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This study explores the biological mechanisms behind colour changes in white wine fermentation using different strains of Starmerella bacillaris. We combined food engineering, genomics, machine learning, and physicochemical analyses to examine interactions between S. bacillaris and Saccharomyces cerevisiae. Significant differences in total polyphenol content were observed, with S. bacillaris fermentation yielding 6 % higher polyphenol content compared to S. cerevisiae EC1118. Genomic analysis identified 12 genes in S. bacillaris with high variant counts that could impact phenotypic properties related to wine color. Notably, SNP analysis revealed numerous missense and synonymous variants, as well as stop-gained and start-lost variants between PAS13 and FRI751, suggesting changes in metabolic pathways affecting pigment production. Besides that, high upstream gene variants in SSK1 and HIP1R indicated potential regulatory changes influencing gene expression. Fermentation trials revealed FRI751 consistently showed high antioxidant activity and polyphenol content (Total Polyphenol: 299.33 ± 3.51 mg GAE/L, DPPH: 1.09 ± 0.01 mmol TE/L, FRAP: 0.95 ± 0.02 mmol TE/L). PAS13 exhibited a balanced profile, while EC1118 had lower values, indicating moderate antioxidant activity. The Weibull model effectively captured nitrogen consumption dynamics, with EC1118 serving as a reliable benchmark. The scale parameter delta for EC1118 was 23.04 ± 2.63, indicating moderate variability in event times. These findings highlight S. bacillaris as a valuable component in sustainable winemaking, offering an alternative to chemical additives for maintaining wine quality and enhancing colours profiles. This study provides insights into the biotechnological and fermented food systems applications of yeast strains in improving food sustainability and supply chain, opening new avenues in food engineering and microbiology., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Protein dynamics are essential to biological function, and methods to determine such structural rearrangements constitute a frontier in structural biology. Synchrotron radiation can track real-time protein dynamics, but accessibility to dedicated high-flux single X-ray pulse time-resolved beamlines is scarce and protein targets amendable to such characterization are limited. These limitations can be alleviated by triggering the reaction by laser-induced activation of a caged compound and probing the structural dynamics by fast-readout detectors. In this work, we established time-resolved X-ray solution scattering (TR-XSS) at the CoSAXS beamline at the MAX IV Laboratory synchrotron. Laser-induced activation of caged ATP initiated phosphoryl transfer in the adenylate kinase (AdK) enzyme, and the reaction was monitored up to 50 ms with a 2-ms temporal resolution achieved by the detector readout. The time-resolved structural signal of the protein showed minimal radiation damage effects and excellent agreement to data collected by a single X-ray pulse approach., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Violence against women or gender-based violence (GBV) is a significant public health issue facing women and girls in different settings. It is reported to have worsened globally during the COVID-19 pandemic. Despite the impact of the COVID-19 pandemic on increased violence against women in general, which has been reported in many settings globally, there is a paucity of evidence of its impact on violence against highly vulnerable women living with HIV or tuberculosis (TB). Using a qualitative design, this study aimed to explore the views and experiences of women living with HIV (n = 19) or TB (n = 23) in Timor Leste regarding the GBV they faced during the COVID-19 pandemic. They were recruited using the snowballing sampling technique. Data were collected using one-on-one, in-depth interviews and focus group discussions. The five steps of qualitative data analysis suggested in Ritchie and Spencer's analysis framework were employed to guide the analysis of the findings. Findings indicated that women in this study experienced intensified physical, verbal, sexual and psychological violence by their partners, spouses, in-laws, and parents or other family members during the COVID-19 pandemic. Several prominent risk factors that worsened violence against women during the pandemic were (i) HIV or TB-positive status, (ii) traditional gender roles or responsibilities and expectations, (iii) economic and financial difficulties reflected in the loss of jobs and incomes due to the pandemic, and (iv) individual factors such as jealousy and increased alcohol drinking developed during the lockdowns. The women's experience of GBV during the pandemic also led to various negative psychological impacts. The findings underscore the urgent need for multifaceted interventions to address GBV, which should encompass challenging traditional gender norms, addressing economic inequalities, and targeting individual-level risk factors. The findings also indicate the need for the development of robust monitoring and evaluation systems to assess the effectiveness of policies and interventions addressing GBV where the results can inform future improvement. The findings also indicate the need to include GBV in the protocol or guidelines for HIV and TB management. Future large-scale quantitative studies to capture the magnitude and specific drivers of GBV against women living with HIV and TB during the pandemic are recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martins 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 effects of intra-hippocampal manipulation of glycine receptors on the reconsolidation of recent and late long-term spatial memory were evaluated and assessed in the Morris water maze. The results obtained from the intra-hippocampal infusion of glycine and taurine demonstrated that taurine at a 100 nmol/side dose impaired the reconsolidation of recent and late long-term spatial memory. In comparison, at a dose of 10 nmol/side, it only affected the reconsolidation of late long-term spatial memory, reinforcing that there are differences between molecular mechanisms underlying recent and late long-term memory reconsolidation. On the other hand, glycine impaired the reconsolidation of early and late spatial memory when infused at a dose of 10 nmol/side, but not at a dose of 100 nmol/side, unless it is co-infused with an allosteric site antagonist of the NMDA receptor. Altogether these results show that glycine acting in situ in the hippocampal CA1 region exerts a pharmacological effect on U-curve, which can be explained by its concomitant action on its ionotropic receptor GlyR and on its NMDA receptor co-agonist site., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Early cutaneous squamous cell carcinomas (cSCCs) generally show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits associated with tumor relapse, metastasis, and poor survival. Currently, the mechanisms involved in cSCC progression are unclear, and the established markers are suboptimal for accurately predicting the clinical course of the disease., Methods: Using a mouse model of cSCC progression, expression microarray analysis, immunofluorescence and flow cytometry assays, we have identified a prognostic biomarker of tumor relapse, which has been evaluated in a cohort of cSCC patient samples. Phosphoproteomic analysis have revealed signaling pathways induced in epithelial plastic cancer cells that promote epithelial-mesenchymal plasticity (EMP) and tumor progression. These pathways have been validated by genetic and pharmacological inhibition assays., Results: We show that the emergence of epithelial cancer cells expressing integrin αV (ITGAV) promotes cSCC progression to a mesenchymal state. Consistently, ITGAV expression allows the identification of patients at risk of cSCC relapse above the currently employed clinical histopathological parameters. We also demonstrate that activation of insulin-like growth factor-1 receptor (IGF1R) pathway in epithelial cancer cells is necessary to induce EMP and mesenchymal state acquisition in response to tumor microenvironment-derived factors, while promoting ITGAV expression. Likewise, ITGAV knockdown in epithelial plastic cancer cells also blocks EMP acquisition, generating epithelial tumors., Conclusions: Our results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs., (© 2024. The Author(s).)

This study analyzed arbuscular mycorrhizal fungi (AMF) activity and soil chemical properties in Aspidosperma pyrifolium, Bauhinia ungulata, Caesalpinia pyramidalis, and Caesalpinia ferrea. AMF spores, root colonization, total glomalin-related soil protein (T-GRSP), easily extracted GRSP (EE-GRSP), and soil chemical properties were measured four times (July 2019, 2020 and December 2019, 2020). Significant differences were observed in AMF spores, root colonization, T-GRSP, and EE-GRSP among the plant species and across seasons. For soil chemical properties, we observed differences among plant species. During the dry season, B. ungulata and C. pyramidalis had the highest AMF spores and root colonization (57.3 ± 0.27 spores 50 g soil -1  and 48.8 ± 1.05, respectively), whereas during the rainy season, C. pyramidalis and C. ferrea showed the highest AMF spores and root colonization (36.6 ± 0.13 spores 50 g soil -1  and 62.2 ± 1.17, respectively). A. pyrifolium showed the highest T-GRSP in both seasons. On the basis of the soil chemical properties, we found that (i) A. pyrifolium, B. ungulata, and C. ferrea showed the highest soil organic carbon (1.32 ± 0.03 g kg -1 ), phosphorus (7.01 ± 0.26 mg kg -1 ), and soil pH (5.85 ± 0.23) and (ii) C. pyramidalis showed the highest Ca 2+ , Mg 2+ , Na + , H +  + Al 3+ , K + , and soil total nitrogen (1.36 ± 0.04, 0.73 ± 0.01, 3.72 ± 0.85, 4.56 ± 0.12 cmol c  kg -1 , 15.43 ± 1.53 mg kg -1 , and 0.16 ± 0.01 g kg -1 , respectively). Our results highlight the advantage of AMF spores as perennating structures over other AM fungal propagules in seasonal vegetation like Caatinga., (© 2024 Wiley‐VCH GmbH.)

Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells., (© 2024. The Author(s).)

T-cell Acute Lymphoblastic Leukemia (T-ALL) is a hematological malignancy in need of novel therapeutic approaches. Here, we identify the ATP-citrate lyase ACLY as overexpressed and as a novel therapeutic target in T-ALL. To test the effects of ACLY in leukemia progression, we developed an isogenic model of NOTCH1-induced Acly conditional knockout leukemia. Importantly, we observed intrinsic antileukemic effects upon loss of ACLY, which further synergized with NOTCH1 inhibition in vivo. Metabolomic profiling upon ACLY loss revealed a metabolic crisis with reduced acetyl-CoA levels, as well as a decreased oxygen consumption rate. Gene expression profiling analyses showed that the transcriptional signature of ACLY loss very significantly correlates with the signature of MYC loss in vivo . Mechanistically, the decrease in acetyl-CoA led to reduced H3K27ac levels in Myc , resulting in transcriptional downregulation of Myc and drastically reduced MYC protein levels. Interestingly, our analyses also revealed a reciprocal relationship whereby ACLY itself is a direct transcriptional target of MYC, thus establishing a feedforward loop that is important for leukemia progression. Overall, our results identified a relevant ACLY-MYC axis and unveiled ACLY as a novel promising target for T-ALL treatment.

The metaproteomics field has recently gained more and more interest as a valuable tool for studying both the taxonomy and function of microbiomes, including those used in food fermentations. One crucial step in the metaproteomics pipeline is selecting a database to obtain high-quality taxonomical and functional information from microbial communities. One of the best strategies described for building protein databases is using sample-specific or study-specific protein databases obtained from metagenomic sequencing. While this is true for high-diversity microbiomes (such as gut and soil), there is still a lack of validation for different database construction strategies in low-diversity microbiomes, such as those found in fermented dairy products where starter cultures containing few species are used. In this study, we assessed the performance of various database construction strategies applied to metaproteomics on two low-diversity microbiomes obtained from cheese production using commercial starter cultures and analyzed by LC-MS/MS. Substantial differences were detected between the strategies, and the best performance in terms of the number of peptides and proteins identified from the spectra was achieved by metagenomic-derived databases. However, extensive databases constructed from a high number of available online genomes obtained a similar taxonomical and functional annotation of the metaproteome compared to the metagenomic-derived databases. Our results indicate that, in the case of low-diversity dairy microbiomes, the use of publically available genomes to construct protein databases can be considered as an alternative to metagenome-derived databases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vinicius da Silva Duarte reports financial support was provided by Norges Forskiningsrad. Davide Porcellato reports financial support was provided by Norges Forskiningsrad. If there are other authors, they 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 Authors. Published by Elsevier B.V. All rights reserved.)

Background: This systematic review was conducted to assess the effects of whole-body vibration (WBV) exercises on muscles responses and on risk of falls in elderly individuals., Methods: Searches were conducted in MEDLINE/PubMed, Physiotherapy Evidence Database (PEDro), Web of Science, CINAHL and Scopus databases in Feb 2023 to identify studies with the potential to be included according to the eligibility criteria. Relevant data from included studies were extracted. The methodological quality was evaluated for each study included by PEDro scale, risk of bias (Cochrane Collaboration's tool), and the level of evidence by National Health and Medical Research Council (NHMRC)., Results: Six randomized clinical trial (RCT) were included. In respect of the level of evidence, all studies were classified as Level II (NHMRC) and regarding to the methodological quality (PEDro scale), four studies were considered 'high' and two were 'fair'. Two publications presented low risk of bias, three with high risk of bias and one unclear. All the selected studies reported positive effects and improvements on risk of falls and muscle response after WBV exercise., Conclusion: WBV exercise may contribute to reduce the risk of falls and improve muscle responses in the elderly individuals., (Copyright© 2024 Meirelles et al. Published by Tehran University of Medical Sciences.)

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by motor and postural impairments. However, early brain injury can promote deleterious effects on the hippocampus, impairing memory. This study aims to investigate the effects of resveratrol treatment on memory, anxiety-like behavior, and neuroinflammation markers in rats with CP. Male Wistar rats were subjected to perinatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). They were treated with resveratrol (10 mg/kg, 0.1 ml/100 g) or saline from P3-P21, being divided into four experimental groups: CS (n = 15), CR (n = 15), CPS (n = 15), and CPR (n = 15). They were evaluated in the tests of novel object recognition (NORT), T-Maze, Light-Dark Box (LDB), and Elevated Plus Maze (EPM). Compared to the CS group, the CPS group has demonstrated a reduced discrimination index on the NORT (p < 0.0001) and alternation on the T-Maze (p < 0.01). In addition, the CPS group showed an increase in permanence time on the dark side in LDB (p < 0.0001) and on the close arms of the EPM (p < 0.001). The CPR group demonstrated an increase in the object discrimination index (p < 0.001), on the alternation (p < 0.001), on the permanence time on the light side (p < 0.0001), and on the open arms (p < 0.001). The CPR group showed a reduction in gene expression of IL-6 (p = 0.0175) and TNF-α (p = 0.0007) and an increase in Creb-1 levels (p = 0.0020). The CPS group showed an increase in the activated microglia and a reduction in cell proliferation in the hippocampus, while CPR animals showed a reduction of activated microglia and an increase in cell proliferation. These results demonstrate promising effects of resveratrol in cerebral palsy behavior impairment through reduced neuroinflammation in the hippocampus., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The National Diabetes Prevention Program (DPP) promotes lifestyle changes to prevent diabetes. However, only one-third of DPP participants achieve weight loss goals, and changes in diet are limited. Continuous glucose monitoring (CGM) has shown potential to raise awareness about the effects of diet and activity on glucose among people with diabetes, yet the feasibility of including CGM in behavioral interventions for people with prediabetes has not been explored. This study assessed the feasibility of adding a brief CGM intervention to the Arizona Cooperative Extension National DPP. Extension DPP participants were invited to participate in a single CGM-based education session and subsequent 10-day CGM wear period, during which participants reflected on diet and physical activity behaviors occurring prior to and after hyperglycemic events. Following the intervention, participants completed a CGM acceptability survey and participated in a focus group reflecting on facilitators and barriers to CGM use and its utility as a behavior change tool. A priori feasibility benchmarks included opt-in participation rates ≥ 50%, education session attendance ≥ 80%, acceptability scores ≥ 80%, and greater advantages than disadvantages of CGM emerging from focus groups, as analyzed using the Key Point Summary (KPS) method. Thirty-five DPP members were invited to participate; 27 (77%) consented, and 24 of 27 (89%) attended the brief CGM education session. Median survey scores indicated high acceptability of CGM (median = 5, range = 1-5), with nearly all ( n = 23/24, 96%) participants believing that CGM should be offered as part of the DPP. In focus groups, participants described how CGM helped them make behavior changes to improve their glucose (e.g., reduced portion sizes, increased activity around eating events, and meditation). In conclusion, adding a single CGM-based education session and 10-day CGM wear to the DPP was feasible and acceptable. Future research will establish the efficacy of adding CGM to the DPP on participant health outcomes and behaviors., Competing Interests: VdS is the State Director of the Arizona Cooperative Extension Diabetes Prevention Program. KMR reports ongoing consultation to WeightWatchers International, Inc. All other authors declare no conflicts of interest., (Copyright © 2024 Kelli M. Richardson et al.)

Wild boars or feral pigs are classified by the Brazilian Institute for the Environment and Renewable Resources (IBAMA) in "Category I of invasive exotic species". They cause economic losses, harm the environment, serve as hosts and reservoirs for several zoonotic disease agents, and provide a blood meal for tick species that act as vectors for zoonotic diseases. The objective of this study was to identify tick species on wild boars, assess host-seeking ticks in the related environment, and identify other potential tick hosts coexisting with wild boars on a farm located in the state of Minas Gerais, southeastern Brazil. Additionally, the study aimed to determine the presence of rickettsiae in these arthropods and assess the exposure of wild boars to rickettsiae species from the Spotted Fever Group and Rickettsia bellii through serology. A total of 3585 host-seeking ticks from three species (Amblyomma sculptum - 41.58%; Amblyomma dubitatum - 0.39% and Rhipicephalus microplus - 0.05%) were collected in the environment and A. sculptum was the most abundant species. Thirty-one wild boars were evaluated, resulting in the collection of 415 ticks, all of which were A. sculptum. Rickettsia DNA was not detected in samples of A. sculptum and R. microplus from the environment or in A. sculptum ticks from wild boars. However, all A. dubitatum ticks (n = 14) had Rickettsia bellii DNA confirmed by the species-specific PCR protocol. Out of the 31 serum samples from wild boars, 24 reacted with at least one Rickettsia antigen. Among these, seven individuals exhibited a reaction to a probable homologous antigen (PHA) of three rickettsiae species: R. rickettsii (n = 3), R. amblyommatis (n = 3) and R. rhipicephali (n = 1). Despite the high prevalence of seroreactivity, titers were low, indicating limited exposure to Rickettsia spp. Camera traps generated 874 animal records, capturing a total of 1688 individuals. At least 11 species of birds and 14 species of mammals (12 wild and two domestic) shared the environment with wild boars and potentially shared ticks with them. These findings provide baseline information for understanding the sharing of ticks and tick-borne pathogens between wild boars and other animals within the Cerrado biome. Further studies are necessary to monitor the potential and actual risk of wild boars to harbor infected ticks and their role in the transmission and maintenance cycle of Rickettsia spp., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest in the research work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The new technology of microbially induced calcium carbonate precipitation (MICP) has been applied in construction materials as a strategy to enhance their properties. In pursuit of solutions that are more localized and tailored to the study's target, this work focused on isolating and selecting bacteria capable of producing CaCO 3 for posterior application in concrete aggregates. First, eleven bacterial isolates were obtained from aggregates and identified as genera Bacillus, Lysinibacillus, Exiguobacterium, and Micrococcus. Then, the strains were compared based on the quantity and nature of calcium carbonate they produced using thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy with energy dispersive spectroscopy. Bacillus sp. dominated the cultured isolates and, along with Lysinibacillus sp., exhibited the highest CaCO 3 conversion (up to 80%). On the other hand, Exiguobacterium and Micrococcus genera showed the poor ability to MICP (21.3 and 20.3%, respectively). Calcite and vaterite were the dominant carbonate polymorphs, with varying proportions. Concrete aggregates have proven to be a source of microorganisms capable of producing stable calcium carbonates with a high conversion rate. This indicates the feasibility of using microorganisms derived from local sources for application in construction materials as a sustainable way to enhance their characteristics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents. We employed a combination of a series of machine learning (ML) techniques to select and evaluate potential compounds with antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains. In the present study, we describe the antibacterial activity of six compounds against MSSA and MRSA reference (American Type Culture Collection (ATCC)) strains as well as two clinical strains of MRSA. These compounds showed minimal inhibitory concentrations (MIC) in the range from 12.5 to 200 μM against the different bacterial strains evaluated. Our results constitute relevant proven ML-workflow models to distinctively screen for novel MRSA antibiotics.

Purpose: Due to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging., Methods: Intrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded., Results: Out of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation., Conclusion: Intrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted., Competing Interests: The Department of Radiation Oncology, University Hospital, LMU Munich, Germany, received grants from Brainlab AG. SC and MN received speaker fees and travel support from Brainlab AG. PF is currently employed by Brainlab AG. However, at the time of the conception and draft of this manuscript, PF was not employed by Brainlab AG. PF declares that his employment had no influence on the design, the collection and the analysis of data, on the writing of the manuscript or the decision to submit the manuscript for publication., (© 2024 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are useful markers to assess the effects of exposure to anticholinesterase insecticides (Anti-AChE). In addition, lymphocyte neuropathy target esterase (LNTE) has been used as biomarker of neuropathic organophosphate compounds (OPs). Thus, this study evaluates the main types of circulating biomarkers related to the cholinergic system and to the neuropathy induced by OPs in standardized human samples. To achieve this objective, total protein of human plasma, erythrocytes and lymphocytes were first standardized, and then AChE, BChE and LNTE activities in human blood were evaluated in the presence of inhibitors. The acceptance criteria of the regulatory agency were respected with coefficients of regression of curves of 0.9972 for cholinesterase and 0.9956 for LNTE analyses. The wavelength established to perform cholinesterase assay was 450 nm and the time of incubation of the enzymes with inhibitors was 30 min. Differences were observed among the IC 50 values regarding the in vitro inhibition of AChE, BChE and LNTE in the presence of OPs. In conclusion, the procedures demonstrated by the present work were simple, fast, inexpensive, sensitive, easy to be replicated and suitable to make conclusions about the neurotoxicity induced by Anti-AChE and neuropathic OPs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guilherme Luz Emerick reports a relationship with Federal University of Mato Grosso that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study analyzed the effects of a physical exercise program compared to the complexity of the motor task on the cognitive function, brain-derived neurotrophic factor (BDNF) levels, and lipid profile of older adults with mild cognitive impairment (MCI). Twenty-seven participants were randomized into three intervention groups: Physical Exercise (PE), Motor Task (MT), and Physical Exercise associated with Motor Task (PE + MT). Six months of intervention twice a week resulted in improvements in cognitive function, total cholesterol (TC), and LDL cholesterol (LDL-C) in the PE (p < 0.05). In the PE + MT, in addition to improved cognitive capacity, there was also a reduction in non-HDL cholesterol (NHDL-C) and LDL cholesterol (LDL-C) levels (p < 0.05), while in the MT, the values of TC, NHDL-C, and LDL-C decreased as a result of the intervention. BDNF levels were not affected by the interventions. In conclusion, PE alone or combined with MT is effective in promoting improvements in overall cognitive function and lipid profile in older adults with MCI; and BDNF seems not to be a sensitive marker for people with mild cognitive impairment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aim of this prospective observational study was to evaluate the dosimetry benefits, changes in pulmonary function, and clinical outcome of online adaptive MR-guided SBRT., Methods: From 11/2020-07/2022, 45 consecutive patients with 59 lesions underwent multi-fraction SBRT (3-8 fractions) at our institution. Patients were eligible if they had biopsy-proven NSCLC or lung cancer/metastases diagnosed via clinical imaging. Endpoints were local control (LC) and overall survival (OS). We evaluated PTV/GTV dose coverage, organs at risk exposure, and changes in pulmonary function (PF). Acute toxicity was classified per the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0., Results: The median PTV was 14.4 cm 3 (range: 3.4 - 96.5 cm 3 ). In total 195/215 (91%) plans were reoptimised. In the reoptimised vs. predicted plans, PTV coverage by the prescribed dose increased in 94.6% of all fractions with a median increase in PTV V PD of 5.6% (range: -1.8 - 44.6%, p < 0.001), increasing the number of fractions with PTV V PD  ≥ 95% from 33% to 98%. The PTV D 95% and D 98% (BED 10 ) increased in 93% and 95% of all fractions with a median increase of 7.7% (p < 0.001) and 10.6% (p < 0.001). The PTV D 95% (BED 10 ) increased by a mean of 9.6 Gy (SD: 10.3 Gy, p < 0.001). At a median follow-up of 21.4 months (95% CI: 12.3-27.0 months), 1- and 2-year LC rates were 94.8% (95% CI: 87.6 - 100.0%) and 91.1% (95% CI: 81.3 - 100%); 1- and 2-year OS rates were 85.6% (95% CI: 75.0 - 96.3%) and 67.1 % (95% CI: 50.3 - 83.8%). One grade ≥ 3 toxicity and no significant reduction in short-term PF parameters were recorded., Conclusions: Online adaptive MR-guided SBRT is an effective, safe and generally well tolerated treatment option for lung tumours achieving encouraging local control rates with significantly improved target volume coverage., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Department of Radiation Oncology of the LMU University Hospital, LMU Munich has research agreements with ViewRay Inc., Elekta, Brainlab, and C-RAD. ViewRay Inc. did not fund this study and was not involved and had no influence on the study design, the collection or analysis of data, or on the writing of the manuscript. MN reports research grants and speaker fees/travel support from Brainlab, ViewRay, AstraZeneca. FM reports a research grant from AstraZeneca and honoraria from AstraZeneca, Novartis, Roche, Lilly, Elekta and Brainlab. FM serves on the advisory board of AstraZeneca, Novartis. CB reports receiving grants or contracts from ViewRay, Brainlab, and Elekta; payment or honoraria from Bristol-Myers Squibb, Roche, Merck, AstraZeneca, Opasca, C-RAD, Elekta, and ViewRay; receiving support for attending meetings or travel from Bristol-Myers Squibb, Roche, Merck, AstraZeneca, Elekta, and View Ray; and having a leadership or fiduciary role with ESTRO, all outside the submitted work. SC reports research grants and speaker fees/travel support from Elekta, Viewray and Brainlab. CE reports consulting fees from Novartis outside the submitted work., (© 2024 The Author(s).)

The aim of this cross-sectional study was to compare workplace conditions and metal exposures in 431 waste pickers who worked nearby at the Estrutural Dump in Brasilia utilizing hair ( n  = 310) and nail ( n  = 355) as matrices of exposure. Waste pickers were grouped according to their workplace (open waste dump: G1 and sorting plants: G2). Hair and nail samples were collected and analyzed using ICP-MS. The work duration in the facilities was significantly different between the groups with averages of 16.46 (8.48) yrs and 9.26 (6.28) yrs for hair donors in G1 and G2, and 15.92 (7.72) yrs and 8.55 (5.77) yrs for toenail donors in G1 and G2, respectively. The arithmetic means (μg/g) of cadmium, copper, lead, and manganese in hair were significantly higher in G2 (0.076 ± 0.133; 19.61 ± 18.16; 2.27 ± .56 and 3.87 ± 5.59, respectively) compared to G1 (0.069 ± 0.235; 15.72 ± 15.18; 1.72 ± 4.04 and 3.65 ± 5.5, respectively). Concentrations of arsenic, barium, cadmium, copper, cobalt, lead, manganese, and molybdenum in nail were significantly higher in G2 (0.57 ± 0.39; 22.74 ± 42.06; 0.1 ± 0.08; 22.7 ± 51.60; 0.48 ± 0.45; 4.69 ± 9.43; 19.07 ± 20.75; 1.80 ± 1.76, respectively) compared to G1 (0.40 ± 0.28; 15.32 ± 22.31; 0.08 ± 0.11; 11.91 ± 16.25; 0.37 ± 0.37; 3.94 ± 15.04; 13.01 ± 19.08; 1.16 ± 1.80, respective. Our findings suggest that the studied population was exposed to toxic metals and indicates the need for chemical exposure prevention policies to monitor chemical risk exposures in waste pickers.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE., (© 2023. The Author(s).)

BACKGROUND: Studies evaluating sputum quality and Xpert ® MTB/RIF positivity in the context of active case finding are scarce. We aimed to determine whether sputum quality is associated with Xpert positivity and whether the association differed according to demographic and clinical characteristics. METHODS: A cross-sectional analysis using data from a mass screening programme in Brazilian prisons was conducted from 2017 to 2021. We administered a standardised questionnaire, obtained a chest X-ray and collected a spot sputum sample for Xpert testing. Sputum quality was classified as 'salivary', 'mucoid/mucopurulent' or 'blood-stained'. We used log binomial regressions to estimate the relationship between sputum quality and Xpert positivity, assessing interactions with participant characteristics. RESULTS: Among 4,368 participants for whom sputum quality was assessed, 957 (21.9%) produced salivary specimens, 3,379 (77.4%) had mucoid/mucopurulent sputum and 32 (0.7%) had blood-stained sputum. Xpert positivity was higher among those with mucoid/mucopurulent sputum than among those with salivary samples (12.0% vs. 3.7%). Mucopurulent sputum independently predicted Xpert positivity among individuals with and without symptoms, current smoking and abnormal chest radiographs on CAD4TB. CONCLUSIONS: In our study, sputum appearance independently predicted Xpert positivity, and could be used together with chest X-ray and symptom screening to inform use of Xpert in individual or pooled testing.

Backgrounds: Restrictions in movement and closure of borders imposed by the Sars-Cov- 2 worldwide pandemic have affected the global illicit drug market, including cocaine trafficking. In this scenario, comparing cutting agents added to the cocaine and the drug purity are valuable strategies to understand how the drug trade has been impacted by the pandemic., Methods: In this work, 204 cocaine salt materials seized in the Brazilian Federal District, before (2019) and during COVID-19 pandemics (2020) were analyzed by two analytical techniques: gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR). Statistical analyses, including Principal Component Analysis (PCA), were applied to evaluate the COVID-19 pandemic impact in the local market. Bibliometric analysis was performed as a forensic intelligence tool., Results: From 2019-2020, cocaine average purity decreased 26 % while the frequency of cutting agents, as caffeine and anesthetics (lidocaine, tetracaine) increased. The high percentage of unknown were increased. Different cocaine profiling seized in 2020 showed new cutting agents, such as Irganox 1076, and Irgafos 168, indicating a trend on new adulterants/diluents introduced in the local market to mitigate the local drug shortage. Also in 2020, there was an increase in the local cocaine seizures, despite of the cocaine drug purity decreased by 26 % compared to 2019., Conclusions: Taken together, these data showed that the covid-19 pandemics has impacted cocaine trafficking in the Brazilian Federal District, an increase in cocaine seizures, which may indicate greater demand for the drug and, specially, changes in the cocaine purity and cutting agents profiling showing how traffickers tried to minimize difficulties in crossing the Brazilian border during COVID-19 restrictions. The information is relevant since Brazil is one of the major departure points for traded cocaine to the world. Bibliometric analysis showed that Irgafos 168 and Irganox 1076 were consistently identified as cocaine cutting agents for the first time., 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. All co-authors have seen and agreed with the contents and declare no financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Treatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors., Objective: We evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC. Comparisons of CTC counts, protein expression profiling, and DNA mutants were made in relation to overall survival and progression-free survival., Methods: CTCs were isolated from 10 mL blood samples using the ISET® system (Isolation by SizE of Tumor Cells; Rarecells, France) and counted. Protein expression was evaluated in immunocytochemistry assays. DNA mutations were identified with next generation sequencing (NGS)., Results: Blood samples (10 mL) were collected from 12 patients with mccRCC before the start of first-line systemic therapy, and again 30 and 60 days after the start of treatment. All 12 patients had CTCs detected at baseline (median, 1.5 CTCs/mL; range: 0.25-7.75). Patients with CTC counts greater than the median had two or more metastatic sites and exhibited worse progression-free survival (19.7 months) compared to those with CTC counts less than the median (31.1 months). Disease progression was observed in 7/12 patients during the study. Five of these patients had baseline CTC counts greater than the median, one had higher CTC levels at the second blood collection, and one patient had CTCs present at 1 CTC/mL which positively stained for PD-L1, N-cadherin, VEGF, and SETD2. CTC DNA from six patients with worse outcomes was subjected to NGS. However, no conclusions could be made due to the low variant allele frequencies., Conclusion: Detection of CTCs in patients with mccRCC receiving first-line treatment is a feasible tool with prognostic potential since increased numbers of CTCs were found to be associated with metastasis and disease progression., Competing Interests: Declaration of Competing Interest All authors declared that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Staphylococcus aureus is one of the most relevant mastitis pathogens in dairy cattle, and the acquisition of antimicrobial resistance genes presents a significant health issue in both veterinary and human fields. Among the different strategies to tackle S. aureus infection in livestock, bacteriophages have been thoroughly investigated in the last decades; however, few specimens of the so-called jumbo phages capable of infecting S. aureus have been described. Herein, we report the biological, genomic, and structural proteomic features of the jumbo phage vB&#95;SauM-UFV&#95;DC4 (DC4). DC4 exhibited a remarkable killing activity against S. aureus isolated from the veterinary environment and stability at alkaline conditions (pH 4 to 12). The complete genome of DC4 is 263,185 bp (GC content: 25%), encodes 263 predicted CDSs (80% without an assigned function), 1 tRNA (Phe-tRNA), multisubunit RNA polymerase, and an RNA-dependent DNA polymerase. Moreover, comparative analysis revealed that DC4 can be considered a new viral species belonging to a new genus DC4 and showed a similar set of lytic proteins and depolymerase activity with closely related jumbo phages. The characterization of a new S. aureus jumbo phage increases our understanding of the diversity of this group and provides insights into the biotechnological potential of these viruses. KEY POINTS: • vB&#95;SauM-UFV&#95;DC4 is a new viral species belonging to a new genus within the class Caudoviricetes. • vB&#95;SauM-UFV&#95;DC4 carries a set of RNA polymerase subunits and an RNA-directed DNA polymerase. • vB&#95;SauM-UFV&#95;DC4 and closely related jumbo phages showed a similar set of lytic proteins., (© 2023. The Author(s).)

Aim In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children's freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children. Materials and methods We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic. Results Of the patients with traumatic brain injury, 1371 visited the trauma center in 2019 and 1052 in 2020. No difference was noted in the incidence rate of abusive head trauma between these periods (p=0.142) or in mortality from violence in Brazil. Recreational causes of pediatric TBI increased during the first year of the COVID-19 pandemic in Brazil and falls from bicycles significantly increased during the pandemic (p<0.001). Conclusion A global reduction in pediatric admissions to emergency rooms as well as no impact on mortality and severity of pediatric TBI were observed during the COVID-19 pandemic in Brazil. Additionally, a public education program regarding child safety during recreational activities, particularly how to avoid falls from bicycles was recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ferreira Furtado et al.)

Nosocomial infections (NIs) appear in patients under medical care in the hospital. The surveillance of the bacterial communities employing high-resolution 16S rRNA profiling, known as metabarcoding, represents a reliable method to establish factors that may influence the composition of the bacterial population during NIs. The present study aimed to utilize high-resolution 16S rRNA profiling to identify high bacterial diversity by analyzing 11 inside and 10 outside environments from the General Hospital of Ribeirão Preto Medical School, Brazil. Our results identified a high bacterial diversity, and among these, the most abundant bacterial genera linked to NIs were Cutibacterium, Streptococcus, Staphylococcus , and Corynebacterium . A Acinetobacter was detected in cafeterias, bus stops, and adult and pediatric intensive care units (ICUs). Data suggest an association between transport and alimentation areas proximal to the hospital ICU environment. Interestingly, the correlation and clusterization analysis showed the potential of the external areas to directly influence the ICU pediatric department microbial community, including the outpatient's clinic, visitor halls, patient reception, and the closest cafeterias. Our results demonstrate that high-resolution 16S rRNA profiling is a robust and reliable tool for bacterial genomic surveillance. In addition, the metabarcoding approach might help elaborate decontamination policies, and consequently reduce NIs.

Anaerobic spore-forming bacteria are a continuous threat to the dairy industry due to their ability to withstand processing conditions, such as those during heat treatment. These ubiquitous microorganisms have ample opportunity for multiple entry points into the milk chain, creating food quality and safety issues. Certain spore-formers, namely bacilli and clostridia, are more problematic due to their ability to spoil dairy products and pathogenicity. In this study, we investigated how milk treatment and milk powder production influenced the composition and survival of anaerobic spore-formers. Samples were obtained on three different days (replicate blocks) during the production of dairy powders and examined in a culture-dependent manner using the most probable number method coupled with 16S rRNA amplicon sequencing and metagenomic analysis of the enriched samples. Results revealed that the milk separation greatly affected the spore-former presence and composition which were detected along the entire production line from raw material to milk powders. Throughout the various points of the production line, the occurrence of species belonging to the Bacillus cereus sensu lato was higher than that of clostridia. Sequence variants (SVs) belonging to the anaerobic spore-forming genus Clostridium were taxonomically assigned to two SVs groups and were detected in all three replicate blocks. A total of 19 metagenome-assembled genomes were recovered from nine enrichments. Four near-complete and two medium-quality genomes were found in raw milk/milk powder samples and further assigned as Clostridium tyrobutyricum and Clostridium diolis, which may constitute a problem in the finished dairy product. In conclusion, our findings highlight spore-formers' importance on dairy quality and may aid in their intervention and control in the dairy production line., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: Despite clear evidence that adherence to dietary and physical activity advice can reduce the risk of cardiometabolic disease, a significant proportion of the population do not follow recommendations. Personalized advice based on genetic variation has been proposed for motivating behavior change, although research on its benefits to date has been contradictory., Objective: To evaluate the efficacy of genotype-based dietary or physical activity advice in changing behavior in the general population and in individuals who are at risk of cardiovascular disease (CVD) or type II diabetes mellitus (T2DM)., Data Sources: MEDLINE, EMBASE, PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to January 7, 2022. Randomized controlled trials of a genotype-based dietary and/or physical activity advice intervention that aimed to change dietary and/or physical activity behavior were included., Data Extraction: Abstracts of 7899 records were screened, and 14 reports from 11 studies met the inclusion criteria., Data Analysis: Genotype-based dietary or physical activity advice was found to have no effect on dietary behavior in any of the studies (standardized mean difference [SMD] .00 [-.11 to .11], P = .98), even when analyzed by subgroup: "at risk" (SMD .00 [-.16 to .16, P = .99]; general population (SMD .01 [-.14 to .16], P = .87). The physical activity behavior findings were similar for all studies (SMD -.01 [-.10 to .08], P = .88), even when analyzed by subgroup: "at risk" (SMD .07 [-.18 to .31], P = .59); general population (SMD -.02 [-.13 to .10], P = .77). The quality of the evidence for the dietary behavior outcome was low; for the physical activity behavior outcome it was moderate., Conclusions: Genotype-based advice does not affect dietary or physical activity behavior more than general advice or advice based on lifestyle or phenotypic measures. This was consistent in studies that recruited participants from the general population as well as in studies that had recruited participants from populations at risk of CVD or T2DM., Systematic Review Registration: PROSPERO registration no. CRD42021231147., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study compared the performance of Reciproc and Reciproc Blue endodontic files in retreatment time and re-establishment of apical patency, plus removal of a bioceramic sealer from the canal surface with the supplementary use of the XP-endo Finisher R. Following preparation, slightly curved oval root canals in mandibular incisors were filled using a corresponding gutta-percha point and a bioceramic sealer. Apical patency achievement was assessed and the time required to reach the original working length was recorded. The samples were split longitudinally and were photographed to assess the material remaining on the canal walls. No significant differences were observed regarding patency achievement or retreatment times when comparing Reciproc and Reciproc Blue. Significant less material remained on the canal walls when Reciproc was followed by XP-endo compared with Reciproc alone, and when the data for Reciproc and Reciproc Blue were pooled., (© 2022 The Authors. Australian Endodontic Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Endodontology Inc.)

Rodents infected with Strongyloides venezuelensis are experimental models applied to strongyloidiasis research. This study evaluated oral and subcutaneous dexamethasone (DEX) treatments to establish immunosuppression in an experimental model of Strongyloides hyperinfection. Rattus norvegicus Wistar were divided: G I (-): untreated and uninfected animals, G II (+): untreated and infected, G III (o -) orally treated and uninfected, G IV (o +) orally treated and infected, G V (sc -) subcutaneously treated and uninfected, G VI (sc +) subcutaneously treated and infected. For oral administration, DEX was diluted in sterile water (5 µg/ml) and made available to the animals on intervals in experimental days - 5-0, 8-13 and 21-26. For subcutaneous administration, animals received daily injections of DEX disodium phosphate (2 mg/kg). Infection was established by the subcutaneous inoculation of 3000 S. venezuelensis filarioid larvae. Groups were evaluated by egg per gram of feces and parasite females counts and IgG, IgG1 and IgG2a detection. GIV (o +) had egg peaks count on days 13 and 26 and maintained egg elimination until the last experimental day. Parasitic females recovery at day 30 was significantly higher in G IV (o +) when compared to G VI (sc +). Levels of IgG, IgG1 and IgG2a of all groups, except the positive control GII (+), were below the detection threshold. Pharmacological immunosuppression induced by oral administration of DEX produced high parasitic burden, and is a noninvasive method, useful to establish immunosuppression in strongyloidiasis hyperinfection model in rats., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Society for Parasitology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: To identify the main ventilatory support medical devices related to the occurrence of pressure injuries in hospitalised adults, as well as the most frequent anatomical localisations of these injuries., Methods: The Integrative review was registered at Open Science Framework as per DOI 10.17605/OSF.IO/P3NTZ. Two independent reviewers, in May 2022, searched the databases: PubMed, Embase, Cochrane Database of Systematic Reviews, LILACS and CINAHL; no language or publication year restriction. The review question was: What are the ventilatory support medical devices that cause PIs in hospitalised adults more often? The terms for searching the database were: "adult," "noninvasive ventilation," "artificial respiration." and "pressure injury," and their synonyms. This review followed the PRISMA checklist., Results: The final sample was 21 articles. Oxygen nasal catheters caused up to 40.7% of the pressure injuries by ventilatory support devices identified, all in the ears. Noninvasive mechanical ventilation oronasal masks presented an incidence of pressure injuries of 63.3%. The nasal bridge was the site most affected by this mask. The Set of Holders for Insight® endotracheal tubes was the device that caused the most pressure injuries, with an incidence of 75%, affecting lip commissure. Tracheostomy cannula accounted for 18.2% of the pressure injuries related to ventilatory support devices; all lesions were in the neck., Conclusion: The ventilatory support devices causing pressure injuries and the most affected sites were, respectively, nasal catheters, ears; masks, nasal bridge; endotracheal tubes, lip commissures; tracheostomy cannulas, neck., Relevance for Clinical Practice: Knowing which respiratory devices cause pressure injuries more often in hospitalised adults and which anatomical localisations are more likely to be affected is fundamental for adopting preventive measures and reducing the occurrence of this problem., No Patient or Public Contribution: No patient or public contribution because of the review., (© 2023 John Wiley & Sons Ltd.)

Cerebral palsy is a neurodevelopmental disease characterized by postural, motor, and cognitive disorders, being one of the main causes of physical and intellectual disability in childhood. To minimize functional impairments, the use of resveratrol as a therapeutic strategy is highlighted due to its neuroprotective and antioxidant effects in different regions of the brain. Thus, this study aimed to investigate the effects of neonatal treatment with resveratrol on postural development, motor function, oxidative balance, and mitochondrial biogenesis in the brain of rats submitted to a cerebral palsy model. Neonatal treatment with resveratrol attenuated deficits in somatic growth, postural development, and muscle strength in rats submitted to cerebral palsy. Related to oxidative balance, resveratrol in cerebral palsy decreased the levels of MDA and carbonyls. Related to mitochondrial biogenesis, was observed in animals with cerebral palsy treated with resveratrol, an increase in mRNA levels of TFAM, in association with the increase of citrate synthase activity. The data demonstrated a promising effect of neonatal resveratrol treatment, improving postural and muscle deficits induced by cerebral palsy. These findings were associated with improvements in oxidative balance and mitochondrial biogenesis in the brain of rats submitted to cerebral palsy., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: The primary objective was to study long-term outcomes in children with idiopathic facial aseptic granuloma (IFAG). The secondary objectives were to describe the clinical polymorphism of this entity, the different therapeutic options, and the occurrence of rosacea in this population., Methods: We selected patients with a clinical diagnosis of IFAG seen in two different hospitals in Normandy between March 2016 and February 2021, and we collected clinical and therapeutic data from computerized medical records. A remote consultation based on recent photographs was performed to collect new data, and the children's parents were asked to complete a questionnaire between February and August 2021., Results: Ten children were included in this study. Nine patients presented with a single red to purplish nodule. One patient presented multiple papulopustular plaques. IFAG healed spontaneously without major sequelae, and this outcome was not influenced by any treatments. During follow-up, two patients developed childhood rosacea., Conclusion: Although some clinical heterogeneity exists, early diagnosis and follow-up of IFAG is necessary to avoid unnecessary topical or systemic antibiotic treatments that do not shorten the disease course. IFAG appears to be a possible mode of entry for infantile rosacea., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Effective and culturally safe pain management can facilitate analgesia and improve the quality of life. Individualised, multimodal and multidisciplinary approaches are highly recommended. There exist gaps in the knowledge on pain management, in terms of the assessment and/or treatment, in indigenous peoples and the currently available information is scattered in the literature. A scoping review will provide an overview or evidence map on the variety of approaches used in different cultures, in different parts of the world., Methods and Analysis: The search strategy comprises three stages. The first stage identified the MeSH terms and keywords in PubMed. The second stage will consist of a search of MEDLINE, EMBASE, LILACS, CINAHL, Web of Science, APA PsycNet and Scopus, followed by a search in Google and Google Scholar, GreyGuide, ProQuest Dissertations and Theses, Theses Canada Portal (Library and Archives Canada), TROVE (National Library of Australia), Aboriginal and Torres Strait Islander Health Bibliography, and Cybertesis. The papers will be screened, selected and extracted independently by two researchers. Descriptive data analysis will be performed, and the results will be presented using a narrative summary, graphs, tables and figures., Ethics and Dissemination: This review does not require ethical approval, as data from the literature available in databases will be collected and analysed. The protocol was registered at the Open Science Framework. The data on pain assessment and treatment in indigenous peoples will be presented through a narrative summary, figures, charts and tables. Results will be submitted to an open-access journal for publication and will be disseminated through scientific events, scientific meetings, public events and conversation circles with indigenous peoples., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil., (© 2023. The Author(s).)

Although new nematicides have appeared, the demand for new products less toxic and more efficient for the control of plant-parasitic nematodes are still high. Consequently, studies on natural secondary metabolites from plants, to develop new nematicides, have increased. In this work, nineteen extracts from eleven Brazilian plant species were screened for activity against Meloidogyne incognita. Among them, the extracts of Piterogyne nitens showed a potent nematostatic activity. The alkaloid fraction obtained from the ethanol extract of leaves of P. nitens was more active than the coming extract. Due to the promising activity from the alkaloid fraction, three isoprenylated guanidine alkaloids isolated from this fraction, galegine (1), pterogynidine (2), and pterogynine (3) were tested, showing similar activity to the alkaloid fraction, which was comparable to that of the positive control Temik at 250 μg/mL. At lower concentrations (125-50 μg/mL), compound 2 showed to be the most active one. As several nematicides act through inhibition of acetylcholinesterase (AChE), the guanidine alkaloids were also employed in two in vitro AChE assays. In both cases, compound 2 was more active than compounds 1 and 3. Its activity was considered moderated compared to the control (physostigmine). Compound 2 was selected for an in silico study with the electric eel (Electrophorus electricus) AChE, showing to bind mostly to the same site of physostigmine in the AChEs, pointing out that this could be the mechanism of action for this compound. These results suggested that the guanidine alkaloids 1,2 and 3 from P. nitens are promising for the development of new products to control M. incognita, especially guanidine 2, and encourage new investigations to confirm the mechanism of action, as well as to determine the structure-activity relationship of the guanidine alkaloids., 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 Inc. All rights reserved.)

Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies have shown that memory function and emotional behaviour are significantly impaired in CP. Current thought is that interventions for neuromotor damaged play a prominent role, but neglects the memory acquisition problems that affect the functioning and quality of life of these children. This systematic review aims to map and analyse pre-clinical interventions used to treat memory formation problems resulting from CP. For this, a search was carried out in the Pubmed, Web of Science, Scopus and Lilacs databases. Then, eligibility, extraction date and evaluation of the methodological quality of the studies were determined. 52 studies were included in this review, and 27 were included in a meta-analysis. Assessing memory performance as a primary outcome, and structural and biochemical changes in the hippocampus as a secondary outcome. CP models were reported to be induced by hypoxia-ischemia, oxygen deprivation and liposaccharide (LPS) exposure, resulting in impairments in the formation of short-term and long-term memory in adult life. A reduction in escape latency and dwell time were observed in the target quadrant as well as an increase in the time needed for the rodents to find the platform in the Morris Water Maze (MWM). Brain injuries during the perinatal period are considered an insult that negatively impacts hippocampus maturation and causes impairment in memory formation in adult life. Some studies reported that regions of the hippocampus such as the dentate gyrus and cornu ammonis 1 were impaired in CP, noting an increase in oxidative stress enzymes and pro-inflammatory cytokines, associated with a reduction in BDNF and neurogenesis levels. These were reported to cause a reduction in the number of neurons and the volume of the hippocampus, in addition to an increase in astrogliosis and apoptosis of neurons and difficulties in forming new memories similar to those that occur in children with CP. Interventions that reduced neuroinflammation and the presence of free radicals were highlighted as a therapy for the memory disturbance present in CP. Preclinical studies registered treatments with oxygen interventions, resveratrol and erythropoietin, which were able to reduce the damage to the hippocampus and promote improvements in memory and behaviour. In the meta-analysis of selected studies, we observed favorable results, through effect size, for the use of oxygen interventions (SDM -6.83 95% CI [-7.91, -5.75], Z = 12.38, p = 0.03; I2 = 71%), erythropoietin (SDM -3.16 95% CI [-4.27, -2.05], Z = 5.58, p = 0.002; I2 = 82%) and resveratrol (SDM -2.42 95% CI [-3.19, - 1.66], Z = 6.21, p = 0.01; I2 = 77%), stimulating plastic responses in the hippocampus and facilitating the memory formation, with these presenting positive effects in general (SDM -2.84 95% CI [-3.10, -2.59], Z = 22.00; p < 0.00001; I2 = 92.9%). These studies demonstrate possible avenues of intervention for memory alterations in experimental models of early brain injuries, highlighting promising interventions that can facilitate the maturation of the hippocampus and memory formation and, consequently, minimize functional problems that arise during development., Competing Interests: Declaration of Competing Interest 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. Reporting no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

Transgender women (TW) are a key population in the dynamics of human immunodeficiency virus (HIV) dissemination, although little is known about their perceptions of HIV risk. In this embedded, nested, mixed-methods study, we assessed factors associated with condomless sexual intercourse among TW and explored their risk perceptions and vulnerabilities regarding HIV exposure. The first phase involved a cross-sectional study, followed by qualitative interviews. Condomless sexual intercourse during their last sexual encounter was reported by 37.3% of participants, and 16.1% previously tested positive for HIV. Age older than 21 years, single status, and being a sex worker were protective factors for condomless intercourse. Otherwise, TW who reported a past sexual partner with a known sexually transmitted infection and those aware of post-exposure prophylaxis had a greater risk of condomless sexual intercourse ( p  < 0.05) during their most recent encounter. The qualitative interviews revealed that, despite TW being aware of their risk of contracting HIV, their vulnerabilities overlapped their risk perception, making them trivialize or ignore the risk. This study will help to understand the HIV dynamics among TW and contribute to further health research, education, policymaking, and planning associated with specific health strategies to promote the sexual health of TW.

Objectives: While persistent symptoms have been reported after the coronavirus disease-2019 (COVID-19), long-term data on outpatients with mild COVID-19 are lacking. The objective was to describe symptoms persisting for 12 months., Methods: This prospective cohort study on 1767 sailors of an aircraft carrier in which a Covid-19 outbreak occurred during a mission in April 2020 described predefined self-reported symptoms of Long-COVID at 6, 9 and 12 months. Logistic-regression analyses were used to identify correlates for Long-COVID at months 6, 9 and 12., Results: Among the 641 participants, 619 (35%) completed at least one follow-up questionnaire (413 COVID-positive and 206 COVID-negative). Symptoms of Long-COVID were reported by 53.7%, 55.2% and 54.3% of COVID-positive participants vs 31.2%, 23.3% and 40.0% in COVID-negative patients, at 6 (p <.002), 9 (p <.002) and 12 months (p =.13), respectively. The most frequent symptoms reported were concentration and memory difficulties, asthenia and sleep disorders., Conclusion: In this study more than half of COVID-positive outpatients reported persistent symptoms up to 12 months post-quarantine. These findings suggests that all patients, including those with mild disease, can be affected by Long-COVID. A lack of difference at 12 months with COVID-negative patienys prompts caution. The symptoms of Long-COVID are so non-specific that they may be viewed as the consequence of multiple intercurrent factors., 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 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: As health systems struggle to tackle the spread of Covid-19, resilience becomes an especially relevant attribute and research topic. More than strength or preparedness, to perform resiliently to emerging shocks, health systems must develop specific abilities that aim to increase their potential to adapt to extraordinary situations while maintaining their regular functioning. Brazil has been one of the most affected countries during the pandemic. In January 2021, the Amazonas state's health system collapsed, especially in the city of Manaus, where acute Covid-19 patients died due to scarcity of medical supplies for respiratory therapy., Methods: This paper explores the case of the health system's collapse in Manaus to uncover the elements that prevented the system from performing resiliently to the pandemic, by carrying out a grounded-based systems analysis of the performance of health authorities in Brazil using the Functional Resonance Analysis Method. The major source of information for this study was the reports from the congressional investigation carried out to unveil the Brazilian response to the pandemic., Results: Poor cohesion between the different levels of government disrupted essential functions for managing the pandemic. Moreover, the political agenda interfered in the abilities of the system to monitor, respond, anticipate, and learn, essential aspects of resilient performance., Conclusions: Through a systems analysis approach, this study describes the implicit strategy of "living with Covid-19", and an in-depth view of the measures that hampered the resilience of the Brazilian health system to the spread of Covid-19., (© 2023. The Author(s).)

Host response to invasive microbes in the bovine udder has an important role on the animal health and is essential to the dairy industry to ensure production of high-quality milk and reduce the mastitis incidence. To better understand the biology behind these host-microbiome interactions, we investigated the somatic cell proteomes at quarter level for four cows (collected before and after milking) using a shotgun proteomics approach. Simultaneously, we identified the quarter microbiota by amplicon sequencing to detect presence of mastitis pathogens or other commensal taxa. In total, 32 quarter milk samples were analyzed divided in two groups depending on the somatic cell count (SCC). The high SCC group (>100,000 cell/mL) included 10 samples and significant different proteome profiles were detected. Differential abundance analysis uncovers a specific expression pattern in high SCC samples revealing pathways involved in immune responses such as inflammation, activation of the complement system, migration of immune cells, and tight junctions. Interestingly, different proteome profiles were also identified in quarter samples containing one of the two mastitis pathogens, Staphylococcus aureus and Streptococcus uberis, indicating a different response of the host depending on the pathogen. Weighted correlation network analysis identified three modules of co-expressed proteins which were correlated with the SCC in the quarters. These modules contained proteins assigned to different aspects of the immune response, but also amino sugar and nucleotide sugar metabolism, and biosynthesis of amino acids. The results of this study provide deeper insights on how the proteome expression changes at quarter level in naturally infected cows and pinpoint potential interactions and important biological functions during host-microbe interaction., (© 2023. The Author(s).)

Mitochondrial fission and a Warburg phenotype of increased cellular glycolysis are involved in the pathogenesis of pulmonary hypertension (PH). The purpose of this study was to determine whether increases in mitochondrial fission are involved in a glycolytic switch in pulmonary arterial endothelial cells (PAECs). Mitochondrial fission is increased in PAEC isolated from a sheep model of PH induced by pulmonary overcirculation (Shunt PAEC). In Shunt PAEC we identified increases in the S 616 phosphorylation responsible for dynamin-related protein 1 (Drp1) activation, the mitochondrial redistribution of Drp1, and increased cellular glycolysis. Reducing mitochondrial fission attenuated cellular glycolysis in Shunt PAEC. In addition, we observed nitration-mediated activation of the small GTPase RhoA in Shunt PAEC, and utilizing a nitration-shielding peptide, NipR1 attenuated RhoA nitration and reversed the Warburg phenotype. Thus, our data identify a novel link between RhoA, mitochondrial fission, and cellular glycolysis and suggest that targeting RhoA nitration could have therapeutic benefits for treating PH., Competing Interests: Conflict of interest The authors declare they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infusion Pumps (IP) are medical devices that were developed in the 1960s and generate fluid flow at pressures higher than that of normal blood pressure. Various hospital sectors make use of them, and they have become indispensable in therapies requiring continuity and precision in the administration of medication and/or food. As they are classified Class III (high risk) equipment, their maintenance is crucial for proper performance of the device, as well as patient and operator safety. The principal consideration of the pump is the volume infused, and the device demands great attention to detail when being calibrated. A lack of necessary care with this equipment can lead to uncertainty in volume and precision during the administration of substances. Because of this, it is essential to evaluate its reliability, to prevent possible failures at time of execution. This control aims at the quality of the intended infusion result, becoming an indication of quality., Methods: This systematic review summarizes studies done over the last 10 years (2011 to December 2021) that address the reliability and accuracy of hospital infusion pumps, in order to identify planning of maintenance and/or other techniques used in management of the equipment. The Prisma method was applied and the databases utilized were Embase, MEDLINE/Pubmed, Web of Science, Scopus, IEEE Xplore, and Science Direct. In addition, similar reviews were studied in Prospero and the Cochrane Library. For data analysis, softwares such as Mendeley, Excel, RStudio, and VOSviewer were used, and Robvis helped in plotting risk of bias results for studies performed with Cochrane tools., Results: The six databases selected produced 824 studies. After applying eligibility criteria (inclusion and exclusion), removing duplicates, and applying filters 1 and 2, 15 studies were included in the present review. It was found that the most relevant sources came from the Institute of Electrical and Electronics Engineers (IEEE) and that the most relevant keywords revolved around the terms ("device failure", "infusion pumps", "adverse effects", "complications", etc.). These results made clear that there remains substantial room for improvement as it relates to the study of accuracy and reliability of infusion., Conclusions: We verified that the reliability and precision analysis of hospital infusion pumps need to be performed in a more detailed and consistent way. New developments, considering the model and IP specification, are intended, clearly explaining the adopted methodology., (© 2023. The Author(s).)

Natural products have important pharmacological activities. This study sought to investigate the activity of the compound betulinic acid (BA) against different strains of bacteria and fungi. The minimum inhibitory concentration (MIC) was determined and then the minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). After performing the in vitro tests, molecular modeling studies were carried out to investigate the mechanism of action of BA against the selected microorganisms. The results showed that BA inhibited the growth of microbial species. Among the 12 species ( Staphylococcus aureus , S. epidermidis , Pseudomonas aeruginosa , Escherichia coli , Mycobacterium tuberculosis , Candida albicans , C. tropicalis , C. glabrata , Aspergillus flavus , Penicillium citrinum , Trichophyton rubrum , and Microsporum canis) investigated, 9 (75%) inhibited growth at a concentration of 561 µM and 1 at a concentration of 100 µM. In general, the MBC and MFC of the products were between 561 and 1122 μM. In silico studies showed that BA presented a mechanism of action against DNA gyrase and beta-lactamase targets for most of the bacteria investigated, while for fungi the mechanism of action was against sterol 14α-demethylase (CYP51) targets and dihydrofolate reductase (DHFR). We suggest that BA has antimicrobial activity against several species.

Gut microbiota imbalance is associated with the occurrence of metabolic diseases such as obesity. Thus, its modulation is a promising strategy to restore gut microbiota and improve intestinal health in the obese. This paper examines the role of probiotics, antimicrobials, and diet in modulating gut microbiota and improving intestinal health. Accordingly, obesity was induced in C57BL/6J mice, after which they were redistributed and fed with an obesogenic diet (intervention A) or standard AIN-93 diet (intervention B). Concomitantly, all the groups underwent a treatment phase with Lactobacillus gasseri LG-G12, ceftriaxone, or ceftriaxone followed by L. gasseri LG-G12. At the end of the experimental period, the following analysis was conducted: metataxonomic analysis, functional profiling of gut microbiota, intestinal permeability, and caecal concentration of short-chain fatty acids. High-fat diet impaired bacterial diversity/richness, which was counteracted in association with L. gasseri LG-G12 and the AIN-93 diet. Additionally, SCFA-producing bacteria were negatively correlated with high intestinal permeability parameters, which was further confirmed via functional profile prediction of the gut microbiota. A novel perspective on anti-obesity probiotics is presented by these findings based on the improvement of intestinal health irrespective of undergoing antimicrobial therapy or not.