Prevalence of kidney disease in HIV-infected and uninfected Rwandan women

Background

In the United States, HIV-related kidney disease disproportionately affects individuals of African descent; however, there are few estimates of kidney disease prevalence in Africa. We evaluated the prevalence of kidney disease among HIV-infected and uninfected Rwandan women.

Methods

The Rwandan Women''s Interassociation Study and Assessment prospectively enrolled 936 women. Associations with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m² and proteinuria were assessed in separate logistic regression models.

Results

Among 891 non-pregnant women with available data, 2.4% had an eGFR<60 mL/min/1.73 m² (calculated by the Modification of Diet in Renal Disease equation, MDRD eGFR) and 8.7% had proteinuria ≥1+. The prevalence of decreased eGFR varied markedly depending on the estimating method used, with the highest prevalence by Cockcroft-Gault. Regardless of the method used to estimate GFR, the proportion with decreased eGFR or proteinuria did not differ significantly between HIV-infected and -uninfected women in unadjusted analysis. After adjusting for age and blood pressure, HIV infection was associated with significantly higher odds of decreased MDRD eGFR but not proteinuria.

Conclusion

In a well-characterized cohort of Rwandan women, HIV infection was associated with decreased MDRD eGFR. The prevalence of decreased eGFR among HIV-infected women in our study was lower than that previously reported in African-Americans and in other Central and East African HIV populations, although there was substantial variability depending on the equation used to estimate GFR. Future studies are needed to optimize GFR estimates and to determine the impact of antiretroviral therapy on kidney disease in this population.     

Association of pre-treatment nutritional status with change in CD4 count after antiretroviral therapy at 6, 12, and 24 months in Rwandan women

Background

Body mass index (BMI) independently predicts mortality in studies of HIV infected patients initiating antiretroviral therapy (ART). We hypothesized that poorer nutritional status would be associated with smaller gains in CD4 count in Rwandan women initiating ART.

Methods and Findings

The Rwandan Women''s Interassociation Study and Assessment, enrolled 710 ART-naïve HIV-positive and 226 HIV-negative women in 2005 with follow-up every 6 months. The outcome assessed in this study was change in CD4 count at 6, 12, and 24 months after ART initiation. Nutritional status measures taken prior to ART initiation were BMI; height adjusted fat free mass (FFMI); height adjusted fat mass (FMI), and sum of skinfold measurements. 475 women initiated ART. Mean (within 6 months) pre-ART CD4 count was 216 cells/µL. Prior to ART initiation, the mean (±SD) BMI was 21.6 (±3.78) kg/m² (18.3% malnourished with BMI<18.5); and among women for whom the following were measured, mean FFMI was 17.10 (±1.76) kg/m²; FMI 4.7 (±3.5) kg/m² and sum of skinfold measurements 4.9 (±2.7) cm. FFMI was significantly associated with a smaller change in CD4 count at 6 months in univariate analysis (−6.7 cells/uL per kg/m², p  = 0.03) only. In multivariate analysis after adjustment for covariates, no nutritional variable was associated with change in CD4 count at any follow up visit.

Conclusion

In this cohort of African women initiating ART, no measure of malnutrition prior to ART was consistently associated with change in CD4 count at 6, 12, and 24 months of follow up, suggesting that poorer pre-treatment nutritional status does not prevent an excellent response to ART.     

Risk factors for cervical precancer and cancer in HIV-infected, HPV-positive Rwandan women

Background

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).

Methods

In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.

Results

Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm³, CI = 0.40-0.97).

Conclusions

In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.     

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity

Background and aimPrevious evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity.MethodsPlasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n = 78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group.ResultsIn the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.390, P < 0.05) and with fatty acid binding protein-4 (FABP4) (r = 0.474, P < 0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r = ?467, P < 0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r = 0.413, P < 0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r = ?0.429, P < 0.05).ConclusionsThese results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.     

Interaction of ergosterol with bovine serum albumin and human serum albumin by spectroscopic analysis

This study was designed to examine the interactions of ergosterol with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with the drug concentrations in the range of 2.99-105.88?μM and the concentration of proteins was fixed at 5.0?μM. The analysis of emission spectra quenching at different temperatures revealed that the quenching mechanism of HSA/BSA by ergosterol was the static quenching. The number of binding sites n and the binding constants K were obtained at various temperatures. The distance r between ergosterol and HSA/BSA was evaluated according to F?ster non-radioactive energy transfer theory. The results of synchronous fluorescence, 3D fluorescence, FT-IR, CD and UV-Vis absorption spectra showed that the conformations of HSA/BSA altered in the presence of ergosterol. The thermodynamic parameters, free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS) for BSA-ergosterol and HSA-ergosterol systems were calculated by the van't Hoff equation and discussed. Besides, with the aid of three site markers (for example, phenylbutazone, ibuprofen and digitoxin), we have reported that ergosterol primarily binds to the tryptophan residues of BSA/HSA within site I (subdomain II A).     

Bilirubin binding properties of pigeon serum albumin and its comparison with human serum albumin

Binding of bilirubin (BR) to pigeon serum albumin (PgSA) was studied by absorption, fluorescence and CD spectroscopy and results were compared with those obtained with human serum albumin (HSA). PgSA was found to be structurally similar to HSA as judged by near- and far-UV CD spectra. However, PgSA lacks tryptophan. Binding of BR to PgSA showed relatively weaker interaction compared to HSA in terms of binding affinity, induced red shift in the absorption spectrum of BR and CD spectral characteristics of BR-albumin complexes. Photoirradiation results of BR-albumin complexes also showed PgSA-bound BR more labile compared to HSA-bound BR.     

Association between age at menarche and early-life nutritional status in rural Bangladesh

Age at menarche is associated with anthropometry in adolescence. Recently, there has been growing support for the hypothesis that timing of menarche may be set early in life but modified by changes in body size and composition in childhood. To evaluate this, a cohort of 255 girls aged <5 years recruited in 1988 were followed up in 2001 in Matlab, Bangladesh. The analysis was based on nutritional status as assessed by anthropometry and recalled age at menarche. Data were examined using lifetable techniques and the Cox regression model. The association between nutritional status indicators and age at menarche was examined in a multivariate model adjusting for potential confounding variables. Censored cases were accounted for. The median age at menarche was 15.1 years. After controlling for early-life predictors (birth size, childhood underweight, childhood stunting) it appeared that adolescent stunting stood out as the most important determinant of age at menarche. Adolescent stunting still resonates from the effect of stunting in early childhood (OR respectively 2.63 (p<0.01 CI: 1.32-5.24) and 8.47 (p<0.001 CI: 3.79-18.93) for moderately and severely stunted under-fives as compared with the reference category). Birth size was not a significant predictor of age at menarche. It is concluded that age at menarche is strongly influenced by nutritional status in adolescence, notably the level of stunting, which is in turn highly dependent on the level of stunting in early childhood. A 'late' menarche due to stunting may be detrimental for reproductive health in case of early childbearing because of the association between height and pelvic size.     

Fertility among HIV-infected Indian women: the biological effect and its implications

In India, nearly one million women of childbearing age are infected with HIV. This study sought to examine the biological effect of HIV on the fertility of HIV-infected Indian women. This is relevant for the provision of pregnancy-related counselling and care to the infected women, and for estimating the HIV prevalence among women and children. The study used retrospectively collected data from the National Family Health Survey (2005-2006) and applied a matched case control study design to compare the effect of HIV on conception, pregnancy rates and pregnancy outcomes among HIV-infected (N=69) and HIV-non-infected (N=345) women, both unaware of their HIV status. Pregnancy rates and pregnancy outcomes were compared through non-parametric statistical tests, whereas the effect of HIV on fecundity was studied by analysing the interval between last two pregnancies using Cox regression. The pregnancy rate was observed to be lower among HIV-infected than HIV-non-infected women (RR=0.77). The difference, however, was not statistically significant (p=0.064). There was also no statistically significant difference in the interval between last two pregnancies (p=0.898). Significantly higher number of pregnancies among HIV-infected women resulted in termination because of miscarriage or stillbirths (p=0.004). Therefore, while providing clinical care and counselling to infected women, the possibility of adverse pregnancy outcomes should be considered. Due to the higher rate of adverse pregnancy outcomes, attendance of HIV-infected women at antenatal clinics might be greater, which could lead to overestimation of HIV prevalence derived from antenatal care surveillance sites.     

Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

Introduction

Genital tuberculosis (GTB) in women is one of the common causes of infertility in emerging countries. As an intracellular pathogen, Mycobacterium tuberculosis in the endometrium significantly alters the host metabolism in dormant GTB cases. Nuclear magnetic resonance (NMR) based metabolic profiling has emerged as a useful tool for identification of biomarkers in biological fluids.

Objective

To investigate NMR based serum metabolic profile of dormant GTB women as compared to controls.

Methods

Dormant GTB women (n = 26) and unexplained infertile women (controls; n = 26), healthy proven fertile women undergoing voluntary sterilization (n = 25) and women undergoing recurrent spontaneous miscarriage (RSM) (n = 27) were included in the study. 700 MHz proton NMR spectra of serum collected from these patients were recorded. Multivariate analysis including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structure-discriminant analysis was applied to all the spectra. Association of dysregulated serum metabolites with our earlier findings related to altered endometrial tissue metabolites in dormant GTB women was studied using multiple correlation analysis.

Results

This study indicates a clear metabolic differentiation between women with dormant GTB and controls. Metabolites including 3-hydroxybutyrate, succinate, citrate, acetate, l-glutamine, l-lysine, glutamate, l-threonine and 1-methyl histidine were found to be significantly upregulated in serum of women with dormant GTB compared with controls. Pearson’s correlation analysis showed a significant correlation between the expression of endometrial tissue and serum metabolites.

Conclusions

The set of identified metabolites may be considered as candidate markers for the diagnosis of dormant GTB and help clinicians in early therapeutic management.

     

Rapid diagnosis of smear-negative tuberculosis using immunology and microbiology with induced sputum in HIV-infected and uninfected individuals

Rationale and Objectives

Blood-based studies have demonstrated the potential of immunological assays to detect tuberculosis. However lung fluid sampling may prove superior as it enables simultaneous microbiological detection of mycobacteria to be performed. Until now this has only been possible using the expensive and invasive technique of broncho-alveolar lavage. We sought to evaluate an immunoassay using non-invasive induced-sputum to diagnose active tuberculosis.

Methods and Results

Prospective cohort study of forty-two spontaneous sputum smear-negative or sputum non-producing adults under investigation for tuberculosis. CD4 lymphocytes specific to purified-protein-derivative of Mycobacterium tuberculosis actively synthesising interferon-gamma were measured by flow cytometry and final diagnosis compared to immunoassay using a cut-off of 0.5%. Sixteen subjects (38%) were HIV-infected (median CD4 count [range] = 332 cells/µl [103–748]). Thirty-eight (90%) were BCG-vaccinated. In 27 subjects diagnosed with active tuberculosis, the median [range] percentage of interferon-gamma synthetic CD4+ lymphocytes was 2.77% [0–23.93%] versus 0% [0–2.10%] in 15 negative for active infection (p<0.0001). Sensitivity and specificity of the immunoassay versus final diagnosis of active tuberculosis were 89% (24 of 27) and 80% (12 of 15) respectively. The 3 positive assays in the latter group occurred in subjects diagnosed with quiescent/latent tuberculosis. Assay performance was unaffected by HIV-status, BCG-vaccination or disease site. Combining this approach with traditional microbiological methods increased the diagnostic yield to 93% (25 of 27) alongside acid-fast bacilli smear and 96% (26 of 27) alongside tuberculosis culture.

Conclusions

These data demonstrate for the first time that a rapid immunological assay to diagnose active tuberculosis can be performed successfully in combination with microbiological methods on a single induced-sputum sample.     

The nature of the nutritional importance of serum albumin to Glossina morsitans

The nutritional significance of albumin protein and its constituent amino acids or associated impurities to Glossina morsitans was evaluated. Flies fed serum-free or albumin-free diets or diets containing delipidated serum or delipidated albumin failed to reproduce. The sizes of offspring produced by flies fed on diets containing different commercial albumins varied in proportion to the amount of bound lipid present in the albumin. FLies fed on albumin-containing diets supplemented with serum lipoproteins produced heavier offspring than flies fed on unsupplemented diets or on diets supplemented by other serum proteins. Delipidation of serum lipoproteins abolished this supplementary effect suggesting a possible similarity between lipoprotein-associated and albumin-bound lipid in terms of their importance to the nutrition and reproduction of tsetse. It is concluded that the observed nutritional importance of albumin to tsetse flies may derive from albumin-associated substances rather than albumin per se.     

Immunocorrection of the physiologic status of white rats by sidnofen conjugates with bovine serum albumin

The effect of immunisation by covalent conjugates of known psychostimulant and antidepressant sydnophen with bovine serum albumin (BSA) on behaviour, formation of conditioned reflex reactions and alcoholization of white rats has been studied. The immunization of sydnophen with BSA by conjugates permits to obtain a long-term alteration of the emotional status: suppression of behavioral activity, learning and alcohol attraction of rats similar in some elements to the action of neuroleptic drugs. The direction of these alterations is opposite to ones caused by the action of sydnophen. It gives possibility to consider fruitful the conception on the ways of long-term immunocorrection of the physiological status of organism.     

Association between parity and risk of suicide among parous women

Background

There are limited empirical data to support the theory of a protective effect of parenthood against suicide, as proposed by Durkheim in 1897. I conducted this study to examine whether there is an association between parity and risk of death from suicide among women.

Methods

The study cohort consisted of 1 292 462 women in Taiwan who had a first live birth between Jan. 1, 1978, and Dec. 31, 1987. The women were followed up from the date of their first birth to Dec. 31, 2007. Their vital status was ascertained by means of linking records with data from a computerized mortality database. Cox proportional hazard regression models were used to estimate hazard ratios of death from suicide associated with parity.

Results

There were 2252 deaths from suicide during 32 464 187 person-years of follow-up. Suicide-related mortality was 6.94 per 100 000 person-years. After adjustment for age at first birth, marital status, years of schooling and place of delivery, the adjusted hazard ratio was 0.61 (95% confidence interval [CI] 0.54–0.68) among women with two live births and 0.40 (95% CI 0.35–0.45) among those with three or more live births, compared with women who had one live birth. I observed a significantly decreasing trend in adjusted hazard ratios of suicide with increasing parity.

Interpretation

This study provides evidence to support Durkheim’s hypothesis that parenthood confers a protective effect against suicide.Childbearing is considered to have long-term effects on women’s health.¹ However, little is known about the relation between parity and mortality among women except for cancers of the reproductive organs.²In his book on suicide published in 1897, Durkheim concluded that the rate of death from suicide was lower among married women than among unmarried women because of the effect of parenthood and not marriage per se.³ Three studies since then have explored Durkheim’s hypothesis. In the first, published almost 100 years later, Hoyer and Lund conducted a prospective study in Norway involving 989 949 married women aged 25 years or older who were followed up for 15 years.⁴ They reported a negative association between suicide-related mortality and number of children. In a nested case–control study in Denmark involving 6500 women who committed suicide between Jan. 1, 1981, and Dec. 31, 1997, and 130 000 matched control subjects, Qin and Mortensen found a significantly decreased risk of suicide with increasing number of children.⁵ In the third study, 12 055 pregnant women in Finland were followed up from delivery in 1966 until 2001; the authors found a decreasing trend in suicide-related mortality with increasing parity.¹One reason for the limited empirical evidence exploring Durkheim’s hypothesis may have to do with sample size and study design.⁴ Only studies involving representative suicides from the general population could make it possible to achieve sufficient power to detect the effect of parity on rare events such as suicide.^1,4,5 Even in the prospective study involving 989 949 women followed for 15 years, only 11 deaths from suicide occurred among women with six or more children.⁴In Taiwan, suicide is the eighth leading cause of death among men and the ninth among women. The age-adjusted rate of death from suicide was 19.7 per 100 000 among men and 9.7 among women in 2007.⁶ Suicide rates in Western countries have been generally lower than those in Asian countries.⁷ A consistent increase in the suicide rate since 1999 has been found in Taiwan.⁶ However, most Western countries have had stable or slightly decreasing rates during the 1990s.^8,9 The male:female ratio of suicide is frequently greater than 3:1 in Western countries,⁷ whereas it is 2:1 in Taiwan.¹⁰ High suicide rates among Chinese women have been well documented.¹¹ One explanation is that Chinese women do not benefit from marriage as much as their male counterparts.¹² The sex difference in suicide rates is largely driven by a high rate of suicide among women in Chinese societies.¹¹ In many Western countries, the trend over the past several years has been in the opposite direction: rates among women have been stable or decreasing, whereas rates among men have been increasing.¹² Furthermore, in an epidemiologic study of suicides in Chinese communities, the prevalence of mental illness among people committing suicide was much lower in those communities than in Western societies.¹³Because the previous studies that related parity and suicide-related mortality were carried out in economically developed countries and because different cultural settings might influence suicide patterns,³ I undertook the present study in Taiwan, using a cohort of women who had a first and singleton live birth between Jan. 1, 1978, and Dec. 31, 1987, to explore further Durkheim’s hypothesis.     

Association of morning illumination and window covering with mood and sleep among post-menopausal women

Sleep and Biological Rhythms - The antidepressant and sleep-promoting effects of light exposure might be useful for treating age-related mood and sleep disorders. In view of recent evidence...