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1.  Changes in weight and weight distribution across the lifespan among HIV-infected and -uninfected men and women 
Medicine  2016;95(46):e5399.
Supplemental Digital Content is available in the text
Examine body composition changes across the lifespan of HIV-infected compared to uninfected adults. Longitudinal study of antiretroviral therapy (ART)-treated HIV-infected and uninfected participants from the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. Body mass index (BMI), waist (WC), hip circumference (HC), and waist-to-height ratio (WHtR) measured at semiannual visits from 1999 to 2014. The age effect on outcomes over time was investigated using multivariate, piecewise, linear mixed-effect regression models adjusted for demographics, substance use, and comorbidities. Person-visits from 2363 men (1059 HIV-infected/1304 HIV-uninfected) and 2200 women (1455 HIV-infected/745 HIV-uninfected), median ages 45 [IQR 39,51] and 40 [32,46], respectively, were included. BMI gains were slower among HIV-infected participants of 40 years or less (P < 0.001), similar between HIV-infected and uninfected persons 40 to 60 years of age, and plateaued after age 60 in both groups. WC and WHtR increased across the age spectrum (P < 0.001) regardless of HIV serostatus, with significantly greater gains in HIV-infected men more than 60. Black race and Hispanic ethnicity were associated with greater BMI and WC. Lower BMI, WC, hip circumference, and WHtR were associated with hepatitis C infection among women only, and with substance use among all participants, and with lower CD4+ cell count and shorter ART duration among HIV-infected participants. Slower BMI gain among younger HIV-infected adults may be partly explained by substance use and hepatitis C infection, and suggests that lower BMI does not represent improved health. Further analysis of muscle and fat abundance and quality will advance understanding of metabolic risk over the lifespan, a key to reducing morbidity in an aging population.
PMCID: PMC5120935  PMID: 27861378
body composition; body mass index; HIV; HIV wasting syndrome; obesity; waist circumference; weight-to-height ratio
2.  Food Perceptions and Dietary Behavior of American-Indian Children, Their Caregivers, and Educators: Formative Assessment Findings from Pathways 
Dietary findings from a school-based obesity prevention project (Pathways) are reported for children from six different American-Indian nations. A formative assessment was undertaken with teachers, caregivers, and children from nine schools to design a culturally appropriate intervention, including classroom curriculum, food service, physical education, and family components. This assessment employed a combination of qualitative and quantitative methods (including direct observations, paired-child in-depth interviews, focus groups with child caregivers and teachers, and semistructured interviews with caregivers and foodservice personnel) to query local perceptions and beliefs about foods commonly eaten and risk behaviors associated with childhood obesity at home, at school, and in the community. An abundance of high-fat, high-sugar foods was detected in children's diets described by caregivers, school food-service workers, and the children themselves. Although children and caregivers identified fruits and vegetables as healthy food choices, this knowledge does not appear to influence actual food choices. Frequent high-fat/high-sugar food sales in the schools, high-fat entrees in school meals, the use of food rewards in the classroom, rules about finishing all of one's food, and limited family resources are some of the competing factors that need to be addressed in the Pathways intervention.
PMCID: PMC5033233  PMID: 27667857
3.  Increased fracture incidence in middle-aged HIV-infected and uninfected women: updated results from the Women’s Interagency HIV Study 
We previously reported that fracture incidence rates did not differ by HIV status among predominantly premenopausal Women's Interagency HIV Study (WIHS) participants. We now conduct a follow-up study with 5 additional observation years, to further characterize fracture risk associated with HIV infection in women as they age.
We measured time to first new fracture at any site in 2375 (1713 HIV-infected, 662 HIV-uninfected) WIHS participants, with median 10 years follow-up. Fractures were self-reported semiannually. Proportional Hazards models assessed predictors of incident fracture.
At index visit, HIV-infected women were older (median age 40 yrs (IQR 34–46) vs. 35 (27–43), p<0.0001) and more likely to be postmenopausal, HCV-infected, and weigh less than HIV-uninfected women. Among HIV-infected women, mean CD4+ count was 480 cells/µL and 63% were taking HAART. Unadjusted incidence rates of any fracture were higher in HIV-infected than uninfected women (2.19/100 person-years (py) vs 1.54/100py, p=0.002). In multivariate models, HIV status, older age, white (vs. black) race, prior fracture, history of cocaine use, and history of injection drug use were significant predictors of incident fracture. Among HIV-infected women, age, white race, prior fracture, smoking, and prior AIDS were predictors of new fracture.
Middle-aged HIV-infected women had a higher adjusted fracture rate than uninfected women. Cocaine use and injection drug use were also associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture associated with cocaine use relates to increased rate of falls, or direct effects on bone metabolism.
PMCID: PMC4557627  PMID: 26322667
HIV; women; bone; fracture; fragility fracture
4.  Racial Differences in Bone Loss and Relation to Menopause Among HIV-infected and Uninfected Women 
Bone  2015;77:24-30.
To characterize changes in bone mineral density (BMD) according to race among HIV-infected and uninfected women, and to evaluate the relationship between race and menopause-related bone loss.
Dual x-ray absorptiometry measured BMD on study entry and a minimum of 18 months later in 246 HIV-infected and 219 HIV-uninfected women in the Menopause Study. Linear regression analyses determined percent annual BMD change at total hip (TH), femoral neck (FN), and lumbar spine (LS) after adjusting for potential confounders. Race-stratified and HIV-infected subgroup analyses were performed.
At baseline, mean age was 45 years, 19% of women were postmenopausal. HIV-infected women were more likely to be black (58% vs. 38%), and had lower BMI and less cigarette exposure when compared to HIV-uninfected women. Women who were perimenopausal at baseline and postmenopausal at follow-up had the greatest TH bone loss (−1.68%/yr, p<.0001) followed by those postmenopausal throughout (−1.02%/yr, p=.007). We found a significant interaction between HIV status and race in multivariate analyses of BMD change at the FN and TH. In race-stratified analyses, HIV infection was associated with TH BMD loss in non-black women. Black women experienced greater menopause-associated decline in TH BMD compared with non-black women.
The association of HIV and BMD differs strikingly by race, as do the effects of the menopausal transition on bone. Determining the extent to which the effect of HIV on fracture risk varies by race will be crucial to identify HIV-infected women at greatest risk for osteoporotic fracture, particularly as they enter menopause.
PMCID: PMC4418198  PMID: 25896953
bone mineral density; menopause; HIV; race; women; osteoporosis
5.  Design and Evaluation of Multi-functional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria 
Biomacromolecules  2011;13(1):239-252.
Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues leading to various pathologies. We report here a mitochondria–targeted nanodelivery system for coenzyme Q10 (CoQ10) which can reach mitochondria, and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A= PEG, B = polycaprolactone (PCL) and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring opening polymerization, self-assembled into nano-sized micelles, and were employed for CoQ10-loading. Drug loading capacity (60 weight%), micelle size (25–60 nm) and stability were determined using a variety of techniques. The micelles had a small critical association concentration, and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by low Flory-Huggins interaction parameter. Confocal microscopy studies of fluorescently labeled polymer analog together with the mitochondria-specific vital dye label, indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range, and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.
PMCID: PMC4911219  PMID: 22148549 CAMSID: cams2055
Coenzyme Q10; mitochondria; drug targeting; miktoarm polymers; click chemistry; polymeric micelles
6.  APOL1 Genotype and Glomerular and Tubular Kidney Injury in Women With HIV 
APOL1 genotype is associated with advanced kidney disease in African-Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury, and with kidney function decline, were evaluated.
Study Design
Observational study.
Setting & Participants
431 HIV-infected African-American women enrolled in Women's Interagency HIV Study (WIHS).
APOL1 genotype.
Albumin-creatinine ratio (ACR), four tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [α1m]), and kidney function estimated using the CKD-EPI cystatin C equation.
Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarker levels were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-up.
At baseline, ACR levels were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs. 11 mg/g; p < 0.001). Compared to women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACR (95% CI, 29-223 mg/g) and 2-fold greater risk of ACR > 30 mg/g (95% CI, 1.17-3.44) after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr, KIM-1:Cr, and NGAL:Cr (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to 1%], and 10% [95% CI, -26% to 64%], respectively), or detectable urine α1m (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared to women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, -2.2 to -0.2) ml/min/1.73 m2 per year, and had 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1-2.5) and 10% annual eGFR decline (95% CI, 1.7-6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarkers.
Results may not be generalizable to men.
Among HIV-infected African-American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.
PMCID: PMC4615696  PMID: 25921719
APOL1 genotype; risk variant; risk allele; G1 allele; G2 allele; single-nucleotide polymorphism (SNP); albumin-creatinine ratio (ACR); proteinuria; tubular injury biomarker; apolipoprotein L1; kidney disease; renal function; glomerular injury; African American; Women's Interagency HIV Study (WIHS)
7.  The structure and duplex context of DNA interstrand crosslinks affects the activity of DNA polymerase η 
Nucleic Acids Research  2016;44(15):7281-7291.
Several important anti-tumor agents form DNA interstrand crosslinks (ICLs), but their clinical efficiency is counteracted by multiple complex DNA repair pathways. All of these pathways require unhooking of the ICL from one strand of a DNA duplex by nucleases, followed by bypass of the unhooked ICL by translesion synthesis (TLS) polymerases. The structures of the unhooked ICLs remain unknown, yet the position of incisions and processing of the unhooked ICLs significantly influence the efficiency and fidelity of bypass by TLS polymerases. We have synthesized a panel of model unhooked nitrogen mustard ICLs to systematically investigate how the state of an unhooked ICL affects pol η activity. We find that duplex distortion induced by a crosslink plays a crucial role in translesion synthesis, and length of the duplex surrounding an unhooked ICL critically affects polymerase efficiency. We report the synthesis of a putative ICL repair intermediate that mimics the complete processing of an unhooked ICL to a single crosslinked nucleotide, and find that it provides only a minimal obstacle for DNA polymerases. Our results raise the possibility that, depending on the structure and extent of processing of an ICL, its bypass may not absolutely require TLS polymerases.
PMCID: PMC5009737  PMID: 27257072
8.  Qualitative study exploring surgical team members' perception of patient safety in conflict-ridden Eastern Democratic Republic of Congo 
BMJ Open  2016;6(4):e009379.
To identify potential barriers to patient safety (PS) interventions from the perspective of surgical team members working in an operating theatre in Eastern Democratic Republic of Congo (DRC).
In-depth interviews were conducted and analysed using qualitative content analysis.
Governmental referral teaching hospital in Eastern DRC.
We purposively selected 2–4 national and expatriate surgical team members from each specialisation. Of the 31 eligible surgical health workers (HWs), 17 volunteered to be interviewed.
Economics issues affected PS throughout the entire health system, from human resources and hospital management, to access to healthcare for patients. Surgical team members seemed embedded in a paternalistic organisational structure and blame culture accompanied by perceived inefficient support services and low salaries. The armed conflict did not only worsen these system failures, it also carried direct threats to patients and HWs, and resulted in complex indirect consequences compromising PS. The increased corruption within health organisations, and population impoverishment and substance abuse among health staff adversely altered safe care. Simultaneously, HWs’ reported resilience and resourcefulness to address barrier to PS. Participants had varying views on external aid depending on its relevance.
The complex links between war and PS emphasise the importance of a comprehensive approach including occupational health to strengthen HWs' resilience, external clinical audits to limit corruption, and educational programmes in PS to support patient-centred care and address blame culture. Finally, improvement of equity in the health financing system seems essential to ensure access to healthcare and safe perioperative outcomes for all.
PMCID: PMC4853980  PMID: 27113232
9.  Occupational health training in India: Need for a competency-driven approach 
In order to cater to the changing business scenario, employment and education profiles of labor, newer occupations, and emerging occupational health challenges, it is time to improve the performance of occupational health professionals by adapting core professional competencies while drawing on global knowledge.
To delineate the competencies required for medical graduates, medical postgraduates, and Masters in Public Health (MPH) graduates practicing occupational health in India.
Materials and Methods:
First, offline and online literature searches were carried out to enlist the core competencies for occupational health. A draft template was prepared for the identified competencies and stakeholders were asked to rank the listed competencies on a three-point scale stating must, desirable, and not required for each of the three categories of professionals, i.e., medical graduates, medical postgraduates, and MPH graduates.
Through the extensive literature search, 23 competencies were identified for occupational health practitioners. According to stakeholders, five competencies were a must, nine were desirable, and nine were not required by a medical graduate. Similarly for a medical postgraduate, except the ability to judge the ergonomic design of the workplace and working tools, which is considered desirable, all other competencies were considered a must while for an MPH graduate all the enlisted 23 competencies were considered a must by the stakeholders.
The framework of occupational health competencies developed through this research can be used to strengthen the training of occupational health professionals in India.
PMCID: PMC4922275  PMID: 27387856
Competency; India; medical graduates; Masters in Public Health; occupational health training
10.  Relationship between Body Mass Index and Mortality in HIV-Infected HAART Users in the Women's Interagency HIV Study 
PLoS ONE  2015;10(12):e0143740.
Early HIV studies suggested protective associations of overweight against mortality, yet data are lacking for the era of potent highly active antiretroviral therapy (HAART). We evaluated associations of pre-HAART initiation body mass index (BMI) with mortality among HAART-using women.
Prospective study of time to death after HAART initiation among continuous HAART users in the Women’s Interagency HIV Study. Unadjusted Kaplan–Meier and adjusted proportional hazards survival models assessed time to AIDS and non-AIDS death by last measured pre-HAART BMI.
Of 1428 continuous HAART users 39 (2.7%) were underweight, 521 (36.5%) normal weight, 441 (30.9%) overweight, and 427 (29.9%) obese at time of HAART initiation. A total of 322 deaths occurred during median follow-up of 10.4 years (IQR 5.9–14.6). Censoring at non-AIDS death, the highest rate of AIDS death was observed among underweight women (p = 0.0003 for all 4 categories). In multivariate models, women underweight prior to HAART died from AIDS more than twice as rapidly vs. normal weight women (aHR 2.04, 95% CI 1.03, 4.04); but being overweight or obese (vs. normal weight) was not independently associated with AIDS death. Cumulative incidence of non-AIDS death was similar across all pre-HAART BMI categories.
Among continuous HAART-using women, being overweight prior to initiation was not associated with lower risk of AIDS or non-AIDS death. Being underweight prior to HAART was associated with over double the rate of AIDS death in adjusted analyses. Although overweight and obesity may be associated with many adverse health conditions, neither was predictive of mortality among the HAART-using women.
PMCID: PMC4689347  PMID: 26699870
11.  Investigating the Effects of Metabolic Dysregulation on Hair Follicles: A Comparison of HIV-Infected Women With and Without Central Lipohypertrophy 
International journal of dermatology  2013;53(10):e443-e448.
Normal lipid metabolism and functioning of the peroxisome proliferator activated receptor gamma (PPAR-gamma) in the sebaceous gland is critical to maintaining a normal hair follicle. Human immunodeficiency virus (HIV) infection affects lipid metabolism; some have hypothesized a link between PPAR-gamma function and lipodystrophy in HIV infection. Our objective was to determine whether lipodystrophy is associated with altered hair characteristics in HIV-infected women from the Women’s Interagency HIV Study (WIHS).
Hair characteristics and scalp inflammation were assessed by an interviewer-administered questionnaire. Central lipohypertrophy and peripheral lipoatrophy was defined by self report of moderate to severe fat gain in central body sites and fat loss in peripheral body sites, respectively confirmed by clinical examination. Additional covariates considered in the analyses included demographics, behavioral characteristics, medical history, and HIV-related factors.
There were 1037 women with data on all study variables. 76 women reported central lipohypertrophy; only 4 women reported lipoatrophy. Women with central lipohypertrophy were more likely to be older, have a self-reported history of injection drug use, statin medication use, diabetes, elevated cholesterol, and have self-reported less hair and shorter eyelashes. After adjustment for age, central lipohypertrophy was associated with shorter eyelashes (OR 2.3; 95% CI 1.4-3.8).
Central lipohypertrophy was not associated with change in scalp hair texture or scalp inflammation in this cohort. Rather, we found an association between central lipohypertrophy and shorter eyelash length. This finding may be explained by an influence of prostaglandin E2 mediators on eyelash follicles.
PMCID: PMC3785560  PMID: 23786579
eyelash; hair; HIV
12.  Serum Albumin and Kidney Function Decline in HIV-Infected Women 
Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in HIV-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women.
Study Design
Retrospective cohort analysis.
Setting & Participants
The study participants were recruited from the Women’s Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and two follow-up measures over an average of 8 years.
The primary predictor was serum albumin concentration.
We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR).
Kidney function decline was determined by cystatin C–based (eGFRcys) and creatinine-based eGFR (eGFRcr) at baseline and follow up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression.
After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFRcys (P<0.001), which was only slightly attenuated to 0.55-mL/min/1.73 m2 after adjustment for albuminuria. Results were similar whether using eGFRcys or eGFRcr. In adjusted analyses, each 0.5-g/dL lower baseline serum albumin was associated with a 1.71-fold greater risk of rapid kidney function decline (p<0.001) and a 1.72-fold greater risk of incident reduced eGFR (p<0.001).
The cohort is composed of only female participants from urban communities within the United States.
Lower levels of serum albumin were strongly associated with kidney function decline and incident reduced eGFR in HIV-infected women, independent of HIV disease status, BMI and albuminuria.
PMCID: PMC4177337  PMID: 25059222
albumin; kidney function; HIV; incident reduced eGFR; albuminuria; disease trajectory; chronic kidney disease (CKD) progression
13.  Family medicine education in India: A panoramic view 
In the recent years, there has been renewed interest in strengthening primary care for improved health services delivery. Family medicine with its holistic principles is an effective approach for building primary care workforce in resource constraint settings. Even though this discipline is well established and mainstreamed in Western countries, the same is yet to occur in low- and middle-income nations. India with its paradigm shift for universal health coverage is strategically poised to embrace family medicine as a core component of its health system. However, till date, a clear picture of family medicine teaching across the country is yet to be available.
This paper makes an attempt to assess the landscape of family medicine teaching in India with an aim to contribute to a framework for bolstering its teaching and practice in coming years. The objective was to obtain relevant information through a detailed scan of the health professional curricula as well as mapping independent academic programs. Specific areas of interest included course content, structure, eligibility criteria, and accreditation.
Our findings indicate that teaching of family medicine is still in infancy in India and yet to be mainstreamed in health professional education. There are variations in family medicine teaching across academic programs.
It is suggested that both medical and nursing colleges should develop dedicated Departments of Family Medicine for both undergraduate and postgraduate teaching. Further, more number of standalone diploma courses adopting blended learning methods should be made available for in-service practitioners.
PMCID: PMC4776598  PMID: 26985405
Family medicine; India; postgraduate; primary care; teaching; undergraduate
14.  Developing core competencies for monitoring and evaluation tracks in South Asian MPH programs 
BMC Medical Education  2015;15:126.
Monitoring and evaluation (M&E) provides vital information for decision-making and its structures, systems and processes are expected to be integrated throughout the life-cycle of public health programs. The acquisition of these skills should be developed in a structured manner and needs educational systems to identify core competencies in M&E teaching. This article presents our work on harmonizing M&E competencies for Masters level programs in the South Asian context and undertaking the global review of M&E track/ concentration offered in various Masters of Public Health (MPH) programs.
Through an online search and snow-balling, we mapped institutions offering M&E tracks/ concentrations in Masters of Public Health (MPH) programs globally. We obtained detailed information about their M&E curriculum from university websites and brochures. The data on curricular contents was extracted and compiled. We analyzed the curricular contents using the framework for core competencies developed by the Association of Schools of Public Health (ASPH); and the Miller’s triangle. This data was then used to inform a consultative exercise aimed at identifying core competencies for an M&E track/ concentration in MPH programs in the South Asian context.
Our curricular review of M&E content within MPH programs globally showed that different domains or broad topic areas relating to M&E are covered differently across the programs. The quantitative sciences (Biostatistics and Epidemiology) and Health Policy and Management are covered in much greater depth than the other two domains (Social & Behavioral Sciences and Environmental Health Sciences). The identification of core competencies for an M&E track/ concentration in the South Asian context was undertaken through a consultative group exercise involving representation from 11 institutions across Bangladesh, India, Nepal and Sri Lanka. During the consultation, the group engaged in a focused discussion to reach consensus on a set of 15 core competencies for an M&E track in South Asian MPH programs.
This work presents an opportunity for institutions to identify and re-examine their M&E competencies as a part of their specialized tracks within MPH programs. Our curricular analysis approach has the potential for adaptation and further use in curriculum analysis across different academic specialties.
PMCID: PMC4523996  PMID: 26238573
Public health education; Monitoring and evaluation; Competencies
15.  Comparison of Polymerase Chain Reaction of Polymorphonuclear Leukocytes and Plasma Identifies Patients Who Control Cytomegalovirus Infection after Hematopoietic Cell Transplantation 
By use of an automated polymerase chain reaction test of plasma and a qualitative polymerase chain reaction assay on polymorphonuclear leukocytes, we identified a subgroup of hematopoietic cell transplant recipients who were able to control cytomegalovirus infection early after hematopoietic cell transplantation without antiviral therapy. Thirty-one percent of patients had cytomegalovirus DNA detected by qualitative polymerase chain reaction assay but had no cytomegalovirus DNA detected by the automated test; this group maintained a lower peak cytomegalovirus load, compared with the group of patients who had cytomegalovirus DNA detected by both tests (P =.03), suggesting a greater degree of functional immune reconstitution.
PMCID: PMC4520826  PMID: 18611158
16.  Urinary Biomarkers of Kidney Injury Are Associated with All-Cause Mortality in the Women’s Interagency HIV Study (WIHS) 
HIV medicine  2013;15(5):291-300.
Chronic kidney disease (CKD) is common in HIV; CKD is associated with mortality. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
We evaluated the association of urinary interleukin-18(IL-18), liver fatty acid binding protein(L-FABP), kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin(NGAL), albumin-to-creatinine ratio(ACR) with 10-year, all-cause death in 908 HIV-infected women. Kidney function was estimated using cystatin C (eGFRcys).
There were 201 deaths during 9,269 person-years of follow-up. After demographic adjustment, compared to the lowest tertile, highest tertiles of IL-18 (HR 2.54,95%CI 1.75–3.68), KIM-1 (2.04,1.44–2.89), NGAL(1.50,1.05–2.14), and ACR(1.63,1.13–2.36) were associated with higher mortality. After multivariable adjustment including eGFRcys, only the highest tertiles of IL-18, (1.88,1.29–2.74) and ACR (1.46,1.01–2.12) remained independently associated with mortality. Findings with KIM-1 were borderline (1.41, 0.99–2.02). We found a J-shaped association between L-FABP and mortality. Compared to persons in the lowest tertile, HR for middle tertile of L-FABP was 0.67 (0.46–0.98) after adjustment. Findings were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools to identify early kidney injury in persons with HIV.
PMCID: PMC3975680  PMID: 24313986
HIV; IL-18; KIM-1; L-FABP; NGAL; urinary biomarkers
17.  Situational analysis of industrial hygienists in India 
Industrial growth in India has resulted in increased employment opportunities thereby inflating the size of the workforce engaged in both organized and unorganized sectors. This workforce is exposed to various occupational factors at workplace and hence is susceptible to occupational diseases, the control of which requires trained occupational health manpower.
The present study was undertaken to map the institutions offering courses to develop industrial hygienist in India, estimate the requirement of such occupational health manpower and to design competencies and curriculum for such a course.
Though there are no norms for the industrial hygienist in the Indian Factories Act, on assumption on the basis of norms provided for Safety Officer, it is estimated that for 26.92 million workforce engaged in organized sector, a total of 5407 Industrial hygienists will be required. Thus there is an estimated deficit of 51% for Industrial hygienist based on current ratio of employment. However on supply side there are only three institutes offering specialized courses on industrial hygiene out of which only one is full time residential course while rest two are offered through distance learning mode.
Therefore, there is a vital need for the development of industrial hygienist not only in quantity but also in quality so that the workers in industries and communities lead socially and environmentally productive lives.
PMCID: PMC4596077  PMID: 26500411
India; Indian factories act; industrial hygienist; occupational health workforce
18.  Changes in Body Mass Index Following HAART Initiation among HIV-Infected Women in the Women's Interagency HIV Study 
Examine changes in, and factors associated with changing body mass index (BMI) in women following highly active antiretroviral therapy (HAART) initiation.
1177 HIV-infected Women's Interagency HIV Study participants who contributed 10,754 years of follow-up following HAART initiation were studied. Changes in median BMI up to 15 years following HAART initiation, and the highest and lowest BMI reached following HAART initiation were summarized by pre-HAART BMI category (<18.5 [underweight], 18.5–<25.0 [normal weight], 25.0–<30.0 [overweight], 30.0–<40.0 [obese], and ≥ 40.0 [morbidly obese]). Multivariate mixed effects ordinal logistic regression estimated the degree of association of each exposure of interest with post-HAART BMI.
Before HAART, 39% percent of women had normal BMI, 31% were overweight, 23% were obese, and 5% were morbidly obese. Following HAART initiation, median BMI change (per 5 years) was 0.21 kg/m2 (90% confidence interval [CI]: −1.33, 0.42) for those with normal pre-HAART BMI, 0.39 kg/m2 (90% CI: 0.15,0.66) for overweight, 0.31 kg/m2 (90% CI: −1.18,0.67) for obese, and −0.36kg/m2 for morbidly obese women. After initiating HAART, 40% with normal pre-HAART BMI became overweight at some point; of those overweight, 46% remained overweight and 47% became obese; 71% of obese women remained obese and 27% became morbidly obese. Each year of nucleoside analog reverse transcriptase inhibitor use was associated with a 3% decreased odds of reaching a higher BMI category (OR 0.97, 95% CI: 0.95, 0.99), while each year of protease inhibitor or non-nucleoside analog reverse transcriptase inhibitor use were associated with a 6% (OR 1.06, 95% CI: 1.04, 1.08) and 5%(OR 1.05, 95% CI: 1.01, 1.08) increased odds of having a higher BMI category, respectively.
Although overweight and obesity are highly prevalent in this large cohort of HIV-infected, minority women, HAART use was associated with only a modest increase in BMI over time.
PMCID: PMC4285631  PMID: 25580365
Obesity; Body mass index; HIV; Women; HAART; Women's interagency HIV study
19.  The Pro-Resolving Lipid Mediator Maresin 1 (MaR1) Attenuates Inflammatory Signaling Pathways in Vascular Smooth Muscle and Endothelial Cells 
PLoS ONE  2014;9(11):e113480.
Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ω-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosis factor alpha (TNF-α) induced inflammatory responses in human vascular endothelial (EC) and smooth muscle cells (VSMC).
Primary cultures of human saphenous vein EC and VSMC were employed. We tested the naturally occurring MaR1 as modulator of TNF-α effects, with examination of monocyte adhesion, oxidant stress, and intracellular inflammatory signaling pathways.
MaR1 attenuated TNF-α induced monocyte adhesion and reactive oxygen species (ROS) generation in both EC and VSMC, associated with down-regulated expression (cell surface) of the adhesion molecule E-selectin (in EC) and NADPH-oxidases (NOX4, NOX1, NOX2). MaR1 attenuated TNF-α induced release of pro-inflammatory mediators by EC and VSMC. MaR1 caused an attenuation of TNF-α induced NF-κB activation in both cell types associated with inhibition of I-κ Kinase (IKK) phosphorylation, IκB-α degradation and nuclear translocation of the NF- κB p65 subunit. MaR1 also caused a time-dependent increase in intracellular cyclic AMP (cAMP) in both naive and TNF-α stimulated VSMC and EC.
MaR1 has broad anti-inflammatory actions on EC and VSMC, which may be partly mediated through up-regulation of cAMP and down-regulation of the transcription factor NF-κB. The results suggest that the pro-resolving lipid mediator MaR1 exerts homeostatic actions on vascular cells that counteract pro-inflammatory signals. These findings may have direct relevance for acute and chronic states of vascular inflammation.
PMCID: PMC4237455  PMID: 25409514
20.  Development of a technical assistance framework for building organizational capacity of health programs in resource-limited settings 
Little information exists on the technical assistance needs of local indigenous organizations charged with managing HIV care and treatment programs funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR). This paper describes the methods used to adapt the Primary Care Assessment Tool (PCAT) framework, which has successfully strengthened HIV primary care services in the US, into one that could strengthen the capacity of local partners to deliver priority health programs in resource-constrained settings by identifying their specific technical assistance needs.
Qualitative methods and inductive reasoning approaches were used to conceptualize and adapt the new Clinical Assessment for Systems Strengthening (ClASS) framework. Stakeholder interviews, comparisons of existing assessment tools, and a pilot test helped determine the overall ClASS framework for use in low-resource settings. The framework was further refined one year post-ClASS implementation.
Stakeholder interviews, assessment of existing tools, a pilot process and the one-year post- implementation assessment informed the adaptation of the ClASS framework for assessing and strengthening technical and managerial capacities of health programs at three levels: international partner, local indigenous partner, and local partner treatment facility. The PCAT focus on organizational strengths and systems strengthening was retained and implemented in the ClASS framework and approach. A modular format was chosen to allow the use of administrative, fiscal and clinical modules in any combination and to insert new modules as needed by programs. The pilot led to refined pre-visit planning, informed review team composition, increased visit duration, and restructured modules. A web-based toolkit was developed to capture three years of experiential learning; this kit can also be used for independent implementation of the ClASS framework.
A systematic adaptation process has produced a qualitative framework that can inform implementation strategies in support of country led HIV care and treatment programs. The framework, as a well-received iterative process focused on technical assistance, may have broader utility in other global programs.
PMCID: PMC4175633  PMID: 25230690
HIV; Health system strengthening; PEPFAR; Technical assistance; ART; Sustainability; Capacity building
21.  Building public health capacity in Madhya Pradesh through academic partnership 
Global Health Action  2014;7:10.3402/gha.v7.24839.
Engaging in partnerships is a strategic means of achieving objectives common to each partner. The Post Graduate Diploma in Public Health Management (PGDPHM) partners in consultation with the government and aims to strengthen the public health managerial capacity. This case study examines the PGDPHM program conducted jointly by the Public Health Foundation of India and the Government of Madhya Pradesh (GoMP) at the State Institute of Health Management and Communication, Gwalior, which is the apex training and research institute of the state government for health professionals. This is an example of collaborative partnership between an academic institution and the Department of Public Health and Family Welfare, GoMP. PGDPHM is a 1-year, fully residential course with a strong component of field-based project work, and aims to bridge the gap in public health managerial capacity of the health system through training of health professionals. The program is uniquely designed in the context of the National Rural Health Mission and uses a multidisciplinary approach with a focus on inter-professional education. The curriculum is competency driven and health systems connected and the pedagogy uses a problem-solving approach with multidisciplinary faculty from different programs and practice backgrounds that bring rich field experience to the classroom. This case study presents the successful example of the interface between academia and the health system and of common goals achieved through this partnership for building capacity of health professionals in the state of Madhya Pradesh over the past 3 years.
PMCID: PMC4134670  PMID: 25128807
public health management; capacity building; partnership; Madhya Pradesh; NRHM; academics; health system
22.  Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia 
AIDS care  2013;25(7):863-873.
There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users. Our application of intervention mapping strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling and Information-Motivation-Behavioral Skills Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial which is underway to evaluate the intervention (results due in spring 2013).
PMCID: PMC3651786  PMID: 23391132
ART; HAART; adherence; intervention
23.  Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: the SMART Body Composition Substudy 
Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomised to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline, months 4 and 12; BMD at the spine (dual X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared to the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p≤0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, while increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.
PMCID: PMC3657331  PMID: 23299909
HIV; bone mineral density; antiretroviral therapy; bone turnover marker
24.  Vitamin D and Insulin Resistance in Non-Diabetic Women's Interagency HIV Study Participants 
AIDS Patient Care and STDs  2013;27(6):320-325.
We explored the relationship between vitamin D levels and insulin resistance (IR) among 1082 nondiabetic (754 HIV-infected) women enrolled in the Women's Interagency HIV study (WIHS), a large and well-established cohort of HIV infected and uninfected women in the US. Vitamin D levels 20–29 ng/mL were considered insufficient and <20 ng/mL deficient. IR was estimated using the homeostasis model assessment (HOMA) and a clinically significant cut-off ≥2.6 was used for HOMA-IR. In the unadjusted analysis, women who were vitamin D insufficient or deficient were 1.62 (95% CI: 1.01–2.61, p=0.05) and 1.70 (95% CI: 1.11–2.60, p=0.02) times more likely to have HOMA values≥2.6 compared to women with sufficient vitamin D. The association did not remain significant after adjustment for factors associated with IR. Among the 754 HIV-infected women, current PI use (OR 1.61, 95% CI: 1.13–2.28, p=0.008) remained independently associated with HOMA ≥2.6 while vitamin D insufficiency (OR 1.80, 95% CI: 0.99–3.27, p=0.05) was marginally associated with HOMA ≥2.6 after adjustment. Ethnicity, body mass index, smoking status, and hepatitis C status were independently associated with insulin resistance in HIV-infected and uninfected women. We found a marginally significant association between vitamin D insufficiency and insulin resistance among nondiabetic HIV-infected WIHS women.
PMCID: PMC3671624  PMID: 23675750
25.  Relationship of vitamin D, HIV, HIV treatment and lipid levels in the Women’s Interagency HIV study (WIHS) of HIV-infected and un-infected women in the US 
Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±ART) were investigated with Women’s Interagency HIV Study data (n=1758 middle-aged women) using multivariable regression. 63 % had vitamin D deficiency. Median 25-OH vitamin D was highest in HIV-infected +ART-treated women (17 ng/mL, p<0.001), but the same in HIV-uninfected or HIV-infected without ART (14 ng/mL). Vitamin D levels were lower if ART included efavirenz (15 vs 19 ng/mL, p<0.001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected +ART, (13%, vs 7% of HIV-infected without ART and 5% of HIV-uninfected (p<0.001) with a positive relationship between 25-OH-D and triglycerides (95% confidence interval 0.32 to 1.69, p<.01). No relationships between 25-OH-D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART treated HIV infected, and unrelated to cholesterol.
PMCID: PMC4016117  PMID: 24668135
Vitamin D; lipids; HIV infected; HIV uninfected; 25-OH vitamin D; cholesterol; LDL-cholesterol; triglycerides; lipids; WIHS

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