How far that little candle throws his beams! An interview with Mats Isaksson

This article adopts a policy-maker perspective on corporate governance, while exploring the role of academia in influencing corporate governance principles, the reasons for the boilerplate approach to governance rules typically adopted by most companies, and the reasons for a possible disconnect between research and corporate governance policies. The article ends with some key lessons about corporate governance and the future research agenda

Effect of a Behavioural Intervention for Adoption and Maintenance of a Physically Active Lifestyle on Psychological Well-Being and Quality of Life in Patients with Type 2 Diabetes: The IDES_2 Randomized Clinical Trial

Background: Psychological well-being and quality of life (QoL) are important outcomes of lifestyle interventions, as a positive impact may favour long-term maintenance of behaviour change. Objective: This study investigated the effect of a behavioural intervention for adopting and maintaining an active lifestyle on psychological well-being and health-related QoL in individuals with type 2 diabetes. Methods: Three hundred physically inactive and sedentary patients were randomized 1:1 to receive 1 month’s theoretical and practical counselling once a year (intervention group, INT) or standard care (control group, CON) for 3 years. Psychological well-being and QoL, assessed using the World Health Organization (WHO)-5 and the 36-Item Short Form (SF-36) questionnaire, respectively, were pre-specified secondary endpoints. The primary endpoint was sustained behaviour change, as assessed by accelerometer-based measurement of physical activity (PA) and sedentary time. Results: WHO-5 and SF-36 physical and mental component summary (PCS and MCS) scores increased progressively in the INT group and decreased in the CON group, resulting in significant between-group differences (WHO-5: mean difference 7.35 (95% confidence interval (CI) 3.15–11.55), P = 0.0007; PCS 4.20 (95% CI 2.25–6.15), P 150 min·wk−1 of moderate-to-vigorous intensity PA versus those who did not (13.06 (95% CI 7.51–18.61), P < 0.0001), whereas no relationship was detected for QoL. Conclusion: A counselling intervention that was effective in promoting a sustained change in PA and sedentary behaviour significantly improved psychological well-being and QoL. Trial Registration: ClinicalTrials.gov; NCT01600937; 10 October 2012

Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment

Background: Transarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy. Methods: Data of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment. Results: The proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p &lt; 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p &lt; 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC). Conclusions: Despite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis

Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms. Hyperglycemia- and dyslipidemia-induced carbonyl stress plays a role in diabetic cardiovascular complications and diabetes-related cancer risk. Moreover, the increased dietary exposure to AGEs/ALEs could mediate the impact of the modern, highly processed diet on cardiometabolic and cancer risk. Finally, the transient carbonyl stress resulting from supraphysiological postprandial spikes in blood glucose and lipid levels may play a role in acute proinflammatory and proatherogenic changes occurring after a calorie dense meal. These findings underline the potential importance of carbonyl stress as a mediator of the cardiometabolic and cancer risk linked to today's unhealthy diet. In this review, current knowledge in this field is discussed along with future research courses to offer new insights and open new avenues for therapeutic interventions to prevent diet-associated cardiometabolic disorders and cancer

Muscle fatigability in patients with type 2 diabetes: relation with long-term complications

Aims: It is unclear whether long-term complications play a role in muscle fatigue characteristic of patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the association between muscle fatigability and microvascular and macrovascular complications in patients with T2DM. Methods: One-hundred forty-six patients with T2DM (80 males, 66 females, aged 66.9 ± 7.9 years) were recruited. Maximal voluntary contraction (MCV) and endurance time (ET, 50% of the MVC) were assessed at the knee extensor muscles with an isometric dynamometer. Univariate and multivariate correlations of ET values with diabetic complications, a wide range of surrogate measures of these sequelae, and cardiovascular risk factors were examined. Results: A higher muscle fatigability was detected in patients with diabetic peripheral neuropathy (DPN, ET: −32.4%), cardiovascular disease (CVD, ET: −32.1%), retinopathy (ET: −35.8%), and nephropathy (ET: −30.4%). At univariate analysis, muscle fatigability was associated with age, physical activity level, diabetes duration, HbA1c, systolic blood pressure, albuminuria, eGFR, and several parameters of nervous and vascular function. Multivariate analysis showed that, after adjusting for covariates, ET was independently associated with sensory nerve conduction velocity, vibration perception threshold at malleolus, and ankle-brachial index. In addition, ET values were independently associated with the presence of DPN, CVD, and retinopathy. Conclusions: In T2DM, muscle fatigability is associated with presence of DPN, CVD, and retinopathy. Such defect appears to be mediated predominantly by sensory nerve and peripheral vascular dysfunction

Neuromuscular and metabolic responses to high-intensity intermittent cycling protocols with different work-to-rest ratios

Purpose: To investigate the effects of work-to-rest-ratio manipulation on neuromuscular and metabolic responses during 2 high-intensity intermittent training (HIT) protocols to exhaustion. Since different exercise durations were expected, the authors hypothesized that the protocol registering a longer duration would have a more pronounced effect on neuromuscular responses, while the other would challenge the cardiopulmonary system more. Methods: Thirteen competitive cyclists (age 19 ± 2 y) performed a preliminary incremental test to identify their maximal power output and 2 intermittent protocols to exhaustion (40: 20s and 30: 30s) at a fixed work rate of 135%Pmax interspersed by passive recovery. Surface electromyographic (sEMG) parameters (including muscle-fiber conduction velocity), cardiopulmonary parameters, and blood lactate concentration [La-] were recorded. Results: Time to exhaustion and total work were significantly higher for the 30: 30s (38 ± 13 min, 495 ± 161 kJ) than for the 40: 20s (10 ± 3 min, 180 ± 51 kJ). No differences were found in sEMG parameters for the 2 protocols. Mean and peak values of VO2, heart rate, ventilatory parameters (except for the peak value of respiratory frequency), and [La -] were significantly higher in the 40: 20s than in the 30: 30s. Conclusions: These results do not support the hypothesis that a longer time spent at high intensity has a more pronounced effect on neuromuscular responses, as no differences in EMG parameters were found in the 2 HIT protocols. Regarding metabolic responses, while the 40: 20s led to maximal values of VO2, [La-], and ventilatory parameters within a few minutes, the 30: 30s allowed maintenance of moderately high values for a considerably longer period, especially for [La-] and ventilatory parameters

Relationships of Changes in Physical Activity and Sedentary Behavior With Changes in Physical Fitness and Cardiometabolic Risk Profile in Individuals With Type 2 Diabetes. The Italian Diabetes and Exercise Study 2 (IDES_2)

OBJECTIVE In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week−1), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day−1), and light-intensity PA (LPA) (+0.8 h ⋅ day−1) and decrease in sedentary time (SED-time) (−0.8 h ⋅ day−1). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS Physical fitness increased and HbA1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min−1 ⋅ kg−1 and HbA1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure

Sedentary behaviour is an independent predictor of diabetic foot ulcer development: An 8-year prospective study

Aims: To prospectively explore the association between sedentary time (SED-time) and the development of diabetic foot ulcer (DFU) in people with diabetic peripheral neuropathy (DPN). Methods: 175 DPN individuals who attended the annual evaluation for the SAMBA Study (2012–2019) were included. Main outcome measure was the first diagnosis of DFU. SED-time was measured by the PAS 2.1 questionnaire. Nerve function was evaluated by nerve conduction studies. Vascular function was assessed by Ankle-brachial index (ABI) and pedal pulses. Foot deformity and skin dryness were examined by visual inspection. Results: 62 participants (35.5%) developed a DFU during the study. SED-time was significantly higher in people who developed DFUs (12.8 ± 3.0 vs 9.4 ± 3.1 h/day). Logistic regression showed that among several nervous (motor amplitude, OR 0.33, 95% CI, 0.18–0.60; sensory amplitude, 0.85, 0.77–0.94) and vascular parameters (ABI, 0.23, 0.1–0.61; pedal pulses, 2.81, 0.12–0.63) and foot characteristics (deformity, 2.63, 1.30–5.32; skin dryness, 2.04, 0.95–4.37), SED-time was one of the strongest variables contributing to the development of DFUs (2.95, 1.45–6.44). Conclusions: SED-time is an independent predictor of the risk of DFU in people with DPN. The monitoring of SED-time with strategies aimed at reducing it should be included in the standard care of diabetic patients