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Objective: To evaluate the plant-derived compound lignin (LIG) as a pretreatment of intraradicular dentin in combination with EDTA on push-out bond strength (PBS) and nanoleakage of the glass fiber posts (GFPs) cemented using adhesive resin cement., Material and Methods: Twenty-eight human incisor roots were prepared for GFP cementation and divided based on dentin pretreatment: (1) CONTROL: no pretreatment, (2) EDTA: 17% EDTA for 3 min, (3) EDTA-LIG: 17% EDTA and 2% lignin for 3 min, (4) EDTA-PAC: 17% EDTA and 2% lignin for 3 min. The GFPs were cemented using the self-adhesive resin cement Multilink Speed. The roots (n = 7) were sectioned into 1 mm-thick discs and subjected to PBS testing after 1 week or 6 months. Nanoleakage was analyzed by SEM. Statistical analysis was performed using two-factor ANOVA and Tukey's test (p < 0.05)., Results: Higher PBS was identified for the CONTROL group (p < 0.001). After 6 months, the EDTA-LIG maintained the bond strength with a predominance of mixed failures, while the EDTA-PAC, EDTA, and CONTROL groups showed reduction of bond strength, with a predominance of adhesive failures along with severe silver infiltration in the interface., Conclusion: LIG associated with EDTA as a pretreatment for intraradicular dentin shows significant potential for attaining stable bond strength and interfacial integrity of self-adhesive resin cement to intraradicular dentin., (© 2024 Wiley Periodicals LLC.)

Glycosylation is one of the most structurally and functionally diverse co- and post-translational modifications in a cell. Addition and removal of glycans, especially to proteins and lipids, characterize this process which has important implications in several biological processes. In mammals, the repeated enzymatic addition of a sialic acid unit to underlying sialic acids (Sia) by polysialyltransferases, including ST8Sia2, leads to the formation of a sugar polymer called polysialic acid (polySia). The functional relevance of polySia has been extensively demonstrated in the nervous system. However, the role of polysialylation in infection is still poorly explored. Previous reports have shown that Trypanosoma cruzi (T. cruzi), a flagellated parasite that causes Chagas disease (CD), changes host sialylation of glycoproteins. To understand the role of host polySia during T. cruzi infection, we used a combination of in silico and experimental tools. We observed that T. cruzi reduces both the expression of the ST8Sia2 and the polysialylation of target substrates. We also found that chemical and genetic inhibition of host ST8Sia2 increased the parasite load in mammalian cells. We found that modulating host polysialylation may induce oxidative stress, creating a microenvironment that favors T. cruzi survival and infection. These findings suggest a novel approach to interfere with parasite infections through modulation of host polysialylation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Barboza 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.)

Substantial sleep impairment in patients with Alzheimer's disease (AD) is one of the emerging points for continued efforts to better understand the disease. Individuals without cognitive decline, an important marker of the clinical phase of AD, may show early alterations in the sleep-wake cycle. The objective of this critical narrative review is to explore the bidirectional pathophysiological correlation between sleep disturbances and Alzheimer's Disease. Specifically, it examines how the disruption of sleep homeostasis in individuals without dementia could contribute to the pathogenesis of AD, and conversely, how neurodegeneration in individuals with Alzheimer's Disease might lead to dysregulation of the sleep-wake cycle. Recent scientific results indicate that sleep disturbances, particularly those related to impaired glymphatic clearance, may act as an important mechanism associated with the genesis of Alzheimer's Disease. Additionally, amyloid deposition and tau protein hyperphosphorylation, along with astrocytic hyperactivation, appear to trigger changes in neurotransmission dynamics in areas related to sleep, which may explain the onset of sleep disturbances in individuals with AD. Disruption of sleep homeostasis appears to be a modifiable risk factor in Alzheimer's disease. Whenever possible, the use of non-pharmacological strategies becomes important in this context. From a different perspective, additional research is needed to understand and treat the dysfunction of the sleep-wake cycle in individuals already affected by AD. Early recognition and correction of sleep disturbances in this population could potentially mitigate the progression of dementia and improve the quality of life for those with AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest. All authors read and approved the final manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The demand of non-toxic and biobased plasticizers is substantially growing, particularly in biodegradable thermoplastics-based packaging applications. Herein, a derivative of citric acid (CITREM-LR10), usually used as food additive, was evaluated for the first time as plasticizer in PLA and Ecovio® biopolymers. Films containing 10 %(w/w) of CITREM-LR10 were prepared and compared with films plasticized with another biobased compound, SOFT-NSAFE, derived from acetic acid. The incorporation of both plasticizers provokes a slight reduction of the glass transition, however, only CITREM-LR10 was able to augment the elongation at break value of PLA films. A further evaluation of the films by Raman confocal microscopy showed the segregation of the CITREM-LR10 in microdomains, which could explain the enhanced elongation at break value, behaving as stress concentrators. In addition, CITREM-LR10 provides antimicrobial activity against S. aureus and both plasticizers give antioxidant properties, and almost negligible diffusion in food simulated solution. Composting studies showed that the plasticizers do not have effect on the disintegration rate of the films. In spite of these outstanding properties, the water vapour and oxygen barrier properties of the films worsen with its incorporation, therefore, the inclusion of fillers in the material together with the plasticizers would be necessary to improve such properties for food packaging applications., 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 B.V. All rights reserved.)

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

The use of babassu agro-industrial residues in animal feed, in addition to being an economic option of great importance in reducing the environmental impact in regions of the Brazilian Cerrado, provides the production of good quality foods of animal origin due to its nutritional characteristics. However, information related to the nutritional components of babassu by-industrial residues has not yet been sufficiently explored. The aim of this study was to evaluate the nutritional potential of some by-products from the babassu production chain through chemical composition and in situ degradability analyses. The experiment was conducted in a completely randomized experimental design, with 4 by-products from babassu processing (cake, greasy, fine flour, and 95  µ m flour) and 5 replications. The by-products differ in terms of chemical composition, except for the hemicellulose content. For the degradability of fraction "a" of dry matter, it presented a higher percentage for 95  µ m flour. Fine flour and 95  µ m flour presented the highest fractions "b" and "c," potential, and effective degradability of dry matter. For the degradation of crude protein, the highest percentages of potential and effective degradability were observed for greasy and 95  µ m flour. The highest standardized potentially degradable fraction and the highest passage rate were obtained by 95  µ m flour, which also showed greater degradation for dry matter, crude protein, and neutral detergent fiber. Among the by-products studied, the babassu cake has superior chemical composition; however, the 95  µ m flour presented nutritional value and satisfactory rumen degradation to be used as an additive or in partial replacement of traditional concentrates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ygor Nascimento Portela et al.)

Introduction: Severe Acute Respiratory Syndrome (SARS) represents a serious public health problem for the indigenous peoples of Brazil, since acute respiratory infections are the main causes of morbidity and mortality in this population., Objective: To assess cases of SARS in Brazilian indigenous peoples in the context of the COVID-19 pandemic, as well as sociodemographic and health factors associated with deaths from SARS in this population., Methods: Ecological study carried out based on secondary data from the Brazilian Database for Epidemiological Surveillance of Influenza referring to the Brazilian indigenous population with SARS in 2020. The variables included sociodemographic factors and health conditions. Statistical analyses were carried out considering absolute (n) and relative (%) frequencies and logistic regression with odds ratios (OR), with death as the outcome of interest., Results: A total of 3062 cases were reported in the analyzed period. Of these, there was a predominance of men (54.6%), adults (41.4%), with comorbidities (52.3%), with low levels of schooling (67.4%) and residents of rural areas (55.8%). Cases and deaths were concentrated in the states of Amazonas and Mato Grosso do Sul, states in the North and Midwest of Brazil. A greater chance of death was observed in elderly indigenous people (OR = 6.29; 95%CI 4.71-8.39), with low levels of schooling (OR = 1.72; 95%CI 1.22-2.28), residents of rural areas (OR = 1.35; 95%CI 1.12-1.62), and with comorbidities (OR = 1.87; 95%CI 1.42-2.46), especially obesity (OR = 2.56; 95%CI 1.07-6.11)., Conclusion: The study was able to trace the clinical-epidemiological profile, as well as identify the groups of indigenous people most vulnerable to SARS as a result of COVID-19 and evolution to death in Brazil. The findings show the high impact on the morbidity and mortality of the Brazilian indigenous population exposed to SARS and are relevant for epidemiological health surveillance, since they can guide preventive public policy actions and quality of life measures for this ethnic group in Brazil., (© 2023. W. Montague Cobb-NMA Health Institute.)

Objective: This study assesses changes and challenges within the nursing curriculum in the Brazilian context, focusing on addressing contemporary professional and societal demands., Design: A systematic literature review (SLR) was conducted to identify and analyze the changes in Brazil's nursing curricula over time., Data Sources: Articles published between 1987 and 2023 were selected from Scopus and Web of Science databases for the systematic review., Review Methods: A hybrid review approach was employed, integrating Systematic Literature Review (SLR), Bibliometrics, and metanarrative. The study adhered to the SPAR-4-SLR (Scientific Procedures and Rationale for Systematic Literature Reviews) protocol, involving three main stages: (i) aggregation, (ii) organization, and (iii) evaluation. The analysis primarily focused on identifying emerging trends and evaluating curricular changes over the specified timeframe., Results: Analysis of the selected literature identified four principal thematic groups that emerged during the review period: (i) longitudinal curriculum assessment, (ii) biological and health sciences, (iii) human and social sciences, and (iv) nursing sciences. Noteworthy trends included the integration of emerging topics like mental health and care for victims of violence, coupled with a notable increase in emphasis on transformative and competency-based education. Nevertheless, significant gaps were observed in the existing literature, particularly concerning the absence of perspectives from students and recent graduates and limited research on vulnerabilities within the curriculum structure., Conclusions: This study underscores the imperative for flexible and adaptable nursing curricula that effectively address Brazil's diverse regional and social realities. It emphasizes the significance of adopting a holistic and inclusive approach to nursing education, preparing professionals to confront contemporary health challenges in a nation characterized by extensive cultural diversity and vast geographical dimensions. Further research and input from students and recent graduates are indispensable to rectify the gaps and ensure the continuous evolution of nursing education in Brazil., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests or personal relationships that could influence the findings reported in this paper. Hence, the authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to identify the dietary patterns of Brazilian children aged 6-23 months and to investigate their association with maternal socio-demographic factors. Data from the 2019 Brazilian National Health Survey were used in this cross-sectional study. Mothers of 1616 children aged 6-23 months reported on their children's dietary intake. Dietary patterns were identified using principal component analysis, and their associations with maternal socio-demographic characteristics were assessed using linear regression models. The first consisted of healthy patterns and the second, unhealthy ones. Linear regression showed that adherence to a healthy dietary pattern was higher among children of mothers who were older (β = 0.02, p = 0.01), had more years of education (β = 0.49, p = 0.04), reported living with a partner (β = 0.29, p = 0.01), and resided in an urban area (β = 0.35, p = 0.01). Conversely, adherence to the unhealthy pattern was positively associated with mothers who declared themselves as black or brown (β = 0.25, p = 0.03). Our results show that older mothers with higher levels of education and paid work and who live with a partner are more likely to contribute to their children's healthy eating patterns. We conclude that socio-demographic factors may influence the quality of the food offered to children. Nevertheless, advocating for public policies promoting nutritious complementary diets emphasising fresh and minimally processed foods remains crucial for children whose mothers do not possess these favourable socio-demographic characteristics.

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1 , an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 da Silva Costa, Ito, da Cruz, De Souza, Rios, Bertozzo, Camargo, Viturino, Lanaro, de Albuquerque, do Canto, Saad, Ospina-Prieto, Ozelo, Costa and de Melo.)

The human protein Abelson kinase (Abl), a tyrosine kinase, plays a pivotal role in developing chronic myeloid leukemia (CML). Abl's involvement in various signaling pathways underscores its significance in regulating fundamental biological processes, including DNA damage responses, actin polymerization, and chromatin structural changes. The discovery of the Bcr-Abl oncoprotein, resulting from a chromosomal translocation in CML patients, revolutionized the understanding and treatment of the disease. The introduction of targeted therapies, starting with interferon-alpha and culminating in the development of tyrosine kinase inhibitors (TKIs) like imatinib, significantly improved patient outcomes. However, challenges such as drug resistance and side effects persist, indicating the necessity of research into novel therapeutic strategies. This review describes advancements in Abl kinase inhibitor development, emphasizing rational compound design from structural and regulatory information. Strategies, including bivalent inhibitors, PROTACs, and compounds targeting regulatory domains, promise to overcome resistance and minimize side effects. Additionally, leveraging the intricate structure and interactions of Bcr-Abl may provide insights into developing inhibitors for other kinases. Overall, this review highlights the importance of continued research into Abl kinase inhibition and its broader implications for therapeutic interventions targeting kinase-driven diseases. It provides valuable insights and strategies that may guide the development of next-generation therapies., (© 2024 Wiley‐VCH GmbH.)

Objectives: Despite the discrepancy between demand and availability of organs for transplantation, controlled circulatory death donation has not been implemented in Portugal. This study aimed to estimate the potential increase in organ donation from implementing such a program., Material and Methods: All deceased patients within the intensive care medicine department at Centro Hospitalar Universitário de São João, throughout the year 2019, were subjected to retrospective analysis. Potential gain was estimated comparing the results with the number of donors and organs collected during the same period at this hospital center. Differences in variables between groups were assessed using t tests for independent samples or Mann-Whitney U tests for continuous variables, and chi-squared tests were used for categorical variables., Results: During 2019, 152 deaths occurred after withdrawal of life-sustaining therapies, 10 of which would have been potentially eligible for donation after controlled circulatory death. We can anticipate a potential increase of 10 prospective donors, a maximum 21% growth in yearly transplantation activity, with a greater impact on kidney transplantation. For most patients, the time between withdrawal of organ support and death surpassed 120 minutes, an outcome explained by variations in withdrawal of life-sustaining measures and insufficient clinical records, underestimating the potential for controlled circulatory arrest donation., Conclusion: This study effectively highlights public health benefits of controlled circulatory arrest donation. Legislation allowing donation through this method represents a social gain and enables patients who will never meet brain death criteria to donate organs as part of the end-of-life process in intensive care medicine, within a framework of complete ethical alignment., Competing Interests: None of the authors has any funding or conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society.)

Background: Plant volatile organic compounds (VOCs) play a crucial role in mediating interactions between plants, herbivores and natural enemies. Among these VOCs, methyl salicylate and (E,E)-α-farnesene are emitted as herbivore-induced plant volatiles (HIPVs) by soybean plants in response to feeding by the brown stink bug Eushistus heros. These HIPVs function as synomones, influencing the foraging behaviour of the egg parasitoid, Telenomus podisi, the main natural enemy of E. heros, one of the major soybean pests in Brazil., Results: Laboratory experiments showed that two soybean cultivars, BRS 7580 and BRS 7880, produced similar qualitative blends of HIPVs, with methyl salicylate, (E,E)-α-farnesene and (Z)-3-hexenyl acetate being produced by both cultivars. Soybean cultivar BRS 7580 produced a significant lower amount of HIPVs compared to BRS 7880 but this difference did not affect the attractiveness of the egg parasitoid Telenomus podisi. Field experiments using these two cultivars and synthetic applications of methyl salicylate and (E,E)-α-farnesene showed a substantial increase in egg parasitism in all treated areas. Parasitism rates ranged from 50% to 80% in areas where these HIPVs were deployed, compared to only 10% in untreated control areas., Conclusions: The egg parasitoid Telenomus podisi demonstrated an adept ability in recognising between HIPVs in soybean blends, even in the presence of significant quantitative differences. The results from the field experiment showed the potential of HIPVs in attracting natural enemies to specific target areas within fields. (E,E)-α-Farnesene showed an improved action during the later stages of soybean growth, notably at R6. In addition, this volatile attracted other families of natural enemies. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objectives: The objective of this study is to describe the rehabilitation of individuals with Congenital Malformations (CMF) during the use of an External Fixator (EF) in Aquatic Therapy (AT) and to analyze the association between diagnosis, EF type and location with rehabilitation process outcomes, surgical intervention, and adverse effects., Methods: This retrospective study included 29 medical records from which the personal and rehabilitation data of the patient were collected. The AT used was described and the outcome variables were associated. The medical records were selected by screening the database of the CMF clinic at the AACD. The inclusion criteria were participants with CMF who used EF treated between 2011 and 2019 of both genders and without age restriction. The exclusion criteria were incomplete medical record data or not undergoing AT while using EF. The extracted data included diagnosis, gender, age, EF type and location, objective of the surgery, adverse events, surgical interventions, time of rehabilitation in AT, physiotherapeutic objectives, and rehabilitation process outcomes in AT., Results: The mean age of the participants was 12.1 ± 3.99 years, with male predominance (55 %) and hemimelia cases (37 %). The most used EF was circular (51 %), located in the femur (37 %), and the main objective of surgery was bone lengthening (52 %). The most recurrent adverse effect was infection (62 %) and 76 % completed AT. There was no association between the variables analyzed., Conclusions: It was possible to describe CMF rehabilitation with EF in AT. There was no association between the variables analyzed., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: A new approach to evaluate whether Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone was as effective as using dydrogesterone in suppress LH pulse surge in young women under stimulation in an oocyte donor programme., Methods: This prospective study included 21 patients aged 19 to 32 years-old stimulated with Elonva® 150, associated or not with Menopur® or Merional® (75 or 150IU) since the beginning of the cycle, plus HMG 150-225IU after the 8th day or just HMG 150-300IU per day. Patients were placed in a PPOS protocol with micronized vaginal progesterone (MVP) 200 mg (Gynpro® Exeltis or Junno Farmoquimica) every 12 hours or dydrogesterone (Duphaston® Abbott) 10 mg every 8 hours from the start of stimulation until the day after the GnRH trigger with Triptorelin 0.2 mg (Gonapeptyl daily®). The primary endpoint was the prevention of untimely LH surge, and secondarily the number of 16 mm follicles, retrieved oocytes and metafase II., Results: Fourteen oocyte donor patients were prescribed MVP while seven others received dydrogesterone (DYG).The gonadotropin protocols included 04 with Corifollitropin alfa 150 plus HMG since the beginning and complemented after the 7th day, and 17 times of just HMG. There was no diferences in the number of follicles >10≤15mm, ≥16mm or number of metafase II oocytes. There was no untimely LH surge on both groups and no OHSS was developed after the agonist trigger., Conclusions: Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone seems to be a compelling choice for preventing premature ovulation without compromising oocyte quality in women undergoing ovarian stimulation.

Duchenne Muscular Dystrophy (DMD) is one of the most frequent childhood dystrophies, affecting cardiopulmonary functions and walking ability. One of the main symptoms is fatigue, which is caused by altered muscle metabolism related to energy expenditure (EE). Aquatic physiotherapy is a therapeutic modality that facilitates the maintenance of this posture because of immersion on the body. This cross-sectional observational study aimed to compare the EE on the ground and water of individuals with DMD through oxygen consumption in the maintenance of sitting posture. The individuals were in a sitting position on the ground and in the water for 20 min for the assessments. The variables peripheral oxygen saturation, heart rate, maximum expiratory pressure, maximum inspiratory pressure, forced vital capacity, respiratory quotient (RQ), and oxygen consumption per kilogram of body weight (VO 2 /kg) were compared, adopting a significance of 5 %. No difference was found between medians and quartiles of RQ when comparing the two environments. The same was observed for VO 2 /Kg values on the ground and in water. The data from this study demonstrate that the EE of individuals with DMD did not change when maintaining a sitting posture on the ground and in water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Iron overload (IO) is a complex condition in which clinical, behavioral and genetic factors contribute to the phenotype. In multiethnic and non-Caucasian populations, mutations in HFE gene alone cannot explain IO in most of the cases, and additional genetic and environmental factors must be investigated. Bone Morphogenetic Proteins (BMPs) play a central role in iron homeostasis by modulating HAMP transcription through the signaling pathway that includes SMAD and HJV. In this study, we aimed to explore the clinical relevance of BMP6 mutations in a cohort of Brazilian patients with IO., Methods: 41 patients with IO were evaluated. Blood samples were collected to analyze BMP6 mutations through New Sequence Generations (NGS). Frequency of variants and mutations were analyzed and correlated with clinical and environmental characteristics., Results: We identified BMP6 mutations in three patients with IO. The p.Arg257His mutation was identified in two patients and the p.Leu71Val mutation was identified in one patient. Two of these patients had additional risk factors for IO (HFE mutations and diabetes mellitus)., Conclusion: BMP6 mutations, when combined to other genetic and clinical risk factors, may contribute to IO. Functional studies and THE evaluation of large cohorts are necessary to fully address BMP6 role in IO., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.)

This study aimed to develop a polymeric matrix of polyamide-6 (P6) impregnated with trimetaphosphate (TMP) nanoparticles and silver nanoparticles (AgNPs), and to evaluate its antimicrobial activity, surface free energy, TMP and Ag + release, and cytotoxicity for use as a support in dental tissue. The data were subjected to statistical analysis ( p < 0.05). P6 can be incorporated into TMP without altering its properties. In the first three hours, Ag + was released for all groups decorated with AgNPs, and for TMP, the release only occurred for the P6-TMP-5% and P6-TMP-10% groups. In the inhibition zones, the AgNPs showed activity against both microorganisms. The P6-TMP-2.5%-Ag and P6-TMP-5%-Ag groups with AgNPs showed a greater reduction in CFU for S. mutans . For C. albicans , all groups showed a reduction in CFU. The P6-TMP groups showed higher cell viability, regardless of time ( p < 0.05). The developed P6 polymeric matrix impregnated with TMP and AgNPs demonstrated promising antimicrobial properties against the tested microorganisms, making it a potential material for applications in scaffolds in dental tissues.

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Baurusuchidae comprises a clade of top-tier terrestrial predators and are among the most abundant crocodyliforms found in the Adamantina Formation, Bauru Basin, Brazil (Campanian-Maastrichtian). Here, we provide a detailed description of the cranial and postcranial osteology and myology of the most complete juvenile baurusuchid found to date. Although the preservation of juvenile individuals is somewhat rare, previously reported occurrences of baurusuchid egg clutches, a yearling individual, and larger, but skeletally immature specimens, comprise a unique opportunity to track anatomical changes throughout their ontogenetic series. Its cranial anatomy was resolved with the aid of a three-dimensional model generated by the acquisition of computed tomography data, and its inferred adductor mandibular musculature was compared to that of mature specimens in order to assess possible ontogenetic shifts. A subsequent phylogenetic analysis included the scoring of Gondwanasuchus scabrosus, the smallest baurusuchid species known to date, to evaluate its phylogenetic relations relative to a known juvenile. We find considerable differences between juveniles and adults concerning skull ornamentation and muscle development, which might indicate ontogenetic niche partitioning, and also anatomical and phylogenetic evidence that G. scabrosus corresponds to a young semaphoront lacking mature cranial features., (© 2024 American Association for Anatomy.)

Asymptomatically nasal colonization by Staphylococcus aureus is a well-established risk factor for S. aureus infections. The aimed of the study was to identify the prevalence and factors associated with nasal carriage of S. aureus and Methicillin-resistant S. aureus (MRSA) from individuals residing in one Brazilian nursing home (NH). Three time-separate nasal swab collections were obtained from the elderly enrolled. The S. aureus isolates identified were submitted to Antimicrobial Susceptibility test (AST). The study showed a high prevalence of S. aureus (n = 9; 60%) and MRSA (n = 4; 26.7%) among elderly. Resistance to erythromycin was the most detected. S. aureus or MRSA colonization could not be associated to the data collected on demographics, personal habits, and medical history of the participants. Despite the small number of individuals enrolled, our study can contribute to improve the control of S. aureus and MRSA dissemination within the community, especially among the most vulnerable like the elderly., 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.)

Background: Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples., Methods: During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry., Results: Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = -0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure., Conclusions: Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Animals move their head and eyes as they explore the visual scene. Neural correlates of these movements have been found in rodent primary visual cortex (V1), but their sources and computational roles are unclear. We addressed this by combining head and eye movement measurements with neural recordings in freely moving mice. V1 neurons responded primarily to gaze shifts, where head movements are accompanied by saccadic eye movements, rather than to head movements where compensatory eye movements stabilize gaze. A variety of activity patterns followed gaze shifts and together these formed a temporal sequence that was absent in darkness. Gaze-shift responses resembled those evoked by sequentially flashed stimuli, suggesting a large component corresponds to onset of new visual input. Notably, neurons responded in a sequence that matches their spatial frequency bias, consistent with coarse-to-fine processing. Recordings in freely gazing marmosets revealed a similar sequence following saccades, also aligned to spatial frequency preference. Our results demonstrate that active vision in both mice and marmosets consists of a dynamic temporal sequence of neural activity associated with visual sampling., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Lysergic acid diethylamide (LSD) is a prevalent psychoactive substance recognized for its hallucinogenic properties, often encountered in blotter papers for illicit consumption. Given that LSD ranks among the most widely abused illicit drugs globally, its prompt identification in seized samples is vital for forensic investigations. This study presents, for the first time, an electrochemical screening method for detecting LSD in forensic samples, utilizing a multi-wall carbon nanotube screen-printed electrode (SPE-MWCNT). The LSD detection process was optimized on SPE-MWCNT in a phosphate buffer solution (0.1 mol L -1 , pH 12.0) using square wave voltammetry (SWV). The combined use of SPE-MWCNT with SWV displayed robust stability in electrochemical responses for both qualitative (peak potential) and quantitative (peak current) LSD assessment, with a relative standard deviation (RSD) of less than 5% across the same or different electrodes ( N = 3). A linear detection range was established between 0.16 and 40.0 μmol L -1 ( R 2 = 0.998), featuring a low limit of detection (LOD) of 0.05 μmol L -1 . Interference studies with twenty-three other substances, including groups of phenethylamines typically found in blotting papers ( e.g. , NBOHs and NBOMes) and traditional illicit drugs, were performed, revealing a highly selective response for LSD using the proposed method. Consequently, the integration of SPE-MWCNT with SWV offers a robust tool for qualitative and quantitative LSD analysis in forensic applications, providing rapid, sensitive, selective, reproducible, and straightforward preliminary identification in seized samples.

Graft-versus-host disease (GVHD) is a serious inflammatory illness that often occurs as a secondary complication of bone marrow transplantation. Current therapies have limited effectiveness and fail to achieve a balance between inflammation and the graft-versus-tumor effect. In this study, we investigate the effects of the endocannabinoid anandamide on the complex pathology of GVHD. We assess the effects of an irreversible inhibitor of fatty acid amine hydrolase or exogenous anandamide and find that they increase survival and reduce clinical signs in GVHD mice. In the intestine of GVHD mice, treatment with exogenous anandamide also leads to a reduction in the number of CD3 + , CD3 + CD4 + , and CD3 + CD8 + cells, which reduces the activation of CD3 + CD4 + and CD3 + CD8 + cells, as assessed by enhanced CD28 expression, a T cell co-stimulatory molecule. Exogenous AEA was also able to reduce TNF-α and increase IL-10 in the intestine of GVHD mice. In the liver, exogenous AEA reduces injury, TNF-α levels, and the number of CD3 + CD8 + cells. Interestingly, anandamide reduces Mac-1α, which lowers the adhesion of transplanted cells in mesenteric veins. These effects are mimicked by JWH133-a CB2 selective agonist-and abolished by treatment with a CB2 antagonist. Furthermore, the effects caused by anandamide treatment on survival were related to the CB2 receptor, as the CB2 antagonist abolished it. This study shows the critical role of the CB2 receptor in the modulation of the inflammatory response of GVHD by treatment with anandamide, the most prominent endocannabinoid., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Upper-limbs (ULs) functional tests which are valid and reliable for individuals with chronic respiratory disease (CRD) are scarce. The aim of this study was to investigate the intra-rater reproducibility, validity, minimal detectable difference (MDD), and learning effect of the Upper Extremity Function Test - simplified version (UEFT&#95;S) functional test and to characterize its performance for adults with moderate-severe asthma and COPD., Methods: The UEFT&#95;S was performed twice, and the number of elbow flexions in 20 s was the outcome. In addition, spirometry, 6-min walk test (6MWT), handgrip dynamometry (HGD), and usual and maximum timed-up-and-go tests (TUG&#95;usual and TUG&#95;max) were also performed., Results: Eighty-four individuals with moderate-severe CRD and 84 control individuals matched by anthropometric data were analyzed. Individuals with CRD presented better performance in the UEFT&#95;S than controls ( P = .023). UEFT&#95;S correlated significantly with HGD, TUG&#95;usual, TUG&#95;max, and 6MWT ( P < .047 for all). The test-retest intraclass correlation coefficient was 0.91 [0.86-0.94], and the MDD was 0.4%., Conclusions: The UEFT&#95;S is a valid and reproducible tool to assess the functionality of the ULs in people with moderate-severe asthma and COPD. When applied in the modified form, the test can be considered simple, fast, and inexpensive, with an easy outcome to interpret., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

The recent COVID-19 pandemic has led many countries to adopt emergency cash transfer policies as a way to contain the economic and humanitarian crisis. Such initiatives were developed in a context of exacerbated gender, race, ethnicity and class inequalities resulting from physical and social distancing measures. The article analyzes, by means of an exploratory study and the so-called theory-driven evaluation of the program, the theoretical premises of the Brazilian Income Transfer Program (2003), Brazilian Emergency Assistance (2020) and Brazil Assistance (2021) programs, and their corresponding implementation dynamics. As cash transfer programs are given centrality in the contemporary public agenda, the conclusion is that evaluating their limits and advances - as to theoretical conception and mechanisms triggered in each context - contributes to trace evidence about their effectiveness in addressing long-term inequalities and those inequalities that arise in health emergency contexts.

Introduction: Although still rare, pulmonary embolism (PE) in children has been increasing over the years. Data regarding this group of patients are still sparse, which contributes to the lack of standardized prophylaxis protocols and the misdiagnosis. This study aimed to determine the incidence of pediatric PE at a Brazilian tertiary hospital, describe clinical characteristics and identify possible risk factors. We also analyzed the diagnosis and management of PE., Methods: This was a retrospective review of tertiary Brazilian single-center data of all pediatric patients (0 - 18 years) with acute PE, diagnosed radiologically, from September 2009 to May 2019., Results: The incidence of PE was 3.3 cases per 10,000 hospitalized children. All the twenty-three cases had some risk factor identified and sixteen of them (69.5%) had more than one risk factor. The most important were central venous catheter (39.1%), malignancy (34.8%) and recent surgery (34.8%). Among the children with identifiable symptoms (69.5%), the most common was dyspnea (56.2%). Only one patient did not receive antithrombotic therapy because of the high bleeding risk and most patients (70.6%) were treated for 3 to 6 months. Among the nineteen patients alive at the end of the six-month follow-up, ten (52.6%) repeated the PE image control. Seven of them (70.0%) had complete or partial resolution of the thrombosis and none had worsening images., Conclusion: Our lower incidence than that of the current literature may reflect underdiagnosis due to low suspicion of PE. At least one risk factor was identified in all patients, which emphasizes the importance of increasing awareness of high-risk children., Competing Interests: Conflicts of interest None., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

This study aimed to characterize hospitalizations of residents in Paraná State, Brazil, that occurred during the neonatal period in a municipality different from their place of residence from 2008 to 2019, and to describe displacement networks for the first and last biennium of the series, corresponding to periods before and after initiatives to regionalize health services in the state. Admissions of children aged from 0 to 27 days were obtained from the Hospital Information System of the Brazilian National Unified Health System (SIH-SUS) database. For each biennium and health region, the proportion of admissions that occurred outside the municipality of residence, the weighted average distance traveled, and indicators of health and service provision were calculated. Mixed models were fitted to evaluate the biennial trend of the indicators and to investigate factors associated with the neonatal mortality rate (NMR). In total, 76,438 hospitalizations were selected, ranging from 9,030 in 2008-2009 to 17,076 in 2018-2019. The comparison of the networks obtained for 2008-2009 and 2018-2019 revealed an increase in the number of frequent destinations and in the proportion of displacements within the same health region. A decreasing trend was observed for distance, the proportion of live births with 5-minute Apgar ≤ 7, and for NMR. In the adjusted analysis for NMR, besides the biennial effect (-0.64; 95%CI: -0.95; -0.28), only the proportion of live birth with gestational age < 28 weeks showed statistical significance (4.26; 95%CI: 1.29; 7.06). The demand for neonatal hospital care increased over the study period. The displacement networks suggest a positive impact of regionalization, although investment in regions with the potential to become healthcare centers is necessary.

Control of the pinewood nematode (PWN), the causal agent of pine wilt disease, can be achieved through the trunk injection of nematicides; however, many pesticides have been linked to environmental and human health concerns. Essential oils (EOs) are suitable alternatives due to their biodegradability and low toxicity to mammals. These complex mixtures of plant volatiles often display multiple biological activities and synergistic interactions between their compounds. The present work profiled the toxicity of eight EOs against the PWN in comparison to their 1:1 mixtures, to screen for successful synergistic interactions. Additionally, the main compounds of the most synergistic mixtures were characterized for their predicted environmental fate and toxicity to mammals in comparison to emamectin benzoate, a commercial nematicide used against PWN. The mixtures of Cymbopogon citratus with Mentha piperita and of Foeniculum vulgare with Satureja montana EOs showed the highest activities, with half-maximal effective concentrations (EC 50 ) of 0.09 and 0.05 µL/mL, respectively. For these, complete PWN mortality was reached after only ca. 15 min or 2 h of direct contact, respectively. Their major compounds had a higher predicted affinity to air and water environmental compartments and are reported to have very low toxicity to mammals, with low acute oral and dermal toxicities. In comparison, emamectin benzoate showed lower nematicidal activity, a higher affinity to the soil and sediments environmental compartments and higher reported oral and dermal toxicity to mammals. Overall, uncovering synergistic activities in combinations of EOs from plants of different families may prove to be a source of biopesticides with optimized toxicity against PWNs.

Soil with excess Mn induces toxicity and impairs crop growth. However, with the development in the soil of an intact extraradical mycelia (ERM) from arbuscular mycorrhizal fungi (AMF) symbiotic to native Mn-tolerant plants, wheat growth is promoted due to a stronger AMF colonization and subsequent increased protection against Mn toxicity. To determine the biochemical mechanisms of protection induced by this native ERM under Mn toxicity, wheat grown in soil from previously developed Lolium rigidum (LOL) or Ornithopus compressus (ORN), both strongly mycotrophic plants, was compared to wheat grown in soil from previously developed Silene gallica (SIL), a non-mycotrophic plant. Wheat grown after LOL or ORN had 60% higher dry weight, ca. two-fold lower Mn levels and almost double P contents. Mn in the shoots was preferentially translocated to the apoplast along with Mg and P. The activity of catalase increased; however, guaiacol peroxidase (GPX) and superoxide dismutase (SOD) showed lower activities. Wheat grown after ORN differed from that grown after LOL by displaying slightly higher Mn levels, higher root Mg and Ca levels and higher GPX and Mn-SOD activities. The AMF consortia established from these native plants can promote distinct biochemical mechanisms for protecting wheat against Mn toxicity.

We report a nanoarchitectonic electronic tongue made with flexible electrodes coated with curcumin carbon dots and zein electrospun nanofibers, which could detect Staphylococcus aureus ( S. aureus ) in milk using electrical impedance spectroscopy. Electronic tongues are based on the global selectivity concept in which the electrical responses of distinct sensing units are combined to provide a unique pattern, which in this case allowed the detection of S. aureus through non-specific interactions. The electronic tongue used here comprised 3 sensors with electrodes coated with zein nanofibers, carbon dots, and carbon dots with zein nanofibers. The capacitance data obtained with the three sensors were processed with a multidimensional projection technique referred to as interactive document mapping (IDMAP) and analyzed using the machine learning-based concept of multidimensional calibration space (MCS). The concentration of S. aureus could be determined with the sensing units, especially with the one containing zein as the limit of detection was 0.83 CFU/mL (CFU stands for colony-forming unit). This high sensitivity is attributed to molecular-level interactions between the protein zein and C-H groups in S. aureus according to polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS) data. Using machine learning and IDMAP, we demonstrated the selectivity of the electronic tongue in distinguishing milk samples from mastitis-infected cows from milk collected from healthy cows, and from milk spiked with possible interferents. Calibration of the electronic tongue can also be reached with the MCS concept employing decision tree algorithms, with an 80.1% accuracy in the diagnosis of mastitis. The low-cost electronic tongue presented here may be exploited in diagnosing mastitis at early stages, with tests performed in the farms without requiring specialized laboratories or personnel., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Patients on renal replacement therapy (RRT) and kidney transplant recipients (KTR) present multiple factors that may increase the risk of death from coronavirus disease 2019 (COVID-19). This study aimed to evaluate the incidence and impact of COVID-19 in RRT patients and KTRs., Methods: Between March 2020 and February 2021, we monitored the RRT population of thirteen dialysis facilities that refer patients for transplantation to our center, a tertiary hospital in Southern Brazil. In the same period, we also monitor COVID-19 incidence and mortality in our KTR population. Demographical, clinical, and COVID-19-related information were analyzed., Results: We evaluated 1545 patients in the dialysis centers, of which 267 (17.4%) were infected by COVID-19 and 53 (19.9%) died. Among 275 patients on the kidney transplant waiting list, 63 patients (22.9%) were infected and seven (11.1%) died. COVID-19 was the leading cause of death (29.2%) among patients on the waiting list. Within the population of 1360 KTR, 134 (9.85%) were diagnosed with COVID-19 and 20 (14.9%) died. The number of kidney transplants decreased by 56.7% compared with the same period in the previous twelve months., Conclusion: In the study period, patients on RRT and KTRs presented a high incidence of COVID-19 and high COVID-19-related lethality. The impact on the patients on the transplant waiting list was less pronounced. The lethality rate observed in both cohorts seems to be related to age, comorbidities, and disease severity.

Background: Alternatively to conventional treatments, chemo-mechanical caries removal agents can be used. A modality of treatment that has been increasing in dentistry is antimicrobial photodynamic therapy (aPDT). Bixa orellana is being researched for application in aPDT. This protocol aims to determine the effectiveness of aPDT with Bixa orellana extract in deep caries lesions., Methods: A total of 160 teeth with deep occlusal dental caries will be selected and divided into 4 groups: G1 - control group (Caries removal with a low-speed drill); G2 - Partial Caries Removal with Papacarie™ (Fórmula e Ação, São Paulo, SP, Brazil); G3 - Partial Caries Removal with Papacarie™ and application Bixa orellana extract (20%) (Fórmula e Ação, São Paulo, SP, Brazil); G4 - Partial Caries Removal with Papacarie™ and application Bixa orellana extract (20%) with LED (Valo Cordless Ultradent®, South Jordan, UT, USA) (aPDT). After treatment, all the teeth will be restored with glass ionomer cement and followed up clinically and radiographically, with evaluations at immediately, 1 week, and 1, 3, 6, and 12 months. Dentin samples before and after treatment will be analyzed microbiologically. The efficacy of treatments will be assessed with microbiological (colony-forming units, before and after carious tissue removal), radiographic (integrity of the periapical area and eventual changes in the radiolucent zones), and clinical examinations (retention of the restorative material in the cavity and occurrence of secondary caries), as well as with the time required for the procedures and the need for anesthesia during the procedures. In case data distribution is normal, analysis of variance (ANOVA) will be used for both the dependent and independent variables. In case the data distribution is not normal, the Friedman test will be used for the dependent variables. For independent variables, the Kruskal-Wallis test will be used., Discussion: Procedures using aPDT have been developed for the treatment of dental caries, but there are few controlled clinical trials in the literature confirming its efficacy., Trial Registration: This protocol is registered at ClinicalTrials.gov under the number NCT05236205 and it was first posted on 01/21/2022 and last updated on 05/10/2022., (© 2023. The Author(s).)

Objective: To analyze simplified adhesive containing pure or silanized bioglass 45S5 (with calcium) or Sr-45S5 (strontium-substituted) fillers applied on dentin and to evaluate the microtensile bond strength (µTBS), interface nanoleakage, degree of conversion of adhesive, collagen degradation and remineralization., Methods: Ambar Universal adhesive (FGM) was doped with 10 wt% bioactive glasses to form following groups: Control (no bioglass), 45S5 (conventional bioglass 45S5), Sr-45S5 (Sr-substituted bioglass 45S5), Sil-45S5 (silanized bioglass 45S5) and Sil-Sr-45S5 (silanized bioglass Sr-45S5). Adhesives were applied after dentin acid-etching using phosphoric acid at extracted human molars. Resin-dentin sticks were obtained and tested for µTBS, nanoleakage at 24 h or 6 months. Degree of conversion was measured using micro-Raman spectroscopy. Dentin remineralization was assessed by FTIR after 6-month storage in PBS. Hydroxyproline (HYP) release was surveyed by UV-Vis spectroscopy. Statistical analysis was performed using ANOVA and Tukey's test (p < 0.05)., Results: Regarding µTBS, Sr-45S5 and 45S5 presented higher and stable results (p > 0.05). Control (p = 0.018) and Sil-Sr-45S5 (p < 0.001) showed µTBS reduction after 6-month aging. Sil-Sr-45S5 showed higher HYP release than that obtained in the 45S5 group. Sil-45S5 showed mineral deposition and increase in µTBS (p = 0.028) after 6-months. All experimental adhesives exhibited higher degree of conversion compared to Control group, except for 45S5. All adhesives created gap-free interfaces, with very low silver impregnation, except for Sil-Sr-45S5., Significance: The incorporation of silanized 45S5 bioglass into the universal adhesive was advantageous in terms of dentin remineralization, bonding performance and adhesive polymerization. Conversely, Sil-Sr-45S5 compromised the µTBS, interface nanoleakage and had a negative impact on HYP outcomes., Competing Interests: Disclosure statement The authors deny any conflicts of interest related to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In 2019, the world witnessed the onset of an unprecedented pandemic. By February 2022, the infection by SARS-CoV-2 has already been responsible for the death of more than 5 million people worldwide. Recently, we and other groups discovered that SARS-CoV-2 infection induces ER stress and activation of the unfolded protein response (UPR) pathway. Degradation of misfolded/unfolded proteins is an essential element of proteostasis and occurs mainly in lysosomes or proteasomes. The N-terminal arginylation of proteins is characterized as an inducer of ubiquitination and proteasomal degradation by the N-degron pathway., Results: The role of protein arginylation during SARS-CoV-2 infection was elucidated. Protein arginylation was studied in Vero CCL-81, macrophage-like THP1, and Calu-3 cells infected at different times. A reanalysis of in vivo and in vitro public omics data combined with immunoblotting was performed to measure levels of arginyl-tRNA-protein transferase (ATE1) and its substrates. Dysregulation of the N-degron pathway was specifically identified during coronavirus infections compared to other respiratory viruses. We demonstrated that during SARS-CoV-2 infection, there is an increase in ATE1 expression in Calu-3 and Vero CCL-81 cells. On the other hand, infected macrophages showed no enzyme regulation. ATE1 and protein arginylation was variant-dependent, as shown using P1 and P2 viral variants and HEK 293T cells transfection with the spike protein and receptor-binding domains (RBD). In addition, we report that ATE1 inhibitors, tannic acid and merbromine (MER) reduce viral load. This finding was confirmed in ATE1-silenced cells., Conclusions: We demonstrate that ATE1 is increased during SARS-CoV-2 infection and its inhibition has potential therapeutic value.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are life-threatening multidrug-resistant bacteria. In this study, CR-Kp strains isolated from sewage treatment plants (STPs) (n = 12) were tested for carbapenemase genes (bla KPC , bla NDM , bla IMP , bla VIM and bla OXA-48 ) and had their sequence types (ST) and clonal complexes (CCs) defined. A collection of clinical CR-Kp strains recovered in local hospitals was added to phylogenetic analyses along with sewage strains in order to infer clonality among CR-Kp strains. A total of 154 CR-Kp strains were isolated from raw sewage [55.8% (86/154)], treated sewage [25.3% (39/154)] and from water body downstream from STPs [18.8% (29/154)]. No CR-Kp strain was isolated from upstream water samples. bla KPC or bla NDM were detected in 143 (92.8%) strains. The occurrence of bla KPC-or-NDM CR-Kp strains was positively associated with the number of hospitalized patients in the areas serviced by STPs. Eleven STs were detected in CR-Kp strains, most of them belonging to the clinically relevant CC11 [ST11 (n = 13-28.2%) and ST340 (n = 7-15.2%)]. CCs 11, 15, 17, 147 and 2703 are shared by clinical and sewage CR-Kp strains. In conclusion, sewage harbors clinically relevant clones of CR-Kp that resist sewage treatments, contaminating water bodies downstream from STPs.

Statement of Problem: Little is known regarding the use of preheated composite resins to bond indirect restorations and its impact on mechanical properties when compared with resin cements., Purpose: The purpose of this in vitro study was to compare the chemical and physical properties and bond strength to enamel and ceramics of preheated composite resins and resin cements., Material and Methods: Two composite resins, the microhybrid Filtek Z250XT and the nanoparticulate Z350XT were tested, and 2 commercially available resin cements, the dual-polymerized Rely-X ARC and the light-polymerized Rely-X Veneer were used as controls. A device (HotSet) was used to preheat the composite resins to 69 °C before light-polymerization. The following properties were tested: flexural strength, modulus of elasticity, fracture toughness, microshear bond strength to enamel and ceramics, degree of conversion, flow, sorption and solubility, and color stability. Statistical analysis was done with ANOVA and Holm-Sidak for multiple comparisons (α=.05)., Results: Preheating had no significant effect on the degree of conversion, flexural strength, fracture toughness, solubility, or microshear bond strength to the enamel of the tested composite resins (P>.05). However, preheating increased the sorption and reduced the microshear bond strength to the ceramic (P<.05). The flowability of the composite resins increased with heating but showed lower values when compared with both resin cements (P<.05). Color stability was more affected in the preheated composite resins than in the resin cements., Conclusions: The preheating process resulted in little to no benefit in the evaluated properties for the composite resins. Resin cements appear to be the best option for cementing indirect restorations., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Visual input during natural behavior is highly dependent on movements of the eyes and head, but how information about eye and head position is integrated with visual processing during free movement is unknown, as visual physiology is generally performed under head fixation. To address this, we performed single-unit electrophysiology in V1 of freely moving mice while simultaneously measuring the mouse's eye position, head orientation, and the visual scene from the mouse's perspective. From these measures, we mapped spatiotemporal receptive fields during free movement based on the gaze-corrected visual input. Furthermore, we found a significant fraction of neurons tuned for eye and head position, and these signals were integrated with visual responses through a multiplicative mechanism in the majority of modulated neurons. These results provide new insight into coding in the mouse V1 and, more generally, provide a paradigm for investigating visual physiology under natural conditions, including active sensing and ethological behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6−8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95−4.55-fold and 1.79−2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions.

In the present study, the objective was to evaluate in situ interaction between Benzo[a]anthracene 7,2-dione 7-oxime (BZA) and calf thymus dsDNA (ct-dsDNA) using electroanalytical genosensor. Analytical techniques based on Ultraviolet/Visible (UV-Vis) spectroscopy and electroanalytical were used to investigate the interaction processes in solution and immobilized on carbon screen-printed electrodes modified with electrochemical mediator Meldola blue. In addition, was possible to evaluate the degree of damage caused to the genetic material by the analyte through of toxicity estimate (S%). The interaction evaluated by genosensor showed processes of intercalation, degradation, and breaks of the double strand of ct-dsDNA, suggesting that the interaction simulates highly toxic (values varying from 0.6 to 0.8 μA in 48 h of interaction), such as 8-oxoguanine (+0.48 V), which is a by-product of guanine oxidation. Furthermore, monitoring A (+1.10 V) after 1 h showed an S% value between 50 and 90%, indicative of high toxicity, and monitoring G (+0.85 V), which showed S>90%, indicated no toxicity after 10 min. Overall, the electroanalytical genosensor developed in a miniaturized system displayed good reproducibility and stability over time being a quick alternative for assesses the degree of toxicity between toxic xenobiotics and biologically electroactive molecules, such as DNA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Composite resins with low flowability are usually handled and manipulated before insertion into the tooth preparation with gloved hands and/or using an instrument covered with a little amount of adhesive to facilitate modeling. We investigated if the modeling techniques (combined or not) affected physicochemical and esthetic properties of a composite resin. Specimens were fabricated and divided into groups according to the handling/modeling technique: Gloved-hands (composite was hand-manipulated with powdered latex gloves); Adhesive (adhesive was used in between the composite layers); Gloved-hands + Adhesive; Control (no adhesive and no touch with gloved-hands). The highest values for flexural strength (MPa), modulus of elasticity (GPa), and fracture toughness (MPa.m0.5) were obtained for Adhesive and Gloved-hands + Adhesive (p < 0.05); the lowest values were obtained for Control and Gloved-hands (p < 0.05). The Control group had the highest sorption. The Gloved-hands (p < 0.05) group had the highest solubility. Adhesive and Gloved-hands + Adhesive had a similar solubility (p > 0.05). The Control group (p < 0.05) had the lowest solubility. There was no statistical interaction between translucency vs. handling/modeling techniques and color stability vs. handling/modeling techniques. Adhesive as a modeling liquid protected the composite against sorption and solubility (if powdered gloves were used) and improved its physical/mechanical properties. Translucency and color stability were not correlated with modeling techniques.

Objective: This study aimed to analyze the time trends of suicide attempts assisted by the Fire Department of the Military Police of the State of São Paulo (Corpo de Bombeiros da Polícia Militar do Estado de São Paulo - CBPMESP) from 2017 to 2021, between sexes., Methods: This is an ecological study of 11,435 suicide attempts assisted by CBPMESP calls from January 2017 to December 2021. Three seasonal auto-regressive integrated moving average with exogenous (SARIMAX) models were adjusted considering total population, only men, and only women., Results: The total occurrences of suicide attempts were stationary in the prepandemic period but had an increased growth pattern after the pandemic began. This trend was higher among men, due to (1) lower assistance of suicide attempts during early pandemic than in the prepandemic period and (2) significant increased assistance after the beginning of vaccination against COVID-19, followed by a decrease, but with a tendency to increase, in the long-term pandemic., Conclusion: Our results indicate a growth in the long-term suicide attempts during COVID-19. The beginning of vaccination was not considered significant in the reduction of CBPMESP attendances. These results corroborate the need for a multisectoral national suicide prevention strategy to mitigate the effects of the pandemic on mental health in the State of São Paulo.

COVID-19 pandemic response with non-pharmaceutical interventions is an intrinsic control problem. Governments weigh social distancing policies to avoid overload in the health system without significant economic impact. The mutability of the SARS-CoV-2 virus, vaccination coverage, and mobility restriction measures change epidemic dynamics over time. A model-based control strategy requires reliable predictions to be efficient on a long-term basis. In this paper, a SEIR-based model is proposed considering dynamic feedback estimation. State and parameter estimations are performed on state estimators using augmented states. Three methods were implemented: constrained extended Kalman filter (CEKF), CEKF and smoother (CEKF & S), and moving horizon estimator (MHE). The parameters estimation was based on vaccine efficacy studies regarding transmissibility, severity of the disease, and lethality. Social distancing was assumed as a measured disturbance calculated using Google mobility data. Data from six federative units from Brazil were used to evaluate the proposed strategy. State and parameter estimations were performed from 1 October 2020 to 1 July 2021, during which Zeta and Gamma variants emerged. Simulation results showed that lethality increased between 11 and 30% for Zeta mutations and between 44 and 107% for Gamma mutations. In addition, transmissibility increased between 10 and 37% for the Zeta variant and between 43 and 119% for the Gamma variant. Furthermore, parameter estimation indicated temporal underreporting changes in hospitalized and deceased individuals. Overall, the estimation strategy showed to be suitable for dynamic feedback as simulation results presented an efficient detection and dynamic characterization of circulating variants., (© 2022. The Author(s).)

In natural contexts, sensory processing and motor output are closely coupled, which is reflected in the fact that many brain areas contain both sensory and movement signals. However, standard reductionist paradigms decouple sensory decisions from their natural motor consequences, and head-fixation prevents the natural sensory consequences of self-motion. In particular, movement through the environment provides a number of depth cues beyond stereo vision that are poorly understood. To study the integration of visual processing and motor output in a naturalistic task, we investigated distance estimation in freely moving mice. We found that mice use vision to accurately jump across a variable gap, thus directly coupling a visual computation to its corresponding ethological motor output. Monocular eyelid suture did not affect gap jumping success, thus mice can use cues that do not depend on binocular disparity and stereo vision. Under monocular conditions, mice altered their head positioning and performed more vertical head movements, consistent with a shift from using stereopsis to other monocular cues, such as motion or position parallax. Finally, optogenetic suppression of primary visual cortex impaired task performance under both binocular and monocular conditions when optical fiber placement was localized to binocular or monocular zone V1, respectively. Together, these results show that mice can use monocular cues, relying on visual cortex, to accurately judge distance. Furthermore, this behavioral paradigm provides a foundation for studying how neural circuits convert sensory information into ethological motor output., Competing Interests: PP, EA, NB, EL, DM, SS, DW, LM, CN No competing interests declared, (© 2022, Parker et al.)

Background: COVID-19 comprises a respiratory infection resulting from contamination by SARS-CoV-2, with acute respiratory failure being one of its main characteristics, leading to a high frequency of orotracheal intubation (OTI), which in turn increases the risk for dysphagia. Since this can lead to pulmonary impairment, knowing the real occurrence of dysphagia in part of the Brazilian population and its associations allows early and effective clinical management of the multidisciplinary team in relation to patients., Objective: To verify the occurrence of dysphagia in COVID-19-positive adult patients in two Brazilian reference hospitals in the care of the pandemic., Methods: This was a prospective, longitudinal observational study carried out in two private hospitals in Brazil, both references in the care of patients with coronavirus isolation. Data were initially collected by consulting the medical records of each patient. Information was collected regarding sex, age, previous diseases, COVID-19 testing, and the OTI period. After data collection, the clinical speech-language assessment of swallowing for each patient was carried out using the adapted Gugging Swallowing Screen (GUSS), the ASHA NOMS and the Functional Oral Intake Scale (FOIS)., Results: A total of 129 participants were evaluated, with a mean age of 72 years. According to the GUSS scale, 9.3% of the patients presented normal/functional swallowing, while 90.7% presented dysphagia, with mild dysphagia in 17.05%, moderate dysphagia in 33.33%, and severe dysphagia in 37.98%. As for the results of the ASHA NOMS, the majority (36.5%) of the patients were at level 1, which represents the patient who is not able to receive his or her food supply orally, having the need to use tube feedings. This is in line with the results observed with the FOIS scale, whereby most patients (42.1%) were classified as Level I, when food intake occurs exclusively through feeding tubes, with no oral supply. Of the 129 participants, 59% of them required OTI. When comparing the time of OTI and the severity of dysphagia, there was a statistically significant difference, with more severe dysphagia, the longer the patient remained intubated., Conclusion: There is a high incidence of oropharyngeal dysphagia in patients with COVID-19, with increased severity during longer periods of OTI.

Objective: The primary objective of this study was to identify the occurrence and factors associated with intensive care unit (ICU)-acquired weakness (ICUAW) in patients with COVID-19. Secondarily, we monitored the evolution of muscle strength and mobility among individuals with ICUAW and those without ICUAW and the association of these variables with length of stay, mechanical ventilation (MV), and other clinical variables., Methods: In this prospective observational study, individuals admitted to the ICU for >72 hours with COVID-19 were evaluated for muscle strength and mobility at 3 times: when being weaned from ventilatory support, discharged from the ICU, and discharged from the hospital. Risk factors for ICUAW were monitored., Results: The occurrences of ICUAW at the 3 times evaluated among the 75 patients included were 52%, 38%, and 13%. The length of the ICU stay (29.5 [IQR = 16.3-42.5] vs 11 [IQR = 6.5-16] days), the length of the hospital stay (43.5 [IQR = 22.8-55.3] vs 16 [IQR = 12.5-24] days), and time on MV (25.5 [IQR = 13.8-41.3] vs 10 [IQR = 5-22.5] days) were greater in patients with ICUAW. Muscle strength and mobility were lower at all times assessed in patients with ICUAW. Bed rest time for all patients (relative risk = 1.14; 95% CI = 1.02 to 1.28) and use of corticosteroids (relative risk = 1.01; 95% CI = 1.00 to 1.03) for those who required MV were factors independently associated with ICUAW. Muscle strength was found to have a positive correlation with mobility and a negative correlation with lengths of stay in the ICU and hospital and time on MV., Conclusion: The occurrence of ICUAW was high on patients' awakening in the ICU but decreased throughout hospitalization; however, strength and mobility remained compromised at hospital discharge. Bed rest time and use of corticosteroids (for those who needed MV) were factors independently associated with ICUAW in patients with COVID-19., Impact: Patients who had COVID-19 and developed ICUAW had longer periods of ICU stay, hospital stay, and MV. Bed rest time and use of corticosteroids (for those who required MV) were factors independently associated with ICUAW., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the diagnostic contribution of grating visual acuity (GVA) measured by sweep pattern-reversal visually evoked potentials (SPRVEP) in unexplained visual loss (UVL)., Methods: This case-control study included adult patients under suspicion of UVL referred to SPRVEP and transient pattern-reversal visually evoked potentials (TPRVEP) testing. Optotype visual acuity (OVA) was measured by ETDRS 4-meter chart and GVA by SPRVEP. UVL patients were assigned into three distinctive categories, according to the presence of ocular disease, motivation, and electrophysiological evaluation, as follows: exaggerators, malingerers, and psychogenic. Healthy controls and patients with organic visual loss were also tested. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of GVA and TPRVEP parameters., Results: A total of 76 patients with UVL were analyzed: 60 (79.0%) exaggerators, 11 (14.4%) malingerers, and 5 (6.6%) psychogenic. Controls were 49 subjects evaluated for TPRVEP and 28 subjects for SPRVEP. There were 13 patients with organic visual loss enrolled. Mean difference between OVA and GVA was 1.19±0.67 (median=0.84; 95% CI: 1.04 to 1.34) in UVL and 0.14 ±0.09 (median= 0.14; 95% CI: 0.08 to 0.20) in organic visual loss. The area under the ROC curve (AUC) of GVA to distinguish UVL from healthy controls was 0.998 with a cutoff of 0.09 logMAR showing specificity of 100% and sensitivity of 96.0%., Conclusions: GVA measured by SPRVEP had good diagnostic validity to discriminate patients with unexplained visual loss from healthy controls and patients with organic visual loss, demonstrating its contribution to the diagnosis of this condition., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)