Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model.

Repetitive mild traumatic brain injuries (rmTBI) may contribute to the development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects and via regulation of neuronal synaptic plasticity by counteracting post-trauma excitotoxicity. This study aimed to investigate mechanisms implicated in the etiology of neurodegeneration in rmTBI mice treated with ALC. Adult male C57BL/6J mice were allocated to sham, rmTBI or ALC + rmTBI groups. 15 rmTBIs were administered across 23 days using a modified weight drop model. Neurological testing and spatial learning and memory assessments via the Morris Water Maze (MWM) were undertaken at 48 h and 3 months. RT-PCR analysis of the cortex and hippocampus was undertaken for MAPT, GFAP, AIF1, GRIA, CCL11, TDP43, and TNF genes. Gene expression in the cortex showed elevated mRNA levels of MAPT, TNF, and GFAP in the rmTBI group that were reduced by ALC treatment. In the hippocampus, mRNA expression was elevated for GRIA1 in the rmTBI group but not the ALC + rmTBI treatment group. ALC treatment showed protective effects against the deficits displayed in neurological testing and MWM assessment observed in the rmTBI group. While brain structures display differential vulnerability to insult as evidenced by location specific postimpact disruption of key genes, this study shows correlative mRNA neurodegeneration and functional impairment that was ameliorated by ALC treatment in several key genes. ALC may mitigate damage inflicted in the various secondary neurodegenerative cascades and contribute to functional protection following rmTBI.

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI).

Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to monitor recovery. Small non-coding RNAs (sncRNAs) including microRNAs can be measured in saliva following TBI and have been investigated as potential diagnostic markers. The aim of this systematic review was to investigate the diagnostic or prognostic ability of microRNAs extracted from saliva in human subjects. PubMed, Embase, Scopus, PsycINFO and Web of Science were searched for studies that examined the association of saliva microRNAs in TBI. Original studies of any design involving diagnostic capacity of salivary microRNAs for TBI were selected for data extraction. Nine studies met inclusion criteria, with a heterogeneous population involving athletes and hospital patients, children and adults. The studies identified a total of 188 differentially expressed microRNAs, with 30 detected in multiple studies. MicroRNAs in multiple studies involved expression change bidirectionality. The study design and methods involved significant heterogeneity that precluded meta-analysis. Early data indicates salivary microRNAs may assist with TBI diagnosis. Further research with consistent methods and larger patient populations is required to evaluate the diagnostic and prognostic potential of saliva microRNAs.

Depression, anxiety, stress, and physical activity of Australian adults during COVID-19: A combined longitudinal and repeated cross-sectional study.

Background: The COVID-19 pandemic has led to a worsening of mental health and health behaviors. While physical activity is positively associated mental health, there is limited understanding of how mental health and physical activity evolve throughout the COVID-19 pandemic. This study aimed to examine changes in depression, anxiety and stress and physical activity, and associations between depression, anxiety, and stress with physical activity in Australian adults across three-time points during the COVID-19 pandemic. Materials and methods: This study collected both longitudinal and cross-sectional data at three-time points during the COVID-19 pandemic in Australia (i.e., April, July/August, and December 2020). Australians aged 18 years and over were invited to complete online surveys hosted on Qualtrics survey platform. Linear mixed models with random subject effect and general linear models were used to analyze the longitudinal and repeated cross-sectional data respectively. Results: The number of participants in cross-sectional surveys and longitudinal surveys was 1,877 and 849, respectively. There was an overall reduction between time 2 vs. time 3 in depression (d = 1.03, 95% CI = 0.20, 1.85), anxiety (d = 0.57, 95% CI = 0.02, 1.12), and stress (d = 1.13, 95% CI = 0.21, 2.04) scores but no significant differences in physical activity across three-time points. On average, participants who met the physical activity guidelines had lower depression (d = -2.08, 95% CI = -2.90, -1.26), anxiety (d = -0.88, 95% CI = -1.41, -0.34), and stress (d = -1.35, 95% CI = -2.13, -0.56) scores compared to those not meeting the guidelines. Conclusion: In the context of the ongoing COVID-19 pandemic, both governments and service providers should continue to provide the public with timely mental health support and promote the benefits of physical activity, as a cost-effective strategy to improve mental health and wellbeing.

The association of resilience with depression, anxiety, stress and physical activity during the COVID-19 pandemic.

BACKGROUND: COVID-19 has resulted in substantial global upheaval. Resilience is important in protecting wellbeing, however few studies have investigated changes in resilience over time, and associations between resilience with depression, anxiety, stress, and physical activity during the COVID-19 pandemic. METHODS: Online surveys were conducted to collect both longitudinal and cross-sectional data at three time points during 2020. Australian adults aged 18 years and over were invited to complete the online surveys. Measures include the six-item Brief Resilience Scale, the 21-item Depression, Anxiety and Stress Scale, and the Active Australia Survey which have eight items identifying the duration and frequency of walking, and moderate and vigorous physical activities (MVPA), over the past 7 days. General linear mixed models and general linear models were used in the analysis. RESULTS: In the longitudinal sample, adjusted differences (aDif) in resilience scores did not significantly change over time (time 2 vs. time 1 [aDif = - 0.02, 95% CI = - 0.08, 0.03], and time 3 vs. time 1 [aDif = < 0.01, 95% CI = - 0.07, 0.06]). On average, those engaging in at least 150 min of MVPA per week (aDif = 0.10, 95% CI = 0.04, 0.16), and having depression (aDif = 0.40, 95% CI = 0.33), anxiety (aDif = 0.34, 95% CI = 0.26, 0.41), and stress scores (aDif = 0.30, 95% CI = 0.23, 0.37) within the normal range had significantly higher resilience scores. The association between resilience and physical activity was independent of depression, anxiety, and stress levels. All results were similar for the cross-sectional sample. CONCLUSIONS: Resilience scores did not change significantly during the COVID-19 pandemic. However, there were significant associations between resilience with physical activity and psychological distress. This research helps inform future interventions to enhance or nurture resilience, particularly targeted at people identified as at risk of psychological distress.

How are COVID-19 knowledge and concern associated with practising preventive behaviours in Australian adults?

OBJECTIVE: This study investigated the association between COVID-19 prevention knowledge and concern and practising preventive behaviour in Australian adults. METHODS: Using an online survey, knowledge of Australian COVID-19 guidelines, concerns about pandemic impact, the practice of preventive behaviours, and sociodemographic variables (i.e. age, gender, information source) were measured. Bivariate analysis and linear regression models were used. RESULTS: A total of 1,491 participants (age 50.5 ±14.9 years, 32.3% males) completed the survey. Higher knowledge and concern scores were associated with a higher practice of preventive behaviour scores (ßs:0.47 & 0.08 respectively, p<0.001). Older adults (>65 years) and women had higher knowledge and practice scores compared to their counterparts. Being younger (<45 years) and male were associated with a lower practice score (ßs:-0.88 & -2.52, respectively, p<0.001). Referring to public and government sources as primary sources of information was associated with a higher practice score (ß:1.21, p<0.001). CONCLUSIONS: Government-run campaigns appear to be effective in promoting preventive practices and achieving a high knowledge of COVID-19 guidelines in Australian adults. Implications for public health: Public health strategies are required to promote the practice of preventive behaviour for COVID-19 (or future pandemics), especially among men and younger adults using social media, given their wide use of these sources.

Willingness to Vaccinate against COVID-19 Declines in Australia, Except in Lockdown Areas.

This study investigates changes in willingness to vaccinate against COVID-19 and the effect of the extended restrictions in metropolitan Victoria on this change. Longitudinal and repeated cross-sectional data were collected from online surveys distributed in April, between July and August, and December 2020. Australian adults who were ≥18 years old were recruited through email lists, social media networks, and paid Facebook advertisement. Willingness to vaccinate against COVID-19 was self-reported. The results showed that participants were more willing to vaccinate if the vaccine was safe at survey 1 (longitudinal: adjusted OR (aOR) = 1.88, 95%CI = 1.38, 2.56; cross-sectional: aOR = 3.73, 95%CI = 2.55, 5.45) and survey 2 (longitudinal: aOR = 1.54, 95%CI = 1.19, 2.00; cross-sectional: aOR = 2.48, 1.67, 3.67), compared to survey 3. The change in willingness to vaccinate if the vaccine was safe and effective was not significant for those in Metropolitan Victoria; but was for those living in other Australian locations at survey 1 (OR = 2.13, 95%CI = 1.64, 2.76) and survey 2 (OR = 1.62, 95%CI = 1.30, 2.01), compared to survey 3. Willingness to vaccinate even if a vaccine had not been proven safe decreased at survey 3 (OR = 2.02, 95%CI = 1.14, 3.57) for those living in Metropolitan Victoria. In conclusion willingness to vaccinate against COVID-19 decreased over time among Australians, except for those living in metropolitan Victoria, where an additional strict and prolonged lockdown was implemented around the time of survey 2. Either the experience of the lockdown, or the presence of the COVID-19 virus itself had a positive influence on participants' willingness to vaccinate, even if such a vaccine was not yet proven to be safe and effective.

Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points.

The cumulative effect of mild traumatic brain injuries (mTBI) can result in chronic neurological damage, however the molecular mechanisms underpinning this detriment require further investigation. A closed head weight drop model that replicates the biomechanics and head acceleration forces of human mTBI was used to provide an exploration of the acute and chronic outcomes following single and repeated impacts. Adult male C57BL/6J mice were randomly assigned into one of four impact groups (control; one, five and 15 impacts) which were delivered over 23 days. Outcomes were assessed 48 hours and 3 months following the final mTBI. Hippocampal spatial learning and memory assessment revealed impaired performance in the 15-impact group compared with control in the acute phase that persisted at chronic measurement. mRNA analyses were performed on brain tissue samples of the cortex and hippocampus using quantitative RT-PCR. Eight genes were assessed, namely MAPT, GFAP, AIF1, GRIA1, CCL11, TARDBP, TNF, and NEFL, with expression changes observed based on location and follow-up duration. The cortex and hippocampus showed vulnerability to insult, displaying upregulation of key excitotoxicity and inflammation genes. Serum samples showed no difference between groups for proteins phosphorylated tau and GFAP. These data suggest that the cumulative effect of the impacts was sufficient to induce mTBI pathophysiology and clinical features. The genes investigated in this study provide opportunity for further investigation of mTBI-related neuropathology and may provide targets in the development of therapies that help mitigate the effects of mTBI.

Minocycline improves cognition and molecular measures of inflammation and neurodegeneration following repetitive mTBI.

OBJECTIVE: To compare the neuroprotective effects of minocycline treatment in a murine model of mTBI on measures of spatial learning and memory, neuroinflammation, excitotoxicity, and neurodegeneration. DESIGN: Adult male C57BL/6 J mice were randomly assigned into vehicle control, vehicle with repetitive mTBI, minocycline without mTBI, or minocycline with repetitive mTBI groups. METHODS: A validated mouse model of repetitive impact-induced rotational acceleration was used to deliver 15 mTBIs across 23 days. Cognition was assessed via Morris water maze (MWM) testing, and mRNA analysis investigated MAPT, GFAP, AIF1, GRIA1, TARDBP, TNF, and NEFL genes. Assessment was undertaken 48 h and 3 months following final mTBI. RESULTS: In the chronic phase of recovery, MWM testing revealed impairment in the vehicle mTBI group compared to unimpacted controls (p < .01) that was not present in the minocycline mTBI group, indicating chronic neuroprotection. mRNA analysis revealed AIF1 elevation in the acute cortex (p < .01) and chronic hippocampus (p < .01) of the vehicle mTBI group, with minocycline treatment leading to improved markers of microglial activation and inflammation in the chronic stage of recovery. CONCLUSIONS: These data suggest that minocycline treatment alleviated some mTBI pathophysiology and clinical features at chronic time-points.

As the Pandemic Progresses, How Does Willingness to Vaccinate against COVID-19 Evolve?

Controversy around the safety and efficacy of COVID-19 vaccines may lead to low vaccination rates. Survey data were collected in April and August 2020 from a total of 2343 Australian adults. A quarter (n = 575, 24%) completed both surveys. A generalized linear mixed model analysis was conducted to determine whether willingness to vaccinate changed in the repeated sample, and a multinominal logistic regression was conducted in all participants to determine whether willingness to vaccinate was associated with demographics, chronic disease, or media use. Willingness to vaccinate slightly decreased between April (87%) and August (85%) but this was not significant. Willingness to vaccinate was lower in people with a certificate or diploma (79%) compared to those with a Bachelor degree (87%), p < 0.01 and lower in infrequent users of traditional media (78%) compared to frequent users of traditional media (89%), p < 0.001. Women were more likely to be unsure if they would be willing to vaccinate (10%) compared to men (7%), p < 0.01. There were no associations between willingness to vaccinate and age, chronic disease, or social media use. Promotion of a COVID-19 vaccine should consider targeting women, and people with a certificate or diploma, via non-traditional media channels.

Depression, Anxiety and Stress during COVID-19: Associations with Changes in Physical Activity, Sleep, Tobacco and Alcohol Use in Australian Adults.

The novel coronavirus (COVID-19) has enforced dramatic changes to daily living including economic and health impacts. Evidence for the impact of these changes on our physical and mental health and health behaviors is limited. We examined the associations between psychological distress and changes in selected health behaviors since the onset of COVID-19 in Australia. An online survey was distributed in April 2020 and included measures of depression, anxiety, stress, physical activity, sleep, alcohol intake and cigarette smoking. The survey was completed by 1491 adults (mean age 50.5 ± 14.9 years, 67% female). Negative change was reported for physical activity (48.9%), sleep (40.7%), alcohol (26.6%) and smoking (6.9%) since the onset of the COVID-19 pandemic. Significantly higher scores in one or more psychological distress states were found for females, and those not in a relationship, in the lowest income category, aged 18-45 years, or with a chronic illness. Negative changes in physical activity, sleep, smoking and alcohol intake were associated with higher depression, anxiety and stress symptoms. Health-promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address increases in psychological distress during the pandemic. Ongoing evaluation of the impact of lifestyle changes associated with the pandemic is needed.

Skeletal muscle - A bystander or influencer of metabolic syndrome?

BACKGROUND AND AIMS: Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been suggested that some of these risk factors can have detrimental effects on the skeletal muscle while others can be a direct result of skeletal muscle abnormalities, showing a two-way directionality in the pathogenesis of the condition. This review aims to explore this bidirectional correlation by discussing the impact of metabolic syndrome on skeletal muscle tissue in general and will also discuss ways in which skeletal muscle alterations may contribute to the pathogenesis of metabolic syndrome. METHODS: Literature searches were conducted with key words (e.g. metabolic syndrome, skeletal muscle, hyperglycemia) using PubMed, EBSCOhost, Science Direct and Google Scholar. All article types were included in the search. RESULTS: The pathological mechanisms associated with metabolic syndrome, such as hyperglycemia and inflammation, have been associated with changes in skeletal muscle fiber composition, metabolism, insulin sensitivity, mitochondrial function, and strength. Additionally, some skeletal muscle alterations, particularly mitochondrial dysfunction and insulin resistance, are suggested to contribute to the development of metabolic syndrome. For example, the suggested underlying mechanisms of sarcopenia development are also contributors to metabolic syndrome pathogenesis. CONCLUSION: Whilst numerous studies have identified a relationship between metabolic syndrome and skeletal muscle abnormalities, further investigation into the underlying mechanisms is needed to elucidate the best prevention and management strategies for these conditions.

Blood biomarkers for assessment of mild traumatic brain injury and chronic traumatic encephalopathy.

Mild traumatic brain injuries (mTBI) are prevalent and can result in significant debilitation. Current diagnostic methods have implicit limitations, with clinical assessment tools reliant on subjective self-reported symptoms or non-specific clinical observations, and commonly available imaging techniques lacking sufficient sensitivity to detect mTBI. A blood biomarker would provide a readily accessible detector of mTBI to meet the current measurement gap. Suitable options would provide objective and quantifiable information in diagnosing mTBI, in monitoring recovery, and in establishing a prognosis of resultant neurodegenerative disease, such as chronic traumatic encephalopathy (CTE). A biomarker would also assist in progressing research, providing suitable endpoints for testing therapeutic modalities and for further exploring mTBI pathophysiology. This review highlights the most promising blood-based protein candidates that are expressed in the central nervous system (CNS) and released into systemic circulation following mTBI. To date, neurofilament light (NF-L) may be the most suitable candidate for assessing neuronal damage, and glial fibrillary acidic protein (GFAP) for assessing astrocyte activation, although further work is required. Ultimately, the heterogeneity of cells in the brain and each marker's limitations may require a combination of biomarkers, and recent developments in microRNA (miRNA) markers of mTBI show promise and warrant further exploration.

Geranylgeraniol prevents statin-induced skeletal muscle fatigue without causing adverse effects in cardiac or vascular smooth muscle performance.

The administration of geranylgeranyl pyrophosphate (GGPP) (or its precursor, geranylgeraniol [GGOH]) has been shown by several in vitro studies to be capable of abrogating statin-induced myotoxicity. Nonetheless, the potential of GGPP repletion to prevent statin-associated muscle symptoms (SAMS) in vivo is yet to be investigated. Therefore, this study aimed to evaluate the ability of GGOH to prevent SAMS in rodents. Female Wistar rats (12 weeks of age) were randomised to 1 of 4 treatment groups: control, control with GGOH, simvastatin or simvastatin with GGOH. Ex vivo assessment of force production was conducted in skeletal muscles of varying fiber composition. Ex vivo left ventricular performance and blood vessel function was also assessed to determine if the administration of GGOH caused adverse changes in these parameters. Statin administration was associated with reduced force production in fast-twitch glycolytic muscle, but coadministration with GGOH completely abrogated this effect. Additionally, GGOH improved the performance of muscles not adversely affected by simvastatin (ie, those with a greater proportion of slow-twitch oxidative fibers), and increased force production in the control animals. Neither control nor statin-treated rodents given GGOH exhibited adverse changes in cardiac function. Vascular relaxation was also maintained following treatment with GGOH. The findings of this study demonstrate that GGOH can prevent statin-induced skeletal muscle fatigue in rodents without causing adverse changes in cardiovascular function. Further studies to elucidate the exact mechanisms underlying the effects observed in this investigation are warranted.

Statins with different lipophilic indices exert distinct effects on skeletal, cardiac and vascular smooth muscle.

AIMS: Data concerning the influence of statin lipophilicity on the myotoxic and pleiotropic effects of statins is conflicting, and mechanistic head-to-head comparison studies evaluating this parameter are limited. In order to address the disparity, this mechanistic investigation aimed to assess the effects of two short-acting statins with different lipophilic indices on skeletal, cardiac and vascular smooth muscle physiology. MATERIALS AND METHODS: Young female Wistar rats were randomised to simvastatin (80 mg kg-1 day-1), pravastatin (160 mg kg-1 day-1) or control treatment groups. Changes in functional muscle performance were assessed, as well as mRNA levels of genes relating to atrophy, hypertrophy, mitochondrial function and/or oxidative stress. KEY FINDINGS: There were no significant differences in the mRNA profiles of isolated skeletal muscles amongst the treatment groups. In terms of skeleletal muscle performance, simvastatin reduced functionality but treatment with pravastatin significantly improved force production. Rodents given simvastatin demonstrated comparable myocardial integrity to the control group. Conversely, pravastatin reduced left ventricular action potential duration, diastolic stiffness and Mhc-ß expression. Pravastatin improved endothelium-dependent relaxation, particularly in muscular arteries, but this effect was absent in the simvastatin-treated rats. The responsiveness of isolated blood vessels to noradrenaline also differed between the statin groups. The findings of this study support that the effects of statins on skeletal, cardiac and vascular smooth muscle vary with their lipophilic indices. SIGNIFICANCE: The results of this work have important implications for elucidating the mechanisms responsible for the myotoxic and pleiotropic effects of statins.

Modeling sports-related mild traumatic brain injury in animals-A systematic review.

Sports-related head trauma has emerged as an important public health issue, as mild traumatic brain injuries (mTBIs) may result in neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Research into mTBI and CTE pathophysiology are difficult to undertake in athletes, with observational trials and post-mortem analysis the current mainstays. Thus, animal models play an important role in the study of mTBI, however, traditional animal models have focused on acute, severe injuries rather than the more typical mTBI's seen in sport injuries. Recently, a number of animal models have been developed that are both appropriately scaled and biomechanically relevant to the forces sustained by athletes. This review aimed to examine the literature for variables included in these animal models, and the resulting neurotrauma as evidenced by pathology and behavioral deficits. A systematic search of the literature was performed in multiple electronic databases. The inclusion criteria required mimicry of athlete mTBI conditions: freedom of head movement, lack of surgical alteration of the skull, and application of direct contact force. Studies were analyzed for variables including apparatus design features (impact force, change in animal head velocity, and kinetic energy transfer to the head), demonstrated pathology (phosphorylated tau, TDP-43 aggregation, diffuse axonal injury, gliosis, cytokine inflammation response, and genetic integrity), and behavioral changes. These studies suggested that appropriate animal models can assist in understanding the pathological and functional outcomes of athlete mTBI, and could be used as a platform for future studies of diagnostic/prognostic markers and in the development of treatment interventions.

Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet.

BACKGROUND: Physical activity (PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat high-carbohydrate (HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training (LIT), and high-intensity interval training (HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats. METHODS: Twelve-week-old Wistar rats were randomly allocated to 4 groups (12 rats/group): control (CTL), sedentary (SED), LIT, and HIIT. Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions. RESULTS: The SED group had slower cardiac conduction (p = 0.0426) and greater thoracic aortic contractile responses (p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group (p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group (both p < 0.05). The LIT and HIIT groups had lower visceral (p = 0.0057 for LIT, p = 0.0120 for HIIT) and epididymal fat (p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group. CONCLUSION: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation, mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

The effect of lipophilicity and dose on the frequency of statin-associated muscle symptoms: A systematic review and meta-analysis.

Addressing the factors which lead to the development of statin-associated muscle symptoms (SAMS) is vital for maintaining patient compliance with these pharmaceuticals, and thus improving patient outcomes. This study aimed to clarify the relationship between statin lipophilicity, or dose, and the frequency of adverse muscle symptoms using a systematic review of randomised controlled trials (RCTs). RCTs, including statin monotherapy and placebo groups, which reported data on muscle adverse events were identified through the PubMed and Scopus databases. Risk ratios (RRs) and 95% confidence intervals (CI) were pooled using a random-effects meta-analysis. A total of 135 RCTs were included in this review. Statin therapy was associated with a significant, but modest, increase in the risk of adverse muscle symptoms compared to placebo (RR=1.050; 95% CI=1.014-1.089; P=0.007; I2=3.291%). This significant association was primarily due to the inclusion of RCTs recruiting participants with a history of statin intolerance. Lipophilic statins had no appreciable impact on the development of SAMS compared to hydrophilic formulations. A univariate meta-regression of dose (standardised to atorvastatin dose equivalents) and the risk of musculoskeletal complaints also showed no significant association. The results obtained from this meta-analysis indicate that there is a slight increase in the risk of SAMS, especially in individuals with a history of statin intolerance. There is limited evidence to suggest that the risk of SAMS would differ between the use of lipophilic and hydrophilic statins, or high- and low-dose therapy.

Δ9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic Wistar-Kyoto Rats.

The aim of this study was to determine if chronic, low-dose administration of a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus. Diabetes was induced in eight-week-old male Wistar-Kyoto rats via a single intravenous dose of streptozotocin (65 mg kg-1). Following the induction of diabetes, Δ9-tetrahydrocannabinol was administered via intraperitoneal injection (0.15 mg kg-1 day-1) for an eight-week period until the animals reached sixteen weeks of age. Upon completion of the treatment regime, assessments of vascular reactivity and left ventricular function and electrophysiology were made, as were serum markers of oxidative stress and lipid peroxidation. Δ9-Tetrahydrocannabinol administration to diabetic animals significantly reduced blood glucose concentrations and attenuated pathological changes in serum markers of oxidative stress and lipid peroxidation. Positive changes to biochemical indices in diabetic animals conferred improvements in myocardial and vascular function. This study demonstrates that chronic, low-dose administration of Δ9-tetrahydrocannabinol can elicit antihyperglycaemic and antioxidant effects in diabetic animals, leading to improvements in end organ function of the cardiovascular system. Implications from this study suggest that cannabinoid receptors may be a potential new target for the treatment of diabetes-induced cardiovascular disease.

Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies.

The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO2 max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD -0.52, 95% CI -0.89 to -0.16; p<0.01) and fasting glucose (SMD -0.35, 95% CI -0.62 to -0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD -0.20, 95% CI -0.38 to -0.01; p<0.05), % body fat (SMD -0.40, 95% CI -0.74 to -0.06; p<0.05), VO2 max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD -0.33, 95% CI -0.56 to -0.09; p<0.01), systolic blood pressure (SMD -0.35, 95% CI -0.60 to -0.09; p<0.01) and DBP (SMD -0.38, 95% CI -0.65 to -0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO2 max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO2 max and improve some cardiometabolic risk factors in overweight/obese populations.