Biological ageing and colorectal cancer: fetuin A, sirtuins and telomeres at the interface between inflammation, metabolism and cancer

Colorectal cancer is a common, age-associated disease with significant comorbidity and mortality. Biomarkers of ageing may have prognostic or predictive value in colorectal cancer. Fetuin A, members of the sirtuin family of proteins and telomeres have shown promise as potential biomarkers of ageing. AIM: To evaluate these potential biomarkers in the context of colorectal cancer. METHODS: Two cohorts of patients were used. Telomere length was measured in peripheral blood leukocytes (PBL), and for a subset of patients, in normal colorectal and colorectal tumour tissue. Serum fetuin A was measured for these patients and data on clinico-pathological factors of accepted significance in colorectal cancer was collected prospectively. Telomere length in the matched samples of leukocytes, normal colorectal and colorectal tumour tissue was compared. Associations between telomere length in the different tissues, serum fetuin A and clinico-pathological factors of accepted significance in colorectal cancer were evaluated. A systematic review of the literature was performed to examine the evidence for correlation between telomere length in different tissues in humans. Tissue from colorectal tumours from the second cohort patients was mounted in a tissue microarray (TMA) and stained for sirtuin proteins (SIRT2-SIRT7). This TMA also contained tissue from a subset of matched samples of adjacent normal colorectal mucosa. Staining of normal colorectal and colorectal tumour tissue was evaluated by the weighted Histoscore method and compared. The effect of staining in tumour tissue on cancer-specific survival was examined. Associations between Histoscores and clinico-pathological factors of accepted significance in colorectal cancer were assessed. RESULTS: Systematic review of the literature did not show robust evidence of correlation between telomere length in different tissues in humans. Telomere length in peripheral blood leukocytes did not show correlation with telomere length in normal colorectal mucosa, or in colorectal tumour tissue. PBL telomere length was potentially related to the presence of distant metastases. Fetuin A was inversely associated with markers of systemic inflammation and with T stage. Novel nuclear localisation was described for SIRT4 and SIRT5. Protein expression of the sirtuins was reduced in tumour tissue in comparison to normal colorectal mucosa, apart from SIRT3 cytoplasmic and nuclear and SIRT6 nuclear stainng. Lowest and highest quartile SIRT2 expression was associated with worse survival. Sirtuin protein expression levels and localisation correlate with increased systemic inflammation and pathological markers of poor prognosis in tumour tissue. Intercorrelations between sirtuin expression levels in normal tissue are not seen in tumour tissue, possibly indicating a breakdown of signalling and control

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Online neuropilates classes in chronic stroke patients: Protocol for a randomised controlled feasibility study

Introduction: Stroke survivors often demonstrate low physical activity levels and experience barriers to physical exercise including embarrassment, low self-efficacy and a shortage of tailored community exercise programmes. Access to physical activity programmes for stroke survivors could be improved by providing tailored, online programmes, although little is known about the safety and feasibility of online exercise classes for stroke survivors. One such programme of exercise which has received little attention in the literature is neuropilates. Neuropilates is the practice of a modified pilates programme in those with neurological conditions and is theorised to have beneficial effects on strength, balance and proprioception in stroke survivors. No previous study has been conducted to investigate online, remotely supervised neuropilates exercise classes in the stroke survivors. Method and Analysis: This single assessor blinded randomised controlled feasibility study will compare a 6-week online, remotely instructed neuropilates programme to a 6-week online, remotely instructed generalised exercise programme and a 6-week unsupervised generalised home exercise programme in chronic stroke patients. Twenty adults, at least 6 months post stroke, and finished their formal rehabilitation will be recruited to the study. Primary feasibility outcome measures will include patient tolerance of the programme, adherence rates, adverse events, recruitment and retention. Secondary clinical outcomes will include; balance, gait, tone and quality of life. Assessments will be completed at baseline, on programme completion and 3 months post completion by a Physiotherapist blinded to the group allocation. Ethics and dissemination: This study has received ethical approval from the Sligo University Hospital Ethics committee and ATU ethics board. Results will be published in peer-reviewed journals and presented at national and international conferences.The trial has been registered on clinicaltrials.gov (Identifier: NCT04491279)

Feasibility, safety and outcomes of an online, remotely supervised neuropilates class in a post stroke patient: A case study

Neuropilates, that is, the practice of pilates in a patient with a neurological condition, may benefit post stroke patients through improving their strength, postural control, alignment and stability, with previous studies showing significant improvements in balance and gait parameters post pilates interventions. This case study aimed to investigate the feasibility and outcomes of an online, remotely supervised one to one pilates class, once a week for 6 weeks with a post stroke patient. Outcomes measured included gait and balance through the “Timed Up and Go (TUG)” test, the “Five Times Sit to Stand (5TSTS)” test, the “Activities specific Balance Confidence (ABC) scale” and the “Tinetti” balance and gait assessment. Quality of life was also measured by the “Stroke Specific Quality of Life (SSQOL)” Scale and muscle tone was measured through use of the “Modified Ashworth Scale (MAS)”. Feasibility was assessed qualitatively based on information gathered from the client satisfaction questionnaire and the patient’s tolerance of the programme. Results demonstrated that the patient enjoyed and tolerated the programme well with modifications and that he would prefer online exercise training over face to face in the future. The patient improved his TUG score and his SSQOL score beyond the minimal detectable change. Smaller improvements were also seen in the 5TSTS test, the ABC scale and the Tinetti assessment. Mixed results were seen for muscle tone. Typical neuropilates exercise sets for post stroke patients in standing and seated positions are given as well as advice and protocols for ensuring high levels of safety with online exercising.</jats:p

Capacitance and conductance for an MOS system in inversion, with oxide capacitance and minority carrier lifetime extractions

Experimental observations for the In 0.53 Ga 0.47 As metal-oxide-semiconductor (MOS) system in inversion indicate that the measured capacitance (C) and conductance (G or G m ), are uniquely related through two functions of the alternating current angular frequency (ω). The peak value of the first function (G/ω) is equal to the peak value of the second function (-dC/dlog e (ω) ≡ -ωdC/dω). Moreover, these peak values occur at the same angular frequency (ω m ), that is, the transition frequency. The experimental observations are confirmed by physics-based simulations, and applying the equivalent circuit model for the MOS system in inversion, the functional relationship is also demonstrated mathematically and shown to be generally true for any MOS system in inversion. The functional relationship permits the discrimination between high interface state densities and genuine surface inversion. The two function peak values are found to be equal to C ox 2 /(2(C ox + C D )) where C ox is the oxide capacitance per unit area and C D is the semiconductor depletion capacitance in inversion. The equal peak values of the functions, and their observed symmetry relation about ω m on a logarithmic ω plot, opens a new route to experimentally determining C ox . Finally, knowing ω m permits the extraction of the minority carrier generation lifetime in the bulk of the In 0.53 Ga 0.47 As layer