Oxidative stress plays an important role in aging-related neurodegeneration. This study used littermates of WT and Nox2-knockout (Nox2KO) mice plus endothelial cell–specific human Nox2 overexpression–transgenic (HuNox2Tg) mice to investigate Nox2-derived ROS in brain aging. Compared with young WT mice (3–4 months), aging WT mice (20–22 months) had obvious metabolic disorders and loss of locomotor activity. Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and γH2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2KO brains. HuNox2Tg brains at middle age (11–12 months) already had high levels of ROS production and activation of stress signaling pathways similar to those found in aging WT brains. The mechanism of Ang II–induced endothelial Nox2 activation in capillary damage was examined using primary brain microvascular endothelial cells. The clinical significance of Nox2-derived ROS in aging-related loss of cerebral capillaries and neurons was investigated using postmortem midbrain tissues of young (25–38 years) and elderly (61–85 years) adults. In conclusion, Nox2 activation is an important mechanism in aging-related cerebral capillary rarefaction and reduced brain function, with the possibility of a key role for endothelial cells.

The p47^phox is a key regulatory subunit of Nox2-containing NADPH oxidase (Nox2) that by generating reactive oxygen species (ROS) plays an important role in Angiotensin II (AngII)-induced cardiac hypertrophy and heart failure. However, the signalling pathways of p47^phox in the heart remains unclear. In this study, we used wild-type (WT) and p47^phox knockout (KO) mice (C57BL/6, male, 7-month-old, n = 9) to investigate p47^phox-dependent oxidant-signalling in AngII infusion (0.8 mg/kg/day, 14 days)-induced cardiac hypertrophy and cardiomyocyte apoptosis. AngII infusion resulted in remarkable high blood pressure and cardiac hypertrophy in WT mice. However, these AngII-induced pathological changes were significantly reduced in p47^phox KO mice. In WT hearts, AngII infusion increased significantly the levels of superoxide production, the expressions of Nox subunits, the expression of PKCα and C-Src and the activation of ASK1 (apoptosis signal-regulating kinase 1), MKK3/6, ERK1/2, p38 MAPK and JNK signalling pathways together with an elevated expression of apoptotic markers, i.e., γH2AX and p53 in the cardiomyocytes. However, in the absence of p47^phox, although PKCα expression was increased in the hearts after AngII infusion, there was no significant activation of ASK1, MKK3/6 and MAPKs signalling pathways and no increase in apoptosis biomarker expression in cardiomyocytes. In conclusion, p47^phox-dependent redox-signalling through ASK1, MKK3/6 and MAPKs plays a crucial role in AngII-induced cardiac hypertrophy and cardiomyocyte apoptosis.

Smoking is one of the strongest modifiable risk factors for coronary artery disease. It is the cause of approximately 10–30% of deaths due to cardiovascular disease around the world. There is a 50% reduction in the risk of myocardial infarction by one year for people who successfully quit smoking. Considering the risk associated with smoking and the benefits of smoking cessation, it is important to identify and implement effective smoking cessation strategies. There are pharmacological as well as non-pharmacological interventions to assist in smoking cessation. Pharmacological therapies including nicotine replacement therapy; bupropion and varenicline have generally been studied more in patients with cardiovascular disease than the non-pharmacological interventions. Non-pharmacological strategies for smoking cessation include behavioural interventions such as counselling sessions and cognitive behavioural therapy. Studies and randomised controlled trials have demonstrated the safety of most of the pharmacological interventions. Nonetheless, the success rates are variable for the different pharmacological options. Data suggest that greater success can be achieved in smoking cessation with a combination of pharmacological and non-pharmacological treatment. However, more studies are needed to explore the best therapeutic options to improve the success of smoking cessation.

Hazardous alcohol consumption is ranked above illicit drug use with regards to health deterioration and social and economic burden. This study sought to clarify the factors influencing alcohol consumption and its prevalence in young adults. Demographics, alcohol consumption and lifestyle information were gathered via anonymous questionnaires during 2011–2019, crossing Reading, Surrey and Farnborough universities, UK. Controlling for confounders, a multinomial logistic regression was performed using SAS^® 9.4 software. A total of 1440 students (43.5% males, 56.5% females; 54.4% Caucasians) with a mean (SD) age of 19.9 (2.73) were included. Among them, 68.9% consumed alcohol frequently and 31.7% had ≥12 units/week. Statistical analysis revealed that males consumed twice more alcohol than females, odds ratio (OR) 1.67 (95% confidence interval (CI) = 1.34–2.09), p-value < 0.01. Caucasians consumed up to five times more alcohol than other ethnicities, OR 4.55 (3.57–5.56), p-value < 0.01. Smokers consumed three times more alcohol than non-smokers, OR 2.69 (1.82, 3.99), p-value < 0.01. In general, the levels of alcohol consumption were positively associated with the levels of physical activity, OR 2.00 (1.17–3.42), p-value < 0.05 and negatively associated with recreational sedentary screen-time activities in males, OR 0.31 (0.12–0.86), p-value = 0.03. Focusing alcohol interventions toward Caucasians, smokers and physically active students, particularly males, may guide university strategies to reduce alcohol-related societal harm and risks of morbidity and mortality.

Background and Aims: Coronary calcification remains a significant challenge for the contemporary interventional cardiologist. We aim to describe the use of intravascular lithotripsy (IVL) in a range of real‐world settings.Methods: A retrospective two‐center analysis of patients treated with IVL between June 2018 and November 2019. Technical and procedural success, as well as procedural complications and 30‐day outcomes (death, myocardial infarction, or repeat target vessel revascularization), was recorded.Results: Sixty‐five patients underwent IVL: 80% were male and the mean age was 70.1 ± 12.0 years. 54% of patients presented with acute coronary syndrome (ACS) and 68% of patients had intracoronary imaging. Twelve patients required IVL within pre‐existing stents, and 12 underwent IVL in the left main stem. All balloons were successfully delivered with 98.5% procedural success. There was a significant gain in MLA post PCI of 261.9 ± 100% following IVL. There were two procedural complications. At 30‐day follow‐up, there was one death, and one patient required a repeat procedure due to stent underexpansion.Conclusions: In this largest real‐world series of imaging‐guided IVL for calcified lesions to date, we demonstrate that IVL is deliverable, safe, and effective at calcium modification especially when intracoronary imaging is used.