Search

Copyright of Texto & Contexto Enfermagem is the property of Universidade Federal de Santa Catarina, Programa de Pos-Graduacao de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut-off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants <2% VAF from background noise (37 FPs reported by 9 laboratories). The impact of low-VAF variants on time-to-second-treatment (TTST) and overall survival (OS) was investigated in a series of 1092 patients. Among patients not treated with targeted agents, patients with low-VAF TP53 variants had shorter TTST and OS versus wt- TP53 patients, and the relative risk of second-line treatment or death increased continuously with increasing VAF. Targeted therapy in ≥2 line diminished the difference in OS between patients with low-VAF TP53 variants and wt- TP53 patients, while patients with high-VAF TP53 variants had inferior OS compared to wild type- TP53 cases. Altogether, NGS-based approaches are technically capable of detecting low-VAF variants. No strict threshold can be suggested from a technical standpoint, laboratories reporting TP53 mutations should participate in a standardized validation set-up. Finally, whereas low-VAF variants affected outcomes in patients receiving chemoimmunotherapy, their impact on those treated with novel therapies remains undetermined. Our results pave the way for the harmonized and accurate TP53 assessment, which is indispensable for elucidating the role of TP53 mutations in targeted treatment., Competing Interests: Bárbara Tazón‐Vega: Honoraria: Bristol Meyer Squibb. Beatriz Bellosillo: Advisory board honoraria, research support, travel support, speaker fees: Astra‐Zeneca, BMS, Janssen, Merck‐Serono, Novartis, Pfizer, Hoffman‐La Roche, ThermoFisher. Christian Brieghel: Travel grant: Octapharma. Carsten U. Niemann: Research funding and/or consultancy fees: Abbvie, AstraZeneca, Beigene, Janssen, Genmab, Lilly, MSD, CSL Behring, Takeda, Octapharma. Davide Rossi: Honoraria: AbbVie, AstraZeneca, BeiGene, BMS, Janssen, Lilly. Research grants: AbbVie, AstraZeneca, Janssen. Travel grants: AstraZeneca, Janssen. Eugen Tausch: Honoraria and research support: Abbvie, AstraZeneca, BeiGene, Janssen, Hoffmann‐La Roche; Research support from Abbvie, Roche, Gilead. Frédéric Davi: Honoraria: Janssen, AstraZeneca. Kostas Stamatopoulos: Research funding, honoraria and/or consultancy fees: Abbvie, AstraZeneca, Janssen, Lilly, Roche. Lydia Scarfo: Consultancy: AbbVie, AstraZeneca, BeiGene, Janssen, Lilly; Speaker Bureau: Octapharma. Miguel Alcoceba: Honoraria and travel grants: Janssen, AstraZeneca. Martin Andres: Consultancy, Honoraria, and travel support: AstraZeneca, Novartis, Roche, Janssen‐Cilag. Maria Gomes da Silva: Consultancy and Research Funding: Janssen Cilag, AstaZeneca, Abbvie, Roche, Takeda. Pau Abrisqueta: Consultancy and Honoraria: Janssen, Abbvie, Roche, BMS, AstraZeneca, Genmab. Panagiotis Baliakas: Honoraria: Abbvie, Gilead, Janssen. Research funding: Gilead. Paolo Ghia: Honoraria: AbbVie, Astrazeneca, BeiGene, BMS, Galapagos, Janssen, Lilly/Loxo Oncology, MSD, Roche. Research funding: AbbVie, AstraZeneca, BMS, Janssen. Richard Rosenquist: Honoraria: AbbVie, AstraZeneca, Janssen, Illumina, Roche. Renata Walewska: Travel support: AbbVie, AstraZeneca, Janssen, Beigene. Sylwia Czekalska: Honoraria: AstraZeneca. Funding: Janssen, AstraZeneca. Stephan Stilgenbauer: Advisory board honoraria, research support, travel support, speaker fees: AbbVie, Acerta, Amgen, AstraZeneca, BeiGene, BMS, Celgene, Gilead, GSK, Hoffmann‐La Roche, Infinity, Janssen, Lilly, Novartis, Sunesis, Verastem. Tiina Kahre: Honoraria: AstraZeneca. Tomasz Stokłosa: Honoraria and Research Funding: Janssen, AstraZeneca. The remaining authors have no competing interests to declare., (© 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least one mutation involving M-CH candidate genes was described in 34 patients (13%), with DNMT3A being the most frequently mutated gene (54%). After a median follow-up of 7 years, the presence of large CH clones (VAF ≥ 10%) predicted worse PFS (HR 2.93 [1.36-6.31], p=0.006) and OS (HR 3.02 [1.21-7.55], p=0.018) compared to CH- patients. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P<0.05). Moreover, large M-CH clones showed longer time to hematologic recovery after ASCT compared to the remaining cohort (p=0.026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in MCL patients., (Copyright © 2025 American Society of Hematology.)

Peptide-polymer systems hold strong potential for applications in nanotherapeutics. Desmopressin, a synthetic analogue of the antidiuretic hormone arginine vasopressin, may serve as a valuable case of study in this context since it is a first-line treatment for disorders affecting water homeostasis, including diabetes insipidus. It also has an established use as a hemostatic agent in von Willebrand disease, and recently, its repurposing has been suggested as a neoadjuvant in the treatment of certain types of cancer. Despite its well-documented clinical uses, studies on the supramolecular organization of desmopressin and its association with polymers remain scarce, limiting the therapeutic benefits of these nanostructured arrays. Here, we investigate the self-assembly of desmopressin and its association with sodium polystyrene sulphonate (NaPSS), a potassium-binding polymer used to treat hyperkalemia. Using structural techniques such as small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and atomic force microscopy combined with infrared nanospectroscopy (AFM-IR), we identified that desmopressin associates with NaPSS to form hybrid fibrillar nanoassemblies characterized by β-turn enriched domains and the appearance of β-sheet content. In vitro cytotoxicity assays conducted on breast cancer cell lines MCF-7 and MDA-MB-231 showed that NaPSS/desmopressin complexes are well-tolerated by the non-metastatic MCF-7 cells while displaying inhibitory effects against the metastatic MDA-MB-231 cells. The findings presented here, which demonstrate the successful association between two clinically validated drugs and the ability of the hybrid matrix to modulate cell interactions, potentially contribute to the design of peptide-polymer therapeutic systems.

Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats., Competing Interests: Declarations Ethics approval This study was approved by the Animal Research Ethic Committee of the University of Southern Santa Catarina (protocol 19.034.4.01.IV). The “Principles of Laboratory Animal Care” (NIH publication n° 80–23, revised 1996) and the “EC Directive 86/609/EEC” were followed in all experiments. Consent to participate Not applicable. Consent for publication All authors gave their consent for publication. Conflicts of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the intraocular pressure (IOP) behavior after applying a standardized protocol to induce psychological stress in patients with primary open-angle glaucoma (POAG)., Design: Randomized controlled trial., Participants: A total of 39 patients with POAG were included: 18 in the stress group and 21 in the control group., Methods: Patients were randomized to undergo the Trier Social Stress Test (TSST) or to be included in the control group. All participants were submitted to a modified diurnal tension curve (DTC) 1-4 weeks before randomization, with 3 IOP measurements performed between 8:00 am and 2:00 pm. We evaluated the response to the TSST by measuring the levels of salivary cortisol, salivary amylase, IOP, mean arterial pressure, and heart rate before, immediately after, and 40 minutes after the TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals., Main Outcome Measures: Changes in IOP (mmHg), salivary cortisol and amylase, heart rate, mean arterial pressure, and STAI scores., Results: At baseline, there were no significant differences between the groups regarding age (P = 0.661), sex (P = 0.669), salivary cortisol (P = 0.104), and mean DTC IOP for the right (P = 0.439) and left (P = 0.576) eyes. We observed a significant mean IOP increase of 3.8 mmHg (right eye; P < 0.001) and 4.1 mmHg (left eye; P < 0.001) when we compared IOP measurements obtained during the DTC and immediately after TSST. Salivary cortisol (5.9 nmol/L; P = 0.004), salivary amylase (323 388 UL; P = 0.004), mean arterial pressure (10.1 mmHg; P < 0.001), and heart rate (12.9 bpm; P < 0.001) also increased significantly after the TSST. In addition, 61.1% (11 of 18) of the patients in the TSST group showed an IOP increase > 4 mmHg following the test. The STAI-state score significantly increased after the TSST compared to baseline (P < 0.001) and decreased from poststress to the recovery period (P < 0.001)., Conclusions: Patients with POAG present significant elevations of IOP, salivary cortisol and amylase, mean arterial pressure, heart rate, and STAI scores after psychological stress induced by the TSST., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

A new method was evaluated and developed for the analysis of pesticides in sandy-loam soil by direct-immersion solid phase microextraction (DI-SPME) followed by gas chromatography tandem-mass spectrometry (GC-MS/MS) determination. Ten pesticides were selected based on a literature survey of the compounds reported to be present in EU soils. The extraction was performed using SPME LC-Tips, a new SPME configuration with the coated fibers attached to a disposable and easy-to-handle micropipette tip, which was immersed into a soil slurry made by the addition of an aqueous solution to the soil sample. Ten experimental parameters were evaluated with a Plackett-Burman design, after which the extraction time and percentage of organic solvent in the aqueous extraction were optimized separately. The two fiber chemistries available (PDMS/DVB and C 18 ) were evaluated in parallel for the entire work. In the final method, slurry samples were made by adding an aqueous solution (6 % methanol v/v) to 2 g of soil. The fiber was conditioned and then inserted, for extraction, into the samples, stirred by a magnetic bar. Afterwards, the analytes were desorbed onto 100 µL of methanol. After the addition of analyte protectants (ethylglycerol, gulonolactone, and sorbitol) the extract was injected into the GC-MS/MS system. Isotopically labelled penconazole was used as internal standard. A calibration was performed by extracting spiked soil with analyte concentrations of 0.1-50 µg/kg. Coefficients of determination of the linear calibration were between 0.94-0.98 for the PDMS/DVB and 0.92-0.99 for the C 18 . Limits of detection range between 0.01-10 µg/kg for the PDMS/DVB and 0.1-10 µg/kg for the C 18 . Overall, the C 18 analytically outperformed the PDMS/DVB but required a longer extraction time (120 min vs 75 min for the PDMS/DVB). This method allows automation and generates low residual toxic waste, having the potential to be introduced as a greener and simpler alternative to currently used sample preparation methodologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Vitamin D activates the vitamin D receptor (VDR), which dimerizes preferentially with the retinoid X receptor-α (RXRα). This heterodimer connects with genetic elements responsive to vitamin D, inhibiting or stimulating gene activity. We performed Nanostring® analysis of VDR/RXRα to compare the mRNA expression of this heterodimer and their correlated transcriptomes in non-melanoma skin cancer (basal cell carcinomas (BCC) and squamous cell carcinomas (SCC)) and melanocytic lesions (intradermal nevi (IN), and melanomas (MM)) with control skin. To evaluate VDR, RXRα and other 22 correlated genes in BCC, SCC, IN and MM, paraffin samples had their transcriptomes analysed using Nanostring®, a platform that allows multiple mRNA analyses. There were 46 samples, including 11 BCC, 10 SCC, 10 IN, 12 MM and 3 pools of control skins. Most mRNAs differed between the lesion groups and the control group. BCC and SCC NCOR2 were upregulated; in MM and IN, RXRγ was higher than in the control group. TP53, FOXO3 and MED1 showed a significant difference when we compared the BCC group to the SCC group. Melanoma and intradermal nevi differed only in AhR. VDR and RXRα were lower than the control in all groups. The panel shows a clear difference between the non-melanocytic cancers and, on the other hand, a slight difference between the melanocytic lesions. The study of vitamin D's influence through its receptor and RXRα is an exciting issue for understanding the importance of this pathway, and the present study can impact the prevention and treatment strategies, mainly in non-melanocytic tumours., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC., Methods: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population., Conclusions: The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Soil contamination by heavy metals (HM) from pesticides poses a serious environmental threat, affecting sustainability and agricultural productivity. Soil enzymes are essential for biochemical reactions such as organic matter decomposition and nutrient cycling and are vital for maintaining soil health. However, the effects of HM on soil enzyme activity are not yet well understood. This study examined the impact of HM contamination on enzymatic stoichiometry in regions with intensive pesticide use. We selected flower cultivation areas with 5 years (CA1) and 10 years (CA2) of pesticide exposure and a native forest area (NFA) as a reference during the dry and rainy seasons. We measured Cd, Cu, Mn, Pb, and Zn levels and employed ecological risk indices to assess contamination levels. We also analyzed enzyme activities (arylsulfatase, β-glucosidase, acid phosphatase, urease) and enzymatic stoichiometry. CA2 exhibited the highest concentrations of Cd, Cu, and Mn in both periods, while Zn was highest in both CA1 and CA2. CA2 had higher values for all indices, indicating significant contamination. Compared with NFA, arylsulfatase activity was lower in cultivated areas during both periods, suggesting decreased soil quality. We found negative correlations between Cu, Mn, Zn, and arylsulfatase, as well as a reduction in urease with Cd; these elements also increased microbial C limitation. Our findings show that continuous pesticide input increases HM levels and that enzyme activity and stoichiometry are effective bioindicator of soil contamination. This study underscores the urgent need for guidelines to protect soils from prolonged HM buildup., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of this study was to evaluate the effect of genetic groups and diets with different sources of nonprotein nitrogen (NPN) on the carcass and meat characteristics of beef heifers. The meat from 40 heifers (20 ½ Angus ½ Nellore (A × N) and 20 ½ Charolais ½ Nellore (L × N)), finished in feedlots, was used. The heifers were fed diets containing different sources of NPN-(1) a diet with livestock urea and protected urea (LPU) and (2) a diet with extruded urea (EU)-in a completely randomized design with a 2 × 2 factorial arrangement. Carcass, composition and meat quality evaluations were carried out. There were no significant interactions between diet and genetic group for most of the variables evaluated ( p > 0.05). The A × N heifers had higher hot carcass weights (305.73 vs. 279.80 kg), loin eye areas (80.87 vs. 75.45 cm 2 ), subcutaneous fat thicknesses (8.69 vs. 6.35 mm) and lower shear forces (6.98 vs. 7.7 kg) compared to the C × N heifers ( p < 0.05). The meat from the A × N heifers had higher proportions of saturated fatty acids (49.41 vs. 47.95%), with no effects on the proportions of monounsaturated (47.57%) and polyunsaturated (4.01%) fatty acids. The A × N heifers had better carcass and meat characteristics, while the C × N heifers had meat and fat with better fatty acid profiles.

This research explores green-technology alternatives to extract vegetable oils as alternatives to hexane, a non-renewable solvent, focussing on sunflower oil. It compares pressurized liquid extraction (PLE) with ethanol and supercritical fluid extraction (SFE) with CO 2 . Both processes aim to maximize oil yield, tocopherol content (α, β, γ, and δ), fatty acid profile (FA), and triacylglycerol (TAG) composition. Results show that SFE at 32 MPa achieves an 87.58% oil recovery, while PLE at 84 °C achieves 93.93%. PLE with ethanol extracts polar minority compounds along with the oil due to its higher temperature, favoring extraction. The total tocopherol content is 91.17 mg/100 g of oil in optimized SFE conditions, with α-tocopherol extraction influenced by temperature, γ and δ-tocopherol by pressure. PLE yields 83.16 mg/100 g of oil in tocopherols influenced less by process variables. The fatty acid (FA) profile do not vary in the oils obtained from different processes or based on the variables within each process, with linoleic and oleic acids being the most abundant. Similarly, triacylglycerols (TAGs) C54:5 and C54:6 are predominant. The optimization of SFE and PLE processes indicates a strong potential for using green solvents in the extraction of tocopherol-rich sunflower oil., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Global Challenges published by Wiley‐VCH GmbH.)

The objective was to investigate the effect of rainfall on sodium (Na) dissolution and total losses by runoff of loose mineral mixtures (MM) available in uncovered feeders to grazing cattle, as well as the possible impacts on their growth performance and fulfilment of Na nutritional needs. Experiments ( n = 7) were conducted to quantify the amount of Na lost due to rainfall and to evaluate the effects of different Na levels in the MM (35, 70, 105, and 140 g Na/kg) on MM assumed intake and growth performance. Cattle grazed Brachiaria sp. pastures and received free-choice MM in uncovered feeders throughout four to nine evaluation periods lasting 14 to 21 d each. MM assumed intake from the feeder was measured in each period as the difference between the supplied MM mass and the unconsumed MM mass. A new methodology was proposed to measure MM losses by runoff (exclusion feeder). The mass of runoff MM and the volume of runoff rainwater were both determined and analysed for their mineral content. The dietary Na requirement was estimated using different feeding systems. The minimum MM Na content to meet dietary Na requirements was estimated in different scenarios. Sodium chloride composed 28% of the runoff MM mass, in average. The action of rain may reduce MM Na content by 28% in a single rainfall event. Na content strongly affected MM assumed intake and, possibly, growth rate. MM losses by runoff were estimated at 25.5%, according to the exclusion feeder methodology. The minimum required MM Na content for meeting dietary Na needs may reach up to 87.3 g Na/kg. About 27% of evaluated periods may have failed to fully meet cattle Na requirements. The action of rain in unsheltered loos MM may result in unbalanced mineral consumption and unmet Na needs, leading to impaired mineral nutrition of grazing cattle, especially in tropical conditions.

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania . Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H 2 DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC 50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC 50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI 50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

The galactomannan-based gel from Cassia grandis seeds was used to incorporate Penicillium sp. UCP 1286 and commercial collagenases. Experiments were carried out according to a 2 3 -full factorial design to identify the most significant parameters for the incorporation process. The pH of the incorporation solution (pH i ), stirring time (t), and initial protein concentration in the crude extract (PC i ) were selected as the three independent variables, and the efficiency of collagenase incorporation (E) and collagenolytic activity (CA) after 360 min as the responses. pH i and PC i showed positive statistically significant effects on E, while CA was positively influenced by pH i and t, but negatively by PC i . The fungi collagenase was released from the gel following a pseudo-Fickian behavior. Additionally, no <76 % of collagenase was efficiently incorporated into the gel retaining a high CA (32.5-69.8 U/mL). The obtained results for the commercial collagenase (E = 93.88 %, CA = 65.8 U/mL, and n = 0.10) demonstrated a pseudo-Fickian behavior similar to the fungi-collagenase. The results confirm the biotechnological potential of the gel as an efficient matrix for the incorporation of catalytic compounds; additionally, the incorporation of collagenases was achieved by retaining the proteases CA and releasing them in a controlled manner., 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 Ltd. All rights reserved.)

To investigate the potential benefits of the catadromous thinlip grey mullet (Chelon ramada Risso, 1827) migration to freshwater, the total lipid content and fatty acid (FA) profile of female's muscle and gonads caught in both the estuary and river were analyzed. The freshwater contingent presented a higher body condition, greater muscle gross energy, and larger gonads with higher lipid reserves. These animals showed a muscle profile rich in C16:1n-7 and lower LC-PUFA that contrast with the higher relative amount of C18:1n-9, n-3 FA, and unsaturated LC-PUFA, such as C18 and C20 FA found in the estuarine contingent. The gonads of both contingents showed a constant and high relative amount of polyunsaturated FAs (PUFA, 37%). However, in terms of essential fatty acids (EFAs), the estuarine contingent had a higher relative amount of C18:2n-6, C20:4n-6, C20:5n-3, and C22:6n-3. On the other hand, the freshwater contingent showed a higher relative amount of n-3 FA precursors, namely C18:3n-3, and a still low relative amount of C22:6n-3. This suggests a mismatch between the metabolic omega-3 pathway and the physiological maturity stages, similar to a phenomenon of dormancy. In this sense, not all these individuals may reproduce annually, and the later stages of gonad development will require supplementary energy derived from feeding at the estuary. Thus, freshwater migration may promote a reproductive strategy enabling adults to take advantage of the warm and food-rich summer/autumn period, adjust spawning and juvenile appearance, and reduce the population's exposure to habitat changes and/or stochastic events., (© 2024. The Author(s).)

Objective: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression., Method: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593., Results: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects., Conclusion: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JAC is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE)—National Health and Medical Research Council (NHMRC). JAC and JEH have received travel support to attend scientific meetings and personal consultation fees from BSPG-Pharm in the past. JAC, JEH, FK, FSG, and AWZ are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; 29 July 2015; INPI on 19 August 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarães FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JAC, JEH, FSG, ACC, and AWZ are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on 16 September 2016 (BR 112018005423-2). MKS reports research grants from SMRI, from the National Council for Scientific and Technological Development, Ministry of Science and Technology, Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq), and Coordination of Superior Level Staff Improvement (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES), and personal fees from SHIRE and Daichii-Sankyo, from FIPE-HCPA (Fundo de Incentivo à Pesquisa e Eventos – HCPA), and from CNPq Produtividade em Pesquisa outside of the submitted work. LNY is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Abbvie, Alkermes, Allergan, Canadian Network for Mood and Anxiety Treatments (CANMAT), Canadian Institutes of Health Research (CIHR), Dainippon Sumitomo Pharma, Gedeon Richter, Intracellular Therapies, Lundbeck, Merck, Otsuka, Sanofi and Sunovion over the past 3 years. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In response to inflammation and other stressors, tryptophan is catalyzed by Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is a serious condition in which the body responds improperly to an infection, and the brain is the inflammation target in this condition., Objective: This study aimed to determine if the induction of TDO contributes to the permeability of the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis., Methods: Male Wistar rats with two months of age were submitted to the sepsis model using Cecal Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO inhibitor, or a vehicle once a day for seven days., Results: Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration restored these parameters. Regarding memory, Allo restored short-term memory impairment and decreased depressive behavior. However, no change in survival rate was verified., Conclusion: In summary, TDO inhibition effectively prevented depressive behavior and memory impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative stress, and mitochondrial alteration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Phthalic acid esters (PAEs) are a class of chemicals widely used as plasticizers. These compounds, considered toxic, do not bond to the polymeric matrix of plastic and can, therefore, migrate into the surrounding environment, posing a risk to human health. The primary source of human exposure is food, which can become contaminated during cultivation, production, and packaging. Therefore, it is imperative to control and regulate this exposure. This review covers the analytical methods used for their determination in two economically significant products: olive oil and wine. Additionally, it provides a summary and analysis of information regarding the characteristics, toxicity, effects on human health, and current regulations pertaining to PAEs in food. Various approaches for the extraction, purification, and quantification of these analytes are highlighted. Solvent and sorbent-based extraction techniques are reviewed, as are the chromatographic separation and other methods currently applied in the analysis of PAEs in wines and olive oils. The analysis of these contaminants is challenging due to the complexities of the matrices and the widespread presence of PAEs in analytical laboratories, demanding the implementation of appropriate strategies.

Problem: Ascending bacterial infection is associated with ∼ 40% of spontaneous preterm birth (PTB), and Ureaplasma spp. is one of the most common bacteria isolated from the amniotic fluid. Developing novel in vitro models that mimic in vivo uterine physiology is essential to study microbial pathogenesis. We utilized the feto-maternal interface organ-on-chip (FMi-OOC) device and determined the propagation of Ureaplasma parvum, and its impact on cell signaling and inflammation., Method of Study: FMi-OOC is a microphysiologic device mimicking fetal membrane/decidua interconnected through microchannels. The impact of resident decidual CD45 + leukocytes was also determined by incorporating them into the decidual chamber in different combinations with U. parvum. We tested the propagation of live U. parvum from the decidual to the amniochorion membranes (immunocytochemistry and quantitative PCR), determined its impact on cytotoxicity (LDH assay), cell signaling (JESS TM Western Blot), cellular transition (immunostaining for vimentin and cytokeratin), and inflammation (cytokine bead array)., Results: U. parvum transversed the chorion and reached the amnion epithelium after 72 hours but did not induce cell signaling kinases (p38MAPK and JNK) activation, or cellular transition (epithelial-mesenchymal), regardless of the presence of immune cells. The inflammatory response was limited to the choriodecidual interface and did not promote inflammation in the amnion layer., Conclusions: Our data suggest that U. parvum is poorly immunogenic and does not produce massive inflammatory changes at the feto-maternal interface. We speculate that the presence of U. parvum may still compromise the feto-maternal interface making it susceptible to other pathogenic infection., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim was to evaluate the animal response and the chemical and physical changes of free-choice mineral mixtures fed to grazing cattle. Growing beef cattle were fed either powder (POW) or agglomerated (AGL) mineral mixtures in three different experiments (Exp.), carried out in pastures of Brachiaria grass. In Exp. 1 and 2, the mineral mixtures were disposed in unsheltered troughs (POWun vs. AGLun), being delivered once (D0, Exp.1) or twice (D0 and D8, Exp. 2), throughout 14-day periods. In Exp. 3, POWun and AGLun were additionally compared to POW in sheltered troughs (POWshe), and the mineral mixtures were disposed in D0, throughout 21-day periods. Non-consumed supplement was removed and sampled on D14 (Exp. 1 and 2) or D21 (Exp. 3). Evaluations included average daily body weight gain (ADG), daily disappearance of the supplement (DSD), penetration force of the supplement mass, faecal chemical composition and serum levels of Ca, P and Mg. In Exp. 1, no effects were observed on ADG and faecal mineral concentrations, however, changes in mineral concentrations and a 40% reduction in Na concentration in the supplement were observed, compared to the initial concentration. AGLun had a lower penetration force. In Exp. 2, there were no effects on DSD and faecal mineral concentrations. POWun showed a smaller reduction in Na content compared to AGLun, and AGLun showed lower penetration force. In Exp. 3, the treatments did not affect ADG, but there was a trend towards higher DSD and serum phosphorus (P) concentration for AGLun ( p = 0.08). Higher faecal Na concentration was observed for AGLun and higher Na concentration occurred in non-consumed mixture of POWshe. Mineral supplements offered in uncovered troughs showed altered chemical and physical characteristics, with possible effects on supplement intake. However, the general changes are unlikely to alter animal performance.

Abstract: Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas ( P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = -0.11, P = 0.29) but directly correlated with histological regression ( P = 0.0293). RXRα inversely correlated with mitosis (r = -0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Disturbed vaginal microbiota have a role in the persistence of high-oncogenic-risk human papillomavirus (hrHPV) and Gardnerella spp. is closely related with this condition. Such bacteria are the major source of cervicovaginal sialidases, important for microbiota alterations. The sialidase-encoding gene nanH3 is account for their sialidase activity. Thus, a subset of 212 women positive for hrHPV at the first visit were included in the analysis of the current study aiming to compare the loads of nanH3 in cervicovaginal fluid (CFV) of women with persistent hrHPV infection and with those cleared the infection after a year. Participants were assigned to two study groups named "persistence" (n = 124, 53.22%) or "clearance" (n = 88, 37.77%), according to the HPV status upon enrollment and follow-up. Absolute quantification of nanH3 gene was performed using quantitative real-time PCR (qPCR). Persistence and clearance group did not show statistical difference in the load of nanH3 gene (p = 0.19). When considering the subset of women with HPV16, differences in number of copies of nanh3 gene was observed between the persistent (7.39E+08 copies/μL) and clearance group (2.85E+07 copies/μL) (p = 0.007). Therefore, baseline loads of nanH3 gene is increased in women that persist with cervical HPV16 infection after 12 months., (© 2023. Springer Nature Limited.)

Background: Sexually Transmitted Infections (STIs) can be caused by viruses, bacteria, and parasites. The World Health Organization estimated more than 300 million new global cases of curable STIs among individuals of reproductive age. Infection by Trichomonas vaginalis is one of the most prevalent curable STI. Despite the current treatments available, the diagnosis of T. vaginalis can be difficult, and the resistance to the treatment increased concern for the healthcare system., Objectives: The aim of this study was to determine the prevalence and factors associated with Trichomonas vaginalis infection among women of reproductive age attending community-based services for cervical screening., Patients and Methods: A total of 1477 reproductive-aged women attending 18 Primary Health Care Units in Botucatu, Brazil, from September to October 2012, were enrolled. A structured questionnaire was used for individual face-to-face interviews for obtaining data on sociodemographic, gynecologic, and obstetrics history, sexual and hygiene practices, among others. Cervicovaginal samples were obtained for detection of T. vaginalis by culture using Diamond's medium and microscopic vaginal microbiota classification according to Nugent. A multivariable logistic regression analysis was carried out to estimate Odds Ratios (OR) and 95% Confidence Intervals (95% CI) for the association between participants' sociodemographic, behavioral factors, and clinical factors with T. vaginalis infection., Results: Median age of study participants was 33 years (ranging from 18 to 50). The overall prevalence of T. vaginalis infection was 1.3% (n = 20). Several factors were independently associated with T. vaginalis infection, such as self-reporting as black or Pardo for ethnicity (OR = 2.70; 95% CI 1.03‒7.08), smoking (OR=3.18; 95% CI 1.23‒8.24) and having bacterial vaginosis (OR = 4.01; 95%CI = 1.55-10.38) upon enrollment. A protective effect of higher educational level (having high school degree) was observed (OR = 0.16; 95% CI 0.05‒0.53)., Conclusions: Our data suggest that screening programs to correctly detect T. vaginalis infection can be helpful to guide prevention strategies to the community. Our study supports an association between abnormal vaginal microbiota and T. vaginalis infection., Competing Interests: Conflicts of interest CM has received consultancy fees from Kimberly-Clark outside of the present work. All other authors declare no conflict of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Childhood obesity is a significant public health problem. Studies show that obese children are more likely to become obese adults. In an attempt to ascertain the factors associated with childhood obesity, research has shown that this condition is associated with changes in food consumption and masticatory performance. The aim of this study was thus to evaluate food consumption and masticatory performance in normal weight, overweight and obese children aged 7 - 12 years. A cross-sectional study was carried out with 92 children aged 7 - 12 years, of both sexes, from a public school in a Brazilian municipality. The children were divided into the following groups: normal weight (n = 48), overweight (n = 26) and obese (n = 18). Anthropometric parameters, food consumption, food consistency preference, and masticatory performance were evaluated. Pearson's chi-square test was used to compare categorical variables. To compare numerical variables, the one-way ANOVA test was applied. For variables not conforming to a normal distribution, the Kruskal-Wallis test was used. The level of statistical significance was set at p ≤ 0.05. Our results show that the children with obesity consumed fewer fresh foods (median = 3, IQI = 4.00-2.00, p = 0.026), consumed more ultra-processed foods (median = 4, IQI = 4.00-2.00, p = 0.011), performed fewer mastication sequences (median = 2, IQI = 3.00-2.00, p = 0.007), and ate faster (median = 58.50, IQI = 69.00-48.00, p = 0.026) compared to children of normal weight. We conclude that children with obesity exhibit differences in food consumption and masticatory performance compared to children of normal weight., Competing Interests: Declaration of Competing Interest Nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The factors associated with bacterial vaginosis in women with homosexual, bisexual and heterosexual practices are still poorly explored. Thus, the aim of this study was to analyze the factors associated with bacterial vaginosis in women with different sexual practices., Methods: Cross-sectional study that included 453 women, 149 Women with Homosexual practice (WSW); 80 bisexual Women (WSWM) and 224 Women with heterosexual practice (WSM). The diagnosis of bacterial vaginosis was performed by microscopic examination of the vaginal smears stained by Gram method and classified according to the Nugent et al. (1991) score. Data analysis was performed by Cox multiple regression., Results: Bacterial vaginosis was associated to years of education among WSW (0.91 [95% CI 0.82‒0.99]; p = 0.048) and non-white skin color (2.34 [95% CI 1.05‒5.19]; p = 0.037) between WSWM. Changing partners in the last 3-months (2.09 [95% CI 1.14‒3.82]; p = 0.017), inconsistent use of condoms (2.61 [95% CI 1.10‒6.20]; p = 0.030) and positive diagnosis of Chlamydia trachomatis (2.40 [95% CI 1.01‒5.73]; p = 0.048) were associated with bacterial vaginoses only in WSH., Conclusions: The factors associated to bacterial vaginosis differ between different sexual practices, suggesting that the type of sexual partner may influence the risk of developing this classic dysbiosis., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stuqui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic caused impact on public health worldwide. Brazil gained prominence during the pandemic due to the magnitude of disease. This study aimed to evaluate the spatial-temporal dynamics of incidence, mortality, and case fatality of COVID-19 and its associations with social determinants in Brazilian municipalities and epidemiological week. We modeled incidence, mortality, and case fatality rates using spatial-temporal Bayesian model. "Bolsa Família Programme" (BOLSAFAM) and "proportional mortality ratio" (PMR) were inversely associated with the standardized incidence ratio (SIR), while "health insurance coverage" (HEALTHINSUR) and "Gini index" were directly associated with the SIR. BOLSAFAM and PMR were inversely associated with the standardized mortality ratio (SMR) and standardized case fatality ratio (SCFR). The highest proportion of excess risk for SIR and the SMR started in the North, expanding to the Midwest, Southeast, and South regions. The highest proportion of excess risk for the SCFR outcome was observed in some municipalities in the North region and in the other Brazilian regions. The COVID-19 incidence and mortality in municipalities that most benefited from the cash transfer programme and with better social development decreased. The municipalities with a higher proportion of non-whites had a higher risk of becoming ill and dying from the disease., (© 2023. The Author(s).)

Introduction: Studies conducted with physicians from different locations and age groups show a tendency to mental illness and low quality of life in this population., Objectives: To describe the socioeconomic and quality-of-life profile of medical doctors in the state of Minas Gerais, Brazil., Methods: Cross-sectional study. A socioeconomic and quality-of-life questionnaire (World Health Organization Quality of Life instrument-Abbreviated version) was applied in a representative sample of physicians working in the state of Minas Gerais. Non-parametric analyses were used to assess outcomes., Results: The sample was composed of 1,281 physicians, with a mean age of 43.7 years (SD, 11.46) and time since graduation of 18.9 years (SD, 12.1); 12.46% were medical residents, of which 32.7% were in the first year of training. Of the total number of physicians, 66.4% reported feeling overwhelmed and 70.7% were satisfed with their profession. The rate of diagnoses related to depression and anxiety was higher than in the general population. Mean World Health Organization Quality of Life instrument-Abbreviated version score was 60.44±21.72. The analysis of the reported quality-of-life scores showed that younger physicians, especially women, in the first year of residence, with lower income or salary ranges, high workload, and no regular time of obtained lower scores, as well as those who reported diagnoses of depression and/or anxiety., Conclusions: Some socioeconomic factors may influence the quality of life of the study population. Further studies are needed to develop effective social support and health protection actions for these workers., Competing Interests: Conflicts of interest: None

The prognosis of diffuse large B cell lymphoma (DLBCL) is inaccurately predicted using clinical features and immunohistochemistry (IHC) algorithms. Nomination of a panel of molecules as the target for therapy and predicting prognosis in DLBCL is challenging because of the divergences in the results of molecular studies. Mass spectrometry (MS)-based proteomics in the clinic represents an analytical tool with the potential to improve DLBCL diagnosis and prognosis. Previous proteomics studies using MS-based proteomics identified a wide range of proteins. To achieve a consensus, we reviewed MS-based proteomics studies and extracted the most consistently significantly dysregulated proteins. These proteins were then further explored by analyzing data from other omics fields. Among all significantly regulated proteins, interferon regulatory factor 4 (IRF4) was identified as a potential target by proteomics, genomics, and IHC. Moreover, annexinA5 (ANXA5) and nucleobindin1 (NUCB1) were two of the most up-regulated proteins identified in MS studies. Functional enrichment analysis identified the light zone reactions of the germinal center (LZ-GC) together with cytoskeleton locomotion functions as enriched based on consistent, significantly dysregulated proteins. In this study, we suggest IRF4 and NUCB1 proteins as potential biomarkers that deserve further investigation in the field of DLBCL sub-classification and prognosis.

Background: Gluteus medius (GM) is a segmented muscle involving three muscular subdivisions. Rehabilitation exercises has been suggested to strengthen specific subdivisions., Objective: This study aimed to evaluate muscular activation of the anterior, middle, and posterior subdivisions of the GM during two different exercises., Methods: A total of 28 healthy active subjects participated in this study. Muscle activity using surface electromyography was recorded for the three GM subdivisions during figure-of-four position (FFP) and wall press (WP). Non-parametric Kruskal-Wallis test was used to detect differences between GM subdivisions on each exercise and the Mann-Whitney U test was used to compare muscular activation across exercises., Results: There were statistically significant differences (P< 0.001) in all GM subdivision during FFP and WP exercises. Both exercises showed greater activation of the posterior subdivision than the middle and anterior subdivisions, with the WP causing highest activation of the posterior subdivision., Conclusion: In line with the WP exercise, the FFP produces sufficient activity to provide potential strength gains on the posterior subdivision and could be a viable option to include in the early stages of the rehabilitation process. Clinicians may use this information to make more informed decisions about exercise selection for strengthening specific GM subdivision.

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

People with COVID-19 may excrete viable SARS-CoV-2 virus through urine and faeces, which has raised concerns about the possibility of transmission of COVID-19 via water contaminated or sewage. These concerns are especially exacerbated in underdeveloped countries like Brazil, where untreated sewage is usually discharged to surface water or soil. Because of that, a hypothesis emerged that was addressed in this study, which seeks to understand whether access to basic sanitation services can influence the proliferation of the virus. A correlation study was carried out between the cases of COVID-19 and the indicators of basic sanitation from all regions of Brazil. The results showed that there was a correlation only with the water supply indicator. A hypothesis that would explain the presented correlation would be the inefficiency of the water treatment systems in Brazil, not totally inactivating the virus, or possible contamination of the water distribution networks by sanitary sewage. In general, the data presented reinforce the need to expand and monitor basic sanitation services, especially to ensure the effective and efficient disinfection of drinking water. This monitoring could be useful for early warning surveillance of the spread of the virus., 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., (© 2022 The Author(s). Published by Elsevier B.V.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, onset in early childhood and associated with cognitive, social, behavioral, and sensory impairments. The pathophysiology is still unclear, and it is believed that genetic and environmental factors are fully capable of influencing ASD, especially cell signaling and microglial functions. Furthermore, the endocannabinoid system (ECS) participates in the modulation of various brain processes and is also involved in the pathophysiological mechanisms of this condition. Due to the health and quality of life impacts of autism for the patient and his/her family and the lack of effective medications, the literature has elucidated the possibility that Cannabis phytocannabinoids act favorably on ASD symptoms, probably through the modulation of neurotransmitters, in addition to endogenous ligands derived from arachidonic acid, metabolizing enzymes and even transporters of the membrane. These findings support the notion that there are links between key features of ASD and ECS due to the favorable actions of cannabidiol (CBD) and other cannabinoids on symptoms related to behavioral and cognitive disorders, as well as deficits in communication and social interaction, hyperactivity, anxiety and sleep disorders. Thus, phytocannabinoids emerge as therapeutic alternatives for ASD., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

SARS-CoV-2 transmission occurs mainly indoors, through virus-laden airborne particles. Although the presence and infectivity of SARS-CoV-2 in aerosol are now acknowledged, the underlying circumstances for its occurrence are still under investigation. The contamination of domiciliary environments during the isolation of SARS-CoV-2-infected patients in their respective rooms in individual houses and in a nursing home was investigated by collecting surface and air samples in these environments. Surface contamination was detected in different contexts, both on high and low-touch surfaces. To determine the presence of virus particles in the air, two sampling methodologies were used: air and deposition sampling. Positive deposition samples were found in sampling locations above the patient's height, and SARS-CoV-2 RNA was detected in impactation air samples within a size fraction below 2.5 μm. Surface samples rendered the highest positivity rate and persistence for a longer period. The presence of aerosolized SARS-CoV-2 RNA occurred mainly in deposition samples and closer to symptom onset. To evaluate the infectivity of selected positive samples, SARS-CoV-2 viability assays were performed, but our study was not able to validate the virus viability. The presented results confirm the presence of aerosolized SARS-CoV-2 RNA in indoor compartments occupied by COVID-19 patients with mild symptoms, in the absence of aerosol-generating clinical procedures., (© 2022. The Author(s).)