Increased activity of cell surface peptidases in HeLa cells undergoing UV-induced apoptosis is not mediated by caspase 3

We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage. All the agents except for DEVD had no effect on the level of caspase 3 activity in the cells. The results suggest that other caspases may cleave PARP in these cells. Both 3AB and DEVD treatment reduced the level of actin cleavage seen in the apoptotic cells. The increase in CSP activity observed in cells undergoing UVB-induced apoptosis appears to involve PARP but not caspase 3

Best practice fleet management and priority actions

This paper reviews relevant literature and publicly available fleet management programs, along with workplace road safety policies and procedures. Discussions were also held with managers of selected companies about their fleet safety achievements. This work identified key vehicle and driver safety interventions from the literature, plus best practice fleet management and workplace road safety policies and priority actions for consideration within fleets. Managers reported progress in organisational acceptance and recognition that road trauma is a social, human, financial, reputation, efficiency and operational risk to an organisation and needs to be given priority at all management levels. The study investigated workplace safety management principles and their application in road safety management. Within standard management processes, companies wishing to reduce their road safety risk should: reassess the need for travel; reorganise work journeys to reduce exposure to risk or use lower risk journey options; invest in the upfront safety quality of vehicles that are being used; and engage their staff and stakeholders about risk management on the road.Small, M., Bailey, T., Lydon, M., & Davern, T.http://www.rsrpe2013.com.au/conference-papers/conference-papers.ph

Australia and Other Nations are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward

BACKGROUND: Australia has joined a growing number of nations which have evaluated the physical activity and sedentary behaviour status of their children. Australia received a 'D minus' in the first Active Healthy Kids Australia Physical Activity Report Card. METHODS: An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer three questions: 1) What are the main sedentary behaviours of children?, 2) What are the potential mechanisms for sedentary behaviour to impact on child health and development? and, 3) What are the effects of different types of sedentary behaviours on child health and development? RESULTS: Neither sedentary time nor screen time are homogeneous activities likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviours may positively or negatively affect cardiometabolic, neuro-musculoskeletal, and psycho-social health, though the strength of evidence varies. National surveillance systems, and mechanistic, longitudinal and experimental studies are needed for Australia and other nations to improve their grade. CONCLUSIONS: Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviours are critical to the healthy growth, development and wellbeing of children. Nations therefore need strategies to address these common behaviours

The Art and Science of Weed Mapping

Land managers need cost-effective and informative tools for non-native plant species management. Many local, state, and federal agencies adopted mapping systems designed to collect comparable data for the early detection and monitoring of non-native species. We compared mapping information to statistically rigorous, plot-based methods to better understand the benefits and compatibility of the two techniques. Mapping non-native species locations provided a species list, associated species distributions, and infested area for subjectively selected survey sites. The value of this information may be compromised by crude estimates of cover and incomplete or biased estimations of species distributions. Incorporating plot-based assessments guided by a stratified-random sample design provided a less biased description of non-native species distributions and increased the comparability of data over time and across regions for the inventory, monitoring, and management of non-native and native plant species

Genes Influencing Circadian Differences in Blood Pressure in Hypertensive Mice

Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the ‘peak’ (n = 12) and ‘trough’ (n = 6) of diurnal BP. Using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between ‘peak’ and ‘trough’ BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension

The Natural History of Severe Acute Liver Injury.

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study

Background: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. Methods: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. Results: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 [plus or minus] 45 IU/L and 55 [plus or minus] 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. Conclusion: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.Funding for this study was provided by McNeil Consumer Healthcare to the Denver Health Authority, Denver, Colorado

Socio-demographic, behavioural and cognitive correlates of work-related sitting time in German men and women

Background: Sitting time is ubiquitous for most adults in developed countries and is most prevalent in three domains: in the workplace, during transport and during leisure time. The correlates of prolonged sitting time in workplace settings are not well understood. Therefore, the aim of this study was to examine the gender-specific associations between the socio-demographic, behavioural and cognitive correlates of work-related sitting time. Methods: A cross-sectional sample of working German adults (n = 1515; 747 men; 43.5 ± 11.0 years) completed questionnaires regarding domain-specific sitting times and physical activity (PA) and answered statements concerning beliefs about sitting. To identify gender-specific correlates of work-related sitting time, we used a series of linear regressions. Results The overall median was 2 hours of work-related sitting time/day. Regression analyses showed for men (β = -.43) and for women (β = -.32) that work-related PA was negatively associated with work-related sitting time, but leisure-related PA was not a significant correlate. For women only, transport-related PA (β = -.07) was a negative correlate of work-related sitting time, suggesting increased sitting times during work with decreased PA in transport. Education and income levels were positively associated, and in women only, age (β = -.14) had a negative correlation with work-related sitting time. For both genders, TV-related sitting time was negatively associated with work-related sitting time. The only association with cognitive correlates was found in men for the belief ‘Sitting for long periods does not matter to me’ (β = .10) expressing a more positive attitude towards sitting with increasing sitting durations. Conclusions: The present findings show that in particular, higher educated men and women as well as young women are high-risk groups to target for reducing prolonged work-related sitting time. In addition, our findings propose considering increasing transport-related PA, especially in women, as well as promoting recreation-related PA in conjunction with efforts to reduce long work-related sitting times