Radiotherapy and technetium-99m-labeled red blood cell scintigraphy for hemoptysis from chronic MRSA infection

AbstractAimTo discuss the application of external beam radiotherapy (EBRT) and technetium-99m-labeled red blood cell scintigraphy (LRBCS) in life-threatening hemoptysis from a non-malignant condition.Materials and methodsThis case report presents a patient with persistent hemoptysis secondary to chronic Methicillin-resistant Staphylococcus aureus (MRSA) infection in whom conventional management failed to localize the site of pulmonary bleeding or to provide effective therapy.ResultsEBRT was successfully given for life-threatening hemoptysis with improvement in quality of life for nearly 1 year. LRBCS was used to localize the source of further bleeding and facilitate targeted therapy.ConclusionEBRT can be an effective and well-tolerated modality in treating life-threatening hemoptysis refractory to conventional methods. LRBCS is a non-invasive diagnostic tool that can be used to detect the source of pulmonary bleeding

Multimodal exercise in older patients with advanced pancreatic cancer undergoing first-line chemotherapy: A case series examining feasibility and preliminary efficacy

Purpose. Exercise is emerging as an adjunct therapy to cancer treatment; however, its role in older patients with advanced pancreatic cancer undergoing first-line chemotherapy is unclear. The aim of this study was to primarily provide evidence on feasibility with an exploratory examination of the initial efficacy of exercise in this clinical setting. Materials and Methods. Six patients aged 60–75 years with de novo or recurrent advanced pancreatic cancer undergoing first-line chemotherapy consented to participate in twice-weekly exercise that included resistance and aerobic training and boxing-related activities for up to 12 weeks. Patients were monitored for attendance, adherence, and adverse events. Body composition, muscle strength, functional ability, patient-reported outcome measures, and patient-reported experience measures were assessed at baseline and/or postintervention. Results. Of the 6 patients, 1 withdrew after baseline testing and 5 attended 42%–95% of planned sessions and adhered to 28%–83% of the prescribed exercise. There were no serious exercise-emergent adverse events. All 5 patients increased or maintained lean mass (0.1%–4.4%) and 4 reduced fat mass (−0.4%–−8.6%). Improvements were observed in 4 or all 5 patients for muscle strength (7.1%–75%), 5 times sit-to-stand (1.3%–21.4%), 6-m backward walk (16.5%–35.8%), and patient-reported outcomes. Furthermore, all patients perceived exercise as very helpful in managing their cancer and expressed a strong willingness to continue exercise in the future. Conclusion. A multimodal exercise program appears feasible with potential physical and psychological benefits for older patients with advanced pancreatic cancer undergoing first-line chemotherapy. Further research including a larger sample size is warranted

Informing the development of online weight management interventions:a qualitative investigation of primary care patient perceptions

Background: The internet is a potentially promising medium for delivering weight loss interventions. The current study sought to explore factors that might influence primary care patients’ initial uptake and continued use (up to four-weeks) of such programmes to help inform the development of novel, or refinement of existing, weight management interventions.Methods: Semi-structured interviews were conducted with 20 patients purposively sampled based on age, gender and BMI from a single rural general practice. The interviews were conducted 4 weeks after recruitment at the general practice and focused on experiences with using one of three freely available weight loss websites. Thematic Analysis was used to analyse the data.Results: Findings suggested that patients were initially motivated to engage with internet-based weight loss programmes by their accessibility and novelty. However, continued use was influenced by substantial facilitators and barriers, such as time and effort involved, reaction to prompts/reminders, and usefulness of information. Facilitation by face-to-face consultations with the GP was reported to be helpful in supporting change.Conclusions: Although primary care patients may not be ready yet to solely depend on online interventions for weight loss, their willingness to use them shows potential for use alongside face–to-face weight management advice or intervention. Recommendations to minimise barriers to engagement are provided

Examining the effects of creatine supplementation in augmenting adaptations to resistance training in patients with prostate cancer undergoing androgen deprivation therapy: A randomised, double-blind, placebo-controlled trial

INTRODUCTION: Creatine supplementation has consistently been demonstrated to augment adaptations in body composition, muscle strength and physical function in a variety of apparently healthy older adults and clinical populations. The effects of creatine supplementation and resistance training in individuals with cancer have yet to be investigated. This study aims to examine the effects of creatine supplementation in conjunction with resistance training on body composition, muscle strength and physical function in prostate cancer patients undergoing androgen deprivation therapy. METHODS AND ANALYSIS: This is a randomised, double-blind, placebo-controlled trial designed to examine the effects of creatine supplementation in addition to resistance training in patients with prostate cancer receiving androgen deprivation therapy. Both supplement and placebo groups will receive a 12-week supervised exercise programme comprising resistance training undertaken three times per week. The primary endpoint (fat-free mass) and secondary endpoints (fat mass, per cent body fat, physical fitness, quality of life and blood biomarkers) will be assessed at baseline and immediately following the intervention. ETHICS AND DISSEMINATION: The Human Research Ethics Committee of Edith Cowan University approved this study (ID: 22243 FAIRMAN). If the results of this trial demonstrate that creatine supplementation can augment beneficial adaptations of body composition, physical function and/or psychosocial outcomes to resistance training, this study will provide effect sizes that will inform the design of subsequent definitive randomised controlled trials. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12619000099123

Skeletal dysplasia-causing TRPV4 mutations suppress the hypertrophic differentiation of human iPSC-derived chondrocytes

Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human-induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype (WT). There were no differences in overall cartilaginous matrix production, but the V620I mutation resulted in reduced mechanical properties of cartilage matrix later in chondrogenesis. mRNA sequencing revealed that both mutations up-regulated several anterio

The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution

NAP-1 fold histone chaperones play an important role in escorting histones to and from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in a characteristic homodimeric conformation. In this study, a combination of small angle X-ray scattering, multi angle light scattering and pulsed electron–electron double resonance approaches were used to show that both Vps75 and Nap1 adopt ring-shaped tetrameric conformations in solution. This suggests that the formation of homotetramers is a common feature of NAP-1 fold histone chaperones. The tetramerisation of NAP-1 fold histone chaperones may act to shield acidic surfaces in the absence of histone cargo thus providing a ‘self-chaperoning’ type mechanism

Domain Walls and Phase Transitions in the Frustrated Two-Dimensional XY Model

We study and compare the critical properties of the two-dimensional (2D) XY model in a transverse magnetic field with magnetic filling factors f=1/3 and f=2/5. In addition to the spin waves, the low energy excitations of the system consist of various domain walls between degenerate ground states. The lowest energy domain wall has a similar structure for both f=1/3 and f=2/5 and its properties dictate the nature of the phase transition. For f=2/5 these lowest energy walls have a negative energy for binding to each other, giving rise to a branching domain-wall structure and leading to a first order phase transition. For f=1/3 this binding energy is positive, resulting in a linear critical interface. In order to make a comparison to recent experiments, we investigate the effect of small quenched bond disorder for f=2/5. A finite-size scaling analysis of extensive Monte Carlo simulations strongly suggests that the critical exponents of the phase transition for f=1/3, and for f=2/5 with disorder, fall into the universality class of the two-dimensional Ising model.Comment: 5 pages, 3 eps figures, REVTEX, revised version with new figure

Does exercise impact gut microbiota composition in men receiving androgen deprivation therapy for prostate cancer? A single-blinded, two-armed randomised controlled trial

Introduction: A potential link exists between prostate cancer (PCa) disease and treatment and increased inflammatory levels from gut dysbiosis. This study aims to examine if exercise favourably alters gut microbiota in men receiving androgen deprivation therapy (ADT) for PCa. Specifically, this study will explore whether: (1) exercise improves the composition of gut microbiota and increases the abundance of bacteria associated with health promotion and (2) whether gut health correlates with favourable inflammatory status, bowel function, continence and nausea among patients participating in the exercise intervention. Methods and analysis: A single-blinded, two-armed, randomised controlled trial will explore the influence of a 3-month exercise programme (3 days/week) for men with high-risk localised PCa receiving ADT. Sixty patients will be randomly assigned to either exercise intervention or usual care. The primary endpoint (gut health and function assessed via feacal samples) and secondary endpoints (self-reported quality of life via standardised questionnaires, blood biomarkers, body composition and physical fitness) will be measured at baseline and following the intervention. A variety of statistical methods will be used to understand the covariance between microbial diversity and metabolomics profile across time and intervention. An intention-to-treat approach will be utilised for the analyses with multiple imputations followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach. Ethics and dissemination: Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (ID: 19827 NEWTON). Findings will be reported in peer-reviewed publications and scientific conferences in addition to working with national support groups to translate findings for the broader community. If exercise is shown to result in favourable changes in gut microbial diversity, composition and metabolic profile, and reduce gastrointestinal complications in PCa patients receiving ADT, this study will form the basis of a future phase III trial. Trial registration number: ANZCTR12618000280202

Weight loss for overweight and obese patients with prostate cancer: A study protocol of a randomised trial comparing clinic-based versus telehealth delivered exercise and nutrition intervention (the TelEX trial)

Introduction Obese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer. Methods and analysis A single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥ 25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7-12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches. Ethics and dissemination Ethics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021-02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings. Trial registration number: ACTRN12621001312831