Epidemiological study of aromatase inhibitors in women diagnosed with breast cancer: evaluation and management of secondary effects

[eng] Aromatase inhibitors (AI) are one of the main therapies to treat estrogen-receptor positive breast cancer. AI use is associated with several side effects that affects patient’s quality of life and reduces treatment adherence. Hence, it is necessary to make further efforts in elucidating and diminishing the AI-related side effects. In this line, this thesis provided new and additional evidence for this purpose. Starting by the importance of assessing vitamin D levels during AI treatment, especially to those who underwent to chemotherapy. We also studied the bone health evolution at the end and one-year after AI cessation, and the impact of oral bisphosphonates (BP). Moreover, we analyzed the arthralgia (VAS score) and health-related quality of life in osteoporosis (ECOS-16 score) progression during the AI treatment until one- year post-treatment. Then, fracture incidence and risk during AI therapy compared to tamoxifen (TAM) was analyzed, as well as the protective effect of BP. Finally, we studied the cardiovascular and thromboembolic risk, and overall survival benefit of AI compared to TAM. Our research leads us to state that bone health and circulant vitamin D levels monitoring, plus calcium and vitamin D supplementation is key for the clinical management of AI patients. BP treatment is proved to diminish bone loss and fracture risk, but cannot reverse risk levels towards patients at low fracture risk. Furthermore, prior TAM treatment enhances the odds to withdraw during the first year, increases bone loss during AI treatment, and restricts the recovery in lumbar spine location at one-year post-treatment. On the other hand, since there are no differences in cardiovascular and thromboembolic risk between AI and TAM users, but AI users have lower all-cause mortality, AI should be the preferable choice. In summary, it is mandatory to clinical monitoring AI patients, especially those who were previously treated with TAM, including fracture risk and related risk factors assessments. These would reduce early cessation of treatment and improve patients’ quality of life

Incidencia de infecciones herpéticas y por trichomonas en un estudio de muestras cervicovaginales en el hospital san juan de dios de santa ana

Muchas décadas han pasado desde que R. Virchow, puso las bases de la patología celular (1858). Desde entonces han surgido investigadores que en sus trabajados nos describen técnicas y metodologías muy variadas de estudio celular; sería interminable describir algunos de los trabajos que en forma concatenada han contribuido al desarrollo y entendimiento del conocimiento de la célula; por tanto sólo mencionaremos algunos hechos de importancia histórica relacionados a este trabajo

Els nivells de vitamina D són més baixos en pacients amb càncer de mama, en la regió mediterrània

Determinats nivells de vitamina D s'han relacionat amb l'aparició, pronòstic i supervivència del càncer de mama. En el següent article, s'han comparat els nivells de la vitamina D en dones diagnosticades de càncer de mama amb dones sanes, a la regió mediterrània. S'ha vist que en general la majoria de dones sanes manquen de vitamina D però les dones intervingudes per càncer de mama tenen nivells encara més baixos. S'ha conclòs remarcant la importància de quantificar la vitamina D en les pacients i la seva ingesta en cas necessari.Determinados niveles de vitamina D se han relacionado con la aparición, pronóstico y supervivencia del cáncer de mama. En el siguiente artículo se han comparado los niveles de vitamina D en mujeres diagnosticadas de cáncer de mama con mujeres sanas, en la región mediterránea. Se ha visto que en general la mayoría de mujeres sanas tienen escasez de vitamina D pero las mujeres intervenidas por cáncer de mama tienen niveles aún más bajos. Se ha concluido remarcando la importancia de cuantificar la vitamina D en las pacientes y su ingesta en caso necesario

Crosstalk between chromatin structure, cohesin activity and transcription

Background: A complex interplay between chromatin and topological machineries is critical for genome architec‑ ture and function. However, little is known about these reciprocal interactions, even for cohesin, despite its multiple roles in DNA metabolism. Results: We have used genome‑wide analyses to address how cohesins and chromatin structure impact each other in yeast. Cohesin inactivation in scc1‑73 mutants during the S and G2 phases causes specific changes in chromatin structure that preferentially take place at promoters; these changes include a significant increase in the occupancy of the − 1 and + 1 nucleosomes. In addition, cohesins play a major role in transcription regulation that is associated with specific promoter chromatin architecture. In scc1‑73 cells, downregulated genes are enriched in promoters with short or no nucleosome‑free region (NFR) and a fragile “nucleosome − 1/RSC complex” particle. These results, together with a preferential increase in the occupancy of nucleosome − 1 of these genes, suggest that cohesins promote transcription activation by helping RSC to form the NFR. In sharp contrast, the scc1‑73 upregulated genes are enriched in promoters with an “open” chromatin structure and are mostly at cohesin‑enriched regions, suggesting that a local accumulation of cohesins might help to inhibit transcription. On the other hand, a dramatic loss of chromatin integrity by histone depletion during DNA replication has a moderate effect on the accumulation and distribution of cohesin peaks along the genome. Conclusions: Our analyses of the interplay between chromatin integrity and cohesin activity suggest that cohesins play a major role in transcription regulation, which is associated with specific chromatin architecture and cohesin‑ mediated nucleosome alterations of the regulated promoters. In contrast, chromatin integrity plays only a minor role in the binding and distribution of cohesins.Spanish Ministry of Economy and Competitivenes BFU2012-38171, BFU2015-63698-PAndalusian Government P12-CTS-227

Aging and structural relaxation of hyper-quenched Mg65Cu25Y10 metallic glass

The structural relaxation, glass transition and crystallization processes of Mg65Cu25Y10 metallic glass are studied by Differential Scanning Calorimetry (DSC) and Mechanical spectroscopy. The relaxation model derived from the mechanical measurements is compared with the kinetics of these transformations obtained from the DSC curves. The structural relaxation kinetics is found to be controlled by the glassy dynamics following an Adams-Gibbs-Vogel function. The glass transition and crystallization kinetics are controlled by the dynamics of the supercooled melt following a Vogel-Fulcher-Tammann behaviour. The results suggest that the microscopic processes responsible of structural relaxation and aging below the glass transition correspond to the same processes generating the a-relaxation peak. (C) 2013 Elsevier B.V. All rights reserved.Peer ReviewedPostprint (author’s final draft

The cytoplasmic LIM domain protein Espinas contributes to photoreceptor layer selection in the visual system

One of the central questions in neurobiology is how neurons discriminate between one another during circuit assembly. A common strategy of many nervous systems is the organization of brain regions in layers, to facilitate that neurons encounter a limited repertoire of synaptic partners. The fly visual system, which is structured in layers like many regions of the vertebrate brain, is used to identify cell surface molecules that mediate recognition between neurons and allow them to extend to specific layers. However, little is known about the intracellular pathways that link cell surface molecules to the cytoskeleton to determine whether or not to stabilize in a layer. Flamingo and its vertebrate homologs CELSR1/2 are cell surface molecules with widespread roles in neurite growth. In the fly visual system in particular, Flamingo regulates layer selection of a particular neuronal type. Our data suggests that in this context, Flamingo signals to the cytoskeleton through the conserved cytoplasmic molecule Espinas/PRICKLE2. Given that Flamingo and Espinas, as well as their respective vertebrate homologs, are broadly expressed in the nervous system, elucidating the interactions between them can reveal conserved mechanisms and provide valuable insights into the assembly of neural circuits

Early stimulation and nutrition:The impacts of a scalable intervention

This paper evaluates the effects of the implementation of a structured early stimulation curriculum combined with a nutritional intervention through public large-scale parenting support services for vulnerable families in rural Colombia, known as FAMI, using a clustered randomized controlled trial. We randomly assigned 87 towns in rural areas to treatment and control and 1,460 children younger than 1 year of age were assessed at baseline. The interventions were also complemented with training, supervision and coaching of FAMI program facilitators. We assessed program effects on children’s nutritional status, and on cognitive and socio-emotional development; as well as on parental practices. The interventions had a positive and significant effect on a cognitive development factor based on the Bayley-III of 0.15 standard deviations. We also report a reduction of 5.8 percentage points in the fraction of children whose height-for-age is below -1 standard deviation. We do not find any effects on socio-emotional development. We report positive and statistically significant effects on the quality of the home environment (0.34 SD)

Early Stimulation and Nutrition: The Impacts of a Scalable Intervention

Early childhood development is becoming the focus of policy worldwide. However, the evidence on the effectiveness of scalable models is scant, particularly when it comes to infants in developing countries. In this paper, we describe and evaluate with a cluster-Randomized Controlled Trial an intervention designed to improve the quality of child stimulation within the context of an existing parenting program in Colombia, known as FAMI. The intervention improved children’s development by 0.16 of a standard deviation (SD) and children’s nutritional status, as reflected in a reduction of 5.8 percentage points of children whose height-for-age is below -1 SD