5α-Reductase Inhibitors and Risk of Prostate Cancer Death.

PURPOSE: 5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group. MATERIALS AND METHODS: Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group. RESULTS: In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers. CONCLUSIONS: We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.

Unsaturated Response of Clayey Soils Stabilised with Alkaline Cements.

The influence of suction on the mechanical behaviour of unsaturated chemically stabilised soils is still mostly unknown and unquantified. This is also motivated by the difficulties associated with the experimental procedure required to fully characterise the unsaturated response of the soil, including its direct influence on traditional strength tests. The present paper presents the soil water retention curves obtained for a Portuguese soil before and after being stabilised with Portland cement (OPC) and an alkali-activated cement (AAC). Saturated undrained triaxial tests were also performed for the same curing conditions (0, 28, and 90 days). Previous attempts to characterise the retention curve of soils stabilised with AAC are unknown, and the results showed that the pore volume structure is already formed after 28 days, prior to the full development of the gel matrix responsible for the strength increase between 28 and 90 days. The curve changed after stabilisation, and with each binder, as the OPC presented a higher air-entry value and a narrower suction range compared to the AAC solution. The significant differences between the curves obtained from each binder suggest the future development of a methodology to assess the quality of the AAC stabilisation.

Stratigraphic Relations of the Ipubi Formation: Siliciclastic-Evaporitic Succession of the Araripe Basin.

The Ipubi Formation represents the Aptian-Albian siliciclastic-evaporitic succession of Araripe Basin, NE Brazil. This succession comprises siliciclastic rocks (bituminous shales and claystones) and evaporites (gypsum and secondary anhydrite) and represents part of the lacustrine-shallow marine post-rift phase I. This study used sequence stratigraphy concepts to define the relations between changes in the relative lake level and the formation of Ipubi deposits. Results show that the organic-rich shales of the Ipubi Formation formed during a transgressive pulse that covered large areas of the proximal domains. These deposits overlie a regional unconformity that marks the end of the deposition of the underlying Crato Formation. A High Stand stage that followed the transgression influenced the formation of evaporitic deposits. Climate conditions played a major role in influencing the triggering and stopping of evaporite deposition. Thus, a new relative lake level fall event caused the exposure of the Ipubi Formation deposits, and created another regional subaerial unconformity accompanied by widespread karstification of evaporite beds. A posterior transgression caused the deposition of siliciclastic rocks of the Romualdo Formation over the Ipubi Formation strata, and also promoted a new event of karstification of the Ipubi upper evaporite beds.

Simultaneous quantitation of chloroquine and primaquine by UPLC-DAD and comparison with a HPLC-DAD method.

BACKGROUND: Chloroquine and primaquine are the first-line treatment recommended by World Health Organization for malaria caused by Plasmodium vivax. Since the problem of counterfeit or substandard anti-malarials is well established all over the world, the development of rapid and reliable methods for quality control analysis of these drugs is essential. Thus, the aim of this study was to develop and validate a novel UPLC-DAD method for simultaneously quantifying chloroquine and primaquine in tablet formulations. METHODS: The UPLC separation was carried out using a Hypersil C18 column (50 × 2.1 mm id; 1.9 µm particle size) and a mobile phase composed of acetonitrile (A) and 0.1% aqueous triethylamine, pH 3.0 adjusted with phosphoric acid (B), at a flow rate 0.6 mL/min. Gradient elution was employed. UV detection was performed at 260 nm. UPLC method was fully validated and the results were compared to a conventional HPLC-DAD method for the analysis of chloroquine and primaquine in tablet formulations. RESULTS: UPLC method was shown to be linear (r2 > 0.99), precise (CV < 2.0%), accurate (recovery rates from 98.11 to 99.83%), specific, and robust. No significant differences were observed between the chloroquine and primaquine contents obtained by UPLC and HPLC methods. However, UPLC method promoted faster analyses, better chromatographic performance and lower solvent consumption. CONCLUSIONS: The developed UPLC method was shown to be a rapid and suitable technique to quantify chloroquine and primaquine in pharmaceutical preparations and may be successfully employed for quality control analysis.

Neurotoxicity, Behavior, and Lethal Effects of Cadmium, Microplastics, and Their Mixtures on Pomatoschistus microps Juveniles from Two Wild Populations Exposed under Laboratory Conditions-Implications to Environmental and Human Risk Assessment.

Microplastics (MPs) were found to modulate the toxicity of other pollutants but the knowledge on the topic is still limited. The goals of this study were to investigate the short-term toxicity of cadmium (Cd) to wild Pomatochistus microps juveniles, the potential modulation of acute Cd toxicity by 1-5 µm polyethylene MPs in this species, and possible differences of sensitivity to Cd and MPs-Cd mixtures between juveniles from two distinct wild populations. Juveniles were collected in the estuaries of Minho (M-est) and Lima (L-est) Rivers (NW Portugal). One 96 h bioassay with M-est juveniles and another one with L-est juveniles were carried out in laboratory conditions. Each bioassay had 12 treatments: control, 5 Cd concentrations, 1 MPs concentration, and 5 MPs-Cd mixtures. No significant differences in Cd-induced mortality between juveniles from distinct estuaries or between juveniles exposed to Cd alone and those exposed to MPs-Cd mixtures were found. The total 96h LC10 and LC50 of Cd alone were 2 mg/L (95% CI: 0-4 mg/L) and 8 mg/L (95% CI: 2-17 mg/L), respectively. Cd alone significantly decreased the post-exposure predatory performance (PEPP) of M-est (≥6 mg/L) and L-est juveniles (≥3 mg/L), and acetylcholinesterase (AChE) activity of M-est juveniles (13 mg/L). MPs alone (0.14 mg/L) significantly reduced the PEPP and AChE activity of L-est juveniles but not of M-est juveniles. MPs-Cd mixtures (3-13 mg/L of Cd + 0.14 mg/L of MPs) significantly inhibited the PEPP of juveniles from both estuaries and AChE of L-est estuary juveniles but not of M-est juveniles. Evidences of toxicological interactions, namely antagonism, between MPs and Cd were found. Overall, the results indicate that MPs modulated the sub-lethal toxic effects of Cd in wild P. microps juveniles, especially neurotoxicity. Moreover, the environmental conditions of the natural habitats to which juveniles were exposed during pre-developmental phases influence the sub-lethal toxicity of Cd, MPs, and their mixtures. The implications to environmental and human risk assessment are discussed and further research is needed.

Portal vein embolization with n-butyl-cyanoacrylate through an ipsilateral approach before major hepatectomy: single center analysis of 50 consecutive patients.

PURPOSE: To evaluate the efficacy of portal vein embolization (PVE) with n-Butyl-cyanoacrylate (NBCA) through an ipsilateral approach before major hepatectomy. Secondary end-points were PVE safety, liver resection and patient outcome. METHODS: Over a 5-year period 50 non-cirrhotic consecutive patients were included with primary or secondary liver cancer treatable by hepatectomy with a liver remnant (FLR) volume less than 25% or less than 40% in diseased livers. RESULTS: There were 37 men and 13 women with a mean age of 57 years. Colorectal liver metastases were the most frequent tumor and patients were previously exposed to chemotherapy. FLR increased from 422 ml to 629 ml (P < 0.001) after PVE, corresponding to anincrease of 52%. The FLR ratio increased from 29.6% to 42.3% (P < 0.001). Kinetic growth rate was 2.98%/week. A negative association was observed between increase in the FLR and FLR ratio and FLR volume before PVE (P = 0.002). In 31 patients hepatectomy was accomplished and only one patient presented with liver insufficiency within 30 days after surgery. CONCLUSIONS: PVE with NBCA through an ipsilateral puncture is effective before major hepatectomy. Meticulous attention is needed especially near the end of the embolization procedure to avoid complications. TRIAL REGISTRATION: Clinical Study ISRCTN registration number: ISRCTN39855523 . Registered March 13th 2017.

DEB TACE for Intermediate and advanced HCC - Initial Experience in a Brazilian Cancer Center.

BACKGROUND: According to Barcelona Clinic Liver Cancer classification transarterial chemoembolization is indicated in patients with Hepatocellular Carcinoma in the intermediate stage. Drug-eluting microspheres can absorb and release the chemotherapeutic agent slowly for 14 days after its intra-arterial administration. This type of transarterial chemoembolization approach appears to provide at least equivalent effectiveness with less toxicity. METHODS: This is a prospective, single-center study, which evaluated 21 patients with intermediate and advanced hepatocellular carcinoma who underwent transarterial chemoembolization with drug-eluting microspheres. The follow up period was 2 years. Inclusion criteria was Child-Pugh A or B liver disease patients, intermediate or advanced hepatocellular carcinoma and performance status equal or below 2. Transarterial chemoembolization with drug-eluting microspheres was performed at 2-month intervals during the first two sessions. The third and subsequent sessions were performed according to the image findings on follow-up, on a "demand schedule". Tumor response and time to progression were evaluated along the two-year follow up period. RESULTS: Of the 21 patients 90% presented with liver cirrhosis, 62% had Barcelona Clinic Liver Cancer stage B and 38% had Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma. Average tumor size was 6.9 cm. The average number of Transarterial chemoembolization with drug-eluting microspheres procedures was 3 with a total of 64 sessions. The predominant toxicity was mild. Liver function was not significantly affected in most patients. Two deaths occurred within 90 days after Transarterial chemoembolization with drug-eluting microspheres (ischemic hepatitis and hydropic decompensation). Technical success was achieved in 63 of 64 procedures. The mean hospital stay was 1.5 days. The progression free and overall survival at 1 and 2 years were 73.0% and 37.1%, 73.7% and 41.6%, respectively. CONCLUSION: Transarterial chemoembolization with drug-eluting microspheres is able to deliver significant tumor response and progression free survival rate with acceptable toxicity. Larger studies are needed to identify exactly which subset of advanced hepatocellular patients may benefit from this treatment. TRIAL REGISTRATION: study ID ISRCTN16295622. Registered October 14th 2016. Retrospectively registered. Website registration: http://www.isrctn.com/ISRCTN16295622.

Jeux vidéo: Espace pour la (proto)construction dans et par le Rorschach / Video games: A space for (proto)construction in and by the Rorschach / Videojogos: espaço de (proto)construção no e pelo Rorschach / Videojuegos: espacio para (proto)construcción en y por el Rorschach

Les jeux vidéo sont une réalité de la culture d'aujourd'hui. Cet article est basé sur un échantillon de neuf protocoles de Rorschach appliques à de jeunes adultes qui sont des joueurs actifs. Les résultats du Rorschach montrent une difficulté à bien appréhender la réalité, une dynamique affective introvertie et un niveau élevé d'angoisse —des caractéristiques liées à un mouvement psychique où se posent des questions de force et d'autorité (I et IV), des arsenaux de guerre (VII), avec inscription dans des relations affectives (II et III) ou des logiques régressives (VIII, IX et X). Cette étude nous a permis de construire un (proto)virtuel, avec de nouveaux Avatars au Rorschach, une construction tridimensionnelle qui entrelace le réel et le virtuel, dans un domaine de la projection sur la perception, où le (proto)mentale est (re)signifié.

Os videojogos são uma realidade da cultura atual. O presente artigo é realizado com base numa amostra de nove protocolos de Rorschach, de jovens adultos jogadores ativos de videojogos. Os resultados encontrados no Rorschach evidenciam uma dificuldade em compreender corretamente a realidade, uma dinâmica afetiva de tipo introversivo e um elevado nível de angústia. Características que se encontram ligadas a um movimento psíquico onde surgem as questões de força e de autoridade (I e IV), arsenais de guerra (VII), com inscrição em relações afetivas (II e III) ou em lógicas regressivas (VIII, IX e X). Através deste estudo foi possível a construção de um (proto)virtual, com novos Avatares no Rorschach, uma construção tridimensional que entretece o real e o virtual, num domínio da projeção sobre a perceção, onde se contém e (re)significa o (proto)mental.

Video games are a reality of today's culture. This article is based on a sample of nine Rorschach protocols applied to young adults who are active gamers. The Rorschach results show a difficulty in correctly understanding reality, an introverted affective dynamic and a high level of anxiety — characteristics linked to a psychic movement where matters of strength and authority (I and IV), arsenals of war (VII), with inscription in affective relations (II and III) or with regressive logics (VIII, IX and X) are posed. This study allowed us to build a (proto)virtual, with new Avatars in the Rorschach, a three-dimensional construction that intertwines the real and the virtual, putting projection over perception, where the (proto)mental is (re)signified.

Los videojuegos son una realidad de la cultura en la actualidad. El presente artículo se fundamenta en una muestra de nueve protocolos del Rorschach, de jugadores jóvenes adultos activos. Los resultados encontrados en el Rorschach muestran una dificultad para comprender correctamente la realidad, una dinámica afectiva introvertida y un alto nivel de angustia. Tales características se vinculan a un movimiento psíquico donde surgen cuestiones de fuerza y autoridad (I e IV), arsenales de guerra (VII), con inscripción en relaciones afectivas (II e III) o en lógicas regresivas (VIII, IX y X). Este estudio posibilitó la construcción de un (proto)virtual, con nuevos Avatares en el Rorschach, una construcción tridimensional que entrelaza lo real y lo virtual en un dominio de la proyección sobre la percepción, que contiene y (re)significa el (proto)mental.

In vitro dissolution kinetic for mycophenolic acid derivatives tablets

Mycophenolate mofetil (MMF) and mycophenolate sodium (MPS) are an ester and a salt of mycophenolic acid. They have different kinetic in vivo characteristics due to differences in molecular structures, physicochemical properties and formulations administered. In this study, dissolution profiles of reference products were tested in different media to evaluate the effect of pH, kinetic dissolution and the best statistical model that can be used to predict the release of both drugs. The drug release was determined by using a validated ultraviolet spectrophotometry method, λ 250 nm. The method showed to be selective, linear, precise and accurate for MMF in 0.1 M HCl and MPS in sodium phosphate buffer pH 6.8. Dissolution kinetics models of zero order, first order, Higuchi, Hixson-Crowell and Weibull were applied to data in order to select the best fit by linear regression. The regression parameters were estimated and the models were evaluated with the results of residuals and coefficient of determination. The residuals obtained from dissolution kinetics models were random, uncorrelated, and normally distributed with constant variance. The R² values (74.7% for MMF and 95.8% for MPS) demonstrated good ability of the Weibull regression to explain the variability and to predict the drugs' release.

Micofenolato de mofetila (MMF) e micofenolato sódico (MPS) são, respectivamente, éster e sal sódico do ácido micofenólico. Os fármacos possuem características farmacocinéticas distintas em função das diferenças na estrutura molecular, nas propriedades físico-químicas e nas formulações administradas. Neste trabalho, os perfis de dissolução dos medicamentos referências foram testados em diferentes meios de dissolução com o objetivo de avaliar o efeito da variação de pH, a cinética de dissolução e o modelo estatístico mais adequado para prever a dissolução dos fármacos. A liberação dos fármacos foi determinada com método validado por espectroscopia no ultravioleta, λ 250 nm. O método mostrou-se seletivo, linear, preciso e exato para dissolução de MMF em 0,1 M HCl e MPS em tampão fosfato pH 6,8. Os modelos cinéticos de dissolução de ordem zero, primeira ordem, Higuchi, Hixson-Crowell e Weibull foram aplicados com o objetivo de selecionar aquele com o melhor ajuste por regressão linear. Os parâmetros de regressão foram estimados e os ajustes dos modelos foram verificados pelos resíduos e coeficientes de determinação. Os resíduos obtidos foram aleatórios, independentes, apresentaram variância constante e seguiram a distribuição normal. Os valores de R² (74,7% para MMF e 95,8% para MPS) indicaram bom ajuste da regressão de Weibull para explicar a variabilidade e estimar a liberação dos fármacos.