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1.
Food Chem ; 458: 140162, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38943964

RESUMO

The objective of this study was to evaluate the viability of juá pulp for fermentation by monoculture L. casei (Lc - 01) and L. acidophilus (La - 05) and co-culture (25 and 37 °C) for 72 h. Viable strain values (> 7 log CFU/g), pH reduction (below 3.7), fructose and glucose and increased of lactic acid showed that the pulp of juá served as a good matrix for fermentation. Catechin, epicatechin, epigallocatechin procyanidin B1, and gallic acid were the main phenolics that contributed to antioxidant activity. Fermentation by mono or co-culture increased or reduced the content of phenolics and antioxidant activity. Results showed that culture, time and temperature have effects in the fermentation of juá pulp. The co-cultivation of La - 05 + Lc - 01 contributed to improving the bioaccessibility of gallic acid (72.9%) of the jua pulp. Finding indicate juá pulp as a promising substrate to obtaining a new probiotic plant-based fermented beverage.

2.
Front Oncol ; 14: 1404351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919524

RESUMO

Background: The short-term complications from chimeric antigen receptor T-cell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART. Methods: We reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies. Results: Grade 3-4 cytopenia beyond 30 days occurs in 30%-40% of patients and beyond 90 days in 3%-22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%-53% of patients have IgG < 400 mg/dL, and approximately 27%-38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm. Conclusion: CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of non-relapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit-risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

3.
Artigo em Inglês | MEDLINE | ID: mdl-38928922

RESUMO

The Brazilian Amazon, a vital tropical region, faces escalating threats from human activities, agriculture, and climate change. This study aims to assess the relationship between forest fire occurrences, meteorological factors, and hospitalizations due to respiratory diseases in the Legal Amazon region from 2009 to 2019. Employing simultaneous equation models with official data, we examined the association between deforestation-induced fires and respiratory health issues. Over the studied period, the Legal Amazon region recorded a staggering 1,438,322 wildfires, with 1,218,606 (85%) occurring during August-December, known as the forest fire season. During the forest fire season, a substantial portion (566,707) of the total 1,532,228 hospital admissions for respiratory diseases were recorded in individuals aged 0-14 years and 60 years and above. A model consisting of two sets of simultaneous equations was constructed. This model illustrates the seasonal fluctuations in meteorological conditions driving human activities associated with increased forest fires. It also represents how air quality variations impact the occurrence of respiratory diseases during forest fires. This modeling approach unveiled that drier conditions, elevated temperatures, and reduced precipitation exacerbate fire incidents, impacting hospital admissions for respiratory diseases at a rate as high as 22 hospital admissions per 1000 forest fire events during the forest fire season in the Legal Amazon, 2009-2019. This research highlights the urgent need for environmental and health policies to mitigate the effects of Amazon rainforest wildfires, stressing the interplay of deforestation, climate change, and human-induced fires on respiratory health.


Assuntos
Florestas , Doenças Respiratórias , Estações do Ano , Incêndios Florestais , Humanos , Brasil/epidemiologia , Adolescente , Lactente , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/etiologia , Pré-Escolar , Recém-Nascido , Criança , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Mudança Climática , Incêndios , Adulto Jovem
4.
Microorganisms ; 12(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930581

RESUMO

Sourdough production is a complex fermentation process. Natural sourdough fermentation without standardization causes great variability in microbial communities and derived products. Starter cultures have emerged as alternatives to natural fermentation processes, which could improve bakery quality and produce bioactive compounds. This study aimed to evaluate the impacts of freeze-drying on the production and viability of sourdoughs with Lactiplantibacillus pentosus 129 (Lp) and Limosilactobacillus fermentum 139 (Lf), as well as their effects on the quality of long-fermentation bread. These strains were selected based on their better performance considering acidification and exopolysaccharide production capacity. Sourdough with Lp and Lf were propagated until the 10th day, when physicochemical and microbiological parameters were determined. The produced sourdoughs were freeze-dried, and bread samples were produced. The freeze-drying process resulted in high survival rates and few impacts on the metabolic activity of Lp and Lf until 60 days of storage. Incorporating Lp and Lf improved the microbiological and physicochemical properties of sourdough and long-fermentation breads. Tested freeze-dried sourdoughs led to reduced bread aging (higher specific volume and decreased starch retrogradation) and increased digestibility. The results show the potential of the freeze-dried sourdoughs produced with Lp and Lf as innovative strategies for standardizing production protocols for the bakery industry, especially for producing long-term fermentation bread.

5.
Foods ; 13(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38731747

RESUMO

This study evaluated the effects of acerola and guava fruit processing co-products fermented with probiotic Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 on the abundance of different intestinal bacterial groups and microbial metabolic activity during 48 h of in vitro fecal fermentation. Digested fermented fruit co-products increased the relative abundance of beneficial bacterial groups while overall decreasing or maintaining the relative abundance of non-beneficial bacterial groups, suggesting selective stimulatory effects on beneficial bacterial intestinal populations. The fermented co-products stimulated microbial metabolic activity due to decreased pH, sugar consumption, short-chain fatty acid production, phenolic compound and metabolic profile alteration, and high antioxidant capacity during fecal fermentation. Acerola and guava co-products have high nutritional value and bioactive compounds whose fermentation with probiotics improves their potential functionalities. The results show that fermented fruit co-products could induce beneficial changes in the relative abundance of several bacterial groups as well as in the metabolic activity of the human intestinal microbiota. These results highlight their potential as novel and circular candidates for use as synbiotic ingredients.

6.
Food Res Int ; 186: 114403, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729705

RESUMO

This study aimed to evaluate the functional, technological, and sensory aspects of mangaba (Hancornia speciosa Gomes) fruit pulp fermented with the probiotic Lacticaseibacillus casei 01 (LC1) during refrigerated storage (7 °C, 28 days). The effects of the fermented mangaba pulp on the modulation of the intestinal microbiota of healthy vegan adults were also assessed. Mangaba pulp allowed high viability of LC1 during storage and after simulated gastrointestinal conditions (≥7 log CFU/g). The fermented mangaba pulp showed lower pH and total soluble solids, and higher titratable acidity, and concentrations of lactic, acetic, citric, and propionic acids during storage compared to non-fermented pulp. Also, it presented a higher concentration of bioaccessible phenolics and volatiles, and improved sensory properties (yellow color, brightness, fresh appearance, and typical aroma and flavor). Fermented mangaba pulp added to in vitro cultured colonic microbiota of vegan adults decreased the pH values and concentrations of maltose, glucose, and citric acid while increasing rhamnose and phenolic contents. Fermented mangaba pulp promoted increases in the abundance of Dorea, Romboutsia, Faecalibacterium, Lachnospira, and Lachnospiraceae ND3007 genera and positively impacted the microbial diversity. Findings indicate that mangaba pulp fermented with LC1 has improved chemical composition and functionality, inducing changes in the colonic microbiota of vegan adults associated with potential benefits for human health.


Assuntos
Fermentação , Microbioma Gastrointestinal , Lacticaseibacillus casei , Humanos , Microbioma Gastrointestinal/fisiologia , Lacticaseibacillus casei/metabolismo , Adulto , Paladar , Probióticos , Masculino , Concentração de Íons de Hidrogênio , Frutas/microbiologia , Frutas/química , Colo/microbiologia , Colo/metabolismo , Adulto Jovem , Feminino
7.
JAMA Oncol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696205

RESUMO

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

8.
Blood Adv ; 8(12): 3140-3153, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38607381

RESUMO

ABSTRACT: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Robust biomarkers and a complete understanding of CAR T-cell function in the postinfusion phase remain limited. Here, we used a 37-color spectral flow cytometry panel to perform high dimensional single-cell analysis of postinfusion samples in 26 patients treated with CD28 costimulatory domain containing commercial CAR T cells for NHL and focused on computationally gated CD8+ CAR T cells. We found that the presence of postinfusion Programmed cell death protein 1 (PD-1)+ CD8+ CAR T cells at the day 14 time point highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR T cells, including PD-1+ T cell factor 1 (TCF1)+ stem-like CAR T cells and PD-1+ T-cell immunoglobulin and mucin-domain containing-3 (TIM3)+ effector-like CAR T cells that correlated with improved clinical outcomes such as response and progression-free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here, we identified robust biomarkers of response to CD28 CAR T cells and highlight the importance of PD-1 positivity in CD8+ CAR T cells after infusion in achieving CR.


Assuntos
Linfócitos T CD8-Positivos , Imunoterapia Adotiva , Linfoma não Hodgkin , Receptor de Morte Celular Programada 1 , Humanos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Imunoterapia Adotiva/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Antígenos CD19/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-38688175

RESUMO

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.


Assuntos
Anacardiaceae , Farinha , Folhas de Planta , Folhas de Planta/química , Anacardiaceae/química , Farinha/análise , Liofilização , Carboidratos/análise , Carboidratos/química , Antioxidantes/análise , Antioxidantes/química , Schinus
10.
Artigo em Inglês | MEDLINE | ID: mdl-38656040

RESUMO

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.


Assuntos
Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antivirais/sangue , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunização Secundária , Imunocompetência/imunologia , Hospedeiro Imunocomprometido/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem
11.
Orthop J Sports Med ; 12(4): 23259671241241091, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38638690

RESUMO

Background: The medial knee structures have a primary role in stabilizing valgus and rotational stress, which makes them important in assessing the ligament-injured knee globally and choosing the most adequate treatment. Purpose: To conduct a layer-by-layer dissection of the knee's anteromedial side and provide a qualitative and quantitative description of the anatomy and histology of a ligament in the anteromedial region of the knee, which we have termed the anterior oblique ligament (AOL). Also, to describe the AOL relationship with what we have termed the medial cross-a ligament complex that stabilizes the medial pivot. Study Design: Descriptive laboratory study. Methods: A total of 35 fresh-frozen knees from transfemoral amputations that were exclusively performed for vascular reasons were dissected. Structures were identified after meticulous dissection, respecting the same protocol, measured with a digital caliper rule, and histologically studied for data. Results: The AOL was found in all dissected knees, with a mean length of 31.47 ± 5.06 mm. This structure presented a ligament histology with densely organized collagen fibrils. The medial cross was represented by the superficial medial collateral ligament, AOL (anterior region), and posterior oblique ligament. Conclusion: This study demonstrated the presence of a ligament in the anteromedial region of the knee, termed the AOL. This structure was in the anterior part of a ligament complex-the medial cross. Clinical Relevance: Studying and revisiting the medial compartment can provide important information for understanding joint instability and promoting better results in ligament reconstructions.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38643029

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has significantly impacted treatment algorithms and clinical outcomes for a variety of patients with hematologic malignancies over the past decade. The field of cellular immunotherapy is currently experiencing a rapid expansion of the number of patients eligible for CAR-T therapies as approvals are being seen in earlier lines of therapy. With the expanded patients eligible for these therapies, more treatment centers will be necessary to keep up with demand. Building a cellular therapy program can be a daunting task, and therefore, we present our experience with building a clinical cellular therapy program.

13.
Nutr Res ; 125: 1-15, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428258

RESUMO

Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1ß; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway.


Assuntos
Euterpe , Fluoruracila , Mucosite , Fator 88 de Diferenciação Mieloide , Extratos Vegetais , Polifenóis , Sementes , Transdução de Sinais , Serina-Treonina Quinases TOR , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Mucosite/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes/química , Polifenóis/farmacologia , Masculino , Euterpe/química , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Fator de Transcrição RelA/metabolismo , Antioxidantes/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo
14.
Int J Clin Oncol ; 29(6): 726-734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38528294

RESUMO

BACKGROUND: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. METHODS: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. RESULTS: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). CONCLUSION: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.


Assuntos
Antígeno B7-H1 , Instabilidade de Microssatélites , Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/patologia , Antígeno B7-H1/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Prognóstico , Microambiente Tumoral , Imuno-Histoquímica
15.
Rev Bras Ortop (Sao Paulo) ; 59(1): e10-e16, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38524709

RESUMO

This article is an update on spondylolysis and spondylolisthesis in athletes, from diagnosis to treatment, based on our service experience and a literature review.

16.
Biomed Pharmacother ; 172: 116212, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364734

RESUMO

Plant polysaccharides have biological activities in the brain and those obtained from Genipa americana leaves present antioxidant and anticonvulsant effects in the mice model of pentylenetetrazole (PTZ)-induced acute seizures. This study aimed to evaluate the polysaccharide-rich extract of Genipa americana leaves (PRE-Ga) in the models of acute seizures and chronic epilepsy (kindling) induced by PTZ. In the acute seizure model, male Swiss mice (25-35 g) received PRE-Ga (1 or 9 mg/kg; intraperitoneal- IP), alone or associated with diazepam (0.01 mg/kg), 30 min before induction of seizures with PTZ (70 mg/kg; IP). In the chronic epilepsy model, seizures were induced by PTZ (40 mg/kg) 30 min after treatment and in alternated days up to 30 days and evaluated by video. Brain areas (prefrontal cortex, hippocampus, striatum) were assessed for inflammatory and oxidative stress markers. Diazepam associated to PRE-Ga (9 mg/kg; i.p.) increased the latency of seizures in acute (222.4 ± 47.57 vs. saline: 62.00 ± 4.709 s) and chronic models (6.267 ± 0.502 vs. saline: 4.067 ± 0.407 s). In hippocampus, PRE-Ga (9 mg/kg) inhibited TNF-α (105.9 ± 5.38 vs. PTZ: 133.5 ± 7.62 pmol/g) and malondialdehyde (MDA) (473.6 ± 60.51) in the chronic model. PTZ increased glial fibrillar acid proteins (GFAP) and Iba-1 in hippocampus, which was reversed by PRE-Ga (GFAP: 1.9 ± 0.23 vs PTZ: 3.1 ± 1.3 and Iba-1: 2.2 ± 0.8 vs PTZ: 3.2 ± 1.4). PRE-Ga presents neuroprotector effect in the mice model of epilepsy induced by pentylenetetrazole reducing seizures, gliosis, inflammatory cytokines and oxidative stress.


Assuntos
Epilepsia , Pentilenotetrazol , Animais , Camundongos , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/prevenção & controle , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Estresse Oxidativo , Diazepam/farmacologia , Diazepam/uso terapêutico , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
17.
PeerJ ; 12: e16656, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344296

RESUMO

The objective of this study was to test a composite of polyester resin and fiberglass in the form of an intramedullary nail for osteosynthesis of femoral fractures in calves. The methodology was established based on a previous study that used a bovine femur finite element model to simulate fractures, which were then stabilized by the same nails as proposed in this study. General anesthesia was induced in six calves followed by fracture creation via an oblique incision in the middle third of the femoral diaphysis, and osteosynthesis was immediately performed by retrograde insertion of the composite nail. Locking was achieved by drilling the bone and nail without using a jig and introducing two stainless steel screws proximal and two distal to the fracture line. Five of the six calves achieved complete fracture healing after 60 days. No signs of incompatibility or toxicity of the composite were observed. However, limitations were observed during the surgery, such as difficulty in drilling the nail and trimming the remainder portion of the nail that extended beyond the length of the bone. Small fragments produced by these maneuvers were considered irritating to soft tissues during the postoperative period. It was also found that small cracks in the nail tended to propagate in the form of longitudinal fractures. In conclusion, an intramedullary nail made of polyester resin and fiberglass (a low-cost and easy-to-acquire material) was considered biocompatible and capable of allowing bone healing of femoral fractures in young cattle. However, the development of solutions for the reported limitations is crucial prior to recommending the proposed composite for clinical use.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Vidro , Animais , Bovinos , Fixação Intramedular de Fraturas/métodos , Pinos Ortopédicos/veterinária , Poliésteres , Fraturas do Fêmur/cirurgia , Consolidação da Fratura , Fêmur/cirurgia
18.
Food Res Int ; 180: 114088, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395581

RESUMO

The present study compared pasteurized and reconstituted (from vacuum-concentrated) watermelon juices with sulfite use (∼40 mg/L) and acidification (pH = 4.2) to fresh watermelon juices. The products were evaluated for phenolics, free amino acids, carotenoids, sugars, organic acids, and alcohols by high-performance liquid chromatography-HPLC and the volatile profile by headspace-gas chromatography/mass spectrometry(HS-GC/MS). Pasteurization had no significant impact on most of the chemical components. Furthermore, it potentiated typical watermelon aromas (E,E)-2,6-nonadienal, (Z)-3-nonen-1-ol, 4-hexen-1-ol, (E,Z)-3,6-nonadien-1-ol, 6-amino-2-methyl-2-heptanol, (E)-6-nonenal, (E)-2-nonenal, pentanal, nonanal and 1-nonanol), without off-flavor compounds formation. On the other hand, the reconstituted juice showed reduced amino acids (serine, glutamine, and tryptophan), phenolics (epicatechin gallate, myricetin, and cis-resveratrol), carotenoids (lycopene, ß-carotene, and violaxanthin) and most volatile compounds. Our results showed that sulfite and acidification could maintain watermelon juice's nutritional and quality parameters after pasteurization. The vacuum concentration and reconstitution processes negatively impacted the evaluated compounds. Our findings contribute to improving thermal processes in watermelon juices for better preservation of nutrients, flavor, and bioactive compounds.


Assuntos
Citrullus , Frutas , Frutas/química , Citrullus/química , Carotenoides/análise , Fenóis/análise , Concentração de Íons de Hidrogênio , Aminoácidos/análise
19.
Food Chem ; 445: 138398, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38394903

RESUMO

A protein hydrolysate of goat viscera added with xylose, cysteine, and thiamine under different pH was used to prepare a meat flavoring. Goat viscera hydrolysate and flavoring were subjected to analysis of physicochemical characteristics, amino acid profile, sugars, fatty acids, and volatile profile. Meat aroma characteristics were initiated in the hydrolysate, in which Strecker's pyrazines and aldehydes were identified, which also had fatty acids and amino acids available for the formation of 96 volatile compounds in the flavorings via lipid manipulation, Maillard occurrence, Strecker manipulation and interactions among these means. Maillard reaction products with intense meat aroma, such as 2-methyl-3-furanthiol, 2-furfurylthiol and, bis(2-methyl-3-furyl) disulfide were isolated only in the flavoring at pH 4. In contrast, the flavoring at pH 6 showed a higher concentration than all the other compounds, providing a lower meat characteristic, but an intense sweet, fatty and goat aroma.


Assuntos
Cisteína , Reação de Maillard , Animais , Cisteína/química , Tiamina/análise , Xilose/química , Hidrolisados de Proteína , Cabras , Aromatizantes/análise , Carne/análise , Ácidos Graxos , Odorantes/análise
20.
Nutrition ; 121: 112370, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38401196

RESUMO

OBJECTIVE: The aim of this article is to investigate the effect of intermittent fasting, associated or not with coconut oil intake, on the gut-liver axis of obese rats. METHODS: A total of 50 rats were divided into five groups: control, obese, obese with intermittent fasting, obese with intermittent fasting plus coconut oil, and obese with caloric restriction. The rats were induced to obesity with a high-sugar diet for 17 wk. The respective interventions were carried out in the last 4 wk. RESULTS: The groups with intermittent fasting protocols had reduced total cholesterol (on average 54.31%), low-density lipoprotein (on average 53.39%), and triacylglycerols (on average 23.94%) versus the obese group; and the obese with intermittent fasting plus coconut oil group had the highest high-density lipoprotein compared with all groups. The obese with intermittent fasting plus coconut oil and obese with caloric restriction groups had lower metabolic load compared with the other groups. The obese group had high citric and succinic acid concentrations, which affected the hepatic tricarboxylic acid cycle, while all the interventions had reduced concentrations of these acids. No histologic changes were observed in the intestine or liver of the groups. CONCLUSION: Intermittent fasting, especially when associated with coconut oil, had effects comparable with caloric restriction in modulating the parameters of the gut-liver axis.


Assuntos
Cocos , Jejum Intermitente , Ratos , Animais , Óleo de Coco/metabolismo , Óleo de Coco/farmacologia , Dieta , Obesidade/metabolismo , Lipoproteínas HDL , Fígado/metabolismo , Óleos de Plantas/metabolismo
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