Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Diversity analysis of Streptomycetes and associated phosphotranspherase genes in soil

An attempt was made to verify the observation that Streptomyces griseus was prevalent in soil based on isolation work. A genus-specific PCR was developed for Streptomyces based on the housekeeping gene atpD and used to investigate species diversity within selected soils. The presence of S. griseus was investigated to determine coexistence of resistance-only streptomycin phosphotransferase (strA) in the same soil as streptomycin producers. Two additional PCR-based assays were developed; one specific for strA in association with production, the other for more diverse strA and other related phosphotranferases. Both the S. griseus atpD and strA genes were below the PCR detection limit in all soils examined. A number of more diverse phosphotransferase genes were amplified, a minority of which may be associated with streptomycin production. We conclude that neither streptomycin producers nor S. griseus are prevalent in the fresh or chitin and starch-amended soils examined (less than 0.1% of soil actinobacteria). One of the soil sites had received plantomycin (active ingredient: streptomycin) and diversity studies suggested that this altered the streptomycete populations present in the soil

Qualidade de vida em mulheres com incontinência urinária

The aim of this study is to examine the relationship among psychological, clinical and sociodemographic variables, and quality of life in women with urinary incontinence. The sample consisted of 80 women diagnosed with urinary incontinence (UI) followed in a Northern Central Hospital in Portugal. Participants answered the Incontinence Quality of Life (I-QOL); Satisfaction with Sexual Relationship Questionnaire (SSRQ); Hospital Anxiety and Depression Scales (HADS) and the Brief Cope. The results revealed that women with higher quality of life considered their symptoms of urine loss as mild or moderated compared to those with severe urine loss. The less severe urine loss was associated with greater sexual satisfaction and less use of religion and self-blame as coping strategies. In terms of coping, women who considered the loss of urine as severe expressed more feelings regarding UI. Stress urinary incontinence, high sexual satisfaction, and less use of denial, distraction, and religion as coping strategies, predicted higher quality of life. According to the results, UI has an impact on women’s sexual satisfaction and quality of life. Therefore, intervention programs should target these women, including their partners, helping them to adjust to their condition and teaching effective coping strategies in order to improve their sexual satisfaction and quality of life.O objetivo deste estudo foi analisar a relação entre variá- veis clínicas, psicológicas, sociodemográficas e de qualidade de vida em mulheres com incontinência urinária. A amostra foi composta de 80 mulheres com diagnóstico de incontinência urinária (IU), seguido em um Hospital Central do Norte de Portugal. As participantes responderam: Incontinence Quality of Life (I-QOL); Satisfaction with Sexual Relationship Questionnaire (SSRQ); Hospital Anxiety and Depression Scales (HADS) e o Brief Cope. Os resultados revelaram que as mulheres com uma maior qualidade de vida consideraram seus sintomas de perda de urina como leves ou moderados, em comparação àquelas com perda de urina grave. A perda de urina menos grave foi associada à maior satisfação sexual e menos uso de religião e autoculpabilização como estratégias de enfrentamento. Em termos de enfrentamento, as mulheres que consideraram a perda de urina como grave expressaram mais sentimentos em relação à IU. Incontinência urinária de esforço, alta satisfação sexual e menos uso da negação, distração e religião, como estratégias de enfrentamento, previram maior qualidade de vida. De acordo com os resultados, a IU tem um impacto na satisfação e na qualidade de vida sexual das mulheres. Assim, os programas de intervenção devem visar a essas mulheres, incluindo seus parceiros, ajudando-as a adaptar-se à sua condição e ensinar-lhes estratégias eficazes de enfrentamento, a fim de melhorar sua satisfação sexual e qualidade de vida