Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Mammography-based screening program: preliminary results from a first 2-year round in a Brazilian region using mobile and fixed units

RLH, TBS and ALF made substantial contributions to the conception and design of the article, the acquisition, analysis and interpretation of the data, and drafting of the article. ECM, JSCM and NB made substantial contributions to the conception and design of the study.Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths among women worldwide. The use of mobile mammography units to offer screening to women living in remote areas is a rational strategy to increase the number of women examined. This study aimed to evaluate results from the first 2 years of a government-organized mammography screening program implemented with a mobile unit (MU) and a fixed unit (FU) in a rural county in Brazil. The program offered breast cancer screening to women living in Barretos and the surrounding area. Methods: Based on epidemiologic data, 54 238 women, aged 40 to 69 years, were eligible for breast cancer screening. The study included women examined from April 1, 2003 to March 31, 2005. The chi-square test and Bonferroni correction analyses were used to evaluate the frequencies of tumors and the importance of clinical parameters and tumor characteristics. Significance was set at p < 0.05. Results: Overall, 17 964 women underwent mammography. This represented 33.1% of eligible women in the area. A mean of 18.6 and 26.3 women per day were examined in the FU and MU, respectively. Seventy six patients were diagnosed with breast cancer (41 (54%) in the MU). This represented 4.2 cases of breast cancer per 1000 examinations. The number of cancers detected was significantly higher in women aged 60 to 69 years than in those aged 50 to 59 years (p < 0.001) or 40 to 49 years (p < 0.001). No difference was observed between women aged 40 to 49 years and those aged 50 to 59 years (p = 0.164). The proportion of tumors in the early (EC 0 and EC I) and advanced (CS III and CS IV) stages of development were 43.4% and 15.8%, respectively. Conclusions: Preliminary results indicate that this mammography screening program is feasible for implementation in a rural Brazilian territory and favor program continuation

Bioassay guided purification of the antimicrobial fraction of a Brazilian propolis from Bahia state

<p>Abstract</p> <p>Background</p> <p>Brazilian propolis type 6 (Atlantic forest, Bahia) is distinct from the other types of propolis especially due to absence of flavonoids and presence of other non-polar, long chain compounds, but presenting good <it>in vitro </it>and <it>in vivo </it>antimicrobial activity. Several authors have suggested that fatty acids found in this propolis might be responsible for its antimicrobial activity; however, so far no evidence concerning this finding has been reported in the literature. The goals of this study were to evaluate the antibacterial activity of the main pure fatty acids in the ethanolic extract and fractions and elucidate the chemical nature of the bioactive compounds isolated from Brazilian propolis type 6.</p> <p>Methods</p> <p>Brazilian propolis type 6 ethanolic extract (EEP), hexane fraction (H-Fr), major fatty acids, and isolated sub-fractions were analyzed using high performance liquid chromatography (HPLC), high resolution gas chromatography with flame ionization detection (HRGC-FID), and gas chromatography-mass spectrometry (GC-MS). Three sub-fractions of H-Fr were obtained through preparative HPLC. Antimicrobial activity of EEP, H-Fr, sub-fractions, and fatty acids were tested against <it>Staphyloccus aureus </it>ATCC 25923 and <it>Streptococcus mutans </it>Ingbritt 1600 using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).</p> <p>Results</p> <p>EEP and H-Fr inhibited the growth of the microorganisms tested; nevertheless, no antimicrobial activity was found for the major fatty acids. The three sub-fractions (1, 2, and 3) were isolated from H-Fr by preparative HPLC and only sub-fraction 1 showed antimicrobial activity.</p> <p>Conclusion</p> <p>a) The major fatty acids tested were not responsible for the antimicrobial activity of propolis type 6; b) Sub-fraction 1, belonging to the benzophenone class, was responsible for the antimicrobial activity observed in the present study. The identification of the bioactive compound will improve the development of more efficient uses of this natural product.</p

Therapeutic communication between health workers and patients concerning diabetes mellitus care

The objective of this cross-sectional study was to analyze therapeutic communication techniques used by health workers with patients under care for diabetes mellitus. Data were collected in 2010 in a public facility in the interior of Ceará, Brazil using video camera equipment and direct observation. Results showed that the most frequently used techniques within the "expression" group were: asking questions, voicing interest, and using descriptive phrases. The most frequently used technique within the "clarification" group was: asking the patient to specify the agent of action. Finally, in regard to the "validation" group, only the technique "summarizing content of the interaction" was employed. The conclusion is that despite the use of communication techniques on the part of professionals, there is still an alarming gap concerning communication skills. Such skills should be allied with technical expertise to enable the delivery of qualified care to individuals with diabetes mellitus.Este estudio transversal tuvo como objetivo analizar las técnicas de comunicación terapéutica entre profesionales y pacientes en la atención en diabetes mellitus. Los datos se recogieron en una institución pública de Ceará-Brasil, en 2010, con equipos de video y observación directa. Los resultados mostraron que las técnicas del grupo de expresión más utilizadas fueron: hacer preguntas, expresar interés y usar frases descriptivas. Con relación a las del grupo de clarificación sobresalió solicitar al paciente que necesite el agente de la acción. Con relación a las de validación, apenas se utilizó las de organizar el contenido de la interacción. Se concluye que a pesar del uso de técnicas de comunicación por los profesionales, aun es preocupante la laguna con relación a la habilidad en comunicación, que debe ser aliada a la capacidad técnica, para así propiciar el cuidado calificado a las personas con diabetes mellitus.Objetivou-se, por este estudo transversal, analisar as técnicas de comunicação terapêutica entre profissionais e pacientes na atenção em diabetes mellitus. Os dados foram coletados em uma instituição pública de um município no interior do Ceará, Brasil, em 2010, por meio de equipamentos de vídeo e observação direta. Os resultados mostraram que as técnicas do grupo de expressão mais utilizadas foram: fazer perguntas, verbalizar interesse e usar frases descritivas. Quanto às do grupo de clarificação, sobressaiu solicitar ao paciente que precise o agente da ação. Em relação às de validação, apenas foi utilizada a técnica de sumarizar o conteúdo da interação. Conclui-se que, apesar do emprego de técnicas comunicacionais pelos profissionais, ainda é preocupante a lacuna referente à habilidade em comunicação, a qual deve ser aliada à competência técnica, para assim propiciar o cuidado qualificado às pessoas com diabetes mellitus

Drug Repurposing in Pancreatic Cancer: A Multi-Stakeholder Perspective to Improve Treatment Options for Pancreatic Cancer Patients

Evelyn Hewitt,1 Gauthier Bouche,2 Alexandre Costa Alencar,3 Stephen J Bigelsen,4 Raluca Radu,5 Violeta Stoyanova-Beninska,6 Alfredo Carrato,7,8 Federica Valsecchi,9 Alicia Soler Cantón,10 Helene G van der Meer,11 María Laura García Bermejo,12 Alfredo Budillon,13 Luca Cardone,14,15 Ilse Rooman,2,16 Hans Platteeuw,17 Judit Baijet,18 Claudia Fuchs18 1Beacon: for Rare Disease, Cambridge, UK; 2The Anticancer Fund, Meise, Belgium; 3Rising Tide Foundation for Clinical Cancer Research, Schaffhausen, Switzerland; 4Patient Advocate, Department of Allergy, Asthma and Immunology, Rutgers New Jersey Medical School, Newark, NJ, USA; 5Medicines for Europe, Brussels, Belgium; 6College ter Beoordeling van Geneesmiddelen, Utrecht, the Netherlands; 7Department of Medical Oncology, Alcalá University, Instituto Ramón Y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica En Red de Cáncer (CIBERONC), Ramon Y Cajal University Hospital, Madrid, Spain; 8Pancreatic Cancer Europe, Brussels, Belgium; 9Fondazione Nadia Valsecchi, Brescia, Italy; 10EATRIS ERIC, European Infrastructure for Translational Medicine, Amsterdam, the Netherlands; 11ZonMw, The Hague, the Netherlands; 12Biomarkers and Therapeutic Targets Group, Instituto Ramón Y Cajal de Investigación Sanitaria (IRYCIS), Ramon Y Cajal University Hospital, Madrid, Spain; 13Scientific Directorate, Istituto Nazionale Tumori – IRCCS - Fondazione G. Pascale, Naples, Italy; 14Institute of BiOChemistry and Cell Biology (IBBC), CNR c/o Campus Internazionale “a.buzzati-Traverso”, Monterotondo Scalo Roma (Rome), Italy; 15Department of Tumour Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 16Translational Oncology Research Center (TORC), Laboratory of Medical and Molecular Oncology, (LMMO) Vrije Universiteit Brussel, Brussels, Belgium; 17Galenicap, Brussels, Belgium; 18EURORDIS - Rare Diseases Europe, Paris, FranceCorrespondence: Claudia Fuchs, EURORDIS - Rare Diseases Europe, Rare Diseases Platform, 96 rue Didot, Paris, 75014, France, Email [email protected] Evelyn Hewitt, Beacon for Rare Diseases, 66 Devonshire Road, Cambridge, CB1 2BL, United Kingdom, Email [email protected]: Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective and less toxic drugs to improve the dismal prognosis of PC. In recent years, drug repurposing (DR) has emerged as an attractive strategy to identify novel treatments for PC by leveraging existing drugs approved for other indications. Through the use of electronic medical records, Artificial Intelligence, study of metabolic pathways, signalling pathways, and many other approaches, it has become much easier in recent years to identify potential novel uses for old drugs. Although policy, funding and research attention in this area are steadily growing, major challenges to efficient and effective patient-centric DR in PC need to be addressed. These include but are not limited to regulatory, financial and funding barriers and the lack of coordination and collaboration among several sectors and stakeholders. To explore the opportunities and challenges associated with DR in PC, a one-day multi-stakeholder meeting was held on 14th of November 2024 in Brussels, Belgium as part of the REMEDi4ALL project. This meeting provided a platform for researchers, clinicians, industry representatives, funders, regulatory experts, and patient advocates to discuss and propose actions to optimize and accelerate DR in PC. Insights from this meeting support the potential of DR to enhance PC treatment options while highlighting the importance of systemic and supportive changes in the regulatory, policy and funding landscapes, interdisciplinary collaboration, data sharing, and patient involvement in driving therapeutic innovation. This summary highlights key outcomes and recommendations from the meeting in informing future efforts to advance DR initiatives in the context of PC.Keywords: drug repurposing, pancreatic cancer, multi-stakeholder discussion, collaboration, patient centricit

Late-stage diagnosis of HIV infection in Brazilian children: evidence from two national cohort studies

This study analyzed data from two consecutive retrospective cohort samples (1983 to 1998 and 1999 to 2002) of Brazilian children with AIDS (N = 1,758) through mother-to-child-transmission. Late-stage diagnosis (CDC category C) was investigated in relation to the following variables: year of birth, year of HIV diagnosis, and time periods related to changes in government treatment guidelines. Late-stage diagnosis occurred in 731 (41.6%) of cases and was more prevalent in infants under 12 months of age. The rate of late-stage diagnosis decreased from 48% to 36% between the two periods studied. We also observed a reduction in the proportion of late-stage diagnoses and the time lapse between HIV diagnosis and ART initiation. A significant association was found between timely diagnosis and having been born in recent years (OR = 0.62; p = 0.009) and year of HIV diagnosis (OR = 0.72; p = 0.002/OR = 0.62; p < 0.001). Infants under the age of 12 months were more likely to be diagnosed at a late stage than older children (OR = 1.70; p = 0.004). Despite advances, there is a need to improve the effectiveness of policies and programs focused on improving early diagnosis and management of HIV/AIDS