Search

The objective was to analyze the longitudinal associations of physical activity (PA) and Sedentary behavior (SB) on bone health indicators (BHI) in healthy young adults. Articles were selected from five databases and 17 longitudinal studies were selected after meeting the inclusion and exclusion criteria. Among these, only one study assessed the association between childhood PA and adult BHI, the results showed no significant association between PA and BHI. Positive associations between adolescence and adulthood were observed between PA with bone mineral content and density and bone microarchitecture. In adulthood, the results were divergent; among the three studies located, two found a positive association. SB was negatively associated with bone mineral density and content from childhood to adulthood. However, from adolescence to adulthood, it was negatively associated with total tibia area but positively associated with trabecular thickness, cortical thickness, and cortical bone mineral. The evidence of the positive effect of PA and its intensities between adolescence and adulthood on BHI seems to be more consolidated, and it is still necessary to understand the role of intensities, volume of PA and SB in different periods of life with BHI in adulthood., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This research introduces a new way to create a composite material (PLA/EG) for 3D printing. It combines polylactic acid (PLA) with exfoliated graphite (EG) using a physical mixing method, followed by direct mixing in a single-screw extruder. Structural and vibrational analyses using X-ray diffraction and Fourier transform infrared spectroscopy confirmed the PLA/EG's formation (composite). The analysis also suggests physical adsorption as the primary interaction between the two materials. The exfoliated graphite acts as a barrier (thermal behavior), reducing heat transfer via TG. Electrochemical measurements reveal redox activity (cyclic voltammetry) with a specific capacitance of ~ 6 F g -1 , low solution resistance, and negligible charge transfer resistance, indicating ion movement through a Warburg diffusion process. Additionally, in terms of complex behavior (electrochemical impedance spectroscopy), the PLA/EG's actual capacitance C'(ω) displayed a value greater than 1000 μF cm -2 , highlighting the composite's effectiveness in storing charge. These results demonstrate that PLA/EG composites hold significant promise as electrodes in electronic devices. The methodology used in this study not only provides a practical way to create functional composites but also opens doors for new applications in electronics and energy storage.

Graphene nanoplatelets (UGZ-1004) are emerging as a promising biomaterial in regenerative medicine. This study comprehensively evaluates UGZ-1004, focusing on its physical properties, cytotoxicity, intracellular interactions, and, notably, its effects on mesenchymal stem cells (MSCs). UGZ-1004 was characterized by lateral dimensions and layer counts consistent with ISO standards and demonstrated a high carbon purity of 0.08%. Cytotoxicity assessments revealed that UGZ-1004 is non-toxic to various cell lines, including 3T3 fibroblasts, VERO kidney epithelial cells, BV-2 microglia, and MSCs, in accordance with ISO 10993-5:2020/2023 guidelines. The study focused on MSCs and revealed that UGZ-1004 supports their gene expression alterations related to self-renewal and proliferation. MSCs exposed to UGZ-1004 maintained their characteristic surface markers. Importantly, UGZ-1004 promoted significant upregulation of genes crucial for cell cycle regulation and DNA repair, such as CDK1, CDK2, and MDM2. This gene expression profile suggests that UGZ-1004 can enhance MSC self-renewal capabilities, ensuring robust cellular function and longevity. Moreover, UGZ-1004 exposure led to the downregulation of genes associated with tumor development, including CCND1 and TFDP1, mitigating potential tumorigenic risks. These findings underscore the potential of UGZ-1004 to not only bolster MSC proliferation but also enhance their self-renewal processes, which are critical for effective regenerative therapies. The study highlights the need for continued research into the long-term impacts of graphene nanoplatelets and their application in MSC-based regenerative medicine.

Background and Objectives: Updates in Alzheimer disease (AD) diagnostic guidelines by the National Institute on Aging-Alzheimer's Association (NIA-AA) and the International Working Group (IWG) over the past 11 years may affect clinical diagnoses. We assessed how these guidelines affect clinical AD diagnosis in a cohort of cognitively unimpaired (CU) and cognitively impaired (CI) individuals., Methods: We applied clinical and biomarker data in algorithms to classify individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort according to the following diagnostic guidelines for AD: 2011 NIA-AA, 2016 IWG-2, 2018 NIA-AA, and 2021 IWG-3, assigning the following generic diagnostic labels: (1) not AD (nAD), (2) increased risk of developing AD (irAD), and (3) AD. Diagnostic labels were compared according to their frequency, convergence across guidelines, biomarker profiles, and prognostic value. We also evaluated the diagnostic discordance among the criteria., Results: A total of 1,195 individuals (mean age 73.2 ± 7.2 years, mean education 16.1 ± 2.7, 44.0% female) presented different repartitions of diagnostic labels according to the 2011 NIA-AA (nAD = 37.8%, irAD = 23.0%, AD = 39.2%), 2016 IWG-2 (nAD = 37.7%, irAD = 28.7%, AD = 33.6%), 2018 NIA-AA (nAD = 40.7%, irAD = 9.3%, AD = 50.0%), and 2021 IWG-3 (nAD = 51.2%, irAD = 8.4%, AD = 48.3%) frameworks. Discordant diagnoses across all guidelines were found in 512 participants (42.8%) (138 [91.4%] occurring in only β-amyloid [CU 65.4%, CI 34.6%] and 191 [78.6%] in only tau-positive [CU 71.7%, CI 28.3%] individuals). Differences in predicting cognitive impairment between nAD and irAD groups were observed with the 2011 NIA-AA (hazard ratio [HR] 2.21, 95% CI 1.34-3.65, p = 0.002), 2016 IWG-2 (HR 2.81, 95% CI 1.59-4.96, p < 0.000), and 2021 IWG-3 (HR 3.61, 95% CI 2.09-6.23, p < 0.000), but not with 2018 NIA-AA (HR 1.69, 95% CI 0.87-3.28, p = 0.115)., Discussion: Over 42% of the studied population presented discordant diagnoses when using the different examined AD criteria, mostly in individuals with a single positive biomarker. Except for 2018 NIA-AA, all guidelines identified asymptomatic individuals at risk of cognitive impairment. Our findings highlight important differences between the guidelines, emphasizing the necessity for updated criteria with enhanced staging metrics, considering clinical, research, therapeutic, and trial design aspects.

Background: Health-related physical fitness (HRPF) attributes are considered important markers beneficial to various health outcomes. However, the literature is divergent regarding HRPF and bone health in adulthood, especially due to the end of the second and beginning of the third decades of life when the peak bone mass period occurs., Objective: To analyze which HRPF variables are areal bone mineral density (aBMD) predictors in adult males and females., Methods: This study evaluated 137 healthy young adults aged 18-25 years (50% males). Dual-energy X-ray absorptiometry (DXA) was used to estimate fat mass and lean mass and aBMD, hand grip strength test, sit-ups test, flexibility test, lower limb muscle strength and 20-meter run were used to evaluate physical fitness. Multiple linear regression using the backward method was used to analyze bone mineral density predictors by sex., Results: HRPF indicators showed correlations from R = 0.28 in the right femoral neck aBMD to R = 0.61 in the upper limbs aBMD in males; in females, correlations from R = 0.27 in total body aBMD to R = 0.68 in the lower limbs aBMD were found. In males, body mass and HRPF indicators were aBMD predictors with HRPF indicators explaining variance from R²=0.214 in the lumbar spine to R²=0.497 in the upper limbs, and in females, with the exception of the lumbar spine, variance from R²=0.237 in the right femoral neck aBMD to R²=0.442 in the lower limbs aBMD was found., Conclusion: Health-related physical fitness components were able to predict aBMD in different anatomical regions in young adults, especially muscle strength and cardiorespiratory fitness indicators for males, while only lean mass and fat mass for females., (© 2024. The Author(s).)

Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.

Regardless of the containment of the SARS-CoV-2 pandemic, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provides anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention strategies. We conducted a cohort study comprising 43 elderly COVID-19 patients admitted to São Lucas Hospital, PUCRS, Brazil. Anthropometric measurements, including calf circumference (CC) and abdominal circumference (AC), were assessed alongside molecular analyses of peripheral blood samples obtained within 48 h of hospital admission. Sociodemographic data were collected from electronic medical records for comprehensive analysis. Our findings revealed a possible relationship between overweight status, increased abdominal adiposity, and prolonged hospitalization duration, alongside heightened disease severity. We also found no significant correlations between BMI, vitamin D levels, and clinical outcomes. Elevated oxygen requirements were observed in both normal and overweight individuals, with the latter necessitating prolonged oxygen therapy. Molecular analyses revealed changes in the inflammatory profile regarding the outcome of the patients. Our study highlights the critical importance of both anthropometric and molecular markers in predicting disease severity and clinical outcomes in elderly individuals with COVID-19.

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps to identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. In addition, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, the analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

Radiotherapy (RT) is the established noninvasive treatment for glioblastoma (GBM), a highly aggressive malignancy. However, its effectiveness in improving patient survival remains limited due to the radioresistant nature of GBM. Metal-based nanostructures have emerged as promising strategies to enhance RT efficacy. Among them, titanate nanotubes (TNTs) have gained significant attention due to their biocompatibility and cost-effectiveness. This study aimed to synthesize zinc-modified TNTs (ZnTNT) from sodium TNTs (NaTNT), in addition to characterizing the formed nanostructures and evaluating their radiosensitization effects in GBM cells (U87 and U251). Hydrothermal synthesis was employed to fabricate the TNTs, which were characterized using various techniques, including transmission electron microscopy (TEM), energy-dispersive spectroscopy, scanning-transmission mode, Fourier-transform infrared spectroscopy, ICP-MS (inductively coupled plasma mass spectrometry), X-ray photoelectron spectroscopy, and zeta potential analysis. Cytotoxicity was evaluated in healthy (Vero) and GBM (U87 and U251) cells by the MTT assay, while the internalization of TNTs was observed through TEM imaging and ICP-MS. The radiosensitivity of ZnTNT and NaTNT combined with 5 Gy was evaluated using clonogenic assays. Monte Carlo simulations using the MCNP6.2 code were performed to determine the deposited dose in the culture medium for RT scenarios involving TNT clusters and cells. The results demonstrated differences in the dose deposition values between the scenarios with and without TNTs. The study revealed that ZnTNT interfered with clonogenic integrity, suggesting its potential as a powerful tool for GBM treatment., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Carbohydrate counting is one of the dietary strategies used for the management of type 1 diabetes (T1DM), and counting proteins and fats allows individuals to achieve better glycemic and metabolic control, reducing glycemic variability and long-term complications. The aim of this paper is to analyze the factors associated with adherence to the protein- and fat-counting strategy in adults with T1DM. This cross-sectional study was conducted from November 2021 to June 2022 through an online questionnaire. We applied Pearson's Chi-square test with adjusted residual analysis and a binomial logistic regression test using SPSS software, version 24.0, considering p < 0.05 as indicative of statistical significance. There was an association between performing protein and lipid counting and having a higher education level, income exceeding three minimum wages, and having adequate glycated hemoglobin. Performing protein and lipid counting increased the chances of having adequate HbA1c by 4.3 times. Protein and lipid counting was a predictor of having adequate HbA1c. The results suggest that considering the practice of counting proteins and fats is important as a strategy to optimize glycemic control.

Muscle weakness has been associated to insulin resistance and metabolic syndrome in the general population. However, it is still unclear whether this association is maintained in older adults. This study investigated correlations between low handgrip strength (HGS) and metabolic syndrome, or some of its components, in older adults through a systematic review of the literature. Searches were conducted in the Virtual Health Library Regional Portal, Scopus, Cochrane, Embase, MEDLINE/ PubMed, SciELO, and Web of Science databases for relevant studiesinvestigating muscle weakness (measured by hand dynamometer) and metabolic syndrome or its components in older adult populations, published up to September 2023. From the 2050 references initially identified, 20 studies, comprising a total of 31,264 older adults of both genders, completely met the inclusion/exclusion criteria. Eighteen studies showed that lower HGS was associated with metabolic syndrome or some of its risk factors, such as abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, or high blood pressure. Two studies found that older men with high blood pressure had increased HGS. Most studies included in this systematic review revealed a significant correlation between reduced HGS and metabolic syndrome or some of its components, especially abdominal obesity and insulin resistance. We conclude that below-average HGS can be associated with metabolic syndrome in older adults.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

Several studies highlighted the complexity of mixing pesticides present in Amazonian aquatic environments today. There is evidence that indicates that ongoing climate change can alter the pattern of pesticide use, increasing the concentration and frequency of pesticide applications. It is known that the combination of thermal and chemical stress can induce interactive effects in aquatic biota, which accentuates cell and molecular damage. However, considering that the effects of climate change go beyond the increase in temperature the objective of this study was to evaluate the effect of climate change scenarios proposed by 6 th IPCC report and a mixture of pesticides on the tambaqui (Colossoma macropomum). The hypothesis of this study is that the negative effects will be accentuated by the combination of an extreme climate changes scenario and a mixture of pesticides. To test the hypothesis, juvenile tambaqui were exposed to a combination of four pesticides (chlorpyrifos, malathion, carbendazim and atrazine) in two scenarios, one that simulates current environmental conditions and another that predicted the environmental scenario for the year 2100. Fish were subjected to the experimental conditions for 96 h. At the end of the experiment, samples of blood, gills, liver, brain, and muscle were obtained for hematological, genotoxic, biochemical, and histopathological analyses. The results demonstrate that environmentally realistic concentrations of pesticides, when mixed, can alter the biochemical responses of tambaqui. The extreme scenario promotes hematological adjustments, but impairs branchial antioxidant enzymes. There is an interaction between the mixture of pesticides and the extreme scenario, accentuating liver tissue damage, which demonstrates that even increased activity of antioxidant and biotransformation enzymes were not sufficient to prevent liver damage., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Increases in temperature can affect the reproduction of fish by decreasing the quality of gametes for fertilization. Therefore, this study aimed to evaluate the in vivo effect of temperature on the production and sperm quality of Colossoma macropomum, which is an economically relevant species for Brazil, and other countries. Broodstock were exposed for 10 days at temperatures of 29 °C (n = 4) and 35 °C (n = 4). After exposure, semen was collected and sperm quality was evaluated for kinetic, biochemical, morphological parameters, membrane integrity, and oxygen consumption. The sperm quality of males of specimens of C. macropomum exposed in vivo to the higher temperature was compromised and showed a difference in all the analyses (P < 0.05). Sperm showed decreased motility (51.9 ± 11.6 s) compared to the control (61.3 ± 5.5 s); curvilinear (CLV), straight line (SLV), and average path (APV) velocities decreased, and straightness (STR) and beat cross frequency (BCF) increased; oxygen consumption decreased (32.8 ± 3.4 pmol. (s.ml) -1 , picomol per second per ml) compared to the control (46.6 ± 3.5 pmol. (s.ml) -1 ); and the activity of catalase (CAT) and glutathione S-transferase (GST) enzymes increased and decreased, respectively, in sperm from fish exposed to high temperatures. Furthermore, an increase in non-viable sperm with damaged membranes and sperm with altered morphology was observed. The observed alterations indicate that C. macropomum confined in environments with high temperatures possibly produces more sperm that are unviable for the fertilization process., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM., Competing Interests: JCDC is a researcher of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Federal District, Brazil), which provided funding for the present study. The other authors declare that they have no competing interests., (Copyright: © 2024 Marinowic et al.)

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n 1  = 30) and their age-paired controls (YC, n 1  = 30), and compare it with octogenarian elder controls (EC, n 1  = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD., (© 2023 Wiley Periodicals LLC.)

Prostate cancer (PC) is the most diagnosed tumor in males and ranks as the second leading cause of male mortality in the western world. The CD39 and CD73 enzymes play a crucial role in cancer regulation by degrading nucleotides and forming nucleosides. This study aimed to investigate the expression of the CD39 and CD73 enzymes as potential therapeutic targets for PC. The initial part of this study retrospectively analyzed tissue samples from 23 PC patients. Using the TissueFAXS TM cytometry platform, we found significantly higher levels of CD39-labeling its intensity compared to CD73. Additionally, we observed a correlation between the Gleason score and the intensity of CD39 expression. In the prospective arm, blood samples were collected from 25 patients at the time of diagnosis and after six months of treatment to determine the expression of CD39 and CD73 in the serum extracellular vesicles (EVs) and to analyze nucleotide hydrolysis. Notably, the expression of CD39 in the EVs was significantly increased compared to the CD73 and/or combined CD39/CD73 expression levels at initial collection. Furthermore, our results demonstrated positive correlations between ADP hydrolysis and the transurethral resection and Gleason score. Understanding the role of ectonucleotidases is crucial for identifying new biomarkers in PC.

Background: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/β-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/β-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II., Methods: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway., Results: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material., Conclusion: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The Carbohydrate Counting (CC) is directly associated with achieving glycemic control by people with Type 1 Diabetes Mellitus (T1DM). Therefore, this study aims to analyze characteristics of the CC practice associated with the adequacy of glycated hemoglobin (HbA1c) in adults with T1DM in Brazil., Methods: The study was cross-sectional, carried out using an online form with questions about knowledge of CC, clinical, anthropometric, sociodemographic data, follow-up with health professionals and understanding of the concepts of CC. Pearson's chi-square test and binomial logistic regression analysis (p<0.05) were applied., Results: 173 adults participated, of which 57.2% had increased HbA1c (≥7%). Having the diabetes duration <10 years (p=0.006), performing the CC at lunch (p=0.040) and dinner (p=0.018), using specific applications to perform the CC (p=0.001), having learned to perform CC with a nutritionist (p=0.037) and knowing how to correctly define the concepts of food bolus (p=0.001), correction bolus (p<0.001) and insulin/carbohydrate ratio (p<0.001) was associated with having adequate HbA1c (<7%). Participants who were undergoing CC practice were 3.273 times more likely to have adequate HbA1c and participants with diabetes duration <10 years were 2.686 times more likely to have adequate HbA1c., Conclusion: It was concluded that variables transversal to CC favor adequate HbA1c values in adults with T1DM and that practicing CC and having a diabetes duration of less than 10 years are predictive factors of having adequate HbA1c., 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 Uliana, Camara, Paracampo, da Costa and Gomes.)

99m Tc-EDDA/HYNIC-TOC is an easily available and cheaper radionuclide that could be used for somatostatin-receptor-based imaging of neuroendocrine tumours (NETs). We aimed to evaluate the diagnostic performance of 99m Tc-EDDA/HYNIC-TOC compared to 111 In-DTPA-octreotide in patients (pts) with NETs. We performed a prospective diagnostic study including pts with biopsy-confirmed NET and at least one visible lesion at conventional imaging. Two independent nuclear medicine physicians evaluated pts who underwent 99m Tc and 111 In scans and images. The primary outcome was comparative diagnostic accuracy of 99m Tc and 111 In. Secondary outcomes include safety. Nine pts were included and performed 14 paired scans. Overall, 126 lesions were identified. 99m Tc demonstrated superior sensitivity both when all images were analysed (93.7, 95% CI 88.1% - 96.8% versus 74.8%, 95% CI 66.6 - 81.6%, p < 0.001) and when liver-specific images were analysed (97.8%, 95% CI 92.7% - 99.5% versus 85.1%, 95% CI 76.6% - 91.0%, p < 0.001). 99m Tc was also associated with a lower negative likelihood ratio (LR) (0.002, 95% CI 0.009 - 0.1 versus 0.19, 95% CI 0.12 - 0.42, p = 0.009) when evaluating hepatic lesions. Adverse events happened in 3 pts after 111 In and in 2 pts after 99m Tc, all grade 1. The 99m Tc demonstrated a higher sensitivity overall and a better negative LR in liver-specific images compared to 111 In in pts with NETs. Our findings suggest that 99m Tc is an alternative to 111 In and is especially useful in ruling out liver metastases. NCT02691078., Competing Interests: Dr Moriguchi-Jeckel and Dr Werutsky report grants from Financiadora de Estudos e Projetos (FINEP) for the conduct of the study. Drs R. Madke, Viana, Nabinger, and Fernandes report employment relationships with the RPH Group. Dr. Werutsky reports personal fees from AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Genentech/Roche, GSK, Lilly, MSD, Novartis, Pfizer, Sanofi, and Seattle Genetics outside the submitted work. The other authors declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Objective: So far, no original studies explored non-randomized, standardized protocols for COVID-19 associated olfactory dysfunction. The main objective was to determine the efficacy of a new protocol for post-COVID olfactopathy while assessing the benefit of adding adjuvant therapies to olfactory training., Methods: Patients suffering from long-lasting post-COVID-19 olfactory dysfunction were evaluated. A non-randomized protocol based on individual nasal endoscopy findings and patient's preferences was applied. Patients were assigned for olfactory training alone or olfactory training + adjuvant therapy. Participants performed olfactory objective and subjective evaluations at first consultation and 3 months after treatment, and results were compared., Results: A total of 47 patients were enrolled. All groups showed significant improvement in olfactory thresholds at 3-month follow-up suggesting protocol effectiveness (olfactory training group alone showed a mean threshold difference of 2.9, P  < .001; Olfactory training + Topical Corticosteroid showed a mean threshold difference of 4, P  = .006; Olfactory training + Topical Corticosteroid + Vitamin B complex showed a mean threshold difference of 4.4, P  = .006; Olfactory training + Intranasal Vitamin A and E showed a mean threshold difference of 4.4, P  < .001). Olfactory training alone showed lower mean olfactory threshold improvement, when compared to patients undergoing olfactory training + adjuvant therapy (olfactory training alone mean improvement 2.9 ± 2.3 vs olfactory training + adjuvants mean improvement 4.3 ± 2.458, P  = .03)., Conclusions: This is one of the first studies to demonstrate results in the treatment of post-COVID-19 persistent olfactory impairment. A customized approach based on endoscopy findings and patient's preferences may be a valid option for the management of persistent post-COVID-19 olfactory disorder. Adjuvant therapy could be considered in addition to olfactory training, but further studies are needed in order to confirm their effectiveness in this setting., Level of Evidence: 2c (outcomes research).

This study aimed to observe the relationships between the maturity status on the network-based centrality measures of young athletes in small-sided soccer games (SSG). The study included 81 male players (14.4 ± 1.1 years). Measurements included height, sitting height, body mass, and bone age (TW3 method). The applied protocols were the following: Countermovement Jump (CMJ), Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1), Repeated Sprints Ability (RSA), observational analysis of techniques, and interactions performed by players in SSG. The relationship between the set of evaluated variables within each maturity status was obtained from the correlational analysis of networks (P < 0.05). The maturity status explained a significant portion of the variance in body mass (η 2  = 0.37), height (η 2  = 0.30), sitting height (η 2  = 0.30), and performance on the YYIRT1 (η 2  = 0.08), CMJ (η 2  = 0.14), and RSA (η 2  = 0.13). No effect of maturity status on network-based centrality measures of young athletes was identified (P > 0.05). For the late maturity group, there was a correlation between the degree of centrality and physical growth indicators (r mean  = 0.88). For players with maturation "on time", physical growth indicators relate to the degree of prestige (r mean  = 0.36). It is concluded that body size and bone age impact how late and on-time maturity groups interact within the match., (© 2023. The Author(s).)

Background: This study was aimed to examine the relationship between muscular fitness indicators in childhood and areal bone mineral density (aBMD) in adulthood and to verify whether the relationship is mediated by performance on muscular fitness indicators in adulthood., Methods: A sample of 138 healthy adults (69 males; 22.3 years) were followed after a previous assessment at the age of 7-10 years. Stature, body mass and muscular fitness indicators (handgrip strength, standing long jump and sit-ups tests) were assessed in childhood and adulthood. Additionally, total body, upper limbs, lower limbs, right femoral neck and lumbar spine aBMD was assessed in adulthood using dual X-ray absorptiometry. Analysis included descriptive statistics; t-test or Mann-Whitney U-test for comparison between males and females, multiple linear regression for the prediction aBMD from muscular fitness indicators in childhood, mediation analysis of the respective muscular fitness indicators in adulthood and the relationship between muscular fitness indicators in childhood and aBMD., Results: Males were stronger compared to females regarding muscular fitness indicators in childhood and adulthood, and presented higher mean values for aBMD in adulthood, except for lumbar spine (p < 0.05). Regression analysis revealed that some muscular fitness indicators in childhood showed significant positive relationship with bone health indicators in adulthood, such as: handgrip strength and total body aBMD (β = 0.005; R 2  = 0.35; p = 0.040) and upper limbs aBMD (β = 0.005; R 2  = 0.55; p = 0.019); and sit-ups test was a significant predictors of lumbar spine BMD (β = 0.003; R 2  = 0.06; p = 0.039). Mediation analysis pointed out the following: adulthood handgrip strength mediated relationships between childhood handgrip strength and total aBMD (indirect effect (IE) = 0.0025; 95%CI = 0.0005-0.0048), and upper limbs aBMD (IE = 0.0040; 95%CI = 0.0017-0.0069)., Conclusions: Muscular fitness indicators in childhood showed significant relationship with bone health indicators in adulthood and the sit-ups test in childhood had direct effect on lumbar spine aBMD in adulthood. Adulthood handgrip strength mediated the relationship between childhood handgrip strength and total body and upper limb aBMD, pointing out that muscular fitness in childhood may be a aBMD determinant in adulthood, especially when higher muscle fitness performance is maintained in adulthood., (© 2023. The Author(s).)

Different classes of pesticides such as fungicides, herbicides, and insecticides, can induce differential expression of genes that are involved in tumorigenesis events in fish, including the expression of tumor suppressor tp53. The degree and duration of the stressful condition is decisive in defining which tp53-dependent pathway will be activated. Herein we evaluate the target genes expression that participates in the regulation pathway of the tumor suppressor tp53 and in the cancerous processes in tambaqui after exposure to malathion. Our hypothesis is that malathion promotes a gene response that is differentially regulated over time, with positive regulation of tp53 target genes related to the apoptotic pathway and a negative regulation of genes that promote antioxidant responses. The fish were exposed to a sublethal concentration of the insecticide for 6 and 48 h. Liver samples were used to analyze the expression of 11 genes using real-time PCR. Overall, the malathion promoted over time increases in tp53 expression and differential expression of tp53 related genes. The exposure resulted in the activation of damage response related genes, caused a positive expression of atm/atr genes. The pro-apoptotic gene bax was up-regulated and the anti-apoptotic bcl2 was down-regulated. Increased expression of mdm2 and sesn1 in the first hours of exposure and no effect on the antioxidant genes sod2 and gpx1 were also observed. We also witnessed an increase in the expression of the hif-1α gene, with no effect on ras proto-oncogene. The extension of this stressful condition accentuated tp53 transcription, and minimized the levels of mdm2, sens1 and bax; however, it down regulated the levels of bcl2 and the bcl2/bax ratio, which indicates the maintenance of the apoptotic response to the detriment of an antioxidant response., 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.)

With the outbreak of coronavirus disease 2019 (COVID-19), the whole world was impacted by a pandemic. With the passage of time and knowledge about the dynamics and viral propagation of this disease, the short-, medium- and long-term repercussions are still being discovered. During this period, it has been learned that various manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the nervous system. In recent months, a variety of studies and case reports have proposed an association between COVID-19 and Guillain-Barré syndrome (GBS). The present work aims to systematically review the publications available to date to verify the relationship between these two pathologies and the characteristics of post-COVID GBS. There were 156 studies included in this work, resulting in a total of 436 patients. The findings show a mean age of the patients of 61,38 years and a male majority. The GBS symptoms began on average 19 days after the onset of COVID-19 infection. Regarding GBS, the main manifestations found included generalized weakness, reflex reduction, facial paresis/paralysis and hypoesthesia. As expected, the most common result in cerebrospinal fluid (CSF) analysis was albuminocytological dissociation. A pattern of blood analysis findings common to all patients was not observed due to non-standardization of case reports. Regarding electrodiagnostic studies, acute inflammatory demyelinating polyneuropathy (AIDP) appeared as the most common subtype of GBS in this study. There have been reports, to a lesser extent, of acute motor axonal neuropathy (AMAN), acute sensorimotor axonal neuropathy (AMSAN), the pharyngeal-cervical-brachial variant (PCB), and Miller-Fisher syndrome (MFS). The GBS treatment used was mainly intravenous immunoglobulin (IVIG) and plasma exchange (PLEX). Therefore, the present study reports a high prevalence of hospitalization and intensive care units ICU admissions, conjecturing a relationship between the development of GBS and the severity of COVID-19. Despite the severity, most patients showed improvement in GBS symptoms after treatment, and their residual symptoms did not include motor involvement. Therefore, the development of GBS seems to be related to COVID-19 infection, as reported by the present systematic review., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

The objective of this study was to investigate the relative contributions of body size, skeletal age, and motor performance variables with technical actions through an ecological model during small-sided soccer games, and the interaction of biological maturation with technical and motor performance in young players. In this cross-sectional study, eighty-two young players (14.4 ± 1.1 years), belonging to state-level soccer teams and divided by category (U-13 and U-15), were included. Players having an injury in the evaluation period were not included in the study. Measurements of body size, skeletal age (SA), motor tests, and technical actions in small-sided games (SSG) were performed (3 × 3 plus goalkeeper) in two periods (halves) of four minutes. Differences between age groups were found for SA (ES = -2.36), chronological age (ES = -3.89), body mass (ES = -2.09), height (ES = -1.90), and fat-free mass (ES = -2.09). Positive associations were found between body size (R = 0.43 to R = 0.48) and manipulation (R = 0.50 to R = 0.52) indicators and numbers of technical actions (CB and SS), except for stature with LB (R = -0.42) in the U-13 age group. In the U-15 category, skeletal age (R = -0.29 to R = -0.30) and body mass (R = -0.28 to R = -0.29) were negatively associated with the number of technical actions (RB, NB, LB, and OB) (P > 0.05) and positively with the balance with LB (R = 0.26). In conclusion, body size, SA, and motor performance influenced technical actions in SSG differentially in each category. U-13 heavier players and those with a better motor performance presented higher involvement due to the higher., Competing Interests: The authors declared no conflict of interests regarding the publication of this manuscript., (Copyright © Biology of Sport 2023.)

Background: Recently some articles presented information related to the possible effect of maturity over the cognitive control and cardiorespiratory fitness, however little is known about the real effects of maturity in the relation of these variables. In this sense, the purpose of this study was to examine the potential mediating role of somatic maturity on the association between cardiorespiratory fitness (CRF) and cognitive control., Methods: This three-year longitudinal research comprises two data collection groups: a baseline conducted in 2016 with 394 adolescents (aged 11.7 ± 0.6 years) and a follow-up in 2019 with 134 adolescents (aged 14.9 ± 0.7 years). Anthropometry data, 20-m shuttle run test and peak height velocity (PHV) to determine the maximum oxygen uptake (VO 2max ) and somatic maturity, respectively, were collected at both sampling times. In parallel, the Sociodemographic and cognitive control function variables were included in the follow-up to evaluate the inhibitory control (by the Stroop test) and the visuo-spatial working memory (by the Corsi block-tapping test). Associations between CRF and cognitive functions were computed by multiple linear regression, with mediation as a function of PHV., Results: CRF exhibited transversal associations with reaction time in congruent (β = -0.004; p = 0.001) and incongruent (β = -0.005; p = 0.004) stimulus-responses. Meanwhile, the variation in VO 2max over the three year-study had a significant impact on the reaction time of congruent (β = -0.006; p = 0.001) and incongruent (β = -0.006; p = 0.012) responses at follow-up. However, PHV did not show a significant association with the cognitive functions, indicating no mediating role., Conclusions: Although the associations between CRF and the cognitive functions exhibited great transversal and longitudinal impacts, somatic maturity did not affect the cognitive control functions, associating exclusively with CRF., (© 2022. The Author(s).)

Paecilomyces variotti ( P. variotti ) is a fungal species found in soil, wood and some foods, and has been associated with some severe systemic infections. P. variotti has not been previously identified in carious tissue, and the aim of the present study is to report the presence of P. variotti in a deep carious lesion discussing its possible local and systemic associations. A 28 year-old male was submitted to extraction of the upper left second premolar (tooth #25) presenting a deep carious lesion. After extraction the tooth was cleaved in its long axis, and the infected dentinal tissue was curetted and submitted to microbiological analysis using CHROMagar® Candida medium and Malt Extract Agar. Macroscopic and microscopic analysis confirmed the presence of P. variotti in the carious tissue. Post-operatory period was uneventful, healing of the dental socket was complete, and the patient remained well during the follow-up period. P. variotti , a fungus not considered saprophyte in the oral cavity, was encountered in a deep caries lesion, and its potential association with local and systemic infections should be considered. Key words: Paecilomyces variotti, dental caries., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright: © 2022 Medicina Oral S.L.)

Drugs used to fight fungal infections may cause toxic or adverse drug interactions. For this reason, there is an increase in the development of natural, semisynthetic and synthetic antifungal peptides. This study aimed to perform a patent review to identify the advances in peptides to treat fungal infections. In a preliminary assessment, 597 patents were identified from the database. Then, duplicated patents (62) and those with titles in disagreement with the scope of this review (196) were excluded. Then, six patents were not in English or Spanish. Following the screening, 288 patents were outside the focus of this review, according to their abstract and description. The final selection covered 45 patents.

Objectives: The aim of this study was to evaluate the time in days between symptom onset and first positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for COVID-19., Methods: This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR", and "diagnosis"., Results: The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and six were cross-sectional studies. The overall mean time between symptom onset and positive test result was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR test results; the best performance was on days 22-24, when 98% of test results were positive., Conclusion: These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The most consistently identified mortality determinants for the new coronavirus 2019 (COVID-19) infection are aging, male sex, cardiovascular/respiratory diseases, and cancer. They were determined from heterogeneous cohorts that included patients with different disease severity and previous conditions. The main goal of this study was to determine if activities of daily living (ADL) dependence measured by Barthel's index could be a predictor for COVID-19 mortality., Methods: A prospective cohort study was performed with a consecutive sample of 340 COVID-19 patients representing patients from all over the northern region of Portugal from October 2020 to March 2021. Mortality risk factors were determined after controlling for demographics, ADL dependence, admission time, comorbidities, clinical manifestations, and delay-time for diagnosis. Central tendency measures were used to analyze continuous variables and absolute numbers (proportions) for categorical variables. For univariable analysis, we used t test, chi-square test, or Fisher exact test as appropriate (α=0.05). Multivariable analysis was performed using logistic regression. IBM SPSS version 27 statistical software was used for data analysis., Results: The cohort included 340 patients (55.3% females) with a mean age of 80.6±11.0 years. The mortality rate was 19.7%. Univariate analysis revealed that aging, ADL dependence, pneumonia, and dementia were associated with mortality and that dyslipidemia and obesity were associated with survival. In multivariable analysis, dyslipidemia (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.17-0.71) was independently associated with survival. Age ≥86 years (pooled OR, 2.239; 95% CI, 1.100-4.559), pneumonia (pooled OR, 3.00; 95% CI, 1.362-6.606), and ADL dependence (pooled OR, 6.296; 95% CI, 1.795-22.088) were significantly related to mortality (receiver operating characteristic area under the curve, 82.1%; p<0.001)., Conclusion: ADL dependence, aging, and pneumonia are three main predictors for COVID-19 mortality in an elderly population.

This study verified the effects of body size and game position on interactions performed by young soccer players in small-sided games (SSG). The sample consisted of 81 Brazilian soccer players (14.4 ± 1.1 years of age). Height, body mass, and trunk-cephalic height were measured. SSG was applied in the GK + 3v3 + GK format, and Social Network Analyses were carried out through filming the games to obtain the following prominence indicators: degree centrality, closeness centrality, degree prestige, and proximity prestige, in addition to network intensity and number of goals scored. Factorial ANCOVA (bone age as covariate) was used to test the effects of game position, body size, and respective interaction on centrality measurements ( p  < 0.05). Similarity between game positions in body size indicators ( p  > 0.05) was observed. The game position affected degree centrality ( p = 0.01, η 2 = 0.16), closeness centrality ( p   = 0.01, η 2 = 0.11), and network intensity ( p = 0.02, η 2 = 0.09), in which midfielders presented the highest network prominence values when compared to defenders and forwards. In conclusion, midfielders are players with high interaction patterns in the main offensive plays, which behavior is independent of body size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered as a potential conflict of interest., (Copyright © 2022 Borges, Costa, Ramos-Silva, Praça and Ronque.)

Purpose: Advances in functional imaging allowed us to visualize brain glucose metabolism in vivo and non-invasively with [ 18 F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging. In the past decades, FDG-PET has been instrumental in the understanding of brain function in health and disease. The source of the FDG-PET signal has been attributed to neuronal uptake, with hypometabolism being considered as a direct index of neuronal dysfunction or death. However, other brain cells are also metabolically active, including astrocytes. Based on the astrocyte-neuron lactate shuttle hypothesis, the activation of the glutamate transporter 1 (GLT-1) acts as a trigger for glucose uptake by astrocytes. With this in mind, we investigated glucose utilization changes after pharmacologically downregulating GLT-1 with clozapine (CLO), an anti-psychotic drug., Methods: Adult male Wistar rats (control, n = 14; CLO, n = 12) received CLO (25/35 mg kg -1 ) for 6 weeks. CLO effects were evaluated in vivo with FDG-PET and cortical tissue was used to evaluate glutamate uptake and GLT-1 and GLAST levels. CLO treatment effects were also assessed in cortical astrocyte cultures (glucose and glutamate uptake, GLT-1 and GLAST levels) and in cortical neuronal cultures (glucose uptake)., Results: CLO markedly reduced in vivo brain glucose metabolism in several brain areas, especially in the cortex. Ex vivo analyses demonstrated decreased cortical glutamate transport along with GLT-1 mRNA and protein downregulation. In astrocyte cultures, CLO decreased GLT-1 density as well as glutamate and glucose uptake. By contrast, in cortical neuronal cultures, CLO did not affect glucose uptake., Conclusion: This work provides in vivo demonstration that GLT-1 downregulation induces astrocyte-dependent cortical FDG-PET hypometabolism-mimicking the hypometabolic signature seen in people developing dementia-and adds further evidence that astrocytes are key contributors of the FDG-PET signal., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Propose: This study aims to explore the use of the Centiloid (CL) method in amyloid-β PET quantification to evaluate distinct cognitive aging stages, investigating subjects' mismatch classification using different cut-points for amyloid-β positivity., Procedures: The CL equation was applied in four groups of individuals: SuperAgers (SA), healthy age-matched controls (AC), healthy middle-aged controls (MC), and Alzheimer's disease (AD). The amyloid-β burden was calculated and compared between groups and quantitative variables. Three different cut-points (Jack CR, Wiste HJ, Weigand SD, et al., Alzheimer's Dement 13:205-216, 2017; Salvadó G, Molinuevo JL, Brugulat-Serrat A, et al., Alzheimer's Res Ther 11:27, 2019; and Amadoru S, Doré V, McLean CA, et al., Alzheimer's Res Ther 12:22, 2020) were applied in CL values to differentiate the earliest abnormal pathophysiological accumulation of Aβ and the established Aβ pathology., Results: The AD group exhibited a significantly increased Aβ burden compared to the MC, but not AC groups. Both healthy control (MC and AC) groups were not significantly different. Visually, the SA group showed a diverse distribution of CL values compared with MC; however, the difference was not significant. The CL values have a moderate and significant relationship between Aβ visual read, RAVLT DR and MMSE. Depending on the cut-point used, 10 CL, 19 CL, or 30 CL, 7.5% of our individuals had a different classification in the Aβ positivity. For the AC group, we obtained about 40 to 60% of the individuals classified as positive., Conclusion: SuperAgers exhibited a similar Aβ load to AC and MC, differing in cognitive performance. Independently of cut-point used (10 CL, 19 CL, or 30 CL), three SA individuals were classified as Aβ positive, showing the duality between the individual's clinics and the biological definition of Alzheimer's. Different cut-points lead to Aβ positivity classification mismatch in individuals, and an extra care is needed for individuals who have a CL value between 10 and 30 CL., (© 2021. World Molecular Imaging Society.)

Objective: To describe veterinarians' communication of the companion animal physical exam (CAPE) to veterinary clients and to identify factors associated with the number of physical exam components communicated by veterinarians to clients., Sample: 376 video-recorded veterinarian-client-patient interactions, involving 60 veterinarians., Procedures: 18 CAPE components were studied in relation to veterinarians' use of 7 communication-related parameters. A mixed linear regression model was used to assess veterinarian, patient, and appointment factors associated with the number of components conveyed by a veterinarian., Results: Veterinarians conveyed 1,566 of 2,794 (56.1%) of the components that they examined to clients, as having been examined. Of those components that were examined and conveyed by veterinarians, the impact of the finding was communicated for 496 of 1,566 (31.7%) of the components. Visual aids and take-home literature were each used in relation to an examined component during 15 of the 376 interactions (4%). A significant association was found between number of CAPE components conveyed and gender of the veterinarian (females conveyed 1.31 more), as well as the type of appointment (2.57 more were conveyed in wellness appointments and 1.37 more in problem appointments, compared to rechecks)., Clinical Relevance: Findings identify an opportunity for veterinarians to further emphasize components of the CAPE, which may in turn increase clients' perceived value of the CAPE due to understanding the benefits for their pet. This may be accomplished with the Talking Physical Exam, in which veterinarians discuss CAPE components findings with clients in real time, and the relevance of the findings to the patient's health.

Background: Zika virus infection during pregnancy is linked to birth defects, most notably microcephaly, which is associated with neurodevelopmental delays., Objective: The goals of the study were to propose a method for severity classification of congenital microcephaly based on neuroradiologic findings of MRI scans, and to investigate the association of severity with neuropsychomotor developmental scores. We also propose a semi-automated method for MRI-based severity classification of microcephaly., Materials and Methods: We conducted a cross-sectional investigation of 42 infants born with congenital Zika infection. Bayley Scales of Infant and Toddler Development III (Bayley-III) developmental evaluations and MRI scans were carried out at ages 13-39 months (mean: 24.8 months; standard deviation [SD]: 5.8 months). The severity score was generated based on neuroradiologist evaluations of brain malformations. Next, we established a distribution of Zika virus-microcephaly severity score including mild, moderate and severe and investigated the association of severity with neuropsychomotor developmental scores. Finally, we propose a simplified semi-automated procedure for estimating the severity score based only on volumetric measures., Results: The results showed a correlation of r=0.89 (P<0.001) between the Zika virus-microcephaly severity score and the semi-automated method. The trimester of infection did not correlate with the semi-automated method. Neuropsychomotor development correlated with the severity classification based on the radiologic readings and semi-automated method; the more severe the imaging scores, the lower the neuropsychomotor developmental scores., Conclusion: These severity classification methods can be used to evaluate severity of microcephaly and possible association with developmental consequences. The semi-automated methods thus provide an alternative for predicting severity of microcephaly based on only one MRI sequence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND: This study evaluated the executive functions of air traffic controllers (ATCs) in relation to demographic and occupational characteristics such as length of service, technical qualifications, and work shifts. METHODS: This was a cross-sectional study based on a convenience sample with sequential selection of 52 Brazilian ATCs using the Wisconsin Card Sorting Test (WCST), questionnaire applied to the ATCs, Student's t-test, and one-way analysis of variance with post hoc Tukey multiple comparisons of WCST with functional characteristics. RESULTS: ATCs with 0 to 5 yr of service presented scores significantly above the cohort average in the WCST [0-5 yr: 0.54 ± 0.01 vs. 6-15 yr: 0.31 ± 0.52 vs. 151 yr: -0.02 ± 0.80]. ATCs working a 3-shift pattern presented an efficient performance and fewer perseverative errors in the WCST (3-shift: -0.63 ± 0.38 vs. 4-shift: -0.45 ± 0.43), that did not rise to significance. In a comparison between executive brain functions and technical qualifications, the controllers who worked in the TWR (Aerodrome Control Tower) only, and those who worked in both the TWR and APP (Approach Control Service) showed no differences in the number of completed categories and in perseverative errors. DISCUSSION: The executive brain functioning of the ATCs, such as mental flexibility, strategic planning and inhibitory control, were identified as being above average when compared to the general population. While alterations in work shifts appear to have a negative (but nonsignificant) impact, newer ATCs showed stronger scores than more experienced ATCs on the WCST. Successful performance as an ATC has complex foundations, such as understanding the context of air navigation and having strong executive function capabilities. de Freitas AM, Portuguez MW, Russomano, T, da Costa JC. Air traffic controllers and executive brain function . Aerosp Med Hum Perform. 2022; 93(5):426-432.

Allergic asthma is characterized by chronic airway inflammation and is constantly associated with anxiety disorder. Recent studies showed bidirectional interaction between the brain and the lung tissue. However, where and how the brain is affected in allergic asthma remains unclear. We aimed to investigate the neuroinflammatory, neurochemical, and neurometabolic alterations that lead to anxiety-like behavior in an experimental model of allergic asthma. Mice were submitted to an allergic asthma model induced by ovalbumin (OVA) and the control group received only Dulbecco's phosphate-buffered saline (DPBS). Our findings indicate that airway inflammation increases interleukin (IL) -9, IL-13, eotaxin, and IL-1β release and changes acetylcholinesterase (AChE) and Na + ,K + -ATPase activities in the brain of mice. Furthermore, we demonstrate that a higher reactive oxygen species (ROS) formation and antioxidant defense alteration that leads to protein damage and mitochondrial dysfunction. Therefore, airway inflammation promotes a pro-inflammatory environment with an increase of BDNF expression in the brain of allergic asthma mice. These pro-inflammatory environments lead to an increase in glucose uptake in the limbic regions and to anxiety-like behavior that was observed through the elevated plus maze (EPM) test and downregulation of glucocorticoid receptor (GR). In conclusion, the present study revealed for the first time that airway inflammation induces neuroinflammatory, neurochemical, and neurometabolic changes within the brain that leads to anxiety-like behavior. Knowledge about mechanisms that lead to anxiety phenotype in asthma is a beneficial tool that can be used for the complete management and treatment of the disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Major depressive disorder is associated with chronic inflammation and deficient production of brain-derived neurotrophic factor (BDNF). Bone marrow mononuclear cell (BMMC) transplantation has an anti-inflammatory effect and has been proven effective in restoring non-depressive behavior. This study investigated whether BMMC transplantation can prevent the development of depression or anxiety in chronic mild stress (CMS), as well as its effect on inflammatory and neurogenic molecules., Method: Three groups of animals were compared: BMMC-transplanted animals subjected to CMS for 45 days, CMS non-transplanted rats, and control animals. After the CMS period, the three groups underwent the following behavioral tests: sucrose preference test (SPT), eating-related depression test (ERDT), social avoidance test (SAT), social interaction test (SIT), and elevated plus maze test (EPMT). Transplanted cell tracking and measurement of the expression of high-mobility group box 1 (HMGB1), interleukin-1β (IL-1β), tumor necrosis factor (TNFα), and BDNF were performed on brain and spleen tissues., Results: BMMC transplantation prevented the effects of CMS in the SPT, ERDT, SAT, and SIT, while prevention was less pronounced in the EPMT. It was found to prevent increased HMGB-1 expression induced by CMS in the hippocampus and spleen, increase BDNF expression in both tissues, and prevent increased IL-1β expression in the hippocampus alone, while no effect of the transplant was observed in the TNFα expression. In addition, no transplanted cells were found in either the brain or spleen., Conclusions: BMMC transplantation prevents the development of depression and anxiety-like behavior triggered by CMS. It could prevent increased HMGB-1 and IL-1β expression in the hippocampus and increased BDNF expression in the same tissue. Cell treatment represents a further perspective in the research and treatment of depression and possible mood disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To establish the components of a best-practice, baseline companion animal physical exam (CAPE)., Sample: 25 small animal veterinary internists and 20 small animal primary care veterinarians, all teaching the CAPE at veterinary colleges in the US, Canada, and Australia., Procedures: Using the Delphi Method of Consensus, 3 rounds of online questionnaires were sent to participants. The first round included demographic questions, questions about teaching the physical exam, and an open-ended question allowing participants to record details of how they conduct a CAPE. In the second round, participants were asked to rate components of the CAPE, which were derived from round 1, as "always examine," "only examine as needed," or "undecided." Following round 2, any component not reaching 90% consensus (set a priori) for the response "always examine" was put forth in round 3, with a summary of comments from the round 2 participants for each remaining component., Results: 35 components of a baseline CAPE were identified from round 1. The 25 components that reached 90% consensus by the end of round 3 were checking the oral cavity, nose, eyes, ears, heart, pulse rate, pulse quality, pulse synchrony, lungs, respiratory rate, lymph nodes, abdomen, weight, body condition score, mucous membranes, capillary refill time, general assessment, masses, haircoat, skin, hydration, penis and testicles or vulva, neck, limbs, and, in cats only, thyroid glands., Clinical Relevance: The findings establish an expert panel's consensus on 25 components of a baseline, best-practice CAPE that can be used to help inform veterinary curricula, future research, and the practice of veterinarians.

The mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces excitotoxicity. The authors hypothesized that CTK 01512-2, a recombinant peptide calcium channel N-type blocker, and the TRPA1 antagonist, could show neuroprotective effects. The male Wistar rats received 3-NP [25 mg/kg (i.p.) for 7 days], and a treatment of CTK 01512-2 was delivered intrathecally (i.t.), thrice a week. The neuroprotective effects were evaluated by [ 18 F]FDG MicroPET analysis. The CTK 01512-2 toxin was able to reestablish similar glucose uptakes on the control animals. To detect the neurobehavioral effects from 3-NP, three protocols (6.25, 12.5, 18.75 mg/kg of 3-NP (i.p.), for 3, 4, and 6 days, respectively) were evaluated by performance tests (open field test, walk footprint, elevated plus-maze, Y-maze, and the object recognition test). Important disabilities in the gait of the rats were seen, as well as memory deficits, and anxious behavior in the animals that were treated with all 3-NP protocols. The dose of 18.75 mg/kg (for 3 days) showed the most pronounced behavioral effects and lethality, while the rats treated with 12.5 mg/kg (for 4 days) showed behavioral effects similar to the 6.25 mg/kg dose (for 6 days). The third protocol was then repeated and the rats were treated with the CTK 01512-2 toxin to be evaluated behaviorally again. The recombinant peptide prevented all of the gait-evaluated parameters that were induced by 3-NP at a 6.25 mg/kg dose, which displayed an improvement in the exploratory activities. Overall, these results have reinforced the positive effects of CTK 01512-2 against the behavioral changes that were induced by the mitochondrial inhibitor 3-NP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Methylphenidate (MPH) has been widely misused by children and adolescents who do not meet all diagnostic criteria for attention-deficit/hyperactivity disorder without a consensus about the consequences. Here, we evaluate the effect of MPH treatment on glucose metabolism and metabolic network in the rat brain, as well as on performance in behavioral tests. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or an equivalent volume of 0.9% saline solution (controls), once a day, from the 15th to the 44th postnatal day. Fluorodeoxyglucose-18 was used to investigate cerebral metabolism, and a cross-correlation matrix was used to examine the brain metabolic network in MPH-treated rats using micro-positron emission tomography imaging. Performance in the light-dark transition box, eating-related depression, and sucrose preference tests was also evaluated. While MPH provoked glucose hypermetabolism in the auditory, parietal, retrosplenial, somatosensory, and visual cortices, hypometabolism was identified in the left orbitofrontal cortex. MPH-treated rats show a brain metabolic network more efficient and connected, but careful analyses reveal that the MPH interrupts the communication of the orbitofrontal cortex with other brain areas. Anxiety-like behavior was also observed in MPH-treated rats. This study shows that glucose metabolism evaluated by micro-positron emission tomography in the brain can be affected by MPH in different ways according to the region of the brain studied. It may be related, at least in part, to a rewiring in the brain the metabolic network and behavioral changes observed, representing an important step in exploring the mechanisms and consequences of MPH treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Global climate change represents a critical threat to the environment since it influences organismic interactions, such as the host-parasite systems, mainly in ectotherms including fishes. Rising temperature and CO 2 are predicted to affect this interaction other and critical physiological processes in fish. Herein, we investigated the effects of different periods of exposure to climate change scenarios and to two degrees of parasitism by monogeneans in the host-parasite interaction, as well as the antioxidant and ionoregulatory responses of tambaqui (Colossoma macropomum), an important species in South American fishing and aquaculture. We hypothesized that temperature and CO 2 changes in combination with parasite infection would interfere with the host's physiological processes that are related to oxidative stress and ionoregulation. We experimentally exposed C. macropomum to low and high levels of parasitism in the current and extreme climate scenarios (4.5 °C and 900 ppm CO 2 above current levels) for periods of seven and thirty days and we use as analyzed factors; the exposure time, the climate scenario and parasitism level in a 2 × 2 × 2 factorial through a three-way ANOVA as being fish the experimental unit (n = 8). An analysis of gill enzymatic and gene expression profile was performed to assess physiological (SOD, GPx and Na + /K + -ATPase enzymes) and molecular (Nrf2, SOD1, HIF-1α and NKA α1a genes) responses. A clear difference in the parasitism levels of individuals exposed to the extreme climate scenario was observed with a rapid and aggressive increase that was higher after 7 days of exposure though showed a decrease after 30 days. The combination of exposure to the extreme climate change scenario and parasitism caused oxidative stress and osmoregulatory disturbance, which was observed through the analysis of gene expression (Nrf2, SOD1, HIF-1α and NKA α1a) and antioxidant and ionoregulatory enzymes (SOD, GPx and Na + /K + -ATPase) on the host, possibly linked to inflammatory processes caused by the high degree of parasitism. In the coming years, these conditions may result in losses of performance for this species, and as such will represent ecological damage and economical losses, and result in a possible vulnerability in relation to food security., (© 2021. The Author(s).)

Despite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use., (© 2021. The Author(s).)

Background: The objective of this paper was to describe the arterial supply of the uncus and quantify the branches directed to the anteromedial aspect of the human temporal cortex., Methods: We studied 150 human cerebral hemispheres identifying main afferent arteries supplying the anteromedial temporal cortex with particular attention to the uncus, determining the territory supplied by each artery through either cortical or perforating branches., Results: The uncus was supplied by 419 branches of the anterior choroidal artery (AChA), 210 branches of the internal carotid artery (ICA), 353 branches of the middle cerebral artery (MCA), and 122 branches of the posterior cerebral artery (PCA). The total of supplying vessels was 1104 among the 150 hemispheres studied, which corresponds to 7.36 arteries per uncus. The average of branches per hemisphere was as follows: 2.79 from AChA, 1.40 from ICA, 2.35 from MCA, and 0.81 from PCA. The relative contribution of each artery for the total of specimens studied was as follows: 38% from AChA, 19% from ICA, 32% from the MCA, and 11% from the PCA. We identified cortical anastomoses mostly between the MCA and PCA (27 cases)., Conclusion: We described and quantified the uncus' vascularization, including anatomical variations. This updated, detailed description of the mesial temporal vascularization is paramount to improve the treatment of neurosurgical conditions., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([ 18 F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression., 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 © 2021 Almeida, Nonose, Ganzella, Loureiro, Rocha, Machado, Bellaver, Fontella, Leffa, Pettenuzzo, Venturin, Greggio, da Costa, Zimmer, Elisabetsky and Souza.)

Prenatal and early postnatal periods are important for brain development and neural function. Neonatal insults such as hypoxia-ischemia (HI) causes prolonged neural and metabolic dysregulation, affecting central nervous system maturation. There is evidence that brain hypometabolism could increase the risk of adult-onset neurodegenerative diseases. However, the impact of non-pharmacologic strategies to attenuate HI-induced brain glucose dysfunction is still underexplored. This study investigated the long-term effects of early environmental enrichment in metabolic, cell, and functional responses after neonatal HI. Thereby, male Wistar rats were divided according to surgical procedure, sham, and HI (performed at postnatal day 3), and the allocation to standard (SC) or enriched condition (EC) during gestation and lactation periods. In-vivo cerebral metabolism was assessed by means of [ 18 F]-FDG micro-positron emission tomography, and cognitive, biochemical, and histological analyses were performed in adulthood. Our findings reveal that HI causes a reduction in glucose metabolism and glucose transporter levels as well as hyposynchronicity in metabolic brain networks. However, EC during prenatal or early postnatal period attenuated these metabolic disturbances. A positive correlation was observed between [ 18 F]-FDG values and volume ratios in adulthood, indicating that preserved tissue by EC is metabolically active. EC promotes better cognitive scores, as well as down-regulation of amyloid precursor protein in the parietal cortex and hippocampus of HI animals. Furthermore, growth-associated protein 43 was up-regulated in the cortex of EC animals. Altogether, results presented support that EC during gestation and lactation period can reduce HI-induced impairments that may contribute to functional decline and progressive late neurodegeneration., (© 2020 International Society for Neurochemistry.)