499 research outputs found

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

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    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

    Promoting access to dental care in South London: adult patients' perspectives.

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    Objective: To evaluate patients' views on health service initiatives established to improve uptake of NHS primary dental care amongst adult patients in a socially deprived area, comparing practices with extended and regular contract capacity. Study design: Service evaluation and cross-sectional survey. Method: Questionnaire survey of patients attending a random sample of dental practices in three inner-metropolitan boroughs of south London following initiatives to improve access to dental care (across dental practices delivering regular and extended contracts for services) exploring attendance patterns and the influence and awareness of local initiatives to promote access. Results: Four hundred fifty adults across 12 dental practices completed questionnaires: 79% reported attending for routine and 21% for urgent care. Patients were most aware of banners outside practices, followed by dental advertisements in newspapers. Vouchers for free treatments were considered of the highest possible influence, followed by vouchers for reduced treatment costs and an emergency out-of-hours helpline. Awareness and influence were not aligned, and there was no evidence of difference by practice contract type whilst there were differences by age and type of attendance. Conclusion: The findings suggest that financial incentives and emergency services are considered the most influential initiatives for adult patients whose attendance patterns appear to be related to personal circumstances rather than merely being influenced by the provision of information

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

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    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

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

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    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

    Sistemas mistos de espécies florestais nativas com eucalipto em propriedades rurais familiares na região Noroeste do estado do Paraná.

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    A regeneração natural e o crescimento de espécies florestais nativas sob plantações de eucalipto têm sido relatadas em vários artigos científicos. Com manejo adequado, estes sistemas possibilitam vários serviços ambientais, como conservação e restauração da diversidade biológica e captura de gases de efeito estufa (GEE). Com base em um modelo formatado como um projeto de mecanismos de desenvolvimento limpo (MDL) florestal, produtores rurais familiares implantaram plantios mistos, com faixas de eucalipto e de espécies nativas, em áreas de pastagem degradada, em seis municípios na região noroeste do estado do Paraná. Os plantios integram o projeto “Implantação e manejo de florestas em pequenas propriedades no estado do Paraná”, coordenado pelo Programa Paraná Biodiversidade, da Secretaria de Meio Ambiente e Recursos Hídricos (SEMA), envolvendo Emater, Embrapa Florestas, IAP, SEPL e SEAB. Os sistemas visaram à recomposição da vegetação em áreas de reserva legal (RL), utilizando o eucalipto como uma espécie facilitadora e com madeira propícia a acréscimos à renda dos produtores. No presente trabalho são apresentados detalhes do projeto e resultados da produção de madeira de eucalipto, carbono sequestrado e crescimento das espécies nativas. O crescimento e produção dos eucaliptos foram avaliados em seis plantios, sendo que em dois deles foram avaliadas as nativas. A regeneração natural das espécies nativas apresentou, nestes dois plantios, 15 espécies com bom crescimento, o que deve garantir a sobrevivência das mesmas nos períodos de seca comuns na região. Os resultados indicaram que a produtividade dos eucaliptos pode ser considerada satisfatória e tem potencial para aumentar e melhorar significativamente a renda das áreas convertidas. Concluiu-se que este modelo inovador é plenamente viável, pois concilia conservação ambiental, conservação genética de espécies ameaçadas ou em risco de extinção, garantindo a sobrevivência de populações locais dessas espécies; produção econômica e inclusão social, pois gera renda com a produção florestal e venda de carbono.Capítulo 24

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

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    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

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    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
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