Social support buffering of the relation between low income and elevated blood pressure in at-risk African-American adults.

Socioeconomic disadvantage has been linked to elevated blood pressure (BP), and the purpose of this study was to assess whether interpersonal social supports buffer these adverse relations in African-American adults. In three communities matched demographically, a subsample of participants (N = 204) of the Positive Action for Today's Health trial provided measures of perceived social support, annual household income, and BP. Multiple regression analyses with cross-product interactions were conducted using follow-up data. The sample had a mean age of 52.8 years (SD = 15.1), and was predominantly female (66 %) with a high body mass index (M = 33.5, SD = 14.7). Results indicated an inverse relation between social support and diastolic BP (B = -.178, p = .005), and also an interaction with income (p = .046), such that higher social support related to lower diastolic BP in the lowest-income individuals (B = -1.05). The same direct (B = -.141, p = .025) and interacting (B = -1.42, p = .040) social support effects were present for systolic BP, however the omnibus model for systolic BP was not significant, F(6, 196) = 1.80, p = .09. The hypothesized buffering effect of social support on the adverse relation of income to BP was partially supported in at-risk African-American adults. Future prevention efforts for reducing the impact of socioeconomic stress on BP may aim to increase perceptions of social support.

A computational study of the effect of windscreen shape and flow resistivity on turbulent wind noise reduction.

In this paper, numerical simulations are used to study the turbulent wind noise reduction effect of microphone windscreens with varying shapes and flow resistivities. Typical windscreen shapes consisting of circular, elliptical, and rectangular cylinders are investigated. A turbulent environment is generated by placing a solid circular cylinder upstream of the microphone. An immersed-boundary method with a fifth-order weighted essentially non-oscillatory scheme is implemented to enhance the simulation accuracy for high-Reynolds number flow around the solid cylinder as well as at the interface between the open air and the porous material comprising the windscreen. The Navier-Stokes equations for incompressible flow are solved in the open air. For the flow inside the porous material, a modified form of the Zwikker-Kosten equation is solved. The results show that, on average, the circular and horizontal ellipse windscreens have similar overall wind noise reduction performance, while the horizontal ellipse windscreen with medium flow resistivity provides the most effective wind noise reduction among all the considered cases. The vertical ellipse windscreen with high flow resistivity, in particular, increases the wind noise because of increased self-generation of turbulence.

Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations.

The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta-barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented.

An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications.

Aldose reductase, which catalyzes the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of a wide variety of aromatic and aliphatic carbonyl compounds, is implicated in the development of diabetic and galactosemic complications involving the lens, retina, nerves, and kidney. A 1.65 angstrom refined structure of a recombinant human placenta aldose reductase reveals that the enzyme contains a parallel beta 8/alpha 8-barrel motif and establishes a new motif for NADP-binding oxidoreductases. The substrate-binding site is located in a large, deep elliptical pocket at the COOH-terminal end of the beta barrel with a bound NADPH in an extended conformation. The highly hydrophobic nature of the active site pocket greatly favors aromatic and apolar substrates over highly polar monosaccharides. The structure should allow for the rational design of specific inhibitors that might provide molecular understanding of the catalytic mechanism, as well as possible therapeutic agents.

Community characteristics modify the relationship between obesity prevention efforts and dietary intake in children: the Healthy Communities Study.

BACKGROUND: The influence of community characteristics on the effectiveness of childhood obesity prevention efforts is not well understood. OBJECTIVE: Examine the interaction of community characteristics with the relationship between community programmes and policies (CPPs) and dietary intake. METHODS: An observational study of 5138 children in grades K-8 in 130 US communities was conducted in 2013-2015. Key informant interviews identified and characterized CPPs. CPP scores were generated for the number of target behaviours (CPP-Behav) and the number of behaviour change strategies (CPP-Strat) addressed by all CPPs and CPPs with nutrition goals over the prior 6 years in each community. Dietary intake was assessed by dietary screener and included intake of sugar from sugar-sweetened beverages; energy-dense foods; fruits and vegetables; whole grains; and fibre. Multivariate statistical models assessed the interactions between US region, urbanicity, community-level income, and community-level race/ethnicity and CPP scores in relation to dietary intake. RESULTS: CPP-Strat was positively associated with healthier dietary intakes in the Northeast and West, and in high Hispanic communities; the reverse was true in the South, and in high African-American and low-income communities. The CPP-Behav was positively associated with healthier dietary intakes in the South and rural areas, and the reverse was true in the West. CONCLUSION: The relationships between CPP index scores and dietary intake were most strongly influenced by region and urbanicity and to a lesser extent by community-level race/ethnicity and income. Findings suggest that different considerations may be needed for childhood obesity prevention efforts in communities with different characteristics.

Objectives of community policies and programs associated with more healthful dietary intakes among children: findings from the Healthy Communities Study.

BACKGROUND: Rational planning of community policies and programs (CPPs) to prevent obesity requires an understanding of CPP objectives associated with dietary behaviours. OBJECTIVE: The objective of the study is to identify objectives of CPPs associated with healthful dietary behaviours. METHODS: An observational study identified 4026 nutrition CPPs occurring in 130 communities in the prior 6 years. Dietary intakes of fruits and vegetables, added sugar and sugar-sweetened beverages, among others, were reported among 5138 children 4-15 years of age from the communities, using a Dietary Screener Questionnaire with children age 9 years and older (parent assisted) or parent proxies for younger children. CPPs were documented through key informant interviews and characterized by their intensity, count, and objectives including target dietary behaviour and food environment change strategy. Associations between dietary intakes and CPP objectives were assessed using hierarchical statistical models. RESULTS: CPPs with the highest intensity scores that targeted fast food or fat intake or provided smaller portions were associated with greater fruit and vegetable intake (0.21, 0.19, 0.23 cup equivalents/day respectively with p values <0.01, 0.04, 0.03). CPPs with the highest intensity scores that restricted the availability of less healthful foods were associated with lower child intakes of total added sugar (-1.08 tsp/day, p < 0.01) and sugar from sugar-sweetened beverages (-1.63 tsp/day, p = 0.04). Similar associations were observed between CPP count and dietary outcomes. No other significant associations were found between CPP target behaviours or environmental strategies and dietary intakes/behaviours. CONCLUSION: CPPs that targeted decreases in intakes of less healthful foods and/or aimed to modify the availability of less healthful foods and portions were associated with healthier child dietary behaviours.

Associations between community programmes and policies and children's physical activity: the Healthy Communities Study.

BACKGROUND: Community initiatives to promote physical activity in children are common, but evidence supporting their effectiveness is limited. OBJECTIVES: The objective of this study is to examine the relationships between community programmes and policies and children's physical activity in a large and diverse sample of US communities. METHODS: Programmes and policies to promote children's physical activity were assessed in 130 communities by key informant interviews, and physical activity behaviours were measured by self-report and parental report in samples of children in each community (total n = 5138). Associations between composite indices of community programmes and policies and indicators of total and moderate-to-vigorous physical activity were examined without and with adjustment for demographic factors. RESULTS: An index reflecting the 6-year history of the number of behaviour change strategies used in community programmes and policies was positively associated with children's moderate-to-vigorous physical activity. This association was attenuated with adjustment for demographic factors. Effect modification analyses found that the association was positive among non-Hispanic children but was negative for Hispanic children. CONCLUSIONS: Community initiatives to promote physical activity in children were positively associated with children's physical activity in non-Hispanic children. Such initiatives were negatively associated with physical activity in Hispanic children, suggesting that future research should consider unique cultural factors when designing community initiatives to promote activity in this population sub-group.

Associations of community programs and policies with children's dietary intakes: the Healthy Communities Study.

BACKGROUND: The impact of community-based obesity prevention efforts on child nutrition has not been adequately studied. OBJECTIVE: Examine relationships between number, type and intensity of community programs and policies (CPPs) and child nutrition. METHODS: An observational study of 5138 children (grades K-8) in 130 U.S. communities was conducted in 2013-2015. CPPs were identified by 10-14 key informant interviews per community. CPPs were characterized based on: count, intensity, number of different strategies used and number of different behaviours targeted. Scores for the prior 6 years were calculated separately for CPPs that addressed primarily nutrition, primarily physical activity (PA) or total combined. Child intakes were calculated from a dietary screener and dietary behaviours were based on survey responses. Multi-level statistical models assessed associations between CPP indices and nutrition measures, adjusting for child and community-level covariates. RESULTS: Implementing more types of strategies across all CPPs was related to lower intakes of total added sugar (when CPPs addressed primarily PA), sugar-sweetened beverages (for nutrition and PA CPPs) and energy-dense foods of minimal nutritional value (for total CPPs). Addressing more behaviours was related to higher intakes of fruit and vegetables (for nutrition and total CPPs) and fibre (total CPPs). Higher count and intensity (PA and total CPPs) were related to more consumption of lower fat compared with higher fat milk. A higher count (PA CPPs) was related to fewer energy-dense foods and whole grains. No other relationships were significant at P < 0.05. CONCLUSION: Multiple characteristics of CPPs to prevent obesity appear important to improve children's diets.

Aldose reductase catalysis and crystallography. Insights from recent advances in enzyme structure and function.

Enhanced metabolism of glucose via the polyol pathway may play an important role in the pathogenesis of diabetic retinopathy, neuropathy, and nephropathy. Aldose reductase catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step in the polyol pathway. Interruption of the polyol pathway by inhibition of aldose reductase holds considerable promise as a therapeutic measure to prevent or delay the onset and severity of these late complications of diabetes. Dramatic advances in our understanding of the molecular biology, enzymology, and three-dimensional structure of aldose reductase have occurred in recent years, providing new and challenging insights into the enzyme's catalytic mechanism. Recent developments in structure determination of aldose reductase and the implications for evaluation and development of aldose reductase inhibitors are summarized.

Refined 2.5 A structure of murine adenosine deaminase at pH 6.0.

The X-ray structure of murine adenosine deaminase complexed with the transition-state analogue 6-hydroxyl-1,6-dihydropurine ribonucleoside has been determined from a single crystal grown at pH 4.2 and transferred to mother liquor of increasing pH up to a final pH of 6.0 prior to data collection. The structure has been refined to 2.5 A to a final crystallographic R-factor of 20% using phases from the previously refined 2.4 A structure at pH 4.2. Kinetic measurements show that the enzyme is only 20% active at pH 4.2 whereas it is fully active between pH 6.0 and pH 8.5. The refined structures at either pH are essentially the same. Consideration of the pKa values of the key catalytic residues and the mechanism proposed on the basis of the structure suggests that the ionization state of these residues is largely responsible for the pH dependence on activity.

Preliminary X-ray analysis of crystals of murine adenosine deaminase.

We have obtained single crystals of a cloned mammalian adenosine deaminase (Mr = 41,000), a key enzyme in purine degradation and in normal development of the immune system, that are suitable for high-resolution structural analysis. The crystals belong to the space group C2 with unit cell parameters a = 101.68 A (1 A = 0.1 nm), b = 94.38 A, c = 85.51 A, and beta = 96.54 degrees. The asymmetric unit contains two enzyme molecules.

Prospective evaluation of HDL cholesterol changes after diet and physical conditioning programs for patients with type II diabetes mellitus.

High-density lipoprotein (HDL) cholesterol is known to be low in patients with diabetes mellitus. Low HDL levels are correlated with premature cardiovascular mortality in several major epidemiologic studies and many investigators believe increases in HDL cholesterol may reduce the risk of coronary heart disease. We evaluated dietary and exercise interventions in relation to HDL cholesterol in patients with type II diabetes mellitus. Sixty-five volunteers were randomly assigned to one of four experimental conditions: diet, exercise, diet plus exercise, or education control. Three months after entering the program, those exposed to the dietary intervention had significant increases in HDL cholesterol. HDL increases for the other two treatment groups did not differ significantly from the education control.

The role of divalent cations in structure and function of murine adenosine deaminase.

For murine adenosine deaminase, we have determined that a single zinc or cobalt cofactor bound in a high affinity site is required for catalytic function while metal ions bound at an additional site(s) inhibit the enzyme. A catalytically inactive apoenzyme of murine adenosine deaminase was produced by dialysis in the presence of specific zinc chelators in an acidic buffer. This represents the first production of the apoenzyme and demonstrates a rigorous method for removing the occult cofactor. Restoration to the holoenzyme is achieved with stoichiometric amounts of either Zn2+ or Co2+ yielding at least 95% of initial activity. Far UV CD and fluorescence spectra are the same for both the apo- and holoenzyme, providing evidence that removal of the cofactor does not alter secondary or tertiary structure. The substrate binding site remains functional as determined by similar quenching measured by tryptophan fluorescence of apo- or holoenzyme upon mixing with the transition state analog, deoxycoformycin. Excess levels of adenosine or N6- methyladenosine incubated with the apoenzyme prior to the addition of metal prevent restoration, suggesting that the cofactor adds through the substrate binding cleft. The cations Ca2+, Cd2+, Cr2+, Cu+, Cu2+, Mn2+, Fe2+, Fe3+, Pb2+, or Mg2+ did not restore adenosine deaminase activity to the apoenzyme. Mn2+, Cu2+, and Zn2+ were found to be competitive inhibitors of the holoenzyme with respect to substrate and Cd2+ and Co2+ were noncompetitive inhibitors. Weak inhibition (Ki > or = 1000 microM) was noted for Ca2+, Fe2+, and Fe3+.

Variability in salt sensitivity classifications in black male versus female adolescents.

Salt sensitivity (changes in blood pressure in response to alterations in salt intake) may be a risk factor for hypertension. In the present study, we examined the prevalence of salt sensitivity based on two different classifications in healthy black male and female adolescents (aged 13 to 16 years). A total of 135 black adolescents participated in a 50 mmol/24 h low sodium diet for 5 days and a 150 mmol/24 h NaCl supplement for 10 days. Dietary compliance was defined as sodium excretion less than or equal to 50 mmol/24 h for the low sodium diet and greater than or equal to 165 mmol/24h for the high NaCl supplement. Salt sensitivity was defined by two classifications: (1) as a decrease in mean blood pressure greater than or equal to 5 mm Hg from baseline to the low sodium diet, and (2) as an increase in mean blood pressure greater than or equal to 5 mm Hg from the low sodium diet to the high NaCl supplement. With classification 1, 14% of boys were identified as salt sensitive compared with 22% of girls. With classification 2, however, 31% of boys were identified as salt sensitive compared with 18% of girls. Analyses based on changes in systolic pressure demonstrated similar findings across sex, although overall classifications based on systolic pressure yielded a greater percentage of salt-sensitive subjects. These sex differences in classification patterns were not due to differences in other important variables, such as changes in sodium excretion, potassium excretion, or Quetelet index. These results suggest that the prevalence of salt sensitivity differs by sex depending on the type of protocol used for the classification of salt sensitivity in a black pediatric population.

Socioeconomic status and blood pressure reactivity in healthy black adolescents.

Adolescents in low-socioeconomic-status environments are more susceptible to illnesses, such as hypertension and cardiovascular diseases. This study examined the influence of both neighborhood- and family-level socioeconomic status (SES) on blood pressure (BP) reactivity in a healthy sample of 76 black adolescents. It was hypothesized that a higher level of parental education and/or income would reduce the elevated BP reactivity associated with living in poorer neighborhoods. Census-derived data were obtained using each participant's address. Neighborhood level of SES was based on percentage of households below the poverty line, female-headed households, owner-occupied housing, percentage vacant housing, and average number of persons per household. Family level of SES was based on self-reported level of parental education and annual family income. Adolescents participated in a competitive video game to establish their BP reactivity scores. As predicted, adolescents who lived in poorer neighborhoods had lower diastolic BPs if their parents were more (versus less) educated (P<0.05; 7+/-8 versus 13+/-6 mm Hg). Adolescents who lived in poorer neighborhoods also had significantly lower diastolic BP reactivity (P<0.05) if their family had a higher (versus lower) annual income (7+/-7 versus 12+/-8 mm Hg). These data are the first to demonstrate the buffering effect of family SES on the negative health consequences of living in low-SES neighborhoods in healthy black adolescents.

Effects of potassium on blood pressure in salt-sensitive and salt-resistant black adolescents.

This study examined the effects of increasing dietary potassium on ambulatory blood pressure nondipping status (<10% decrease in blood pressure from awake to asleep) and cardiovascular reactivity in salt-sensitive and salt-resistant black adolescents. A sample of 58 normotensive (blood pressure, 101/57+/-9/4 mm Hg) black adolescents (aged 13 to 16 years) participated in a 5-day low sodium diet (50 mmol/24 h) followed by a 10-day high sodium diet (150 mmol/24 h NaCl supplement) to determine salt-sensitivity status. Participants showed a significant increase in urinary sodium excretion (24+/-19 to 224+/-65 mmol/24 h) and were identified as salt-sensitive if their mean blood pressure increase was >/=5 mm Hg from the low to high sodium diet. Sixteen salt-sensitive and 42 salt-resistant subjects were then randomly assigned to either a 3-week high potassium diet (80 mmol/24 h) or usual diet control group. Urinary potassium excretion significantly increased in the treatment group (35+/-7 to 57+/-21 mmol/24 h). At baseline, a significantly greater percentage of salt-sensitive (44%) compared with salt-resistant (7%) subjects were nondippers on the basis of diastolic blood pressure classifications (P<0.04). After the dietary intervention, all of the salt-sensitive subjects in the high potassium group achieved dipper status as a result of a drop in nocturnal diastolic blood pressure (daytime, 69 versus 67 mm Hg; nighttime, 69 versus 57 mm Hg). No significant group differences in cardiovascular reactivity were observed. These results suggest that a positive relationship between dietary potassium intake and blood pressure modulation can still exist even when daytime blood pressure is unchanged by a high potassium diet.

Theoretical study of inhibition of adenosine deaminase by (8R)-coformycin and (8R)-deoxycoformycin.

Molecular dynamics and free energy simulations were performed to examine the binding of (8R)-deoxycoformycin and (8R)-coformycin to adenosine deaminase. The two inhibitors differ only at the 2' position of the sugar ring; the sugar moiety of conformycin is ribose, while it is deoxyribose for deoxycoformycin. The 100 ps molecular dynamics trajectories reveal that Asp 19 and His 17 interact strongly with the 5' hydroxyl group of the sugar moiety of both inhibitors and appear to play an important role in binding the sugar. The 2' and 3' groups of the sugars are near the protein-water interface and can be stabilized by either protein residues or water. The flexibility of the residues at the opening of the active site helps to explain the modest difference in binding of the two inhibitors and how substrates/inhibitors can enter an otherwise inaccessible binding site.

Ambulatory blood pressure recordings in children and adolescents.

OBJECTIVE: To provide reference data for ambulatory blood pressure monitoring (ABPM) and to determine the influence of age, sex, and race on these values. METHODS: ABPM was performed on 300 healthy, normotensive boys and girls between the ages of 10 and 18 years, including 160 boys and 140 girls, of whom 149 were white and 151 were black. Mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) while awake and during sleep were calculated for black and white boys and girls aged 10 to 12 years, 13 to 15 years, and 16 to 18 years. RESULTS: Boys compared with girls 10 to 12 years of age had higher mean (+/- SD) SBP (115 +/- 9 vs 112 +/- 9 mm Hg; P < .01) and DBP (67 +/- 7 vs 65 +/- 5 mm Hg; P < .01) while awake. Boys compared to girls 13 to 15 years of age had higher SBP while awake (116 +/- 11 vs 112 +/- 8 mm Hg; P < .01). Boys compared with girls 16 to 18 years of age had higher SBP while awake (125 +/- 12 vs 111 +/- 9 mm Hg); P < .01) and during sleep (116 +/- 11 vs 106 +/- 9 mm Hg). Comparisons within sex showed similar changes with age for boys and girls. Blacks compared with whites 13 to 15 years of age had higher SBP during sleep (109 +/- 11 vs 105 +/- 10 mm Hg; P < .01), and blacks compared with whites 16 to 18 years of age had higher DBP during sleep (66 +/- 7 vs 58 +/- 6 mm Hg; P < .01). Comparisons across age groups within race showed that blacks 16 to 18 years of age had higher SBP during sleep than blacks 10 to 12 years of age (109 +/- 11 vs 104 +/- 10 mm Hg), and higher DBP during sleep (66 +/- 7 mm Hg; P < .01) than blacks 10 to 12 years of age (61 +/- 7 mm Hg; P < .01) and 13 to 15 years of age (61 +/- 8; P < .01 mm Hg). The changes with age were not significant for white subjects. CONCLUSION: These results provide age-specific reference data for ABPM in youths. These values differ by sex (boys more than girls) and race (Blacks more than Whites).

Structural features of the aldose reductase and aldehyde reductase inhibitor-binding sites.

The three-dimensional structures of aldose reductase and aldehyde reductase, members of the aldo-keto reductase superfamily, are composed of similar alpha/beta TIM-barrels. However, examination of the structures reveals that the inhibitor-binding site of aldose reductase differs from that of aldehyde reductase due to the participation of non-conserved residues in its formation. This information will be useful in the design of inhibitors to prevent or delay diabetic retinopathy. A review of the structures of the inhibitor-binding sites is presented.