Mohan Thanikachalam

Evidence for the healthy immigrant effect in older Chinese immigrants: a cross-sectional study

BackgroundPrevious work has found that first-generation immigrants to developed nations tend to have better health than individuals born in the host country. We examined the evidence for the healthy immigrant effect and convergence of health status between Chinese immigrants (n = 147) and U.S. born whites (n = 167) participating in the cross-sectional Community Assessment of Freeway Exposure and Health study and residing in the same neighborhoods.MethodsWe used bivariate and multivariate models to compare disease prevalence and clinical biomarkers.ResultsDespite an older average age and lower socioeconomic status, Chinese immigrants were less likely to have asthma (OR = 0.20, 95% CI = 0.09–0.48) or cardiovascular disease (OR = 0.44, 95% CI = 0.20–0.94), had lower body mass index (BMI), lower inflammation biomarker levels, lower average sex-adjusted low-density lipoprotein (LDL) cholesterol, and higher average sex-adjusted high-density lipoprotein (HDL) cholesterol. However, there was no significant difference in the prevalence of diabetes or hypertension. Duration of time in the U.S. was related to cardiovascular disease and asthma but was not associated with diabetes, hypertension, BMI, HDL cholesterol, LDL cholesterol, socioeconomic status, or health behaviors.ConclusionsThe lower CVD and asthma prevalence among the Chinese immigrants may be partially attributed to healthier diets, more physical activity, lower BMI, and less exposure to cigarette smoke. First generation immigrant status may be protective even after about two decades.

Combined host-conditioning with CTLA4-Ig, tacrolimus, anti-lymphocyte serum, and low-dose radiation leads to stable mixed hematopoietic chimerism

The toxic dose of irradiation required to achieve stable mixed hematopoietic chimerism is the major limitation to its clinical application in transplantation and other nonmalignant conditions such as hemoglobinopathies. This study examines the additive effect of costimulatory blockage, to our previously described tacrolimus-based conditioning regimen, in further reducing the dose of total-body irradiation to achieve stable mixed chimerism in rats. Fully mismatched, 4- to 6-week-old ACI and Wistar Furth rats were used as donors and recipients, respectively. Recipients were administered CTLA4-Ig 2mg/kg/day (alternate days) in combination with tacrolimus 1 mg/kg/day (daily) from day 0 through day +10, anti-lymphocyte serum 10 mg at day +10 (single dose), and total-body irradiation ranging from 100-600 cGy, prior to bone marrow transplantation (day 0) with 100 x 10(6) of T-cell-depleted bone marrow cells. Levels of donor chimerism were determined over a period of 12 months. The short course of CTLA4-Ig, tacrolimus, and ALS led to dramatic engraftments at reduced doses of irradiation: 100% (5/5) and 93% (13/14) of the animals developed mixed chimerism at 400 cGy and 300 cGy, respectively. At 300 cGy, recipients exhibited durable, multilineage mixed chimerism at 365 days with donor cells ranging from 19-42% (mean 23.4%) with no evidence of graft-vs-host disease. These mixed chimeras exhibited in vitro (mixed lymphocyte reaction) and in vivo (skin grafts) donor-specific tolerance. This study suggests that addition of costimulatory blockade to a tacrolimus-based conditioning regimen reduces the dose of irradiation required to achieve stable multilineage chimerism in rats.

A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts

BACKGROUND We determined whether a nontoxic CTLA4-Ig-based conditioning regimen effected mixed chimerism and donor-specific tolerance when heart and bone marrow were transplanted simultaneously. METHODS Fully mismatched rat strain combinations were used. Recipients received total-body irradiation (300 centigrays), bone marrow (10(8) cells), and cardiac transplants from the donor on day 0. Subsequently, recipient animals received CTLA4-Ig (2 mg/kg, every other day, x 5 doses), tacrolimus (1 mg/kg/day; days 0 to 9), and one dose (10 mg) of antilymphocyte serum on day 10. RESULTS All bone marrow recipients (n = 7) developed mixed chimerism (mean = 25% +/- 9% at 1 year) and accepted cardiac allografts permanently (> 375 +/- 32 days). Recipients that received conditioning regimen but no bone marrow (n = 5) rejected donor hearts within 51 +/- 13 days (p < 0.01). Recipients that accepted heart grafts also permanently accepted (> 180 days) donor-specific skin grafts, but rapidly rejected (< 10 days) third-party skin grafts. CONCLUSIONS A nontoxic CTLA4-Ig-based conditioning regimen effects mixed chimerism and donor-specific tolerance when heart and bone marrow are transplanted simultaneously. This regimen may have clinical application.

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system

Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.

Sodium Intake, Blood Pressure, and Dietary Sources of Sodium in an Adult South Indian Population

BACKGROUND The association between prevalence of hypertension and its relationship with dietary sodium intake has never been published from large epidemiological studies in the South Indian population before. OBJECTIVES To assess sodium intake and its association with blood pressure, and major dietary sources of sodium in an adult population in southeastern India. METHODS This study included a representative population-based sample of 8080 individuals (57% women) >20 years of age. Individuals with previous history of hypertension and outliers for sodium intake were excluded, resulting in a sample size of 6876, with 4269 from semi-urban/urban and 2607 from rural areas. Baseline measurements included evaluation of systolic (SBP) and diastolic (DBP) blood pressures, anthropometric, sociodemographic, and psychosocial parameters. Based on 24-hour recall, we calculated total daily sodium intake and the percentage contributed by each food group to the total sodium intake. Participants were assigned based on quintiles of dietary sodium intake. Mixed-effects multivariable linear regression models assessed the association of SBP and DBP with sodium intake. FINDINGS Men had higher mean sodium intake (4.1 ± 2 versus 3.2 ± 1.7 g/day; P < 0.01) with higher mean SBP and DBP (123/77 versus 117/74 mm Hg; P < 0.01), and higher prevalence of hypertension (22.2% versus 12.9%; P < 0.01) compared with women. Mean dietary sodium intake was significantly higher in the hypertensive men (4.2 ± 2 g/day) and women (3.2 ± 1.7 g/day) compared with normotensive men (4 ± 2 g/day), and women (3.2 ± 1.7 g/day; P < 0.05). Significant (P < 0.01) increases in SBP and DBP were evident in men, but not women with increasing quintile of sodium intake. After multivariable adjustments, sodium intake was independently associated with SBP, but not DBP, in both sexes. The predominant source of dietary sodium in both semi-urban/urban and rural populations was from homemade foods where salt is part of the traditional recipe. CONCLUSION In a South Indian population, the dietary intake of sodium was higher than recommendations by major dietary guidelines and was an independent predictor of SBP.

The History and Development of Direct Coronary Surgery without Cardiopulmonary Bypass

Abstract  The history of direct myocardial revascularization without cardiopulmonary bypass dates to 1961 in the dawn of coronary artery surgery. With the introduction and development of techniques of extracorporeal circulation around the same time, beating heart surgery was largely abandoned. Over the subsequent decades, cardiopulmonary bypass and electromechanical cardioplegic arrest became popular as means of revascularization in a bloodless and motionless field. While coronary artery surgery on the arrested heart remained undisputed for decades, myocardial revascularization on the beating heart was pursued by a few pioneering surgeons around the world, based on the belief that coronary revascularization could be performed equally well without the detrimental effects of cardiopulmonary bypass and electromechanical arrest. Various concepts and techniques developed during the 1980s by these pioneers enabled minimally invasive coronary surgery to be performed in the early 1990s. This break from the mainstream allowed selective myocardial revascularization using a minimal incision and no cardiopulmonary bypass to develop and constructed a base for future extensive revascularizations off‐pump. With the subsequent explosion of new techniques for coronary exposure and myocardial stabilization, complete revascularization without cardiopulmonary bypass became possible with consistent results. Emerging from the preview of only a few surgeons just a decade ago, off‐pump surgery is currently one of the accepted modalities for complete myocardial revascularization worldwide. This paradigm shift in the approach to myocardial revascularization has led to exiting new future possibilities, such as beating heart totally endoscopic coronary artery surgery.

Population Study of Urban, Rural, and Semiurban Regions for the Detection of Endovascular Disease and Prevalence of Risk Factors and Holistic Intervention Study Rationale, Study Design, and Baseline Characteristics of PURSE-HIS

We designed and implemented the PURSE-HIS (Population Study of Urban, Rural and Semiurban Regions for the Detection of Endovascular Disease and Prevalence of Risk Factors and Holistic Intervention Study) to understand the prevalence and progression of subclinical and overt endovascular disease (EVD) and its risk factors in urban, semiurban, and rural communities in South India. The study is also designed to generate clinical evidence for effective, affordable, and sustainable community-specific intervention strategies to control risks factors for EVD. As of June 2012, 8,080 (urban: 2,221; semiurban: 2,821; rural: 3,038) participants >20 years of age were recruited using 2-stage cluster sampling. Baseline measurements included standard cardiovascular disease risk factors, sociodemographic factors, lifestyle habits, psychosocial factors, and nutritional assessment. Fasting blood samples were assayed for putative biochemical risk factors and urine samples for microalbuminuria. All nondiabetic participants underwent oral glucose tolerance test with blood and urine samples collected every 30 min for 2 h. Additional baseline measurements included flow-mediated brachial artery endothelial vasodilation, assessment of carotid intimal medial wall thickness using ultrasonography, screening for peripheral vascular disease using ankle and brachial blood pressures, hemodynamic screening using a high-fidelity applanation tonometry to measure central blood pressure parameters, and aortic pulse wave velocity. To assess prevalence of coronary artery disease, all participants underwent surface electrocardiography and documentation of ventricular wall motion abnormality and function using echocardiography imaging. To detect subclinical lesions, all eligible participants completed an exercise treadmill test. Prospectively, the study will assess progression of subclinical and overt EVD, including risk factor-outcome relation differences across communities. The study will also evaluate community-specific EVD prevention using traditional Indian system of medicine versus recognized allopathic (mainstream) systems of medicine.

Association of Long-Term Near-Highway Exposure to Ultrafine Particles with Cardiovascular Diseases, Diabetes and Hypertension

Ultrafine particle (UFP) concentrations are elevated near busy roadways, however, their effects on prevalence of cardiovascular diseases, diabetes, and hypertension are not well understood. To investigate these associations, data on demographics, diseases, medication use, and time of activities were collected by in-home surveys for 704 participants in three pairs of near-highway and urban background neighborhoods in and near Boston (MA, USA). Body mass index (BMI) was measured for a subset of 435 participants. Particle number concentration (PNC, a measure of UFP) was collected by mobile monitoring in each area. Intra-neighborhood spatial-temporal regression models (approximately 20 m resolution) were used to estimate hourly ambient PNC at the residences of participants. We used participant time activity information to adjust annual average residential PNC values and assign individualized time activity adjusted annual average PNC exposures (TAA-PNC). Using multivariate logistic regression models, we found an odds ratio (OR) of 1.35 (95% CI: 0.83, 2.22) of TAA-PNC with stroke and ischemic heart diseases (S/IHD), an OR of 1.14 (95% CI: 0.81, 1.62) with hypertension, and an OR of 0.71 (95% CI: 0.46, 1.10) for diabetes. A subset analysis controlling for BMI produced slightly stronger associations for S/IHD (OR = 1.61, 95% CI: 0.88, 2.92) and hypertension (OR = 1.28, 95% CI: 0.81, 2.02), and no association with diabetes (OR = 1.09, 95% CI = 0.61, 1.96). Further research is needed with larger sample sizes and longitudinal follow-up.

Design Optimization of Thoracic Endovascular Stent Graft (EVSG)

AIM: EVSG, a tube composed of fabric supported by stent, is inserted percutaneously using a catheter to treat thoracic aortic aneurysm (TAA).The study seeks to improve the mechanical performance of EVSG by design optimization by Finite Element Analysis (FEA).

Urbanization as a risk factor for aortic stiffness in a cohort in India

Urbanization is associated with higher prevalence of cardiovascular disease worldwide. Aortic stiffness, as measured by carotid-femoral pulse wave velocity is a validated predictor of cardiovascular disease. Our objective was to determine the association between urbanization and carotid-femoral pulse wave velocity. The analysis included 6166 participants enrolled in an ongoing population-based study (mean age 42 years; 58% female) who live in an 80 × 80 km region of southern India. Multiple measures of urbanization were used and compared: 1) census designations, 2) satellite derived land cover (crops, grass, shrubs or trees as rural; built-up areas as urban), and 3) distance categories based on proximity to an urban center. The association between urbanization and carotid-femoral pulse wave velocity was tested in sex-stratified linear regression models. People residing in urban areas had significantly (p < 0.05) elevated mean carotid-femoral pulse wave velocity compared to non-urban populations after adjustment for other risk factors. There was also an inverse association between distance from the urban center and mean carotid-femoral pulse wave velocity: each 10 km increase in distance was associated with a decrease in mean carotid-femoral pulse wave velocity of 0.07 m/s (95% CI: -0.09, -0.06 m/s). The association was stronger among older participants, among smokers, and among those with other cardiovascular risk factors. Further research is needed to determine which components in the urban environment are associated with higher carotid-femoral pulse wave velocity.