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1.
Int J Food Sci Nutr ; : 1-9, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797529

RESUMO

Over the last decades, the abandonment of traditional dietary patterns, such as the Mediterranean diet, represents an important threat for human health and environmental safeguard. The DELICIOUS project aims to promote healthy lifestyles among children and adolescents by implementing activities and tools to increase the adherence to the Mediterranean Diet with an attention to the environmental impacts of the diet. This study protocol describes the DELICIOUS project as a single-arm, uncontrolled behavioural intervention providing formal and non-formal education activities, development of new snacks and recipe reformulation, web/mobile app development, and physical activities to school children and adolescents in five European countries. The project aims to increase awareness of the nutritional benefits and the sustainability aspects of the Mediterranean Diet and to promote consumers' empowerment through an online platform for sustainable and healthy meal planning in the school canteen.

2.
Ann Behav Med ; 56(2): 137-145, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33991085

RESUMO

BACKGROUND: Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). PURPOSE: The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. METHODS: Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. RESULTS: A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p's ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p's ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. CONCLUSIONS: CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings.


Assuntos
Terapia Cognitivo-Comportamental , Leucemia Mielogênica Crônica BCR-ABL Positiva , Cognição , Fadiga/psicologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Projetos Piloto , Resultado do Tratamento
3.
Mol Phylogenet Evol ; 155: 107006, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33160038

RESUMO

The Balkan Peninsula is recognized as one of the hotspots of biodiversity in Europe. This area has shown since the Last Glacial Maximum appropriate conditions for species diversification and hybridization, which has led to the existence of numerous taxonomically unresolved entities. Here, we focus on the Western Balkans and explore the genetic structure and relationships among species belonging to the V. austriaca - V. orbiculata diploid-polyploid complex, including populations showing intermediate morphologies. A combination of nuclear markers (microsatellites), plastid DNA regions (trnH-psbA, ycf6-psbM) and ploidy level estimations using flow cytometry are employed to assess the genetic structure and evolutionary dynamics of this polyploid complex. To reconstruct the evolutionary history, an approximate Bayesian computation approach is combined with projections of the species distribution models onto the climatic scenarios of the Mid-Holocene (6 ka BP) and Last Glacial Maximum (22 ka BP). Four main groups were found: one well-established entity within the diploid level, V. dalmatica, a second diploid-tetraploid group which corresponds to V. orbiculata, a hexaploid cluster harboring V. austriaca subsp. jacquinii individuals, and an enigmatic tetraploid group. According to the molecular data obtained, this latter cluster represents an allopolyploid cryptic lineage −with V. orbiculata and V. dalmatica as putative parents− morphologically similar to V. orbiculata, but genetically more related to V. austriaca subsp. jacquinii. Veronica dalmatica and this "uncertain tetraploid" group are involved in the formation of the hexaploid taxon V. austriaca subsp. jacquinii, with the possibility of recent gene flow among different cytotypes. The present study supports a scenario of diversification from a diploid common ancestor leading to two different but interrelated lineages. The first one would correspond with the diploid V. orbiculata plus tetraploid individuals of this species arising through allo- and autopolyploidization, and the second one would involve all ploidy levels with allopolyploidization being prevalent.


Assuntos
Biodiversidade , Poliploidia , Alelos , Península Balcânica , Teorema de Bayes , DNA de Cloroplastos/genética , Diploide , Análise Discriminante , Variação Genética , Genética Populacional , Geografia , Humanos , Hibridização Genética , Repetições de Microssatélites/genética , Modelos Teóricos , Filogenia , Plastídeos/genética , Análise de Componente Principal , Veronica/genética
4.
Occup Environ Med ; 71(7): 459-65, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24652231

RESUMO

OBJECTIVE: To describe the survey methodology and initial general findings of the first Central American Survey of Working Conditions and Health. METHODS: A representative sample of 12,024 workers was interviewed at home in Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama. Questionnaire items addressed worker demographics, employment conditions, occupational risk factors and self-perceived health. RESULTS: Overall, self-employment (37%) is the most frequent type of employment, 8% of employees lack a work contract and 74% of the workforce is not covered by social security. These percentages are higher in Guatemala, Honduras and El Salvador, and lower in Costa Rica, Panama and Nicaragua. A third of the workforce works more than 48 h per week, regardless of gender; this is similar across countries. Women and men report frequent or usual exposures to high ambient temperature (16% and 25%, respectively), dangerous tools and machinery (10%, 24%), work on slippery surfaces (10%, 23%), breathing chemicals (12.1%, 18%), handling toxic substances (5%, 12.1%), heavy loads (6%, 20%) and repetitive movements (43%, 49%). Two-thirds of the workforce perceive their health as being good or very good, and slightly more than half reports having good mental health. CONCLUSIONS: The survey offers, for the first time, comparable data on the work and health status of workers in the formal and informal economy in the six Spanish-speaking Central American countries, based on representative national samples. This provides a benchmark for future monitoring of employment and working conditions across countries.


Assuntos
Países em Desenvolvimento , Emprego , Saúde , Exposição Ocupacional , Acidentes de Trabalho , Adulto , América Central , Contratos , Transtornos Traumáticos Cumulativos , Coleta de Dados , Feminino , Substâncias Perigosas , Temperatura Alta , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Previdência Social , Estresse Mecânico , Propriedades de Superfície , Inquéritos e Questionários , Carga de Trabalho
5.
Oncol Res ; 32(6): 1031-1036, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827319

RESUMO

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Linfoma de Zona Marginal Tipo Células B , Rituximab , Humanos , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Idoso , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/patologia , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Estadiamento de Neoplasias , Intervalo Livre de Progressão
6.
Clin Lymphoma Myeloma Leuk ; 23(8): 606-609, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37210271

RESUMO

INTRODUCTION: L-asparaginase-based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer- (NK-) cell neoplasms. To treat these lymphoma subtypes in Asia, where NK/T-cell lymphomas are more prevalent, the NK-Cell Tumor Study Group developed the SMILE regimen, which includes a steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide. In the US however, the only commercially available form of asparaginase is the pegylated form (PEG-asparaginase) which has been incorporated into a modified SMILE (mSMILE). We sought to study the toxicity associated with replacing L-asparaginase with PEG-asparaginase in mSMILE. PATIENTS AND METHODS: We retrospectively identified all adult patients treated with the mSMILE chemotherapy regimen in our database at Moffitt Cancer Center (MCC) between December 1, 2009, and July 30, 2021. Patients were included if they were treated with mSMILE irrespective of their underlying diagnosis. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The rate of toxicity in our mSMILE treatment group was numerically compared to data published in a metanalysis of the SMILE regimen's toxicity (Pokrovsky et al., 2019). RESULTS: A total of 21 patients were treated with mSMILE at MCC during the 12-year analysis window. Compared to patients receiving the L-asparaginase-based SMILE, patients receiving mSMILE experienced grade 3 or 4 leukopenia less often, with a toxicity rate of 62% (median with SMILE, 85% [95% CI, 74%-95%]); thrombocytopenia, however, was more common, with a toxicity rate of 57% (median with SMILE, 48% [95% CI, 40%-55%]). Other hematological, hepatic and coagulation related toxicities were also reported. CONCLUSION: In a non-Asian population, the mSMILE regimen with PEG-asparaginase is a safe alternative to the L-asparaginase-based SMILE regimen. There is a comparable risk of hematological toxicity, and no treatment-related mortality was seen in our population.


Assuntos
Linfoma Extranodal de Células T-NK , Trombocitopenia , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Asparaginase/toxicidade , Linfoma Extranodal de Células T-NK/diagnóstico , Polietilenoglicóis/toxicidade , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
7.
Enferm Infecc Microbiol Clin (Engl Ed) ; 41(10): 604-611, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36624033

RESUMO

INTRODUCTION: HIV continues to represent a problem of great relevance for public health in Spain. This study aims to carry out an analysis that will provide in-depth knowledge of the resources, clinical care, and management during the diagnosis, follow-up, and treatment phases of HIV infection in Spain. METHODS: In the first phase, a multidisciplinary Scientific Committee designed an information collection tool in the form of a survey. In the second phase, carried out in the autonomous communities of Andalusia, Catalonia, and La Rioja, a multidisciplinary group of 42 experts, representatives of the public administration, clinical profiles, and representatives of NGOs in the field of HIV answered the survey. RESULTS: The assessment of HIV resources is generally positive. As regards diagnosis, the experts considered that there was good coordination between Primary and Hospital care. Regarding treatment, the evaluations reflected good opinions on therapeutic conciliation and adherence, with a negative opinion in the evaluation of drug interactions with antiretroviral treatment. Regarding follow-up, the perception expressed was disparate concerning the coordination between Hospital and Primary Care as well as the adaptation of care to chronicity, aging, fragility, mental health, and oncological processes. CONCLUSION: There are certain processes that can be improved in the management of HIV infection in people with HIV in Spain, including protocols for follow-up and coordination between primary and hospital care in the treatment and follow-up of the disease.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha , Instalações de Saúde , Inquéritos e Questionários , Atenção à Saúde
8.
J Cancer Res Clin Oncol ; 149(7): 3607-3621, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35962814

RESUMO

PURPOSE: History of keratinocyte carcinoma (KC) has been associated with survival following the diagnosis of a second primary malignancy (SPM), with the direction of the association varying by cancer type. Research is needed to elucidate the role of other key factors in this association. METHODS: A retrospective cohort study was conducted among patients newly diagnosed and/or treated at Moffitt Cancer Center in December 2008-April 2020 with breast cancer, lung cancer, melanoma, colon cancer, prostate cancer, and non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) (n = 29,156). History of KC was obtained from new patient intake questionnaires. Age- and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the association between history of KC and survival following each cancer, stratified by demographic/clinical characteristics. RESULTS: KC history was most prevalent in patients with melanoma (28.7%), CLL (19.8%) and lung cancer (16.1%). KC history was associated with better overall survival following prostate cancer (HR = 0.74, 95% CI = 0.55-0.99) and poorer overall survival following CLL (HR = 1.73, 95% CI = 1.10-2.71). Patients with a history of KC experienced better survival within the first four years of a melanoma diagnosis (HR = 0.79, 95% CI = 0.67-0.92); whereas poorer survival was observed for patients who survived 7 + years after a melanoma diagnosis (HR = 2.18, 95% CI = 1.17-4.05). Stratification by treatment and stage revealed directional differences in the associations between KC history and survival among patients with breast cancer and melanoma. CONCLUSIONS: KC history may be a predictor of survival following an SPM, possibly serving as a marker of immune function and/or DNA damage repair capacity.


Assuntos
Neoplasias da Mama , Carcinoma , Leucemia Linfocítica Crônica de Células B , Neoplasias Pulmonares , Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Masculino , Humanos , Neoplasias Cutâneas/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Segunda Neoplasia Primária/diagnóstico , Estudos Retrospectivos , Melanoma/patologia , Carcinoma/patologia , Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Queratinócitos/patologia , Avaliação de Resultados da Assistência ao Paciente
9.
Cancer Control ; 19(3): 245-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22710900

RESUMO

BACKGROUND: Bendamustine is indicated for the treatment of chronic lymphocytic leukemia (CLL) and rituximab refractory indolent non-Hodgkin lymphoma. Clinical trials have reported a 25% incidence of infusion-related reactions (IRRs) in patients receiving bendamustine. While these reactions are well documented, there is no consensus on the optimal premedication regimen for the prevention of these adverse effects. At our center, we utilize a regimen of ondansetron 16 mg orally and dexamethasone 10 mg IV push prior to each infusion of bendamustine. This report describes our experience with our current premedication regimen with regard to IRRs and the incidence of febrile neutropenia (FN). METHODS: We retrospectively analyzed 73 consecutive patients receiving bendamustine infusions at our institute from June 2008 to June 2010 to determine the incidence of IRRs and FN. The primary objective was to determine the incidence of IRRs. Secondary objectives included incidence of FN and hospital admission rate. RESULTS: A total of 478 infusions of bendamustine were administered to 73 consecutive patients. The median patient age was 69 years. IRRs affected 19% of our population, and 10.9% experienced FN. Notably, all IRRs were attributed to rituximab infusions and no patients experienced an IRR when receiving bendamustine alone. This compares favorably to the initial reported IRRs of 25% with bendamustine alone. CONCLUSIONS: Based on our experience with bendamustine, ondansetron and dexamethasone provide a safe and effective prevention of IRRs associated with bendamustine. By avoiding the use of other premedications, the likelihood of additional complications or adverse affects can be minimized.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Dexametasona/administração & dosagem , Compostos de Mostarda Nitrogenada/efeitos adversos , Ondansetron/administração & dosagem , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Cloridrato de Bendamustina , Feminino , Humanos , Masculino , Compostos de Mostarda Nitrogenada/administração & dosagem , Pré-Medicação/métodos , Estudos Retrospectivos
10.
Ecol Evol ; 12(12): e9613, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36523522

RESUMO

Preserving the genetic diversity of forest species is critical for maintaining their adaptive potential and allowing for generation turnover in forest ecosystems. Considering an uncertain future, it is necessary to establish reliable genetic conservation strategies to optimize the genetic variation preserved within populations in a spatially explicit context to assist decision-makers. Hence, we aimed to incorporate genetic information into spatially designed conservation actions. Cedrus atlantica is a large, long-lived conifer native to the mountains of North Africa, threatened by extinction. The relevant genetic units for conservation were selected using Bayesian analysis. The relative contribution of the populations to the genetic pool that maximized the species' genetic diversity was calculated to design an optimal seed bank. Finally, the relationship between the genetic composition and bioclimatic variables was estimated and projected throughout the study area under current and future climatic conditions. Three relevant genetic units were found for C. atlantica conservation that maximizes genetic diversity in a spatial context. Bioclimatic variables with the highest influence on genetic composition were closely related to climate warming and decreased soil water availability. We identified the role of genetic markers in designing a reliable conservation strategy for forest trees considering climate change, increased deforestation, and aridity. Projections of genetic composition due to the climate in the study region of North Africa provide spatially explicit guidance for optimizing the selection and preservation of seed banks.

11.
BMC Infect Dis ; 10: 267, 2010 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-20840743

RESUMO

BACKGROUND: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Latente/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resultado do Tratamento
13.
Enferm Infecc Microbiol Clin ; 28(4): 215-21, 2010 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-19683364

RESUMO

INTRODUCTION: Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. PATIENTS AND METHODS: Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. RESULTS: A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1-6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3-1.0), having a CD4 cell count >200 (CD4 200-499: OR 0.5, 95% CI 0.3-0.9. CD4> or =500: OR 0.3, 95% CI 0.2-0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1-0.5) were associated with a lower probability. CONCLUSIONS: In this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians' expectations regarding the results of the test and the patients' adherence to treatment for latent TB infection.


Assuntos
Infecções por HIV/complicações , Teste Tuberculínico/estatística & dados numéricos , Tuberculose/diagnóstico , Adulto , Estudos de Coortes , Comorbidade , Diagnóstico Tardio , Testes Diagnósticos de Rotina/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sexual , Fatores Socioeconômicos , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Reação Transfusional , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto Jovem
14.
Clin Cancer Res ; 26(18): 4823-4831, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669372

RESUMO

PURPOSE: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel). EXPERIMENTAL DESIGN: Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression. RESULTS: We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity. CONCLUSIONS: These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.


Assuntos
Produtos Biológicos/efeitos adversos , Síndrome da Liberação de Citocina/epidemiologia , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/terapia , Microambiente Tumoral/imunologia , Adulto , Idoso , Biópsia , Síndrome da Liberação de Citocina/induzido quimicamente , Síndrome da Liberação de Citocina/imunologia , Feminino , Humanos , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos Quiméricos/imunologia , Fatores de Risco , Adulto Jovem
16.
AoB Plants ; 10(5): ply047, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30254727

RESUMO

Quaternary glacial cycles appear to have had a consistent role in shaping the genetic diversity and structure of plant species. Despite the unusual combination of the characteristics of the western Mediterranean-Macaronesian area, there are no studies that have specifically examined the effects of palaeoclimatic and palaeogeographic factors on the genetic composition and structure of annual herbs. Astragalus edulis is a disjunct endemic found in the easternmost Canary Islands and the semi-arid areas of north-eastern Africa and south-eastern Iberian Peninsula. This endangered species shows no evident adaptations to long-distance dispersal. Amplified fragment length polymorphism (AFLP) data and plastid DNA sequences were analysed from a total of 360 individuals distributed throughout the range of this species. The modelled potential distribution of A. edulis under current conditions was projected over the climatic conditions of the Last Interglacial (130 ka BP) and Last Glacial Maximum (21 ka BP) to analyse changes in habitat suitability and to look for associations between the modelling and genetic results. Amplified fragment length polymorphism analysis showed clear phylogeographic structure with four distinct genetic clusters. Approximate Bayesian computation (ABC) models based on plastid DNA sequences indicated a Middle Pleistocene long-distance dispersal event as the origin of the populations of the Canary Islands. The models also suggested south-western Morocco as the ancestral area for the species, as well as subsequent colonization of north-eastern Morocco and the Iberian Peninsula. The data compiled indicated the possibility of the presence of refuge areas at favourable locations around the High Atlas and Anti-Atlas mountain ranges. Moreover, palaeodistribution models strongly support the events inferred by ABC modelling and show the potential distribution of the species in the past, suggesting a putative colonization route.

17.
HIV Clin Trials ; 8(5): 328-36, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17956834

RESUMO

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Organofosfonatos/administração & dosagem , Carga Viral , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/efeitos adversos , Contagem de Linfócito CD4 , Colesterol/sangue , Ciclopropanos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde , RNA Viral/sangue , Tenofovir , Resultado do Tratamento , Recusa do Paciente ao Tratamento , Triglicerídeos/sangue
18.
Reprod Toxicol ; 24(3-4): 414-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17698320

RESUMO

The product label of ribavirin states that it is contraindicated during pregnancy, so the risk in its administering during pregnancy is concerned. We show a case of an infant of 22 months of age with no anomalies born from an HCV- and HIV-infected mother under treatment with pegylated interferon, ribavirin and antiretroviral therapy during the first 16 weeks of pregnancy. The infant is neither HIV- nor HCV-infected.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Ribavirina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Quimioterapia Combinada , Feminino , Humanos , Indinavir/uso terapêutico , Lactente , Interferon alfa-2 , Lamivudina/uso terapêutico , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Proteínas Recombinantes , Ribavirina/efeitos adversos , Resultado do Tratamento , Zidovudina/uso terapêutico
19.
PeerJ ; 4: e1474, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26844014

RESUMO

Astragalus edulis (Fabaceae) is an endangered annual species from the western Mediterranean region that colonized the SE Iberian Peninsula, NE and SW Morocco, and the easternmost Macaronesian islands (Lanzarote and Fuerteventura). Although in Spain some conservation measures have been adopted, it is still necessary to develop an appropriate management plan to preserve genetic diversity across the entire distribution area of the species. Our main objective was to use population genetics as well as ecological and phylogeographic data to select Relevant Genetic Units for Conservation (RGUCs) as the first step in designing conservation plans for A. edulis. We identified six RGUCs for in situ conservation, based on estimations of population genetic structure and probabilities of loss of rare alleles. Additionally, further population parameters, i.e. occupation area, population size, vulnerability, legal status of the population areas, and the historical haplotype distribution, were considered in order to establish which populations deserve conservation priority. Three populations from the Iberian Peninsula, two from Morocco, and one from the Canary Islands represent the total genetic diversity of the species and the rarest allelic variation. Ex situ conservation is recommended to complement the preservation of A. edulis, given that effective in situ population protection is not feasible in all cases. The consideration of complementary phylogeographic and ecological data is useful for management efforts to preserve the evolutionary potential of the species.

20.
PeerJ ; 4: e2618, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27833802

RESUMO

Although it has been traditionally accepted that Arenaria balearica (Caryophyllaceae) could be a relict Tertiary plant species, this has never been experimentally tested. Nor have the palaeohistorical reasons underlying the highly fragmented distribution of the species in the Western Mediterranean region been investigated. We have analysed AFLP data (213) and plastid DNA sequences (226) from a total of 250 plants from 29 populations sampled throughout the entire distribution range of the species in Majorca, Corsica, Sardinia, and the Tuscan Archipelago. The AFLP data analyses indicate very low geographic structure and population differentiation. Based on plastid DNA data, six alternative phylogeographic hypotheses were tested using Approximate Bayesian Computation (ABC). These analyses revealed ancient area fragmentation as the most probable scenario, which is in accordance with the star-like topology of the parsimony network that suggests a pattern of long term survival and subsequent in situ differentiation. Overall low levels of genetic diversity and plastid DNA variation were found, reflecting evolutionary stasis of a species preserved in locally long-term stable habitats.

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