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This study explores the deployment of Artificial Intelligence (AI) in Canadian hospitals from 2000 to 2021, focusing on metropolitan areas. We investigate how local public and private research ecosystems and links to national and international AI hubs influence the adoption of AI in healthcare. Our analysis shows that AI research outputs from public institutions have a significant impact on AI competences in hospitals. In addition, collaborations between hospitals are critical to the successful integration of AI. Metropolitan areas such as Toronto, Montreal, and Vancouver are leading the way in AI deployment. These findings highlight the importance of local AI research capabilities and international hospital collaborations and provide guidance to policy-makers and health leaders to drive the diffusion of AI technology in healthcare., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection., Methods: Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D)., Results: In vitro protocols have shown that rhein, diacerein's primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs ( p < 0.05), and suppressed viral replication when administered either before or after the virus incubation ( p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CL pro ) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PL pro ) virus and in the phosphorylation of proteins related cytoskeleton network ( p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo ( p < 0.05)., Conclusion: The indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials., Competing Interests: DB discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hô pitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and United States national co-leader, funded by Bayer), WebMD (CME steering committees), (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women' s Hospital who assigned to Lexicon; neither I nor Brigham and Women' s Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo. AS discloses the following relationships - Research Funding: Amgen, AstraZeneca, National Council for Scientific and Technological Development (CNPq) and Fundaç and#227; o de Apoio and#224; Pesquisa do Estado de Sã o Paulo (FAPESP). Dr. Pedro Gonç alves de Oliveira is responsible for R&D activities at TRB Pharma Indú stria Quí mica e Farmace utica Ltda, SP, Brazil. TRB Pharma is the owner of the product ARTRODAR® a diacerein-based product for osteoarthritis treatment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Carmo, Castillo, Bonilha, Gomes, Barreto, Moura, Davanzo, de Brito Monteiro, Muraro, Fabiano de Souza, Morari, Galdino, Brunetti, Reis-de-Oliveira, Carregari, Nadruz, Martins-de-Souza, Farias, Velloso, Proenca-Modena, Mori, Loh, Bhatt, Yellon, Davidson, De Oliveira, Moraes-Vieira and Sposito.)

Pediatric brain tumors, particularly those affecting the brainstem, present a significant challenge due to their intricate anatomical location and diverse classification. This review explores the classification, anatomical considerations, and surgical approaches for pediatric brainstem tumors, focusing on recent updates from the World Health Organization (WHO) classification. Brainstem tumors encompass a spectrum from diffuse gliomas to focal intrinsic and exophytic types, each presenting unique clinical and surgical challenges. Surgical strategies have evolved with advancements in neuroimaging and surgical techniques, emphasizing approaches such as neuroendoscopy and tailored incisions to minimize damage to critical structures. Despite the complexities involved, recent developments offer promising outcomes in tumor resection and patient management, highlighting ongoing advancements in neurosurgical care for pediatric brain tumors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, we present an all-solid-state electrochromic device (ECD) that eliminates the need for hard-to-obtain materials and conventional liquid/gel electrolytes. Using a cost-effective and industrially scalable spray coating technique, we developed an ECD containing a layer of zinc oxide nanorods (ZnO nano ) synthesized via a simple solochemical route. The device configuration includes a preformed Al-coated glass substrate, acting as a counter electrode, within a glass/Al/ZnO nano /PEDOT:PSS architecture. The device exhibits reversible switching between light blue and dark blue states upon application of -1.2 V and +2.8 V, respectively, with a significant difference in transmittance between bleached and colored states in the visible-NIR spectrum, featuring a high coloration efficiency of 275.62 cm 2 /C at 600 nm. The response times required for both coloring and bleaching states were 9.92 s and 7.51 s, respectively, for a sample with an active area of 5.5 × 2.5 cm 2 . Regarding the electrochemical stability of the ZnO-based ECD, the transmittance modulation reached around 8.01% at 600 nm after 12,800 s, following initial variations observed during the first 10 cycles. These results represent significant progress in electrochromic technology, offering a sustainable and efficient alternative to traditional ECDs. The use of economical fabrication techniques and the exclusion of critical materials highlight the potential for widespread industrial adoption of this novel ECD design.

The present study was carried out to investigate the proximate composition, fatty acid (FA) profile and volatile compounds (VC) of cooked green licuri (Syagrus coronata) - an unripe stage that is then cooked - and naturally ripe licuri almonds. The FA profiles were determined by gas chromatography (GC) and the VC composition was evaluated using headspace-solid-phase microextraction coupled with GC-MS. The cooked green licuri presented higher moisture, and lower contents of ashes, proteins and lipids than naturally ripe licuri almonds. The FA profiles of cooked green licuri and naturally ripe licuri almonds showed that saturated FAs were predominant (80%) in both samples, and the concentrations of lauric, palmitic, and oleic acids in naturally ripe licuri almonds were higher than those in cooked green licuri. Limonene was the predominant compound in naturally ripe licuri almonds. The main class of VC in the cooked green licuri were aldehydes, with 3-methyl-butanal and furfural being the main species. Alcohols, such as 3-methyl-butanol and 2-heptanol, were the main class of VC in naturally ripe licuri almonds. Among the volatile compounds, 1-hexanol and 2-nonanone contributed to the aroma of cooked green licuri almonds, whereas 2-heptanone, ethanol, and limonene contributed to the aroma of naturally ripe licuri almonds (almonds not subjected to any cooking process). In a word, cooked green licuri and naturally riped licuri almonds, despite having different proximate compositions, present similar fatty acid profile and distinct aromatic characteristics. Therefore, cooked green licuri and naturally riped licuri almonds are an alternative source of nutrient and could be investigated for the use in the food industry to enhance flavor and aroma to new products., 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. Published by Elsevier Ltd.)

Competing Interests: The authors report no conflicts of interest.

American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4 + /CD8 + T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4 + and CD8 + T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4 + /CD8 + IFN-γ + TNF-α + and CD4 + /CD8 + CD44 high CD62L high/low T cells, IgG Total , IgG 2a , and lower rates of IgG 1 and CD4 + /CD8 + IL-10 + . This data suggests that proposed formulations could be considered potential tools to prevent ATL., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As one of the most important cellular housekeepers, autophagy directly affects cellular health, homeostasis, and function. Even though the mechanisms behind autophagy are well described, how molecular alterations and dysfunctions can lead to pathology in disease contexts still demands deeper investigation. Proteomics is a widely employed tool used to investigate molecular alterations associated with pathological states and has proven useful in identifying alterations in protein expression levels and post-translational modifications in autophagy. In this narrative review, we expand on the molecular mechanisms behind autophagy and its regulation, and further compile recent literature associating autophagy disturbances in context of brain disorders, utilizing discoveries from varying models and species from rodents and cellular models to human post-mortem brain samples. To outline, the canonical pathways of autophagy, the effects of post-translational modifications on regulating each step of autophagy, and the future directions of proteomics in autophagy will be discussed. We further aim to suggest how advancing proteomics can help further unveil molecular mechanisms with regard to neurological disorders., (© 2024 International Society for Neurochemistry.)

Proteomic analysis of human cerebral organoids may reveal how psychedelics regulate biological processes, shedding light on drug-induced changes in the brain. This study elucidates the proteomic alterations induced by lysergic acid diethylamide (LSD) in human cerebral organoids. By employing high-resolution mass spectrometry-based proteomics, we quantitatively analyzed the differential abundance of proteins in cerebral organoids exposed to LSD. Our findings indicate changes in proteostasis, energy metabolism, and neuroplasticity-related pathways. Specifically, LSD exposure led to alterations in protein synthesis, folding, autophagy, and proteasomal degradation, suggesting a complex interplay in the regulation of neural cell function. Additionally, we observed modulation in glycolysis and oxidative phosphorylation, crucial for cellular energy management and synaptic function. In support of the proteomic data, complementary experiments demonstrated LSD's potential to enhance neurite outgrowth in vitro , confirming its impact on neuroplasticity. Collectively, our results provide a comprehensive insight into the molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Shotgun proteomics analysis presents multifaceted challenges, demanding diverse tool integration for insights. Addressing this complexity, OmicScope emerges as an innovative solution for quantitative proteomics data analysis. Engineered to handle various data formats, it performs data pre-processing - including joining replicates, normalization, data imputation - and conducts differential proteomics analysis for both static and longitudinal experimental designs. Empowered by Enrichr with over 224 databases, OmicScope performs Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA). Additionally, its Nebula module facilitates meta-analysis from independent datasets, providing a systems biology approach for enriched insights. Complete with a data visualization toolkit and accessible as Python package and a web application, OmicScope democratizes proteomics analysis, offering an efficient and high-quality pipeline for researchers., (© 2024. The Author(s).)

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K + (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K + currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The present study aimed to investigate the effects of post-activation performance enhancement (PAPE) after three warm-up protocols on back squat performance in trained men., Methods: Fourteen resistance-trained men performed conditioning activity (CA) with high-load (HL-CA), low-load (LL-CA), or usual specific warm-up as a control (CON). HL-CA consisted of one set of three repetitions with 90% of one repetition maximum (RM); LL-CA consisted of one set of six repetitions with 45% of 1 RM performed at maximal velocity; CON involved eight repetitions with 45% of 1 RM at controlled velocity. The participant's performance was measured using the total number of repetitions and volume load (reps × load × sets)., Results: There were no significant differences between warm-up for the total number of repetitions ( p = 0.17) or total volume load ( p = 0.15). There was no difference between conditions for the number of repetitions (main condition effect; p = 0.17); however, participants achieved a significantly higher volume load after HL-PAPE than after CON for the first set ( p = 0.04)., Conclusion: High or low equated-load CA used as warm-up strategies did not potentiate subsequent performance enhancement in multiple-set back squat exercise performed until muscle failure in comparison with usual warm-up., Competing Interests: Daniel Souza, Anderson Silva, Arthur Vale, Alana Pessoni, Luan Galvão, Murilo Araujo, Celio de Paula Júnior, Carlos Vieira, Amilton Vieira and Paulo Gentil declare that they have no competing interests., (© 2024 Souza et al.)

Objective: Investigate the relationship between resting-state EEG-measured brain oscillations and clinical and demographic measures in Stroke patients. Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), Stroke arm, with 85 patients, considering demographic, clinical, and stroke characteristics. Resting-state EEG relative power from delta, theta, alpha, and beta oscillations were measured from the central region. Multivariate regression models were used for both affected and non-affected hemispheres. Results: Motor function was negatively associated with Delta and Theta oscillations, while positively associated with Alpha oscillations (both hemispheres). Similarly, cognition levels measured were negatively associated with Delta activity. Depression levels were negatively associated with Alpha activity specifically in the affected hemisphere, while positively associated with Beta activity in both hemispheres. Regarding pain measures, no significant association was observed, while CPM measure showed a positive association with Alpha activity in the non-affected hemisphere. Finally, we found that theta/alpha ratio was negatively associated with motor function and CPM scores. Conclusion: The results lead us to propose a framework for brain oscillations in stroke, whereas Delta and Beta would represent disrupted mal-adaptive brain plasticity and Theta and Alpha would represent compensatory and functional brain oscillations for motor and sensory deficits in stroke, respectively., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bioluminescence, the emission of light by living organisms, is a captivating and widespread phenomenon with diverse ecological functions. This comprehensive review explores the biodiversity, mechanisms, ecological roles, and conservation challenges of bioluminescent organisms in Brazil, a country known for its vast and diverse ecosystems. From the enchanting glow of fireflies and glow-in-the-dark mushrooms to the mesmerizing displays of marine dinoflagellates and cnidarians, Brazil showcases a remarkable array of bioluminescent species. Understanding the biochemical mechanisms and enzymes involved in bioluminescence enhances our knowledge of their evolutionary adaptations and ecological functions. However, habitat loss, climate change, and photopollution pose significant threats to these bioluminescent organisms. Conservation measures, interdisciplinary collaborations, and responsible lighting practices are crucial for their survival. Future research should focus on identifying endemic species, studying environmental factors influencing bioluminescence, and developing effective conservation strategies. Through interdisciplinary collaborations, advanced technologies, and increased funding, Brazil can unravel the mysteries of its bioluminescent biodiversity, drive scientific advancements, and ensure the long-term preservation of these captivating organisms., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

Hearing impairments and dental anomalies are found in many genetic syndromes. Otodental syndrome is a rare combination of hearing loss and the presence of a pathognomonic dental phenotype known as globodontia, in which the tooth exhibits an abnormal globe shape. There is no histologic evidence of structural anomalies in the enamel, dentin, or pulp. This report describes the case of a 12-year-old boy who had hearing loss and 2 supernumerary globe-shaped teeth in the sites of the permanent maxillary central incisors. The diagnosis of otodental syndrome was established based on the clinical, radiographic, and histologic features, but other conditions, including dens evaginatus, talon cusp, dens invaginatus, and compound odontoma, should be included in the differential diagnosis. Dental treatment consisted of the extraction of both anomalous teeth, allowing spontaneous eruption of the impacted permanent central incisors. Early diagnosis of otodental syndrome permits a multidisciplinary approach to prevent other pathologic conditions, reduce functional damage, and avoid social problems., Competing Interests: No conflicts of interest reported.

In this review, we discuss the cutting-edge developments in mass spectrometry proteomics and metabolomics that have brought improvements for the identification of new disease-based biomarkers. A special focus is placed on psychiatric disorders, for example, schizophrenia, because they are considered to be not a single disease entity but rather a spectrum of disorders with many overlapping symptoms. This review includes descriptions of various types of commonly used mass spectrometry platforms for biomarker research, as well as complementary techniques to maximize data coverage, reduce sample heterogeneity, and work around potentially confounding factors. Finally, we summarize the different statistical methods that can be used for improving data quality to aid in reliability and interpretation of proteomics findings, as well as to enhance their translatability into clinical use and generalizability to new data sets.

This study aimed to investigate whether modifying the pre-gestational lipid content could mitigate metabolic damage in offspring from dams exposed to a high-fat (HF) diet before conception and during pregnancy and lactation, with a focus on sex-specific outcomes. Specific effects of maternal normolipidic diets on offspring were also assessed. Female Wistar rats received control (C) or HF diets before conception. During pregnancy and lactation, females were distributed in five groups: C-C, HF-HF, HF-C, HF-saturated (HF-S) or HF-polyunsaturated n-3 group (HF-P). Saturated and PUFA n-3 diets were normolipidic. In 21-day-old offspring, corporal parameters, adiposity, serum metabolites, OGTT, liver phenotype, and miR-34a-5p hepatic expression were determined. Pre-gestational HF diet impaired glycemic response in females, independent of any change in body weight. Female and male offspring from dams continuously exposed to HF diet exhibited hyperglycemia, increased adiposity, and disrupted serum lipid profiles. Male offspring showed increased hepatic fat accumulation and miR-34a-5p expression. Shifting maternal dietary lipid content to normolipidic diets restored offspring's phenotype; however, decreased SIRT1, IRβ and IRS1 expression in offspring from dams exposed to HF diet before conception suggested early indicators of glucose metabolism damage. Our findings indicated a pronounced metabolic impact on males. In conclusion, glucose tolerance impairment in females before conception disturbed intrauterine environment, influencing in offspring's phenotype. Modifying maternal dietary lipid content mitigated effects of pre-gestational HF diet exposure on young offspring. Nevertheless, decreased hepatic levels of critical insulin signaling proteins indicated that independently of the maternal diet, pre-existing HF diet-induced glucose intolerance before conception may adversely program the offspring's phenotype., 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 Inc. All rights reserved.)

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62-62.23 vs. Mild 3.91 pg/mL CI 1.5-10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4-4.4 vs. Non-Pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases., Competing Interests: none., (© 2024 The Authors.)

Study Design: Using a cross-sectional design, we extracted sociodemographic and clinical data from 488 Spinal Cord Injury (SCI) patients during their initial assessment before receiving intensive rehabilitation treatment., Objectives: The primary objectives of this study were to ascertain the prevalence of cognitive impairment in the study sample and specify the key clinical and demographic predictors of cognitive functioning in SCI patients., Setting: Lucy Montoro Rehabilitation Institute (LMRI), University of Sao Paulo, Sao Paulo, Brazil., Methods: We utilized independent univariate and multivariate regression models with the Montreal Cognitive Assessment (MoCA) scale, adapted for individuals with visual impairment. Moreover, we consider scores from the execution tasks (visuospatial/executive) as the dependent variable., Results: Our findings demonstrate that approximately 80% of the evaluated study sample exhibited cognitive impairment. Through the multivariate regression models, we show that several factors, including age, education, depression levels, and the use of analgesics and/or opioids, are significant predictors of total cognitive scores. These factors are independent of the clinical features associated with SCI, such as age, sex, education, and time since the injury., Conclusions: The results indicate a high prevalence of significant cognitive impairment within the sample, with age, education, depression levels, and the use of analgesics and/or opioids emerging as the primary predictors of total cognitive scores, independent of the clinical features correlated to SCI. These findings hold significant implications for both clinical research and practice, offering valuable guidance for comprehensive management throughout hospitalization and rehabilitation., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Introduction: The species Lantana camara is used in folk medicine. The biological activities of this medicinal plant are attributable to the presence of various derivatives of triterpenoids and phenolic compounds present in its preparations, indicating excellent economic potential., Objective: In this study, the operational conditions of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) were optimized using Box-Behnken design to improve the total phenolic content (TPC) recovered in hydroethanolic extracts of L. camara leaves., Material and Methods: The TPC, total flavonoid content (TFC), and antioxidant activities of the hydroalcoholic extracts of L. camara, prepared by UAE and MAE under the optimized extraction conditions, were compared with those of the extracts obtained by conventional extraction methods., Results: Under the optimal conditions, the extracts obtained by UAE (35% ethanol, 25 min, and a solvent-to-solid ratio of 60:1 mL/g) and by MAE (53% ethanol, 15 min, and 300 W) provided high yields of 32.50% and 38.61% and TPC values of 102.89 and 109.83 mg GAE/g DW, respectively. The MAE extract showed the best results with respect to TPC, TFC, and antioxidant activities, followed by extracts obtained by UAE, Soxhlet extraction, decoction, maceration, and infusion, in that order., Conclusion: The results obtained indicate that L. camara may be used as an important source of antioxidant phenolic compounds to obtain products with high biological and economic potential, especially when the extraction process is performed under appropriate conditions using MAE and/or UAE, employing environmentally friendly solvents such as water and ethanol., (© 2024 John Wiley & Sons Ltd.)

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to a complex family of RNA-binding proteins that are essential to control alternative splicing, mRNA trafficking, synaptic plasticity, stress granule formation, cell cycle regulation, and axonal transport. Over the past decade, hnRNPs have been associated with different brain disorders such as Alzheimer's disease, multiple sclerosis, and schizophrenia. Given their essential role in maintaining cell function and integrity, it is not surprising that dysregulated hnRNP levels lead to neurological implications. This review aims to explore the primary functions of hnRNPs in neurons, oligodendrocytes, microglia, and astrocytes, and their roles in brain disorders. We also discuss proteomics and other technologies and their potential for studying and evaluating hnRNPs in brain disorders, including the discovery of new therapeutic targets and possible pharmacological interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the context of neglected diseases, tegumentary leishmaniasis (TL) presents an emerging and re-emerging character in the national territory and in the world. The treatment of TL has limitations, such as intravenous administration route, high toxicity, and high treatment costs. Thus, several researchers work on new therapeutic strategies to improve the effectiveness of the treatment of leishmaniasis. In this light, the present study used a topical formulation, containing 8-hydroquinoline (8-HQN), for the treatment of Balb/c mice infected with L. amazonensis. After the treatment, the mean diameter of the lesion was measured, as well as the parasite load in organs and immunological parameters associated with the treatment. The results showed that the animals treated with 8-HQN 5%, when compared to controls, showed a reduction in the mean diameter of the lesion and in the parasite load. The animals treated with the ointment showed a type 1 cellular immune response profile associated with the production of cytokines such as INF-γ and TNF-α. In addition, the treatment did not demonstrate toxicity to mice. Therefore, the topical formulation containing 8-HQN 5% is a promising candidate in the topical treatment and could be considered, in the future, as an alternative for the treatment of TL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Low-carbohydrate and high-fat diet (LCHF) models have been widely explored as alternatives for treating obesity and promoting weight loss. Their effect is attributed to the change in energy substrate that stimulates ketogenic pathways that can metabolically overload the liver. However, little has been studied about the impact of lipid sources prioritized in the LCHF diet., Objectives: This study aims to evaluate the impact of different fat sources in the LCHF diet on markers of liver injury, oxidative stress, and epigenetics in obesity., Methods: Adult male mice were initially induced to obesity by a high-fat and high-sugar diet for 10 wk. Subsequently, they underwent a weight-loss treatment intervention involving an LCHF diet with various sources of fats, including saturated, omega-3 (ω-3) (n-3), omega-6 (ω-6) (n-6), and omega-9 (ω-9) (n-9). At the end of the treatment, markers of liver injury, oxidative stress, and epigenetics were evaluated., Results: The LCHF diet was effective in inducing weight loss. However, unsaturated lipid sources (omegas) exhibited superior outcomes. Specifically, the ω-9 group displayed diminished oxidative stress concentrations and decreased markers of liver injury. The ω-3 group demonstrated efficacy in modulating epigenetic markers, thereby reducing oxidative stress, mutagenicity, and markers of liver injury. Correlation tests demonstrated that there was an interaction between the activity of antioxidants and epigenetic enzymes., Conclusions: Our results suggest that LCHF diets associated with ω-3 and ω-9 have the potential for weight loss and liver health recovery in obesity through antioxidant and epigenetic mechanisms., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy., Methods: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat., Results: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups., Conclusion: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC 50  < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔG bind ) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro., (© 2024. The Author(s).)

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections., Competing Interests: Declaration of interests M.S.D. is a consultant or advisor for Inbios, Ocugen, Vir Biotechnology, Topspin Therapeutics, Moderna, Merck, and Immunome. The Diamond laboratory has received funding support from Emergent BioSolutions, Moderna, and Vir Biotechnology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To summarize the scientific evidence on the prevalence of maxillary sinus hypoplasia (MSH) and associated anatomical variations as assessed by computed tomography scans., Study Design: This PROSPERO-registered systematic review followed the recommendations of the PRISMA guidelines. Search algorithms were constructed for each of the six databases and gray literature. After screening the references (Rayyan ® ), the extracted data were meta-analyzed according to a random-effects model. The joanna briggs critical appraisal tool assessed the methodological quality of the included studies. The GRADE approach was used to estimate the certainty of the evidence., Results: From a total of 2781 studies screened, 22 were considered for four meta-analysis. The prevalence of MSH in 7358 patients was 5.65% (CI95% = 4.07-7.47%) with significant heterogeneity between studies (p < 0.001, I 2  = 89.30%). MSH was identified in 295 patients, of whom 82.38% (CI95% = 75.82-88.09%) had unilateral hypoplasia and 17.62% (CI95% = 11.91-24.18%) bilateral hypoplasia with moderate heterogeneity between studies (p < 0.0503, I 2  = 42.87%). The prevalence of MSH in 9998 maxillary sinuses was 3.77% (95% CI = 2.44-5.38%), with significant heterogeneity between studies (p < 0.001, I 2  = 92.84%). Hypoplastic/aplastic uncinate process, concha bullosa and paradoxical concha were the most reported anatomical variations. The studies presented a low-moderate methodological quality. The certainty of the evidence was very low to moderate., Conclusion: The prevalence of maxillary sinus hypoplasia observed was 5.65%, with most cases being unilateral., (© 2023. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome&#95;App/ ) to enrich and expand this knowledgebase., (© 2024. The Author(s).)

(1) Background: Species of the genus Cymbopogon and its essential oil are known for their antioxidant and hypoglycemic effects. This study aimed to investigate the impact of the essential oil of Cymbopogon flexuosus (EOCF), and its major component, citral, on glycemic, lipid, antioxidant parameters, and oxidative stress in a type 1 diabetes (DM1) rat model. (2) Methods: Initially, EOCF was analyzed by Gas chromatography-mass spectrometry (GC-MS) and the antioxidant activity of EOCF and citral was evaluated. Next, male Wistar rats (3 months old, 200-250 g) induced with DM1 using Streptozotocin (STZ) were divided into four groups: negative control supplemented with an 80% Tween solution, two groups of animals supplemented with EOCF (32 mg/kg and 64 mg/kg) and with citral (32 mg/kg), and treated for 14 days. Measurements of blood glucose levels and body weight were taken; after euthanasia, biochemical markers, including lipid profile, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. (3) Results: The predominant compounds in EOCF were α-citral (53.21%) and neral (19.42%), constituting 72.63% citral. EOCF showed good antioxidant activity, significantly greater than citral. EOCF supplementation demonstrated a mitigating effect on glycemic, lipid, and hepatic abnormalities induced by DM1. (4) Conclusions: EOCF emerges as a promising therapeutic option for the management of DM1.

Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass-spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK-801 and antipsychotics in the human brain., (© 2024 International Society for Neurochemistry.)

The investigation of neurodegenerative diseases advanced significantly with the advent of cell-reprogramming technology, leading to the creation of new models of human illness. These models, derived from induced pluripotent stem cells (iPSCs), facilitate the study of sporadic as well as hereditary diseases and provide a comprehensive understanding of the molecular mechanisms involved with neurodegeneration. Through proteomics, a quantitative tool capable of identifying thousands of proteins from small sample volumes, researchers have attempted to identify disease mechanisms by detecting differentially expressed proteins and proteoforms in disease models, biofluids, and postmortem brain tissue. The integration of these two technologies allows for the identification of novel pathological targets within the realm of neurodegenerative diseases. Here, we highlight studies from the past 5 years on the contributions of iPSCs within neuroproteomic investigations, which uncover the molecular mechanisms behind these illnesses., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background Suicide is one of the leading global causes of death. Behavior patterns from suicide ideation to completion are complex, involving multiple risk factors. Advances in technologies and large-scale bioinformatic tools are changing how we approach biomedical problems. The "omics" field may provide new knowledge about suicidal behavior to improve identification of relevant biological pathways associated with suicidal behavior. Methods We reviewed transcriptomic, proteomic, and metabolomic studies conducted in blood and post-mortem brains from individuals who experienced suicide or suicidal behavior. Omics data were combined using systems biology in silico, aiming at identifying major biological mechanisms and key molecules associated with suicide. Results Post-mortem samples of suicide completers indicate major dysregulations in pathways associated with glial cells (astrocytes and microglia), neurotransmission (GABAergic and glutamatergic systems), neuroplasticity and cell survivor, immune responses and energy homeostasis. In the periphery, studies found alterations in molecules involved in immune responses, polyamines, lipid transport, energy homeostasis, and amino and nucleic acid metabolism. Limitations We included only exploratory, non-hypothesis-driven studies; most studies only included one brain region and whole tissue analysis, and focused on suicide completers who were white males with almost none confounding factors. Conclusions We can highlight the importance of synaptic function, especially the balance between the inhibitory and excitatory synapses, and mechanisms associated with neuroplasticity, common pathways associated with psychiatric disorders. However, some of the pathways highlighted in this review, such as transcriptional factors associated with RNA splicing, formation of cortical connections, and gliogenesis, point to mechanisms that still need to be explored., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To systematically evaluate randomised controlled trials (RCTs) on whether adjuvant application of antimicrobial photodynamic therapy (aPDT) through the technique of irradiation in the external region of the periodontal pocket with optic-fibre tip offers benefits to scaling and root planning (SRP)., Methods: Five databases were searched by two independent reviewers according to pre-specified eligibility criteria up to April 2023. No restrictions regarding date of publication, language and minimum follow-up period were imposed. The Cochrane Collaboration's Risk of Bias tool (RoB 2.0) was used for quality appraisal and Grading of Recommendations, Assessment, Development and Evaluation for assessing the certainty of evidence., Results: A total of 1388 publications were identified and reviewed for eligibility. Four of them fulfilled the inclusion criteria. The sample consisted of a total of 83 patients with periodontitis. In these, 330 periodontal sites were evaluated. The clinical findings of the majority of the included studies demonstrated that patients who received the association of aPDT + RAR with the protocol evaluated here, obtained clinical results similar to patients who received only the SRP alone. In none of the evaluated RCTs, clinical advantages were observed that would categorise this aPDT protocol as superior to conventional treatment., Conclusion: Applying aPDT after SRP with external irradiation of the periodontal pocket does not seem to result in any clinical benefit compared to the use of SRP alone in patients with periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to assess the feasibility and safety of using a bipolar radiofrequency track cautery device during percutaneous image-guided abdominal biopsy procedures in at-risk patients., Methods: Forty-two patients (26-79 years old; female 44%) with at least one bleeding risk factor who underwent an abdominal image-guided (CT or US) biopsy and intended bipolar radiofrequency track cautery (BRTC) were retrospectively studied. An 18G radiofrequency electrode was inserted through a 17G biopsy introducer needle immediately following coaxial 18G core biopsy, to cauterize the biopsy track using temperature control. Bleeding risk factors, technical success, and adverse events were recorded., Results: BRTC was technically successful in 41/42 (98%) of procedures; in one patient, the introducer needle retracted from the liver due to respiratory motion prior to BRTC. BRTC following percutaneous biopsy was applied during 41 abdominal biopsy procedures (renal mass = 12, renal parenchyma = 10, liver mass = 9, liver parenchyma = 5, splenic mass or parenchyma = 4, gastrohepatic mass = 1). All patients had one or more of the following risk factors: high-risk organ (spleen or renal parenchyma), hypervascular mass, elevated prothrombin time, renal insufficiency, thrombocytopenia, recent anticoagulation or anticoagulation not withheld for recommended interval, cirrhosis, intraprocedural hypertension, brisk back bleeding observed from the introducer needle, or subcapsular tumor location. No severe adverse events (grade 3 or higher) occurred. Two (2/41, 5%) mild (grade 1) bleeding events did not cause symptoms or require intervention., Conclusion: Bipolar radiofrequency track cautery was feasible and safe during percutaneous image-guided abdominal biopsy procedures. IRB approval: MBG 2022P002277., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The demand for organic vegetables is increasing worldwide, which has led to the growth of organic agriculture. However, information on chemical composition and antioxidant activity in vegetables grown organically under controlled conditions remains uncertain. For this study, 3 vegetables widely consumed in Brazil were cultivated in controlled organic and conventional cultivation systems: lettuce, coriander and tomato. Their chemical composition, mineral concentration, phenolic compound content, flavonoids and antioxidant activity (AA) were evaluated. The analyses of chemical and mineral composition revealed differences between the cultivation systems. Organic lettuce presented higher content of ashes, calcium and potassium. A higher content of phenolic compounds and flavonoids was observed in most organic vegetables. Using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, the organic tomato exhibited higher AA compared to conventional, while the ferric-reducing antioxidant power (FRAP) method showed higher AA for organic coriander and tomato than theirs conventional version. The correlation between bioactive compounds and AA was positive, higher and stronger for organic vegetables, considering phenolic compounds (including flavonoids) and DPPH or FRAP antioxidant activity. Principal Component Analysis (PCA) disclosed that organic lettuce and coriander were grouped according bioactive components. In general, organic vegetables showed better results for bioactive compounds and antioxidant activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: Professional development is important to academic radiologists. We developed, implemented, and assessed an internal professional development lecture series focusing on the non-interpretative themes of Quality, Research, Education, and Wellness (QREW)., Materials and Methods: The faculty of a 29-member abdominal radiology division at an academic hospital were invited to deliver 1-hour virtual lectures on noninterpretative topics to division colleagues. Topics were curated by division leadership based on the perceived needs of faculty. Anonymous feedback was collected from attendees for quality improvement purposes and analyzed using descriptive statistics and Fisher's exact test., Results: Over 17 months, 13 QREW lectures were delivered. In total, 91 feedback forms were completed by faculty (mean 7 forms, range 2-12 per session). Of these, 57 responses (63%) were by those <7 years post training ("junior faculty"), 34 responses (37%) by those ≥ 7 years from training ("senior faculty"). Most respondents reported low levels of prior instruction (80/90, 89%) and personal knowledge (49/91, 54%) on topics. Compared to senior faculty, a greater proportion of junior faculty reported less prior instruction (73% vs 98%, P < 0.001) and less personal knowledge (32% vs 65%, P < 0.01). Most respondents agreed or strongly agreed that the topics were important to their clinical practice (87/90, 97%), professional development (86/90, 96%), and personal well-being (82/91, 90%). Faculty identified the QREW program as a major contributor to their professional development., Conclusion: A noninterpretative professional development lecture series delivered by radiology faculty in a virtual, interactive format is feasible and effective, particularly for junior faculty., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae . transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.

Schizophrenia is a severe psychiatric disorder of neurodevelopmental origin that affects around 1% of the world's population. Proteomic studies and other approaches have provided evidence of compromised cellular processes in the disorder, including mitochondrial function. Most of the studies so far have been conducted on postmortem brain tissue from patients, and therefore, do not allow the evaluation of the neurodevelopmental aspect of the disorder. To circumvent that, we studied the mitochondrial and nuclear proteomes of neural stem cells (NSCs) and neurons derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients versus healthy controls to assess possible alterations related to energy metabolism and mitochondrial function during neurodevelopment in the disorder. Our results revealed differentially expressed proteins in pathways related to mitochondrial function, cell cycle control, DNA repair and neuritogenesis and their possible implication in key process of neurodevelopment, such as neuronal differentiation and axonal guidance signaling. Moreover, functional analysis of NSCs revealed alterations in mitochondrial oxygen consumption in schizophrenia-derived cells and a tendency of higher levels of intracellular reactive oxygen species (ROS). Hence, this study shows evidence that alterations in important cellular processes are present during neurodevelopment and could be involved with the establishment of schizophrenia, as well as the phenotypic traits observed in adult patients. Neural stem cells (NSCs) and neurons were derived from induced pluripotent stem cells (iPSCs) from schizophrenia patients and controls. Proteomic analyses were performed on the enriched mitochondrial and nuclear fractions of NSCs and neurons. Whole-cell proteomic analysis was also performed in neurons. Our results revealed alteration in proteins related to mitochondrial function, cell cycle control, among others. We also performed energy pathway analysis and reactive oxygen species (ROS) analysis of NSCs, which revealed alterations in mitochondrial oxygen consumption and a tendency of higher levels of intracellular ROS in schizophrenia-derived cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis?, Material and Methods: The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting., Results: A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak., Conclusion: In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions.

Tegumentary leishmaniasis (TL) is the main clinical manifestation of leishmaniasis, and it can cause the infected hosts to self-healing cutaneous lesions until mutilating scars in mucosal membranes, particularly in the nose and throat. The treatment against disease presents problems, and the diagnosis is hampered by variable sensitivity and/or specificity of the tests. In this context, the development of prophylactic vaccines could be considered as a strategy to control the disease. Previously, we showed that the recombinant LiHyp1 protein plus adjuvant protected mice from infection with Leishmania infantum, which causes visceral leishmaniasis. In the present study, we tested whether rLiHyp1 could induce protection against infection with L. amazonensis, a parasite species able to cause TL. We immunized BALB/c mice with rLiHyp1 plus saponin (rLiHyp1/S) or incorporated in micelles (rLiHyp1/M) as adjuvants and performed parasitological and immunological evaluations before and after infection. Results showed that after in vitro stimulation from spleen cell cultures using rLiHyp1 or a Leishmania antigenic extract (SLA), rLiHyp1/S and rLiHyp1/M groups developed a Th1-type immune response, which was characterized by high levels of IFN-γ, IL-2, TNF-α and IL-12 cytokines, nitrite, and IgG2a isotype antibodies when compared to values found in the control (saline, saponin, micelles alone) groups, which showed higher levels of anti-SLA IL-4, IL-10, and IgG1 antibodies before and after challenge. In addition, mice receiving rLiHyp1/S or rLiHyp1/M presented significant reductions in the lesion average diameter and parasite load in the infected tissue and internal organs. Blood samples were collected from healthy subjects and TL patients to obtain PBMC cultures, which were in vitro stimulated with rLiHyp1 or SLA, and results showed higher lymphoproliferation and IFN-γ production after stimulus using rLiHyp1, as compared to values found using SLA. These results suggest that rLiHyp1 plus adjuvant was protective against experimental TL and could also be considered for future studies as a vaccine candidate against human disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This pilot study aimed to evaluate the mutagenic effects in cells of the oral mucosa after exposure to two different cone beam computed tomography (CBCT)., Methods: Eighteen adults were submitted to the different CBCT (Carestream CS8100 3D and I-CAT). The cells were collected immediately before the CBCT exposure and 10 days later, when the material was placed on a slide and stained using the Feulgen/Fast Green technique. Microscopic analysis counted micronuclei and other nuclear alterations, which are indicative of cytotoxicity such as pyknosis, karyolysis, karyorrhexis, and binucletion. 2000 cells were analyzed. The statistical analysis was performed with the Wilcoxon Signed-Rank test to compare the frequency of cellular alterations, and the Mann-Whitney U test to compare different CBCTs, both with a significance level of 5%., Results: There was no statistically significant difference in the micronucleated cell count before and after the exposition to the ionizing radiation from I-CAT (p = .298) and CS8100 3D (p = .203) A significate increase of pyknosis (p < .001), karyolysis (p < .001), karyorrhexis (p < .001), and binucletion (p < .001) were noted on I-CAT CBCT. There was no statistically significant difference in cellular alterations in CS8100 3D CBCT., Conclusion: Despite the increase in micronuclei after exposure, this study indicates that there is no evidence of genotoxicity. On the other hand, the I-CAT CBCT produced cytotoxic effects., (© 2023 Wiley Periodicals LLC.)

Modeling time series has been a particularly challenging aspect due to the need for constant adjustments in a rapidly changing environment, data uncertainty, dependencies between variables, volatile fluctuations, and the need to identify ideal hyperparameters. The present study presents a Framework capable of making projections from time series related to cases and deaths by COVID-19 in the Amazonian state of Pará, in Brazil. For the first time, deep learning models such as TCN, TRANSFORMER, TFT, N-BEATS, and N-HiTS were assessed for this purpose. The ARIMA statistical model was also used in post-processing for residual adjustment and short-term smoothing of the generated forecasts. The Framework generates probabilistic forecasts, with multivariate support, considering the following variables: daily cases per day of the first symptom, cases published daily, the occurrence of deaths, deaths published daily, and percentage of daily vaccination. The generated predictions are statistically evaluated by determining the best model for 7-day moving average projections using evaluating metrics such as MSE, RMSE, MAPE, sMAPE, r2, Coefficient of Variation, and residual analysis. As a result, the generated projections showed an average error of 5.4% for Cases Publication, 8.0% for Cases Symptoms, 11.12% for Deaths Publication, and 4.6% for Deaths Occurrence, with the N-HiTS and N-BEATS models obtaining better results. In general terms, the use of deep learning models to predict cases and deaths from COVID-19 has proven to be a valuable practice for analyzing the spread of the virus, which allows health managers to better understand and respond to this kind of pandemic outbreak., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 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.)

Objective: The objective of this study was to evaluate cytogenetic changes in individuals submitted to oral human immunodeficiency virus pre-exposure prophylaxis use through the micronucleus test in oral mucosa., Methods: This study consisted of 37 individuals, of whom 17 comprised the pre-exposure prophylaxis group and 20 comprised the control group. A total of 2,000 cells per slide were analyzed for the determination of micronuclei, binucleation, nuclear buds, and cytotoxicity parameters: pyknosis, karyolysis, and karyorrhexis (KR), in a double-blind manner. The repair index was also evaluated in this setting., Results: In the mutagenicity parameters, the pre-exposure prophylaxis group showed increased frequencies of micronuclei (p=0.0001), binucleation (p=0.001), and nuclear buds (p=0.07). Regarding the cytotoxicity parameters, there was an increase with a statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.001). Additionally, the repair system efficiency decreased in the pre-exposure prophylaxis group., Conclusion: These results indicate that individuals undergoing pre-exposure prophylaxis use have geno- and cytotoxicity in oral mucosal cells.

The aim of this systematic review was to evaluate published papers regarding the micronucleus assay in oral mucosal cells of patients undergoing orthodontic therapy (OT). A search of the scientific literature was made in the PubMed, Scopus, and Web of Science databases for all data published until November, 2021 using the combination of the following keywords: "fixed orthodontic therapy," "genetic damage", "DNA damage," "genotoxicity", "mutagenicity", "buccal cells", "oral mucosa cells," and "micronucleus assay". The systematic review was designed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Nine studies were retrieved. Some authors demonstrated that OT induces cytogenetic damage in oral mucosal cells. Out of the nine studies included, two were classified as strong, five as moderate, and two as weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed no relationship between mutagenicity in oral cells and OT in different months of treatment. At one month, the SMD = 0.65 and p = 0.08; after three months of OT, the SMD = 1.21 and p = 0.07; and after six months of OT, the SMD = 0.56 and p = 0.11. In the analyzed months of OT, I2 values were >75%, indicating high heterogeneity. In summary, this review was not able to demonstrate that OT induces genetic damage in oral cells. The study is important for the protection of patients undergoing fixed OT, given that mutagenesis participates in the multi-step process of carcinogenesis.

The present study aimed to investigate the effects of combined physical training (CPT) on social skills and physical fitness (PF) in children with ASD. Sixteen children with autism (age 6-10 years) were randomly assigned into two groups: CPT and control. The CPT group participated in a program involving ball game, rhythmic movements, and resistance training for eight weeks (three sessions per week). PF and behavior profile were assessed before and after training. CPT program had a significant effect on indicators of social skills such as stereotypic behavior and communication, as well as PF such as handgrip strength, upper and lower body power, flexibility, balance, and agility (P < 0.05). CPT in autistic children can improve indicators of social skills and PF., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mitigating the substantial public health impact of concussion is a particularly difficult challenge. This is partly because concussion is a highly prevalent condition, and diagnosis is predominantly symptom-based. Much of contemporary concussion management relies on symptom interpretation and accurate reporting by patients. These types of reports may be influenced by a variety of factors for each individual, such as preexisting mental health conditions, headache disorders, and sleep conditions, among other factors. This can all be contributory to non-specific and potentially misleading clinical manifestations in the aftermath of a concussion. This review aimed to conduct an examination of the existing literature on emerging approaches for objectively evaluating potential concussion, as well as to highlight current gaps in understanding where further research is necessary. Objective assessments of visual and ocular motor concussion symptoms, specialized imaging techniques, and tissue-based concentrations of specific biomarkers have all shown promise for specifically characterizing diffuse brain injuries, and will be important to the future of concussion diagnosis and management. The consolidation of these approaches into a comprehensive examination progression will be the next horizon for increased precision in concussion diagnosis and treatment.