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The relationship of alcohol consumption to risky sexual behavior at the most recent encounter with a new sexual partner in representative samples of white, Hispanic, and black adults was examined. Drinking at the new partner event was more prevalent among whites than either blacks or Hispanics. Multivariate analyses indicated that drinking in the event was an important predictor on having a casual partner and using condoms with a casual partner for men but not for women. For women, drinking during the event predicted failure to use a condom. Some of these associations were dependent on ethnicity. Hispanics who consumed alcohol at the encounter were more likely to engage in protected sex than whites or blacks. These findings suggest that alcohol is but one of many influences regulating the riskiness of a particular encounter with a new partner and that the interplay of personal, situational, and behavioral factors with risky sex are culturally dependent. [ABSTRACT FROM AUTHOR]

The present study examined the relationship between acculturation, alcohol consumption and AIDS-related risky sexual behavior in a national probability sample of 533 African American women. Results indicated that women who were the heaviest drinkers were also the least acculturated. However, women most likely to engage in risky sexual behavior, including having multiple partners, being nonmonogamous or in a nonmonogamous relationship, and being nonmonogamous or in a nonmonogamous relationship and not using a condom consistently, were high in acculturation rather than low. Alcohol use proved related to risky sexual behavior when considered in conjunction with respondents' level of acculturation. Women at risk for contracting AIDS were not low acculturated African American women who drank heavily, but high acculturated African American women. Findings from this study extend our understanding of risk and contain implications for research and prevention efforts in the area of alcohol use and AIDS-related sexual behavior among African American women. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the effect of an evidence-based practice (EBP) education and mentoring program on the knowledge, practice, and attitudes toward EBP among staff nurses and clinicians in a rural critical access hospital., Background: While rural nurses value EBP, they often have more limited resources to engage in EBP activities compared with urban-based nurses., Methods: Direct care nurses and clinicians participated in a 5-month EBP education and mentoring program following the Iowa Model Revised: Evidence-Based Practice to Promote Excellence in Health Care. The Evidence-Based Practice Questionnaire was used to assess pretest-posttest knowledge, practice, and attitudes toward EBP., Results: Knowledge and practice of EBP increased significantly (P = .008 and P = .015, respectively) after the EBP education and mentoring intervention. Attitudes toward EBP also increased, although the increase was not statistically significant (P = .106)., Conclusions: Education and mentoring of healthcare clinicians in rural settings are crucial to the translation of evidence-based research into practice to improve patient outcomes.

A potential indicator of female lifetime productivity in swine is age of puberty, when a gilt achieves her first behavioral estrus. Follicular activity, as determined by tertiary follicle development, in prepubertal gilts begins during postnatal day (PND) 75 to 115. The central hypothesis of this study is that gilts demonstrating tertiary follicle development earlier in life, assessed using vulva size as a proxy, achieve puberty earlier in life compared with counterparts of a similar age and weight that lack tertiary follicle development. The objectives of this project were to identify a developmental time point when variation in ovarian development exists and to determine whether a relationship between the age prepubertal ovarian development and the age at onset of puberty exists. To accomplish this, 155 gilts of similar age (± 2 d) were weighed and vulva size measured on PND 75, 85, 95, 105, and 115. Vulva measures, including vulva width (VW), vulva length (VL), and vulva area (VA), were utilized as developmental proxies for follicular activity. At each time point, gilts ( n = 10) were sacrificed and ovarian follicular activity recorded. In a subset of gilts ( n = 105), estrus detection was conducted daily on PND days 126 to 200. Mean VA on PND 75, 85, 95, 105, and 115 was 596 ± 206, 683 ± 190, 864 ± 212, 1014 ± 228, and 1265 ± 252 mm 2 , respectively. Of the gilts demonstrating behavioral estrus, 28 were within PND 140 to 160, 36 between PND 161 to 180, 15 between PND 181 to 200, and 26 did not demonstrate estrus behavior within 200 d of age. All gilts euthanized at PND 75 lacked follicular activity as defined by having a minimum of 2 antral follicles per ovary, whereas 60%, 80%, 90%, and 100% demonstrated follicular activity on PND 85, 95, 105, and 115, respectively. Body weight at PND 75 and VW at PND 115 were correlated to age at first estrus ( P < 0.05). Of the gilts whose VA was less than 1 SD from the mean on PND 95 (i.e., <652 mm 2 ), 31% and 50% demonstrated their first behavioral estrus by PND 180 and 200, respectively. However, of gilts whose VA was within or greater than 1 SD of the mean (i.e., ≥652 mm 2 ), 66% and 79% exhibited estrus prior to PND 180 and 200, respectively. These data support utilization of VA changes between 95 and 115 d of age as a useful tool to identify replacement gilts prior to puberty for inclusion into the sow herd., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Mitigating heat stress (HS) in swine production is important as it detrimentally affects multiple aspects of overall animal production efficiency. Study objectives were to determine if gilts characterized as tolerant (TOL) or susceptible (SUS) in response to HS maintain that phenotype later in life and if that phenotype influences reproductive ability during HS. Individual gilts identified as TOL (n = 50) or SUS (n = 50) from a prepubertal HS challenge were selected based on their rectal temperature (TR) during acute HS. The study consisted of 4 experimental periods (P). During P0 (2 d), all pigs were exposed to thermoneutral (TN) conditions (21.1 °C). During P1 (14 d), all gilts received Matrix (15 mg altrenogest per day) to synchronize estrus, and were maintained in TN conditions. During P2 (9 d), Matrix supplementation was terminated and gilts were subjected to diurnal HS with ambient temperatures set at 35 °C from 1000 to 2200 h and 21 °C from 2200 to 1000 h. Also during P2 gilts underwent estrus detection and artificial insemination. During P3 gilts were housed in TN conditions for 41 d at which they were sacrificed and reproductive tracts were collected. During the last 2 d of P1 and throughout the entirety of P2, TR and skin temperature (TS) were recorded. During P2, SUS had increased TR relative to TOL pigs during P2 (0.27 °C; P < 0.01). Overall, uterine wet weight, ovarian weight, corpora lutea (CL) count, and embryo survival were 5.6 ± 0.1 kg, 21.6 ± 0.3 g, 17.8 ± 0.3 CLs, and 79 ± 2%, respectively, and not influenced by prepubertal HS tolerance classification (P ≥ 0.37). Tolerant gilts had a longer return-to-estrus (6.1 vs. 5.5 d, respectively; P = 0.01) following altrenogest withdrawal and tended to have larger CL diameters (10.3 vs. 10.1 mm; P = 0.06) compared to SUS gilts. Fetal weight (25.4 vs. 23.6 g; P = 0.01) and fetal crown-rump length (74.8 vs. 72.8 mm; P < 0.01) were higher in gilts previously classified as SUS compared to those previously classified as TOL. Additionally, neither litter size nor the number of fetuses detected as a percentage of ovulations was influenced by classification. In summary, SUS gilts had a shorter return-to-estrus, increased fetus size, and tended to have smaller CL diameters compared to TOL gilts. Additionally, SUS gilts also retained their inability to maintain euthermia postpubertally relative to TOL gilts. In conclusion, there appeared to be little reproductive advantage of maintaining a lower TR during HS.

Heat stress is one of the limiting factors negatively affecting pig production, health, and fertility. Characterizing genomic regions responsible for variation in HS tolerance would be useful in identifying important genetic factor(s) regulating physiological responses to HS. In the present study, we performed genome-wide association analyses for respiration rate (RR), rectal temperature (TR), and skin temperature (TS) during HS in 214 crossbred gilts genotyped for 68,549 single nucleotide polymorphisms (SNP) using the Porcine SNP 70K BeadChip. Considering the top 0.1% smoothed phenotypic variances explained by SNP windows, we detected 26, 26, 21, and 14 genes that reside within SNPs explaining the largest proportion of variance (top 25 SNP windows) and associated with change in RR (ΔRR) from thermoneutral (TN) conditions to HS environment, as well as the change in prepubertal TR (ΔTR), change in postpubertal ΔTR, and change in TS (ΔTS), respectively. The region between 28.85 Mb and 29.10 Mb on chromosome 16 explained about 0.05% of the observed variation for ΔRR. The growth hormone receptor (GHR) gene resides in this region and is associated with the HS response. The other important candidate genes associated with ΔRR (PAIP1, NNT, and TEAD4), ΔTR (LIMS2, TTR, and TEAD4), and ΔTS (ERBB4, FKBP1B, NFATC2, and ATP9A) have reported roles in the cellular stress response. The SNP explaining the largest proportion of variance and located within and in the vicinity of genes were related to apoptosis or cellular stress and are potential candidates that underlie the physiological response to HS in pigs.

Identifying traits associated with susceptibility or tolerance to heat stress (HS) is a prerequisite for developing strategies to improve efficient pork production during the summer months. Study objectives were to determine the relationship between the thermoregulatory and production responses to acute HS in pigs. Prepubertal gilts (n = 235; 77.9 ± 1.2 kg BW) were exposed to a thermoneutral (TN) period (P1, 24 h; 21.9 ± 0.5 °C, 62 ± 13% RH; fed ad libitum) followed immediately by a subsequent acute HS period (P2, 24 h; 29.7 ± 1.3 °C, 49 ± 8% RH; fed ad libitum). Rectal temperature (TR), skin temperature (TS), and respiration rate (RR) were monitored and BW and feed intake (FI) were determined. All pigs had increased TR, TS, and RR (0.80 °C, 5.65 °C, and 61.2 bpm, respectively; P < 0.01) and decreased FI and BW (29% and 1.10 kg, respectively; P < 0.01) during P2 compared to P1. Interestingly, body temperature indices did not explain variation in FI during P2 (R2 ≤ 0.02). Further, the percent change in BW during P2 was only marginally explained by each body temperature index (R2 ≤ 0.06) or percent change in FI (R2 = 0.14). During HS, TR was strongly correlated with P1 TR (r = 0.72, P < 0.01), indicating a pig's body temperature during TN conditions predicts the severity of hyperthermia during HS. Additionally, the change in TR (ΔTR, HS TR - TN TR) was larger in pigs retrospectively classified as susceptible (SUS) as compared to tolerant (TOL) pigs (1.05 vs. 0.51 °C, respectively; P < 0.01). In summary, thermoregulatory responses and production variables during acute HS are only marginally related. Further, changes in BW and FI were unexpectedly poorly correlated during acute HS (r = 0.34; P < 0.01). Collectively, suboptimal growth is largely independent on the thermoregulatory response and hypophagia during acute HS. Consequently, incorporating solely body temperature indices into a genetic index is likely insufficient for substantial progress in selecting HS tolerant pigs.

Over the past decade significant advancement has occurred in the biological and pathological role that Hp has in cardiovascular disease. Hp is an acute-phase protein with a role in the neutralization and clearance of free heme. Iron has tremendous potential for initiating vascular oxidation, inflammation and exacerbating coronary atherosclerosis. Hp genotype has been linked as a prognostic biomarker of acute myocardial infarction, heart failure, restenosis and cardiac transplant rejection. The increased understanding of Hp as a biomarker has provided new insights into the mechanisms of inflammation after cardiac injury and support the concept that Hp is not only an important antioxidant in vascular inflammation and atherosclerosis, but also an enhancer of inflammation in cardiac transplant.

Objectives were to investigate the effects of prolonged gestational and/or postnatal heat stress on performance and carcass composition of market weight pigs. Pregnant gilts were exposed to gestational heat stress (GHS, 28°C to 34°C, diurnal) or thermal neutral (18°C to 22°C, diurnal) conditions during the entire gestation or during the first or second half of gestation. At 14 wk of age (58 ± 5 kg), barrows were housed in heat stress (32°C, HS) or thermal neutral (21°C, TN) conditions. Feed intake and BW were recorded weekly, and body temperature parameters were monitored twice weekly until slaughter (109 ± 5 kg). Organs were removed and weighed, and loin eye area (LEA) and back fat thickness (BF) were measured after carcass chilling. Carcass sides were separated into lean, separable fat, bone, and skin components and were weighed. Moisture, lipid, and protein content were determined in the LM at the 10th rib. Data were analyzed using a split plot with random effect of dam nested within gestational treatment. Carcass measurements included HCW as a covariate to control for weight. Planned orthogonal contrast statements were used to evaluate the overall effect of GHS in the first half, second half, or any part of gestation. Gestational heat stress did not alter postnatal performance or most body temperature parameters (P > 0.10). However, ADFI in the finishing period was increased (P < 0.05) in response to GHS, particularly in pigs receiving GHS in the first half of gestation. Gestational heat stress during the first half of gestation decreased head weight as a percent of BW (P = 0.02), whereas GHS in the second half of gestation decreased bone weight as a percent of BW (P = 0.02). Heat stress reduced ADG, BW, and HCW (P < 0.0001). Lean tissue was increased in HS pigs on both a weight and percentage basis (P < 0.0001), but LEA was similar to TN carcasses (P = 0.38). Carcasses from HS barrows also had less carcass separable fat (P < 0.01) and tended to have less BF (P = 0.06) compared with those from TN barrows, even after controlling for HCW. However, percent intramuscular fat did not differ between treatments (P = 0.48). The LM from HS carcasses had a greater moisture to protein ratio (P = 0.04). HS barrows also had decreased heart (P < 0.001) and kidney (P < 0.0001) as a percent of BW compared with TN pigs. In summary, GHS may affect head and bone development, subsequently affecting carcass composition. Chronic HS during finishing results in longer times to reach market weight and a leaner carcass once market weight is achieved.

Background: Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion., Methods: Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L)., Results: Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015)., Conclusion: This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.

The goal of this study was to examine behaviors related to AIDS protection and contraception among African American, Hispanic, and white women. Data were collected in 1991 and 1992 as part of a large-scale National Alcohol Survey in which respondents were asked questions about AIDS-related sexual behavior and attitudes in face-to-face interviews. Results indicated that a significant proportion of women and their partners in each ethnic group did not use any form of protection during their most recent sexual encounter. The findings suggest that it may be useful to combine efforts to reduce unintended pregnancies with efforts for AIDS protection.

Aims: This is the third of a set of three papers evaluating drinking status and mortality risk. Analysis of three general population surveys of women evaluated all-cause mortality rates by drinking pattern., Design and Participants: Raw data from three studies of adult women were evaluated. Logistic regression models controlled for confounding characteristics. Meta-analysis combined study results., Measurements: Drinking pattern was alternatively defined by quantity, frequency and volume of drinking. Final models included drinking pattern (including long-term abstainers and former drinkers) as well as age and other confounding variables. Models also evaluated interactions of age and, respectively, long-term abstinence and former drinking., Findings: In models in which age was controlled, odds of death for long-term abstainers and former drinkers (defined by volume or quantity) were greater than those for light drinkers; odds of death for moderate and heavy drinkers (defined by quantity) were greater than those for light drinkers. When other psychosocial attributes were controlled, odds of death were similar for abstainers and light drinkers. When other psychosocial attributes were controlled, odds of death for heavy drinkers (defined by volume and quantity) were greater than those for light drinkers. When interactions of age and the two forms of abstinence were introduced, one study showed a significant effect of age and former drinking., Conclusions: Results were consistent with the hypothesis that characteristics of abstainers other than their non-use of alcohol may account for their higher mortality risk. With the exception of former drinkers compared to light drinkers, when interactions were introduced into models (for measures of quantity and frequency) findings were homogeneous across studies, lending generalizability to results.

Aims: This is the second of a set of three papers evaluating drinking status and mortality risk. Analysis of eight general population surveys of men evaluated all-cause mortality rates by drinking pattern., Design and Participants: Raw data from three studies of youth and five studies of adults were evaluated. Logistic regression models controlled for confounding characteristics. Meta-analysis combined study results., Measurements: Drinking pattern was alternatively defined by quantity, frequency and volume of drinking. Final models included drinking pattern (as well as abstinence in the youth models and long-term abstainers and former drinkers in adult models), age and other confounding variables. Models also evaluated interactions of age and, respectively, long-term abstinence and former drinking., Findings: No evidence was found for the hypothesis that abstinence is associated with greater mortality risk than light drinking. In the youth samples, abstainers had a lower risk of dying than those drinking less than 15 times per month. One study of the adult samples showed a significant age by former drinker interaction; this did not alter the lack of association of former drinking with mortality risk or the homogeneity of results across studies for this finding. The most consistent finding was the association of heavy drinking with mortality among youth. Among adults, drinking 43 or more drinks per month and drinking 21 or more times per month were associated with increased mortality risk. Quantity per occasion was not significantly associated with mortality risk among adults., Conclusions: That frequent drinking was related to mortality risk, whereas heavier quantity was unrelated, is inconsistent with the belief that daily consumption of a few glasses of wine has salutary effects. Empirically, however, this pattern tends to be unusual. Findings were homogeneous across studies lending generalizability to results.

Aims: This is the first of a set of three papers evaluating drinking status and mortality risk. Analyses of multiple studies describe associations of drinking patterns with characteristics hypothesized to confound the relationships between drinking status and mortality. Characteristics which both significantly differentiate drinking groups and are consistent across studies would suggest that mortality studies not controlling for them may be compromised., Design and Participants: Associations are evaluated from the raw data of 10 general population studies which contained mortality data. Long-term abstainers are compared to former drinkers, long-term abstainers and former drinkers are compared to light drinkers (by quantity, frequency and volume in separate analyses) and moderate to heavy drinkers are compared to light drinkers. Tetrachoric correlation coefficients assess statistical significance; meta-analysis determines if associations are homogeneous across studies., Measurements: Measures of alcohol consumption are quantity, frequency and volume; long-term abstainers are differentiated from former drinkers. Multiple measures of health, social position, social integration and mental health characteristics are evaluated., Findings: Across studies, adult male former drinkers are consistently more likely to be heavier smokers, depressed, unemployed, lower SES and to have used marijuana than long-term abstainers. Adult female former drinkers are consistently more likely to be heavier smokers, in poorer health, not religious, and unmarried than long-term abstainers. Both types of abstainers tend to be of lower SES than light drinkers and report poorer health (not consistent). Female abstainers are more likely to be of normal or overweight than light drinkers., Conclusions: Characteristics of two groups of abstainers, other than their non-use of alcohol, may confound the associations found between drinking and mortality risk.

The relationship of alcohol consumption to risky sexual behavior at the most recent encounter with a new sexual partner in representative samples of white, Hispanic, and black adults was examined. Drinking at the new partner event was more prevalent among whites than either blacks or Hispanics. Multivariate analyses indicated that drinking in the event was an important predictor on having a casual partner and using condoms with a casual partner for men but not for women. For women, drinking during the event predicted failure to use a condom. Some of these associations were dependent on ethnicity. Hispanics who consumed alcohol at the encounter were more likely to engage in protected sex than whites or blacks. These findings suggest that alcohol is but one of many influences regulating the riskiness of a particular encounter with a new partner and that the interplay of personal, situational, and behavioral factors with risky sex are culturally dependent.

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammation. One potential regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To determine the potential effects of FN on interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was abolished by costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL-1ra ratio in response to mixed matrices containing FN and type I collagen may be an important regulatory point in inflammation.

Purpose: To examine the relationship between alcohol use and sexual activity in a sample of young adults., Design: Data were collected as part of a 1990 survey of a multistage area household probability sample., Setting: In-home interviews were conducted by experienced interviewers., Subjects: In total, 1006 persons from 18 to 30 years of age living in the contiguous United States were contacted., Measures: Detailed information was collected on alcohol use and sexual behavior. To minimize the reluctance of respondents to answer queries on sexual behavior, those questions were contained in a self-administered questionnaire., Results: At the population level, having had multiple sexual partners in the past year was more likely among men who consumed five or more drinks per sitting. Condom use was less likely among respondents who had consumed five or more drinks on at least one occasion in the past year. In multivariate analyses, the amount of alcohol consumed at the new partner event was not associated with condom use with a new partner. When the effects of other demographic and psychosocial factors were removed, the number of drinks consumed during the heaviest drinking event was a significant predictor of engaging in sex for women but not for men., Conclusion: In young adults, alcohol use with sex does not necessarily lead directly to lapses in judgment about safe sexual practices. Alcohol is but one of a number of factors that play an important role in determining the riskiness of a particular sexual encounter.

Thymidylate synthase (TS) and dCMP hydroxymethylase (CH) are homologous enzymes which catalyze the alkylation of C5 of pyrimidine nucleotides. One of the first catalytic steps is isomerization of the alkyl donor, methylenetetrahydrofolate, from its N5,N10 bridged form to the N5 iminium ion upon enzyme binding. Glu58 in TS has been postulated [Matthews et al. (1990) J. Mol. Biol. 214, 937-948] to be involved in this isomerization and the deprotonation of C5 of the nucleotide. Substitution by Asp or Gln of Glu58 in Escherichia coli TS, or of the corresponding Glu60 in CH from phage T4, decreases the activity of either enzyme. Alkylation is slowed much more than deprotonation, indicating uncoupling of steps which are tightly coupled for the wild-type enzymes. The data support minor roles for Glu58/60 in nucleotide binding and in isomerization of methylenetetrahydrofolate, but no major roles in nucleotide deprotonation, product dissociation, or hydration catalyzed by CH. The primary role of Glu58/60 is to accelerate bond cleavage between N5 of tetrahydrofolate and the methylene being transferred. The influence of Glu58/60 on the rate of bond cleavage is proposed to arise from electrostatic destabilization due to the proximity of the glutamyl carboxylate, of the anionic species formed when C5 of the nucleotide is deprotonated. The proposal explains the uncoupling of deprotonation and alkylation with the Glu58/60 variants and the reduced kinetic isotope effect on hydride transfer for TS(Glu58Gln). The inability of 5-deazatetrahydrofolate to stimulate enzyme-catalyzed tritium exchange from [5-(3H)]nucleotides into solvent suggests that N5 of tetrahydrofolate is the base which deprotonates the nucleotide.

Data on substance use and sexual activity from a nationally representative, probability-based sample of young adults aged 18-30 in 1990 indicate that 86% of respondents had had sex in the previous 12 months, with three-fourths reporting no more than one sexual partner. Seventy-five percent of respondents had consumed alcohol in the past 12 months, 40% had smoked cigarettes and 20% had used marijuana. After adjustment for demographic factors, both sexual activity and a history of multiple partners were positively associated with some measures of substance use. Respondents who drank more frequently, those who were heavy drinkers, those who smoked cigarettes and those who used marijuana in the past year were more likely than others to be sexually active. Those who consumed five or more drinks at a sitting and those who used marijuana were more likely than others to have had more than one sexual partner. Heavy drinkers were also less likely to use condoms; however, the results showed no association between having sex under the influence of alcohol and engaging in unsafe sexual practices.

Deoxycytidylate (dCMP) hydroxymethylase (CH) catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate (CH2THF). The nucleotide analog 5-fluorodeoxuridylate (FdUMP) stoichiometrically inactivates CH by formation of a covalent complex containing enzyme, FdUMP, and CH2THF. Similar FdUMP complexes are formed by dTMP synthase and dUMP hydroxymethylase, enzymes which are homologous to CH. Both the association and the dissociation rate of the FdUMP complex are shown to be increased by the mutation of active site Asp179 to Asn. The mutated enzyme, CH(D179N), has an altered substrate preference, favoring dUMP rather than dCMP [Graves, K. L., et al. (1992) Biochemistry 31, 10315]. A value of 0.8 was determined for the alpha-secondary tritium equilibrium isotope effect on the binding of [6-3H]FdUMP to wild-type CH and to CH(D179N), using a mixture of 2-14C- and 6-3H-labeled FdUMP. These effects, similar to that found for TS, indicate that C6 of the nucleotide is saturated (i.e., sp3 hybridized) in the covalent complex of CH, FDUMP, and CH2THF. This strongly suggests that catalysis by CH proceeds via sequential sp2-->sp3-->sp2 hybridization changes at C6 of substrate nucleotides, and it is consistent with a transient covalent linkage of C6 to the thiol of an essential CH residue, Cys148. The values of the alpha-secondary 3H kinetic isotope effect (KIE) on kcat/KM for CH-catalyzed formation of Hm5dCMP caused by 6-3H-substitution of dCMP, with both wild-type CH and CH(D179N), were very close to 1.0. However, the KIE for CH-(D179N) with dUMP was 0.82.(ABSTRACT TRUNCATED AT 250 WORDS)

18O exchange experiments were designed to identify the final intermediate in the catalytic mechanism of bacteriophage T4 deoxycytidylate (dCMP) hydroxymethylase (CH). CH catalyzes the formation of 5-(hydroxymethyl)-dCMP (HmdCMP) from dCMP and methylenetetrahydrofolate (CH2-THF). CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. The final intermediate in the reaction catalyzed by TS or CH has been proposed to be the nucleotide with an exocyclic 5-methylene group covalently linked to the enzyme. This intermediate is then hydrated to HmdCMP (by CH) or reduced to deoxythymidylate (by TS). We report here that CH catalyzes the incorporation of 18O from solvent water into the product, HmdCMP, in the presence of tetrahydrofolate (THF). The cause of this exchange is a reverse reaction followed by a resynthesis. CH also catalyzes the exchange of 18O from solvent water into HmdCMP in the absence of exogenous THF and in the presence of THF analogues that lack N-5. N-5 is the nitrogen that is likely to be bound to the methylene as it is transferred to dCMP. A CH variant that lacks the nucleophilic Cys 148 is incapable of promoting these 18O exchange reactions. The THF analogues lacking N-5 do not promote a CH-catalyzed reverse reaction. Rather, we propose that the CH-catalyzed 18O exchange reaction promoted by these THF analogues occurs via 5-methylene-dCMP linked to the enzyme through Cys 148. We conclude here that enzyme-bound 5-methylene-dCMP is the final intermediate during catalysis by CH, as has also been proposed for TS and dUMP.

We assessed dietary intake and serum total cholesterol trends during the 1980s, in the Minneapolis-St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to 74 years old participated in independent, cross-sectional, population-based surveys of risk factors for cardiovascular disease in 1980 to 1982 (n = 1611) and 1985 to 1987 (n = 2231). Age-adjusted total energy intake was similar in 1980 to 1982 and 1985 to 1987: 2528 kcal (10.6 MJ) versus 2574 kcal (10.8 MJ) for men and 1683 kcal (7.1 MJ) versus 1689 kcal (7.1 MJ) for women. However, significant changes were observed in macronutrient intake. The percent of energy from total fat intake decreased from 39.3 to 38.1% in men and 38.9 to 36.6% in women (both P < 0.01). The composition of fat consumed changed, such that the Keys score, an index of dietary fat and cholesterol, decreased by 3.3 units in both sexes (both P < 0.01). The predicted changes in serum total cholesterol (Keys score) were generally consistent with observed declines of 5.4 mg/dL (0.1 mmol/L) in men and 5.8 mg/dL (0.15 mmol/L) in women during this time period. These data suggest that members of this community are on average modifying their fat consumption and that these dietary changes are resulting in more favorable serum total cholesterol levels.

The proposed roles of Cys148 and Asp179 in deoxycytidylate (dCMP) hydroxymethylase (CH) have been tested using site-directed mutagenesis. CH catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate. CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. Conversion of Cys148 to Asp, Gly, or Ser decreases CH activity at least 10(5)-fold, consistent with a nucleophilic role for Cys148 (analogous to the catalytic Cys residue in TS). In crystalline TS, hydrogen bonds connect O4 and N3 of the substrate dUMP to the side-chain amide of an Asn; the corresponding residue in CH is Asp179. Conversion of Asp179 to Asn reduces the value of kcat/KM for dCMP by (1.5 x 10(4))-fold and increases the value of kcat/KM for dUMP by 60-fold; as a result, CH(D179N) has a slight preference for dUMP. Wild-type CH and CH(D179N) are covalently inactivated by 5-fluoro-dUMP, a mechanism-based inactivator of TS. Asp179 is proposed to stabilize covalent catalytic intermediates, by protonating N3 of the pyrimidine-CH adduct.

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions.

Background: Dietary intervention to reduce fat consumption and increase fiber consumption has been recommended by the National Cancer Institute, but there is little evidence concerning the effectiveness of self-help materials. The purpose of this study was to evaluate such self-help materials, introduced by a nurse in a primary care setting., Methods: A randomized controlled trial involving 242 subjects was conducted in two primary care clinics in Chapel Hill, NC, in 1987. Changes in fat and fiber consumption in the intervention and control groups during the 3-month interval between interviews were compared using analysis of covariance., Results: The estimated reduction in fat was 3.8g larger for the intervention group than for the control group, but the confidence interval included zero. For those individuals who had some responsibility for meal preparation there was a larger difference (-6.9g) in favor of the intervention group, although the difference using calorie-adjusted values was -3.8g with a 95% confidence interval (-7.1, -0.4). The differences for fiber change were smaller., Conclusions: We found significant small but consistent differential changes associated with a minimal self-help intervention, but we cannot rule out the possibility of some response bias. Nonetheless, this study demonstrates that the use of self-help materials for dietary change is feasible, and may be effective.

An oxygen saturation sensor, for the purpose of chronically controlling the heart rhythm produced by a pacemaker, should be specific to oxygen saturation and should be minimally affected by the harsh blood environment. For the sensor type we tested we found: (1) one sensor failure in 205.5 canine-months of chronic implantation (n = 11, range 4 to 50 months); (2) hematocrit-induced error of less than 5 percentage points of SvO2 over the range of 50% to 80% SvO2 and 15% to 45% hematocrit; (3) carboxyhemoglobin (HbCO)-induced error of less than 4 percentage points of SvO2 with HbCO up to 20%; (4) a fibrotic sheath-induced error of less than 3 percentage points of SvO2 in the range of 50% to 80% SvO2 due to fibrotic sheath thicknesses up to 0.22 mm; (5) no significant error induced by velocity variations local to the sensor; (6) no significant error due to temperature in the range of 30 degrees to 42 degrees C; and (7) that the sensor could be as close as 0.3mm to the ventricular wall and still only produce an error of 5% SvO2.

Because misconceptions about nutrition are prevalent in athletics, we assessed the knowledge of sports-related nutrition concepts of high school athletic personnel. A questionnaire was mailed to all athletic directors and teacher athletic trainers in North Carolina high schools. Of the 821 surveys sent, 303 were returned (a response rate of 37%). The sample was grouped into three categories on the basis of the perceived role of the respondent: coach (n = 152), trainer (n = 91), and dual coach-trainer (n = 29). Thirty-one individuals who indicated that they held administrative positions with little or no contact with students were omitted from the analysis. One-way analysis of variance or chi 2 was used to examine differences in questionnaire responses among the three groups. In comparison with high school coaches, trainers had taken more workshops or courses related to nutrition (2.9 compared with 1.8) and had more frequently used professional meetings (62% vs 39%), workshops (64% vs 41%), and textbooks (75% vs 50%) as sources of information. Trainers were more knowledgeable about nutrition (9.6 correct responses vs 8.9 for coaches) and recommended desirable nutrition practices more often than coaches (7 of 9 vs 6 of 9). There was some disagreement between coaches and trainers in their perceptions of who was more important in dispensing nutrition information. Future nutrition education efforts should take into account the differences among these groups.

In both nonpregnant and pregnant rats as dietary protein increased, increases in urinary calcium were observed. In nonpregnant rats, urinary calcium excretion was significantly increased as the level of dietary protein increased from 16 to 24 to 32%, but in the pregnant rats increases in urinary calcium as protein intake was raised from 24 to 32% were not observed. The present data indicated that the increase in urinary calcium was probably a result of a shift of the endogenous excretion of calcium from the feces to urine and not from intestinal absorption of dietary calcium or bone resorption of calcium. Responses of parameters indicative of intestinal absorption either were inconsistent or were not affected as protein intake increased. A high protein diet had no effect on the amount of calcium lost from the bones. Although the results were inconsistent with regard to calcium retention, a positive calcium balance was achieved by all rats fed the three different levels of dietary protein. Urinary phosphorus excretion increased with increased protein intake, but the response was modified by the physiological state. In pregnant rats, the increase from 16 to 24% dietary protein had a greater influence on urine phosphorus than the increase from 24 to 32%; this pattern was reversed in the nonpregnant rats.