Combining prostate cancer radiotherapy with therapies targeting the androgen receptor axis.

Background: Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (adt) and radiotherapy (rt). New androgen-receptor-axis targeted therapies (arats), which await validation, offer an option to intensify therapy. Methods: In this narrative review, we report the relevant history that has supported combining adt with rt. The literature in PubMed was searched for studies involving pca and novel arats (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored. Results: Early results from three phase i/ii trials demonstrated that concurrent abiraterone acetate, adt, and rt is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single in vitro study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.

Higgs physics at the CLIC electron-positron linear collider.

The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.

Rendimiento diagnóstico de la histerosalpingografía por resonancia magnética: resultados iniciales / Diagnostic performance of magnetic resonance hysterosalpingography: initial results Abstract

Objetivo: Determinar el rendimiento diagnóstico de la histerosalpingografía por resonancia magnética (HSG-RM), utilizando la laparoscopia como método de referencia. Materiales y métodos: Se incluyeron 22 pacientes. A todas se les realizó una HSG-RM con un resonador 1.5 Tesla y luego una laparoscopia con cromotubación. Dos radiólogos examinaron las RM, determinando la permeabilidad tubaria por consenso. Se realizaron análisis descriptivos y de rendimiento diagnóstico. Resultados: La HSG-RM tuvo una tasa de éxito del 91%. La duración del estudio fue 49ą15 minutos, el volumen inyectado 26 ą 16 cm³ y la escala de dolor 30ą 19 de 100. La sensibilidad y especificidad de la HSG-RM fueron del 100% para la prueba de Cotte global y a la izquierda, y del 25% y 93,3% para la prueba de Cotte a la derecha, respectivamente. Hubo 2 complicaciones menores y ninguna importante. Discusión: Nuestros resultados iniciales demostraron una alta sensibilidad y especificidad. Si bien otros estudios analizaron la capacidad de la HSG-RM para evaluar la permeabilidad tubaria con buenos resultados, el uso de un patrón de referencia defectuoso dejaba margen para una duda razonable, impidiendo una recomendación basada en pruebas sólidas. Sin embargo, al cotejar nuestros resultados con los publicados, observamos un alto grado de concordancia en tanto el derrame positivo se diagnostica correctamente con una especificidad de 100% o con un porcentaje cercano a esta cifra. Conclusión: La HSG-MR es una alternativa factible y segura de la HSG convencional o virtual, la histerosonografía y la cromotubación.

Objective: To determine the diagnostic performance of magnetic resonance hysterosalpingography (MRHSG) using laparoscopic chromotubation as a method of reference. Materials and methods: Twenty-two patients were included. The MRHSG was performed in a 1.5 Tesla MR scanner. Afterwards, patients underwent laparoscopic chromotubation. MR images were examined by two trained radiologists, and tubal patency was determined by consensus. A descriptive analysis was carried out, as well as an analysis of the diagnostic performance. Results: MRHSG had a 91% success rate. Exam duration of the examination was 49ą15min, with an injected volume 26ą 16cc, and pain scale 30ą 19 out of 100. Sensitivity and specificity of MRHSG was 100% for global and left Cotte, and 25% and 93.3% for right Cotte, respectively. Only 2 minor and no major complications were observed. Discussion: The initial results of MRHSG have shown high sensitivity and specificity. Even though other studies have analysed the potential of MRHSG with good results, the use of a flawed reference standard left a margin for a reasonable doubt as regards its true potential, thus preventing a solid evidence based recommendation. Nevertheless, if our results are compared to those published, a high level of agreement is observed in that positive spillage is correctly diagnosed with specificities near or at 100%. Conclusion: MRHSG is a feasible and safe alternative to conventional or virtual HSG, ultrasound-hysterography and chromotubation.

Decomposition of xenobiotics during visible light irradiation in the presence of immobilised photosensitisers: kinetics study.

The objective of this work was to study the photosensitised oxidation of the xenobiotics benzylparaben (BeP) and 2,4dichlorophenol (2,4DCP) in aqueous solutions using photosensitisers immobilised into chitosan carrier particles and visible light radiation. Zn(II) phthalocyanine tetrasulfonate tetrasodium salt and Al(III) phthalocyanine chloride tetrasulfonic acid were used as photosensitisers. The major role of the singlet oxygen during photodegradation was proven by using scavengers of reactive oxygen species. The influence of initial xenobiotic concentration and temperature on degradation rate was examined. The investigations were focused on kinetics (Langmuir-Hinshelwood model) as well as activation energy determination. Moreover, the adsorption isotherms of BeP and 2,4DCP into chitosan carrier were determined using the Brunauer-Emmett-Teller model.

Brain glucose metabolism in an animal model of depression.

An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to all experimental conditions, i.e., prenatal stress, acute stress, and glucose administration. Our data indicate that glycolysis is increased and the Krebs cycle is decreased in the brain of a prenatal stress animal model of depression.

Performance of the LHCb RICH detector at the LHC.

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2-100 GeV/c. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (π, K, p) is achieved.

The emerging role of viruses in the treatment of solid tumours.

There is increasing optimism for the use of non-pathogenic viruses in the treatment of many cancers. Initial interest in oncolytic virotherapy was based on the observation of an occasional clinical resolution of a lymphoma after a systemic viral infection. In many cancers, by comparison with normal tissues, the competency of the cellular anti-viral mechanism is impaired, thus creating an exploitable difference between the tumour and normal cells, as an unimpeded viral proliferation in cancer cells is eventually cytocidal. In addition to their oncolytic capability, these particular viruses may be engineered to facilitate gene delivery to tumour cells to produce therapeutic effects such as cytokine secretion and anti -tumour immune responses prior to the eventual cytolysis. There is now promising clinical experience with these viral strategies, particularly as part of multimodal studies, and already several clinical trials are in progress. The limitations of standard cancer chemotherapies, including their lack of specificity with consequent collateral toxicity and the development of cross-resistance, do not appear to apply to viral-based therapies. Furthermore, virotherapy frequently restores chemoradiosensitivity to resistant tumours and has also demonstrated efficacy against cancers that historically have a dismal prognosis. While there is cause for optimism, through continued improvements in the efficiency and safety of systemic delivery, through the emergence of alternative viral agents and through favourable clinical experiences, clinical trials as part of multimodal protocols will be necessary to define clinical utility. Significant progress has been made and this is now a major research area with an increasing annual bibliography.

Transpupillary thermotherapy for choroidal metastases.

INTRODUCTION: We report on a case with bilateral choroidal metastases derived from a renal cell carcinoma 13 years after nephrectomy. The treatment modality is discussed. METHODS: A male patient (58 years of age) presented with asymptomatic bilateral choroidal metastases deriving from renal cell carcinoma. The right kidney had been removed because of renal cell carcinoma 13 years before the appearance of the choroidal metastases. He had full visual acuity (20/20) and normal intraocular pressure in both eyes. Fundus examination showed a small tumor in the peripheral choroidea of his right eye and an intermediate-sized solid tumor in the periphery of his left eye. RESULTS: The tumor of the right eye was treated by TTT and the tumor of the left eye by (106)Ru plaque radiotherapy. The tumors showed total regression into flat chorioretinal atrophies in both eyes and no tumor could be found 13 moths after treatment maintaining full visual acuity (20/20). CONCLUSION: Asymptomatic ocular metastases can develop even many years after removal of the primary tumor. TTT and (106)Ru brachytherapy are useful treatment modalities in cases of small and intermediate-sized choroidal metastases.

Management of simple elbow dislocations. Does the period of immobilization affect the eventual results?

METHODS: Forty-five patients with a simple elbow dislocation were re-examined at an average time of 61 months after injury. All patients were treated by means of closed reduction. Only patients with minor associated injuries were included in the study. The Morrey score was used to evaluate pain, limitation of motion, instability, and daily activities. The overall results were good or excellent with regard to pain and function. The most common finding was a loss of terminal extension. Nine percent of all patients had a lack of extension up to 30 degrees, while 36% had a flexion contracture of less than 10 degrees. Periarticular ossification was seen in 28 patients, but did not lead to loss of motion. For further analysis, the patients were divided into three groups of immobilization: group I, less than 2 weeks, group II, 2-3 weeks, and group III, more than 3 weeks. RESULTS: We encountered better results from those in groups I and II with regard to pain and score results without any statistical significance. CONCLUSION: Our results suggest that splintage of the reduced elbow for 2 weeks enhances patient comfort and does not adversely affect the eventual outcome. Splintage for over 3 weeks may result in worse function.