Chlorination for low-cost household water disinfection - A critical review and status in three Latin American countries.

Chlorination has historically provided microbiologically safe drinking water in public water supplies. Likewise, chlorine has also been introduced as a low-cost disinfection method in rural and marginalized communities, both at community and household level, as well as during emergencies. Although this practice is common and well established for use as a household water treatment technology in the Global South, several challenges in effective and efficient implementation still need to be addressed. Here, we explored these issues by a literature review and narrowed them to the status of three Latin American countries (Mexico, Colombia, and Brazil). Overall, it was found that although guidance on household-based chlorination includes information on health risks and hygiene, this may not create enough incentive for the user to adapt the method satisfactorily. Physicochemical quality of the water influences chlorination efficiency and it is found that variations in quality are rarely considered when recommending chlorine doses during implementation. These are far more often based on a few measurements of turbidity, thereby not considering dissolved organic matter, or seasonal and day-to-day variations. Other factors such as user preferences, chlorine product quality and availability also represent potential barriers to the sustainable use of chlorination. For chlorination to become a sustainable household water treatment, more focus should therefore be given to local conditions prior to the intervention, as well as support and maintenance of behavioural changes during and after the intervention.

Prevalence and correlates of depressive symptoms in older adults across the glycaemic spectrum: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To document the prevalence of current depressive symptoms and history of depression across the glycaemic spectrum in older adults, and examine if measures of health status and healthcare satisfaction, access and utilization explain differences in the prevalence of current depressive symptoms by diabetes status. METHODS: We conducted a cross-sectional study of 6226 participants aged 67-90 years who attended the 2011-2013 visit of the Atherosclerosis Risk in Communities (ARIC) study. Diabetes was based on self-report, medication use and HbA1c . Current depressive symptoms were defined using the Center for Epidemiologic Studies Depression 11-item questionnaire, and history of depression was assessed via self-report. We examined obesity, history of cardiovascular disease, hypertension, kidney disease, cognitive function, and self-reported health compared with others. Prevalence and prevalence ratios were estimated using age-, race-, and sex-adjusted Poisson regression. RESULTS: The prevalence of current depressive symptoms was 5.4% in people without diabetes and 11.0% in people with diabetes (prevalence ratio 2.04, 95% CI 1.60, 2.48); the prevalence of history of depression was 11% in people without diabetes and 17.7% in people with diabetes (prevalence ratio 1.61, 95% CI 1.28,1.95). Strong correlates of current depressive symptoms were history of depression (prevalence ratio 3.86, 95% CI 3.05, 4.90) and reporting poor health compared with others (prevalence ratio 3.88, 95% CI 2.93, 5.15). No variables had significantly different associations with depressive symptoms across glycaemic categories (P for interaction >0.10). CONCLUSIONS: In older adults, current depressive symptoms were twice as prevalent in people with diabetes compared with those without. Measures of health status and healthcare did not explain differences in depressive symptoms between people with and without diabetes.

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice.

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression.

Association between prediabetes and risk of chronic kidney disease: a systematic review and meta-analysis.

AIMS: To assess the effect of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) on the incidence of chronic kidney disease. METHODS: PubMed and EMBASE were searched (for studies published up to March 2015). Effects estimated from cohort studies reporting the relationship of prediabetes to incident chronic kidney disease [kidney damage (microalbuminuria, albuminuria or proteinuria) and/or decreased glomerular filtration rate] were pooled using a random-effects model meta-analysis. RESULTS: Nine cohort studies with a total of 185 452, mainly Asian and white, participants were followed for a total of 835 146 person-years. In eight cohort studies defining impaired fasting glucose as fasting glucose 6.1-6.9 mmol/l, the summary relative risk of chronic kidney disease after adjustment for established risk factors was 1.11 (95% CI 1.02-1.21). When a study defining impaired fasting glucose as fasting glucose 5.6-6.9 mmol/dl was added, the overall relative risk of chronic kidney disease was 1.12 (95% CI 1.02-1.21). Exclusion of the only study with information on impaired glucose tolerance did not change the relative risk (1.12; 95% CI 1.02-1.21). There was no evidence of publication bias (P value for Egger test = 0.12). CONCLUSION: Prediabetes is modestly associated with an increase in chronic kidney disease risk, but this remains to be robustly confirmed. Chronic kidney disease screening among people with prediabetes, and aggressive management of prediabetes in those with chronic kidney disease may be warranted.

Change in neighborhood environments and depressive symptoms in New York City: the Multi-Ethnic Study of Atherosclerosis.

Physical and social features of neighborhoods, such as esthetic environments and social cohesion, change over time. The extent to which changes in neighborhood conditions are associated with changes in mental health outcomes has not been well-established. Using data from the MultiEthnic Study of Atherosclerosis, this study investigated the degree to which neighborhood social cohesion, stress, violence, safety and/or the esthetic environment changed between 2002 and 2007 in 103 New York City Census tracts and the associations of these changes with changes in depressive symptoms. Neighborhoods became less stressful, more socially cohesive, safer, and less violent. White, wealthy, highly educated individuals tended to live in neighborhoods with greater decreasing violence and stress and increasing social cohesion. Individuals living in neighborhoods with adverse changes were more likely to have increased CES-D scores, although due to limited sample size associations were imprecisely estimated (P>0.05). Changes in specific features of the neighborhood environment may be associated with changes in level of depressive symptoms among residents.

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. SUBJECTS: Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). RESULTS: In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. CONCLUSION: Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

Associations of salivary cortisol levels with inflammatory markers: the Multi-Ethnic Study of Atherosclerosis.

Socioeconomic and psychosocial factors have been found to be associated with systemic inflammation. Although stress is often proposed as a contributor to these associations, no population studies have investigated the links between inflammation and biomarkers of stress. The current study examines associations between daily cortisol profiles and inflammatory markers interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor (TNF-a) in a population-based sample of 869 adults with repeat measures of cortisol over multiple days. Persons with higher levels of IL-6 had a less pronounced cortisol awakening response, a less steep daily decline, and higher cortisol area under the curve for the day with associations persisting after controls for risk factors and other cytokines. Persons with higher levels of TNF-a had lower cortisol levels upon waking, and flatter daily decline, although associations with decline were attenuated when controlling for inflammatory risk factors. Higher levels of IL-10 were associated with marginally flatter daily cortisol decline (p<.10). This study is the first to identify associations of basal cortisol activity and inflammatory markers in a population based sample. Findings are consistent with the possibility that HPA axis activity may mediate associations between psychosocial stressors and inflammatory processes. Additional prospective data are necessary to clarify the directionality of associations between cortisol and inflammatory markers.

Associations of salivary cortisol levels with metabolic syndrome and its components: the multi-ethnic study of atherosclerosis.

CONTEXT: Prior research has identified associations between social-environmental factors and metabolic syndrome (MetS) components. The physiological mechanisms underlying these associations are not fully understood, but alterations in activity of the hypothalamic-pituitary-adrenal axis, a stress-responsive biological system, have been hypothesized to play a role. OBJECTIVE: The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, high-density lipoproteins, glucose, and blood pressure) are associated with cortisol levels. DESIGN AND SETTING: We conducted cross-sectional analyses of data from the Multi-Ethnic Study of Atherosclerosis (MESA) study in the general community. PATIENTS OR OTHER PARTICIPANTS: We studied a population-based sample of 726 adults (ages 48 to 89 yr) who do not have clinical diabetes. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): Cortisol awakening response, cortisol decline across the waking day, and total cortisol output were analyzed (using 18 timed measures of salivary cortisol over 3 d). RESULTS: Overall, we found little evidence that the presence of MetS or its components is related to cortisol output or patterns. Contrary to expectation, the presence of MetS was associated with lower rather than higher area under the curve, and no consistent pattern was observed when MetS components or subsets of components were examined in relation to cortisol. CONCLUSIONS: Our findings do not support the hypothesis that differences in level or diurnal pattern of salivary cortisol output are associated with MetS among persons without clinical diabetes.

Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and reinstatement of food seeking in rats.

BACKGROUND AND PURPOSE: Many studies have demonstrated a role of hypocretin 1 (orexin 1) receptors in home-cage food consumption in rodents. However, the role of these receptors in operant food self-administration or relapse to food seeking in animal models is unknown. EXPERIMENTAL APPROACH: In Experiment 1, we trained food-restricted rats (16-20 g per day) to lever press for high-fat (35%) pellets (3-6 h per day, every other day). We then tested the effect of the hypocretin 1 receptor antagonist SB 334867 (10, 20 mg kg(-1), i.p) on pellet self-administration. In Experiment 2, we trained rats to self-administer the food pellets, and following extinction of the food-reinforced responding, we tested the effect of hypocretin 1 (3 and 6 mug, i.c.v) on reinstatement of food-seeking and the effect of SB 334867 on this reinstatement. In Experiment 3, we tested the effect of SB 334867 on reinstatement induced by non-contingent pellet exposure (pellet-priming) or the pharmacological stressor yohimbine (2 mg kg(-1), i.p). KEY RESULTS: SB 334867 attenuated high-fat pellet self-administration. In contrast, SB 334867 had no effect on reinstatement of lever presses induced by hypocretin 1, pellet-priming or yohimbine. CONCLUSIONS AND IMPLICATIONS: These data indicate that during dieting, hypocretin 1 receptors contribute to operant high-fat pellet self-administration, but not to relapse to food seeking induced by acute re-exposure to the food itself or by the induction of a stress-like state.

Depression and osteoporosis: epidemiology and potential mediating pathways.

INTRODUCTION: There have been numerous studies examining the association between depression and bone mineral density (BMD), but the underlying nature of this relationship remains unclear. Independent of this association, there is a growing body of evidence that depression impacts the risk for fracture in older adults. This article reviews the current epidemiological evidence regarding comorbidity of depression, low bone mineral density, and fracture. METHODS: A review of the literature on depression, depressive symptoms, low BMD, osteoporosis, and fracture using electronic databases. RESULTS: We reviewed 20 studies of the association between depression and BMD and five reports of the relationship between depression and fractures. Potential mediating mechanisms (both physiological and behavioral) are discussed, as well as potential confounding influences (e.g., medication use). CONCLUSIONS: Most studies support the finding that depression is associated with increased risk for both low BMD and fractures, but variation in study design, sample composition, and exposure measurement make comparisons across studies difficult. Researchers should be aware of potential confounders, such as medication use, that may influence results. Future research should focus on identifying mediating pathways and targets for intervention in the relationships between depression, low BMD, and fracture.

Integrating the circadian oscillator into the life of the cyanobacterial cell.

In two decades, the study of circadian rhythms in cyanobacteria has gone from observations of phenomena in intractable species to the development of a model organism for mechanistic study, atomic-resolution structures of components, and reconstitution of a circadian biochemical oscillation in vitro. With sophisticated biochemical, biophysical, genetic, and genomic tools in place, the circadian clock of the unicellular cyanobacterium Synechococcus elongatus is poised to be the first for which a systems-level understanding can be achieved.

Quantum and classical studies of the O(3P) + H2(v = 0-3,j = 0) --> OH + H reaction using benchmark potential surfaces.

We present results of time-dependent quantum mechanics (TDQM) and quasiclassical trajectory (QCT) studies of the excitation function for O(3P) + H2(v = 0-3,j = 0) --> OH + H from threshold to 30 kcal/mol collision energy using benchmark potential energy surfaces [Rogers et al., J. Phys. Chem. A 104, 2308 (2000)]. For H2(v = 0) there is excellent agreement between quantum and classical results. The TDQM results show that the reactive threshold drops from 10 kcal/mol for v = 0 to 6 for v = 1, 5 for v = 2 and 4 for v = 3, suggesting a much slower increase in rate constant with vibrational excitation above v = 1 than below. For H2(v > 0), the classical results are larger than the quantum results by a factor approximately 2 near threshold, but the agreement monotonically improves until they are within approximately 10% near 30 kcal/mol collision energy. We believe these differences arise from stronger vibrational adiabaticity in the quantum dynamics, an effect examined before for this system at lower energies. We have also computed QCT OH(v',j') state-resolved cross sections and angular distributions. The QCT state-resolved OH(v') cross sections peak at the same vibrational quantum number as the H2 reagent. The OH rotational distributions are also quite hot and tend to cluster around high rotational quantum numbers. However, the dynamics seem to dictate a cutoff in the energy going into OH rotation indicating an angular momentum constraint. The state-resolved OH distributions were fit to probability functions based on conventional information theory extended to include an energy gap law for product vibrations.

A cyanobacterial circadian timing mechanism.

Cyanobacteria such as Synechococcus elongatus PCC 7942 exhibit 24-h rhythms of gene expression that are controlled by an endogenous circadian clock that is mechanistically distinct from those described for diverse eukaryotes. Genetic and biochemical experiments over the past decade have identified key components of the circadian oscillator, input pathways that synchronize the clock with the daily environment, and output pathways that relay temporal information to downstream genes. The mechanism of the cyanobacterial circadian clock that is emerging is based principally on the assembly and disassembly of a large complex at whose heart are the proteins KaiA, KaiB, and KaiC. Signal transduction pathways that feed into and out of the clock employ protein domains that are similar to those in two-component regulatory systems of bacteria.

Relative androgen excess and increased cardiovascular risk after menopause: a hypothesized relation.

Many studies have investigated the role of estrogen during menopause; however, less attention has been paid to the role of androgen. Given the possible opposite effects of estrogen and androgen on cardiovascular disease risk, it is suggested that relative androgen excess may better predict the increased risk of cardiovascular disease in women over the age of 50 years than estrogen levels alone. Three phases of hormonal milieu changes are hypothesized as a better way to identify the hormone-cardiovascular disease risk association. A first phase, prepause, occurs before estrogen levels decline (approximately 2 years before menopause). A second phase, interpause, occurs from the end of prepause until approximately age 55. A third phase, postpause, occurs after interpause. The duration of the interpause phase, characterized by relative androgen excess, may be an independent risk factor of cardiovascular disease. This hypothesis could provide a basis for further clinical and epidemiologic research, and it could have important implications for establishing the initiation and duration of estrogen replacement therapy use as a means to prevent cardiovascular disease.

An exploratory study of variations in exposure to environmental tobacco smoke in the United States.

There is considerable interest in assessing exposure to environmental tobacco smoke (ETS) and in understanding the factors that affect exposure at various venues. The impact of these complex factors can be researched only if monitoring studies are carefully designed. Prior work by Jenkins et al. gathered personal monitor and diary data from 1,564 nonsmokers in 16 metropolitan areas of the United States and compared workplace exposures to ETS with exposures away from work. In this study, these data were probed further to examine (1) the correspondence between work and away-from-work exposure concentrations of ETS; (2) the variability in exposure concentration levels across cities; and (3) the association of ETS exposure concentrations with select socioeconomic, occupation, and lifestyle variables. The results indicate (1) at the population level, there was a positive association between ETS concentrations at the work and away-from-work environments; (2) exposure concentration levels across the 16 cities under consideration were highly variable; and (3) exposure concentration levels were significantly associated with occupation, education, household income, age, and dietary factors. Workplace smoking restrictions were associated with low ETS concentration levels at work as well as away from work. Generally, the same cities that exhibited either lower or higher away-from-work exposure concentration levels also showed lower or higher work exposure concentration levels. The observations suggest that similar avoidance characteristics as well as socioeconomic and other lifestyle factors that affect exposure to ETS may have been in operation in both away-from-work and work settings.

Unusual regulatory elements for iron deficiency induction of the idiA gene of Synechococcus elongatus PCC 7942.

Expression of a thylakoid membrane-associated protein called IdiA (iron-deficiency-induced protein A) is highly elevated and tightly regulated by iron limitation in Synechococcus elongatus PCC 6301 and PCC 7942. Although this protein is not essential for photosystem II (PSII) activity, it plays an important role in protecting the acceptor side of PSII against oxidative damage, especially under iron-limiting growth conditions, by an unknown mechanism. We defined the iron-responsive idiA promoter by using insertional inactivation mutagenesis and reporter gene assays. A 67-bp DNA region was sufficient for full iron deficiency-inducible idiA promoter activity. Within this fragment is a palindromic sequence 4 bp upstream of a putative -35 promoter element, which resembles the binding site of FNR/CAP-type helix-turn-helix transcription factors. The absence of this palindromic sequence or a 3-bp mutation in a putative -10 region eliminated promoter activity completely. A previously identified candidate for a positively acting transcription factor is the IdiB protein, whose gene lies immediately downstream of idiA. IdiB shows strong similarity to helix-turn-helix transcription factors of the FNR/CAP family. A His(6x)-tagged IdiB that was overexpressed in Escherichia coli bound to a 59-bp fragment of the idiA regulatory region that included the palindrome. Although the idiA promoter lacks a consensus binding site for the iron-sensing regulator Fur, we attempted to inactivate fur in order to investigate the potential role of this factor. The resulting merodiploid mutants showed constitutive partial derepression of IdiA expression under iron-sufficient growth conditions. We concluded that IdiB is a specific iron-responsive regulator of idiA and that Fur has an indirect role in influencing idiA expression.

Functional elements of the strong psbAI promoter of Synechococcus elongatus PCC 7942.

The psbAI gene of the cyanobacterium Synechococcus elongatus PCC 7942 is one of three psbA genes that encode a critical photosystem II reaction center protein, D1. Regulation of the gene family in response to changes in the light environment is complex, occurs at transcriptional and posttranscriptional levels, and results in an interchange of two different forms of D1 in the membrane. Expression of psbAI is downregulated under high-intensity light (high light) in contrast to induction of the other two family members. We show that, in addition to a known accelerated degradation of the psbAI message, promoter activity decreases upon exposure to high light. Unlike the other psbA genes, additional sequences upstream of the psbAI -35 element are required for expression. Mutagenizing the atypical psbAI -10 element from TCTCCT to TATAAT increased the magnitude of expression from both psbAI::lacZ and psbAI::luxAB fusions but did not affect downregulation under high light. Inactivation of group 2 sigma factor genes rpoD2 and sigC, in both wild-type and -10-element mutagenized backgrounds, resulted in elevated psbAI::luxAB expression but did not alter the response to high light. The results are consistent with redundancy of promoter recognition among cyanobacterial group 2 sigma factors. Electrophoretic mobility shift assays showed that the DNA sequence corresponding to the untranslated leader of the psbAI message binds one or more proteins from an S. elongatus extract. The corresponding region of psbAII efficiently competed for this binding activity, suggesting a shared regulatory factor among these disparately regulated genes.