Abstract Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-β-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

Resumo A onicomicose é a doença mais comum que afeta a unidade ungueal e representa pelo menos 50% de todas as doenças ungueais. Além disso, a Candida albicans é responsável por aproximadamente 70% das onicomicoses causadas por leveduras. Nesse estudo, foi investigado o efeito antifúngico dos enantiômeros (R) e (S)-citronelal, bem como seu mecanismo de ação preditivo sobre C. albicans de onicomicoses resistentes ao voriconazol. Para este propósito, foram aplicadas técnicas in vitro de microdiluição em caldo e docking molecular de forma preditiva e complementar para os mecanismos de ação. Os principais resultados deste estudo indicam que C. albicans foi resistente ao voriconazol e sensível aos enantiômeros (R) e (S)-citronelal na dose de 256 e 32 µg/mL respectivamente. Além disso, houve aumento da concentração inibitória mínima (CIM) dos enantiômeros na presença do sorbitol e do ergosterol, indicando que estas moléculas possivelmente afetem a integridade da parede e da membrana celular de C. albicans. O docking molecular com proteínas chave da biossíntese e manutenção da parede celular e da membrana plasmática fúngica, demonstraram a possibilidade do (R) e (S)-citronelal interagir com duas importantes enzimas: 1,3-β-glucan sintase e lanosterol 14α-demetilase. Portanto, os achados desse estudo indicam que os enantiômeros (R) e (S)-citronelal são fungicidas sobre C. albicans de onicomicoses e provavelmente essas substâncias causem danos a parede e a membrana celular desses microrganismos possivelmente por interagir com as enzimas da biossíntese destas estruturas fúngicas.

Os aneurismas da artéria esplénica são raros, mas constituem cerca de 60% de todos os aneurismas arteriais viscerais. A grande maioria dos doentes (80%) é assintomática sendo o diagnóstico realizado através de um achado em exames de imagem. O risco de rotura estimado é de 3% a 10%, com uma taxa de mortalidade associada à rotura de 25 a 70%. Critérios para tratamento eletivo incluem aneurismas sintomáticos, aneurismas com dimensões superiores a 20 mm ou com o aumento rápido do diâmetro. Adicionalmente, aneurismas diagnosticados em pacientes com hipertensão portal ou mulheres em idade fértil também têm indicação para tratamento, independentemente do diâmetro. O tratamento endovascular é a primeira linha em doentes com aneurismas da artéria esplenica, e inclui várias opções, como embolização com coils, oclusão com recurso a balões destacáveis e colocação de endoprótese vascular. Esta última é mais adequada para aneurismas localizados proximalmente e sua principal vantagem consiste no potencial para preser- var o fluxo arterial esplénico e a função esplénica. É de salientar que a colocação de endoprótese para o tratamento de aneurismas da artéria esplénica está pouco descri- ta na literatura, consistindo sobretudo em pequenas séries de casos, todas com menos de 10 doentes. Trata-se de um procedimento que pode ser tecnicamente desafiante devido à tortuosidade da artéria esplênica. Não há resultados de follow-up a longo prazo na literatura. Neste artigo descrevemos dois casos de reparação de aneurisma da artéria utilizando stent grafts, com um follow-up máximo de 8 anos. Atingiu-se sucesso técnico em ambos os casos, sem crescimento pós-procedimento, endoleak, kink- ing, migração, re-intervenções ou outras complicações. Como conclusão, os dados na literatura sobre o uso de stents recobertos em aneurismas da artéria esplénica são escas- sos. Os resultados destes dois casos no nosso centro são encorajadores com um período de seguimento excecional

Splenic artery aneurysms are rare, but constitute nearly 60% of all visceral arterial aneurysms. Most patients (80%) are asymptomatic and diagnosed incidentally. Rupture risk is estimated in 3%-10%, with a mortality rate of 25-70%. Elective treatment criteria include symptomatic patients, aneurysms larger than 2 cm in diameter or with rapid enlarge- ment and aneurysms of any size diagnosed in patients with portal hypertension or women of childbearing age; Endovascular treatment is first line of treatment in patients with splenic artery aneurysms, and include several options such as coil embolization, detachable balloon occlusion and stent graft placement. The latter is more suitable for proxi- mally located aneurysms and its main advantage is the potential to preserve splenic blood flow and splenic function. It is noteworthy that stent graft placement to treat splenic artery aneurysms is rarely described in the literature with the largest series having 10 cases, and can be technically challenging due to splenic artery tortuosity. There are no long term results in the literature. In this paper we describe two cases of splenic artery aneurysm repair using stent grafts, with a maximum follow-up of 8 years. We achieved technical success in both cases, with no post-procedure growth, endoleak, kinking, migration re-interven- tion or other complications. As a conclusion, there is paucity of data on the use of stent grafts in splenic artery aneurysms, however our single center small series results are encouraging with a considerable follow-up period.

Although sudden cardiac death is one of the most important mode of death in Western Countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed, and the accurate diagnosis of the causes of sudden cardiac death is now of particular importance. Pathologists are responsible for determining the precise cause of sudden death but there is considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology developed guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate assessment of sudden cardiac death, including not only a protocol for heart examination and histological sampling, but also for toxicology and molecular investigation. Our recommendations apply to university medical centres, regional and district hospitals and all types of forensic medicine institutes. If a uniform method of investigation is adopted throughout the European Union, this will lead to improvements in standards of practice, allow meaningful comparisons between different communities and regions and, most importantly, permit future trends in the patterns of disease causing sudden death to be monitored.

A pesar de que la muerte súbita cardíaca es una de las formas más importantes de muerte en los países occidentales, este problema no ha recibido la atención que merece por parte de los patólogos y de los médicos de los sistemas públicos de salud. Se han desarrollado nuevos métodos de prevención de arritmias potencialmente mortales, y el diagnóstico de certeza de las causas de muerte súbita cardíaca es en este momento de particular importancia. Los patólogos son responsables de determinar la causa exacta de la muerte súbita pero existen diferencias considerables en el modo en el que se aborda esta cada vez más compleja tarea. La Asociación Europea de Patología Cardiovascular desarrolló unas guías que representan el estándar mínimo necesario en la práctica habitual de la autopsia para la valoración de la muerte súbita cardíaca, incluyendo no sólo un protocolo para el examen del corazón y el muestreo histopatológico, sino también para la investigación toxicológica y molecular. Nuestras recomendaciones son aplicables a centros médicos universitarios, a hospitales regionales y locales y a todo tipo de Institutos de Medicina Forense. La adopción a lo largo de la Unión Europea de un método uniforme de investigación supondrá la mejora de la práctica habitual, permitirá realizar comparaciones significativas entre distintas comunidades y regiones y, lo que es más importante aún, favorecerá que se monitoricen los patrones de las enfermedades que causan una muerte súbita.

Most industrial processes generate liquid waste, which requires treatment prior to disposal. These processes are divided into sectors that generate effluents with time dependent characteristics. Each sector sends the effluent to wastewater treatment plants through pumping-stations. In general, activated sludge is the most suitable treatment and consists of equalization, aeration and settling tanks. During the treatment, there is an increase in the mass of microorganisms, which needs to be removed. Sludge removal represents the major operating costs for wastewater treatment plants. The objective of this work is to propose an optimization model to minimize sludge generation using a superstructure in which the streams from pumping-stations can be sent to the equalization tank. In addition, the aeration tank is divided into cells that can be fed in series and parallel. The model relies on mass balances, kinetic equations, and the resulting Nonlinear Programming problem generates the best operational strategy for the system feed streams with a high substrate removal. Reductions of up to 30 % can be achieved with the proposed strategy maintened BOD efficiency removal upper than 98 %.