Partial breast irradiation: Targeting volume or breast molecular subtypes?

The eligibility criteria for partial breast irradiation (APBI) are mainly based on histopathological factors, which not always explain the clinical behaviour of breast cancers. International guidelines represent useful platform to collect data for continued refinement of patient selection, but the clinical applicability to APBI series showed some limitations, particularly among the intermediate and high-risk groups. The heterogeneity of APBI techniques, along with the heterogeneity of breast cancer, generates clinical results, where the predictive value of the histopathological factors can assume different weight. There is a need of further refinement and implementation of risk factors. Currently, the impact of breast cancer subtype on local control is matter of investigation, and treatment decision about radiotherapy is generally made without regard to the breast cancer subtype. However, receptor status information is easily available and some histopathological factors have not a definite role, there is no uniform interpretation. As molecular classification becomes more feasible in the clinical practice, it will provide added value to conventional clinical tumour characteristics in predicting local recurrence in breast cancer and may play an important role as predictor of eventual patient outcomes

Best practices for the manual curation of Intrinsically Disordered Proteins in DisProt

The DisProt database is a significant resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional (3D) structure. Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes significantly to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses, or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions, and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection, and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. Database URL: https://disprot.org

MMP-7 and MMP-9 Are Overexpressed in The Synovial Tissue from Severe Temporomandibular Joint Dysfunction

Matrix metalloproteinases (MMPs) are tissue-enzymes that play a key role during the remodeling process, such as in inflammatory diseases. MMP-7 and MMP-9 have been shown to be implicated in extracellular matrix homeostasis and in joint disc remodeling. The objective of this study was to determine the relation of MMP-7 and MMP-9 expression with severe temporomandibular joint dysfunction, in particular with anterior disk displacement without reduction (ADDwoR), using an immunohistochemical approach. Therefore, twenty human temporomandibular synovia in the test group and ten in the control group were collected. The results showed there was a statistically significant difference (P\u3c0.001) for morphometric and densitometric analysis of both detected MMPs in control and test groups. In conclusion, MMP-7 and MMP-9 were overexpressed in the synovial tissue of patients with ADDwoR

Recent advances in the treatment of Chagas disease

Descoberta há cem anos, a doença de Chagas afeta a mais de quinze milhões de pessoas em toda a América Latina e, ainda hoje, não há tratamentoeficaz. O fármaco benznidazol, utilizado como única opção de tratamento no Brasil, é ineficaz na fase crônica da doença. Problemas relacionados à biodisponibilidade do medicamento comercial limitam sua eficácia, principalmente na fase crônica, quando os parasitos estão confinados em tecidos profundos e em lenta replicação. Nesse contexto, pesquisas lideradas por grupos brasileiros e argentinos vêm sendo conduzidas com o objetivo de desenvolver formulações de benznidazol mais eficientes. Diversas formas farmacêuticas sólidas e líquidas foram propostas nos últimos anos com resultados pré-clínicos promissores, sendo descritas melhorias acentuadas nas características farmacocinéticas desse fármaco. Espera-se que as formas inovadoras apresentadas possam ser avaliadas em ensaios clínicos e incorporadas à produção industrial em breve.Discovered about a hundred years ago, Chagas disease currently affects more than fifteen million people in Latin America, and it still remains without any effective treatment. Although benznidazole has been used as the only pharmacotherapeutic option to treat Chagas disease in Brazil, it is ineffective in the chronic phase of the disease, when the parasites are confined to deep tissue layers and slowly replicate. This happens mainly due to problems related to the bioavailability of the drug, which is currently in the market. In this context, Brazilian and Argentinean research groups have conducted studies to develop more efficient benznidazole formulations. Several solid and liquid formulations have been proposed over the last few years with promising preclinical results. Improvements in the pharmacokinetic properties of this drug have been described. Therefore, it is expected, that such innovative drugs and formulations be assessed in clinical trials and soon incorporated to industrial production.Fil: da Cunha Filho, Marcílio Sérgio Soares . Universidade Do Brasilia; BrasilFil: de Sá-Barreto, Lívia Cristina lira . Universidade Do Brasilia; BrasilFil: Leonardi, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Lamas, Maria Celina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentin

Impacts of air pollution on human and ecosystem health, and implications for the National Emission Ceilings Directive. Insights from Italy

Across the 28 EU member states there were nearly half a million premature deaths in 2015 as a result of exposure to PM2.5, O3 and NO2. To set the target for air quality levels and avoid negative impacts for human and ecosystems health, the National Emission Ceilings Directive (NECD, 2016/2284/EU) sets objectives for emission reduction for SO2, NOx, NMVOCs, NH3 and PM2.5 for each Member State as percentages of reduction to be reached in 2020 and 2030 compared to the emission levels into 2005. One of the innovations of NECD is Article 9, that mentions the issue of “monitoring air pollution impacts” on ecosystems. We provide a clear picture of what is available in term of monitoring network for air pollution impacts on Italian ecosystems, summarizing what has been done to control air pollution and its effects on different ecosystems in Italy. We provide an overview of the impacts of air pollution on health of the Italian population and evaluate opportunities and implementation of Article 9 in the Italian context, as a case study beneficial for all Member States. The results showed that SO42− deposition strongly decreased in all monitoring sites in Italy over the period 1999–2017, while NO3− and NH4+ decreased more slightly. As a consequence, most of the acid-sensitive sites which underwent acidification in the 1980s partially recovered. The O3 concentration at forest sites showed a decreasing trend. Consequently, AOT40 (the metric identified to protect vegetation from ozone pollution) showed a decrease, even if values were still above the limit for forest protection (5000 ppb h−1), while PODy (flux-based metric under discussion as new European legislative standard for forest protection) showed an increase. National scale studies pointed out that PM10 and NO2 induced about 58,000 premature deaths (year 2005), due to cardiovascular and respiratory diseases. The network identified for Italy contains a good number of monitoring sites (6 for terrestrial ecosystem monitoring, 4 for water bodies monitoring and 11 for ozone impact monitoring) distributed over the territory and will produce a high number of monitored parameters for the implementation of the NECD

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients

Design and Preparation of Pharmaceutical Solid Dosage Forms of Benznidazole for the Treatment of Chagas Disease

INTRODUCCIÓN: En Argentina se emplea el benznidazol como terapéutica de primera línea para el tratamiento etiológico del Chagas. Desde su lanzamiento (hace más de 40 años), sólo se dispone de comprimidos convencionales de 100 mg; no se han desarrollado nuevas formas farmacéuticas que aumenten la eficacia y seguridad, ni alternativas con dosis pediátricas. OBJETIVOS: Desarrollar formas farmacéuticas de benznidazol que ofrezcan ventajas farmacoterapéuticas. MÉTODOS: Preformulación y diseño de nuevas formulaciones de benznidazol, con caracterización físico-química y selección de las formulaciones más favorables. Frente a la discontinuidad de producción del ingrediente activo benznidazol, se desarrolló una metodología de extracción a partir de la única alternativa comercial disponible. RESULTADOS: Se obtuvieron nuevas formulaciones de comprimidos de 50 y 100 mg de benznidazol, con una rápida disolución del producto de referencia. Además, se obtuvieron formulaciones masticables de 50 mg bajo la forma de hidrogeles azucarados, con un efectivo enmascaramiento del mal sabor. Todas las formulaciones cumplieron los ensayos de evaluación de las propiedades farmacotécnicas y biofarmacéuticas, superando los perfiles de referencia. CONCLUSIONES: Se desarrollaron nuevas alternativas farmacéuticas de benznidazol de rápida disolución, que podrían mejorar el tratamiento etiológico de la enfermedad (especialmente en pediatría) y convertirse en herramientas aptas para su explotación comercial.INTRODUCTION: In Argentina, benznidazole is the drug of choice for the etiological treatment of Chagas disease. Since it was launched (more than 40 years ago), there are only 100 mg tablets available; the development included neither new pharmaceutical forms improving efficacy and safety, nor a pediatric dosage option. OBJECTIVES: To develop pharmaceutical forms of benznidazole with pharmacotherapeutic advantages. METHODS: Preformulation and design of new formulations of benznidazole, with physicochemical characterization and selection of the most favorable formulations. Due to the discontinuity in the production of the active ingredient benznidazole, a specific methodology was developed in order to obtain it from the only commercially available alternative. RESULTS: New benznidazole tablet formulations were obtained (50 and 100 mg), with a rapid dissolution of the reference product, as well as chewable formulations of 50 mg as sugar hydrogels featuring an effective taste masking. All formulations passed the evaluation tests for pharmacotechnical and biopharmaceutical properties, outperforming the reference profiles. CONCLUSIONS: New fast-dissolving pharmaceutical dosage forms of benznidazole were developed, which could improve the etiological treatment of the disease (especially in the pediatric field) and become a proper tool for its commercial exploitationFil: Tarragona, Sonia. Fundación Mundo Sano; ArgentinaFil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Jimenez Kairuz, Alvaro Federico. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; ArgentinaFil: Lamas, Maria Celina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Orlandi, Silvina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Leonardi, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Maggia, Norma Graciela. Universidad Nacional de Cordoba. Facultad de Cs.quimicas; ArgentinaFil: Paredes, Alejandro Javier. Universidad Nacional de Cordoba. Facultad de Cs.quimicas; ArgentinaFil: Romañuk, Carolina Beatriz. Universidad Nacional de Cordoba. Facultad de Cs.quimicas; ArgentinaFil: García, Mónica Cristina. Universidad Nacional de Cordoba. Facultad de Cs.quimicas; Argentin

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments

Disponibilidade de luz, tipo de vedação e de frasco na germinação e crescimento inicial in vitro de plântulas de cubiu (Solanum sessiliflorum Dunal)

This work aimed to evaluate the different types of sealing and flask size in relation to the rates of germination and biomass partitioning in seedlings of two varieties of Solanum sessiliflorum Dunal. Seeds of varieties Santa Luzia and Thais were inoculated into flasks of varying sizes, containing culture medium Murashige and Skoog (1962) with 50% of the concentration and sealed with different materials. It was found shriveling leaf in plantlets of both varieties grown in sealed flasks with polyvinyl chloride (PVC). The varieties Santa Luzia and Thais showed high germination percentage in flasks sealed with PVC and aluminum foil. Furthermore, the type of flask and sealing influenced the accumulation of assimilates in both varieties. It was found yet, the highest average of fresh matter in large flasks and sealed with aluminum for the Thais variety, while the Santa Luzia variety, the flask size does not interfere with weight, but those sealed with aluminum have a higher average weight. The dry matter accumulation for Thais variety were higher for plantlets cultivated in large flasks sealed with PVC, and for Santa Luzia variety were large flasks or sealed with PVC. Both varieties, when grown with aluminum foil have the highest average length of the aerial part. Plantlets cultivated in small flasks and sealed with PVC presented higher rootlength. It was concluded that the leaf shriveling was remarkable in flasks sealed with PVC and the accumulation of assimilates is influenced by the type of flask and seal for both varieties in the presence of light.O presente trabalho teve como objetivo avaliar os diferentes tipos de vedação e o tamanho do frasco em relação às taxas de germinação e partição de biomassa em plântulas de duas variedades de Solanum sessiliflorum Dunal. Sementes das variedades de cubiu, Santa Luzia e Thaís, foram inoculadas em frascos com diferentes tamanhos, contendo meio de cultura com Murashige e Skoog (1962), com 50% da concentração e vedados com diferentes materiais. Verificou-se encarquilhamento foliar das plântulas de ambas as variedades que foram inoculadas em frascos vedados com policloreto de vinila (PVC). As variedades Santa Luzia e Thais apresentaram alta porcentagem de germinação em frascos vedados com PVC e papel alumínio. Além disso, detectou-se que, para ambas as variedades, que o tipo de frasco e vedação interferem no acúmulo de fotoassimilados. Verificou-e-se ainda que, para a variedade Thais, existe a maior média de matéria fresca em frascos grandes e vedados com alumínio, enquanto na variedade Santa Luzia o tamanho do frasco não interfere na biomassa, mas aqueles vedados com alumínio apresentam maior massa. O acúmulo de matéria seca para a variedade Thais foi maior em frascos grandes vedados com PVC e para variedade Santa Luzia foram frascos grandes ou vedados com PVC. Ambas as variedades, quando cultivadas em frascos vedados com papel alumínio, apresentam a maior média no comprimento da parte aérea. Plântulas de cubiu cultivadas em frascos pequenos e vedados com PVC apresentaram maior comprimento radicular. Concluiu-se que o encarquilhamento foliar foi marcante em frascos vedados com PVC e o acúmulo de fotoassimilados é influenciado pelo tipo de frasco e vedação para ambas as variedades na presença de luz