Dietary nitrate-induced increases in human muscle power: High versus low responders

Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex

Are students less likely to respond to routinely delivered psychological treatment? A retrospective cohort analysis

BACKGROUND: Depression and anxiety disorders are increasingly prevalent among university students, making the provision of effective treatment in this population a priority. Whilst campus-based services provide some psychological treatments, many students are treated by routine adult psychological treatment services which have no focus or adaptations to treatment for student populations. We aimed to compare psychological treatment outcomes between university students and young adults (aged 18-25) in employment to explore whether routinely delivered psychological interventions are equally effective for these groups, or whether students report poorer outcomes. METHODS: A retrospective cohort was formed of 19,707 patients treated by eight National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services in England. Associations between student status (compared to same-age employed adults) and psychological treatment outcomes were explored using logistic regression models. Models were adjusted for important treatment, clinical and demographic characteristics, and propensity score matching was used to explore the robustness of effects. RESULTS: Students and the employed comparison group were similar on baseline characteristics at assessment, but students were less likely to reliably recover (OR = 0.90 [95% CI = 0.83;0.96]) and reliably improve (OR = 0.91 [95% CI = 0.84;0.98]) by the end of treatment in fully adjusted models. Students and the employed group did not differ regarding the likelihood of deterioration (OR = 0.89 [95% CI = 0.78;1.02]) or treatment dropout (OR = 1.01 [95% CI = 0.93;1.11]). CONCLUSIONS: Students appear at risk of poorer outcomes compared to employed younger adults when treated in routine psychological treatment services. Students may require additional support and treatment adaptations that account for student-specific stressors as this might improve psychological treatment outcomes

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction

Background Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3−), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3− ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. Methods and Results Plasma NO3−, nitrite (NO2−), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3−. NO3− intake increased (P < .05–0.001) plasma NO3− and NO2− and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3− ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min−1.kg−1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). Conclusions Acute dietary NO3− intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3− also improves muscle contractile function, suggest that dietary NO3− supplementation may be a valuable means of enhancing exercise capacity in this population

Effects of Web-Based Self-Reporting: College Students’ Self-Efficacy Regarding Fruit and Vegetable Intake

This study evaluated the effect of an online diet-tracking tool on college students’ self-efficacy regarding fruit and vegetable intake. A convenience sample of students completed online self-efficacy surveys before and after a six-week intervention in which they tracked dietary intake with an online tool. Group one (n=22 fall, n=43 spring) accessed a tracking tool without nutrition tips; group two (n=20 fall, n=33 spring) accessed the tool and weekly nutrition tips. The control group (n=36 fall, n=60 spring) had access to neither. Each semester there were significant changes in self-efficacy from pre- to post-test for men and for women when experimental groups were combined (p<0.05 for all); however, these changes were inconsistent. Qualitative data showed that participants responded well to the simplicity of the tool, the immediacy of feedback, and the customized database containing foods available on campus. Future models should improve user engagement by increasing convenience, potentially by automation

Limited Awareness and Low Immediate Uptake of Pre-Exposure Prophylaxis among Men Who Have Sex with Men Using an Internet Social Networking Site

Background: In 2010, the iPrEx trial demonstrated that oral antiretroviral pre-exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk men who have sex with men (MSM). The impact of iPrEx on PrEP knowledge and actual use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP awareness, interest and experience among at-risk MSM before and after iPrEx, and to determine demographic and behavioral factors associated with these measures. Methods and Findings: Cross-sectional, national, internet-based surveys were administered to U.S. based members of the most popular American MSM social networking site 2 months before (n = 398) and 1 month after (n = 4 558) publication of iPrEx results. Comparisons were made between these samples with regards to PrEP knowledge, interest, and experience. Data were collected on demographics, sexual risk, and experience with post-exposure prophylaxis (PEP). Regression analyses were performed to identify factors associated with PrEP awareness, interest, and experience post-iPrEx. Most participants were white, educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited pre- and post-iPrEx (13% vs. 19%), whereas interest levels after being provided with a description of PrEP remained high (76% vs. 79%). PrEP use remained uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI 1.52–36.6) and PEP experience (OR 34.2; CI 13.3–88.4). PrEP interest was associated with older age (OR 1.01; CI 1.00–1.02), unprotected anal intercourse with ≥1 male partner in the prior 3 months (OR 1.40; CI 1.10–1.77), and perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13–1.27). Conclusions: Among MSM engaged in online networking, awareness of PrEP was limited 1 month after the iPrEx data were released. Utilization was low, although some MSM who reported high-risk behaviors were interested in using PrEP. Studies are needed to understand barriers to PrEP utilization by at-risk MSM

Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial

BACKGROUND: Cabozantinib is an orally available inhibitor of tyrosine kinases including VEGFR2 and c-MET. We performed a post hoc analysis to find associations between select plasma biomarkers and treatment response in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) who received cabozantinib 100 mg daily as part of a phase 2 non-randomized expansion cohort (NCT00940225). METHODS: Plasma samples were collected at baseline, 6 weeks and at time of maximal response from 81 mCRPC pts with bone metastases, of which 33 also had measurable soft-tissue disease. Levels of 27 biomarkers were measured in duplicate using enzyme-linked immunosorbent assay. Spearman correlation coefficients were calculated for the association between biomarker levels or their change on treatment and either bone scan response (BSR) or soft tissue response according to RECIST. RESULTS: A BSR and RECIST response were seen in 66/81 pts (81 %) and 6/33 pts (18 %) respectively. No significant associations were found between any biomarker at any time point and either type of response. Plasma concentrations of VEGFA, FLT3L, c-MET, AXL, Gas6A, bone-specific alkaline phosphatase, interleukin-8 and the hypoxia markers CA9 and clusterin significantly increased during treatment with cabozantinib irrespective of response. The plasma concentrations of VEGFR2, Trap5b, Angiopoietin-2, TIMP-2 and TIE-2 significantly decreased during treatment with caboznatinib. CONCLUSIONS: Our data did not reveal plasma biomarkers associated with response to cabozantinib. The observed alterations in several biomarkers during treatment with cabozantinib may provide insights on the effects of cabozantinib on tumor cells and on tumor micro-environment and may help point to potential co-targeting approaches

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Background Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations

Tin-based nanocomposite alloy anodes for lithium-ion batteries

textLithium-alloying anode materials have attracted much attention as an alternative to carbon due to their high theoretical gravimetric capacities (e.g. Li4.4Si: 4200 mAh g-1, Li4.4Sn: 990 mAh g-1, and Li3Sb: 660 mAh g-1). An additional benefit of lithium alloying metals is that some of the react at a higher potentials vs. Li/Li+ than carbon, which can mitigate safety issues caused by solid-electrolyte interface layer formation and lithium plating. One of the most promising lithium -alloying anode materials that are being pursued are Sn-based materials due to their high capacity and tap density. This thesis investigates the synthesis and characterization of Sn-based lithium-ion battery anodes. SnSb-TiC-C and FeSn2-TiC nanocomposite alloy anodes for lithium-ion batteries have been synthesized by a mechanochemical process involving high-energy mechanical milling of Ti/Sn, Ti/M (M = Fe or Sb), and C. Characterization of the nanocomposites formed with x-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) reveals that these alloys are composed of crystalline nanoparticles of FeSn2 and SnSb dispersed in a matrix of TiC and carbon. The SnSb-TiC-C alloy shows an initial gravimetric capacity of 653 mAh g-1 (1384 mAh cm-3), an initial coulombic efficiency of 85%, and a tap density of 1.8 g cm-3. The FeSn2-TiC alloy shows an initial gravimetric capacity of 510 mAh g-1 (1073 mAh cm-3), an initial coulombic efficiency of 71%, and a tap density of 2.1 g cm-3. The TiC-C buffer matrix in the nanocomposite alloy anodes accommodates the large volume change occurring during the charge-discharge process and leads to good cyclability compared to pure FeSn2 and SnSb anodes.Materials Science and Engineerin