measures, and treatment, should be elaborated to answer the increasing demand for renal replacement therapy, including dialysis and transplant., (© 2021 S. Karger AG, Basel.)

The human intestinal anaerobic commensal and opportunistic pathogen Bacteroides fragilis does not synthesize the tetrapyrrole protoporphyrin IX in order to form heme that is required for growth stimulation and survival in vivo Consequently, B. fragilis acquires essential heme from host tissues during extraintestinal infection. The absence of several genes necessary for de novo heme biosynthesis is a common characteristic of many anaerobic bacteria; however, the uroS gene, encoding a uroporphyrinogen III synthase for an early step of heme biosynthesis, is conserved among the heme-requiring Bacteroidales that inhabit the mammalian gastrointestinal tract. In this study, we show that the ability of B. fragilis to utilize heme or protoporphyrin IX for growth was greatly reduced in a Δ uroS mutant. This growth defect appears to be linked to the suppression of reverse chelatase and ferrochelatase activities in the absence of uroS In addition, this Δ uroS suppressive effect was enhanced by the deletion of the yifB gene, which encodes an Mg 2+ -chelatase protein belonging to the A TPases a ssociated with various cellular a ctivities (AAA + ) superfamily of proteins. Furthermore, the Δ uroS mutant and the Δ uroS Δ yifB double mutant had a severe survival defect compared to the parent strain in competitive infection assays using animal models of intra-abdominal infection and intestinal colonization. This shows that the presence of the uroS and yifB genes in B. fragilis seems to be linked to pathophysiological and nutritional competitive fitness for survival in host tissues. Genetic complementation studies and enzyme kinetics assays indicate that B. fragilis UroS is functionally different from canonical bacterial UroS proteins. Taken together, these findings show that heme assimilation and metabolism in the anaerobe B. fragilis have diverged from those of aerobic and facultative anaerobic pathogenic bacteria., (Copyright © 2020 American Society for Microbiology.)