Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility

Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed

OPA1 mutations associated with Dominant Optic Atrophy influence optic nerve head size

Purpose: To analyze the influence of OPA1 gene mutations on the optic nerve head (ONH) morphology in patients with dominant optic atrophy (DOA). Design: Cross-sectional study. Participants: Twenty-eight patients with DOA from 11 pedigrees, which were positive for the presence of OPA1 gene mutations, and 56 age-matched control subjects, were enrolled. Methods: The ONH of DOA patients was studied by optical coherence tomography and compared with an age-matched control group of 56 individuals. Main Outcome Measures: ONH area, and vertical and horizontal diameters. Results: The ONH analysis of DOA patients showed a significantly smaller optic disc area (P0.0001), vertical (P 0.018), and horizontal (P0.0001) disc diameters, compared with controls. Stratification of the results for the single OPA1 mutation revealed normal ONH area with 2 mutations, whereas the only missense mutation linked to a “DOA plus” phenotype had the smallest ONH measurements. Conclusions: The DOA patients carrying OPA1 gene mutations present, as a group, a significantly smaller ONH compared with the range of size observed in a control population; this feature may be mutation specific. This observation suggests that OPA1 is involved in shaping the anatomic conformation of the ONH in patients with DOA. The relevance of OPA1 in regulating apoptosis and modeling the eye development has been recently shown by others. Thus, mutations in the OPA1 gene may determine the previously unrecognized feature of a smaller optic disc size and this in turn may have relevance for DOA pathogenesis. Furthermore, OPA1 gene polymorphic variants may contribute to the normal variability of ONH size in the general population. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010;117:1547–1553 © 2010 by the American Academy of Ophthalmology

Self-assembling of large ordered DNA arrays using superhydrophobic patterned surfaces

In the present paper we draw a simple and robust method to realize highly ordered arrays of stretched and suspended DNA molecules over the millimeter length scale. To this end we used an ad-hoc designed superhydrophobic surface made of high aspect-ratio silicon pillars, where we deposited a droplet containing genomic DNA. A precise positioning of DNA strands has been achieved by shaping the silicon pillars so that sharpened features resembling tips are included. Such features allowed us to accurately control the droplet dewetting dynamics, pinning DNA strands in a well-defined position above pillars. The proposed technique has the potential to positively impact on the development of novel DNA chips for genetic analysi

Ceritinib compassionate use for patients with crizotinib-refractory, anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer

Ceritinib was evaluated within a compassionate use program of Italian patients

Be-TeaM: An Italian real-world observational study on second-line therapy for EGFR-mutated NSCLC patients

Molecular diagnostics and care of non-small cell lung cancer (NSCLC) are continuously evolving. Few data document the current strategies to manage advanced NSCLC patients beyond progression in clinical practice

Listening Understanding and acting (lung): focus on communicational issue in thoracic oncology

Background: In the field of oncological assistance, nowadays we have to deal with a complex scenario where patients got used to obtain a huge amount of information through internet or social media and to apply them in performing their health-related decisions. This landscape requires that clinicians become able to handle therapeutical approaches and adequate skills in communication tools to satisfy the current needs. Our project aimed to build a communication model based on clinical oncologists’ real experiences in order to find a simple way to share with patients all the innovative therapeutical opportunities today available in lung cancer. The final goal is to design a flexible and personalized model adaptable to clinician’s personal characteristics and to the specific patient he is facing. We applied both traditional educational tools and innovative techniques in order to make the results effective and applicable to support peer learning. Methods: The first step consisted in a Board synthesized the definition of the diagnostic process, the identification of treatment strategies and any potential communication barrier clinicians may face dealing with patients. The second step consisted in teamwork including a theoretical part and a training part. In the third step we produce five training videos and video interviews regarding communication praxis and a “Small communication manual”. The last step consisted in the publication of the produced material on website and its diffusion through the social media. Results: In medicine, the universal application of a single model of communication does not represent the optimal solution. By contrary, the availability of simple and practical suggestions to improve the communicative style could allow clinicians to abandon stereotyped formulas identically repurposed to all patients. The “from bottom to top” training, starting from real-life to take advantage of the clinician’s experience, give the clinicians the possibility to meditate about their own communicative style and to train in the context of a protected environment. Applying these rules, we design an effective communication model, based on healthcare humanization, which could represent a fundamental support for the patient in order to be gently driven by the clinician to the most appropriate therapeutical choice, balancing efficacy and quality of life. The relational training may improve the quality of clinician-patient communication and could be widespread to other clinicians through the media. Conclusions: Considering the innovative therapeutical options available, particularly for lung cancer patients, and the increasing access of health-related information through internet or social media the clinician-patient communication has become crucial to support the achievement of the most appropriate therapeutical choice for the patient, facing the intricate illness experience. Building a shareable and easy-toapply communication model represents a challenge aimed to help clinicians and including technology not as a threat, but as a positive tool

Study on psychoeducation enhancing results of adherence in patients with schizophrenia (SPERA-S): Study protocol for a randomized controlled trial

Background: Poor adherence to pharmacotherapy negatively affects the course and the outcome of schizophreniaspectrum psychoses, enhancing the risk of relapse. Falloon and coworkers developed a Psychoeducation Program aimed at improving communication and problem-solving abilities in patients and their families. This study set out to evaluate changes in adherence to pharmacotherapy in patients diagnosed with schizophrenia-spectrum psychoses, by comparing one group exposed to the Falloon Psychoeducation Program (FPP) with another group exposed to family supportive therapy with generic information on the disorders.Methods: 340 patients diagnosed with schizophrenia and related disorders according to standardized criteria from 10 participating units distributed throughout the Italian National Health System (NHS), will be enrolled with 1:1 allocation by the method of blocks of randomized permutations. Patients will be reassessed at 6, 12 and 18 months after start of treatment (duration: 6 months). The primary objective is to evaluate changes in adherence to pharmacotherapy after psychoeducation. Adherence will be assessed at three-month intervals by measuring blood levels of the primary prescribed drug using high pressure liquid chromatography, and via the Medication Adherence Questionnaire and a modified version of the Adherence Interview. Secondary objectives are changes in the frequency of relapse and readmission, as the main indicator of the course of the disorder. Enrolled patients will be allocated to the FPP (yes/no) randomly, 1:1, in a procedure controlled by the coordinating unit; codes will be masked until the conclusion of the protocol (or the occurrence of a severe negative event). The raters will be blind to treatment allocation and will be tested for blinding after treatment completion. Intention-to-treat will be applied in considering the primary and secondary outcomes. Multiple imputations will be applied to integrate the missing data. The study started recruitment in February 2013; the total duration of the study is 27 months.Discussion: If the psychoeducation program proves effective in improving adherence to pharmacotherapy and in reducing relapse and readmissions, its application could be proposed as a standard adjunctive psychosocial treatment within the Italian NHS. Trial registration: Protocol Registration System of ClinicalTrials.gov NCT01433094; registered on 20 August 2011; first patient was randomized on 12 February 2013. © 2013 Petretto et al.; licensee BioMed Central Ltd

Multimorbidity and polypharmacy in the elderly: Lessons from REPOSI

The dramatic demographic changes that are occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the related prescription of multiple medications are becoming typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of medications has been generated by clinical trials involving patients completely different from those currently admitted to internal medicine: much younger, affected by a single disease and managed in a highly controlled research environment. Because only registries can provide information on drug effectiveness in real-life conditions, REPOSI started in 2008 with the goal of acquiring data on elderly people acutely admitted to medical or geriatric hospital wards in Italy. The main goals of the registry were to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most often concomitantly occur in the elderly. The findings of 3-yearly REPOSI runs (2008, 2010, 2012) suggest the following pertinent tasks for the internist in order to optimally handle their elderly patients: the management of multiple medications, the need to become acquainted with geriatric multidimensional tools, the promotion and implementation of a multidisciplinary team approach to patient health and care and the corresponding involvement of patients and their relatives and caregivers. There is also a need for more research, tailored to the peculiar features of the multimorbid elderly patient