La evaluación de la calidad de vida en personas con demencia

Quality of life (QoL) is one of the most important outcome variables in the study of the efficacy of interventions with people with dementia. However, its assessment is difficult 1) because it is a complex construct for which there is no unified theoretical or conceptual approach, and 2) because of the inherent difficulties in the cognitive impairments of the people under study. In this work different methods and instruments to this end are reviewed, and related findings are discussed. It is important to take into account the subjective view of the assessed person, as assessments done by proxies tend to underestimate QoL. In spite of the need for further development in this field, it is concluded that the instrument of choice is the QOL-AD, as it is change-sensitive, it correlates with health measurements, it is translated into several languages and it can be administered to people with low MMSE scores.     

A New Species of the Genus Paravelia Breddin 1898 from Argentina (Heteroptera: Veliidae)

A new species of the genus Paravelia (Heteroptera: Veliidae) is described, increasing the number of species of the genus known from Argentina to three: P. platensis Berg 1883, P. paxila Drake 1957, and the new sp. P. correntina. Some ecological and statistical notes are included. Scanning electron micrographs and illustrations are provided.     

Pharmacological screening and transcriptomic functional analyses identify a synergistic interaction between dasatinib and olaparib in triple-negative breast cancer

Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening.     

A process‐based metacommunity framework linking local and regional scale community ecology

The metacommunity concept has the potential to integrate local and regional dynamics within a general community ecology framework. To this end, the concept must move beyond the discrete archetypes that have largely defined it (e.g. neutral vs. species sorting) and better incorporate local scale species interactions and coexistence mechanisms. Here, we present a fundamental reconception of the framework that explicitly links local coexistence theory to the spatial processes inherent to metacommunity theory, allowing for a continuous range of competitive community dynamics. These dynamics emerge from the three underlying processes that shape ecological communities: (1) density‐independent responses to abiotic conditions, (2) density‐dependent biotic interactions and (3) dispersal. Stochasticity is incorporated in the demographic realisation of each of these processes. We formalise this framework using a simulation model that explores a wide range of competitive metacommunity dynamics by varying the strength of the underlying processes. Using this model and framework, we show how existing theories, including the traditional metacommunity archetypes, are linked by this common set of processes. We then use the model to generate new hypotheses about how the three processes combine to interactively shape diversity, functioning and stability within metacommunities.     

Functional microbiome deficits associated with ageing: Chronological age threshold

Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well‐defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4‐fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p < 2.8e^?8). Indeed, the synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated (r² > .987) and progressively decrease with age (r² > .948). An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years. Based on recent investigations linking tryptophan with abundance of indole and other “healthy” longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively “young” age of 34 and, particularly, in the elderly are recommended.     

Challenges and advice for MD/PhD applicants who are underrepresented in medicine

The importance of diversity is self-evident in medicine and medical research. Not only does diversity result in more impactful scientific work, but diverse teams of researchers and clinicians are necessary to address health disparities and improve the health of underserved communities. MD/PhD programs serve an important role in training physician-scientists, so it is critical to ensure that MD/PhD students represent diverse backgrounds and experiences. Groups who are underrepresented in medicine and the biomedical sciences include individuals from certain racial and ethnic backgrounds, individuals with disabilities, individuals from disadvantaged backgrounds, and women. However, underrepresented students are routinely discouraged from applying to MD/PhD programs due to a range of factors. These factors include the significant cost of applying, which can be prohibitive for many students, the paucity of diverse mentors who share common experiences, as well as applicants’ perceptions that there is inadequate support and inclusion from within MD/PhD programs. By providing advice to students who are underrepresented in medicine and describing steps programs can take to recruit and support minority applicants, we hope to encourage more students to consider the MD/PhD career path that will yield a more productive and equitable scientific and medical community.