Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/ results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. Lay abstract: Head and neck cancers often have a poor treatment outcome. In order to study the response of the tissue, a miniaturized culture system has been developed to keep a small piece of tumor alive. In the current study, we show that small pieces of cancer tissue can be maintained in the system, using tissue structure and viability of single cells as a guide. In future work, patient equivalent treatments can be applied to these microculture systems to investigate individual patient tumor responses, which could help to guide treatment selection

Using Low-Fix Rate GPS Telemetry to Expand Estimates of Ungulate Reproductive Success

Background Population parameters such as reproductive success are critical for sustainably managing ungulate populations, however obtaining these data is often difficult, expensive, and invasive. Movement-based methods that leverage Global Positioning System (GPS) relocation data to identify parturition offer an alternative to more invasive techniques such as vaginal implant transmitters, but thus far have only been applied to relocation data with a relatively fine (one fix every  \u3c 8 h) temporal resolution. We employed a machine learning method to classify parturition/calf survival in cow elk in southeastern Kentucky, USA, using 13-h GPS relocation data and three simple movement metrics, training a random forest on cows that successfully reared their calf to a week old. Results We developed a decision rule based upon a predicted probability threshold across individual cow time series, accurately classifying 89.5% (51/57) of cows with a known reproductive status. When used to infer status of cows whose reproductive outcome was unknown, we classified 48.6% (21/38) as successful, compared to 85.1% (40/47) of known-status cows. Conclusions While our approach was limited primarily by fix acquisition success, we demonstrated that coarse collar fix rates did not limit inference if appropriate movement metrics are chosen. Movement-based methods for determining parturition in ungulates may allow wildlife managers to extract more vital rate information from GPS collars even if technology and related data quality are constrained by cost

Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer : a randomised controlled trial

INTRODUCTION: Many women experience emotional distress, depression and anxiety after a diagnosis of breast cancer. Psychological stress and depression have been associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation that may adversely affect immune system functioning and impact upon survival. This study investigated the effects of a lifestyle intervention on indices of psychological health status, HPA axis regulation and immune function in overweight women recovering from early-stage breast cancer treatment. METHODS: A total of 85 women treated for breast cancer 3 to 18 months previously were randomly allocated to a 6-month exercise and hypocaloric healthy eating program plus usual care or usual care alone (control group). Women in the intervention group received three supervised exercise sessions per week and individualized dietary advice, supplemented by weekly nutrition seminars. Depressive symptoms (Beck Depression Inventory version II: BDI-II), perceived stress (Perceived Stress Scale: PSS), salivary diurnal cortisol rhythms; inflammatory cytokines (IL-6 and Tumor necrosis factor-α), leukocyte phenotype counts, natural killer (NK) cell cytotoxicity and lymphocyte proliferation following mitogenic stimulation were assessed at baseline and 6-month follow up. RESULTS: Compared with the control group, the intervention group exhibited a reduction in depressive symptoms (adjusted mean difference, 95% confidence intervals (95% CI): -3.12, -1.03 to -5.26; P = 0.004) at the 6-month follow-up but no significant decrease in PSS scores (-2.07, -4.96 to 0.82; P = 0.16). The lifestyle intervention also had a significant impact on diurnal salivary cortisol rhythm compared with usual care alone, as evidenced by an increase in morning salivary cortisol at the 6-month follow-up (P <0.04), indicating a change in HPA axis regulation. Women in the control group had higher total leukocyte, neutrophil and lymphocyte counts in comparison to the intervention group at the 6-month follow-up (P ≤0.05), whereas there was no difference in NK cell counts (P = 0.46), NK cell cytotoxicity (P = 0.85) or lymphocyte proliferation responses (P = 0.11) between the two groups. CONCLUSION: Our results show that the lifestyle intervention resulted in a reduction in depressive symptoms and a normalisation of HPA axis regulation. Such changes could have important implications for long-term survival in women recovering from early-breast cancer treatment. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN08045231

Qualitative investigation of exercise perceptions and experiences in people with multiple sclerosis before, during, and after participation in a personally tailored exercise program

Objective To undertake a qualitative investigation of exercise perceptions and experiences in people with multiple sclerosis (PwMS) before, during, and after participation in a personally tail ored program designed to promote long-term maintenance of self-directed exercise. Design Focus groups and semistructured telephone interviews. Setting University exercise science department close to the recruiting hospital. Participants PwMS (N=33; mean age ± SD, 47.6±7.9y). Interventions Participants were recruited after participation in a randomized controlled exercise trial; all had been allocated to a 12-week exercise program comprising supervised and self-directed exercise sessions. Main Outcome Measures Exercise perceptions and experiences before, during, and after participation in the program. Results Four themes emerged from the analysis: (1) the transition to inactivity; (2) lack of knowledge and confidence; (3) positive exercise experiences; and (4) perspectives on exercise adherence. Conclusions Lack of confidence and exercise knowledge, coupled with negative perceptions about physical capabilities after an MS diagnosis, are clear barriers to exercise participation in PwMS. These issues are not being adequately addressed as part of the health care pathway or in community settings. Perceptions of improved posture, ability to overcome everyday difficulties, acute mood enhancements during and after exercise, and increased opportunities for social interaction were among the reported benefits of exercise participation. Despite the provision of a personally tailored exercise plan and use of cognitive behavioral strategies, self-directed exercise continued to present challenges to PwMS, and the importance of seeking cost-effective ways to maintain motivational support was implicit in participant responses

Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin \u3e 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (\u3e 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, 14%) and bone/joint (25, 10%). The median dose and duration of HD-daptomycin was 8.2 mg/kg/day (IQR 7.7-9.7) and 10 days (IQR 6-15), respectively. Overall clinical success rate was 89% (193/218) and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR 2-5). Thirty-day all cause mortality rate was 27% and 5 (2%) patients developed daptomycin nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult to treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections