HIV Prevalence and Associated Risk Factors among Individuals Aged 13-34 Years in Rural Western Kenya

Objectives

To estimate HIV prevalence and characterize risk factors among young adults in Asembo, rural western Kenya.

Design

Community-based cross-sectional survey.

Methods

From a demographic surveillance system, we selected a random sample of residents aged 13-34 years, who were contacted at home and invited to a nearby mobile study site. Consent procedures for non-emancipated minors required assent and parental consent. From October 2003 - April 2004, consenting participants were interviewed on risk behavior and tested for HIV and HSV-2. HIV voluntary counseling and testing was offered.

Results

Of 2606 eligible residents, 1822 (70%) enrolled. Primary reasons for refusal included not wanting blood taken, not wanting to learn HIV status, and partner/parental objection.Females comprised 53% of 1762 participants providing blood. Adjusted HIV prevalence was 15.4% overall: 20.5% among females and 10.2% among males. HIV prevalence was highest in women aged 25-29 years (36.5%) and men aged 30-34 years (41.1%). HSV-2 prevalence was 40.0% overall: 53% among females, 25.8% among males. In multivariate models stratified by gender and marital status, HIV infection was strongly associated with age, higher number of sex partners, widowhood, and HSV-2 seropositivity.

Conclusions

Asembo has extremely high HIV and HSV-2 prevalence, and probable high incidence, among young adults. Further research on circumstances around HIV acquisition in young women and novel prevention strategies (vaccines, microbicides, pre-exposure prophylaxis, HSV-2 prevention, etc.) are urgently needed.     

Behavioral and Psychological Factors in the Assessment and Treatment of Obesity Surgery Patients

Objective: To provide evidence‐based guidelines on the psychological and behavioral screening of weight loss surgery (WLS) candidates and the impact of psychosocial factors on behavior change after gastric bypass surgery. Research Methods and Procedures: The members of the Behavioral and Psychological subgroup of the Multidisciplinary Care Task Group conducted searches of MEDLINE and PubMed for articles related to WLS, behavior changes, and mental health, including quality of life (QOL) and behavior modification. Pertinent abstracts and literature were reviewed for references. A total of 198 abstracts were identified; 17 papers were reviewed in detail. Search periods were from 1980 to 2004. Results: We found a high incidence of depression, negative body image, eating disorders, and low QOL in severely obese patients. Our task subgroup recommended that all WLS candidates be evaluated by a licensed mental health care provider (i.e., psychiatrist, psychologist, or social worker), experienced in the treatment of severely obese patients and working within the context of a multidisciplinary care team. We also recommended development of pre‐ and postsurgical treatment plans that address psychosocial contraindications for WLS and potential barriers to postoperative success. Discussion: The psychological consequences of obesity can range from lowered self‐esteem to clinical depression. Rates of anxiety and depression are three to four times higher among obese individuals than among their leaner peers. A comprehensive multidisciplinary program that incorporates psychological and behavior change services can be of critical benefit in enhancing compliance, outcome, and QOL in WLS patients.     

Adipocyte Differentiation‐related Protein in Human Skeletal Muscle: Relationship to Insulin Sensitivity

Objective: To determine whether adipocyte differentiation‐related protein (ADRP), a lipid droplet—associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non‐diabetic (OND) and obese diabetic (OD) subjects. Research Methods and Procedures: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A_1C, fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting. Results: ADRP was highly expressed in SkM from OND (4.4 ± 1.54 AU/10 μg, protein, n = 10) and OD (5.02 ± 1.33 AU/10 μg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 ± 2.15 AU/10 μg to 9.92 ± 1.57 AU/10 μg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 ± 1.07 AU/10 μg, n = 6) displayed up‐regulation of ADRP expression (to 9.27 ± 2.76 AU/10 μg, p < 0.025). Discussion: ADRP is the predominant lipid droplet—associated protein in SkM, and low ADRP expression is up‐regulated in circumstances of improved glucose tolerance. Up‐regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.     

Estradiol and the estradiol metabolite, 2-hydroxyestradiol, activate AMP-activated protein kinase in C2C12 myotubes

Objective: Systemic loss of estradiol (E2) during menopause is associated with increased adiposity which can be prevented with E2 replacement. Rodent studies suggest that E2, or lack of, is a key mediator in menopause‐related metabolic changes. We have previously demonstrated that E2 treatment produces a rapid, dose‐dependent activation of AMP‐activated protein kinase (AMPK) in murine skeletal muscle. Activation of AMPK is implicated in the therapeutic benefits of many insulin sensitizing agents including metformin and thiazolidinediones. Here, we expand our observations and provide novel data which demonstrate that in addition to E2, its metabolite 2‐hydroxyestradiol (2‐HE2), activate AMPK in C2C12 myotubes. Methods and Procedures: C2C12 myotubes were used to examine the effects on E2 and the by‐products of its metabolism on AMPK activation. Results: Low concentrations of E2 (10 and 100 nmol/l) were found to increase AMPK phosphorylation by ～1.6‐fold, while a higher concentration (10 μmol/l) resulted in a ～3.0‐fold increase. In comparison to E2 treatment alone, incubation of myotubes with E2 and 1‐aminobenzotriazole (ABT) (a CYP450 inhibitor that blocks metabolism of E2) caused AMPK activation to be enhanced at low E2 concentrations, but attenuated at higher concentrations. The effects of ABT suggested that one or more E2 metabolites contribute to the maximal activation of AMPK at high E2 concentrations. Indeed, the estrogen metabolite 2‐HE2, but not 2‐methoxyestradiol (2‐ME2), directly activated AMPK in C2C12 myotubes. Discussion: We propose a model where E2, acting through its metabolite 2‐HE2 and the estrogen receptors (ERs), activates AMPK in myotubes. Finally, activation is abolished when all E2 is metabolized to 2‐ME2.     

Spermatogonial stem cell sensitivity to capsaicin: An in vitro study

Background

The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction.

Methods

In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells), placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3) and abnormal (n = 9) pregnancies.

Results

Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p < 0.001) when compared to placentae from abnormal ones (gestational diabetes, pregnancy induced hypertension, drug abuse).

Conclusion

These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.     

Preneoplastic lesions of the lung

Lung cancer is the leading cause of cancer deaths worldwide. If we can define and detect preneoplastic lesions, we might have a chance of improving survival. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. In this review we summarize the data supporting the preneoplastic nature of these lesions, and delve into some of the genetic changes found in atypical adenomatous hyperplasia and squamous dysplasia/carcinoma in situ.     

Gender‐Specific Association of a Perilipin Gene Haplotype with Obesity Risk in a White Population

Objective: Perilipin is a class of protein‐coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single‐nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI ≥ 30 kg/m². Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. Discussion: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.     

Evolutionary constraint and adaptation in the metabolic network of Drosophila

Organisms must carefully control their metabolism in order to survive. On the other hand, enzymes must adapt in response to evolutionary pressures on the pathways in which they are imbedded. Taking advantage of the newly available whole-genome sequences of 12 Drosophila species, we examined how protein function and metabolic network architecture influence rates of enzyme evolution. We found that despite high overall constraint, there were significant differences in rates of amino acid substitution among functional classes of enzymes. This heterogeneity arises because proteins involved in the metabolism of foreign compounds evolve relatively rapidly, whereas enzymes that act in "core" metabolism exhibit much slower rates of amino acid replacement, suggesting strong selective constraint. Network architecture also influences enzymes' rates of amino acid replacement. In particular, enzymes that share metabolites with many other enzymes are relatively constrained, although apparently not because they are more likely to be essential. Our analyses suggest that this pattern is driven by strong constraint of enzymes acting at branch points in metabolic pathways. We conclude that metabolic network architecture and enzyme function separately affect enzyme evolution rates.