Microbiome and epigenetic variation in wild fish with low genetic diversity.

Non-genetic sources of phenotypic variation, such as the epigenome and the microbiome, could be important contributors to adaptive variation for species with low genetic diversity. However, little is known about the complex interaction between these factors and the genetic diversity of the host, particularly in wild populations. Here, we examine the skin microbiome composition of two closely-related mangrove killifish species with different mating systems (self-fertilising and outcrossing) under sympatric and allopatric conditions. This allows us to partition the influence of the genotype and the environment on their microbiome and (previously described) epigenetic profiles. We find the diversity and community composition of the skin microbiome are strongly shaped by the environment and, to a lesser extent, by species-specific influences. Heterozygosity and microbiome alpha diversity, but not epigenetic variation, are associated with the fluctuating asymmetry of traits related to performance (vision) and behaviour (aggression). Our study identifies that a proportion of the epigenetic diversity and microbiome differentiation is unrelated to genetic variation, and we find evidence for an associative relationship between microbiome and epigenetic diversity in these wild populations. This suggests that both mechanisms could potentially contribute to variation in species with low genetic diversity.

Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals.

PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.

[Nonpharmaceutical concepts for prevention and treatment of delirium]. / Nichtmedikamentöse Konzepte zu Prävention und Behandlung eines Delirs.

BACKGROUND: Cognitive impairment is common among older patients in German hospitals (40%). Dementia, other brain diseases and frailty significantly increase the risk of delirium and pose great challenges to interdisciplinary and interprofessional teams. Delirium prevention is achievable but requires complex interdepartmental strategies with specific components for timely recognition of the individual delirium risk, to carry out structured and sustained implementation of appropriate measures for delirium prevention as well as prompt etiological diagnostics and immediate treatment when delirium occurs. OBJECTIVE: The present work aims to shed light on the role of interprofessional and interdisciplinary collaboration in evidence-based, nonpharmacological delirium prevention programs. MATERIAL AND METHODS: Narrative review of international best practice programs. RESULTS: Nonpharmacological prevention of delirium is effective but requires differentiated risk identification, regular delirium screening and daily targeted cognitive activation and sleep promotion. This can only be achieved in close interprofessional collaboration and is mostly carried out interdepartmentally by specialized teams. DISCUSSION: Interprofessional multicomponent programs for delirium prevention hold the potential to reduce delirium and complication rates in older high-risk patients in regular care, thereby improving treatment and long-term quality of life. Additional interprofessional delirium prevention teams are deployed in different settings simultaneously and provide regular training on optimal delirium management. Demonstration of the effectiveness of cross-setting programs requires large multicenter studies and is therefore particularly laborious.

Exercise for individuals with bone metastases: A systematic review.

BACKGROUND: Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases. METHODS: MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched to July 16, 2020. RESULTS: A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n = 4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n = 16, 94%) and were delivered by qualified exercise professionals (n = 13, 76%). CONCLUSIONS: Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction.

Safety and Effects of Football in Skeletal Metastatic Prostate Cancer: a Subgroup Analysis of the FC Prostate Community Randomised Controlled Trial.

BACKGROUND: Skeletal metastatic disease excludes many cancer patients from participating in exercise and physical activity due to safety concerns. Empirical evidence from high-quality trials is warranted to guide clinicians and patients. OBJECTIVE: To evaluate the safety and potential benefits of high-impact aerobic exercise in patients with prostate cancer with skeletal metastases. DESIGN: Exploratory subgroup analysis of a pragmatic, multicentre, parallel randomised controlled trial. SETTING: The trial recruited 214 patients from five hospital urological departments in Denmark. PARTICIPANTS: Patients with prostate cancer with skeletal metastases (n = 41). INTERVENTION: Six months of football training twice weekly at a local club or usual care. Both groups received brief information on physical activity recommendations at the time of randomisation. MAIN OUTCOME(S) AND MEASURE(S): Safety, defined as falls, fractures and hospital admissions. Effects were evaluated on the primary outcome (prostate cancer-specific quality of life) and secondary outcomes (lean body mass, fat mass, hip and spine bone mineral density, and general physical and mental health). RESULTS: The original trial comprised 214 participants, 41 of whom had skeletal metastases at enrolment. Of these, 22 were allocated to football and 19 to usual care. The trial retention rate was 95% at 12 weeks and 88% at 6 months. Football participants attended 13 sessions on average at 12 weeks and 23 at 6 months. There were two falls, one in each group after 6 months, and no fractures. There were four unplanned hospital admissions in the study period, all four in the usual care group. Statistically significant between-group difference was observed in the primary outcome change in prostate cancer-specific quality of life at 12 weeks (7.6 points [95% CI 0.5 to 15.0]; P = 0.038). No statistical changes were found in the secondary outcomes. CONCLUSION: The analysis showed that football training was safe in patients with skeletal metastatic prostate cancer and significantly improved quality of life. Larger analyses and/or trials are warranted to confirm the safety of exercise more broadly in cancer patients with skeletal metastatic disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02430792 . Date of registration 30 April 2015.

Rising to the challenge: designing, implementing and reporting exercise oncology trials in understudied populations.

Exercise can improve cancer-related fatigue, quality of life and physical fitness, but is understudied in less common cancers such as multiple myeloma. Studying less common cancers and the adoption of novel study designs and open-science practices would improve the generalisability, transparency, rigour, credibility and reproducibility of exercise oncology research.

Factors associated with exercise preferences, barriers and facilitators of prostate cancer survivors.

OBJECTIVE: The purpose of this study was to understand the exercise levels, preferences and interests of prostate cancer survivors in Canada. METHODS: An electronic survey was administered via a prostate cancer-specific website and assessed self-reported exercise levels, exercise preferences and interests, exercise barriers and facilitators to exercise. RESULTS: Based on 103 participants, the majority (75.7%) of prostate cancer survivors did not meet both aerobic and resistance exercise guidelines, despite an interest in exercise. Strongest exercise preferences were shown for resistance exercise, walking, flexibility and bicycling and for performing exercise from a community-based gym or from home. Significant differences in exercise interests and facilitators were found between individuals who were meeting exercise guidelines compared to those who were not. CONCLUSION: The majority of Canadian prostate cancer survivors are insufficiently active. Exercise preferences and facilitators appear to be influenced by current exercise levels. Resistance and aerobic exercise should be considered when programming exercise for prostate cancer survivors.

Impact of exercise on chemotherapy completion rate: A systematic review of the evidence and recommendations for future exercise oncology research.

Receipt of full chemotherapy dose is associated with improved treatment efficacy and survival following a diagnosis of cancer. Exercise has emerged as a supportive care intervention that may improve chemotherapy completion rate by managing dose-limiting toxicities. We conducted a systematic review to evaluate the impact of exercise interventions on outcomes of chemotherapy completion rate in adult cancer patients. Relevant literature was retrieved from CINAHL, Medline (Ovid) and EMBASE based on subject headings and keywords pertaining to cancer, exercise and antineoplastic agents. Eligible articles were randomized control trials (RCTs) that prescribed aerobic or resistance exercise and included end-points relating to chemotherapy completion rate. Overall, eight RCTs were included in the final analysis. Only two RCTs (25%) that enrolled women with early-stage breast cancer reported a significant beneficial effect of exercise on chemotherapy completion rate, including higher mean relative dose intensity and fewer chemotherapy dose adjustments, relative to usual care. The remaining six studies reported no difference with exercise. Altogether, despite the growing number of exercise oncology trials to-date, information pertaining to the effect of exercise on chemotherapy completion rate is limited. Current data suggest exercise does not worsen chemotherapy tolerability. However, full interpretation of these findings is limited by the small number of trials. Future research involving rigorous study design is needed to confirm whether exercise can influence chemotherapy treatments.

A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis.

FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 with high affinity and recognizes an epitope that does not overlap with those of trastuzumab or pertuzumab. In tumor cells that express high levels of HER2, FS102 caused profound HER2 internalization and degradation leading to tumor cell apoptosis. The antitumor effect of FS102 in patient-derived xenografts (PDXs) correlated strongly with the HER2 amplification status of the tumors. Superior activity of FS102 over trastuzumab or the combination of trastuzumab and pertuzumab was observed in vitro and in vivo when the gene copy number of HER2 was equal to or exceeded 10 per cell based on quantitative polymerase chain reaction (qPCR). Thus, FS102 induced complete and sustained tumor regression in a significant proportion of HER2-high PDX tumor models. We hypothesize that the unique structure and/or epitope of FS102 enables the Fcab to internalize and degrade cell surface HER2 more efficiently than standard of care antibodies. In turn, increased depletion of HER2 commits the cells to apoptosis as a result of oncogene shock. FS102 has the potential of a biomarker-driven therapeutic that derives superior antitumor effects from a unique mechanism-of-action in tumor cells which are oncogenically addicted to the HER2 pathway due to overexpression.

Health-related physical fitness assessment in a community-based cancer rehabilitation setting.

PURPOSE: Assessment of physical fitness is important in order to set goals, appropriately prescribe exercise, and monitor change over time. This study aimed to determine the utility of a standardized physical fitness assessment for use in cancer-specific, community-based exercise programs. METHODS: Tests anticipated to be feasible and suitable for a community setting and a wide range of ages and physical function were chosen to measure body composition, aerobic fitness, strength, flexibility, and balance. Cancer Exercise Trainers/Specialists at cancer-specific, community-based exercise programs assessed new clients (n = 60) at enrollment, designed individualized exercise programs, and then performed a re-assessment 3-6 months later (n = 34). RESULTS: Resting heart rate, blood pressure, body mass index, waist circumference, handgrip strength, chair stands, sit-and-reach, back scratch, single-leg standing, and timed up-and-go tests were considered suitable and feasible tests/measures, as they were performed in most (≥88 %) participants. The ability to capture change was also noted for resting blood pressure (-7/-5 mmHg, p = 0.02), chair stands (+4, p < 0.01), handgrip strength (+2 kg, p < 0.01), and sit-and-reach (+3 cm, p = 0.03). While the submaximal treadmill test captured a meaningful improvement in aerobic fitness (+62 s, p = 0.17), it was not completed in 33 % of participants. Change in mobility, using the timed up-and-go was nominal and was not performed in 27 %. CONCLUSION: Submaximal treadmill testing, handgrip dynamometry, chair stands, and sit-and-reach tests were feasible, suitable, and provided meaningful physical fitness information in a cancer-specific, community-based, exercise program setting. However, a shorter treadmill protocol and more sensitive balance and upper body flexibility tests should be investigated.

Compressive rib fracture: peri-mortem and post-mortem trauma patterns in a pig model.

Despite numerous studies on high impact fractures of ribs, little is known about compressive rib injuries. We studied rib fractures from a biomechanical and morphological perspective using 15, 5th ribs of domestic pigs Sus scrofa, divided into two groups, desiccated (representing post-mortem trauma) and fresh ribs with intact periosteum (representing peri-mortem trauma). Ribs were axially compressed and subjected to four-point bending in an Instron 3339 fitted with custom jigs. Morphoscopic analysis of resultant fractures consisted of standard optical methods, micro-CT (µCT) and scanning electron microscopy (SEM). During axial compression, fresh ribs had slightly higher strength because of energy absorption capabilities of their soft and fluidic components. In flexure tests, dry ribs showed typical elastic-brittle behaviour with long linear load-extension curves, followed by relatively short non-linear elastic (hyperelastic) behaviour and brittle fracture. Fresh ribs showed initial linear-elastic behaviour, followed by strain softening, visco-plastic responses. During the course of loading, dry bone showed minimal observable damage prior to the onset of unstable fracture. In contrast, fresh bone showed buckling-like damage features on the compressive surface and cracking parallel to the axis of the bone. Morphologically, all dry ribs fractured precipitously, whereas all but one of the fresh ribs showed incomplete fracture. The mode of fracture, however, was remarkably similar for both groups, with butterfly fractures predominating (7/15, 46.6% dry and wet). Our study highlights the fact that under controlled loading, despite seemingly similar butterfly fracture morphology, fresh ribs (representing perimortem trauma) show a non-catastrophic response. While extensive strain softening observed for the fresh bone does show some additional micro-cracking damage, it appears that the periosteum may play a key role in imparting the observed pseudo-ductility to the ribs. The presence of fibrous pull-out and grooving of the outer tensile surface associated with periosteal stretching suggests that the periosteum under tension is able to sustain very high strain and bridge the mouth of the extending butterfly crack, thereby contributing to the observed strain-softening behaviour.