Making sense of risk. Donor risk communication in families considering living liverdonation to a child

This paper contributes to the growing line of thought in bioethics that respect for autonomy should not be equated to the facilitation of individualistic self determination through standard requirements of informed consent in all healthcare contexts. The paper describes how in the context of donation for living related liver transplantation (LRLT) meaningful, responsible decision making is often embedded within family processes and its negotiation. We suggest that good donor risk communication in families promote “conscientious autonomy” and “reflective trust”. From this, the paper offers the suggestion that transplant teams and other relevant professionals have to broaden their role and responsibility for risk communication beyond proper disclosure by addressing the impact of varied psychosocial conditions on risk interpretation and assessment for potential donors and family stakeholders. In conclusion, we suggest further research questions on how professional responsibility and role-taking in risk communication should be morally understood

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

<div><h3>Background</h3><p>Primary hyperparathyroidism (PHPT) is an endocrine disorder most commonly affecting women, suggesting a role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr) which is associated with tumours of the breast and other organs.</p> <h3>Methodology/Principal Findings</h3><p>PRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumours and its functionality in cultured parathyroid tumour cells. In comparison with other tissues and breast cancer cells, high levels of prolactin receptor gene (<em>PRLR</em>) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was uniformly expressed in the cytoplasm and granulae. In <em>in vitro</em> studies of short-term cultured human parathyroid tumour cells, prolactin stimulation was associated with significant transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover, <em>PRLR</em> gene expression in parathyroid tumours was inversely correlated with the patients’ plasma calcium levels.</p> <h3>Conclusions</h3><p>We demonstrate that the prolactin receptor is highly abundant in human parathyroid tissues and that PRLr isoforms expression and PRLr subcellular localisation are altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of prolactin was observed in the form of increased PTH secretion and altered gene transcription with significant increase of RIG-I like receptor, JAK-STAT and Type II interferon signalling pathways. These data suggest a role of the prolactin receptor in parathyroid adenomas.</p> </div

Use of postmenopausal hormone replacement therapy and risk of non-Hodgkin's lymphoma: a Danish Population-based Cohort Study

Use of postmenopausal hormone replacement therapy (HRT) has been hypothesised to be associated with a reduced risk of non-Hodgkin's lymphoma (NHL), but the epidemiologic evidence is conflicting. To examine the risk of NHL in HRT users aged 40 and older, we conducted a cohort study in the County of North Jutland, Denmark (population 0.5 million) using data from population-based health registries for the period 1989–2002. We computed age-standardised NHL incidence rates and used Cox regression analysis to compute the relative risk (RR) and corresponding 95% confidence intervals (CI) of NHL among HRT users compared with non-users, adjusting for age and calendar period. The number of prescriptions redeemed (1, 2–4, 5–9, 10–19, or 20 or more prescriptions) was used as a proxy for duration of HRT. We identified 40 NHL cases among HRT users during 179 838 person-years of follow-up and 310 NHL cases among non-users during 1 247 302 person-years of follow-up. The age-standardised incidence rates of NHL were 25.7 per 100 000 among HRT users and 24.2 per 100 000 among non-users, yielding an adjusted RR of 0.99 (95% CI: 0.71–1.39). Our data did not support an association between HRT use and risk of NHL

Perceived needs and satisfaction with care in people with multiple sclerosis: A two-year prospective study

<p>Abstract</p> <p>Background</p> <p>Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration.</p> <p>Methods</p> <p>The sample consisted of 219 outpatients at a MS specialist clinic. Data on perceived needs and satisfaction with care were collected every six months using a questionnaire which included various dimensions of care. The data was analysed for the whole sample and on an individual level, as well as in subgroups with regard to sex and disease severity.</p> <p>Results</p> <p>There were no statistically significant variations in the proportion of PwMS with perceived needs concerning different health-related services during the study period. However, individual variations were found with regard to both perceived needs and satisfaction with care. Few PwMS perceived a continuous need for a specific service. However, the majority perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at least sometimes. Severe MS was associated with a greater perceived need for almost all the services studied and women experienced a need for psychosocial support/counselling to a greater extent than men. In relation to the different categories of health care staff, PwMS were most satisfied with nurses with regard to all dimensions of care. They were least satisfied with the availability of psychosocial support/counselling; and information about social insurance/vocational rehabilitation.</p> <p>Conclusion</p> <p>Despite the large proportion of individuals with mild disease severity in our sample, a considerable number of needs were identified of which many, on an individual level, varied over time. Key services demanded by PwMS were identified. Also the level of satisfaction with care varied and areas with a potential for improvement were identified such as the availability of rehabilitation services including an increase in the supply of psychosocial support and counselling.</p

From research to practice: Lay adherence counsellors' fidelity to an evidence-based intervention for promoting adherence to antiretroviral treatment in the Western Cape, South Africa

In the Western Cape, lay counsellors are tasked with supporting antiretroviral (ARV) adherence in public healthcare clinics. Thirty-nine counsellors in 21 Cape Town clinics were trained in Options for Health (Options), an evidence-based intervention based on motivational interviewing (MI). We evaluated counsellors’ ability to deliver Options for addressing poor adherence following 5 days training. Audio-recordings of counselling sessions collected following training were transcribed and translated into English. Thirty-five transcripts of sessions conducted by 35 counsellors were analysed for fidelity to the Options protocol, and using the Motivational Interviewing Treatment and Integrity (MITI) code. Counsellors struggled with some of the strategies associated with MI, such as assessing readiness-to-change and facilitating change talk. Overall, counsellors failed to achieve proficiency in the approach of MI according to the MITI. Counsellors were able to negotiate realistic plans for addressing patients’ barriers to adherence. Further efforts aimed at strengthening the ARV adherence counselling programme are needed.Department of HE and Training approved lis

Evidence for a Minimal Eukaryotic Phosphoproteome?

BACKGROUND: Reversible phosphorylation catalysed by kinases is probably the most important regulatory mechanism in eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: We studied the in vitro phosphorylation of peptide arrays exhibiting the majority of PhosphoBase-deposited protein sequences, by factors in cell lysates from representatives of various branches of the eukaryotic species. We derived a set of substrates from the PhosphoBase whose phosphorylation by cellular extracts is common to the divergent members of different kingdoms and thus may be considered a minimal eukaryotic phosphoproteome. The protein kinases (or kinome) responsible for phosphorylation of these substrates are involved in a variety of processes such as transcription, translation, and cytoskeletal reorganisation. CONCLUSIONS/SIGNIFICANCE: These results indicate that the divergence in eukaryotic kinases is not reflected at the level of substrate phosphorylation, revealing the presence of a limited common substrate space for kinases in eukaryotes and suggests the presence of a set of kinase substrates and regulatory mechanisms in an ancestral eukaryote that has since remained constant in eukaryotic life

Pride and confidence at work: potential predictors of occupational health in a hospital setting

BACKGROUND: This study focuses on determinants of a healthy work environment in two departments in a Swedish university hospital. The study is based on previously conducted longitudinal studies at the hospital (1994–2001), concerning working conditions and health outcomes among health care personnel in conjunction with downsizing processes. Overall, there was a general negative trend in relation to mental health, as well as long-term sick leave during the study period. The two departments chosen for the current study differed from the general hospital trend in that they showed stable health development. The aim of the study was to identify and analyse experiential determinants of healthy working conditions. METHODS: Thematic open-ended interviews were carried out with seventeen managers and key informants, representing different groups of co-workers in the two departments. The interviews were transcribed verbatim and an inductive content analysis was made. RESULTS: In the two studied departments the respondents perceived that it was advantageous to belong to a small department, and to work in cooperation-oriented care. The management approaches described by both managers and co-workers could be interpreted as transformational, due to a strain of visionary, delegating, motivating, confirmative, supportive attitudes and a strongly expressed solution-oriented attitude. The daily work included integrated learning activities. The existing organisational conditions, approaches and attitudes promoted tendencies towards a work climate characterised by trust, team spirit and professionalism. In the description of the themes organisational conditions, approaches and climate, two core determinants, work-pride and confidence, for healthy working conditions were interpreted. Our core determinants augment the well-established concepts: manageability, comprehensiveness and meaningfulness. These favourable conditions seem to function as a buffer against the general negative effects of downsizing observed elsewhere in the hospital, and in the literature. CONCLUSION: Research illuminating health-promoting aspects is rather unusual. This study could be seen as explorative. The themes and core dimensions we found could be used as a basis for further intervention studies in similar health-care settings. The result could also be used in future health promotion studies in larger populations. One of the first steps in such a strategy is to formulate relevant questions, and we consider that this study contributes to this