Acute human lethal toxicity of agricultural pesticides: a prospective cohort study

BACKGROUND: agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000-370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. METHODS AND FINDINGS: we examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides-from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. CONCLUSION: the human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner.

The effects of a protein enriched diet with lean red meat combined with a multi-modal exercise program on muscle and cognitive health and function in older adults: study protocol for a randomised controlled trial

BACKGROUND: Age-related muscle wasting has been strongly implicated with falls and fractures in the elderly, but it has also been associated with cognitive decline and dementia. Progressive resistance training (PRT) and adequate dietary protein are recognised as important contributors to the maintenance of muscle health and function in older adults. However, both factors also have the potential to improve brain function and prevent cognitive decline via several pathways, including the regulation of various growth and neurotrophic factors [insulin-like growth factor-1 (IGF-1)]; brain-derived growth factor (BDNF)] and/or the modulation of systemic inflammation. The primary aim of this study is to investigate whether a modest increase in dietary protein achieved through the consumption of lean red meat three days per week, when combined with PRT, can enhance muscle mass, size and strength and cognitive function in community-dwelling older people. METHODS/DESIGN: The study design is a 48-week randomised controlled trial consisting of a 24-week intervention with a 24-week follow-up. Men and women (n=152) aged 65 years and over residing in the community will be randomly allocated to: 1) PRT and provided with 220 g (raw weight) of lean red meat to be cooked and divided into two 80 g servings on each of the three days that they complete their exercise session, or 2) control PRT in which participants will be provided with and advised to consume ≥1 serving (~1/2 cup) of rice and/or pasta or 1 medium potato on each of the three training days. The primary outcome measures will be muscle mass, size and strength and cognitive function. Secondary outcomes will include changes in: muscle function, neural health (corticospinal excitability and inhibition and voluntary activation), serum IGF-1 and BDNF, adipokines and inflammatory markers, fat mass and inter-/intra-muscular fat, blood pressure, lipids and health-related quality of life. All outcome measures will be assessed at baseline and 24 weeks, with the exception of cognitive function and the various neurobiological and inflammatory markers which will also be assessed at week 12. DISCUSSION: The findings from this study will provide important new information on whether a modest increase in dietary protein achieved through the ingestion of lean red meat can enhance the effects of PRT on muscle mass, size and strength as well as cognitive function in community-dwelling older adults. If successful, the findings will form the basis for more precise exercise and nutrition guidelines for the management and prevention of age-related changes in muscle and neural health and cognitive function in the elderly. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001153707 . Date registered 16(th) October, 2013.

Fluid intake, hydration, work physiology of wildfire fighters working in the heat over consecutive days

PURPOSE: (i) To evaluate firefighters' pre- and post-shift hydration status across two shifts of wildfire suppression work in hot weather conditions. (ii) To document firefighters' fluid intake during and between two shifts of wildfire suppression work. (iii) To compare firefighters' heart rate, activity, rating of perceived exertion (RPE), and core temperature across the two consecutive shifts of wildfire suppression work. METHOD: Across two consecutive days, 12 salaried firefighters' hydration status was measured immediately pre- and post-shift. Hydration status was also measured 2h post-shift. RPE was also measured immediately post-shift on each day. Work activity, heart rate, and core temperature were logged continuously during each shift. Ten firefighters also manually recorded their food and fluid intake before, during, and after both fireground shifts. RESULTS: Firefighters were not euhydrated at all measurement points on Day one (292±1 mOsm l(-1)) and euhydrated across these same time points on Day two (289±0.5 mOsm l(-1)). Fluid consumption following firefighters' shift on Day one (1792±1134ml) trended (P = 0.08) higher than Day two (1108±1142ml). Daily total fluid intake was not different (P = 0.27), averaging 6443±1941ml across both days. Core temperature and the time spent ≥ 70%HRmax were both elevated on Day one (when firefighters were not euhydrated). Firefighters' work activity profile was not different between both days of work. CONCLUSION: There was no difference in firefighters' pre- to post-shift hydration within each shift, suggesting ad libitum drinking was at least sufficient to maintain pre-shift hydration status, even in hot conditions. Firefighters' relative hypohydration on Day one (despite a slightly lower ambient temperature) may have been associated with elevations in core temperature, more time in the higher heart rate zones, and 'post-shift' RPE.

Multiple days of heat exposure on firefighters' work performance and physiology

This study assessed the accumulated effect of ambient heat on the performance of, and physiological and perceptual responses to, intermittent, simulated wildfire fighting tasks over three consecutive days. Firefighters (n = 36) were matched and allocated to either the CON (19°C) or HOT (33°C) condition. They performed three days of intermittent, self-paced simulated firefighting work, interspersed with physiological testing. Task repetitions were counted (and converted to distance or area) to determine work performance. Participants were asked to rate their perceived exertion and thermal sensation after each task. Heart rate, core temperature (Tc), and skin temperature (Tsk) were recorded continuously throughout the simulation. Fluids were consumed ad libitum. Urine volume was measured throughout, and urine specific gravity (USG) analysed, to estimate hydration. All food and fluid consumption was recorded. There was no difference in work output between experimental conditions. However, significant variation in performance responses between individuals was observed. All measures of thermal stress were elevated in the HOT, with core and skin temperature reaching, on average, 0.24 ± 0.08°C and 2.81 ± 0.20°C higher than the CON group. Participants' doubled their fluid intake in the HOT condition, and this was reflected in the USG scores, where the HOT participants reported significantly lower values. Heart rate was comparable between conditions at nearly all time points, however the peak heart rate reached each circuit was 7 ± 3% higher in the CON trial. Likewise, RPE was slightly elevated in the CON trial for the majority of tasks. Participants' work output was comparable between the CON and HOT conditions, however the performance change over time varied significantly between individuals. It is likely that the increased fluid replacement in the heat, in concert with frequent rest breaks and task rotation, assisted with the regulation of physiological responses (e.g., heart rate, core temperature).

Bioavailability of long chain omega-3 polyunsaturated fatty acids

It has been well documented that the ingestion of omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) can improve health. However, little scientific attention has been paid on the actual bioavailability of n-3 LC-PUFA. In this thesis, several nutritional questions related to bioavailability of n-3 LC-PUFA have been answered.

Randomized controlled study of the urinary excretion of biophenols following acute and chronic intake of olive leaf supplements

Olive leaf supplement was characterised by HPLC and administered to healthy young adults over 28 d (three tablets or equivalent liquid dose per day), or in a single bolus dose of three tablets (or liquid equivalent). Oleuropein was the major biophenol in the extracts. There are no data on the excretion of urinary end-products of the metabolism of the olive leaf biophenols. Following both chronic and acute ingestion neither oleuropein, nor its hydrolysis product, hydroxytyrosol, were detected in urine samples. However, glucuronic acid conjugates, derived from oleuropein aglycone were detected in all urine samples up to 6 h following acute ingestion. The data suggest that oleuropein is bioavailable, which is a necessary pre-condition for bioactivity.