Patients' and doctors' views and experiences of the patient safety trajectory of breast cancer care.

INTRODUCTION: Successful breast cancer outcomes can be jeopardised by adverse events. Understanding and integrating patients' and doctors' perspectives into care trajectories could improve patient safety. This study assessed their views on, and experiences of, medical error and patient safety. METHODS: A cross-sectional, quantitative 20-40 item questionnaire for patients attending Cork University Hospital Cancer Centre and breast cancer doctors in the Republic of Ireland was developed. Domains included demographics, medical error experience, patient safety opinions and concerns. RESULTS: 184 patients and 116 doctors completed the survey. Of the doctors, 41.4% felt patient safety had deteriorated over the previous five years and 54.3% felt patient safety measures were inadequate compared to 13.0% and 27.7% of patients respectively. Of the 30 patients who experienced medical errors/negligence claims, 18 reported permanent or long-term physical and emotional effects. Forty-two of 48 (87.5%) doctors who experienced medical errors/negligence claims reported emotional health impacts. Almost half of doctors involved in negligence claims considered early retirement. Forty-four patients and 154 doctors didn't experience errors but reported their patient safety concerns. Doctors were more concerned about communication and administrative errors, staffing and organisational factors compared to patients. Multiple barriers to error reporting were highlighted. CONCLUSION: This is the first study to assess patients' and doctors' patient safety views and medical error/negligence claims experiences in breast cancer care in Ireland. Experience of medical error/negligence claims had long-lasting implications for both groups. Doctors were concerned about a multitude of errors and causative factors. Failure to embed these findings is a missed opportunity to improve safety.

Dealing with digital paralysis: Surviving a cyberattack in a National Cancer center.

INTRODUCTION: Cyberattacks represent a growing threat for healthcare delivery globally. We assess the impact and implications of a cyberattack on a cancer center in Ireland. METHODS: On May 14th 2021 (day 0) Cork University Hospital (CUH) Cancer Center was involved in the first national healthcare ransomware attack in Ireland. Contingency plans were only present in laboratory services who had previously experienced information technology (IT) failures. No hospital cyberattack emergency plan was in place. Departmental logs of activity for 120 days after the attack were reviewed and compared with historical activity records. Daily sample deficits (routine daily number of samples analyzed - number of samples analyzed during cyberattack) were calculated. Categorical variables are reported as median and range. Qualitative data were collected via reflective essays and interviews with key stakeholders from affected departments in CUH. RESULTS: On day 0, all IT systems were shut down. Radiotherapy (RT) treatment and cancer surgeries stopped, outpatient activity fell by 50%. hematology, biochemistry and radiology capacity fell by 90% (daily sample deficit (DSD) 2700 samples), 75% (DSD 2250 samples), and 90% (100% mammography/PET scan) respectively. Histopathology reporting times doubled (7 to 15 days). Radiotherapy (RT) was interrupted for 113 patients in CUH. The median treatment gap duration was six days for category 1 patients and 10 for the remaining patients. Partner organizations paused all IT links with CUH. Outsourcing of radiology and radiotherapy commenced, alternative communication networks and national conference calls in RT and Clinical Trials were established. By day 28 Email communication was restored. By day 210 reporting and data storage backlogs were cleared and over 2000 computers were checked/replaced. CONCLUSION: Cyberattacks have rapid, profound and protracted impacts. While laboratory and diagnostic deficits were readily quantified, the impact of disrupted/delayed care on patient outcomes is less readily quantifiable. Cyberawareness and cyberattack plans need to be embedded in healthcare. POLICY SUMMARY: Cyberattacks pose significant challenges for healthcare systems, impacting patient care, clinical outcomes, and staff wellbeing. This study provides a comprehensive review of the impact of the Conti ransomware attack on cancer services in Cork University Hospital (CUH), the first cyberattack on a national health service. Our study highlights the widespread disruption caused by a cyberattack including shutdown of information technology (IT) services, marked reduction in outpatient activity, temporary cessation of essential services such as radiation therapy. We provide a framework for other institutions for mitigating the impact of a cyberattack, underscoring the need for a cyberpreparedness plan similar to those made for natural disasters and the profound legacy of a cyberattack on patient care.

Shatavari supplementation in postmenopausal women alters the skeletal muscle proteome and pathways involved in training adaptation.

PURPOSE: Shatavari is an understudied, widely available herbal supplement. It contains steroidal saponins and phytoestrogens. We previously showed that six weeks of shatavari supplementation improved handgrip strength and increased markers of myosin contractile function. Mechanistic insights into shatavari's actions are limited. Therefore, we performed proteomics on vastus lateralis (VL) samples that remained from our original study. METHODS: In a randomised double-blind trial, women (68.5 ± 6 years) ingested either placebo or shatavari (equivalent to 26,500 mg/d fresh weight) for six weeks. Tandem mass tag global proteomic analysis of VL samples was conducted (N = 7 shatavari, N = 5 placebo). Data were normalized to total peptides and scaled using a reference sample. Data were filtered using a 5% FDR. For each protein, the pre to post supplementation difference was expressed as log2 fold change. Welch's t tests with Benjamini-Hochberg corrections were performed for each protein. Pathway enrichment (PADOG, CAMERA) was interrogated in Reactome (v85). RESULTS: No individual protein was significantly different between supplementation conditions. Both PADOG and CAMERA indicated that pathways related to (1) Integrin/MAPK signalling, (2) metabolism/insulin secretion; (3) cell proliferation/senescence/DNA repair/cell death; (4) haemostasis/platelets/fibrin; (5) signal transduction; (6) neutrophil degranulation and (7) chemical synapse function were significantly upregulated. CAMERA indicated pathways related to translation/amino acid metabolism, viral infection, and muscle contraction were downregulated. CONCLUSION: Our analyses indicate that shatavari may support muscle adaptation responses to exercise. These data provide useful signposts for future investigation of shatavari's utility in conserving and enhancing musculoskeletal function in older age. TRIAL REGISTRATION: NCT05025917 30/08/21, retrospectively registered.

Room to Improve: An Audit of In-Hospital End-of-Life Care for Oncology Patients in a Tertiary Cancer Centre in Ireland During the COVID-19 Pandemic.

The COVID-19 pandemic compounded isolation for patients through social distancing measures and staff shortages. We were concerned about the impact of COVID-19 on the quality of care provided at end-of-life in 2021 in a national cancer centre, and instigated the first ever review of the care of the dying. Quality of care was assessed retrospectively using a validated instrument developed by the United Kingdom's National Quality Board. Sixty-six patient deaths occurred in our cancer centre in 2021. The 'risk of dying' was documented in 65.2% of records. Palliative care services were involved in 77%, and pastoral care in 10.6%. What was important to the patient was documented in 24.2%. The 'quality-of-death' score was satisfactory for most but poor in 21.2%. Our study prompted change, including appointment of an end-of-life coordinator, development of a checklist to ensure comprehensive communication, expansion of the end-of-life committee to include junior doctors, and regular audit.

Attitudes and knowledge of emergency doctors towards end-of-life care in the emergency department: a national survey.

BACKGROUND: Emergency departments (EDs) are seeing an increase in patients requiring end-of-life (EOL) care. There is paucity of data of attitudes and knowledge of physicians providing EOL care in the ED both internationally and in Ireland. OBJECTIVE: The aim of this project was to assess the attitudes and knowledge of ED physicians towards EOL care. METHODS: This was a cross-sectional electronic survey of ED physicians working in Irish EDs and was facilitated through the Irish Trainee Emergency Research Network over a 6-week period. The questionnaire covered the following domains: demographic data, awareness of EOL Care, views and attitudes towards EOL care. RESULTS: Of a potential 679 respondents, 441 responses were received, of which 311 (response rate of 44.8%) had fully completed the survey across 23 participant sites. Majority of the respondents were under the age of 35 (62%), were male (58%) and at Senior House Officer level (36%). In terms of awareness, 32% (98) of respondents were not aware of palliative care services in their hospitals while only 29% (91) were aware of national EOL guidance. Fifty-five percent (172) reported commencing EOL care in the ED, however 75.5% (234) respondents reported their knowledge of EOL care to be limited or non-existent. Only 30.2% respondents felt comfortable commencing EOL care in the ED without speciality team input. There appears to be a lack of clarity on the roles and responsibilities of emergency medicine nurses and doctors in the care of the dying patient in ED with only 31.2% (95) being clear on this role. Significant differences were observed associated with clinical experience and physician grade. CONCLUSION: This study has highlighted a lack of awareness and knowledge of EOL care particularly amongst less experienced emergency medicine doctors. Formalized training and education programs in the provision of EOL care in the ED will improve comfort levels and knowledge amongst the emergency medicine doctors and improve the quality of care provided.

Impact of the COVID-19 pandemic on cancer care in Ireland - Perspectives from a COVID-19 and Cancer Working Group.

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021. The Irish Cancer Society, a national cancer charity with a role in advocacy, research and patient supports, convened a multi-disciplinary stakeholder group (COVID-19 and Cancer Working Group) to reflect on and understand the impact of the pandemic on cancer patients and services in Ireland, and discuss potential mitigation strategies. Perspectives on experiences were gathered across domains including timeliness of data acquisition and its conversion into intelligence, and the resourcing of cancer care to address cancer service impacts. The group highlighted aspects for future research to understand the long-term pandemic impact on cancer outcomes, while also highlighting potential strategies to support cancer services, build resilience and address delayed diagnosis. Additional measures include the need for cancer workforce recruitment and retention, increased mental health supports for both patients and oncology professionals, improvements to public health messaging, a near real-time multimodal national cancer database, and robust digital and physical infrastructure to mitigate impacts of the current pandemic and future challenges to cancer care systems.

Tart Cherry Supplement Enhances Skeletal Muscle Glutathione Peroxidase Expression and Functional Recovery after Muscle Damage.

INTRODUCTION: Montmorency cherry concentrate (MCC) supplementation enhances functional recovery from exercise, potentially due to antioxidant and anti-inflammatory effects. However, to date, supporting empirical evidence for these mechanistic hypotheses is reliant on indirect blood biomarkers. This study is the first to investigate functional recovery from exercise alongside molecular changes within the exercised muscle after MCC supplementation. METHODS: Ten participants completed two maximal unilateral eccentric knee extension trials after MCC or placebo (PLA) supplementation for 7 d before and 48 h after exercise. Knee extension maximum voluntary contractions, maximal isokinetic contractions, single leg jumps, and soreness measures were assessed before, immediately, 24 h, and 48 h after exercise. Venous blood and vastus lateralis muscle samples were collected at each time point. Plasma concentrations of interleukin-6, tumor necrosis factor alpha, C-reactive protein, creatine kinase, and phenolic acids were quantified. Intramuscular mRNA expressions of superoxide dismutase 1 (SOD1), SOD3, glutathione peroxidase 1 (GPX1), GPX3, GPX4, GPX7, catalase, and nuclear factor erythroid 2-related factor 2 and relative intramuscular protein expressions of SOD1, catalase, and GPX3 were quantified. RESULTS: MCC supplementation enhanced the recovery of normalized maximum voluntary contraction 1-s average compared with PLA (postexercise PLA, 59.5% ± 18.0%, vs MCC, 76.5% ± 13.9%; 24 h PLA, 69.8% ± 15.9%, vs MCC, 80.5% ± 15.3%; supplementation effect P = 0.024). MCC supplementation increased plasma hydroxybenzoic, hippuric, and vanillic acid concentrations (supplementation effect P = 0.028, P = 0.002, P = 0.003); SOD3, GPX3, GPX4, GPX7 (supplement effect P < 0.05), and GPX1 (interaction effect P = 0.017) gene expression; and GPX3 protein expression (supplementation effect P = 0.004) versus PLA. There were no significant differences between conditions for other outcome measures. CONCLUSIONS: MCC supplementation conserved isometric muscle strength and upregulated antioxidant gene and protein expression in parallel with increased phenolic acid concentrations.

Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover.

Shatavari has long been used as an Ayurvedic herb for women's health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 years) ingested either placebo (N = 10) or shatavari (N = 10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented as difference scores (Week 6-baseline, median ± interquartile range). Handgrip (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo -0.4 ± 1.3 kg; p = 0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo -0.08 ± 0.5 a.u., shatavari +0.3 ± 1 arbitrary units (a.u.); p = 0.03). Shatavari increased the phosphorylation of Aktser473 (Aktser473 (placebo -0.6 ± 0.6 a.u., shatavari +0.2 ± 1.3 a.u.; p = 0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, ß-CTX) and stimulation of human osteoblasts with pooled sera (N = 8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity. Shatavari may improve muscle function and contractility via myosin conformational change and further investigation of its utility in conserving and enhancing musculoskeletal function, in larger and more diverse cohorts, is warranted.

A Feasibility Study of Primary Care Liaisons: Linking Older Adults to Community Resources.

INTRODUCTION: Programs and services available through the aging services network can help community-dwelling older adults to age in place but are often not discussed in routine primary care. The primary care liaison was developed as a novel integration intervention to address this disconnect. METHODS: Employed by an Area Agency on Aging, primary care liaisons performed outreach to primary care with the goal of raising awareness of community-based programs, resources, and services available to older adults and their caregivers and facilitating referrals. The evaluation of the primary care liaison model, conducted from December 2015 to February 2019, used the Reach, Effectiveness, Adoption, Implementation, Maintenance framework and assessed reach (number of clinics contacted), adoption (number of referrals to the Area Agency on Aging), implementation (number of follow-up contacts with a practice), and effectiveness (proportion of referrals reached and provided relevant resources). RESULTS: The primary care liaisons contacted a median of 18.5 clinics per month (IQR=15-31). Primary care referrals averaged >100 per month, and referrals increased over time. Successful follow-up outreach visits had a median of 3 (IQR=2-10), and follow-up contacts had a median of 3 (IQR=1-7) per practice. Three quarters of caregivers for people with dementia reached by Area Agency on Aging staff were provided with information about relevant resources. CONCLUSIONS: The primary care liaison model is feasible, fosters ongoing interactions between primary care and Area Agencies on Aging, and connects older adults and their caregivers to relevant programs and services. Adoption of the primary care liaison model by other Area Agencies on Aging across the U.S. may help further the vision of optimized health and well-being of older adults.

Use, Practices and Attitudes of Elite and Sub-Elite Athletes towards Tart Cherry Supplementation.

Tart cherry (TC) supplementation can improve exercise recovery and performance; and may also improve sleep duration and quality. This study investigated the use and knowledge of TC supplementation by athletes of all competitive levels. Eighty participants (52.5% elite (international, national, professional), 47.5% sub-elite (semi-professional, state/regional, county level, club level, recreational)) completed an online questionnaire investigating their attitudes towards and use of TC supplementation. Overall, 22.6% of participants were using or had previously used TC supplements, and 12.5% of participants planned to used TC supplements. Improved recovery (71.4%), sleep (32.1%) and immunity and general health (32.1%) were the most frequently indicated goals by respondents using TC supplements. In total, 32.1% of respondents were supplemented with TC chronically, 39.3% acutely and 28.6% used a combination of chronic and acute supplementation. The majority of those employing TC supplementation chronically used TC either over 2-3 days (37.0%) or continuously (37.0%). The most popular TC pre- and post-loading period was one day (34.3% and 41.5%, respectively). There were no significant differences between elite and sub-elite athletes in any parameters assessed (p > 0.05). TC supplementation is not widely used by the athletes surveyed, and athletes using TC supplements showed poor awareness of an evidence-led dosing strategy, regardless of competitive level.

Review of Analytical Methods and Reporting of the Polyphenol Content of Tart Cherry Supplements in Human Supplementation Studies Investigating Health and Exercise Performance Effects: Recommendations for Good Practice.

Tart cherries (TC) are a rich source of polyphenols that elicit antioxidant and anti-inflammatory effects. As a consequence, the effects of TC derived supplements on markers of human health, exercise performance and sleep have been investigated. Supplementation protocols have been highly variable across studies and the dose of bioactive compounds used has often been poorly characterized. Specific and non-specific analytical methods were employed for measuring the total polyphenol and anthocyanin content in TC supplements. This review critically analyses the supplementation protocols and the analytical methods used for the characterization of TC supplements, culminating in recommendations for good practice in the analysis and reporting of the polyphenol content and profile of TC products. A literature search was conducted using PubMed/Medline and Web of Science up to May 4th, 2020, including studies published in all years prior. Only articles written in English that provided a TC dietary supplement as opposed to fresh whole TC were included in this review. Forty-three studies were identified as eligible and included for analysis in this review. The studies investigated the effects of TC supplementation on various aspects of human health, exercise recovery and performance and sleep. Twenty studies conducted an analysis of TC supplement and reported total polyphenol/anthocyanin content. Six studies did not report the polyphenol content of the TC supplement used. Seventeen studies reported the TC supplement polyphenol content but this was derived from previously published studies and presumably different supplement batches. The duration of the supplementation protocol ranged from acute supplementation to 84 days, meanwhile the total polyphenol and anthocyanin dose ranged from 143 to 2,140 mg/day and 15 to 547 mg/day, respectively. Due to the variety of specific and non-specific analytical methods used, the relative efficacy of different doses and polyphenol blends cannot reliably be extrapolated from critical analysis of the literature. Future studies should conduct an analysis of the study supplement batch. In addition to analysis and reporting of total polyphenol content, specific analytical methods such as HPLC UV/MS should be used to quantify total and individual anthocyanin contents.

Use, Practices and Attitudes of Sports Nutrition and Strength and Conditioning Practitioners towards Tart Cherry Supplementation.

Tart cherry (TC) supplementation has been shown to accelerate post-exercise recovery, enhance endurance performance and improve sleep duration and quality. This study aimed to identify the use, practices and attitudes of sports nutrition and strength and conditioning practitioners towards tart cherry supplementation. Thirty-five practitioners anonymously completed an online survey investigating their use, practices and attitudes towards tart cherry supplements. Forty-six percent of the responders were currently recommending TC supplements, 11% had previously recommended TC supplements and 26% have not previously recommended TC supplements but were planning on doing so in the future. Of those recommending TC, 50% recommended or were planning on recommending TC supplements to enhance exercise recovery and 26% to improve sleep duration and quality. Acute supplementation and daily use during multi-day competition or demanding training blocks with a 2-3-day pre-load were the most reported supplementation recommendations (28% and 18%, respectively). Fifty-two percent of responders indicated uncertainty about the daily polyphenol dose to recommend as part of a TC supplementation protocol. Despite the high use and interest from sports nutrition and strength and conditioning practitioners in TC supplements, their practices did not align with the protocols found to be effective within the literature.

Protein-carbohydrate ingestion alters Vps34 cellular localization independent of changes in kinase activity in human skeletal muscle.

NEW FINDINGS: What is the central question of the study? Is Vps34 a nutrient-sensitive activator of mTORC1 in human skeletal muscle? What is the main finding and its importance? We show that altering nutrient availability, via protein-carbohydrate feeding, does not increase Vps34 kinase activity in human skeletal muscle. Instead, feeding increased Vps34-mTORC1 co-localization in parallel to increased mTORC1 activity. These findings may have important implications in the understanding nutrient-induced mTORC1 activation in skeletal muscle via interaction with Vps34. ABSTRACT: The Class III PI3Kinase, Vps34, has recently been proposed as a nutrient sensor, essential for activation of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1). We therefore investigated the effects of increasing nutrient availability through protein-carbohydrate (PRO-CHO) feeding on Vps34 kinase activity and cellular localization in human skeletal muscle. Eight young, healthy males (21 ± 0.5 yrs, 77.7 ± 9.9 kg, 25.9 ± 2.7 kg/m2 , mean ± SD) ingested a PRO-CHO beverage containing 20/44/1 g PRO/CHO/FAT respectively, with skeletal muscle biopsies obtained at baseline and 1 h and 3 h post-feeding. PRO-CHO feeding did not alter Vps34 kinase activity, but did stimulate Vps34 translocation toward the cell periphery (PRE (mean ± SD) - 0.273 ± 0.040, 1 h - 0.348 ± 0.061, Pearson's Coefficient (r)) where it co-localized with mTOR (PRE - 0.312 ± 0.040, 1 h - 0.348 ± 0.069, Pearson's Coefficient (r)). These alterations occurred in parallel to an increase in S6K1 kinase activity (941 ± 466% of PRE at 1 h post-feeding). Subsequent in vitro experiments in C2C12 and human primary myotubes displayed no effect of the Vps34-specific inhibitor SAR405 on mTORC1 signalling responses to elevated nutrient availability. Therefore, in summary, PRO-CHO ingestion does not increase Vps34 activity in human skeletal muscle, whilst pharmacological inhibition of Vps34 does not prevent nutrient stimulation of mTORC1 in vitro. However, PRO-CHO ingestion promotes Vps34 translocation to the cell periphery, enabling Vps34 to associate with mTOR. Therefore, our data suggests that interaction between Vps34 and mTOR, rather than changes in Vps34 activity per se may be involved in PRO-CHO activation of mTORC1 in human skeletal muscle.

Evaluating the Effect of a Home-Delivered Meals Service on the Physical and Psychological Wellbeing of a UK Population of Older Adults - A Pilot and Feasibility Study.

We evaluated the effectiveness of a 3-week, daily meal provision service by a non-profit provider on the physical and psychological wellbeing of an older adult population. We further examined the feasibility of carrying out such measures in participant's homes. 19 older adult participants (8M, 11F; 78.3 ± 8.7 years) received 3 meals per day for 21 days and supplemented these meals ad libitum. Risk of malnutrition (Mini Nutritional Assessment; MNA) body composition, blood pressure, handgrip strength, balance, mobility, loneliness, social capital, satisfaction with life and mood were evaluated in participant's homes before and after the intervention. Following the intervention, MNA score increased significantly and participants rated themselves as significantly less depressed. We describe a methodology that was largely feasible and outline ways in which it could be improved. We have demonstrated that even short-term, home meal deliveries improve MNA scores and can positively alter some measures of mood.

Tart Cherry Concentrate Does Not Alter the Gut Microbiome, Glycaemic Control or Systemic Inflammation in a Middle-Aged Population.

Limited evidence suggests that the consumption of polyphenols may improve glycaemic control and insulin sensitivity. The gut microbiome produces phenolic metabolites and increases their bioavailability. A handful of studies have suggested that polyphenol consumption alters gut microbiome composition. There are no data available investigating such effects in polyphenol-rich Montmorency cherry (MC) supplementation. A total of 28 participants (aged 40-60 years) were randomized to receive daily MC or glucose and energy-matched placebo supplementation for 4 wk. Faecal and blood samples were obtained at baseline and at 4 wk. There was no clear effect of supplementation on glucose handling (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Gutt indices), although the Matsuda index decreased significantly in the MC group post-supplementation, reflecting an increase in serum insulin concentration. Contrastingly, placebo, but not MC supplementation induced a 6% increase in the Oral Glucose Insulin Sensitivity (OGIS) estimate of glucose clearance. Serum IL-6 and C reactive protein were unaltered by either supplement. The faecal bacterial microbiome was sequenced; species richness and diversity were unchanged by MC or placebo and no significant correlation existed between changes in Bacteroides and Faecalibacterium abundance and any index of insulin sensitivity. Therefore, 4 weeks of MC supplementation did not alter the gut microbiome, glycaemic control or systemic concentrations of IL-6 and CRP in a middle-aged population.

MyoCount: a software tool for the automated quantification of myotube surface area and nuclear fusion index.

It is often desirable to characterise the morphology of myogenic cultures. To achieve this, the surface area of myotubes is often quantified, along with the nuclear fusion index (NFI). Existing methods of such quantification are time-consuming and subject to error-prone human input. We have developed MyoCount, an open-source program that runs via the freely available MATLAB Runtime and quantifies myotube surface area and NFI. MyoCount allows the user to adjust its parameters to account for differences in image quality, magnification and the colour channels used in generating the image. MyoCount measures of myotube surface area and NFI were compared to the mean of measures performed by two blinded investigators using ImageJ software (surface area R 2 = 0.89, NFI R 2 =0.87). For NFI, the mean coefficient of variation (CV) between two investigators (17.6 ± 2.3%) was significantly higher than that between the investigator mean and MyoCount (13.5 ± 1.4%). For measurements of myotube area, the CV did not differ between both analysis methods. Given these results and the advantages of applying the same image analysis method uniformly across all images in an experiment, we suggest that MyoCount will be a useful research tool and we publish its source code and instructions for its use alongside this article.

Evaluation of Targeted Pharmacist Interventions to Reduce Length of Stay in an Acute Care Practice Model.

BACKGROUND: Despite widespread recognition of the need for innovative pharmacy practice approaches, the development and implementation of value-based outcomes remains difficult to achieve. Furthermore, gaps in the literature persist because the majority of available literature is retrospective in nature and describes only the clinical impact of pharmacists' interventions. OBJECTIVE: Length of stay (LOS) is a clinical outcome metric used to represent efficiency in health care. The objective of this study was to evaluate the impact of pharmacist-driven interventions on LOS in the acute care setting. METHODS: A separate samples pretest-posttest design was utilized to compare the effect of pharmacist interventions across 3 practice areas (medicine, hematology/oncology, and pediatrics). Two time periods were evaluated: preimplementation (PRE) and a pilot period, postimplementation of interventions (POST). Interventions included targeted discharge services, such as discharge prescription writing (with provider cosignature). Participating pharmacists completed semistructured interviews following the pilot. RESULTS: A total of 924 patients (466 PRE and 458 POST) were included in the analysis. The median LOS decreased from 4.95 (interquartile range = 3.24-8.5) to 4.12 (2.21-7.96) days from the PRE versus POST groups, respectively ( P < 0.011). There was no difference in readmission rates between groups (21% vs 19.1%, P = 0.7). Interviews revealed several themes, including positive impact on professional development. Conclusion and Relevance: This pilot study demonstrated the ability of pharmacist interventions to reduce LOS. Pharmacists identified time as the primary barrier and acknowledged the importance of leaders prioritizing pharmacists' responsibilities. This study is novel in targeting LOS, providing a value-based outcome for clinical pharmacy services.

Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB.

Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age and in several chronic disease states. The aim of this study was to determine the effects of human obese and lean subcutaneous adipose tissue secretome on myogenesis and metabolism in skeletal muscle cells derived from both young (18-30 yr) and elderly (>65 yr) individuals. Obese subcutaneous adipose tissue secretome impaired the myogenesis of old myoblasts but not young myoblasts. Resistin was prolifically secreted by obese subcutaneous adipose tissue and impaired myotube thickness and nuclear fusion by activation of the classical NFκB pathway. Depletion of resistin from obese adipose tissue secretome restored myogenesis. Inhibition of the classical NFκB pathway protected myoblasts from the detrimental effect of resistin on myogenesis. Resistin also promoted intramyocellular lipid accumulation in myotubes and altered myotube metabolism by enhancing fatty acid oxidation and increasing myotube respiration and ATP production. In conclusion, resistin derived from human obese subcutaneous adipose tissue impairs myogenesis of human skeletal muscle, particularly older muscle, and alters muscle metabolism in developing myotubes. These findings may have important implications for the maintenance of muscle mass in older people with chronic inflammatory conditions, or older people who are obese or overweight.

IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development.

Studies in murine cell lines and in mouse models suggest that IL-15 promotes myogenesis and may protect against the inflammation-mediated skeletal muscle atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human skeletal muscle growth and development remain largely uncharacterised. Myogenic cultures were isolated from the skeletal muscle of young and elderly subjects. Myoblasts were differentiated for 8 d, with or without the addition of recombinant cytokines (rIL-15, rTNFα) and an IL-15 receptor neutralising antibody. Although myotubes were 19% thinner in cultures derived from elderly subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15rα in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNFα stimulation alone. IL-15rα neutralisation and rTNFα decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNFα stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an effective therapeutic target for the attenuation of inflammation-mediated skeletal muscle atrophy.