Evaluating differences in the clinical impact of a free online weight loss programme, a resource-intensive commercial weight loss programme and an active control condition: a parallel randomised controlled trial

Background: Finding effective intervention strategies to combat rising obesity levels could significantly reduce the burden that obesity and associated non-communicable diseases places on both individuals and the National Health Service. Methods: In this parallel randomised-controlled trial, 76 participants who are overweight or obese (50 female) were given free access to a fitness centre for the duration of the 12-week intervention and randomised to one of three interventions. The commercial intervention, the Healthy Weight Programme, (HWP, n = 25, 10/15 men/women) consisted of twelve 1-h nutrition coaching sessions with a nutritionist delivered as a mixture of group and 1 to 1 sessions. In addition, twice-weekly exercise sessions (24 in total) were delivered by personal trainers for 12 weeks. The NHS intervention (n = 25, 8/17 men/women) consisted of following an entirely self-managed 12-week online NHS resource. The GYM intervention (n = 26, 8/18 men/women) received no guidance or formal intervention. All participants were provided with a gym induction for safety and both the NHS and GYM participants were familiarised with ACSM physical activity guidelines by way of a hand-out. Results: The overall follow-up rate was 83%. Body mass was significantly reduced at post-intervention in all groups (HWP: N = 18, − 5.17 ± 4.22 kg, NHS: N = 21–4.19 ± 5.49 kg; GYM: N = 24–1.17 ± 3.00 kg; p < 0.001) with greater reductions observed in HWP and NHS groups compared to GYM (p < 0.05). Out with body mass and BMI, there were no additional statistically significant time x intervention interaction effects. Conclusions: This is the first study to evaluate the efficacy of both a free online NHS self-help weight-loss tool and a commercial weight loss programme that provides face-to-face nutritional support and supervised exercise. The findings suggest that both interventions are superior to an active control condition with regard to eliciting short-term weight-loss. Trial registration: ISRCTN Registry - ISRCTN31489026. Prospectively registered: 27/07/16

Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

Patient-rated satisfaction and improvement following hip and knee replacements: Development of prediction models

Rationale: Effective preoperative assessments of determinants of health status and function may improve postoperative outcomes. Aims and Objectives: We developed risk scores of preoperative patient factors and patient-reported outcome measures (PROMs) as predictors of patient-rated satisfaction and improvement following hip and knee replacements. Patients and Methods: Prospectively collected National Health Service and independent sector patient data (n = 30,457), including patients' self-reported demographics, comorbidities, PROMs (Oxford Hip/Knee score (OHS/OKS) and European Quality of Life (EQ5D index and health-scale), were analysed. Outcomes were defined as patient-reported satisfaction and improvement following surgery at 7-month follow-up. Univariable and multivariable-adjusted logistic regressions were undertaken to build prediction models; model discrimination was evaluated with the concordance index (c-index) and nomograms were developed to allow the estimation of probabilities. Results: Of the 14,651 subjects with responses for satisfaction following hip replacements 564 (3.8%) reported dissatisfaction, and 1433 (9.2%) of the 15,560 following knee replacement reported dissatisfaction. A total of 14,662 had responses for perceived improvement following hip replacement (lack of improvement in 391; 2.7%) and 15,588 following knee replacement (lack of improvements in 1092; 7.0%). Patients reporting poor outcomes had worse preoperative PROMs. Several factors, including age, gender, patient comorbidities and EQ5D, were included in the final prediction models: C-indices of these models were 0.613 and 0.618 for dissatisfaction and lack of improvement, respectively, for hip replacement and 0.614 and 0.598, respectively, for knee replacement. Conclusions: Using easily accessible preoperative patient factors, including PROMs, we developed models which may help predict dissatisfaction and lack of improvement following hip and knee replacements and facilitate risk stratification and decision-making processes

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Improved clinical outcomes in response to a 12-week blended digital and community-based long-COVID-19 rehabilitation programme

IntroductionTwo million people in the UK are experiencing long COVID (LC), which necessitates effective and scalable interventions to manage this condition. This study provides the first results from a scalable rehabilitation programme for participants presenting with LC.Methods601 adult participants with symptoms of LC completed the Nuffield Health COVID-19 Rehabilitation Programme between February 2021 and March 2022 and provided written informed consent for the inclusion of outcomes data in external publications. The 12-week programme included three exercise sessions per week consisting of aerobic and strength-based exercises, and stability and mobility activities. The first 6 weeks of the programme were conducted remotely, whereas the second 6 weeks incorporated face-to-face rehabilitation sessions in a community setting. A weekly telephone call with a rehabilitation specialist was also provided to support queries and advise on exercise selection, symptom management and emotional wellbeing.ResultsThe 12-week rehabilitation programme significantly improved Dyspnea-12 (D-12), Duke Activity Status Index (DASI), World Health Orginaisation-5 (WHO-5) and EQ-5D-5L utility scores (all p &lt; 0.001), with the 95% confidence intervals (CI) for the improvement in each of these outcomes exceeding the minimum clinically important difference (MCID) for each measure (mean change [CI]: D-12: −3.4 [−3.9, −2.9]; DASI: 9.2 [8.2, 10.1]; WHO-5: 20.3 [18.6, 22.0]; EQ-5D-5L utility: 0.11 [0.10, 0.13]). Significant improvements exceeding the MCID were also observed for sit-to-stand test results (4.1 [3.5, 4.6]). On completion of the rehabilitation programme, participants also reported significantly fewer GP consultations (p &lt; 0.001), sick days (p = 0.003) and outpatient visits (p = 0.007) during the previous 3 months compared with baseline.DiscussionThe blended and community design of this rehabilitation model makes it scalable and meets the urgent need for an effective intervention to support patients experiencing LC. This rehabilitation model is well placed to support the NHS (and other healthcare systems worldwide) in its aim of controlling the impacts of COVID-19 and delivering on its long-term plan.Clinical trial registrationhttps://www.isrctn.com/ISRCTN14707226, identifier 14707226

Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR

The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum we have obtained the products of branching fractions for the omega and phi mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range 1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18 +/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.

Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-$and their resonant submodes$B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics

With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays to ppbar. We measure a branching fraction Br(B+ --> p pbar K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ --> Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid Communications