Cost-utility analysis of propranolol versus corticosteroids in the treatment of proliferating infantile hemangioma in Italy

Objectives Infantile hemangioma (IH) is the most common childhood benign tumour. A recent phase II/III study has demonstrated the success of propranolol for involution of infantile hemangioma as well as a better efficacy and safety when indirectly compared with corticosteroids. The purpose of this study was to estimate the cost-utility of propranolol (Hemangiol), a new medicinal product and the first to be authorized for this specific paediatric indication, versus corticosteroids in the treatment of proliferating infantile hemangioma requiring systemic therapy

Tumor growth rate to assess therapy response to immune-based combinations for metastatic renal cell carcinoma

Background: Radiological response assessment is becoming challenging with novel immune-based combinations for metastatic renal cell carcinoma (mRCC). RECIST criteria appear not exhaustively adequate to capture the kinetics of treatment response, which is better reflected by tumor growth rate (TGR). We explored TGR changes during first-line treatments and its association with clinical outcomes in mRCC. Research design and methods: We retrospectively evaluated TGR in untreated patients undergoing pembrolizumab/axitinib (P/A) or tyrosine-kinase inhibitors (TKI). TGR was calculated at the first (TGR1, after 3 months) and the second (TGR2, after 6 months) evaluation, thus assessing the TGR2-TGR1 difference. Results: Thirty-three patients were included (P/A n = 15, TKIs n = 18). Volumes firstly decreased more rapidly with TKIs, and then more slowly. Volumes initially remained stable with P/A, quickly decreasing until the second evaluation. TGR1 was related to progression-free survival (PFS; p = 0.023) and overall survival (p = 0.046) with P/A. TGR2 was correlated with PFS in all patients (p = 0.025). Patients with higher velocity volume reduction appeared to have improved survival benefits than patients with lower velocity considering both treatments, but especially with P/A. Conclusion: Combining immunotherapy with TKIs has an important role in enhancing the rapidity of tumor shrinkage. A rapid disease volume reduction correlates with better OS and PFS

Dose response assessment of conventional Fricke: a relationship between UV-Visible and nuclear magnetic resonance techniques

Conventional Fricke is an aqueous ferrous sulfate solution that has been widely studied in the field of chemical dosimetry. The feasibility of its use has become attractive for high dose measurements that are of clinical interest in the field of radiotherapy and for industrial purposes, in the irradiation of blood bags and the sterilization of surgical material. The derivation of the absorbed dose of Fricke depends on the radiation-induced oxidation of iron (II) ions (Fe2+) present in the aqueous solution to iron (III) ions (Fe3+), which occurs after exposure to ionising radiation. In this paper, it is proposed to evaluate the dose response of the Fricke dosimeter using two different analytical techniques, ultraviolet-visible spectrophotometry (UV-Vis) and nuclear magnetic resonance spectroscopy (NMR). Twelve groups of samples were analysed in triplicate, irradiated with doses between 0 and 800 Gy, using a cobalt-60 source (60Co). The dose rate of Fricke dosimeters was evaluated against the practical values obtained. The different methods allowed an analytical correlation of the species of oxidised iron (Fe3+) using a linearity curve as a function of the applied radiation dose

Sentido de la vida y comunidad

En el contexto de las “vidas líquidas” propias del mundo contemporáneo y con la coyuntura del aislamiento social por la pandemia de COVID-19 de por medio, los catorce artículos reunidos en este volumen pretenden reflexionar sobre el sentido de la vida, desde perspectivas teológicas, filosóficas, artísticas o pedagógicas, pero siempre teniendo a la comunidad como un horizonte de llegada. Desde la encíclica del papa Francisco Fratelli Tutti y la pedagogía del amor en Don Bosco, hasta el humanismo de José Martí y el Epimeleia Heautou de Foucault, pasando por figuras como Ignacio Ellacuría y Estanislao Zuleta, todos los conceptos y autores trabajados en estos textos echan una mirada crítica sobre las perspectivas individualistas de la vida, que pretenden darle sentido desde el disfrute egoísta y el aislamiento. Así, cada artículo nos interpela a buscar la mejor forma de habitar el mundo con los otros y entonces preguntarnos por el sentido de nuestras vidas

Diseño regenerativo, Parque Bicentenario, residencias – comercio – actividades Recreativas

La propuesta urbana / arquitectónica se realiza en la zona de influencia del Antiguo Aeropuerto “Mariscal Sucre” (QUIPORT, 2019) que comprende los siguientes barrios: Aeropuerto, El Rosario, Rumiñahui, Lucía Albán Romero, Cofavi, California Bonanza, La Kennedy, La Victoria, Dammer 1 y 2, La Luz, Las Acacias, Jipijapa, Julio Matovelle, La Concepción, La Florida, Maldonado, San Carlos, San Pedro Chavel, Unión Nacional, Zaldumbide, Betania, Baker, Chaupicruz y Franklin Tello. La presente investigación busca analizar el impacto, la relación, la ausencia de servicios y equipamientos que permiten definir una buena calidad de vida. Los protagonistas urbanos son componentes que dan carácter al lugar, donde se identificaron los siguientes: la distribución territorial, los espacios públicos, la infraestructura existente, las tensiones de acuerdo a la condición de cada edificación, la población flotante y migrante, la movilización, la economía y el estado de las áreas verdes. La reincidencia en el uso de suelo provoca monotonía y desorganiza el territorio. Se identifican los comercios formales e informales que rodean la zona de estudio, mismos que causan actividades rutinarias en los habitantes. De esta manera, se impide la diversificación del suelo. Las barreras urbanas provocan divisiones territoriales, que se expresan en una ruptura física, misma que se origina por la falta de cuidado en los espacios públicos y los cerramientos existentes. De esta manera, da lugar a los refugios improvisados que ocasionan inseguridad en la zona

Evaluation of Cl, K and Ca concentration in urine, hemolymph and Malpighian tubules of Rhodnius prolixus using total reflection X-Ray fluorescence by synchrotron radiation (SR-TXRF)

Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorNeste trabalho utilizou-se a técnica fluorescência de raios X usando radiação síncrotron (SR-TXRF) para estudar, quantitativamente, o transporte de cloro, potássio e cálcio na hemolinfa, urina e túbulos de Malpighi (TM) em ninfas de quinto estágio do Rhodnius prolixus (R. prolixus), considerando a excreção destes elementos em diferentes dias após o repasto sanguíneo. R. prolixus é um dos principais vetores do Trypanosoma cruzi, agente causador da doença de Chagas. R. prolixus fornece um sistema modelo particularmente útil porque seus TMs tanto secretam quanto reabsorvem íons a taxas elevadas. Os TMs filtram a hemolinfa e secretam um líquido que é muitas vezes comparado com a urina primária em vertebrados. Os resultados obtidos mostram que a concentração de potássio na urina é substancialmente maior do que na hemolinfa. A concentração de cloro na hemolinfa é menor do que na urina, mas a diferença não é tão marcada como no caso do potássio. No caso do Rhodnius é razoável interpretar a elevada concentração de potássio na urina como adaptativo para o problema de excreção imediato do inseto. A concentração de cálcio nos TMs é substancialmente maior em comparação com os valores encontrados na hemolinfa e urina. Este resultado mostra que o cálcio é retido no corpo do R. prolixus e pouco eliminado. Os resultados obtidos estão coerentes com a literatura. Avaliou-se também o efeito no transporte de Cl, K e Ca após um repasto de sangue de coelho contaminado com HgCl2 de modo a avaliar o efeito da presença deste metal tóxico no balanço iônico nos fluidos de excreção urina e hemolinfa e também pelo principal órgão de transporte, os túbulos de Malpighi. As excreções de Cl e K pela urina são afetadas pela ingestão. Este resultado é esperado levando-se em consideração a ingestão de excesso de Cl através do HgCl2. O transporte de Cl, K e Ca na hemolinfa do Rhodnius prolixus não é afetada pela ingestão de HgCl2. Nos túbulos de Malpighi, as altas concentrações de Ca obtidas foram comparáveis àquelas encontradas nos insetos controle. Pode-se concluir que SR-TXRF é um método muito promissor para análises diretas, rápidas e confiáveis para a quantificação simultânea de elementos envolvidos na regulação do transporte e em todo o sistema excretor de insetos. Além disso, o estudo do transporte e a excreção de elementos no inseto Rhodnius prolixus abrem oportunidade para a maior compreensão de efeitos da poluição em espécies de invertebrados.In this work, we investigated changes in the concentrations of Cl, K and Ca, in 5th instar using total reflection X-ray fluorescence Rhodnius prolixus with synchrotron radiation (SR-TXRF). The elements were quantified using urine, hemolymph and Malpighian tubules samples collected on different days after a blood meal. Rhodnius prolixus is one of the most important vectors of the Trypanosoma cruzi, causative agent of Chagas? disease. R. prolixus provides a particularly useful model system because its MTs both secrete and reabsorb ions at high rates. The TMs filter hemolymph and secrete a liquid that is often compared with the primary urine in vertebrates. The experimental results showed that the concentration of potassium in the urine is substantially greater than in the hemolymph. The concentration of chlorine in the hemolymph is generally less than in the urine, but the difference is not so marked as in the case of potassium. In the case of Rhodnius, it is reasonable to interpret the high concentration of potassium in the urine as adaptive to the animals? immediate excretory problem. The concentration of calcium in the TMs is substantially greater than in both the hemolymph and the urine. This result shows that that calcium is retained in the body and not eliminated. These results are in accordance with the literature. We also investigated whether dietary mercury contamination may influence the transport of Cl, K and Ca by the hemolymph, urine and Malpighian tubules of R. prolixus fed on blood containing HgCl2. The results suggested that dietary Hg contamination may influence the Cl and K contents during excretion of the urine. It was expected considering the large amounts of chlorine ingested by Rhodnius prolixus in its meals of blood containing HgCl2. Statistical analysis showed no significant variation in all elements contents for hemolymph samples. The main conclusion which can be drawn from the results is that in all the insects studied calcium is deposited in Malpighian tubules. These observations point out that the analytical approach of the SR-TXRF method can be efficiently used to measure elements involved in the transport regulation into insect Malpighian tubules and also provides useful data concerning the biological effects of pollution on invertebrate species

A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation

To clarify the population history of dentatorubropallidoluysian atrophy ( DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers

Ergogenic Effect of BCAAs and L-Alanine Supplementation: Proof-of-Concept Study in a Murine Model of Physiological Exercise

Background: Branched-chain amino acids (BCAAs: leucine, isoleucine, valine) account for 35% of skeletal muscle essential amino acids (AAs). As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Although substantial evidence has been collected about the potential usefulness of BCAAs in supporting muscle function and structure, dietary supplements containing BCAAs alone may not be effective in controlling muscle protein turnover, due to the rate-limiting bioavailability of other AAs involved in BCAAs metabolism. Methods: We aimed to evaluate the in vivo/ex vivo effects of a 4-week treatment with an oral formulation containing BCAAs alone (2:1:1) on muscle function, structure, and metabolism in a murine model of physiological exercise, which was compared to three modified formulations combining BCAAs with increasing concentrations of L-Alanine (ALA), an AA controlling BCAAs catabolism. Results: A preliminary pharmacokinetic study confirmed the ability of ALA to boost up BCAAs bioavailability. After 4 weeks, mix 2 (BCAAs + 2ALA) had the best protective effect on mice force and fatigability, as well as on muscle morphology and metabolic indices. Conclusion: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution

Preliminary Pre-Clinical studies on the side effects of breast cancer treatment

Technological advancement in the treatment of cancer together with early detection and diagnosis have considerably improved the survival of breast cancer patients. On the other hand, the potential of patients developing side effects from cancer treatment are not negligible. Despite the progress that has been made in terms of early diagnosis, therapy, and survival, including improvements in the chemotherapeutic agents, radiation and molecular targeted therapies, cardiotoxicity of cancer therapy is still cause for concern. Radiation therapy for breast cancer is associated with increased risk of heart disease and myocardial infarction. Furthermore, the association of radiation therapy to chemotherapy is an important aspect to be considered in the development of cardiac disease, as this could play an additional role as a risk factor. Besides the heart effect, other side effects can be observed in the bone, ovary, uteri, and other organs. This paper aims to review the recent literature to present the current understanding of side effects associated with breast cancer treatment. The focus is on recent preclinical studies that have assessed potential changes in different organs that may be injured after breast cancer treatment, both due to both radiation and chemotherapy agents. Conclusion: Radiation-induced heart disease is one important side effect that must be considered during the treatment planning and patient follow-up. The cardiac damage can be potentialized when chemotherapy is associated to radiotherapy, and the literature findings indicate that heart fibrosis plays an important role at the radio-chemotherapy induced cardiac damage. Literature findings also showed important side effects at the bone, that can lead to ospeoporosis, due to the decrease of calcium, after radio or chemotherapy treatments. This decrease could be explained by the ovarian failure observed at rats after chemotherapy treatment. It is of great importance to acknowledge the complications originating from the treatment, so that new strategies can be developed. In this way, it will be possible to minimize side effects and improve the patients’ quality of life