REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

Structural effects of the highly protective V127 polymorphism on human prion protein

Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease

A randomised, open label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes

Aim To compare the effects of a glucagon‐like peptide‐1 receptor agonist and a dipeptidyl peptidase‐4 inhibitor on magnetic resonance imaging‐derived measures of cardiovascular function. Materials and methods In a prospective, randomized, open‐label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non‐insulin treated young (aged 18‐50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. Results Seventy‐six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m−2), of whom 65% had ≥1 cardiovascular risk factor. Sixty‐one participants had primary outcome data available. There were no statistically significant between‐group differences (intention‐to‐treat; mean [95% confidence interval]) in PEDSR change (−0.01 [−0.07, +0.06] s−1), left ventricular ejection fraction (−1.98 [−4.90, +0.94]%), left ventricular mass (+1.14 [−5.23, +7.50] g) or aortic distensibility (−0.35 [−0.98, +0.28] mmHg−1 × 10−3) after 26 weeks. Reductions in HbA1c (−4.57 [−9.10, −0.37] mmol mol−1) and body weight (−3.88 [−5.74, −2.01] kg) were greater with liraglutide. Conclusion There were no differences in cardiovascular structure or function after short‐term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin‐based therapies

Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial

OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s−1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function

Growth behavior of titanium dioxide thin films at different precursor temperatures

The hydrophilic TiO2 films were successfully deposited on slide glass substrates using titanium tetraisopropoxide as a single precursor without carriers or bubbling gases by a metal-organic chemical vapor deposition method. The TiO2 films were employed by scanning electron microscopy, Fourier transform infrared spectrometry, UV-Visible [UV-Vis] spectroscopy, X-ray diffraction, contact angle measurement, and atomic force microscopy. The temperature of the substrate was 500°C, and the temperatures of the precursor were kept at 75°C (sample A) and 60°C (sample B) during the TiO2 film growth. The TiO2 films were characterized by contact angle measurement and UV-Vis spectroscopy. Sample B has a very low contact angle of almost zero due to a superhydrophilic TiO2 surface, and transmittance is 76.85% at the range of 400 to 700 nm, so this condition is very optimal for hydrophilic TiO2 film deposition. However, when the temperature of the precursor is lower than 50°C or higher than 75°C, TiO2 could not be deposited on the substrate and a cloudy TiO2 film was formed due to the increase of surface roughness, respectively

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

&lt;p&gt;Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.&lt;/p&gt; &lt;p&gt;Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.&lt;/p&gt; &lt;p&gt;Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.&lt;/p&gt; &lt;p&gt;Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.&lt;/p&gt

IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister

BACKGROUND: Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective. METHODS: A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH/LH superovulation regime. These eggs were fertilised with sperm from the recipient\u27s husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. RESULTS: A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks\u27 gestation. Additionally, four embryos were cryopreserved for the recipient\u27s future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. CONCLUSION: POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation

A comparison of liver fat fraction measurement on MRI at 3T and 1.5T

Purpose Volumetric liver fat fraction (VLFF) measurements were made using the HepaFat-Scan® technique at 1.5T and 3T to determine the agreement between the measurements obtained at the two fields. Methods Sixty patients with type 2 diabetes (67% male, mean age 50.92 ± 6.56yrs) and thirty healthy volunteers (50% male, mean age 48.63 ± 6.32yrs) were scanned on 1.5T Aera and 3T Skyra (Siemens, Erlangen, Germany) MRI scanners on the same day using the HepaFat-Scan® gradient echo protocol with modification of echo times for 3T (TEs 2.38, 4.76, 7.14 ms at 1.5T and 1.2, 2.4, 3.6 ms at 3T). The 3T analyses were performed independently of the 1.5T analyses by a different analyst, blinded from the 1.5T results. Data were analysed for agreement and bias using Bland-Altman methods and intraclass correlation coefficients (ICC). A second cohort of 17 participants underwent interstudy repeatability assessment of VLFF measured by HepaFat-Scan® at 3T. Results A small, but statistically significant mean bias of 0.48% was observed between 3T and 1.5T with 95% limits of agreement -2.2% to 3.2% VLFF. The ICC for agreement between field strengths was 0.983 (95% CI 0.972–0.989). In the repeatability cohort studied at 3T the repeatability coefficient was 4.2%. The ICC for agreement was 0.971 (95% CI 0.921–0.989). Conclusion There is minimal bias and excellent agreement between the measures of VLFF using the HepaFat-Scan® at 1.5 and 3T. The test retest repeatability coefficient at 3T is comparable to the 95% limits of agreement between 1.5T and 3T suggesting that measurements can be made interchangeably between field strengths