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The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I 2  = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I 2  = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I 2  = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I 2  = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I 2  = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I 2  = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I 2  = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I 2  = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I 2  = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group., Methods: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage., Results: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001)., Conclusion: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Bacterial pustule (BP), caused by Xanthomonas citri pv. glycines , is an important disease that, under favorable conditions, can drastically affect soybean production. We performed a genome-wide association study (GWAS) with a panel containing Brazilian and American cultivars, which were screened qualitatively and quantitatively against two Brazilian X. citri isolates (IBS 333 and IBS 327). The panel was genotyped using a genotyping by sequencing (GBS) approach, and we identified two main new regions in soybeans associated with X. citri resistance on chromosomes 6 (IBS 333) and 18 (IBS 327), different from the traditional rxp gene located on chromosome 17. The region on chromosome 6 was also detected by QTL mapping using a biparental cross between Williams 82 (R) and PI 416937 (S), showing that Williams 82 has another recessive resistance gene besides rxp , which was also detected in nine BP-resistant ancestors of the Brazilian cultivars (including CNS, S-100), based on haplotype analysis. Furthermore, we identified additional SNPs in strong LD (0.8) with peak SNPs by exploring variation available in WGS (whole genome sequencing) data among 31 soybean accessions. In these regions in strong LD, two candidate resistance genes were identified (Glyma.06g311000 and Glyma.18g025100) for chromosomes 6 and 18, respectively. Therefore, our results allowed the identification of new chromosomal regions in soybeans associated with BP disease, which could be useful for marker-assisted selection and will enable a reduction in time and cost for the development of resistant cultivars.

Effector proteins in Phakopsora pachyrhizi (Pp), the causative agent of Asian Soybean rust, are involved in the infection process. A previous study identified a rust effector Egh16-like family based expression profile during the interaction with soybean. Herein, we scrutinized available the Pp genomes to validate the predicted Egh16-like family of Pp and identify new family members. We described 22 members of the Egh16-like gene family in the Pp MT2006 genome and 18 in the UFV02 and K8108 genomes, highlighting a family expansion. Family members have a small signal peptide, conserved cysteine-rich R/Y/FxC motifs in the C-terminal region, and a virulence-related Egh16-like domain and were able to suppress PTI related responses in Benthamiana. Phylogenetic analysis placed the family members into eight clusters, with members induced during the early stages of rust infection. Members of clusters VI and VII are present in different copy numbers in Pp genomes and suppressed PAMP-related responses.

Competing Interests: The authors declare that they have no conflict of interest.

Microtubules are components of the cytoskeleton that perform essential functions in eukaryotes, such as those related to shape change, motility and cell division. In this context some characteristics of these filaments are essential, such as polarity and dynamic instability. In trypanosomatids, microtubules are integral to ultrastructure organization, intracellular transport and mitotic processes. Some species of trypanosomatids co-evolve with a symbiotic bacterium in a mutualistic association that is marked by extensive metabolic exchanges and a coordinated division of the symbiont with other cellular structures, such as the nucleus and the kinetoplast. It is already established that the bacterium division is microtubule-dependent, so in this work, it was investigated whether the dynamism and remodeling of these filaments is capable of affecting the prokaryote division. To this purpose, Angomonas deanei was treated with Trichostatin A (TSA), a deacetylase inhibitor, and mutant cells for histone deacetylase 6 (HDAC6) were obtained by CRISPR-Cas9. A decrease in proliferation, an enhancement in tubulin acetylation, as well as morphological and ultrastructural changes, were observed in TSA-treated protozoa and mutant cells. In both cases, symbiont filamentation occurred, indicating that prokaryote cell division is dependent on microtubule dynamism., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Coffee farming constitutes a substantial economic resource, representing a source of income for several countries due to the high consumption of coffee worldwide. Precise management of coffee crops involves collecting crop attributes (characteristics of the soil and the plant), mapping, and applying inputs according to the plants' needs. This differentiated management is precision coffee growing and it stands out for its increased yield and sustainability., Results: This research aimed to predict yield in coffee plantations by applying machine learning methodologies to soil and plant attributes. The data were obtained in a field of 54.6 ha during two consecutive seasons, applying varied fertilization rates in accordance with the recommendations of soil attribute maps. Leaf analysis maps also were monitored with the aim of establishing a correlation between input parameters and yield prediction. The machine-learning models obtained from these data predicted coffee yield efficiently. The best model demonstrated predictive fit results with a Pearson correlation of 0.86. Soil chemical attributes did not interfere with the prediction models, indicating that this analysis can be dispensed with when applying these models., Conclusion: These findings have important implications for optimizing coffee management and cultivation, providing valuable insights for producers and researchers interested in maximizing yield using precision agriculture. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Monitoring intracranial pressure (ICP) is pivotal in the management of severe traumatic brain injury (TBI), but secondary brain injuries can arise despite normal ICP levels. Cerebral tissue oxygenation monitoring (PbtO2) may detect neuronal tissue infarction thresholds, enhancing neuroprotection. We performed a systematic review and meta-analysis to evaluate the effects of combined cerebral tissue oxygenation (PbtO2) and ICP compared to isolated ICP monitoring in patients with TBI. PubMed, Embase, Cochrane, and Web of Sciences databases were searched for trials published up to June 2023. A total of 16 studies comprising 37,820 patients were included. ICP monitoring was universal, with additional placement of PbtO2 in 2222 individuals (5.8%). The meta-analysis revealed a reduction in mortality (OR 0.57, 95% CI 0.37-0.89, p = 0.01), a greater likelihood of favorable outcomes (OR 2.28, 95% CI 1.66-3.14, p < 0.01), and a lower chance of poor outcomes (OR 0.51, 95% CI 0.34-0.79, p < 0.01) at 6 months for the PbtO2 plus ICP group. However, these patients experienced a longer length of hospital stay (MD 2.35, 95% CI 0.50-4.20, p = 0.01). No significant difference was found in hospital mortality rates (OR 0.81, 95% CI 0.61-1.08, p = 0.16) or intensive care unit length of stay (MD 2.46, 95% CI - 0.11-5.04, p = 0.06). The integration of PbtO2 to ICP monitoring improved mortality outcomes and functional recovery at 6 months in patients with TBI. PROSPERO (International Prospective Register of Systematic Reviews) CRD42022383937; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=383937., (© 2024. Fondazione Società Italiana di Neurologia.)

The diagnosis of Moyamoya disease (MMD) relies heavily on imaging, which could benefit from standardized machine learning tools. This study aims to evaluate the diagnostic efficacy of deep learning (DL) algorithms for MMD by analyzing sensitivity, specificity, and the area under the curve (AUC) compared to expert consensus. We conducted a systematic search of PubMed, Embase, and Web of Science for articles published from inception to February 2024. Eligible studies were required to report diagnostic accuracy metrics such as sensitivity, specificity, and AUC, excluding those not in English or using traditional machine learning methods. Seven studies were included, comprising a sample of 4,416 patients, of whom 1,358 had MMD. The pooled sensitivity for common and random effects models was 0.89 (95% CI: 0.85 to 0.92) and 0.92 (95% CI: 0.85 to 0.96), respectively. The pooled specificity was 0.89 (95% CI: 0.86 to 0.91) in the common effects model and 0.91 (95% CI: 0.75 to 0.97) in the random effects model. Two studies reported the AUC alongside their confidence intervals. A meta-analysis synthesizing these findings aggregated a mean AUC of 0.94 (95% CI: 0.92 to 0.96) for common effects and 0.89 (95% CI: 0.76 to 1.02) for random effects models. Deep learning models significantly enhance the diagnosis of MMD by efficiently extracting and identifying complex image patterns with high sensitivity and specificity. Trial registration: CRD42024524998 https://www.crd.york.ac.uk/prospero/displayrecord.php?RecordID=524998., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The advancement of technology has significantly transformed the livestock landscape, particularly in the management of dairy cattle, through the incorporation of digital and precision approaches. This study presents a bibliometric analysis focused on these technologies involving dairy farming to explore and map the extent of research in the scientific literature. Through this review, it was possible to investigate academic production related to digital and precision livestock farming and identify emerging patterns, main research themes, and author collaborations. To carry out this investigation in the literature, the entire timeline was considered, finding works from 2008 to November 2023 in the scientific databases Scopus and Web of Science. Next, the Bibliometrix (version 4.1.3) package in R (version 4.3.1) and its Biblioshiny software extension (version 4.1.3) were used as a graphical interface, in addition to the VOSviewer (version 1.6.19) software, focusing on filtering and creating graphs and thematic maps to analyze the temporal evolution of 198 works identified and classified for this research. The results indicate that the main journals of interest for publications with identified affiliations are "Computers and Electronics in Agriculture" and "Journal of Dairy Science". It has been observed that the authors focus on emerging technologies such as machine learning, deep learning, and computer vision for behavioral monitoring, dairy cattle identification, and management of thermal stress in these animals. These technologies are crucial for making decisions that enhance health and efficiency in milk production, contributing to more sustainable practices. This work highlights the evolution of precision livestock farming and introduces the concept of digital livestock farming, demonstrating how the adoption of advanced digital tools can transform dairy herd management. Digital livestock farming not only boosts productivity but also redefines cattle management through technological innovations, emphasizing the significant impact of these trends on the sustainability and efficiency of dairy production.

A deeper understanding of gas emissions in milk production is crucial for promoting productive efficiency, sustainable resource use, and animal welfare. This paper aims to analyze ammonia and greenhouse gas emissions in dairy farming using bibliometric methods. A total of 187 English-language articles with experimental data from the Scopus and Web of Science databases (January 1987 to April 2024) were reviewed. Publications notably increased from 1997, with the highest number of papers published in 2022. Research mainly focuses on ammonia and methane emissions, including quantification, volatilization, and mitigation strategies. Other gases like carbon dioxide, nitrous oxide, and hydrogen sulfide were also studied. Key institutions include the University of California-Davis and Aarhus University. Bibliometric analysis revealed research evolution, identifying trends, gaps, and future research opportunities. This bibliometric analysis offers insights into emissions, air quality, sustainability, and animal welfare in dairy farming, highlighting areas for innovative mitigation strategies to enhance production sustainability. This research contributes to academia, enhancing agricultural practices, and informing environmental policies. It is possible to conclude that this research is a valuable tool for understanding the evolution of research on gas emissions in dairy cattle facilities, providing guidance for future studies and interventions to promote more sustainable production.

Environmental enrichment (EE) is a paradigm that offers the animal a plethora of stimuli, including physical, cognitive, sensory, and social enrichment. Exposure to EE can modulate both anxiety responses and plasma corticosterone. In this study, our objective was to explore how chronic unpredictable stress (CUS) impacts anxiety-related behaviors in male Swiss mice raised in EE conditions. Additionally, we investigated corticosterone and adrenocorticotropic hormone (ACTH) levels to assess the involvement of the hypothalamic-pituitary-adrenal (HPA) axis in mediating these responses. Mice were housed under either EE or standard housing conditions for 21 days. Afterward, they were exposed to 11 days of CUS while still reared in their distinct housing conditions, with half of the mice receiving daily pretreatment with the vehicle and the other half receiving daily metyrapone (MET) injections, an inhibitor of steroid synthesis, 30 mins before CUS exposure. Blood samples were obtained to assess plasma corticosterone and ACTH levels. The 11-day CUS protocol induced anxiety-like phenotype and elevated ACTH levels in EE mice. Chronic MET pretreatment prevented anxiety-like behavior in the EE-CUS groups, by mechanisms involving increased plasma corticosterone levels and decreased ACTH. These results suggest a role of the HPA axis in the mechanism underlying the anxiogenic phenotype induced by CUS in EE mice and shed light on the complex interplay between environmental factors, stress, and the HPA axis in anxiety regulation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Delayed cerebral ischemia (DCI) is a common and severe complication after subarachnoid hemorrhage (SAH). Logistic regression (LR) is the primary method to predict DCI, but it has low accuracy. This study assessed whether other machine learning (ML) models can predict DCI after SAH more accurately than conventional LR. PubMed, Embase, and Web of Science were systematically searched for studies directly comparing LR and other ML algorithms to forecast DCI in patients with SAH. Our main outcome was the accuracy measurement, represented by sensitivity, specificity, and area under the receiver operating characteristic. In the six studies included, comprising 1828 patients, about 28% (519) developed DCI. For LR models, the pooled sensitivity was 0.71 (95% confidence interval [CI] 0.57-0.84; p < 0.01) and the pooled specificity was 0.63 (95% CI 0.42-0.85; p < 0.01). For ML models, the pooled sensitivity was 0.74 (95% CI 0.61-0.86; p < 0.01) and the pooled specificity was 0.78 (95% CI 0.71-0.86; p = 0.02). Our results suggest that ML algorithms performed better than conventional LR at predicting DCI.Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42023441586; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=441586., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Spatiotemporal regulation of gene expression is controlled by transcription factor (TF) binding to regulatory elements, resulting in a plethora of cell types and cell states from the same genetic information. Due to the importance of regulatory elements, various sequencing methods have been developed to localise them in genomes, for example using ChIP-seq profiling of the histone mark H3K27ac that marks active regulatory regions. Moreover, multiple tools have been developed to predict TF binding to these regulatory elements based on DNA sequence. As altered gene expression is a hallmark of disease phenotypes, identifying TFs driving such gene expression programs is critical for the identification of novel drug targets. In this study, we curated 84 chromatin profiling experiments (H3K27ac ChIP-seq) where TFs were perturbed through e.g., genetic knockout or overexpression. We ran nine published tools to prioritize TFs using these real-world datasets and evaluated the performance of the methods in identifying the perturbed TFs. This allowed the nomination of three frontrunner tools, namely RcisTarget, MEIRLOP and monaLisa. Our analyses revealed opportunities and commonalities of tools that will help to guide further improvements and developments in the field., Competing Interests: All authors are, or were, employees or affiliates of the Novartis Pharma AG. The authors declare that they have no competing interests., (© 2024 The Authors.)

Introduction: The increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity., Methodology: Thirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation., Results: In the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group., Conclusion: Studies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity., 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: Carla Barbosa Nonino, Fernando Barbosa Júnior, and Lígia Moriguchi Watanabe report financial support provided by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)., (Copyright © 2024. Published by Elsevier GmbH.)

Ruptured anterior communicating artery (ACoA) aneurysms are frequently associated with neuropsychological deficits. This review aims to compare neuropsychological outcomes between surgical and endovascular approaches to ACoA. We systematically searched PubMed, Embase, and Web of Science for studies comparing the endovascular and surgical approaches to ruptured ACoA aneurysms. Outcomes of interest were the cognitive function, covered by memory, attention, intelligence, executive, and language domains, as well as motor and visual functions. Nine studies, comprising 524 patients were included. Endovascularly-treated patients showed better memory than those treated surgically (Standardized Mean Difference (SMD) = -2; 95% CI: -3.40 to -0.61; p < 0.01). Surgically clipped patients had poorer motor ability than those with coiling embolization (p = 0.01). Executive function (SMD = -0.20; 95% CI: -0.47 to 0.88; p = 0.55), language (SMD = -0.33; 95% CI: -0.95 to 0.30; p = 0.30), visuospatial function (SMD = -1.12; 95% CI: -2.79 to 0.56; p = 0.19), attention (SMD = -0.94; 95% CI: -2.79to 0.91; p = 0.32), intelligence (SMD = -0.25; 95% CI: -0.73 to 0.22; p = 0.30), and self-reported cognitive status (SMD = -0.51; 95% CI: -1.38 to 0.35; p = 0.25) revealed parity between groups. Patients with ACoA treated endovascularly had superior memory and motor abilities. Other cognitive domains, including executive function, language, visuospatial function, attention, intelligence and self-reported cognitive status revealed no statistically significant differences between the two approaches. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42023461283; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=461283., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Endosymbiotic relationships are pervasive across diverse taxa of life, offering key avenues for eco-evolutionary dynamics. Although a variety of experimental and empirical frameworks have shed light on critical aspects of endosymbiosis, theoretical frameworks (mathematical models) are especially well-suited for certain tasks. Mathematical models can integrate multiple factors to determine the net outcome of endosymbiotic relationships, identify broad patterns that connect endosymbioses with other systems, simplify biological complexity, generate hypotheses for underlying mechanisms, evaluate different hypotheses, identify constraints that limit certain biological interactions, and open new lines of inquiry. This Essay highlights the utility of mathematical models in endosymbiosis research, particularly in generating relevant hypotheses. Despite their limitations, mathematical models can be used to address known unknowns and discover unknown unknowns., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Souza 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.)

It is more than recognized and accepted that the environment affects the physiological responses of all living things, from bacteria to superior vertebrates, constituting an important factor in the evolution of all species. Environmental influences range from natural processes such as sunlight, seasons of the year, and rest to complex processes like stress and other mood disorders, infections, and air pollution, being all of them influenced by how each creature deals with them. In this chapter, it will be discussed how some of the environmental elements affect directly or indirectly neuropathic pain, a type of chronic pain caused by a lesion or disease of the somatosensory nervous system. For that, it was considered the edge of knowledge in translational research, thus including data from human and experimental animals as well as the applicability of such findings., 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.)

Introduction: In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression., Methods: To investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4 + and CD8 + T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure., Results: We found that the frequency of IFN-γ-producingCD4 + T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4 + T cells peaked on day 7 following the start of treatment. Although the frequency of CD4 + IL-17 + cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4 + T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4 + IL-10 + cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4 + producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8 + single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8 + single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8 + double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8 + T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels., Discussion: Our results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4 + Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8 + single-producers of IFN-γ and double producers of IFN-γ and IL-17., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 de Franca, Rodrigues, Barreto, da Cruz, Aragão-Santos, da Silva, de Jesus, Palatnik-de-Sousa, de Almeida and Corrêa.)

Background and Objectives: High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage., Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality., Results: Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%., Conclusion: This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Studies focusing on characterizing circRNAs with the potential to translate into peptides are quickly advancing. It is helping to elucidate the roles played by circRNAs in several biological processes, especially in the emergence and development of diseases. While various tools are accessible for predicting coding regions within linear sequences, none have demonstrated accurate open reading frame detection in circular sequences, such as circRNAs. Here, we present cirCodAn, a novel tool designed to predict coding regions in circRNAs. We evaluated the performance of cirCodAn using datasets of circRNAs with strong translation evidence and showed that cirCodAn outperformed the other tools available to perform a similar task. Our findings demonstrate the applicability of cirCodAn to identify coding regions in circRNAs, which reveals the potential of use of cirCodAn in future research focusing on elucidating the biological roles of circRNAs and their encoded proteins. cirCodAn is freely available at https://github.com/denilsonfbar/cirCodAn., (Copyright © 2024. Published by Elsevier Inc.)

It has been 70 years since Barbara McClintock discovered transposable elements (TE), and the mechanistic studies and functional applications of transposable elements have been at the forefront of life science research. As an essential part of the genome, TEs have been discovered in most species of prokaryotes and eukaryotes, and the relative proportion of the total genetic sequence they comprise gradually increases with the expansion of the genome. In humans, TEs account for about 40% of the genome and are deeply involved in gene regulation, chromosome structure maintenance, inflammatory response, and the etiology of genetic and non-genetic diseases. In-depth functional studies of TEs in mammalian cells and the human body have led to a greater understanding of these fundamental biological processes. At the same time, as a potent mutagen and efficient genome editing tool, TEs have been transformed into biological tools critical for developing new techniques. By controlling the random insertion of TEs into the genome to change the phenotype in cells and model organisms, critical proteins of many diseases have been systematically identified. Exploiting the TE's highly efficient in vitro insertion activity has driven the development of cutting-edge sequencing technologies. Recently, a new technology combining CRISPR with TEs was reported, which provides a novel targeted insertion system to both academia and industry. We suggest that interrogating biological processes that generally depend on the actions of TEs with TEs-derived genetic tools is a very efficient strategy. For example, excessive activation of TEs is an essential factor in the occurrence of cancer in humans. As potent mutagens, TEs have also been used to unravel the key regulatory elements and mechanisms of carcinogenesis. Through this review, we aim to effectively combine the traditional views of TEs with recent research progress, systematically link the mechanistic discoveries of TEs with the technological developments of TE-based tools, and provide a comprehensive approach and understanding for researchers in different fields., 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 Han, Perkins, Novaes, Xu and Chang.)

The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineer endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Context: Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved., Objective: To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis., Methods: We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA., Results: The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test., Conclusion: The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Incidental durotomies are frequent complications of spine surgery associated with cerebrospinal fluid (CSF) leak-related symptoms. Management typically involves prolonged bed rest to reduce CSF pressure at the durotomy site. However, early ambulation may be a safer, effective alternative. PubMed, Web of Science, Embase, Cochrane, and Scopus were systematically searched for studies comparing early ambulation (bed rest ≤ 24 h) with prolonged bed rest (> 24 h) for patients with incidental durotomies in spine surgeries. The outcomes of interest were CSF leak, hypotensive headache, additional surgical repair, pseudomeningocele, and pulmonary complications. Systematic reviews and meta-analysis were performed following the Cochrane Handbook for Systematic Reviews of Interventions. We included a total of 704 patients from 6 studies. There was a significant reduction in the incidence of pulmonary complications (RR 0.23; 95% CI 0.08-0.67; p = 0.007) in the early mobilization group. The incidence of CSF leak (RR 1.34; 95% CI 0.83-2.14; p = 0.23), hypotensive headache (RR 0.72; 95% CI 0.27-1.90; p = 0.50), additional repair surgery (RR 1.29; 95% CI 0.76-2.2; p = 0.35), and pseudomeningocele (RR 1.29; 95% CI 0.20-8.48; p = 0.79) did not differ significantly. In patients with incidental durotomy following spinal surgery, early mobilization was associated with a lower incidence of pulmonary complications as compared with prolonged bed rest. There was no significant difference between groups in terms of CSF leak, need for additional repair, pseudomeningocele, and hypotensive headache., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the beliefs, attitudes and feelings about work of healthcare professionals (HCPs) and teachers living in the Canary Islands (Spain) during the COVID-19 pandemic., Methods: The study had two parts. In Part 1, the Delphi technique was used to adapt a questionnaire. Part 2 was a cross-sectional, comparative study, performed from August 31st to October 25th, 2021 using the questionnaire online distributed to samples of HCPs and teachers. The questionnaire had three dimensions each separated into three sections (i.e., beliefs [coping ability, prevention and organisation]; attitudes [risks, commitments, and obligations]; feelings about work [burnout, support and work satisfaction])., Results: In total 1423 questionnaires were available for analysis, 640 from teaching staff and 783 from HCPs. Significant differences were found in eight of the nine sections. HCPs had a more positive attitude towards work compared with teachers, but had more negative beliefs and feelings about work. In addition, by comparison with teachers, HCPs were more committed to their work, more predisposed to take risks and fulfill their obligations, even though our sample of teachers felt more supported and satisfied at work., Conclusions: Our results show that the pandemic caused a greater negative impact on job satisfaction of HCPs compared with teachers because they felt less supported by their superiors, which had a greater impact on their psychological health., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Introduction: Several observational studies have evaluated the effects of pre-operative steroids (STER) for transsphenoidal pituitary removal in patients with an intact hypothalamus-pituitary-adrenal axis. However, a consensus built upon randomized studies has not been previously performed., Purpose: To comprehensively evaluate the clinical effects of patients receiving STER when compared to those not receiving steroids (NOSTER) in transsphenoidal pituitary resection, a meta-analysis of randomized clinical trials (RCT) was conducted., Methods: A systematic review of the literature of RCTs comparing STER and NOSTER was performed in accordance with the PRISMA guidelines. Databases, including PUBMED, Cochrane Library, Web of Science, and Embase were queried. The primary outcomes were adrenal insufficiency (AI) and diabetes insipidus (DI) post-operatively., Results: A total of 4 final studies were included, in which 530 total patients were analyzed. The meta-analysis suggested that there was no significant difference between STER and NOSTER groups post-operatively related to transient AI (RR= 0.83, 95% CI [0.51-1.35], p = 0.45; I² = 52%), permanent AI (RR= 0.97, 95% CI [0.41-2.31], p = 0.95; I² = 0%), and permanent DI (RR= 0.62, 95% CI [0.16-2.33], p = 0.48; I² = 0%). Nevertheless, STER group had significantly lower rates of transient DI (RR= 0.60, 95% CI [0.38-0.95], p = 0.03; I² = 5%), and post-op hyponatremia (RR = 0.49, 95% CI [0.28-0.87], p = 0.02; I² = 0%)., Conclusion: This study demonstrates evidence from RCTs that patients receiving pre-operative STER are both safe and effective pre-operatively for resection of pituitary adenomas with an intact hypothalamus-pituitary-adrenal axis., Competing Interests: Declaration of Competing Interest Authors declare none., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In recent years, unmanned aerial vehicles (UAVs) have been increasingly used to monitor and assess air quality. The interest in the application of UAVs in monitoring air pollutants and greenhouse gases is evidenced by the recent emergence of sensors with the most diverse specifications designed for UAVs or even UAVs designed with integrated sensors. The objective of this study was to conduct a comprehensive review based on bibliometrics to identify dynamics and possible trends in scientific production on UAV-based sensors to monitor air quality. A bibliometric analysis was carried out in the VOSViewer software (version 1.6.17) from the Scopus and Web of Science reference databases in the period between 2012 and 2022. The main countries, journals, scientific organizations, researchers and co-citation networks with greater relevance for the study area were highlighted. The literature, in general, has grown rapidly and has attracted enormous attention in the last 5 years, as indicated by the increase in articles after 2017. It was possible to notice the rapid development of sensors, resulting in smaller and lighter devices, with greater sensitivity and capacity for remote work. Overall, this analysis summarizes the evolution of UAV-based sensors and their applications, providing valuable information to researchers and developers of UAV-based sensors to monitor air pollutants.

Routine use of antibiotics for dental implant installation is widely applied in dental practice to prevent postoperative infection and implant loss. However, the effectiveness and necessity of such protocols have not been consensual in the literature. This study aimed to evaluate the effect of antibiotic prophylaxis on survival of dental implants placed in clinically healthy patients by unexperienced operators. A double-blind, randomized, placebo-controlled trial was conducted. Ninety patients who received between 2 and 4 dental implants by unexperienced operators were enrolled in this study. Patients were randomly allocated in 2 groups. For the antibiotic group (n = 47), patients received 1 g of preoperative amoxicillin; in the placebo group (n = 43), patients received preoperative placebo administration. Each patient was evaluated preoperatively, 2 days, and 7 days postoperatively. Factors evaluated were mouth opening amplitude, assessment of referred pain through a visual analogue scale, and characteristic signs of infection (presence of fistula, ulceration in the surgical wound, tissue necrosis at the edges of the wound, dehiscence of the surgical flap, and presence of purulent exudate in the surgical wound). Implant survival was evaluated until 90 days postsurgical procedure. Results showed that there were no statistically significant differences in postoperative healing, swelling, and pain. However, more loss of dental implants was observed in the placebo group (14.9% vs 2.3%). Use of antibiotic prophylaxis reduced implant loss that was previously placed by unexperienced operators.

Background: The carotid artery stenting (CAS) has two common access sites: transradial access (TRA) and transfemoral access (TFA). However, there's no definitive answer to which one is superior., Objective: Compare TRA and TFA for the CAS., Methods: A systematic review of the literature of studies reporting both TRA and TFA results was conducted following the PRISMA guidelines. PubMed, Cochrane Library, Web of Science and Embase were queried., Results: The meta-analysis examined nine studies comprising 7513 patients who underwent CAS. Of these, 6750 patients had TFA (90%), while 763 had TRA (10%). There was no significant difference in procedure success rates between TRA and TFA, with a risk ratio (RR) of 0.99 (6/9; 95% CI 0.98 to 1.00; I² = 9%, fixed effects). However, cross-over to TFA was more frequent in TRA (odds ratio (OR) 10.37 (6/9; 95% CI 5.18 to 20.77; I² = 17%, fixed effects)). There were no significant differences in terms of major access complications (RR = 0.88 (7/9; 95% CI: 0.29 to 2.63; I² = 0, fixed effects)), total access complications (RR = 1.10 (6/9; 95% CI: 0.56 to 2.15; I² = 7%, fixed effects)), and mean difference in length of stay (Mean difference of -0.08 (3/9; 95% CI -0.18 to 0.02; I² = 0%, fixed effects))., Conclusion: There were no significant differences between TFA and TRA in terms of procedure success rates, time, complications, and length of stay, although cross-over to TFA was more common in TRA cases.

Context: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula., Objective: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs., Methods: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint., Results: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin., Conclusion: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The relationship between serotonin dysfunction and schizophrenia commenced with the discovery of the effects of lysergic acid diethylamide (LSD) that has high affinity for 5-HT 2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperactivity. Using prepulse inhibition (PPI) of the acoustic startle, which is impaired in schizophrenia,we aimed to investigate:i) the existence of a direct and potentially inhibitory neural pathway between the inferior colliculus (IC) and the pedunculopontine tegmental nucleus (PPTg) involved in the mediation of PPI responses by a neural tract tracing procedure;ii) if the microinjection of the 5-HT 2A receptors agonist DOI in IC would activate neurons in this structure and in the PPTg by a c-Fos protein immunohistochemistry study;iii) whether the deficits in PPI responses, observed after the administration of DOI in the IC, could be prevented by the concomitant microinjection of the GABA A receptor antagonist bicuculline in the PPTg.Male Wistar rats were used in this study. An IC-PPTg reciprocated neuronal pathway was identified by neurotracing. The number of c-Fos labelled cells was lower in the DOI group in IC and PPTg, suggesting that this decrease could be due to the high levels of GABA in both structures. The concomitant microinjections of bicuculline in PPTg and DOI in IC prevented the PPI deficit observed after the IC microinjection of DOI. Our findings suggest that IC 5-HT 2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures., Competing Interests: Declaration of Competing Interest All authors have seen and agree with the contents of the manuscript and there is no financial interest or personal relationships with other people or organizations that could inappropriately influence their work. There is not a conflict of interest with respect to the work presented herein., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To analyze the transitions experienced by mothers and children/adolescents with sickle cell disease after the emergence of the COVID-19 pandemic., Method: A qualitative study involving 19 mothers of children and adolescents with sickle cell disease. Data were obtained through semi-structured interviews via WhatsApp, followed by Thematic Analysis and Descending Hierarchical Classification with the help of Interface de R pour les Analyses Multidimensionnelles de Texteset de Questionnaires and interpreted in the light of Afaf Meleis' Transition Theory., Results: Support from family members for displacement; mothers' adherence to the routine of daily stimuli and physical exercises favored healthy transitions; lack of remote health care; low socioeconomic resources; interruption of the physiotherapy service; and maternal overload favor unhealthy transitions., Final Considerations: Efforts/movements by mothers ensure the healthy transition of children/adolescents with sickle disease during the pandemic, while supporting their unhealthy transition.

Background: Tuberous sclerosis (TS) is a multisystem genetic disease in which epilepsy is a frequent manifestation and is often difficult to control. Everolimus is a drug with proven efficacy in the treatment of other conditions related to TS, and some evidence suggests that its use benefits the treatment of refractory epilepsy in these patients., Objective: To evaluate the efficacy of everolimus in controlling refractory epilepsy in children with TS., Methods: A literature review was conducted in the Pubmed, BVS, and Medline databases, using the descriptors Tuberous sclerosis , Children , Epilepsy , and Everolimus . Original clinical trials and prospective studies published in Portuguese or English in the last decade that evaluated the use of everolimus as an adjuvant therapy in the control of refractory epilepsy in pediatric patients with TS were included., Results: Our search screened 246 articles from electronic databases, 6 of which were chosen for review. Despite the methodological variations between the studies, most patients benefited from the use of everolimus to control refractory epilepsy, with response rates ranging from 28.6 to 100%. Adverse effects were present in all studies leading to dropouts of some patients; however, the majority were of low severity., Conclusion: The selected studies suggest a beneficial effect of everolimus in the treatment of refractory epilepsy in children with TS, despite the adverse effects observed. Further studies involving a larger sample in double-blind controlled clinical trials should be performed to provide more information and statistical credibility., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Neonatal diabetes mellitus (NDM) is defined as the occurrence of severe hyperglycemia in infants under 6 months old and may be permanent (PNDM) or transient (TNDM). When diabetes is diagnosed at 6-12 months of age (early onset diabetes [EOD]), the etiology may be monogenic; however, most cases consist of type 1 diabetes mellitus (T1DM). Molecular diagnosis was determined in a cohort of 35 unrelated Brazilian patients with NDM or EOD based on targeted next-generation sequencing panel and/or chromosome 6q24 abnormalities. The impact of genetic testing on treatment and follow-up was evaluated. Overall, 24 patients had NDM: with 18 (75.0%) having PNDM, 5 TNDM (20.8%) and 1 case in which this information was unknown. Eleven patients had EOD. Genetic testing was positive in 20/24 patients with NDM (83.3%) and in 18.2% of cases of EOD. The commonest causes were ATP-sensitive potassium (KATP) channel genes, and GCK and IPEX mutations (37.1%, 11.4% and 5.7%, respectively). Patients with PNDM due to KCNJ11 and ABCC8 mutations transitioned successfully to sulfonylureas in almost 60% of cases, reinforcing the benefit of performing genetic testing in NDM as early as possible. This report refers to the largest series of cases of NDM (TNDM and PNDM) and EOD in Brazil in which patients were submitted to molecular investigation and in which the clinical impact of genetic diagnosis was also evaluated., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In most animals, pain can compromise physiological functions and delay healing so, rapid detection of pain through behavior and inflammatory reaction with biomarkers are necessary. This study aimed to evaluate pain, physiological variations and Acute Phase Proteins (APP) in donkeys undergoing orchiectomy technique by inguinal access. For this research, 15 male northeastern donkeys kept in extensive management were selected, with a mean age of 4.5±3.1 years. All animals had the same anesthetic protocol, using dissociative anesthesia and local block with lidocaine, followed by orchiectomy by inguinal access. Due to their predisposition to complications, the inguinal technique is the most indicated to minimize complications and excessive inflammation in donkeys' orchiectomy, the donkeys were evaluated regarding behavioral assessment of pain, hematological parameters, APP and the surgical wound, during 0 hour, 24 hours, 48 hours and 72 hours. As for the physiological parameters and APP, no significant differences were observed between times, due to the use of nonsteroidal antiinflammatory drugs. In the macroscopic evaluation of the surgical wound, it was observed that there were no significant differences between the times, with animals presenting mean scores of 1.8±0.414, in 48 hours 1.6 ± 0.507, and in 72 hours 1.6 ± 0.507. Most animals had mild to moderate edema in the scrotum and foreskin regions. As for pain assessment, the average scores were between 2 and 3, representing mild and moderate pain, not requiring intervention. However, further research is needed to elucidate the behavior of PFAs in the face of variables and the creation of new pain scales for animals raised in an extensive system., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases. Despite P. pachyrhizi's impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity., (© 2023. The Author(s).)

Studies investigated how stressful experiences modulate physiological and behavioral responses and the consequences of stress-induced corticosterone release in anxiety-like behavior. Adolescence is crucial to brain maturation, and several neurobiological changes in this period lead individuals to increased susceptibility or resilience to aversive situations. Despite the effects of stress in adults, information about adolescents' responses to acute stress is lacking. We aimed to understand how adolescence affects acute stress responses. Male adolescent rats (30 days old) were 2 h restrained, and anxiety-like behaviors were measured immediately or 10 days after stress in the elevated plus-maze (EPM) and the light-dark box (LDB) tests. To verify the importance of CORT modulation in stress-induced anxiety, another group of rats was treated, 30 min before restraint, with metyrapone to blunt the stress-induced CORT peak and tested immediately after stress. To show that stress effects on behavior were age-dependent, another set of rats was tested in two different periods - early adolescence (30 days old) and mid-adolescence (40 days old) and were treated or not with metyrapone before the stress session and tested immediately or ten days later in the LDB test. Only early adolescent male rats were resilient to delayed anxiety-like behavior in EPM and LDB tests. Metyrapone treatment increased the rats' exploration immediately and ten days after stress. These data suggest a specific age at which adolescent rats are resilient to the delayed effects of acute restraint stress and that the metyrapone treatment has long-term behavioral consequences., (Copyright © 2022. Published by Elsevier Ltd.)

Background: A maturity-onset diabetes of the young (MODY) calculator has been described and validated for use in European Caucasians. This study evaluated its performance in Brazilians diagnosed with diabetes mellitus (DM) before 35 years of age., Methods: The electronic records of 391 individuals were reviewed in 2020 at the diabetes clinic of a quaternary hospital in São Paulo were analyzed: 231 with type 1 DM (T1DM), 46 with type 2 (T2DM) and 114 with MODY. The MODY calculator was applied to the three groups. A receiver operating characteristic curve was calculated to obtain cut-off points for this population., Results: The principal differences between the MODY and the T1DM and T2DM groups were body mass index, a positive family history of diabetes and mean HbA1c level. Age at diagnosis in the MODY group was only significantly different compared to the T2DM group. Specificity and sensitivity were good for the cut-off points of 40%, 50% and 60%, with the accuracy of the model for any of these cut-off points being > 95%., Conclusion: The capacity of the calculator to identify Brazilian patients with MODY was good. Values ≥ 60% proved useful for selecting candidates for MODY genetic testing, with good sensitivity and specificity., (© 2023. The Author(s).)

Introduction:  The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties., Objective:  This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10 -1 , 1×10 -2 potency (VAD1D2)., Methods:  MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test., Results:  At the concentration of 10 μL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 μL/mL presented absolute percentages of initial apoptosis twice as high as at 10 μL/mL, which was similar to the control (untreated group)., Conclusion:  The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics., Competing Interests: None declared., (The Faculty of Homeopathy. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Knowledge on the neurobiological systems underlying psychiatric disorders has considerably evolved due to findings on basic research using animal models. Anxiety-like behaviors in rodents are widely explored in neuroethological apparatuses, such as the light-dark box (LDB) test through different protocols, which have been shown to influence the behavioral outcomes and probably the activation of the hypothalamic-pituitary-adrenal (HPA) axis., New Method: Adult male Wistar rats were submitted to LDB in different room illumination conditions (25/0, 65/0 and/or 330/0 lux), initial positioning in the LDB compartments and previous stressful experience in the Elevated Plus Maze (EPM) or restraint stress (RS). Rats' behavior (exploratory and risk assessment) was registered during a 15 min period, divided into blocks of 5 min RESULTS: Exploration of the lit compartment decreased in higher luminosity condition, as after positioning rats in the dark compartment or previous exposure to the EPM, while low luminosity increased exploration of the LDB. No differences were observed on serum corticosterone in all groups and experimental conditions., Comparison With Existing Methods: Light intensity and test duration influenced exploration of the LDB jeopardizing the anxiolytic/anxiogenic effects. Low light intensity increased exploration, while high intensity decreased it. These results suggest that 65/0 lux is a neutral condition to investigate possible anxiolytic/anxiogenic effects of drugs and/or exposure to previous aversive stimuli as the EPM., Conclusions: Different factors impact on exploratory and risk assessment behaviors which may be related to safety maximization behavior. Unraveling how different factors affect behavior may be a crucial step towards understanding its expression and the contributions on advances in the physiopathology 1 and treatment of psychiatric disorders., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microorganisms produce costly cooperative goods whose benefit is partially shared with nonproducers, called 'mixed' goods. The Black Queen Hypothesis predicts that partial privatization has two major evolutionary implications. First, to favor strains producing several types of mixed goods over nonproducing strains. Second, to favor the maintenance of cooperative traits through different strains instead of having all cooperative traits present in a single strain (metabolic specialization). Despite the importance of quorum sensing regulation of mixed goods, it is unclear how partial privatization affects quorum sensing evolution. Here, we studied the influence of partial privatization on the evolution of quorum sensing. We developed a mathematical population genetics model of an unstructured microbial population considering four strains that differ in their ability to produce an autoinducer (quorum sensing signaling molecule) and a mixed good. Our model assumes that the production of the autoinducers and the mixed goods is constitutive and/or depends on quorum sensing. Our results suggest that, unless autoinducers are costless, partial privatization cannot favor quorum sensing. This result occurs because with costly autoinducers: (1) a strain that produces both autoinducer and goods (fully producing strain) cannot persist in the population; (2) the strain only producing the autoinducer and the strain producing mixed goods in response to the autoinducers cannot coexist, i.e., metabolic specialization cannot be favored. Together, partial privatization might have been crucial to favor a primordial form of quorum sensing-where autoinducers were thought to be a metabolic byproduct (costless)-but not the transition to nowadays costly autoinducers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Souza 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.)

Eating behavior is regulated by central and peripheral signals, which interact to modulate the response to nutrient intake. Central control is mediated by the hypothalamus through neuropeptides that activate the orexigenic and anorexigenic pathways. Energy homeostasis depends on the efficiency of these regulatory mechanisms. This neuroendocrine regulation of hunger and appetite can be modulated by nutritional sensors such as adenosine monophosphate-activated protein kinase (AMPK). Thus, this systematic review discusses the literature on correlations between AMPK and hypothalamic neuropeptides regarding control of eating behavior. Lilacs, PubMed/Medline, ScienceDirect, and Web of Science were searched for articles published from 2009 to 2021 containing combinations of the following descriptors: "eating behavior," "hypothalamus," "neuropeptide," and "AMPK." Of the 1330 articles found initially, 27 were selected after application of the inclusion and exclusion criteria. Of the selected articles, 15 reported decreased AMPK activity, due to interventions using angiotensin II infusion, fructose, glucose, cholecystokinin, leptin, or lipopolysaccharide (LPS) injection; dietary control through a low-protein diet or a high-fat diet (60 % fat); induction of hyperthyroidism; or injection of AMPK inhibitors. Seven studies showed a decrease in neuropeptide Y (NPY) through CV4 AICAR administration; fructose, glucose, leptin, or angiotensin II injections; or infusion of LPS from Escherichia coli and liver kinase B1 (LKB1) overexpression. Eleven studies reported a decrease in food consumption due to a decrease in AMPK activity and/or hypothalamic neuropeptides such as NPY. The results indicate that there is a relationship between AMPK and the control of eating behavior: a decrease in AMPK activity due to a dietary or non-dietary stimulus is associated with a consequent decrease in food intake. Furthermore, AMPK activity can be modulated by glucose, thyroid hormones, estradiol, leptin, and ghrelin., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Labor is a physiological process triggered by mechanical and hormonal events that promote uterine contractions to expel the fetus., Objective: This study aimed to evaluate the effectiveness of a nonpharmacologic childbirth care protocol in women in the active phase of labor in improving obstetrical and perinatal outcomes., Study Design: This was a randomized trial with concealed allocation, assessor blinding, and intention-to-treat analysis. A total of 80 low-risk primigravida women at the end of pregnancy admitted at the beginning of the active phase of labor participated in the study. The participants were divided into an experimental group (n=40) and a control group (n=40). Women in the experimental group received 4 interventions: ambulation at 4 to 6 cm of cervical dilation, alternation of maternal postures, transcutaneous electrical nerve stimulation at 6 to 7 cm, and a warm shower bath at >7 cm. The control group received only routine obstetrical care during labor. The parturient could request pharmacologic analgesia at any time during the study. The main outcome measures were the duration of the active phase of the first stage of labor, the duration of the expulsive phase of labor, and the prevalence of labor dystocia as assessed by the partograph. The researchers collected other maternal and neonatal data from official birth records., Results: The parturients who received the nonpharmacologic protocol had a shorter active phase of the first stage of labor (444 minutes in the control group and 373 minutes in the experimental group; P =.02), presented rupture of membranes later in labor (7 cm in the control group and 8 cm in the experimental group; P <.01), requested pharmacologic analgesia with more significant cervical dilation (5 cm in the control group and 8 cm in the experimental group; P <.01), requested fewer additional doses of analgesics, and had lower labor dystocia rates than the patients in the control group. In addition, there was no difference in other maternal and perinatal variables between the control group and the experimental group., Conclusion: The implementation of a sequential nonpharmacologic protocol composed of ambulation, transcutaneous electrical nerve stimulation with change of upright positions, and warm shower bath has the potential to reduce labor pain, as reflected in decreased and delayed use of pharmacologic analgesia and reduced duration of the active phase of labor and dystocia rates. Maternity hospitals should provide this protocol, and women should be encouraged to request this childbirth care protocol., (© 2022 The Authors.)

Background and Aim: Cortisol binds to mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) found in the hippocampus. The balanced expression of these receptors is essential to neuronal survival as MR and GR activations have antiapoptotic and proapoptotic effects, respectively. Given the aging changes in dogs' dentate gyrus (DG) and the possible involvement of cortisol receptors in this process, this study aimed to evaluate the expression of MR and GR and neuronal degeneration in this hippocampal region of aged dogs., Materials and Methods: This study included cadaveric histologic hippocampus sections from six dogs aged 10 years and older (AG group) and 12 young/adult dogs aged up to 8 years (YAd group). Nissl staining and immunohistochemistry were performed to identify cells and investigate MR and GR expression, respectively. Furthermore, fluorescent labeling (fluoro-Jade B) was used to detect degenerating neurons., Results: The AG group's polymorphic layer of the DG had a lower cell count (16%) and more degenerating neurons than the YAd group. In addition to these cellular changes, the AG group had lower MR immunoreactivity and MR-to-GR ratio. Furthermore, the lowest MR expression was associated with neuronal degeneration in the polymorphic layer of the DG of dogs., Conclusion: An imbalance in the MR-to-GR ratio was observed in the polymorphic layer of the DG of aged dogs, along with lower MR expression and a greater number of degenerating neurons. These findings have clinical implications for understanding the decline in hippocampal memory formation associated with cognitive changes in aged dogs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Szriber, et al.)

Introduction: University entrance is often associated with changes in quality of life, individuals' cognitive and physical behavior. The present study aimed to evaluate health-related quality of life (HRQoL), sleep quality and sleepiness index in dentistry students at a university in Southeast Brazil, in different semesters of their course., Materials and Methods: Samples were obtained from 55 students from the dentistry course at the Federal University of Alfenas (UNIFAL-MG). For collecting information, validated SF-36 questionnaires (Medical Outcomes Study 36-item Short-Form Health Survey), namely, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), were used as instruments in an educational environment. The relationship between the association of demographic factors and academic performance with SF-36, PSQI and ESS was assessed with an alpha of 0.05., Results: The worst HRQoL parameters reported by the participants were observed in the domains of body pain, vitality, general health perception, and limitations due to emotional and social aspects when associated with the investigated variables. Regarding the relative sleep quality index, differences in the PSQI domains were observed when related to demographic factors and academic performance. There was no significant difference in the sleepiness index of these students according to the mean values of the ESS domains., Conclusion: The SF-36, PSQI and ESS questionnaires indicated that it is a reliable instrument for measuring the impact of quality of life on dentistry students. In addition, dentistry students of UNIFAL-MG had poor indicators of quality of life associated with health and an inadequate index of quality of sleep., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The increased demand for cheese and the limited availability of calf rennet justifies the search for milk-clotting enzymes from alternative sources. Trypsin-like protease by Penicillium roqueforti was produced by solid-state fermentation using cocoa shell waste as substrate. The production of a crude enzyme extract that is rich in this enzyme was optimized using a Doehlert-type multivariate experimental design. The biochemical characterization showed that the enzyme has excellent activity and stability at alkaline pH (10-12) and an optimum temperature of 80°C, being stable at temperatures above 60°C. Enzymatic activity was maximized in the presence of Na + (192%), Co 2+ (187%), methanol (153%), ethanol (141%), and hexane (128%). Considering the biochemical characteristics obtained and the milk coagulation activity, trypsin-like protease can be applied in the food industry, such as in milk clotting and in the fabrication of cheeses., (© 2021 International Union of Biochemistry and Molecular Biology, Inc.)

This study investigated the effects of functional (FT) and combined (CT) training on memory T cells and functional fitness of postmenopausal women. 108 participants were randomly allocated to the control (CG), FT and CT groups. Functional fitness was assessed through physical tests similar to daily activities, such as dressing on and taking off a t-shirt (DTTS), 10-meter walking and countermovement jump. The CCR7 and CD45RA surface markers were used to characterize the memory T cells. Regarding the frequency of memory T cells, both training protocols reduced the percentage of CD4 + Terminally Differentiated Effector Memory T Cells Re-Expressing CD45RA (T EMRA ) (FT: -38.73 %, p = 0.0455; CT: -30.43 %, p = 0.0036) and CD8 + T EMRA cells (FT: -22.24 %, p < 0.0013; CT: -13.13 %, p = 0.0051). Also, both FT and CT increased the percentage of central memory (T CM ) CD4 + (FT: +55.22 %, p = 0.0104; CT: +68.03 %, p = 0.0167) and CD8 + (FT: +142.00 %, p < 0.0001; CT: +83.76 %, p = 0.0001) T cells. Furthermore, FT and CT increased the percentages of CD8 + effector memory T cells (T EM ) (FT: +63.58 %, p < 0.0001; CT: +14.12 %, p = 0.0041). Regarding functional fitness, both training protocols reduced the time required to perform the DTTS (FT: -19.71 %, p < 0.0001; CT: -14.69 %, p < 0.0001) and 10-m walk tests (FT: -13.05 %, p < 0.0001; CT: -12.83 %, p < 0.0001), in addition to improving jumping ability (FT: +29.97 %, p < 0.0001; CT: +20.00 %, p < 0.0001), both compared to the pre-test or to the CG. Therefore, both FT and CT seem to be equally effective alternatives for promoting the reduction of CD4 + and CD8 + T EMRA cells, increasing the frequency of T CM and T EM cells, and improving functional fitness of postmenopausal women., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)