Do crashed drivers need more drug testing? A retrospective analysis of blood samples from hospitalised post-crash drivers in New Zealand.

Driving under the influence of alcohol and other drugs is a prominent safety concern in New Zealand and across the world. While alcohol testing is routinely performed for drivers involved in hospitalisation crashes, testing for other drugs is often not undertaken. The present study refers to 530 traffic crashes that occurred from October 2019 to January 2020 on New Zealand roads. The blood samples from 550 drivers who were injured in a crash and were admitted to a hospital (66% of all drivers involved in these crashes), previously tested for drugs and/or alcohol, were retested for a wider range of drugs. Alcohol above the applicable limit was found to be present in 38% of hospitalised drivers, while other drugs of interest were found in 47% of hospitalised drivers. Binary logistic regression was used to predict the presence of drugs of interest for a crashed driver using previous offence data. A driver having at least one prior drink and drug driving offence is 61% more likely to be positive for a drug of interest when involved in a crash. Similarly, a driver having at least one prior non-traffic drug offence is 4.7 times more likely to be positive for at least a drug of interest when involved in a crash. While the presence of a drug or drugs cannot be presumed to have played a role in the occurrence of the crash, this study has provided a unique and comprehensive picture of the presence of various drugs present in New Zealand drivers' blood. It is recommended to consider standardising drug testing on all blood specimens taken in relation to a serious injury or fatal crash. This procedure is not only of interest for information purposes but may importantly inform appropriate charging decisions.

New Psychoactive Substances and Violence within a UK Prison Setting.

Background and aims: New Psychoactive Substances (NPS) have affected prison populations, threatening the safety of prisoners and staff. We investigated the prevalence of substance use within a prison in the United Kingdom, focusing on NPS and its links with violence and impulsivity. Method: Cross-sectional questionnaire of 158 male category C prisoners with a mean age of 34.82 years (SD = 8.78). During their current sentence, 23% reported NPS use (NPS), 11% "traditional substances" (TD), 23% both, and 43% no substance use (ND). Lifetime use was reported as 62% NPS, 20% TD, and 18% ND. Findings: More participants used NPS exclusively than participants using TD exclusively, although the definition of NPS is problematic. The odds of violence against other prisoners, staff, and property were higher for NPS users and they were more likely to be impulsive compared to other groups. However, there was no significant interaction between NPS use and impulsivity in participation in violent acts. Conclusion: NPS use is a complex term and is prevalent in the prison, impacting on levels of violence and influenced by impulsivity. The findings emphasize the need for tailored treatment and prevention initiatives for NPS users.

Ambulance attendance for substance and/or alcohol use in a pandemic: Interrupted time series analysis of incidents.

INTRODUCTION: The ambulance attendance for substance and/or alcohol use in a pandemic (ASAP) study explores incidents during the COVID-19 lockdown in the East Midlands region of the United Kingdom (23 March-4 July 2020). METHOD: Retrospective cross-sectional count per day of ambulance attendances from the East Midlands Ambulance Service Trust. Ambulance attendances relating to alcohol or other drug use in the year prior, during lockdown and weeks following, were examined using interrupted time series analysis by patient demographics and geographical location. RESULTS: A total of 36 104 records were identified (53.7% male, 84.5% ethnicity classified as White, mean age 38.4 years). A significant drop in the number of attendances per day at the start of lockdown (-25.24, confidence interval - 38.16, -12.32) was observed, followed by a gradual increase during the ongoing lockdown period (0.36, confidence interval 0.23, 0.46). Similar patterns were found across genders, age groups 16-64 and urban/rural locations. DISCUSSION AND CONCLUSION: The pattern of ambulance attendances for alcohol or other drug use changed during the COVID-19 lockdown period. Lockdown significantly affected the use of ambulances for incidents involving alcohol or other drug use, impacting on health-care services. Further research into hazardous use of alcohol or other drugs during the lockdown periods is needed to inform policy, planning and public health initiatives.

Alcohol and other substance use during the COVID-19 pandemic: A systematic review.

BACKGROUND: Although evidence suggests substance and alcohol use may change during the Covid-19 pandemic there has been no full review of the evidence around this. METHODS: A systematic review of all available evidence was carried out to document and interpret the frequency and severity of alcohol and other substance use during the Covid-19 pandemic and their relationship to demographic and mental health variables that may suggest further clinical implications. Peer reviewed articles in MEDLINE, Embase, PsycINFO, CINAHL complete and Sociological Abstracts were searched from December 2019 until November 2020. RESULTS: The search and screening identified 45 articles from 513 deduplicated records. The evidence suggests a mixed picture for alcohol use. Overall, there was a trend towards increased alcohol consumption. The proportion of people consuming alcohol during the pandemic ranged from 21.7% to 72.9% in general population samples. Unlike alcohol use, there was a clear trend towards increased use of other substances use during the COVID-19 pandemic. The proportion of people consuming other substances during the pandemic ranged from 3.6% to 17.5% in the general population. Mental health factors were the most common correlates or triggers for increased use of both alcohol and other substances. CONCLUSION: There is an increased need for treatment for alcohol and other substance use related problems during the pandemic. Increased targeting and evidence-based interventions will also be important in the period which follows this pandemic, to improve the quality of life for individuals and families, but also to prevent additional costs to society and health systems.

ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity in skeletal muscle.

Emerging evidence indicates that skeletal muscle lipid droplets are an important control point for intracellular lipid homeostasis and that regulating fatty acid fluxes from lipid droplets might influence mitochondrial capacity. We used pharmacological blockers of the major triglyceride lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase, to show that a large proportion of the fatty acids that are transported into myotubes are trafficked through the intramyocellular triglyceride pool. We next tested whether increasing lipolysis from intramyocellular lipid droplets could activate transcriptional responses to enhance mitochondrial and fatty acid oxidative capacity. ATGL was overexpressed by adenoviral and adenoassociated viral infection in C2C12 myotubes and the tibialis anterior muscle of C57Bl/6 mice, respectively. ATGL overexpression in C2C12 myotubes increased lipolysis, which was associated with increased peroxisome proliferator-activated receptor (PPAR)-∂ activity, transcriptional upregulation of some PPAR∂ target genes, and enhanced mitochondrial capacity. The transcriptional responses were specific to ATGL actions and not a generalized increase in fatty acid flux in the myotubes. Marked ATGL overexpression (20-fold) induced modest molecular changes in the skeletal muscle of mice, but these effects were not sufficient to alter fatty acid oxidation. Together, these data demonstrate the importance of lipid droplets for myocellular fatty acid trafficking and the capacity to modulate mitochondrial capacity by enhancing lipid droplet lipolysis in vitro; however, this adaptive program is of minor importance when superimposing the normal metabolic stresses encountered in free-moving animals.

Unraveling the roles of PLIN5: linking cell biology to physiology.

The discovery of perilipin (PLIN) 1 provided a major conceptual shift in the understanding of adipose tissue lipolysis and generated intense interest in lipid droplet biology research. The subsequent discovery of other PLIN proteins revealed unique tissue distribution profiles, subcellular locations, and lipid-binding properties and divergent cellular functions. PLIN5 is highly expressed in oxidative tissues such as skeletal muscle, liver, and heart and is central to lipid homeostasis in these tissues. Studies in cell systems have ascribed several metabolic roles to PLIN5 and demonstrated interactions with other proteins that are requisite for these functions. We examine recent in vivo studies and ask whether the evidence from the cell biology approaches is consistent with the physiological roles of PLIN5.

PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle.

Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)(-/-) mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5 (-/-) mice developed skeletal muscle insulin resistance, which was associated with ceramide accumulation. Liver insulin sensitivity was improved in Plin5 (-/-) mice, indicating tissue-specific effects of PLIN5 on insulin action. We conclude that PLIN5 plays a critical role in coordinating skeletal muscle triacylglycerol metabolism, which impacts sphingolipid metabolism, and is requisite for the maintenance of skeletal muscle insulin action.

Cellular localization and associations of the major lipolytic proteins in human skeletal muscle at rest and during exercise.

Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis.

Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance.

AIMS/HYPOTHESIS: Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. METHODS: Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. RESULTS: Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 µmol kg body weight(-1) min(-1); p < 0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups. CONCLUSIONS/INTERPRETATION: Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01680133.

Phosphorylation of adipose triglyceride lipase Ser(404) is not related to 5'-AMPK activation during moderate-intensity exercise in humans.

Intramyocellular triacylglycerol provides fatty acid substrate for ATP generation in contracting muscle. The protein adipose triglyceride lipase (ATGL) is a key regulator of triacylglycerol lipolysis and whole body energy metabolism at rest and during exercise, and ATGL activity is reported to be enhanced by 5'-AMP-activated protein kinase (AMPK)-mediated phosphorylation at Ser(406) in mice. This is a curious observation, because AMPK activation reduces lipolysis in several cell types. We investigated whether the phosphorylation of ATGL Ser(404) (corresponding to murine Ser(406)) was increased during exercise in human skeletal muscle and with pharmacological AMPK activation in myotubes in vitro. In human experiments, skeletal muscle and venous blood samples were obtained from recreationally active male subjects before and at 5 and 60 min during exercise. ATGL Ser(404) phosphorylation was not increased from rest during exercise, but ATGL Ser(404) phosphorylation correlated with myosin heavy chain 1 expression, suggesting a possible fiber type dependency. ATGL Ser(404) phosphorylation was not related to increases in AMPK activity, and immunoprecipitation experiments indicated no interaction between AMPK and ATGL. Rather, ATGL Ser(404) phosphorylation was associated with protein kinase A (PKA) signaling. ATGL Ser(406) phosphorylation in C(2)C(12) myotubes was unaffected by 5-aminoimidazole-4-carboxaminde-1-ß-d-ribofuranoside, an AMPK activator, and the PKA activator forskolin. Our results demonstrate that ATGL Ser(404) phosphorylation is not increased in mixed skeletal muscle during moderate-intensity exercise and that AMPK does not appear to be an activating kinase for ATGL Ser(404/406) in skeletal muscle.

Is 8 weeks of side-alternating whole-body vibration a safe and acceptable modality to improve functional performance in multiple sclerosis?

PURPOSE: To examine whether an 8-week period of side-alternating whole-body vibration (WBV) exercise is an acceptable and effective exercise intervention to improve and maintain functional performance in multiple sclerosis people. METHODS: A total of 15 participants with MS (11 women [mean age 50.2 ± 6.9 years; body mass 65.7 ± 19.2 kg; height 165.3 ± 6.1 cm; EDSS 3.5 ± 0.9] and 4 males [mean age 50.5 ± 5.2 years; body mass 85.3 ± 16.0 kg; height 175.3 ± 3.2 cm; EDSS 3.4 ± 0.5]) were selected for this study. Quality of life, timed up-and-go, functional reach, standing balance and 10-m walk test were performed prior to and after 4 and 8 weeks of vibration exercise, and 2 weeks after cessation of vibration exercise. RESULTS: There was no evidence of vibration exercise producing any anxiety or discomfort. Compared with baseline measurements, the 10-m walk test showed significant improvements in 2, 8 and 10 m times at 8 week (p < 0.05) and 2 week post-vibration (p < 0.05). Timed up-and-go demonstrated a significant and positive time effect (p < 0.05). Standing balance showed significant improvements from baseline, at 4- (p < 0.05) and 2-weeks post-vibration (p < 0.05). CONCLUSION: This is the first study to investigate side-alternating WBV as an exercise training modality for MS people. From an active MS population, this study has shown that WBV training not only improved the standing balance and walking time but there were also no adverse effects from using this modality.