The drinking water crises of Flint and Havelock North: a failure of public health risk management.

Between 2014 and 2016, there were two severe community water system (CWS) failures in Flint, Michigan (MI), USA and Havelock North, Hawkes Bay, New Zealand. These events had profound implications for public health in their respective countries. While the nature of both crises was different, certain aspects of the failings were strikingly similar. These included: failure of authorities to protect the integrity of their source water, 'wait-and-see approach' to address problems if and when they occurred, negligent approach to regulatory oversight and responsibility, substandard facilities and lack of knowledge and training of staff, failure of consultants and advisory services engaged by suppliers, and failure of government agencies to enforce regulations. The lessons from both incidents must be learned, or similar tragic events are likely to reoccur. The six principles identified in the Government Inquiry into the Havelock North outbreak are an essential first step. The next step is to implement them throughout the drinking water sector.

Oxygen (O2) kinetics during early recovery from peak exercise in patients with Type 2 diabetes.

AIMS: To examine the oxygen (O(2)) kinetics during early recovery from peak exercise in patients with Type 2 diabetes and to examine whether oxygen O(2) recovery is associated with fasting glucose and HbA(1c) in this population. METHODS: Eighty-nine participants (52 men) aged 51.8 ± 7.1 years (mean ± SD) were divided into three groups: normal weight (BMI ≤ 25.0 kg/m(2)), overweight/obese without diabetes (BMI ≥ 26 kg/m(2)) and overweight/obese with Type 2 diabetes. Participants were assessed for their aerobic power (VO(2peak)) on a cycle ergometer, provided a fasting blood sample and underwent a series of anthropometric measurements. Early recovery period was measured for 60 s from cessation of exercise and expressed as percentage of VO(2peak) (higher percentage represents slower recovery). RESULTS: No significant differences were observed for age between the three study groups. Both the overweight/obese groups without diabetes and with Type 2 diabetes had higher BMI than the normal weight group, with no significant differences between overweight/obese participants without diabetes and those with diabetes. Participants with Type 2 diabetes had lower VO(2peak) than overweight/obese participants without diabetes and normal weight individuals (19.6 ± 4.8, 22.6 ± 5.4 and 25.7 ± 5.3 ml kg(-1) min(-1), respectively, P < 0.004 for overall trends). Participants with Type 2 diabetes also had slower recovery in oxygen O(2) kinetics after exercise, compared with both normal weight and overweight/obese individuals without diabetes (56.5 ± 7.7, 49.2 ± 7.2, 47.7 ± 7.4%, P < 0.004 for overall trends). Multiple regression analysis revealed that percentage of oxygen O(2) recovery was a stronger predictor than VO(2peak), BMI or age for fasting glucose and HbA(1c). CONCLUSIONS: Patients with Type 2 diabetes have lower VO(2peak) and prolonged oxygen O(2) recovery from peak exercise. However, only prolonged oxygen O(2) recovery was associated with fasting glucose and HbA(1c).

The effect of acute exercise on undercarboxylated osteocalcin in obese men.

SUMMARY: The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC. INTRODUCTION: Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese individuals and individuals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC. METHODS: Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m(-2)) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO(2peak)) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood samples were taken at baseline and up to 2 h post-exercise. RESULTS: At baseline, unOC was negatively correlated with glucose levels (r = -0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = -0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L(-1), p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L(-1), p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = -0.46, p = 0.013 and r = -0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = -0.51, p = 0.038). CONCLUSIONS: This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.

Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors.

AIMS: Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in individuals with a high number of metabolic risk factors (HiMF, 2.9 +/- 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 +/- 0.5). METHODS: Twenty-eight men and 27 women aged 50.8 +/- 6.5 years (mean +/- sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40-50% of one repetition maximum (1RM) to 75-85% of 1RM], blood samples were obtained for the measurement of pro-inflammatory cytokines, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT). RESULTS: At baseline, HiMF had higher interleukin-6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P < 0.05). RT did not significantly alter inflammatory markers or hepatic enzymes (all P > 0.05). CONCLUSIONS: HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in individuals with HiMF.

Ammonia, cyclohexane, nitrogen and water adsorption capacities of an activated carbon impregnated with increasing amounts of ZnCl(2), and designed to chemisorb gaseous NH(3) from an air stream.

The adsorption capacity of ZnCl(2)-impregnated activated carbon (AC) for NH(3) is reported in terms of stoichiometric ratio of reaction (NH(3) per ZnCl(2)). This ratio depends on the testing conditions used. Compared to the ratio obtained under dry conditions, the ratio is higher under humid conditions or increased NH(3) concentrations. The linear increase of the NH(3) capacity with increasing loading of ZnCl(2) breaks down at about 3.5 mmol ZnCl(2)/g AC. This behavior is explained in terms of preferential adsorption of a monolayer of salt followed by aggregation of the impregnant once a monolayer is completed. The effect of increasing the loading of ZnCl(2) on the capacity for gases for which the impregnants are not intended, namely cyclohexane, nitrogen, and water vapor, is also discussed. A break in the linear relationship between water capacity and impregnant loading at about 3.5 mmol ZnCl(2) seems to correspond to a full monolayer coverage of ZnCl(2) on AC. The monolayer of ZnCl(2) is shown to reduce the uptake of water into AC, while the ZnCl(2) aggregates are shown to be hydrophilic.

HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.

A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4(+) T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0. 001]. Antigen-specific CD8(+) T cells were enumerated by flow cytometric detection of intracellular IFN-gamma in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8(+) T cell responses were observed between B*57(+) LTNP and five B*57(+) progressors (P = 0.4). Although similar frequencies of peptide specific CD8(+) T cells were also found, the gag-specific CD8(+) T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57(+) LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.

HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.

Binding of HIV type 1 (HIV-1) envelope glycoproteins to the surface of a CD4(+) T cell transduces intracellular signals through the primary envelope receptor, CD4, and a coreceptor, either CCR5 or CXCR4. Furthermore, envelope-CD4(+) cell interactions increase rates of apoptosis in peripheral blood mononuclear cells (PBMCs). We demonstrate that in primary T lymphocytes, recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspase-6, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death. Envelope-mediated activation of caspase-3 and caspase-6 depended on envelope-CD4 receptor interactions; CCR5-utilizing as well as CXCR4-utilizing envelopes elicited this response. Focal adhesion kinase (FAK) is a substrate of both caspase-3 and caspase-6, and inactivation of FAK by these caspases promotes apoptosis. En-velope treatment of lymphocytes led to the cleavage of FAK in a manner consistent with caspase-mediated cleavage.

Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance.

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 x (5 g Cr-H(2)O + 5 g dextrose)/day)] or a placebo (6 x 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P < 0.05) at 0 [by 22.9 +/- 4.2, 8.9 +/- 1.9, and 14.0 +/- 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS.

Position effect of human telomeric repeats on replication timing.

Telomeres are distinct structures, composed of short, repeated sequences, at the ends of all eukaryotic chromosomes. Telomeres have been shown in yeast to induce late replication in S phase and to silence transcription of neighboring genes. To examine the possibility of similar effects in human chromosomes, we studied cells from a subject with a microdeletion of 130 kb at the end of one copy of chromosome arm 22q, repaired by the addition of telomere repeats. Using fluorescence in situ hybridization of S phase nuclei, a distinct difference was found in the replication timing of the breakpoint region between the intact and truncated copies of chromosome 22. This difference was evident as a shift from middle to late replication time of the breakpoint region adjacent to the repaired telomere. This finding suggests that the human telomere sequence influences activation of adjacent replication origin(s). The difference in replication timing between the two chromosomes was not associated with differences in sensitivity to digestion by DNase I or with methylation of regions immediately adjacent to the breakpoint. Furthermore, both alleles of arylsulfatase A, a gene located at a distance of approximately 54 kb from the breakpoint, were expressed. We conclude that as in yeast, the proximity of telomeric DNA may induce a positional effect that delays the replication of adjacent chromosomal regions in humans.

Resistance exercise training increases muscle strength, endurance, and blood flow in patients with chronic heart failure.

Resistance exercise training was well tolerated in patients with stable, chronic heart failure, resulting in increased strength and endurance, and lower oxygen consumption at submaximum workloads but no improvement in VO2peak. There was also a significant increase in basal forearm blood flow following this form of exercise training.

Pre-exercise carbohydrate ingestion: effect of the glycemic index on endurance exercise performance.

PURPOSE: This study aimed to examine the effect of glycemic index of pre-exercise carbohydrate (CHO) ingestion on exercise metabolism and performance. METHODS: Eight endurance trained men ingested a high glycemic index (HGI), low glycemic index (LGI), or a placebo (CON) meal 45 min before exercise and then cycled for 50 min at 67% VO2max. Subjects subsequently performed a 15-min self-paced performance ride in which total work (kJ) was recorded. RESULTS: Plasma glucose concentrations were higher (P < 0.01) after ingestion in HGI compared with LGI and CON (7.53 +/- 0.64 vs 5.55 +/- 0.21 and 4.65 +/- 0.14 mmol.L-1 for HGI, LGI, and CON, respectively, 30 min postprandial; mean +/- SE) but declined at the onset of exercise and were lower (P < 0.01) compared with LGI and CON (4.03 +/- 0.31 vs 4.64 +/- 0.24 and 5.09 +/- 0.16 mmol.L-1 for HGI, LGI, and CON respectively; mean +/- SE) at 10 min of exercise. Plasma glucose remained depressed (P < 0.01) until 30 min into exercise in HGI compared with other trials. Plasma insulin concentrations were higher (P < 0.01) following ingestion during rest and exercise in HGI compared with LGI and CON. Plasma FFA concentrations were lower (P < 0.05) following ingestion in HGI and LGI compared with CON and higher (P < 0.05) in LGI compared with HGI at the start and end of exercise. RER and CHO oxidation was higher (P < 0.01) in HGI compared with LGI and CON during submaximal exercise. There were no differences in work output during the performance cycle. CONCLUSIONS: These data indicate that pre-exercise CHO feedings with varying glycemic indexes do not affect exercise performance following short term submaximal exercise despite alterations in metabolism.

Effect of creatine supplementation on sprint exercise performance and muscle metabolism.

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.

A two-step intervention of increase mammography among women aged 65 and older.

OBJECTIVES: This study evaluated a two-step intervention for mammography screening among older women. METHODS: Four hundred and sixty women, identified from physician practices, were randomized to a control or a two-step intervention (physician letter and peer counseling call) group. Women in the intervention group who obtained a mammogram received a grocery coupon. RESULTS: Over the 12 months of the study, more women in the intervention group than in the control group obtained mammograms (38% vs 16%). The most dramatic difference was in the higher odds that women in the intervention group would obtain a mammogram within 2 months (odds ratio = 10.5). CONCLUSIONS: The intervention significantly increased screening mammography. Future efforts must be multifaceted and incorporate the unique concerns of older women.

Psychophysiological stress in elite golfers during practice and competition.

This study examined self-reported state anxiety (cognitive anxiety, somatic anxiety and self-confidence) measured by the Competitive State Anxiety Inventory-2 (CSAI-2; Martens, Vealey, Bump, & Smith, 1990) and physiological responses (salivary cortisol concentration and heart rate) in elite golfers prior to, during and on completion of a tournament and practice round. The relationships between psychophysiological variables were investigated by comparing physiological and psychological responses during competition and practice to each other, and to performance. Performance was determined for each player as the difference between 18 hole score and handicap. Fifteen male Professional Golfing Association (PGA) trainees (aged 21-25 years) competed in a PGA sanctioned tournament and a practice round on the same, or similar golf course. Players completed the CSAI-2 and collected saliva for cortisol analysis on four occasions: prior to tee off, and after completing holes 6, 12 and 18. Cortisol concentration was corrected for circadian variations in cortisol secretion, using baseline cortisol measures. Within-subject analysis revealed elite golfers experienced elevated cortisol, heart rate, cognitive and somatic anxiety, and lower self-confidence during competition compared to practice. For both game conditions, the highest cortisol response was measured prior to the commencement of play, whilst state anxiety measures did not change significantly during the golf rounds. Univariate and multivariate analyses failed to reveal significant correlations between the psychophysiological variables and golf performance. In conclusion, competition and practice were clearly discriminated by the psychophysiological variables, but none of these predicted performance.

Molecular characterization of Br-cadherin, a developmentally regulated, brain-specific cadherin.

Cadherins are a family of transmembrane proteins that play a crucial role in cell adhesion and in morphogenesis. Several of the cadherins are expressed in the nervous system, but none is neuron-specific. We characterize a new member of the cadherin family, Br-cadherin, which is present exclusively in the central nervous system. Although the Br-cadherin protein is confined to the central nervous system, its mRNA is present in several additional tissues, suggesting that there is posttranscriptional control of this gene's expression. Within the central nervous system, Br-cadherin appears to be expressed specifically by neurons. In the mouse, its expression becomes detectable during the first postnatal week, which corresponds temporally to the onset of synaptogenesis and dendrite outgrowth in the brain. This pattern of expression is consistent with a role for Br-cadherin in neuronal development, perhaps specifically with synaptogenesis.

Accumulated oxygen deficit measurements during and after high-intensity exercise in trained male and female adolescents.

The purpose of this study was to compare accumulated oxygen deficits and markers of anaerobic metabolism [plasma ammonia (NH3) and lactate (La-) concentrations] in anaerobically trained male [n = 8, age 14.8 (0.5) years; maximal oxygen consumption VO2max 61.74 (2.23) ml x kg(-1) x min(-1)] and female [n = 8, age 14.5 (0.2) years; VO2max 49.62 (3.52) ml x kg(-1) x min(-1)] adolescents. The exercise protocol consisted of runs to exhaustion at speeds predicted to represent 120% and 130% of VO2max. Arterialised blood samples were obtained from a pre-warmed hand via a catheter inserted into a forearm vein. Samples were taken at rest and after 1, 3, 5, 7, 10, 15 and 20 min of recovery. The high-intensity exercise resulted in mean accumulated oxygen deficits that were less (P < 0.05) in females (52.3 ml x kg(-1)) than in males (68.6 ml x kg(-1)). Lower (P < 0.05) plasma concentrations of NH3 and La(-1), and a higher pH were evident in females compared with males during various stages of the 20-min recovery period. The increase in anaerobic performance in the male adolescent athletes when compared with their female counterparts was associated with an increased plasma concentration of selected plasma and blood metabolites. The observed results may reflect well-established differences between the sexes in the morphology and metabolic power of muscle.

Effect of CHO ingestion on exercise metabolism and performance in different ambient temperatures.

Two series of experiments were conducted to examine the effect of ingesting beverages with differing carbohydrate (CHO) concentrations and osmolalities on metabolism and performance during prolonged exercise in different environmental conditions. In series 1, 12 subjects performed three cycling exercise trials to fatigue at 70% VO2peak in either 33 degrees C (N = 6) (HT1) or 5 degrees C (N = 6) (CT). Subjects ingested either a 14% CHO solution (osmolality = 390 mosmol.1(-1) (HCHO); a 7% CHO solution (330 mosmol.1(-1) (NCHO) or a placebo (90 mosmol.1(-1) (CON1). In series 2, six subjects performed the same three trials at 33 degrees C (HT2), while ingesting either NCHO, a 4.2% CHO solution (240 mosmol.1(-1) (LCHO) or a placebo) (240 mosmol.1(-1) (CON2). Plasma glucose was higher (P < 0.05) in HCHO than NCHO, which in turn was higher (P < 0.05) than CON1 in both CT and HT1. Plasma glucose was lower (P < 0.05) in CON2 compared with NCHO and LCHO in HT2. The fall in plasma volume was greater (P < 0.05) in HCHO than other trials in both CT and HT1 but was not different when comparing the three trials in HT2. Exercise time was not different when comparing the trials in either HT1 or HT2 but was longer (P < 0.05) in NCHO compared with HCHO, which, in turn, was longer (P < 0.05) than CON1 in CT. These data demonstrate that, during prolonged exercise in the heat, fatigue is related to factors other than CHO availability. In addition, during exercise in 5 degrees C a 7% CHO solution is more beneficial for exercise performance than a 14% CHO solution.