Psychosocial impact of human papillomavirus on women's sexual dissatisfaction and quality of life

Purpose: This study assessed how psychological, socio-demographic and clinical variables were associated and moderated the relationship between sexual dissatisfaction and the psychosocial impact of the human papillomavirus (HPV) on the quality of life (QOL) of infected women. Methods: A cross-sectional design was used with a sample of 194 women. Participants completed a sociodemographic and clinical questionnaire, and were assessed on the psychosocial impact of HPV on quality of life (HPV Impact Profile), sexual dissatisfaction (Index of Sexual Satisfaction), psychological morbidity (Hospital Anxiety and Depression Scale), emotional suppression (Courtauld Emotional Control Scale) and spirituality (Spiritual and Religious Attitudes in Dealing with Illness). Results: Women with greater psychological morbidity and emotional suppression showed greater psychosocial impact of HPV on QOL. Greater psychological morbidity and emotional suppression, being older, having less education and not using condoms were associated with greater sexual dissatisfaction. Sexual dissatisfaction, psychological morbidity and age were associated with the impact of HPV on QOL. The variables that contributed to sexual dissatisfaction were age, emotional suppression and condom use. The use of condoms moderated the relationship between emotional suppression and sexual dissatisfaction. Conclusion: Interventions should focus on psychological morbidity and condom use, particularly in older and less educated women

Quality of Life Changes Following Peripheral Blood Stem Cell Transplantation and Participation in a Mixed-Type, Moderate-intensity, Exercise Program

Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 200

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P&gt;1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: A mixed methods study

Background: Limited negotiation around care decisions is believed to undermine collaborative working between parents of children with long-term conditions and professionals, but there is little evidence of how they actually negotiate their respective roles. Using chronic kidney disease as an exemplar this paper reports on a multi-method study of social interaction between multidisciplinary teams and parents as they shared clinical care. Methods. Phases 1 and 2: a telephone survey mapping multidisciplinary teams' parent-educative activities, and qualitative interviews with 112 professionals (Clinical-psychologists, Dietitians, Doctors, Nurses, Play-specialists, Pharmacists, Therapists and Social-workers) exploring their accounts of parent-teaching in the 12 British children's kidney units. Phase 3: six ethnographic case studies in two units involving observations of professional/parent interactions during shared-care, and individual interviews. We used an analytical framework based on concepts drawn from Communities of Practice and Activity Theory. Results: Professionals spoke of the challenge of explaining to each other how they are aware of parents' understanding of clinical knowledge, and described three patterns of parent-educative activity that were common across MDTs: Engaging parents in shared practice; Knowledge exchange and role negotiation, and Promoting common ground. Over time, professionals had developed a shared repertoire of tools to support their negotiations with parents that helped them accomplish common ground during the practice of shared-care. We observed mutual engagement between professionals and parents where a common understanding of the joint enterprise of clinical caring was negotiated. Conclusions: For professionals, making implicit knowledge explicit is important as it can provide them with a language through which to articulate more clearly to each other what is the basis of their intuition-based hunches about parents' support needs, and may help them to negotiate with parents and accelerate parents' learning about shared caring. Our methodology and results are potentially transferrable to shared management of other conditions. © 2013 Swallow et al.; licensee BioMed Central Ltd

All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes

This is the final version. Available from F1000Research via the DOI in this record.Data availability Underlying data Data is not freely available due to it consisting of potentially identifiable information, and as such is held securely to protect the interests of research participants in line with the guidance from the relevant ethics committees. However, the ethics committees will allow data analysed and generated in this study to be available to researchers through open collaboration. For access to the data used in this study please contact Dr Rachel Freathy ([email protected]) and Professor William Lowe Jr ([email protected]) in relation to HAPO and Dr Rachel Freathy and Professor Fidelma Dunne ([email protected]) in relation to Atlantic DIP. Requests will be reviewed as soon as possible on receipt and will be facilitated with an agreement to ensure that data is transferred and held securely and results of new analyses shared with the relevant study investigators. The websites describing the studies and other data available are https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000096.v4.p1 for HAPO and http://atlanticdipireland.com/for Atlantic DIP. Extended data Figshare: Extended data Wellcome Open Research 16097.pdf. https://doi.org/10.6084/m9.figshare.14180033 The file contains an extended data table with sensitivity analyses adjusting the genetic scores for maternal pre-pregnancy BMI and age and a figure with a directed acyclic graph (DAG) showing how the relationships between the genetic scores and GDM diagnostic category are not driven by maternal pre-pregnancy BMI or age.Background: Using genetic scores for fasting plasma glucose (FPG GS) and type 2 diabetes (T2D GS), we investigated whether the fasting, 1-hour and 2-hour glucose thresholds from the WHO 2013 criteria for gestational diabetes (GDM) have different implications for genetic susceptibility to raised fasting glucose and type 2 diabetes in women from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and Atlantic Diabetes in Pregnancy (DIP) studies. Methods: Cases were divided into three subgroups: (i) FPG ≥5.1 mmol/L only, n=222; (ii) 1-hour glucose post 75 g oral glucose load ≥10 mmol/L only, n=154 (iii) 2-hour glucose ≥8.5 mmol/L only, n=73; and (iv) both FPG ≥5.1 mmol/L and either of a 1-hour glucose ≥10 mmol/L or 2-hour glucose ≥8.5 mmol/L, n=172. We compared the FPG and T2D GS of these groups with controls (n=3,091) in HAPO and DIP separately. Results: In HAPO and DIP, the mean FPG GS in women with a FPG ≥5.1 mmol/L, either on its own or with 1-hour glucose ≥10 mmol/L or 2-hour glucose ≥8.5 mmol/L, was higher than controls (all P <0.01). Mean T2D GS in women with a raised FPG alone or with either a raised 1-hour or 2-hour glucose was higher than controls (all P <0.05). GDM defined by 1-hour or 2-hour hyperglycaemia only was also associated with a higher T2D GS than controls (all P <0.05). Conclusions: The different diagnostic categories that are part of the WHO 2013 criteria for GDM identify women with a genetic predisposition to type 2 diabetes as well as a risk for adverse pregnancy outcomes.Wellcome TrustNational Institute for Health ResearchEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Human Genome Research InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesAmerican Diabetes AssociationIreland Health Research Boar

Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation

<p>Abstract</p> <p>Background</p> <p>Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.</p> <p>Methods</p> <p>Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.</p> <p>Results</p> <p>After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.</p> <p>Conclusions</p> <p>Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.</p

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

$\textbf{Aim}$ We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. $\textbf{Methods}$ In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). $\textbf{Results}$ Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10$^{-4}$) and INS rs2585 (P-value = 7 × 10$^{-4}$), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10$^{-3}$) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10$^{-3}$), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10$^{-6}$, n = 981, r$^{2}$ = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10$^{-3}$, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10$^{-8}$, rs2585, P-value = 3.6 × 10$^{-5}$) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10$^{-8}$), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). $\textbf{Conclusion}$ This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.This work was supported by the Evelyn Trust (grant number EW9035322); Diabetes UK (grant number 11/0004241); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (grant number RG1644); the Medical Research Council (grant number 7500001180); European Union Framework 5 (grant number QLK4-1999-01422); the Mothercare Charitable Foundation (grant number RG54608); Newlife Foundation for Disabled Children (grant number 07/20); the World Cancer Research Fund International (grant number 2004/03); and the National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study work was supported by the National Institutes of Health (grant numbers HD-34242, HD-34243, HG-004415, and CA-141688); the Institutes of Health Research–INMD (grant number 110791); and by the American Diabetes Association

Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.

By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range

Comparison of long-term mortality risk following normal exercise vs adenosine myocardial perfusion SPECT

A higher frequency of clinical events has been observed in patients undergoing pharmacological vs exercise myocardial perfusion single-photon emission computed tomography (SPECT). While this difference is attributed to greater age and co-morbidities, it is not known whether these tests also differ in prognostic ability among patients with similar clinical profiles. We assessed all-cause mortality rates in 6,069 patients, followed for 10.2 ± 1.7 years after undergoing exercise or adenosine SPECT. We employed propensity analysis to match exercise and adenosine subgroups by age, gender, symptoms, and coronary risk factors. Within our propensity-matched cohorts, adenosine patients had an annualized mortality rate event rates that was more than twice that of exercise patients (3.9% vs 1.6%, P &lt; .0001). Differences in mortality persisted among age groups, including those &lt;55 years old. In the exercise cohort, mortality was inversely related to exercise duration, with comparable mortality noted for patients exercising &lt;3 min and those undergoing adenosine testing. Among patients with normal stress SPECT tests, those undergoing adenosine testing manifest a mortality rate that is substantially higher than that observed among adequately exercising patients, but comparable to that observed among very poorly exercising patients. This elevated risk underscores an important challenge for managing patients undergoing pharmacological stress testing