Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110594/1/bju12802.pd

Rapamycin-Loaded Leukosomes Reverse Vascular Inflammation

Rationale: Through localized delivery of rapamycin via a biomimetic drug delivery system, it is possible to reduce vascular inflammation and thus the progression of vascular disease. Objective: Use..

Addressing Educational Needs of Teachers in the EU for Inclusive Education in a Context of Diversity (INNO4DIV): Volume 3 - Part 1: Assessment guidelines for teacher education and training practices on intercultural and democratic competence development.

In spite of policy impetus, research shows that teachers struggle to address the increasing diversity in classrooms, among others, due to the lack of competences to deal with it. The acquisition of Intercultural Competence (IC), which could be defined as “the ability to mobilise and deploy relevant attitudes, skills, knowledge and values in order to interact effectively and appropriately in different intercultural situations”, is a crucial need for teachers to deal with diversity and to be successful in their teaching. In this context, in 2019 the JRC launched the INNO4DIV project with the aim to support polices in the field of IC of teachers, through the analysis of literature and innovative good practices which have successfully addressed the existing barriers for teacher´s IC development. In this context, it was necessary to identify innovative practices for overcoming barriers in the development of intercultural and democratic competences (IDC) of teachers. Given the wealth and variety of educational practices, and in order to preserve the scientific rigour of the identification process, this report offers the rationale and the description of the selection criteria that have been developed according to the conceptual framework of the project, Volume 1. Teachers ́ Intercultural Competence: Working definition and implications for teacher education. Similarly, the process for case identification and selection is also described. Following a brief explanation of the sources for the selection of cases (Section 2), the report focuses on establishing the selection criteria, which are divided into generic and specific criteria (Section 3). The generic criteria apply to all the cases. The specific criteria, however, relate to the scope of each specific Key Enabling Component (KEC), and are the most direct reference to the particular features of the cases. Finally, the document contains an elaborate protocol for case selection that will lead to the final list of selected cases.JRC.B.4-Human Capital and Employmen

Development of anthracycline-induced dilated cardiomyopathy due to mutation on LMNA gene in a breast cancer patient: a case report

Background Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines. Case presentation We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment. Conclusions This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies.Background Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines. Case presentation We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment. Conclusions This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies

Non-disclosure of chronic kidney disease in primary care and the limits of instrumental rationality in chronic illness self-management

Early detection of long term conditions is predicated on assumptions that lifestyle changes and medications can be used to reduce or manage the risk of condition progression. However, ambiguity remains about the nature and place of diagnostic disclosure to people in newly recognised or asymptomatic ‘pre’ conditions such as early stage chronic kidney disease (CKD). The disclosure of a diagnosis is relevant to instigating strategies which rely on actively engaging patients as self-managers of their own care. Whilst primary care routinely records a diagnosis of early stage CKD, little is known about how patients learn about the fact that they have CKD or how they respond to this. This study aimed to explore patients' experiences of disclosure of CKD in primary care settings. A nested qualitative study of participants recruited to a trial of an intervention for CKD patients in Greater Manchester, UK was undertaken. A purposive sample of 26 patients, with a mean age of 72 years (range 59e89, median 71), were interviewed during 2012. Interview transcripts were analysed using constant comparative techniques. Narrative accounts reflected limited or partial disclosure of CKD; often cast in vague terms as “nothing to worry about”. How patients described themselves in terms of participation and their tendencies towards ‘active’ or ‘passive’ involvement in consultations emerged as important components of narratives around disclosure. The findings illuminate the ways in which diagnosis is oriented in a context where it is possible to meet the requirements for remuneration under a pay for performance system of primary care, whilst apparently not disclosing a label or a diagnosis to patients. This challenges the presumptions inherent in wider health policy objectives that are increasingly built on the notion of responsible patients and the ethos of the active support of self-management for pre-conditions

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT–PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6–20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level

Reversing the Outcome of Synapse Elimination at Developing Neuromuscular Junctions In Vivo: Evidence for Synaptic Competition and Its Mechanism

Competition between neurons for the same synaptic sites at the developing neuromuscular junction drives synaptic rearrangements