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PubMed2001

Therapy naivete in the era of potent antiretroviral therapy.

Antiretroviral therapy (ART) use was examined in a cohort of homosexual men infected with HIV-1 for long periods. Multivariate logistic regression models, stratified by clinical indication (below and above 500 CD4 cells/microl or prior AIDS), were used to determine predictors of ART naivete. Of the 673 men seen at visit 28 (10/97-4/98), 89 (13.2%) never used ART and 548 (81.4%) were current users; 55% of the therapy-naive were ART eligible. Lower CD4 cell counts predicted (P <.001) ART use. Determinants of therapy naivete differed by clinical indication. African-American race and no prior ambulatory visit predicted (P <.05) ART naivete in men with > or =500 CD4 cells/microl. Among those with clinical indications, less education, younger age, multiple sexual partners, and no prior ambulatory visit significantly predicted ART naivete. In this era of effective ART, use was not universal. Besides disease markers, these nonclinical determinants need to be considered for promoting population therapy effectiveness.

Adult↗
PubMed1998

Neural cell recognition molecule L1: from cell biology to human hereditary brain malformations.

The neural cell recognition molecule L1 is a member of the immunoglobulin superfamily implicated in embryonic brain development. L1 is engaged in complex extracellular interactions, with multiple binding partners on cell surfaces and in the extracellular matrix. It is the founder of a neural group of related cell surface receptors that share with L1 a highly conserved cytoplasmic domain that associates with the cytoskeleton. Phenotypic analyses of human patients with mutations in the L1 gene and characterizations of L1-deficient mice suggest that L1 is important for embryonic brain histogenesis, in particular the development of axon tracts.

Animals↗
PubMed2000

Use of reproductive health services among young men, 1995.

PURPOSE: To analyze the extent to which teenage males receive preventive reproductive health services and identify demographic and health factors associated with their receipt. METHODS: Bivariate and multivariate analyses of nationally representative data from the 1995 National Survey of Adolescent Males were conducted using logistic regression to determine which factors predicted whether teenagers had a physical examination and whether they discussed reproductive health topics with a medical professional, had a human immunodeficiency virus (HIV) test, or had a sexually transmitted disease (STD) test. RESULTS: Although 71% of males aged 15-19 years received a physical examination in the past year, only 39% of them received any of the three reproductive health services. Less than one-third of all young men discussed reproductive health with their doctor or nurse. Among sexually experienced males, one-sixth had an STD test and one-quarter an HIV test. In multivariate analysis, males who had a physical examination were more likely to have an STD or HIV test, but were no more likely to discuss reproductive health topics. Minority and low-income youth were more likely to receive these reproductive health services, as were young men with multiple sex partners and those with health problems. CONCLUSIONS: In general, the proportion of teenage men receiving reproductive health services is low, although levels are higher among minority youth and certain groups at risk. To reduce rates of teen pregnancy and STDs, physicians and nurses need to incorporate reproductive health care into routine health services for teenage males, as well as females.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Effects of a brief, theory-based STD-prevention program for female college students.

PURPOSE: To evaluate a brief, theoretically guided sexually transmitted disease (STD) risk-reduction intervention tailored to college-aged women. METHODS: The participants were 78 undergraduate females (M = 20 years; 76% European-American) who reported inconsistent condom use or multiple sexual partners. Participants were randomly assigned to one of three groups: (a) a one-session intervention based on the information-motivation-behavioral skills (IMB) model, (b) a one-session information-only intervention (INFO), or (c) a wait-list control (WLC) group. Consistent with Fisher and Fisher's (1992) IMB model, we predicted that risk reduction would be greater when information about HIV was supplemented with motivational enhancement strategies and skills training. To evaluate this hypothesis, groups were compared at the post-intervention assessment and at a 2-month follow-up using analyses of covariance and log odds ratios. RESULTS: At the post-intervention assessment, the IMB and INFO groups demonstrated increased STD-related knowledge. At 2-month follow-up, the IMB and INFO groups showed sustained STD-related knowledge, and the IMB group showed reductions in number of sexual partners compared to the WLC group. CONCLUSIONS: These results provide partial support for the hypothesis that an IMB model-based intervention leads to reductions in sexual risk behavior and suggest directions for future research.

Adult↗
PubMed2002

Increasing MDMA use among college students: results of a national survey.

PURPOSE: To examine the prevalence and changing patterns of ecstasy use among college students, and to determine characteristics, associated behaviors, and interests of ecstasy users. METHODS: The study analyzes data regarding ecstasy use and related behaviors from the 1997 and 1999 Harvard School of Public Health College Alcohol Study. This is a survey of a nationally representative sample of over 14,000 college students at 119 U.S. four-year colleges. Changes in self-reported annual ecstasy use were examined, and lifestyle and high-risk behaviors associated with Ecstasy use were identified. Data were analyzed using 2 x 2 Chi-square tests and multiple logistic regression fitted by the generalized estimating equations (GEE). RESULTS: The prevalence of past year ecstasy use rose from 2.8% to 4.7% between 1997 and 1999, an increase of 69%. This increase was observed across nearly all subgroups of student and college type. A smaller sample of ten colleges revealed that the increase continued in 2000. Ecstasy users were more likely to use marijuana, engage in binge drinking, smoke cigarettes, have multiple sexual partners, consider arts and parties as important, religion as less important, spend more times socializing with friends, and spend less times studying. Unlike other illicit drug users, ecstasy users were not academic underachievers and their satisfaction with education was not different from that of non-ecstasy users. CONCLUSION: Ecstasy use is a high-risk behavior among college students which has increased rapidly in the past decade.

Adolescent↗
PubMed1997

Genital Chlamydia trachomatis infection in pregnant adolescents in east Tennessee: a 7-year case-control study.

STUDY OBJECTIVE: To examine the prevalence, symptomatology, risk factors, and other infections associated with urogenital chlamydial infection in pregnant teenagers. DESIGN: Retrospective case-control study by medical record review. SETTING: Prenatal care clinic for adolescents at University of Tennessee Medical Center, Knoxville, Tennessee. PARTICIPANTS: Pregnant adolescents younger than 19 years of age who were diagnosed with chlamydial infection on the first prenatal visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and socioeconomic background who came in the same day for the first prenatal visit, but were not infected, made up the control group. INTERVENTION: Routine prenatal questionnaires regarding personal and medical histories, and routine prenatal screening, including pelvic examination with Papanicolaou (PAP) smear and laboratory investigations for common genital infections and sexual transmitted disease (STDs), were obtained. MAIN OUTCOME MEASURES: Analyzed the prevalence of chlamydial infection and compared the infected group to the control group with regard to race, behavioral factors, symptoms, prenatal screening results, other concurrent genital infections, and histories of STDs. RESULTS: Of a total population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were independently associated with chlamydial infection. Age, marital status, number of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and multiple sex partners were not associated with the infection. Likewise, the symptom of vaginal discharge (a complaint of > 70% in each group), other genital co-infections (found > 50% in each group, mainly candidiasis and bacterial vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs or previous chlamydial infection were not significantly different between case and control groups. Human papillomavirus infection, trichomonal infection, and dysplasia or atypia were found more often in patients infected with chlamydia, but were not statistically significant. CONCLUSION: Pregnant adolescents in east Tennessee were at risk for chlamydial infection as well as for other genital infections and abnormal PAP smears. Routine prenatal chlamydial screening is warranted because of a lack of specific symptoms.

Adolescent↗
PubMed2003

Hepatitis C virus: prevalence and routes of infection among blood donors of West Mexico.

In Latin America few studies have explored frequency and risk factors predicting hepatitis C virus (HCV) infection in blood donors. In this study we determined the prevalence of HCV infection in blood donors from West Mexico. Potential risk factors, clinical, histological and virologic characteristics presented in this group were also evaluated. METHODS: HCV antibodies were evaluated in 57108 blood donors with commercial second-generation enzyme immunoassays. Positive results were confirmed by a recombinant immunoblot assay. Repeatedly seropositive donors were further studied for risk factors, history for hepatitis, hepatic enzymes (aspartate aminotransferase and alanine aminotransferase (AST and ALT)), liver histology and hepatitis C virus-ribonucleic acid (HCV-RNA) detection. RESULTS: A total of 499 blood donors were initially tested positive doubtful for antibodies to HCV Ab (0.8%). While there was no difference in HCV prevalence with respect to age or gender, the most frequent risk factors identified were transfusion (42%), household exposure (14.8%), multiple sex partner (6.8%) and intranasal cocaine use (2.3%). Also, we found that from a subgroup of donors tested for histological analysis, 19% presented abnormal ALT levels and 90% showed abnormal liver histology. No correlation was found between abnormal ALT levels and the presence of HCV-RNA in serum. CONCLUSION: These results demonstrate a low prevalence (0.8%) of HCV infection among Western Mexican blood donors, which was comparable to those established for Western countries, but in contrast in our study the most frequent risk factor continues being transfusion followed by household exposure.

Journal Article↗
PubMed2001

Changing epidemiology of parenterally transmitted viral hepatitis: results from the hepatitis surveillance system in Italy.

BACKGROUND: In 1991, compulsory hepatitis B virus vaccination and screening for anti-hepatitis C virus of blood banks were introduced in Italy. AIM: To evaluate the impact of preventive measures on the incidence and risk factors for parenterally transmitted viral hepatitis. METHODS: Data from the surveillance system for acute viral hepatitis for the period 1985-99 were used. Temporal trends in distribution of reported risk factors were analysed by comparing three-year periods: 1987-89 and 1997-99. RESULTS: The incidence (no. cases per 100,000 population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of hepatitis non-A, non-B decreased from 5 to 1 in the same period. These decreases were more evident among young adults and before rather than after 1991. Multiple sexual partners, other parenteral exposures and dental treatment remain the most common risk factors for parenterally transmitted viral hepatitis. An increase in frequency over time was observed for other parenteral exposures, whereas a marked decrease was evident for blood transfusion and household contact with an HB-sAg carrier. Invasive medical procedures continue to represent an important source of infection. Intravenous drug use was reported particularly by young adults with non-A, non-B hepatitis, with increased frequency over time. CONCLUSIONS: Non-immunologic measures for preventing hepatitis B and non-A, non B due to iatrogenic and other parenteral exposures, combined with hepatitis B virus vaccination, could further reduce parenteral transmission.

Acute Disease↗
PubMed2000

Contemporary patterns of adolescent sexuality in urban Botswana.

In Botswana, as in other areas in southern Africa, there is a growing concern about the risks associated with adolescent sexuality. To facilitate the design of policies that can address these problems, it is necessary to gain a thorough understanding of contemporary patterns of adolescent sexual behaviour, and the factors that affect them. This paper examines these issues using data from the 1995 Botswana Adolescent Reproductive Health Survey in conjunction with data from focus group discussions. The results suggest that adolescents become sexually active at an early age, and that many of them, males and females alike, have multiple sex partners. This early sexual initiation implies that adolescent reproductive health programmes should target youths aged 13 or younger. For school-based programmes this implies starting no later than Grade 6 or Standard 1, and preferably earlier. Young males appear to be a particularly vulnerable group that needs further attention. Adolescents perceive that teachers, peers and parents have the largest influence on their reproductive health attitudes. Schools appear to have the most potential for providing reproductive health information, because they reach youths both directly and indirectly by educating their peers. The results also show that male and female sexual behaviour is affected by different factors. Among males, having secondary education strongly increases the odds of being sexually active, presumably because such males make attractive partners. Among females, on the other hand, being in school significantly reduces the odds of being sexually active. This finding is consistent with the policy imposing a one-year school expulsion for pregnant schoolgirls, which was implemented as a deterrent to schoolgirl pregnancy.

Adolescent↗
PubMed1994

Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK).

The introduction of screening for hepatitis C virus (HCV) by the National Blood Transfusion Service identified donors who had acquired HCV infection. We undertook a case-control study amongst blood donors in the Trent Region to determine risks for HCV infection. A total of 74 blood donors confirmed positive for hepatitis C infection and 150 age, sex and donor venue matched controls were included in the study. Fifty-three percent of hepatitis C infected blood donors reported previous use of injected drugs compared to no controls; relative risk (RR) not estimatable (lower limit 95% CI = 20). Other risk factors were a history of: receipt of a blood transfusion or blood products RR = 3.6 (95% CI 1.5-8.3), having been a 'health care worker' RR = 2.8 (95% CI 1.1-7.6), tattooing RR = 3.3 (95% CI 1.2-8.7), and an association with having been born abroad RR = 3.2 (95% CI 1.1-9.5). No risk was shown for a history of multiple sexual partners, ear piercing or acupuncture. Injecting drug use explains more than 50% of hepatitis C infections in blood donors, a group who are less likely to have injected drugs than the general population.

Adult↗
PubMed2006

Analysis of ligand binding and protein dynamics of human retinoid X receptor alpha ligand-binding domain by nuclear magnetic resonance.

Retinoid X receptors (RXRs) are nuclear receptors that can activate transcription as homodimers or as obligate heterodimeric partners of other nuclear receptors. While the crystal structures of the RXR ligand-binding domains (LBD) have been previously determined, the dynamics of activation is less well characterized at an atomic level. To probe the effect of ligand binding on RXR LBD dynamics, we initiated nuclear magnetic resonance studies of recombinant human RXRalpha LBD (T223-T462) with and without bound 9-cis-retinoic acid (9cRA). The 1HN, 15N, 13C(alpha), 13CO, and 13C(beta) resonance assignments were established for 164 of 240 residues in apo-RXRalpha LBD. Resonances corresponding to an additional 47 residues emerged upon 9cRA binding. These additional residues included those located in the vicinity of the ligand-binding pocket (helices H3, H5, and strands S1, S2), as well as residues located at the dimerization interface (helices H9 and H10). Thus 9cRA binding stabilized the ligand-binding pocket and had allosteric effects on the dimerization interface. Ligand-induced chemical shift perturbations outside the binding cavity were mapped to helix H3 and the AF-2 helix H12, indicating conformational changes in these regions. However, helix H11, a component of the tetramerization interface, and a large part of helix H10, a component of the dimerization interface, remained undetectable even after 9cRA binding. Although apo- and holo-hRXRalpha LBD existed predominantly as homodimers in solution, exchange between monomeric, dimeric, and tetrameric forms of the protein could have contributed to line broadening of cross-peaks corresponding to helices H10 and H11. 15N T1, T2, and steady-state {1H}-15N NOE data collected at 500 and 700 MHz static magnetic fields showed that the internal motions for the residues in the H1-H3 loop (K245-D263) were much less restricted than those in the protein core for both apo- and holo-forms. Significant exchange R(ex) contributions to the transverse relaxation rate were detected for most of the residues measured in both apo- and holo-RXRalpha LBDs by transverse relaxation optimized spectroscopy-Carr-Purcell-Meiboom-Gill (CPMG) experiments at two B1 field strengths. Taken together these results suggest that the RXRalpha LBD exists as a dynamic ensemble of conformations, even after binding its cognate ligand. Such dynamic characteristics may allow RXRalpha to partner with multiple nuclear receptors.

Alitretinoin↗
PubMed2006

B-myc: N-terminal recognition of myc binding proteins.

B-Myc is an endogenous, N-terminal homologue of transcription factor c-Myc that lacks the C-terminal DNA binding and protein dimerization domain of c-Myc. Clinical mutations in the c-Myc N-terminal region, and the subsequent misregulation of Myc, are implicated in the development of numerous human cancers. Myc functions to both activate and repress transcription by associating with multiple binding partners. We investigated the structural and dynamical properties of B-Myc, free or associated with the transactivation inhibitor, MM-1, and the activator, TBP, using NMR spectroscopy. B-Myc has no persistent tertiary structure, yet regions corresponding to Myc homology boxes 1 and 2 (MBI and MBII, respectively) have molten globule-like characteristics. B-Myc binds to MM-1 in a specific manner without becoming highly structured. The local regions of B-Myc involved in binding differ for MM-1 and TBP, and regions not identified by mutagenesis are found to be involved in MM-1 binding. The results provide new insights into Myc N-terminal protein-protein interactions. We propose a model for Myc regulation through differential involvement of MBI and MBII in the binding of Myc interacting proteins.

Amino Acid Sequence↗
PubMed2007

Cytochrome c(2) Exit Strategy: Dissociation Studies and Evolutionary Implications.

Small, water-soluble, type c cytochromes form a transient network connecting major bioenergetic membrane protein complexes in both photosynthesis and respiration. In the photosynthesis cycle of Rhodobacter sphaeroides, cytochrome c2 (cyt c2) docks to the reaction center (RC), undergoes electron transfer, and exits for the cytochrome bc1 complex. Translations of cyt c2 about the RC-cyt c2 docking interface and surrounding membrane reveal possible exit pathways. A pathway at a minimal elevation allowed by the architecture of the RC is analyzed using both an all-atom steered molecular dynamics simulation of the RC-cyt c2 complex and a bioinformatic analysis of the structures and sequences of cyt c. The structure-based phylogenetic analysis allows for the identification of structural elements that have evolved to satisfy the requirements of having multiple functional partners. The patterns of evolutionary variation obtained from the phylogenetic analysis of both docking partners of cyt c2 reveal conservation of key residues involved in the interaction interfaces that would be candidates for further experimental studies. Additionally, using the molecular mechanics Poisson-Boltzmann surface area method we calculate that the binding free energy of reduced cyt c2 to the RC is nearly 6 kcal/mol more favorable than with oxidized cyt c2. The redox-dependent variations lead to changes in structural flexibility, behavior of the interfacial water molecules, and eventually changes in the binding free energy of the complex.

Amino Acid Sequence↗
PubMed2000

HIV risk sensitization following a detailed sexual behavior interview: a preliminary investigation.

We administered a detailed structured interview of sexual HIV risk behavior to 110 college students (46% women; mean age = 19.7 years; range = 18-41 years) and assessed their perceived risk of HIV infection before and after the interview. The sexual behavior assessment consisted of 29 single-item frequency questions, followed by a 90-day Timeline Followback interview. Results indicate that sexually active participants experienced HIV risk sensitization during the interview, whereas participants who were not sexually active did not. Among the sexually active participants, those who had multiple sexual partners were more sensitized to their risk than participants with only one partner, and those who engaged in vaginal sex evidenced increased risk perception, but participants who had only oral sex did not. These findings indicate that detailed sexual behavior assessments influence participants' motivation to reduce their risk behavior. This may be helpful in increasing the effectiveness of brief risk behavior interventions such as HIV counseling and testing. These findings may also have implications for the generalizability of HIV prevention interventions to contexts that do not include such detailed assessments.

Adolescent↗
PubMed2000

Implicit cognition and HIV risk behavior.

Implicit cognition theory differs from most other approaches to health behavior in that it emphasizes neurobiologically plausible and experimentally documented memory association processes rather than rational decisions, considerations of pros and cons, or beliefs. The present study of adults from a community population investigated the predictive effects of implicit cognition, as well as behavioral and personality variables (sensation seeking, hostility, conscientiousness, and polydrug use), on risky sexual behaviors (lack of condom use, sex after drug use, and multiple sexual partners). In addition, this study simultaneously investigated the predictors in both a high-risk and a low-risk sample. Results showed that the implicit cognition indicator was a significant, independent predictor of lack of condom use in the high-risk sample. Polydrug use and sensation seeking also had important predictive effects. The results encourage more research on implicit cognition in health behavior and further document links among drug use, personality, and HIV risk behavior.

Adult↗
PubMed2001

Multiple impacts of the HIV/AIDS epidemic on the aged in rural Uganda.

This paper reports research conducted among the aged residents of a rural, Southwestern Ugandan village. It documents their knowledge of HIV/AIDS, their perceptions of their own risk of infection, and the multiple impacts of the current HIV/AIDS epidemic on their lives. Most older individuals have a sound understanding of the sexual transmission of HIV, and some consider themselves to be at risk of infection through having multiple sexual partners. They attempt to limit their children's exposure to HIV, but many of these children have left the village to live in urban areas of relatively high HIV prevalence. The loss of adult children deprives the aged of any support these children might have provided as their parents' capabilities declined with advancing age. Female-headed households were more affected in this way than were male-headed households. The AIDS epidemic has increased the number of burials taking place in the village, and their accumulated costs, both in time and money, and created new hardships for the aged, who also have to cope with grief that accompanies continuing deaths among their children and their contemporaries' children.

Journal Article↗
PubMed2001

Smoking and high-risk sexual behavior among young adults in Hong Kong.

Young adults (n = 964; never married; age, 18-27 years) in Hong Kong were surveyed to obtain information about their smoking habits and sexual behaviors. Current smokers (15% of the entire sample) and those who had ever had sexual intercourse (28%) were more likely to be male, to have ended their education at secondary school, and to report less life satisfaction. After controlling for demographic and psychosocial correlates, sexual intercourse was associated with smoking status for both males and females. Among those who were sexually active, those who had multiple sexual partners, had their first sexual experience prior to age 18 years, and (for males) reported visiting massage parlors were more likely to have a history of smoking. Our findings extend those of our previous study with community adolescents in Hong Kong and suggest that smoking may be a marker for other high-risk behaviors among young Chinese adults.

Adolescent↗