Spatio-temporal development of the urban heat island in a socioeconomically diverse tropical city.

Urban heat islands, where temperatures are elevated relative to non-urban surrounds, are near-ubiquitous in cities globally. Yet, the magnitude and form of urban heat islands in the tropics, where heat has a large morbidity and mortality burden, is not well understood, especially for those of urban informal settlements. We used 29 years of Landsat satellite-derived surface temperature, corroborated by in situ temperature measurements, to provide a detailed spatial and temporal assessment of urban heat islands in Makassar, Indonesia, a city that is representative of rapidly growing urban settlements across the tropics. Our analysis identified surface urban heat islands of up to 9.2 °C in long-urbanised parts of the city and 6.3 °C in informal settlements, the seasonal patterns of which were driven by change in non-urban areas rather than in urban areas themselves. In recently urbanised areas, the majority of urban heat island increase occurred before land became 50% urbanised, whereas the established heat island in long-urbanised areas remained stable in response to urban expansion. Green and blue space protected some informal settlements from the worst urban heat islands observed across the city and maintenance of such space will be essential to mitigate the growing heat burden from urban expansion and anthropogenic climate change. Settlements further than 4 km from the coast and with Normalised Difference Vegetation Index (NDVI) less than 0.2 had higher surface temperatures, with modelled effects of more than 5 °C. Surface temperature measurements were representative of in situ heat exposure, measured in a subset of 12 informal settlements, where mean indoor temperature had the strongest relationship with surface temperature (R2 = 0.413, P = 0.001). We advocate for green space to be prioritised in urban planning, redevelopment and informal settlement upgrading programs, with consideration of the unique environmental and socioeconomic context of tropical cities.

A standardised low-cost membrane blood-feeder for Aedes aegypti made using common laboratory materials.

Blood feeding is a necessary part of laboratory studies involving mosquitoes and other hematophagous arthropods of interest in medical and ecological research. However, methods involving hosts may present serious risks, require ethics approvals and can be expensive. Here we describe an insect blood feeder made using common laboratory materials, which is low cost (

Chronic heat stress in tropical urban informal settlements.

The health and economic impacts of extreme heat on humans are especially pronounced in populations without the means to adapt. We deployed a sensor network across 12 informal settlements in Makassar, Indonesia to measure the thermal environment that people experience inside and outside their homes. We calculated two metrics to assess the magnitude and frequency of heat stress conditions, wet bulb temperature and wet bulb globe temperature, and compared our in situ data to that collected by weather stations. We found that informal settlement residents experience chronic heat stress conditions, which are underestimated by weather stations. Wet bulb temperatures approached the uppermost limits of human survivability, and wet bulb globe temperatures regularly exceeded recommended physical activity thresholds, both in houses and outdoors. Under a warming climate, a growing number of people living informally will face potentially severe impacts from heat stress that have likely been previously overlooked or underestimated.

A planetary health model for reducing exposure to faecal contamination in urban informal settlements: Baseline findings from Makassar, Indonesia.

BACKGROUND: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing. METHODS: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children < 5 years, and health and wellbeing data for children 5-14 years and adult respondents. We collected environmental data including temperature, mosquito and rat species abundance, and water and sediment samples. Demographic, built environment and household asset data were also collected. We combined our data with existing literature to generate a novel planetary health model of health and environment in informal settlements. RESULTS: Across the 12 settlements, 593 households and 2764 participants were enrolled. Two-thirds (64·1%) of all houses (26·3-82·7% per settlement) had formal land tenure documentation. Cough, fever and diarrhoea in the week prior to the survey were reported among an average of 34.3%, 26.9% and 9.7% of children aged < 5 years, respectively; although proportions varied over time, prevalence among these youngest children was consistently higher than among children 5-14 years or adult respondents. Among children < 5 years, 44·3% experienced stunting, 41·1% underweight, 12.4% wasting, and 26.5% were anaemic. There was self- or carer-reported poor mental health among 16.6% of children aged 5-14 years and 13.9% of adult respondents. Rates of potential risky exposures from swimming in waterways, eating uncooked produce, and eating soil or dirt were high, as were exposures to flooding and livestock. Just over one third of households (35.3%) had access to municipal water, and contamination of well water with E. coli and nitrogen species was common. Most (79·5%) houses had an in-house toilet, but no houses were connected to a piped sewer network or safe, properly constructed septic tank. Median monthly settlement outdoor temperatures ranged from 26·2 °C to 29.3 °C, and were on average, 1·1 °C warmer inside houses than outside. Mosquito density varied over time, with Culex quinquefasciatus accounting for 94·7% of species. Framed by a planetary health lens, our model includes four thematic domains: (1) the physical/built environment; (2) the ecological environment; (3) human health; and (4) socio-economic wellbeing, and is structured at individual, household, settlement, and city/beyond spatial scales. CONCLUSIONS: Our planetary health model includes key risk factors and faecal-oral exposure pathways but extends beyond conventional microbiological faecal-oral enteropathogen exposure pathways to comprehensively account for a wider range of variables affecting health in urban informal settlements. It includes broader ecological interconnections and planetary health-related variables at the household, settlement and city levels. It proposes a composite framework of markers to assess water and sanitation challenges and flood risks in urban informal settlements for optimal design and monitoring of interventions.

Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji.

INTRODUCTION: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries. METHODS AND ANALYSIS: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being. ETHICS: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University. TRIAL REGISTRATION NUMBER: ACTRN12618000633280; Pre-results.

Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure.

OBJECTIVES: Weight loss (WL) is associated with a decrease in total and resting energy expenditure (EE). We aimed to investigate whether (1) diets with different rate and extent of WL determined different changes in total and resting EE and if (2) they influenced the level of adaptive thermogenesis, defined as the decline in total or resting EE not accounted by changes in body composition. METHODS: Three groups of six, obese men participated in a total fast for 6 days to achieve a 5% WL and a very low calorie (VLCD, 2.5 MJ/day) for 3 weeks or a low calorie (LCD, 5.2 MJ/day) diet for 6 weeks to achieve a 10% WL. A four-component model was used to measure body composition. Indirect calorimetry was used to measure resting EE. Total EE was measured by doubly labelled water (VLCD, LCD) and 24-hour whole-body calorimetry (fasting). RESULTS: VLCD and LCD showed a similar degree of metabolic adaptation for total EE (VLCD = -6.2%; LCD = -6.8%). Metabolic adaptation for resting EE was greater in the LCD (-0.4 MJ/day, -5.3%) compared to the VLCD (-0.1 MJ/day, -1.4%) group. Resting EE did not decrease after short-term fasting and no evidence of adaptive thermogenesis (+0.4 MJ/day) was found after 5% WL. The rate of WL was inversely associated with changes in resting EE (n = 30, r = 0.-42, p=0.01). CONCLUSIONS: The rate of WL did not appear to influence the decline in total EE in obese men after 10% WL. Approximately 6% of this decline in total EE was explained by mechanisms of adaptive thermogenesis.

Measurement of body composition changes during weight loss in obese men using multi-frequency bioelectrical impedance analysis and multi-compartment models.

BACKGROUND: The accurate measurement of changes in body composition is important to assess the contribution of fat and fat free mass to total body mass change as a measure of the effectiveness of weight loss programmes. Bioelectrical impedance spectroscopy (BIS) is a rapid and non-invasive technique which could be applied to assess body composition changes. The aim of the study was to evaluate the accuracy of the BIS for the measurement of fat mass (FM), total body water (TBW) and extracellular water (ECW) changes induced by different degrees of caloric deficit in obese men. METHODS: Three groups of six, obese men participated in either (i) a total fast (for 6 days); (ii) a VLCD (2.5 MJ/day for 3 weeks); or (iii) LCD (5.2 MJ/day for 6 weeks). FM was measured using a 4-compartment (4-C) model. TBW and ECW were determined by dilution methods, respectively. TBW, ECW and FM were also assessed with BIS. RESULTS: Body weight loss in the fasting group was 6.0 ± 1.3 kg over 6 days; the VLCD group lost 9.2 ± 1.2 kg over 21 days and the LCD group lost 12.6 ± 2.4 kg over 42 days. BIS underestimated FM changes (bias = -3.3 ± 3.8 kg) and overestimated changes in TBW and ECW by +1.8 ± 4.8 kg and +2.3 ± 6.4 kg, respectively. The measurement error was consistently larger in the fasting group and the magnitude of the bias interacted significantly with the rate of weight loss. CONCLUSION: Rapid weight loss affects the accuracy of the BIS in detecting changes in body composition. A careful interpretation of the results is needed when sizable changes in body water compartments occurs.

Development of a gas diffusion probe for the rapid measurement of pCO2 in aquatic samples.

A probe for the direct measurement of the partial pressure of carbon dioxide (pCO(2)) in aqueous samples is described. It consists of a gas permeable membrane tube containing a flowing acceptor stream of bromothymol blue indicator solution. Carbon dioxide diffuses across the membrane causing a pH change in the acceptor. This pH change decreases the absorbance of the acid-base indicator which is detected photometrically, with high sensitivity using a multi-reflection photometric detector with an LED light source. Unlike many other common methods used to measure pCO(2), this probe has the advantage of not requiring sampling to perform measurements, and avoids potential losses and contamination. This probe has the potential to perform experiments requiring in situ measurements of pCO(2), allowing regular measurements of closed system experiments, without removing any of the water column. Compared to indirect methods used to measure pCO(2), this probe has the potential to provide more portable and faster measurements. The sensitivity, sampling rate and linear range of the probe can be tuned depending on the required sensitivity and range of measurements, and a measurement rate of at least 36 h(-1) can be achieved. An application of this probe in real-time analysis of pCO(2) flux in a sediment core during a large deposition of organic matter has been described. As a comparison, the measurements of the probe have been plotted against pCO(2) calculated from alkalinity using a Gran titration. It is envisaged that the probe could be used for experiments in the laboratory requiring real time in situ measurements, or incorporated into a portable instrument so that field measurements can be easily performed. Although the linear range and sensitivity of this probe can be tuned, the configuration described gave a linear response over the calibration range of 0-5800 µatm pCO(2), with a detection limit of 144 µatm. The precision was 1.2% RSD (n=13) at 430 µatm.

A compact portable flow analysis system for the rapid determination of total phosphorus in estuarine and marine waters.

The development and evaluation of a portable flow analysis system for the in situ determination of total phosphorus is described. The system has been designed with rapid underway monitoring in mind. The system employs an ultra-violet photo-reactor and thermal heating for peroxodisulfate digestion of total phosphorus to orthophosphate, followed by spectrophotometric detection with a multi-reflective flow cell and low-power light emitting diode using the molybdenum blue method. Reagents are stored under gas pressure and delivered using software controlled miniature solenoid valves. The fully automated system has a throughput of 115 measurements per hour, a detection limit of 1 microg PL(-1), and gives a linear response over the calibration range of 0-200 microg PL(-1) (r(2)=0.9998), with a precision of 4.6% RSD at 100 microg PL(-1) (n=10). Field validation of the instrument and method was performed in Port Philip and Western Port Bays in Victoria, SE Australia, where 2499 analyses were performed over a 25 h period, over a cruise path of 285 km. Good agreement was observed between determinations of samples taken manually and analysed in the laboratory and those measured in situ with the flow analysis system.

Acute kidney injury and renal replacement therapy in the intensive care unit.

BACKGROUND: Renal replacement therapy (RRT) is now offered as a routine treatment in most intensive care units (ICU) in the UK for patients suffering from acute kidney injury (AKI). It is important for all ICU staff to understand the underlying principles of the available therapeutic options and the possible complications thereof. AIMS AND OBJECTIVES: The objective of this review was to provide an accessible theoretical and practical update on the management of RRT. In addition to a detailed discussion of the underlying principles and indications for the various modes of RRT, we will discuss the assessment of kidney function, possible complications and anticoagulation during RRT, following a review of the current literature. SEARCH STRATEGIES: Pubmed, Medline and the Cumulative Index to Nursing and Allied Health Literature were searched using the keywords renal function, RRT, dialysis, renal failure kidney injury, together with intensive care, intensive therapy and critical care. We included only studies published in English from 1998 to 2008 and from these identified and included additional publications. The 12 most relevant publications are referenced in this review. CONCLUSION: AKI is associated with increased mortality in ICU, and RRT should be considered early in the disease process. Continuous haemofiltration is the most common modality of treatment in this group of patients, and a detailed knowledge of the management of such patients is required.

Theoretical and practical aspects of anaesthesia for thoracic surgery.

Thoracic surgical procedures account for only a small fraction of all surgery undertaken in the NHS. Thoracic surgery is performed in specialist centres as patients often suffer serious co-morbidities and require vigilant care and observation by staff involved in their treatment. Anaesthesia for thoracic surgery challenges the theoretical and practical experience of all involved. This review briefly summarises the anaesthetic skills and knowledge required to deliver a safe and professional service to patients with thoracic pathology.

The effect of total starvation and very low energy diet in lean men on kinetics of whole body protein and five hepatic secretory proteins.

It is unclear whether the rate of weight loss, independent of magnitude, affects whole body protein metabolism and the synthesis and plasma concentrations of specific hepatic secretory proteins. We examined 1) whether lean men losing weight rapidly (starvation) show greater changes in whole body protein kinetics, synthesis, and circulating concentrations of selected hepatic secretory proteins than those losing the same amount of weight more slowly [very low energy diet (VLED)]; and 2) whether plasma concentrations and synthetic rates of these proteins are related. Whole body protein kinetics were measured using [1-(13)C]leucine in 11 lean men (6 starvation, 5 VLED). Fractional and absolute synthetic rates of HDL-apolipoprotein A1 (apoA1), retinol binding protein, transthyretin, alpha(1)-antitrypsin (alpha(1)-AT), and transferrin were measured using a prime-constant intravenous infusion of [(13)C(2)]glycine. Compared with VLED group, the starvation group showed greater increases (at a 5% weight loss) in whole body protein oxidation (P < 0.05); fractional synthetic rates of HDL-apoA1 (25.3 vs. -1.52%; P = 0.003) and retinol binding protein (30.6 vs. 7.1%; P = 0.007); absolute synthetic rates of HDL-apoA1 (7.1 vs. -3.8 mg.kg(-1).day(-1); P = 0.003) and alpha(1)-AT (17.8 vs. 3.6 mg.kg(-1).day(-1); P = 0.02); and plasma concentration of alpha(1)-AT (P = 0.025). Relationships between synthetic rates and plasma concentrations varied between the secreted proteins. It is concluded that synthetic rates of hepatic secreted proteins in lean men are more closely related to the rate than the magnitude of weight loss. Changes in concentration of these secreted proteins can occur independently of changes in synthetic rates, and vice versa.

What is the optimal level of anticoagulation in adult patients receiving warfarin following implantation of a mechanical prosthetic mitral valve?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was what is the optimal target INR for warfarin therapy in patients who have undergone implantation of a prosthetic mechanical mitral heart valves? Altogether 894 papers were identified on Medline and 1235 on Embase using the reported search including all major international guidelines. Twelve papers and publications represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that after implantation of new generation prosthetic mechanical mitral valves, patients should receive warfarin to a target INR of 2.5-3.5. For older types of valve the target INR should be 3.5-4.5. Warfarin therapy should be administered to maintain stable INR values ensuring lowest possible variation in the intensity of anticoagulation. In selected patients with a history of thromboembolic disease and/or coronary artery disease warfarin therapy consideration should be given to supplementing warfarin with low-dose aspirin.

Plasma concentrations of alpha-MSH, AgRP and leptin in lean and obese men and their relationship to differing states of energy balance perturbation.

OBJECTIVE: A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (alpha-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and alpha-MSH in humans. We aimed to determine whether circulating alpha-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions. DESIGN AND MEASUREMENTS: Circulating alpha-MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4-6 days) for rapid weight loss or a very low calorie diet (VLCD, 2.6 MJ/day) (11-12 days) for less rapid weight loss, in both the lean and obese volunteers. RESULTS: At baseline, prior to any weight loss both plasma alpha-MSH (15.8 +/- 1.2 vs. 5.8 +/- 1.0 pmol/l +/- SEM; P < 0.001) and AgRP (49.4 +/- 2.4 vs. 10.1 +/- 0.9 pg/ml +/- SEM; P < 0.001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P < 0.001), percentage body fat (P < 0.001) and leptin (P < 0.05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11.1 +/- 1.6 vs. 21.6 +/- 3.1 pg/ml +/- SEM; P < 0.05) but not in the VLCD subjects or in the obese, while alpha-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers. CONCLUSION: We show a difference in alpha-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.

Influence of short-term dietary weight loss on cortisol secretion and metabolism in obese men.

OBJECTIVES: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5alpha- and 5beta-reductases, impaired hepatic regeneration of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. DESIGN: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. METHODS: Otherwise healthy males (aged 20-55 years; body mass index (BMI) 30-40 kg/m2) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n=6) or 3 weeks of VLCD (2.55 MJ; n=6); then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. RESULTS: Data are mean+/-S.E.M. BMI fell (kg/m3) from 34.8+/-0.8 at baseline to 31.8+/-1.4 on VLCD and 32.7+/-1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143+/-17 to 216+/-11 nM, P<0.001) but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8+/-1.1 mg/day at baseline to 7.0+/-1.1 mg/day, P<0.001). Relative excretion of 5alpha-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. CONCLUSIONS: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss.

The effect of rate and extent of weight loss on urea salvage in obese male subjects.

It is well established that in human subjects a proportion of urea production undergoes hydrolysis in the gastrointestinal tract with release of N potentially available for amino acid synthesis. Previous studies have suggested adaptive changes in urea kinetics, with more urea-N retained within the metabolic pool during reduced dietary intakes of energy and protein. We therefore investigated the effect of rate and extent of weight loss on adaptive changes in urea kinetics in two groups (each n 6) of obese men (mean age 43 (sd 12) years, BMI 34.8 (sd 2.9) kg/m(2)) during either total starvation for 6 d or a very-low-energy diet (2.55 MJ/d) for 21 d. Subjects were resident in the Human Nutrition Unit of the Rowett Research Institute (Aberdeen, Scotland, UK) and lost 6 and 9 % initial body weight within the starvation and dieting groups respectively. Changes in urea-N metabolism were assessed by stable isotope tracer kinetics using [(15)N(15)N]urea infused intravenously for 36 h before, during and after weight loss. In response to weight loss, urea production decreased (P<0.01) by 25 % from 278 to 206 micromol urea-N/h per kg within the dieting group only. However, no changes were observed in the proportion of urea being hydrolysed in the gastrointestinal tract (range 20-25 %) or in the proportion of N retained for anabolic purposes (80-85 % urea-N from gastrointestinal hydrolysis) within either group. It was concluded that no adaptive changes in urea kinetics occurred in response to either the different rate or extent of weight loss.

Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity.

Huntington's disease is a progressive neurodegenerative disease caused by a polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971-983]. To understand the mechanism by which polyQ repeats cause neurodegeneration and cell death, we modeled polyQ neurotoxicity in Caenorhabditis elegans. In our model, expression of N-terminal fragments of human huntingtin causes polyQ-dependent degeneration of neurons. We conducted a genetic screen to identify proteins that protect neurons from the toxic effects of expanded polyQ tracts. Loss of polyQ enhancer-1 (pqe-1) gene function strongly and specifically exacerbates neurodegeneration and cell death, whereas overexpression of a pqe-1 cDNA protects C. elegans neurons from the toxic effects of expanded huntingtin fragments. A glutamineproline-rich domain, along with a charged domain, is critical for PQE-1 protein function. Analysis of pqe-1 suggests that proteins exist that specifically protect neurons from the toxic effects of expanded polyQ disease proteins.

The effect of rate of weight loss on erythrocyte glutathione concentration and synthesis in healthy obese men.

Obesity is commonly associated with a high incidence and prevalence of dyslipidaemia, cardiovascular disease and Type II diabetes. Interestingly, studies have also reported decreased antioxidant levels in obese subjects. This may constitute an independent risk factor in the pathogenesis of coronary artery disease as obese subjects would have a decreased capacity to prevent the oxidative modification of low-density lipoproteins, which is a mechanism suggested as central to the development of atherogenesis. As part of a study to investigate responses to weight loss, we have assessed the effects on GSH status of a decrease in body mass of 5%, either after 6 days of complete starvation or 11 days of a very low calorie diet (2.55 MJ/day). There were significant differences between the two groups in the synthesis rate of erythrocyte GSH in response to weight loss. Both the fractional and the erythrocyte synthesis rate of GSH decreased significantly (P<0.01) in the starvation group by 22% and 16% respectively. In contrast, no change in synthesis rates was observed in the very low calorie diet group (P>0.05). Total erythrocyte concentration of GSH was unaffected by the weight loss within both groups. These results suggest that erythrocyte GSH synthesis is depressed in response to a very rapid weight loss induced by fasting. An acute reduction in GSH synthesis in response to a rapid weight loss may constitute a risk factor during periods of increased GSH demands.