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1.
PeerJ ; 12: e17347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006036

RESUMO

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.


Assuntos
Exercício de Aquecimento , Humanos , Masculino , Exercício de Aquecimento/fisiologia , Adulto , Treinamento Resistido/métodos , Adulto Jovem , Força Muscular/fisiologia , Desempenho Atlético/fisiologia
2.
JHEP Rep ; 6(7): 101075, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961853

RESUMO

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

3.
Brain Behav Immun Health ; 39: 100805, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39022627

RESUMO

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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39028452

RESUMO

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.

5.
Gen Dent ; 72(4): 31-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38905602

RESUMO

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.


Assuntos
Incisivo , Humanos , Masculino , Criança , Incisivo/anormalidades , Dente Supranumerário/complicações , Dente Supranumerário/diagnóstico por imagem , Dente Supranumerário/cirurgia , Anormalidades Dentárias/diagnóstico , Diagnóstico Diferencial , Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Fácies
6.
Photochem Photobiol Sci ; 23(7): 1373-1392, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733516

RESUMO

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.


Assuntos
Biodiversidade , Brasil , Animais , Luminescência , Dinoflagellida , Vaga-Lumes , Cnidários , Ecossistema
7.
Neuroscience ; 551: 153-165, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38821242

RESUMO

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.


Assuntos
Coração , Pulmão , Neurônios Motores , Nervo Vago , Animais , Neurônios Motores/fisiologia , Masculino , Coração/fisiologia , Coração/inervação , Pulmão/fisiologia , Pulmão/inervação , Nervo Vago/fisiologia , Bulbo/fisiologia , Bulbo/citologia , Bulbo/metabolismo , Potenciais de Ação/fisiologia , Ratos Sprague-Dawley , Ratos , Técnicas de Patch-Clamp
8.
J Surg Oncol ; 129(8): 1413-1419, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664921

RESUMO

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Cefazolina , Metronidazol , Pancreaticoduodenectomia , Combinação Piperacilina e Tazobactam , Infecção da Ferida Cirúrgica , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Antibioticoprofilaxia/métodos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/administração & dosagem , Idoso , Pessoa de Meia-Idade , Cefazolina/uso terapêutico , Cefazolina/administração & dosagem , Cefoxitina/administração & dosagem , Cefoxitina/uso terapêutico , Neoplasias Pancreáticas/cirurgia , Seguimentos , Prognóstico
9.
Spinal Cord ; 62(6): 336-342, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609569

RESUMO

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.


Assuntos
Disfunção Cognitiva , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Brasil/epidemiologia , Prevalência , Adulto Jovem , Idoso , Fatores Etários , Depressão/epidemiologia , Depressão/etiologia , Depressão/diagnóstico , Escolaridade
10.
Eur J Pharm Biopharm ; 199: 114306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679213

RESUMO

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.


Assuntos
Leishmaniose Cutânea , Camundongos Endogâmicos BALB C , Oxiquinolina , Carga Parasitária , Animais , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Camundongos , Oxiquinolina/administração & dosagem , Oxiquinolina/química , Feminino , Administração Tópica , Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Citocinas/metabolismo , Pomadas , Interferon gama , Modelos Animais de Doenças
11.
Sci Rep ; 14(1): 8991, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637583

RESUMO

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 IC50 < 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 (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.


Assuntos
COVID-19 , Proteases 3C de Coronavírus , Peptidomiméticos , Humanos , SARS-CoV-2/metabolismo , Peptidomiméticos/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Aminoácidos , Simulação de Dinâmica Molecular , Antivirais/farmacologia , Antivirais/química
12.
Rev Assoc Med Bras (1992) ; 70(3): e20231167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656003

RESUMO

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.


Assuntos
Resistência à Insulina , Janus Quinases , Ratos Wistar , Transdução de Sinais , Animais , Feminino , Gravidez , Transdução de Sinais/efeitos dos fármacos , Resistência à Insulina/fisiologia , Janus Quinases/metabolismo , Ácidos Graxos/análise , Gorduras na Dieta/farmacologia , Gorduras na Dieta/efeitos adversos , Feto/efeitos dos fármacos , Imuno-Histoquímica , Fator de Transcrição STAT3/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Ratos , Olho/embriologia , Olho/efeitos dos fármacos
13.
J Nutr Biochem ; 129: 109639, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38583498

RESUMO

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, IRß 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.


Assuntos
Dieta Hiperlipídica , Lactação , Fígado , Fenômenos Fisiológicos da Nutrição Materna , MicroRNAs , Ratos Wistar , Animais , Feminino , Gravidez , Masculino , Fígado/metabolismo , MicroRNAs/metabolismo , Dieta Hiperlipídica/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Fenótipo , Gorduras na Dieta , Ratos , Ácidos Graxos/metabolismo
14.
Cell Host Microbe ; 32(4): 606-622.e8, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38479396

RESUMO

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.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Animais , Humanos , Febre de Chikungunya/complicações , Proteômica , Vírus Chikungunya/genética , Citocinas/metabolismo
15.
Clin EEG Neurosci ; 55(4): 496-507, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38460956

RESUMO

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.


Assuntos
Depressão , Eletroencefalografia , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Idoso , Depressão/fisiopatologia , Depressão/diagnóstico , Estudos Transversais , Encéfalo/fisiopatologia , Biomarcadores , Estudos de Coortes , Descanso/fisiologia , Adulto , Atividade Motora/fisiologia
16.
Ann Surg ; 280(1): 108-117, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38482665

RESUMO

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.


Assuntos
Hepatectomia , Laparoscopia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/métodos , Feminino , Masculino , Laparoscopia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Hepatopatias/cirurgia
18.
Life (Basel) ; 14(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38541661

RESUMO

(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.

19.
Sci Rep ; 14(1): 7375, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548777

RESUMO

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_App/ ) to enrich and expand this knowledgebase.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Proteômica , Pandemias
20.
J Nutr ; 154(5): 1517-1531, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484979

RESUMO

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.


Assuntos
Dieta com Restrição de Carboidratos , Epigênese Genética , Fígado , Camundongos Endogâmicos C57BL , Obesidade , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Obesidade/dietoterapia , Obesidade/metabolismo , Masculino , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Biomarcadores/metabolismo
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