Quality of life as a prognostic marker in pulmonary arterial hypertension

Background: Improvement in quality of life together with better survival are the ultimate goals in the treatment of pulmonary arterial hypertension (PAH) patients. the objective of this study was to evaluate the health-related quality of life (HRQL) of pulmonary arterial hypertension (PAH) patients with the SF-36 generic questionnaire and to identify the prognostic implication of this assessment.Methods: Fifty-four consecutive newly diagnosed PAH patients (WHO classification group I) in a single PAH reference center were included. Patients were evaluated at baseline for clinical and hemodynamic parameters, and they subsequently received first-line therapy with either an endothelin receptor antagonist or a phosphodiesterase-5 inhibitor. After 16 weeks of specific PAH therapy, all patients were re-evaluated using a 6MWT and a SF 36 questionnaire, and then they were followed up for at least 36 months.Results: After treatment, the patients demonstrated an improved 6MWT (414 +/- 124 m vs. 440 +/- 113 m, p = 0.001). Specific PAH therapy also improved the HRQL scores.Patients with a baseline Physical Component Score (PCS) higher than 32 had a better survival rate than those who had a score under 32 (p = 0.04). Similarly, patients with a PCS of at least a 38 after the 16 week therapy period had a better survival rate when compared with those who did not achieve this value (p = 0.016). Unlike the absolute PCS values, the post-treatment PCS variability was unable to predict better survival rates (p = 0.58).Conclusions: Our findings suggest that HRQL is associated with prognosis in PAH. Furthermore, achieving pre-determined PCS scores might represent a specific goal to be reached in treatment-to-target strategies.Univ São Paulo, Sch Med, Pulm Dept, Inst Heart, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Rheumatol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Rheumatol Dept, São Paulo, BrazilWeb of Scienc

Doses cumulativas de iodo radioativo no tratamento do carcinoma diferenciado de tireoide: sabendo a hora de parar

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and &gt; 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs &gt; 600 mCi in patients &gt; 45 years old and with CDs &gt; 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.OBJETIVO: Avaliar a eficácia de doses cumulativas (DCs) da terapia com iodeto-131I (RIT) no câncer diferenciado de tiroide (CDT). SUJEITOS E MÉTODOS: A probabilidade de doença em progressão conforme a DC foi calculada em pacientes com idade < 45 e &gt; 45 anos e correlacionada com o TNM, valores de tiroglobulina sérica, tipos histológicos e variantes, idade e tempo de doença. RESULTADOS: Ao final de um seguimento de 69 ± 56 meses, 85 dos 150 pacientes CDT submetidos a doses fixas de RIT não tinham evidência de doença, 47 tinham doença estável e 18, doença progressiva. DCs mais elevadas foram usadas nas variantes agressivas (p < 0,0001), maior estágio TNM (p < 0,0001) e nos carcinomas foliculares (p = 0,0034). A probabilidade de doença em progressão foi maior com DCs &gt; 600 mCi em pacientes &gt; 45 anos e com DCs &gt; 800 mCi em pacientes < 45 anos. CONCLUSÃO: Apesar de alguns pacientes ainda responderem a altas DCs, o impacto de RITs deve ser cuidadosamente avaliado e outras estratégias terapêuticas devem ser consideradas.80781

Cumulative Doses Of Radioiodine In The Treatment Of Differentiated Thyroid Carcinoma: Knowing When To Stop.

Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). The probability of progressive disease according to CDs was evaluated in patients 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.54807-1

A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP-2 and Sm29 was able to induce protection against infection in mice

Schistosoma mansoni is a blood fluke parasite responsible for schistosomiasis. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. In this study, we cloned, expressed and purified SmTSP-2 fused to the N- and C-terminal halves of Sm29 and tested these chimeras as vaccine candidates using an adjuvant approved to be used in humans. The results demonstrated that vaccination with SmTSP-2 fused to N- or C-terminus of Sm29-induced reduction in worm burden and liver pathology when compared to control animals. Additionally, we detected high levels of mouse-specific IgG, IgG1 and IgG2a against both chimeras and significant amounts of IFN-γ and TNF-α and no IL-4. Finally, studies with sera from patients resistant to infection and living in schistosomiasis endemic areas revealed high levels of specific IgG to both chimeras when compared to healthy individuals. In conclusion, SmTSP-2/Sm29 chimeras tested here induced partial protection against infection and might be a potential vaccine candidate

Incidence and Duration of Type-Specific Human Papillomavirus Infection in High-Risk HPV-Naïve Women: Results from the Control Arm of a Phase II HPV-16/18 Vaccine Trial

OBJECTIVES: Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners. METHODS: Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition. RESULTS: Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged(RR=1.33, 95% CI 1.1 to 1.7) and women having \u3e1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline. CONCLUSIONS: HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners

Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection Against S. mansoni Infection in Mice

Current schistosomiasis control strategies are mainly based on chemotherapy, but the development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. When it comes to vaccine candidates, several genes encoding Schistosoma mansoni proteins expressed at the mammalian host–parasite interface have been tested. Among the most promising molecules are the proteins present on the tegument and digestive tract of the parasite. In this study, we evaluate the potential of SmKI-1, the first Kunitz-type protease inhibitor functionally characterized in S. mansoni, as a vaccine candidate. Bioinformatic analysis points to the C-terminal fragment as the main region of the molecule responsible for the development of a potential protective immune response induced by SmKI-1. Therefore, for the vaccine formulations, we produced the recombinant (r) SmKI-1 and two different fragments, its Kunitz (KI) domain and its C-terminal tail. First, we demonstrate that mice immunized with recombinant SmKI-1 (rSmKI-1) or its fragments, formulated with Freund’s adjuvant, induced the production of IgG-specific antibodies. Further, all vaccine formulations tested here also induced a Th1-type of immune response, as suggested by the production of IFN-γ and TNF-α by protein-stimulated cultured splenocytes. However, the protective effect conferred by vaccination was only observed in groups which received rSmKI-1 or C-terminal domain vaccines. Mice administered with rSmKI-1 demonstrated reduction of 47% in worm burden, 36% in egg number in mouse livers, and 33% in area of liver granulomas. Additionally, mice injected with C-terminal domain showed reduction of 28% in worm burden, 38% in egg number in liver, and 25% in area of liver granulomas. In contrast, KI domain immunization was unable to reduce worm burden and ameliorate liver pathology after challenge infection. Taken together, our data demonstrated that SmKI-1 is a potential candidate for use in a vaccine to control schistosomiasis, and its C-terminal tail seems to be the main region of the molecule responsible for protection conferred by this antigen

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop Doses cumulativas de iodo radioativo no tratamento do carcinoma diferenciado de tireoide: sabendo a hora de parar

ABSTRACT Objective: Evaluate the efficacy of cumulative doses (CDs) of 131 I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). Subjects and methods: The probability of progressive disease according to CDs was evaluated in patients ≤ 45 years old and &gt; 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. Results: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p &lt; 0.0001), higher TNM stages (p &lt; 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs ≥ 600 mCi in patients &gt; 45 years old and with CDs ≥ 800 mCi in patients ≤ 45 years. Conclusion: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted

Scientific diving in Brazil: history, present and perspectives

Scientific diving (SD) is defined as any diving activity that applies scientific procedures to produce subsidies forstudies and technical works in underwater environments. The first report of an underwater scientific study inBrazil dates to the 19th century, in the Abrolhos reefs. Currently, in Brazil, scientific diving has been performedin various areas, from shallow coastal regions to remote and sometimes hard-to-reach places, such as oceanicislands, flooded caves, and icy areas like Antarctica. However, the regulation of SD in Brazil still lacks moreconcrete actions towards an effective and efficient self-regulation that offers physical safety to practitioners andinstitutional safeguards for organizations that use it in their research projects. Thus, this article aims to contributeto a better understanding of this critical issue in Brazil and to serve as a reference and incentive for the trainingof professionals and the development of these activities in the country. It includes: 1) a historical review ofSD; 2) a diagnosis of the training and application of SD in Brazil; 3) the evolution of marine sciences in Brazilfrom the perspective of SD; 4) a review of the use of environmental assessment and underwater conservationtechniques in oceans and internal waters; 5) an analysis of the evolution of scientific diver training in Brazil,including a diagnosis on training; 6) the history and updates of the rules, regulations, and safety of SD. Givenall the potential of diving combined with specific techniques for research, monitoring, and marine and limnicscience in Brazil, we aim to understand the evolution of scientific diving teaching and to outline perspectives inthe country, as it is crucial for the training of qualified scientists capable of performing these underwater tasks.Finally, we present futture plans for the development of this activity in Brazil from the point of view of researchand the labor market

Canine distemper virus induces apoptosis in cervical tumor derived cell lines

Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases