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Background: There are a few studies about preceptorship in primary health care settings, but they didn't assess all possible contributions of this experience, such as preceptor behavioral changes and impact on health services., Objective: This study aimed to analyze the perspective of pharmacy student preceptors on a service-learning program carried out in a primary health care setting., Methods: This was a qualitative descriptive study, with semi-structured interviews and thematic analysis. The themes were defined deductively, according to levels of Kirkpatrick's theory about the impact of educational activities., Results: The preceptors showed positive and negative reactions to the structure of the service-learning program, developed their knowledge, changed behaviors such as collaborative interprofessional practice, and reported improvements in the health units., Conclusions: From the perspective of pharmacy student preceptor preceptors, the service-learning program had an impact on all levels expected for an educational activity according to Kirkpatrick's theory: reaction, learning, behavior, and results. These findings may inform the design of service-learning programs., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Marina Guimaraes Lima took part in the service-learning analyzed in the manuscript., (© 2023 The Authors. Published by Elsevier Inc.)

The physicochemical and structural properties of antimicrobial peptides (AMPs) determine their mechanism of action and biological function. However, the development of AMPs as therapeutic drugs has been traditionally limited by their toxicity for human cells. Tuning the physicochemical properties of such molecules may abolish toxicity and yield synthetic molecules displaying optimal safety profiles and enhanced antimicrobial activity. Here, natural peptides were modified to improve their activity by the hybridization of sequences from two different active peptide sequences. Hybrid AMPs (hAMPs) were generated by combining the amphipathic faces of the highly toxic peptide VmCT1, derived from scorpion venom, with parts of four other naturally occurring peptides having high antimicrobial activity and low toxicity against human cells. This strategy led to the design of seven synthetic bioactive variants, all of which preserved their structure and presented increased antimicrobial activity (3.1-128 μmol L -1 ). Five of the peptides (three being hAMPs) presented high antiplasmodial at 0.8 μmol L -1 , and virtually no undesired toxic effects against red blood cells. In sum, we demonstrate that peptide hybridization is an effective strategy for redirecting biological activity to generate novel bioactive molecules with desired properties., (© 2023. Springer Nature Limited.)

Background: Translation into practice of effective physical activity interventions in primary care is difficult, due to a complex interaction of implementation determinants. We aimed to identify implementation barriers and facilitators of four primary care interventions: physical activity assessment, counselling, prescription, and referral., Methods: A systematic review of qualitative, quantitative and mixed-methods studies published since 2016 was conducted. The "Tailored Implementation for Chronic Diseases" (TICD) framework was adapted to extract and synthesize barriers and facilitators., Results: Sixty-two studies met the inclusion criteria. Barriers (n = 56) and facilitators (n = 55) were identified across seven domains, related to characteristics of the intervention, individual factors of the implementers and receivers, organizational factors, and political and social determinants. The five most frequently reported determinants were: professionals' knowledge and skills; intervention feasibility/compatibility with primary health care routine; interventions' cost and financial incentives; tools and materials; and professionals' cognitions and attitudes. "Social, political and legal factors" domain was the least reported. Physical activity counselling, prescription, and referral were influenced by determinants belonging to all the seven domains., Conclusion: The implementation of physical activity interventions in primary care is influenced by a broader range of determinants. Barriers and facilitators related with health professionals, intervention characteristics, and available resources were the most frequently reported. A deep understanding of the local context, with particularly emphasis on these determinants, should be considered when preparing an intervention implementation, in order to contribute for designing tailored implementation strategies and optimize the interventions' effectiveness., (© 2023. BioMed Central Ltd., part of Springer Nature.)

COVID-19 is an infectious disease caused by coronavirus 2 of the severe acute syndrome (SARS-CoV-2). Single nucleotide polymorphisms (SNPs) in genes, such as TLR2 , responsible for an effective human immune response, can change the course of infection. The objective of this article was to verify associations between epidemiological factors and TLR2 SNP rs3804100 (Thymine [T] > Cytosine [C]) in professionals from Health Institutions (HI) who worked during the first pandemic wave and COVID-19. A case-control study was conducted with Belém-PA HI workers (Northern Brazil), divided into symptomatology groups (Asymptomatic-AS; n = 91; and Symptomatic-SI; n = 123); and severity groups classified by Chest Computerized Tomography data (symptomatic with pulmonary involvement-SCP; n = 35; symptomatic without pulmonary involvement-SSP; n = 8). Genotyping was performed by Sanger sequencing, and Statistical Analysis was conducted through the SPSS program. Bioinformatics servers predicted the biological functions of the TLR2 SNP. There were associations between the presence of comorbidities and poor prognosis of COVID-19 (especially between symptomatology and severity of COVID-19 and overweight and obesity) and between the sickness in family members and kinship (related to blood relatives). The homozygous recessive (C/C) genotype was not found, and the frequency of the mutant allele (C) was less than 10% in the cohort. No significant associations were found for this SNP in this cohort. The presence of SNP was indicated to be benign and causes a decrease in the stability of the TLR2 protein. These data can help the scientific community and medicine find new forms of COVID-19 containment.

Background: In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes-rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)-and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon., Methods: Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL., Results: Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736-3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185-0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281-0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113-1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104-4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211-1.669)., Conclusions: In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To compare the accuracy and reliability of cone-beam computed tomography (CBCT) and laser scanner in measuring minor volume changes such as the root canal space., Methods: 35 maxillary incisors were endodontically prepared. A dimensionally stable silicone material was injected into the root canal space and scanned with CBCT. The root canal volume was measured using Romexis 3.0.1 R software. Replicas were carefully removed from the teeth and scanned using an extraoral laser scanner. These images were exported to the Rhinoceros software for volume measurement. The volume of each replica was also assessed using the gravimetric method. To determine the accuracy, the volume obtained from both devices was compared with the gravimetric method. Statistical analysis was done using a paired t-test. The reliability was assessed using the intraclass correlation coefficient., Results: There was no statistically significant difference between the mean volume of CBCT 27.04 ± 7.25 mm³ and the mean volume of the gravimetric method 27.87 ± 7.17 mm³ (P< 0.05). A statistically significant difference was seen with the laser scanner at 25.31 ± 6.89 mm³ and the gravimetric method at 27.87 ± 7.17 mm³ (P< 0.05). CBCT showed a good degree of agreement (ICC 0.899), while the laser scanner showed a moderate degree of agreement (ICC 0.644) with the gravimetric method. CBCT proved accurate and reliable in measuring minor volumes like the root canal space, ideally in the range of 20-25 mm³. The laser scanner presented acceptable reliability., Clinical Significance: The laboratory data showed satisfactory outcomes, providing an evidence-based approach and potentially motivating clinicians to integrate cone-beam computed tomography for volume analysis into clinical practice. The accuracy and reliability of laser scanners for small-volume analysis have not previously been evaluated. Consequently, the findings from this study warrant further clinical investigations., Competing Interests: The authors declared no conflict of interest., (Copyright©American Journal of Dentistry.)

A carbonylation-carboxylation synthetic sequence, via double CO 2 fixation, is described. The productive merger of a Ni-catalyzed cross-electrophile coupling manifold, with the use of AlCl 3 , triggered a cascade reaction with the formation of three consecutive C-C bonds in a single operation. This strategy traces an unprecedented synthetic route to ketones under Lewis acid assisted carbon dioxide valorization. Computational insights revealed a unique double function of AlCl 3 , and labeling ( 13 CO 2 ) experiments validate the genuine incorporation of CO 2 in both functional groups.

Breast cancer (BC) is the type of neoplasm that most affects women worldwide. It is known that one of the hallmarks of cancer is the resistance to cell death with the evasion of apoptosis. Considering the relevance of TP53 , BCL2 , CASP3, and CASP9 genes for the occurrence of the intrinsic apoptosis, this study investigated the distribution of the genetic variants rs17880560 ( TP53 ), rs11269260 ( BCL2 ), rs4647655 ( CASP3 ), rs4645982, and rs61079693 ( CASP9 ), as well as genetic ancestry and clinical data, in a BC cohort from the Brazilian Amazon that other variants in these genes might play a role in this process. In the present study, 22 breast cancer tissues and 10 non-cancerous tissues were used, therefore, 32 samples from different patients were subjected to genotyping. We observed that breastfeeding and cancer history were factors that need to be considered for BC ( p = 0.022). Therefore, this study contributed to a greater understanding of intrinsic apoptosis in BC, reinforcing previous data that suggest that the history of cancer might be a condition that affects the development of BC and that breastfeeding may act as a protective factor for this type of cancer. We recommend more studies on the genetic factors investigated here, aiming at a future with tools that can help in the early diagnosis.

Objectives: Arboviruses represent a major challenge to public health in Brazil. Dengue (DENV) virus has been endemic for decades, and the introduction of Zika (2015) and Chikungunya (2014) viruses (CHIKV) has imposed a significant burden on the country. The present study aimed to investigate the seroprevalence of Zika virus (ZIKV), DENV and CHIKV in women in Salvador, Bahia-Brazil., Methods: Cross-sectional study involving postpartum women admitted to a maternity hospital in Salvador, Brazil. Anti-ZIKV, anti-DENV and anti-CHIKV immunoglobulin G was measured by enzyme-linked immunosorbent assay., Results: A total of 302 women were enrolled with a median age: 26 years, interquartile range (21-33). Most self-declared as mixed-race or black skin color (92.4%). The seroprevalence was 57% for ZIKV); 91.4% for DENV, and 7.6% for CHIKV. Most participants denied awareness of previous arboviral infection, although 67 (22.3%) reported a previous history of ZIKV infection, 34 (11.1%) DENV infection and 9 (3%) CHIKV infection., Conclusion: Our data indicate a high prevalence of past ZIKV and DENV infections in the population studied. Most of the participants remain susceptible to future CHIKV infection, highlighting the need for preventive and educational interventions. Our results suggest the need for continuous epidemiological surveillance of arboviral diseases, particularly among women residing in at-risk regions., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors.)

Genetic polymorphisms in genes that encode natural ligands of CCR5 (the main human HIV coreceptor), such as CCL5/RANTES , can alter the levels of secretion of these peptides. This article sought to review the relationship between single nucleotide polymorphisms (SNPs) of CCL5/RANTES and HIV-1 disease susceptibility. A meta-analysis was conducted through 17 articles found from January 1999 to December 2022 in the PUBMED, Science Direct, Medline, and SciELO databases. A total of three SNPs were identified and investigated under their dominant genotypic model and through a fixed-effects model. In terms of the SNP rs2107538 (G > A), in Africa and Asia, it has a protective role (OR = 0.56; 95% CI = 0.41-0.76; p = 0.0002, and OR = 0.88; 95% CI = 0.76-1.02; p = 0.08, respectively). In terms of the SNP rs2280788 (C > G), in Europe and America, it shows a higher risk role (OR = 1.92; 95% CI = 1.06-3.47; p = 0.03, and OR = 0.94; 95% CI = 0.94-1.11; p = 0.04, respectively), but in the population of Asia, with its mutant allele, it has a protective role (OR = 0.76; 95% CI = 0.63-0.93; p = 0.007). In terms of the SNP rs2280789 (T > C), no significant associations were found. Both SNPs rs2107538 and rs2280788 have a positive transcriptional effect on the RANTES/CCL5 gene, while SNP rs2280789 causes a decrease in gene expression levels. This study suggests that there is an association between the increased expression of CCL5/RANTES and a lower risk of AIDS. Therefore, further studies are needed to arrive at a definitive conclusion, and these results may help establish scientific bases for effective HIV/AIDS control strategies.

Background: Patient safety is a key priority for healthcare organisations. It impacts directly on patient health and wellbeing. The increasing complexity of current healthcare settings, which are associated with high work demands and increasingly stressful professional practice environments, contributes to an increased likelihood of errors and adverse events. Primary health care, given its comprehensiveness of care, makes up a large proportion of the care delivered to the population., Aim: To map the knowledge about the impact that nursing practice environments have on safety culture in the primary healthcare setting. This knowledge is essential for a more effective and appropriate understanding of this phenomenon and to enable the definition of strategies that can promote the provision of safer care to the population., Design & Setting: A scoping review will be conducted based on the method proposed by the JBI, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) will be used., Method: Study selection, data extraction, and synthesis will be performed by two independent reviewers. Based on the Population (or participants), Concept, and Context (PCC) framework, this scoping review will consider studies that address nurses' practice environment and patient safety culture in primary health care. The review will consider all studies, published or unpublished, from 2002 to the present., Conclusion: The results from this scoping review are expected to provide an overview of the importance of the nursing practice environments on patient safety culture, which will be crucial to define an appropriate range of strategies to promote the delivery of the safest health care to the population., (Copyright © 2023, The Authors.)

3D bioprinting has opened new possibilities and elevated tissue engineering complexity. Here, we present a protocol to design a 3D model with two cell lineage layers (A549 and HUVEC) to recreate multi-cell constructs. We describe the steps for slicing the constructs, handling hydrogels, and detailing the bioprinting setup. These 3D-bioprinted constructs can be adapted to various cell models-from primary cell cultures to commercial cell lines and induced pluripotent stem cells (IPCs)-and applications, including drug screening and disease modeling. For complete details on the use and execution of this protocol, please refer to Cruz et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was developed under the scope of the provisional patent application nr. 116970 “Polymeric substrates for nerve regeneration, methods and uses thereof”, priority date 3 December 2020., (Copyright © 2023. Published by Elsevier Ltd.)

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8 + memory T cells develop at the location of infection: tissue-resident memory T cells (T RM ). CD8 + T-cell responses are associated with type-1 infections and type-1 regulatory T cells (T REG ) are important for CD8 + T-cell development, however, if CD8 + T RM cells develop under other infection types and require immune type-specific T REG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8 + T RM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching T REG population contributing transforming growth factor-β. Nevertheless, type-1 T REG cells remain the most important population for T RM cell development. Once established, T RM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8 + T RM cells., (© 2023. Springer Nature Limited.)

Intense stimulation of most living cells triggers the activation of immediate early genes, such as Fos and Jun families. These genes are important in cellular and biochemical processes, such as mitosis and cell death. The present study focused on determining the temporal expression pattern of Fos and Jun families in fibroblasts and neural stem cells of cerebellum, hippocampus, and subventricular zone (SVZ) of rats of different ages at 0, 0.5, 1, 3, and 6 h after stimulation with fibroblast growth factor (FGF)-2. In neonates, a similar expression pattern was observed in all cells analyzed, with lower expression in basal condition, peak expression at 0.5 h after stimulation, returning to baseline values between 1 and 3 h after stimulation. On the other hand, cells from adult animals only showed Fra1 and JunD expression after stimulation. In fibroblasts and hippocampus, Fra1 reached peak expression at 0.5 h after stimulation, while in the SVZ, peak level was observed at 6 h after stimulation. JunD in fibroblasts presented two peak expressions, at 0.5 and 6 h after stimulation. Between these periods, the expression observed was at a basal level. Nevertheless, JunD expression in SVZ and hippocampus was low and without significant changes after stimulation. Differences in mRNA expression in neonate and adult animals characterize the significant differences in neurogenesis and cell response to stimulation at different stages of development. Characterizing these differences might be important for the development of cell cultures, replacement therapy, and the understanding of the physiological response profile of different cell types.

Aims: This study investigated the phylogenetic relatedness of multidrug-resistant Elizabethkingia anophelis recovered from an industrial wastewater treatment plant (WWTPi)., Methods and Results: The wastewater samples were plated in brain heart infusion agar (4 mg/L ceftazidime, 8 mg/L meropenem, and 2 mg/L polimixin). Four isolates recovered from four stages of WWTPi (influent, aeration, decantation, and treated effluent) were identified and evaluated of susceptibility profiles in the VITEK 2 system. These strains identified as E. meningoseptica were confirmed to be E. anophelis by whole genomic sequencing (Miseq-Illumina) and showed antimicrobial resistance genes of β-lactams, aminoglycosides, and tetracycline's classes. The ribosomal multilocus sequence typing showed that they belong to the rST 65620 together with clinical strains. The phylogenomic tree revealed the similarity of our strains to those belonging to sublineage 11 and the single nucleotide polymorphism analysis confirmed that they belong to a single clade., Conclusions: To the best of our knowledge, this is the first study reporting the persistence of multidrug-resistant E. anophelis sublineage 11 along the wastewater treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Enrofloxacin (Enro) has been widely encountered in natural water sources, and that water is often used for irrigation in crop production systems. Due to its phytotoxicity and accumulation in plant tissues, the presence of Enro in water used for crop irrigation may represent economical and toxicological concerns. Here, we irrigated two ornamental plant species (Zantedeschia rehmannii Engl. and Spathiphyllum wallisii Regel.) with water artificially contaminated with the antimicrobial enrofloxacin (Enro; 0, 5, 10, 100, and 1000 μg L -1 ) to evaluate its effects on ornamental plant production, as well as its accumulation and distribution among different plant organs (roots, leaves, bulbs, and flower stems), and examined the economic and environmental safety of commercializing plants produced under conditions of pharmaceutical contamination. The presence of Enro in irrigation water was not found to disrupt plant growth (biomass) or flower production. Both species accumulated Enro, with its internal concentrations distributed as the following: roots > leaves > bulbs > flower stems. In addition to plant tolerance, the content of Enro in plant organs indicated that both Z. rehmannii and S. wallisii could be safety produced under Enro-contaminated conditions and would not significantly contribute to contaminant transfer. The high capacity of those plants to accumulate Enro in their tissues, associated with their tolerance to it, indicates them for use in Enro-phytoremediation programs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Early plant diseases and pests identification reduces social, economic, and environmental deficiencies entailing toxic chemical utilization on agricultural farms, thus posing a threat to global food security., Methodology: An enhanced convolutional neural network (CNN) along with long short-term memory (LSTM) using a majority voting ensemble classifier has been proposed to tackle plant pest and disease identification and classification. Within pre-trained models, deep feature extractions have been obtained from connected layers. Deep features have been extracted and are sent to the LSTM layer to build a robust, enhanced LSTM-CNN model for detecting plant pests and diseases. Experiments were carried out using a Turkey dataset, with 4447 apple pests and diseases categorized into 15 different classes., Results: The study was evaluated in different CNNs using logistic regression (LR), LSTM, and extreme learning machine (ELM), focusing on plant disease detection problems. The ensemble majority voting classifier was used at the LSTM layer to detect and classify plant disease labels. Furthermore, an autonomous selection of the optimal LSTM layer network parameters was applied. Finally, the performance was validated based on sensitivity, F 1 score, accuracy, and specificity using LSTM, ELM, and LR classifiers., Conclusion: The presented model attained 99.2% accuracy compared to the cutting-edge models on different classifiers such as LSTM, LR, and ELM, and performed better compared to transfer learning. Pre-trained models, such as VGG19, VGG18, and AlexNet, demonstrated better accuracy when the fc6 layer was compared with other layers. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Fatty acids (FAs) stored as triacylglycerols (TAGs) are an important source of carbon and energy for germination and seedling development, particularly for plants with small wind-dispersed seeds, allowing greater efficiency in storing both energy and carbon. These plants should be under strong selection to produce seeds rich in FAs and with large amounts of saturated FAs. Their closely packed single-chain configuration allows greater packing, more carbon and energy per unit mass, and are less costly to produce. Efficient carbon storage would be less crucial for zoochorous species, which can reach much larger seed sizes (mass). We analysed the transesterified FA profile from seeds of 22 anemochorous and zoochorous tree species from the Cerrado savannas of Central Brazil. We tested if seed FA content covaried with seed mass and if anemochorous and zoochorous seeds differed in FA contents and distribution. Fatty acids were an important seed source of carbon and energy for most species. Fifteen different FAs were identified. Oleic, linoleic and linolenic tended to be the predominant unsaturated FAs. Oleic acid corresponded to more than 60 % of the total transesterified FAs in seeds of Kielmeyera coriacea, Qualea dichotoma and Triplaris americana . Linoleic acid corresponded to more than 50 % of total FA in Dalbergia miscolobium, Parkia platycephala and Ferdinandusa elliptica while linolenic acid was the dominant component in Inga cylindrica . Across species, palmitic and stearic were the dominant saturated FAs. The only exception was lauric acid (68 % of total FA) in seeds of Qualea grandiflora . On a log 10 scale, as the seed increased in mass, accumulation of FAs tends to proceed at a faster rate in anemochorous species than in zoochorous species. They also became increasingly richer in saturated FAs. Zoochorous species had seed TAGs with higher proportion of polyunsaturated FAs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company.)

This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.

Mitophagy is an important process that participates in mitochondrial quality control. Dysfunctions in this process can be caused by mutations in genes like PRKN and are associated with the development and progression of Parkinson's Disease (PD). The most used drug in the treatment of PD is levodopa (LD), but it can cause adverse effects, such as dyskinesia. Currently, few studies are searching for biomarkers for an effective use of lLD for this disease, especially regarding mitophagy genetics. Thus, this work investigates the association of 14 variants of the PRKN gene with LD in the treatment of PD. We recruited 70 patients with PD undergoing treatment with LD (39 without dyskinesia and 31 with dyskinesia). Genotyping was based on Sanger sequencing. Our results reinforce that age at onset of symptoms, duration of PD, and treatment and dosage of LD can influence the occurrence of dyskinesia but not the investigated PRKN variants. The perspective presented here of variants of mitophagy-related genes in the context of treatment with LD is still underexplored, although an association has been indicated in previous studies. We suggest that other variants in PRKN or in other mitophagy genes may participate in the development of levodopa-induced dyskinesia in PD treatment.

Sustainability - the new hype of the 21 st century has brought discomfort for the government and society. Sustainable agriculture is essential to face our most concerning challenges: climate change, food security, and the environmental footprint, all of which add to consumers' opinions and choices. Improvements in reproductive indexes can enhance animal production and efficiency, guaranteeing profit and sustainability. Estrus detection, artificial insemination (AI), embryo transfer (ET), estrus synchronization (ES), and multiple ovulations are some strategies used to improve animal reproduction. This review highlights how reproductive strategies and genetic selection can contribute to sustainable ruminant production. Improved reproductive indices can reduce the number of nonproductive cows in the herd, reducing methane emissions and land use for production while preserving natural resources., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Researchers recognize the silent, negative and deleterious effects caused by mercury pollution in gold mining areas. Freshwater turtles are culturally part of the diet of riverside populations in the Amazon region and this area presents mercury (Hg) pollution issues mainly due to gold mining activities. Thus, this research aimed to evaluate the total mercury (THg) content in the different organs of Amazonian giant river turtle ( Podocnemis expansa ) and carry out a human health risk assessment associated with the consumption of these animals. This study was conducted in the Vila Balbina, municipality of Presidente Figueiredo, state of Amazonas, Brazil. Skin ( n = 28), muscle ( n = 19) and brain ( n = 2) samples were analyzed by Atomic Absorption Spectrometry (TDA-AAS) and a DMA-80™ mercury analyzer was used for the total mercury determinations. The average values found for THg in the skin, muscle and brain samples were, respectively, 0.1045 mg·kg -1 , 0.1092 mg·kg -1 and 0.0601 mg·kg -1 . Thus, THg was observed even though the P. expansa were kept in captivity, possibly due to previous contamination by air, water and food. The Hazard Quotient (HQ) was calculated considering a 9.07 g·day -1 intake dose of P. expansa and the consumption of turtles once a week showed an HQ = 2.45, which may cause long-term injuries to human health. Although the muscle concentrations were below the maximum limit established by the World Health Organization (WHO) and Brazilian regulatory agencies, it is important to evaluate consumption factors such as amount ingested, frequency and animal gender, which may cause a potential risk to regular consumers due to mercury bioaccumulation. The WHO may consider various aspects in order to warn the Amazon population about the severity and silent hazard of this metal, especially due to the importance of this matrix in the region. This region urgently needs government actions to inhibit clandestine mining and to prevent future serious, chronic health problems of the entire population.

The growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections is associated with increased mortality rates, which has generated interest in the development of antimicrobial peptides (AMP), such as those found in the giant ant Dinoponera quadríceps. In order to improve the net positive charge and the antibacterial activity of the AMP, amino acids with positive side chain single substituted analogues have been proposed, mainly arginine or lysine. The present work aims to study the antimicrobial activity of the analogues of M-PONTX-Dq3a, a 23 amino acid AMP identified in the D. quadriceps venom. M-PONTX-Dq3a[1-15], a fragment containing the 15 central amino acids, and eight derivatives of single arginine or lysine substituted analogues were proposed. The antimicrobial activity of peptides was evaluated against Staphylococcus aureus ATCC 6538 P (MSSA) and ATCC 33591 (MRSA) strains, followed by minimum inhibitory concentration (MIC), minimum lethal concentration (MLC), and minimum biofilm inhibitory concentration (MBIC) measurement. The membrane permeability was then assessed via crystal violet assay and flow cytometry analysis. The effect of exposure time on microbial viability (Time-Kill) was evaluated. Finally, ultrastructural alterations were evaluated through scanning electron microscopy (SEM). Both arginine-substituted peptides [Arg] 3 M-PONTX-Dq3a[1-15] and [Arg] 4 M-PONTX-Dq3a[1-15], showed lowest MIC and MLC values (each 0.78 μM). In the biofilm formation assays, the peptide [Arg] 3 M-PONTX-Dq3a [1-15] showed MBIC of 3.12 μM against the two tested strains. Both peptides were able to alter the membrane permeability approximately by 80%. The treatment with MIC was able to eliminate bacteria after 2 h of contact on the other hand, treatment with half of the MIC, the population of both bacterial strains remained constant for up to 12 h, indicating a possible bacteriostatic effect. The SEM results showed that the treatment with the lowest concentration (0.78 μM) of both peptides caused disruption of the cell membrane, destabilization of the intercellular interaction and the CLM of [Arg] 4 M-PONTX-Dq3a [1-15] resulted in the complete eradication of the bacteria. Thus, this study describes two AMPs active against MSSA and MRSA and also inhibits the biofilm formation of these stains. This study finds [Arg] 3 M-PONTX-Dq3a[1-15] and [Arg] 4 M-PONTX-Dq3a[1-15] as alternative substances to treat resistant and/or biofilm-forming strains., 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 Ltd. All rights reserved.)

COVID-19, along with most respiratory diseases in the medical field, demonstrates significant ability to take its toll on global population. There is a particular difficulty in studying these conditions, which stems especially from the short supply of in vitro models for detailed investigation, the specific therapeutic knowledge required for disease scrutinization and the occasional need of BSL-3 [Biosafety Level 3] laboratories for research. Based on this, the process of drug development is hampered to a great extent. In the scenario of COVID-19, this difficulty is even more substantial on account of the current undefinition regarding the exact role of the ACE2 [Angiotensin-converting enzyme 2] receptor upon SARS-CoV-2 kinetics in human cells and the great level of demand in the investigation process of ACE2, which usually requires the laborious and ethically complicated usage of transgenic animal models overexpressing the receptor. Moreover, the rapid progression of the aforementioned diseases, especially COVID-19, poses a crucial necessity for adequate therapeutic solutions emergence. In this context, the work herein presented introduces a groundbreaking set of 3D models, namely spheroids and MatriWell cell culture inserts, whose remarkable ability to mimic the in vivo environment makes them highly suitable for respiratory diseases investigation, particularly SARS-CoV-2 infection. Using MatriWells, we developed an innovative platform for COVID-19 research: a pulmonary air-liquid interface [ALI] associated with endothelial (HUVEC) cells. Infection studies revealed that pulmonary (BEAS-2B) cells in the ALI reached peak viral load at 24h and endothelial cells, at 48h, demonstrating lung viral replication and subsequent hematogenous dissemination, which provides us with a unique and realistic framework for studying COVID-19. Simultaneously, the spheroids were used to address the understudied ACE2 receptor, aiming at a pronounced process of COVID-19 investigation. ACE2 expression not only increased spheroid diameter by 20% (p<0.001) and volume by 60% (p≤0.0001) but also led to a remarkable 640-fold increase in intracellular viral load (p≤0.01). The previously mentioned finding supports ACE2 as a potential target for COVID-19 treatment. Lastly, we observed a higher viral load in the MatriWells compared to spheroids (150-fold, p<0.0001), suggesting the MatriWells as a more appropriate approach for COVID-19 investigation. By establishing an advanced method for respiratory tract conditions research, this work paves the way toward an efficacious process of drug development, contributing to a change in the course of respiratory diseases such as COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Gabriel Romero Liguori and Tácia Tavares Aquinas Liguori are, respectively, the Chief Executive Officer and the Chief Scientific Officer of TissueLabs Sagl (Manno, Switzerland), the company which developed and produced MatriWell cell culture inserts. The remaining authors have no conflict of interest to declare., (© 2023 The Author(s).)

Introduction: After three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population&#95;based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics., Methods: We sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases., Results: Regarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43  years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p  = 8.65e-08; male, p  = 0.008961) and age ( p  = 3.6e-10)., Discussion: Although gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents., 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 © 2023 Pinho, Vidal, Negri Rocha, Oliveira, da Costa Barros, Closset, Azevedo-Pinheiro, Braga-da-Silva, Silva, Magalhães, do Carmo Pinto, Souza, dos Santos Vieira, Burbano, de Sousa, de Souza, Nunes, da Silva, da Costa, Salgado, Sousa, Degrave, Ribeiro-dos-Santos, Oliveira and on behalf of Research Network for the Genomic Sequencing of SARS-CoV-2.)

Background: Worldwide, it is estimated that over 6 million people are infected with Chagas disease (ChD). It is a neglected disease that can lead to severe heart conditions in its chronic phase. While early treatment can avoid complications, the early-stage detection rate is low. We explore the use of deep neural networks to detect ChD from electrocardiograms (ECGs) to aid in the early detection of the disease., Methods: We employ a convolutional neural network model that uses 12-lead ECG data to compute the probability of a ChD diagnosis. Our model is developed using two datasets which jointly comprise over two million entries from Brazilian patients: The SaMi-Trop study focusing on ChD patients, enriched with data from the CODE study from the general population. The model's performance is evaluated on two external datasets: the REDS-II, a study focused on ChD with 631 patients, and the ELSA-Brasil study, with 13,739 civil servant patients., Findings: Evaluating our model, we obtain an AUC-ROC of 0.80 (CI 95% 0.79-0.82) for the validation set (samples from CODE and SaMi-Trop), and in external validation datasets: 0.68 (CI 95% 0.63-0.71) for REDS-II and 0.59 (CI 95% 0.56-0.63) for ELSA-Brasil. In the latter, we report a sensitivity of 0.52 (CI 95% 0.47-0.57) and 0.36 (CI 95% 0.30-0.42) and a specificity of 0.77 (CI 95% 0.72-0.81) and 0.76 (CI 95% 0.75-0.77), respectively. Additionally, when considering only patients with Chagas cardiomyopathy as positive, the model achieved an AUC-ROC of 0.82 (CI 95% 0.77-0.86) for REDS-II and 0.77 (CI 95% 0.68-0.85) for ELSA-Brasil., Interpretation: The neural network detects chronic Chagas cardiomyopathy (CCC) from ECG-with weaker performance for early-stage cases. Future work should focus on curating large higher-quality datasets. The CODE dataset, our largest development dataset includes self-reported and therefore less reliable labels, limiting performance for non-CCC patients. Our findings can improve ChD detection and treatment, particularly in high-prevalence areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jidling 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.)

Objectives: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives., Methods: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission., Results: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively., Conclusions: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes., Methods: Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression., Results: The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-β1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed., Conclusion: Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation., (© 2023. The Author(s).)

As the host's first line of defense against pathogens, Toll-like receptors ( TLRs ), such as the TLR3 , are genes encoding transmembrane receptors of the same name. Depending on their expression, TLRs cause a pro- or anti-inflammatory response. The purpose of the article was to determine whether there is an association between the Toll-like receptor 3 ( TLR3 ) rs3775291 Single Nucleotide Polymorphism-SNP and susceptibility to infections. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered in PROSPERO under the code CRD42023429533. A systematic search for relevant studies was performed using PubMed, Scopus, SciELO, Google Scholar, and Science Direct by the MeSH descriptors and the Boolean Operator "AND": "Infections"; "TLR3"; "SNP", between January 2005 and July 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for genotypic comparison assuming a dominant genetic model (CT + TT vs. CC). A meta-analysis of 18 studies consisting of 3118 cases and 4368 controls found a significant association for risk between the presence of the TLR3 SNP rs3775291 and infections as part of the general analysis (OR = 1.16, 95% CI = 1.04-1.28, p = 0.004). In the subgroups of continents, the SNP had a protective role in Europe for 1044 cases and 1471 controls (OR = 0.83, 95% CI = 0.70-0.99, p = 0.04); however, the Asian (for 1588 patients and 2306 controls) and American (for 486 patients and 591 controls) continents had an increase in infectious risk (OR = 1.37, 95% CI = 1.19-1.58, p < 0.001; OR = 1.42, 95% CI = 1.08-1.86, and p = 0.01, respectively). Heterogeneity between studies was detected (I 2 = 58%) but was explained in meta-regression by the subgroup of continents itself and publication bias was not evident. The results of the meta-analysis suggest a significant association between the TLR3 rs3775291 polymorphism and susceptibility to infections. Thus, when analyzing subgroups, the Asian and American continents showed that this SNP confers a higher risk against infections in a dominant genotypic model. Therefore, more studies are necessary to fully elucidate the role of TLR3 rs3775291 in infections.

Gastrointestinal mucositis is a serious and dose-limiting toxic side effect of oncologic treatment. Interruption of cancer treatment due to gastrointestinal mucositis leads to a significant decrease in cure rates and consequently to the deterioration of a patient's quality of life. Natural polysaccharides show a variety of beneficial effects, including a gastroprotective effect. Treatment with soluble dietary fiber (SDF) from yellow passion fruit (Passiflora edulis) biomass residues protected the gastric and intestinal mucosa in models of gastrointestinal injury. In this study, we investigated the protective therapeutic effect of SDF on 5-FU-induced mucositis in male and female mice. Oral treatment of the animals with SDF did not prevent weight loss but reduced the disease activity index and preserved normal intestinal function by alleviating diarrhea and altered gastrointestinal transit. SDF preserved the length of the colon and histological damage caused by 5-FU. SDF significantly restored the oxidative stress and inflammation in the intestine and the enlargement and swelling of the spleen induced by 5-FU. In conclusion, SDF may be a promising adjuvant strategy for the prevention and treatment of intestinal mucositis induced by 5-FU.

Context: The gradual impact of the Covid-19 pandemic had important effects on routines in surgical environments. In order to cope with the impact and re-establish anaesthesiology and surgery procedures, it was imperative to pursue in-depth studies with a view to ensuring safe surgical care, reducing hazards, as well as protecting the health, safety and wellbeing of the health personnel involved. The purpose of this study was to evaluate quantitative and qualitative approaches to domains of safety climate among multi-professional staffs of surgical centres during the Covid-19 pandemic and to identify intersections., Methods: This mixed-method project employed a concomitant triangulation strategy on a quantitative approach in an exploratory, descriptive, cross-sectional study, as well as a qualitative approach by way of a descriptive study. Data were collected using the validated, self-applicable Safety Attitudes Questionnaire/Operating Room (SAQ/OR) questionnaire and a semi-structured interview script. The 144 participants were the surgical, anaesthesiology, nursing and support teams working in the surgical centre during the Covid-19 pandemic., Results: The study found an overall safety climate score of 61.94, the highest-scoring domain being 'Communication in the surgical environment' (77.91) and the lowest, 'Perception of professional performance' (23.60). On integrating the results, a difference was found between the domains 'Communication in the surgical environment' and 'Working conditions'. However, there was intersection by the 'Perception of professional performance' domain, which permeated important categories of the qualitative analysis., Conclusions: For care practice, it is hoped to encourage improved patient safety, educational interventions to strengthen the patient safety climate and promote in-job wellbeing on the job for health personnel working in surgical centres. It is suggested that further studies explore the subject in greater depth among several surgical centres with mixed methods, so as to permit future comparisons and to monitor the evolving maturity of safety climate., (© 2023. The Author(s).)

The historical and social vulnerability of quilombola communities in Brazil can make them especially fragile in the face of COVID-19, considering that several individuals have precarious health systems and inadequate access to water. This work aimed to characterize the frequency of SARS-COV-2 infections and the presence of IgM and IgG SARS-CoV-2 antibodies in quilombola populations and their relationship with the presence of risk factors or preexisting chronic diseases in the quilombola communities. We analyzed the sociodemographic and clinical characteristics, serological status, comorbidities, and symptoms of 1,994 individuals (478 males and 1,536 females) from 18 Brazilian municipalities in the State of Sergipe of quilombola communities, which were evaluated at different epidemiological weeks, starting at the 32nd (August 6th) and ending at the 40th (October 3rd) epidemiological week. More than 70% of studied families live in rural areas and they have an extreme poverty social status. Although we found a higher number of SARS-COV-2 infections in quilombola communities than in the local population, their SARS-CoV-2 reactivity and IgM and IgG positivity varied across the communities investigated. Arterial hypertension was the most risk factor, being found in 27.8% of the individuals (9.5% in stage 1, 10.8% in stage 2, and 7.5% in stage 3). The most common COVID-19 symptoms and comorbidities were headache, runny nose, flu, and dyslipidemia. However, most individuals were asymptomatic (79.9%). Our data indicate that mass testing must be incorporated into public policy to improve the health care system available to quilombola populations during a future pandemic or epidemic., 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 © 2023 Martins, de Souza, de Rezende Neto, Santos, da Invenção, Matos, dos Santos, de Jesus, da Silva, de Almeida, do Vale, Fonseca, Schimke, Matos, Oliveira, Ferreira, de Paula Dias, dos Santos, Barbosa, de Carvalho Barreto, Moreno, Gonçalves, de Mello Silva, Cabral-Marques and Borges.)

Objective: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population., Methods: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo., Results: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs)., Conclusion: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The thymus is responsible for the selection and development of T cells, having an essential role in the establishment of adaptive immunity. Thymic epithelial cells (TECs) are key players in T cell development interacting with thymocytes in the thymic 3D environment. Feeder-layer cells have been frequently used as platforms for the successful establishment of TEC cultures. Nevertheless, the role of the feeder cell-derived extracellular matrix (ECM) on TEC cultures was not previously reported. Therefore, this work aimed at assessing the effect of the ECM produced by feeder cells cultured at two different densities on the establishment of TEC culture. Due to the high surface area and porosity, electrospun fibrous meshes were used to support ECM deposition. The feeder cell-derived ECM was efficiently recovered after decellularization, maintaining the composition of major proteins. All the decellularized matrices were permeable and showed an increase in surface mechanical properties after decellularization. TEC cultures confirmed that the ECM density impacts cellular performance, with higher densities showing a decreased cellular activity. Our findings provide evidence that feeder cell-derived ECM is a suitable substrate for TEC culture and can potentially be applied in thymus bioengineering.

The total and soluble contents of three potentially toxic elements (PTEs) (Cd, Cr, and Pb) and two essential elements (Cu and Ni) in commercial green and roasted mate (Ilex paraguariensis St. Hil.) and their hot infusions were accessed by inductively coupled plasma mass spectrometry. Total polyphenolic (TP) contents in the infusions were accessed by Folin-Ciocalteu method, and the presence of soluble melanoidins (SM) was evaluated by measuring absorbances at 420 nm. The soluble element contents in hot infusions of green mate were present in the following increasing order: Pb < Cd < Cr < Cu, and Ni. For hot infusions of roasted mate, the increasing order was: Cu < Pb < Cd < Cr < Ni. Except for Cr, hot infusions of roasted mate supply lower contents of the soluble PTEs than hot infusions of green mate. Cadmium was the only of evaluated trace element found in hot infusions of green and roasted mate as well as in some of their mate samples above the maximum allowed contents established by Brazilian legislation. Despite this, polyphenol and melanoidin contents in green and roasted mate infusions may reduce Cd bioavailability. The soluble trace elements that correlated directly with total polyphenols in hot infusions of green or roasted mate are indirectly correlated with the presence of soluble melanoidins. Moreover, this is the first study to evaluate the correlations of soluble forms of Cd, Cr, Cu, Ni, and Pb with the presence of SM and TP contents in hot infusions of green and roasted mate., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wastewater-based epidemiology can be a complementary approach for monitoring SARS-CoV-2 prevalence, diversity, and geographic distribution. It is a complementary approach regarding its prevalence and diversity, and geographic distribution. The study aimed to evaluate the genetic diversity of SARS-CoV-2 in two wastewater treatment plants (WWTPs) in Rio de Janeiro, Brazil. Samples were collected over a period of January to December 2021 and were concentrated with PEG8000 and the presence of SARS-CoV-2 was detected using E and N1 genes. Partial sequencing of the SARS-CoV-2 genomes resulted in the identification of variants of concern and variants of interest throughout the collection period. It was possible to identify the Mu, Delta, Gamma and Omicron variants in WWTP1; on the contrary, no variants were observed in WWTP2. To the best of our knowledge, we detected the variant Mu (B.1.621) containing characteristic mutations (S:E484K, S:N501Y) from WWTP, for the first time, in Brazil. Another Mu variant detected from clinical surveillance was announced one month after our finding. The detection of SARS-CoV-2 in wastewater can serve as a tool to monitor the prevalence and epidemiology in each community, helping to understand the spread of the virus among the population.

The experiments reported in this research paper address the effects of replacing ground corn (GC) with full-fat corn germ (FFCG) on nutrient intake and digestibility, nitrogen utilization efficiency, performance, and predicted methane production in dairy cows fed cactus cladodes and sugarcane. We hypothesized that the inclusion of FFCG in the diet would not alter the performance of lactating cows but would reduce the predicted methane production in vivo. Ten multiparous Holstein cows at 90 ± 10 d of lactation and yielding 24.2 ± 3.5 kg milk/d were assigned to dietary treatments consisting of different levels of replacement of GC by FFCG (0; 25; 50; 75 and 100% of diet dry matter) in a replicated 5 × 5 Latin square design with 21-d periods. Methane production was predicted using an automated gas in vitro production system. Except for ether extract intake, which increased, the intake of all nutrients decreased linearly with the replacement of GC by FFCG. The digestibility of dry matter, organic matter and neutral detergent fiber reduced, whereas the digestibility of ether extract increased linearly with FFCG. There were no changes in the digestibility of crude protein. The nitrogen intake and daily excretion in urine and feces decreased, while nitrogen use efficiency increased linearly. There was no significant effect of diets on nitrogen balance or microbial protein synthesis and efficiency. The yield of protein, lactose and total solids in milk showed a quadratic behavior. On the other hand, milk fat yield and energy-corrected milk yield decreased linearly with the replacement of GC by FFCG. No effect on pH or ammonia nitrogen was observed. The production of methane (CH 4 , g/kg DM) and total CH 4 (g/d), and CH 4 intensity decreased linearly with the replacement of GC by FFCG. In conclusion, FFCG has been shown to be an effective source of fat to reduce methane production in dairy cows, partially supporting our initial hypothesis. However, as it decreases milk fat production, it is not recommended to replace more than 50% of GC by FFCG for lactating cows fed cactus cladodes and sugarcane.

Dengue fever is among the most significant public health concerns in Brazil. To date, the highest number of Dengue notifications in the Americas has been reported in Brazil, with cases accounting for a total number of 3,418,796 reported cases as of mid-December 2022. Furthermore, the northeastern region of Brazil registered the second-highest incidence of Dengue fever in 2022. Due to the alarming epidemiological scenario, in this study, we used a combination of portable whole-genome sequencing, phylodynamic, and epidemiological analyses to reveal a novel DENV-1 genotype V clade and the persistence of DENV-2 genotype III in the region. We further report the presence of non-synonymous mutations associated with non-structural domains, especially the NS2A (non-structural protein 2A), as well as describe synonymous mutations in envelope and membrane proteins, distributed differently between clades. However, the absence of clinical data at the time of collection and notification, as well as the impossibility of monitoring patients in order to observe worsening or death, restricts our possibility of correlating mutational findings with possible clinical prognoses. Together, these results reinforce the crucial role of genomic surveillance to follow the evolution of circulating DENV strains and understand their spread across the region through inter-regional importation events, likely mediated by human mobility, and also the possible impacts on public health and outbreak management.

Arthropods transmit arboviruses via mosquito and tick bites to humans and other animals. The genus flavivirus, which causes diseases, sequelae, and thousands of deaths, mainly in developing and underdeveloped countries, is among the arboviruses of interest to public health. Given the importance of early and accurate diagnosis, this review analyzes the methods of direct detection of flaviviruses, such as reverse transcription loop-mediated isothermal amplification, microfluidics, localized surface plasmon resonance, and surface-enhanced Raman scattering, and presents the advantages, disadvantages, and detection limits identified in studies reported in the literature for each methodology. Among the different methods available, it is essential to balance four fundamental indicators to determine the ideal test: good sensitivity, high specificity, low false positive rate, and rapid results. Among the methods analyzed, reverse transcription loop-mediated isothermal amplification stands out, owing to result availability within a few minutes, with good sensitivity and specificity; in addition, it is the best-characterized methodology.

Objective: to evaluate the association between quality of life and presence of symptoms of depression, anxiety, and stress in college students in the health area., Method: cross-sectional study that included 321 students from undergraduate courses in the health area. Quality of life was measured using the World Health Organization scale, abbreviated version, in the physical, psychological, social relations and environment domains, and symptoms were assessed by the depression, anxiety and stress scale. Multivariate analysis was performed using robust linear regression to evaluate the association between quality of life and symptoms., Results: a negative association was observed between the quality of life and depression symptoms in all domains, while anxiety symptoms showed a negative association in the environment domain, and stress symptoms had a negative association in the psychological domain. Symptom severity was unfavorably associated with quality of life, that is, the greater the symptom severity, the lower the mean scores in all domains., Conclusion: symptoms of depression, anxiety, and stress were prevalent and had a negative impact on students' quality of life, especially in the presence of depressive symptoms. The decrease in scores was significantly associated with the severity of symptoms.

Numerous tests employed to predict cardiac and functional status are expensive and not widely accessible for a considerable number of patients, particularly those diagnosed with Chagas disease (CD) residing in remote and endemic regions. To date, there is no knowledge of studies that have validated instruments that address functionality in an expanded way, including the biopsychosocial factors in patients with CD. This study aims to evaluate the psychometric properties of the World Health Organization Disability Assessment Schedule (WHODAS 2.0), in its 12-item shortened version (WHODAS-12) when applied to patients with CD. This is a cross-sectional study of a prospective cohort that follows individuals with CD (SaMi-Trop). Data collection took place between October 2019 and March 2020. In the interviews, sociodemographic information, life habits, clinical information, and indicators of disability measured by WHODAS-12 were collected. Descriptive analysis, internal consistency and construct validity of the instrument were performed. A total of 628 patients with CD were interviewed, most were women (69.5%), their mean age was of 57 years, and most declared an average self-perception of health (43.4%). The 12 items of WHODAS-12 were distributed into three factors, which together account for 61% of the variance. The Kaiser-Meyer-Olkin (KMO) index was 0.90, indicating adequacy of the sample for factor analysis. The internal consistency of the global scale showed alpha = 0.87. The percentage of incapacity was 16.05%, indicating mild incapacity for the evaluated patients. WHODAS-12 is a valid and reliable measure to assess the disability of the Brazilian population with CD.

Background: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis., Objective: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population., Methods: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models., Results: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with "combined" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed., Conclusion: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest in any form., (Copyright © 2022. Published by Elsevier Inc.)

The thymus coordinates the development and selection of T cells. It is structured into two main compartments: the cortex and the medulla. The replication of such complex 3D environment has been challenged by bioengineering approaches. Nevertheless, the effect of the scaffold microstructure on thymic epithelial cell (TEC) cultures has not been deeply investigated. Here, we developed bilayered porous silk fibroin scaffolds and tested their effect on TEC co-cultures. The small and large pore scaffolds presented a mean pore size of 84.33 ± 21.51 μm and 194.90 ± 61.38 μm, respectively. The highly porous bilayered scaffolds presented a high water absorption and water content (> 94 %), together with mechanical properties in the range of the native tissue. TEC (i.e., medullary (mTEC) and cortical (cTEC) cell lines) proliferation is increased in scaffolds with larger pores. The co-culture of both TEC lines in the bilayered porous silk scaffolds presents enhanced cell proliferation and metabolic activity when compared with mTEC in single culture. Also, when the co-culture occurred with cTEC in the small pores layer and mTEC in the large pores layer, a 9.2- and 18.9-fold increase in Foxn1 and Icam1 gene expression in cTEC is evident. These results suggest that scaffold microstructure and the co-culture influence TEC's behaviour. Bilayered silk scaffolds with adjusted microstructure are a valid alternative for TEC culture, having possible applications in advanced thymus bioengineering strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aimed to select high-quality spermatozoa by sperm separation by magnetic activation of the fresh equine semen, compared to density gradient centrifugation and evaluating cell quality after selection. The semen of 10 stallions was collected by the artificial vagina technique. The samples analyzed were: (1) fresh semen; (2) density gradient centrifugation (DGC); (3) separation by magnetic activation (MASS) (nonapoptotic portion NAP); (4) separation by MASS (apoptotic portion-APT). Was analyzed: motility (light microscopy), concentration (Neubauer chamber), semen morphology (humid chamber in phase contrast), and supravital test (eosin/nigrosine). In DGC, 20 × 10 6 spermatozoa were used in the gradient of Percoll at 90% and 45% (400 μL each), centrifugation at 900 G/5 min, the pellet was diluted in HEPES. In MASS, 10 × 10 6 spermatozoa were diluted in 1.5 mL of HEPES, centrifugation at 300 G/10 min, pellet was resuspended in 150 μL of HEPES with 20 μL of nanoparticles bound to annexin V, incubation for 15 minutes and filtered in the magnetic separation column. The nonapoptotic fraction was collected directly and the apoptotic fraction after removal the column from the magnet and adding 300 μL of HEPES. The total abnormalities were 43.2% ± 2.78%, with the DGC and MASS being effective in reducing sperm abnormality by 15.6% ± 2.10% and 24.30% ± 1.63%, respectively, like the observed for the number of cells with intact membranes (50% lower in the APT portion). This nanotechnological method is efficient in producing high-quality semen samples for assisted reproduction procedures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence of syphilis and its associated factors in women who were treated at public maternity hospitals and received prenatal care in a primary healthcare unit., Methods: This cross-sectional study included 399 postpartum women. Interviews were conducted, and additional data were extracted from the pregnant woman's booklet, medical records, and printed tests. The dependent variable was a gestational syphilis diagnosis. The independent variables were grouped into socioeconomic and demographic, behavioral, reproductive, and prenatal blocks. The prevalence, prevalence ratios, and 95% confidence intervals (95%CI) were calculated. The χ 2 test was also performed (p≤0.05). Multivariate analysis was performed using Poisson regression models., Results: The prevalence of gestational syphilis was 9.61% (95%CI: 7.14-12.83). We identified the following determining factors (adjusted prevalence ratios): history of sexually transmitted infections (2.3), first sexual intercourse by the age of 15 (2.42), partner having a history of syphilis (5.98), partner using crack/cocaine (6.42) and marijuana and others (3.02), not having a partner (3.07), low income (2.85), history of stillbirth (5.21), beginning prenatal care in the third trimester (3.15), and prenatal care received in a primary healthcare unit (without a Family Health Strategy team) (0.35)., Conclusion: Individual and prenatal factors were associated with gestational syphilis. To control congenital syphilis, targeted interventions are needed to control syphilis in the adult population including expansion of access to quality prenatal care with identification of risks for syphilis and connection between prevention and treatment actions, implementation of strategies focused on early sexual education, effective establish prenatal care involving both partners, and effective implementation of the National Men's Health Policy (PNAISH - Política Nacional de Atenção Integral à Saúde dos Homens ).

Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H 2 O), EtOH:H 2 O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery.