Produtividade de plantações de eucalipto intercaladas com espécies nativas em áreas de pastagens degradadas no noroeste do Estado do Paraná.

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Potential Immune Health Benefits of Nasal Breathing Exercise on Inflammatory Cytokines in Plasma and Peripheral Blood Mononuclear Cells

Nasal breathing (NB) is gaining popularity in exercise routines to enhance performance and overall health. However, its effects on intracellular and extracellular inflammatory cytokines, which are crucial to the immune response, remain unclear. PURPOSE: This study examined the acute responses of pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs – representing intracellular cytokines) and plasma (representing extracellular cytokines) following maximal aerobic exercise with NB. METHODS: Eleven physically healthy, sedentary men (age = 20.63±1.36, BMI=26.03±3.16 kg/m2, and VO2max = 32.60±6.46 mL/kg/min) were randomly assigned to either the NB (N=6) or the combined (control) breathing (CB, N=5) group. Both groups performed maximal aerobic exercise on a recumbent bike. Blood samples were collected in EDTA-containing vacutainer tubes before and immediately after maximal exercise to assess changes in pro- (IL-6 and IL-1β) and anti-inflammatory cytokines (IL-10) in plasma and PBMCs. PBMCs were isolated using density gradient centrifugation over Lymphoprep. RESULTS: The concentrations of intracellular cytokines were significantly lower than those of extracellular cytokines. For instance, the intracellular IL-6 was 1.92±1.55 pg/mL, while the extracellular IL-6 was 10.10±9.3 pg/mL (p=0.001). The intracellular IL-10 (2.55±1.41 pg/mL) was 7 times lower than the extracellular IL-10 (18.18±17.66 pg/mL, p=0.008), and the intracellular IL-1β was 0.80±0.82 pg/mL, whereas the extracellular IL-1β was 17.73±16.77 pg/mL (p=0.004). Although no differences were observed in IL-10 and IL-1β between the NB and CB groups following maximal exercise, the intracellular IL-6 was significantly lower (p=0.029) in the NB (1.24±1.27 pg/mL) than in the CB (2.79 ± 1.5 pg/mL) group. CONCLUSIONS: This study revealed that intracellular cytokine concentrations were lower than extracellular cytokine levels. This discrepancy likely results from the accumulation of secreted cytokines in plasma, derived from multiple cellular and tissue sources, systemic pooling, and the transient presence of cytokines within PBMCs. Additionally, the decrease in intracellular IL-1β levels following exercise with nasal breathing (NB) suggests potential immune health benefits. Further research is necessary to validate and extend these findings across various exercise modalities and diverse populations

P16-17. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV suppressive activity

International audiencen.

HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection

Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification

Background: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor. Methods: Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed. Results: Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (p < 0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worst OS (p = 0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%; p = 0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54-1.28; p = 0.40). Conclusion: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.info:eu-repo/semantics/publishedVersio

Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity.

Many amniote vertebrate species including humans can form identical twins from a single embryo, but this only occurs rarely. It has been suggested that the primitive-streak-forming embryonic region emits signals that inhibit streak formation elsewhere but the signals involved, how they are transmitted and how they act has not been elucidated. Here we show that short tracks of calcium firing activity propagate through extraembryonic tissue via gap junctions and prevent ectopic primitive streak formation in chick embryos. Cross-regulation of calcium activity and an inhibitor of primitive streak formation (Bone Morphogenetic Protein, BMP) via NF-κB and NFAT establishes a long-range BMP gradient spanning the embryo. This mechanism explains how embryos of widely different sizes can maintain positional information that determines embryo polarity. We provide evidence for similar mechanisms in two different human embryo models and in Drosophila, suggesting an ancient evolutionary origin

Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma

Introduction: Although preoperative α-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined. Methods: Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined. Results: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP 10 vs. 10 vs. 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04). Conclusion: AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC.info:eu-repo/semantics/publishedVersio

Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: an International Multi-Institutional Analysis

Introduction: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1 cm) versus narrow (< 1 cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy. Methods: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins. Results: Among 404 patients, median patient age was 66 years (IQR: 58-73). Most patients (n = 326, 80.7%) had surgical margin 1 cm margin. The majority of patients had early recurrences ( 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic ( 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin 1 cm remained protective against recurrence (HR = 0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09-4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence. Conclusion: Resection margins > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.info:eu-repo/semantics/publishedVersio

Prognostic Utility of Albumin-Bilirubin Grade for Short- and Long-Term Outcomes Following Hepatic Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis of 706 Patients

Background: The objective of the current study was to define the impact of albumin-bilirubin (ALBI) grade on short- as well as long-term outcomes among patients with intrahepatic cholangiocarcinoma (ICC). Methods: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified using an international multi-institutional database. Clinicopathologic factors including ALBI score were assessed using bivariate and multivariable analyses, as well as standard survival analyses. Results: Among 706 patients, 453 (64.2%) patients had ALBI grade 1, 231 (32.7%) ALBI grade 2, and 22 (3.1%) had ALBI grade 3. After adjusting for all competing factors, patients with ALBI grade 2/3 had higher odds of a prolonged length-of-stay (>10 days, odds ratio [OR] = 2.37, 95% confidence interval [CI]:1.47-3.80), perioperative transfusion (OR = 2.15, 95% CI:1.45-3.18) and 90-day mortality (OR = 2.50, 95% CI:1.16-5.38). Median and 5-year overall survival (OS) for the entire cohort was 41.5 months (IQR:15.7-107.8) and 39.8%, respectively. Of note, median OS incrementally worsened with increased ALBI grade: grade 1, 49.6 months (IQR:18.3-NR) vs grade 2, 29.6 months (IQR:12.6-98.4) vs grade 3, 16.9 months (IQR:6.5-32.4; P < 0.001). On multivariable analysis, higher ALBI grade remained associated with higher hazards of death (grade 2/3: hazard ratio = 1.36, 95% CI:1.04-1.78). Conclusion: The ALBI score was associated with both short- and long-term outcomes following resection for ICC and could prove a useful surrogate marker to identify patients at risk for adverse outcomes.info:eu-repo/semantics/publishedVersio