There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear.
To understand the relationships among adiposity, gender, and asthma control in inner-city adolescents with asthma.
We prospectively followed 368 adolescents with moderate to severe asthma (ages 12–20 years) living in 10 urban areas for one year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide were measured every 6 weeks. Adiposity measures (BMI, DEXA scans) were made, and blood was collected for allergy markers, adiponectin, leptin, TNF-α, IL-6 and CRP.
More than 60% of females and 50% of males were above the 85th percentile of BMI-for-age. Higher BMI was associated with more symptom days (R= 0.18, P<0.01) and exacerbations (R=0.18, P=0.06) among females only. Adiponectin was inversely related to asthma symptoms (R=− 0.18, P<0.05) and exacerbations (R=− 0.20, P<0.05) and positively with FEV1/FVC (R=0.15, P<0.05) in males only, independent of body size. There was no relationship between adiposity or adipokines and total IgE, blood eosinophils and exhaled nitric oxide. DEXA provided little additional value in relating adiposity to asthma outcome in this population of adolescents.
Adiposity is associated with poorer asthma control in females. Adiponectin is associated with improved asthma control in males.
Obesity; Asthma; Adipokines; Leptin; Adiponectin
Current robotic training approaches lack criteria for automatically assessing and tracking (over time) technical skills separately from clinical proficiency. We describe the development and validation of a novel automated and objective framework for assessment of training.
We are able to record all system variables (stereo instrument video, hand and instrument motion, buttons and pedal events) from the da Vinci surgical systems using a portable archival system integrated with the robotic surgical system. Data can be collected unsupervised, and the archival system does not change system operation in any way. Our open-ended multi-center protocol is collecting surgical skill benchmarking data from 24 trainees to surgical proficiency, subject only to their continued availability. Two independent experts performed structured (OSATS) assessments on longitudinal data from 8 novice and 4 expert surgeons to generate ground truth for training and to validate our computerized statistical analysis methods in identifying ranges of operational and clinical skill measures.
Objective differences in operational and technical skill between known experts and other subjects were quantified. Longitudinal learning curves and statistical analysis for trainee performance measures are reported. Graphical representations of skills developed for feedback to the trainees are also included.
We describe an open-ended longitudinal study and automated motion recognition system capable of objectively differentiating between clinical and technical operational skills in robotic surgery. Our results demonstrate a convergence of trainee skill parameters towards those derived from expert robotic surgeons over the course of our training protocol.
robotic surgery; robotic surgery training; assessment; learning curves
With increased use of robotic surgery in specialties including urology, development of training methods has also intensified. However, current approaches lack the ability of discriminating operational and surgical skills.
An automated recording system was used to longitudinally (monthly) acquire instrument motion/telemetry and video and for 4 basic surgical skills -- suturing, manipulation, transection, and dissection. Statistical models were then developed to discriminate the human-machine skill differences between practicing expert surgeons and trainees.
Data from 6 trainee and 2 experts was analyzed to validate the first ever statistical models of operational skills, and demonstrate classification with very high accuracy (91.7% for masters, and 88.2% for camera motion) and sensitivity.
We report on our longitudinal study aimed at tracking robotic surgery trainees to proficiency, and methods capable of objectively assessing operational and technical skills that would be used in assessing trainee progress at the participating institutions.
Robotic surgery training; objective skill assessment; automated skill assessment
The developing human brain shows rapid myelination and axonal changes during childhood, adolescence and early adulthood, requiring successive evaluations to determine normative values for potential pathological assessment. Fiber characteristics can be examined by axial and radial diffusivity procedures, which measure water diffusion parallel and perpendicular to axons, and primarily show axonal status and myelin changes, respectively. Such measures are lacking from wide-spread sites for the developing brain. Diffusion tensor imaging data were acquired from 30 healthy subjects (age, 17.7±4.6, range 8–24 years; body-mass-index, 21.5±4.5 kg/m2; 18 male) using a 3.0-Tesla MRI scanner. Diffusion tensors were calculated, principal eigenvalues determined, and axial and radial diffusivity maps calculated and normalized to a common space. A set of regions-of-interest were outlined from wide-spread brain areas within rostral, thalamic, hypothalamic, cerebellar, and pontine regions, and average diffusivity values were calculated using normalized diffusivity maps and these regions-of-interest masks. Age-related changes were assessed with Pearson’s correlations, and gender differences evaluated with Student’s t-tests. Axial and radial diffusivity values declined with age in the majority of brain areas, except for mid hippocampus, where axial diffusivity values correlated positively with age. Gender differences emerged within putamen, thalamic, hypothalamic, cerebellar, limbic, temporal, and other cortical sites. Documentation of normal axial and radial diffusivity values will help assess disease-related tissue changes. Axial and radial diffusivity change with age, with fiber structure and organization differing between sexes in several brain areas. The findings may underlie gender-based functional characteristics, and mandate partitioning age- and gender-related changes during developmental brain pathology evaluation.
Diffusion tensor imaging; Axons; Myelin; Brain maturation; Water diffusion
This study was conducted to evaluate the performance of World Health Organisation (WHO) verbal autopsy tool in determining major causes of neonatal deaths.
From a tertiary care hospital and a government multispecialty hospital, the attending paediatricians ascertained a clinical cause of death for 371 neonatal deaths. Trained field workers conducted verbal autopsy (VA) interviews. Two independent paediatricians, who had no access to the clinical information, assigned cause of death as per verbal autopsy. Analysis was based on 313 cases in which both clinical diagnosis and VA diagnosis was obtained.
As per the clinical diagnosis, four most common causes of neonatal deaths were sepsis (29.1%), preterm birth (27.8%), birth asphyxia (27.2%), and congenital anomalies (11.5%). Cause specific mortality fractions by VA diagnosis were statistically similar to those obtained by clinical diagnosis except for birth asphyxia (16.3%). Diagnostic accuracy of verbal autopsy diagnosis against clinical diagnosis ranged from 78% to 92% in ascertaining different underlying causes of death. Area under the Receiver-Operator Characteristics curve (95% confidence interval) was 0.75 (0.69–0.80) for sepsis, 0.74 (0.68–0.80) for preterm birth, 0.73 (0.65–0.82) for congenital anomaly and 0.70 (0.64–0.75) for birth asphyxia. Kappa for all four causes was moderate (0.46–0.55).
The WHO verbal autopsy tools can provide reasonably good estimates of predominant causes of neonatal deaths in countries where neonatal mortality is high. Caution is required to interpret cause specific mortality fraction (CSMF) for birth asphyxia by VA because it is likely to be an underestimate.
Increased density of fast food restaurants is associated with increased prevalence of obesity in developed countries. However, less is known about this relationship in developing countries undergoing rapid urbanization and how differences in neighbourhood income affect the patronage of fast food outlets. The purpose of the study is to explore the differences in fast food preferences, perceptions, and patronage between Indians living in high- and low-income neighbourhoods.
This cross-sectional study recruited 204 men and women (35 to 65 years in age) from high- and low-income neighbourhoods who completed a questionnaire on fast food consumption. The questionnaire asked participants to define fast food and to provide reasons for and frequency of visits to fast food restaurants. The differences were analyzed using Chi square and t-tests for categorical and continuous variables, respectively.
Participants from a high-income neighbourhood were more likely to perceive Western -style fast food as fast food, while people from the low-income neighbourhood were more likely to identify food sold by street vendors as fast food (p <0.001). Furthermore, compared to participants from the high-income neighbourhood, people from the low-income neighbourhood were more likely to report buying food from street vendors while less likely to dine out at both fast food and non-fast food restaurants (p<0.001). Although the high-income neighbourhood group was more likely to report enjoying eating at fast food restaurants than their low-income neighbourhood counterparts, there were no significant differences in the reasons for visiting fast food restaurants (convenience, price, social enjoyment, and quality of meals) between the two groups. Both groups preferred home cooked over restaurant meals, and they recognized that home cooked food was healthier.
Overall, consumption of fast food was low. People from a high-income neighbourhood dined out more frequently and were more likely to perceive Western-style food as fast food compared to their counterparts from the low-income neighbourhood.
Fast food; Neighbourhood income; Street food; India; South Asian
We propose that the DNA within the chromatin behaves as a dynamic combinatorial library capable of forming novel structures by
reversible processes. We also hypothesize that states within the library may be linked via quantum tunneling. RNA polymerase
then could scan these states and the system decoheres to the “appropriate” state. Two ways of sustaining quantum coherence at
relevant time scales could be possible, first, screening: the quantum system can be kept isolated from its decohering environment,
second, the existence of decoherence free subspaces .We discuss the role of superconductivity in context of avoiding decoherence in
context of our hypothesis.
Tautomeric; Decoherence; Superconductivity
Asthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, individuals with asthma may have waxing and waning adherence to controller therapy.
To measure changes in inhaled corticosteroid (ICS) adherence over time, and to estimate the effect of this changing pattern of use on asthma exacerbations.
ICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). For each individual we calculated a moving average of ICS adherence for each day of follow-up. Asthma exacerbations were defined as the need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization. Proportional hazard models were used to assess the relationship between ICS medication adherence and asthma exacerbations.
Adherence to ICS medications began to increase prior to the first asthma exacerbation and continued afterward. Adherence was associated with a reduction in exacerbations, but was only statistically significant among individuals whose adherence was >75% of the prescribed dose (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.41–0.90) when compared with individuals whose adherence was ≤25%. This pattern was largely confined to individuals whose asthma was not well controlled initially. An estimated 24% of asthma exacerbations were attributable to ICS medication non-adherence.
Inhaled corticosteroid adherence varies in the time period leading up to and following an asthma exacerbation, and non-adherence likely contributes to a large number of these exacerbations. High levels of adherence are likely required to prevent these events. [ClinicalTrials.gov number NCT01142947]
medication adherence; inhaled corticosteroids; asthma; patient compliance; asthma exacerbations
Limited information exists on the antibody responses elicited against the viral envelope in HIV-1-infected children. In this cross-sectional study, we assessed the antibody responses against three different immunogenic regions of HIV-1 envelope, namely V3 region of gp120, membrane proximal external region (MPER), and immunodominant loop (IDL) of gp41 in HIV-1-infected children from north India. We recruited 75 HIV-1-infected (40 antiretroviral naive and 35 treated) children, with age ranging from 1.5 to 16 y. Antibodies to V3 and the IDL region were found in a majority of the infected children, whereas antibodies to MPER were found in approximately one-third of the children studied. Higher antibody titers to the immunogenic regions corresponded to the symptomatic stages of HIV-1 infection in both naive and antiretroviral therapy (ART)-treated children. High titers of anti-V3C and anti-IDL antibodies were observed in a subset of antiretroviral-naive patients with suppressed viremia (<47 RNA copies/mL), suggesting that antibodies to these immunogenic regions are present regardless of their viremic status. Further, the antibody titers were significantly lower in the plasma of treated patients compared to naive patients, regardless of whether they were virologically suppressed or not. This is the first report on the antibody responses elicited in HIV-1-infected children in India. The study may help to understand the humoral antibody responses directed against viral envelope in HIV-1-infected children.
Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date. Isolation of antibodies by the hybridoma technology is a cumbersome process with fewer yields. Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost. This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs) against the third variable region (V3) of the clade C HIV-1 envelope.
An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells. By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct. Expression of the positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA. Preliminary neutralization assays indicated varying degrees of neutralization of clade C and B viruses. EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology. Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding phage. After selection, the phage clones were propagated in a clonal manner.
This strategy can be efficiently used and is cost effective for the generation of diverse recombinant antibodies. This is the first study to generate anti-V3 scFvs against HIV-1 Clade C.
HIV-1; Clade C; V3; scFv
It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine if cord blood VDD is associated with FS and if such association can be modified by genetic variants in a prospective birth cohort.
This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11ng/ml, and FS as specific IgE ≥ 0.35kUA/L to any of eight common food allergens in early childhood. We genotyped potentially functional single nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs.
Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (pinteraction=0.003, pFDR=0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR=1.79, 95%CI: 1.15–2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (pinteraction=9×10−6).
Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS.
cord blood plasma 25(OH)D; food sensitization; gene-vitamin D deficiency interaction; SNP
The lack of epidemiologic data on invasive Streptococcus pyogenes infections in many developing countries is concerning, as S. pyogenes infections are commonly endemic in these areas. Here we present the results of the first prospective surveillance study of invasive Streptococcus pyogenes infections in India. Fifty-four patients with invasive S. pyogenes infections were prospectively enrolled at two study sites, one in the north and one in the south of India. Sterile-site isolates were collected, and clinical information was documented using a standardized questionnaire. Available acute-phase sera were tested for their ability to inhibit superantigens produced by the patient's own isolate using a cell-based neutralizing assay. The most common clinical presentations were bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis were identified. Characterization of the isolates revealed great heterogeneity, with 32 different emm subtypes and 29 different superantigen gene profiles being represented among the 49 sterile-site isolates. Analyses of acute-phase sera showed that only 20% of the cases in the north cohort had superantigen-neutralizing activity in their sera, whereas 50% of the cases from the south site had neutralizing activity. The results demonstrate that there are important differences in both clinical presentation and strain characteristics between invasive S. pyogenes infections in India and invasive S. pyogenes infections in Western countries. The findings underscore the importance of epidemiologic studies on streptococcal infections in India and have direct implications for current vaccine developments.
Background & objectives:
User charges have been advocated on efficiency grounds despite the widespread criticism about their adverse effect on equity. We assessed the effect of user charges on inpatient hospitalizations rate and equity in Haryana State.
The inpatient department (IPD) statistics of the public sector facilities in Yamuna Nagar district where user charges had been introduced were analysed and compared with Rohtak district which did not have user charge between 2000 and 2006. National Sample Survey data of Haryana for the 2004-2005 period were analyzed to compare utilization of public sector facilities for hospitalization, cost of hospitalization, and prevalence of catastrophic out-of-pocket (OOP) expenditure by income quintiles in three districts which had user charges and 17 districts of Haryana which did not levy user charges.
During 2000 and 2006, hospital admissions declined by 23.8 per cent in Yamuna Nagar district where user charges had been introduced compared to an almost static hospitalization rate in Rohtak district which did not have user charges (P<0.01). Public sector hospital utilization for inpatient services had a pro-rich (concentration index 0.144) distribution in the three districts with user charges and pro-poor (concentration index -0.047) in the 17 districts without user charges. Significantly higher prevalence of catastrophic health expenditure was observed in public sector institutions with user charges (48%) compared to those without user charges (35.4%) (P<0.001).
Interpretation & conclusions:
The findings of our study showed that user charges had a negative influence on hospitalizations in Haryana especially among the poor. Public policies for revenue generation should avoid user charges.
Access the health care; demand-side cost sharing; equity; health system research; India; service utilization; user charges
It is estimated that India has more deaths from rabies than any other
country. However, existing estimates are indirect and rely on
Methods and Principal Findings
We examined rabies deaths in the ongoing Million Death Study (MDS), a
representative survey of over 122,000 deaths in India that uses enhanced
types of verbal autopsy. We estimated the age-specific mortality rates of
symptomatically identifiable furious rabies and its geographic and
demographic distributions. A total of 140 deaths in our sample were caused
by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000
to 15,500) symptomatically identifiable furious rabies deaths in India. Most
rabies deaths were in males (62%), in rural areas (91%), and
in children below the age of 15 years (50%). The overall rabies
mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to
1.4). One third of the national rabies deaths were found in Uttar Pradesh
(4,300) and nearly three quarters (8,900) were in 7 central and
south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh,
Bihar, Assam, and Madhya Pradesh.
Conclusions and Significance
Rabies remains an avoidable cause of death in India. As verbal autopsy is not
likely to identify atypical or paralytic forms of rabies, our figure of
12,700 deaths due to classic and clinically identifiable furious rabies
underestimates the total number of deaths due to this virus. The
concentrated geographic distribution of rabies in India suggests that a
significant reduction in the number of deaths or potentially even
elimination of rabies deaths is possible.
Rabies, a disease of antiquity, has been partially controlled in many countries
and eliminated in a few. However, according to the World Health Organization,
rabies continues to kill thousands of people in India each year, more than in
any other country. We used an enhanced type of verbal autopsy (a structured
interview of the relatives or close associates of the dead by non-medical staff
with central medical coding by at least two doctors) to identify the causes of
over 122,000 deaths in a large scale, representative sample in India in 2001–03.
Using these data, we estimate that in 2005 approximately 12,700 people died from
symptomatically identifiable furious rabies. Because verbal autopsy is not able
to identify atypical presentations of rabies, our figure underestimates the
actual number of rabies deaths in India. The majority of rabies deaths occurred
in males, in rural areas, in children below the age of 15 years, and in a few
states. The concentrated geographic distribution of rabies in India suggests
that targeting with preventive campaigns including vaccination of animals and
post exposure vaccination of humans might achieve a significant reduction in the
number of deaths or potentially even elimination of deaths from this
We examined whether the risk of food-allergen sensitization varied according to self-identified race or genetic ancestry.
We studied 1104 children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food sensitization was defined as specific immunoglobulin E (sIgE) levels of ≥0.35 kilo–units of allergen (kUA)/L for any of 8 common food allergens. Multivariate logistic regression analyses were used to evaluate the associations of self-identified race and genetic ancestry with food sensitization. Analyses also examined associations with numbers of food sensitizations (0, 1 or 2, and ≥3 foods) and with logarithmically transformed allergen sIgE levels.
In this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of subjects exhibited food sensitizations. In multivariate models, both self-reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24–4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02–1.14]) were associated with food sensitization. Self-reported black race (OR: 3.76 [95% CI: 1.09–12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07–1.32]) were associated with a high number (≥3) of food sensitizations. African ancestry was associated with increased odds of peanut sIgE levels of ≥5 kUA/L (OR: 1.25 [95% CI: 1.01–1.52]). Similar ancestry associations were seen for egg sIgE levels of ≥2 kUA/L (OR: 1.13 [95% CI: 1.01–1.27]) and milk sIgE levels of ≥5 kUA/L (OR: 1.24 [95% CI: 0.94–1.63]), although findings were not significant for milk.
Black children were more likely to be sensitized to food allergens and were sensitized to more foods. African ancestry was associated with peanut sensitization.
food allergy; sensitization; racial disparities; genetic ancestry
Analysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies.
Thirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20–57 years (median = 33 years) were recruited in this study for mAb production. The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein. We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays.
We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals. The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides showed exclusive binding to V3 crown. The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition.
Our study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses. Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.
HIV-1; Envelope glycoprotein; Third variable region; Anti-V3 monoclonal antibodies; Viral neutralization
Background & objectives:
Income inequality is associated with poor health. Inequities exist in service utilization and financing for health care. Health care costs push high number of households into poverty in India. We undertook this study to ascertain inequities in health status, service utilization and out-of-pocket (OOP) health expenditures in two States in north India namely, Haryana and Punjab, and Union Territory of Chandigarh.
Data from National Sample Survey 60th Round on Morbidity and Health Care were analyzed by mean consumption expenditure quintiles. Indicators were devised to document inequities in the dimensions of horizontal and vertical inequity; and redistribution of public subsidy. Concentration index (CI), and equity ratio in conjunction with concentration curve were computed to measure inequity.
Reporting of morbidity and hospitalization rate had a pro-rich distribution in all three States indicating poor utilization of health services by low income households. Nearly 57 and 60 per cent households from poorest income quintile in Haryana and Punjab, respectively faced catastrophic OOP hospitalization expenditure at 10 per cent threshold. Lower prevalence of catastrophic expenditure was recorded in higher income groups. Public sector also incurred high costs for hospitalization in selected three States. Medicines constituted 19 to 47 per cent of hospitalization expenditure and 59 to 86 per cent OPD expenditure borne OOP by households in public sector. Public sector hospitalizations had a pro-poor distribution in Haryana, Punjab and Chandigarh.
Interpretation & conclusions:
Our analysis indicates that public sector health service utilization needs to be improved. OOP health care expenditures at public sector institutions should to be curtailed to improve utilization of poorer segments of population. Greater availability of medicines in public sector and regulation of their prices provide a unique opportunity to reduce public sector OOP expenditure.
Equity; hospitalization expenditure; India; service utilization; user charges
Broadly cross neutralizing antibodies (NAbs) are generated in a group of HIV-1 infected individuals during the natural infection, but little is known about their prevalence in patients infected with viral subtypes from different geographical regions. We tested here the neutralizing efficiency of plasma antibodies from 80 HIV-1 infected antiretroviral drug naive patients against a panel of subtype-B and C tier 2 viruses. We detected cross-neutralizing antibodies in approximately 19–27% of the plasma, however the subtype-C specific neutralization efficiency predominated (p = 0.004). The neutralizing activity was shown to be exclusively mediated by the immunoglobulin G (IgG) fraction in the representative plasma samples. Epitope mapping of three, the most cross-neutralizing plasma (CNP) AIIMS206, AIIMS239 and AIIMS249 with consensus-C overlapping envelope peptides revealed ten different binding specificities with only V3 and IDR being common. The V3 and IDR were highly antigenic regions but no correlation between their reciprocal Max50 binding titers and neutralization was observed. In addition, the neutralizing activity of CNP was not substantially reduced by V3 and gp41 peptides except a modest contribution of MPER peptide. The MPER was rarely recognized by plasma antibodies though antibody depletion and competition experiments demonstrated MPER dependent neutralization in two out of three CNP. Interestingly, the binding specificity of one of the CNP (AIIMS206) overlapped with broadly neutralizing mAb 2F5 epitope. Overall, the data suggest that, despite the low immunogenicity of HIV-1 MPER, the antibodies directed to this region may serve as crucial reagents for HIV-1 vaccine design.
Although gray matter injury appears in heart failure (HF) patients, the presence, extent, and nature of axonal injury impacting on cardiovascular regulation and other functions is unclear. We performed diffusion tensor imaging (3.0-Tesla magnetic resonance imaging scanner) in 16 HF and 26 control subjects, and assessed whole-brain water diffusion parallel (axial diffusivity; axonal status) and perpendicular (radial diffusivity; myelin changes) to fibers. Regions with increased axial diffusivity only, indicating impaired axonal integrity, emerged in cardiovascular, hedonic, and pain regulatory areas, including basal forebrain, hypothalamic and limbic projections through the medial forebrain bundle and raphé magnus projections to the medulla and cerebellum. Other fiber paths between sites implicated in cognition, including limbic, basal-ganglia, thalamic, internal capsule, and corpus callosum were also altered. Sites with increased radial diffusivity only, indicating myelin breakdown, appeared in the corpus callosum, cingulate, and temporal, parietal, occipital, and frontal regions. Both higher axial and radial diffusivity, indicating loss of tissue integrity, appeared in parietal and occipital lobes, limbic regions, insula, internal capsule, cerebellum, and dorsolateral medulla. Axons and myelin are altered in HF, likely resulting from ischemic/hypoxic processes acting chronically and sub-acutely, respectively. The alterations would contribute to the multiple autonomic and neuropsychological symptoms found in HF.
Axial diffusivity; Radial diffusivity; Nucleus of the solitary tract; Cerebellar peduncles; Autonomic; Cognition
The impact of breastfeeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
To evaluate the effect of breastfeeding and gene-breastfeeding interactions on food sensitization (FS) in a prospective U.S. birth cohort.
This study included 970 children who were prospectively followed since birth. Breastfeeding history was obtained from a standardized questionnaire interview. FS was defined as specific IgE ≥0.35 kUA/L to any of eight common food allergens. Eighty-eight potentially functional SNPs were genotyped from 18 genes involved in innate immunity or TH1/TH2 balance. Logistic regression models were used to test the effects of breastfeeding and gene-breastfeeding interactions on FS, with adjustment for pertinent covariates.
Children who were ever breastfed (n=739), including exclusively breastfed children, were at a 1.5 (95%CI=1.1-2.1, p=0.019) times higher risk of FS than never breastfed children (n=231). This association was significantly modified by rs425648 in the IL12RB1gene (pinteraction=0.0007): breastfeeding increased the risk of FS (OR=2.0, 95%CI=1.4-3.1, p= 0.0005) in children carrying the GG genotype but decreased the risk (OR=0.6, 95%CI=0.3-1.4, p=0.252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the TLR9 (rs352140) and TSLP (rs3806933) genes. The interaction between the combined genotypes of the three SNPs and breastfeeding on FS was even stronger (pinteraction<10-5).
Our data suggest that the effect of breastfeeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
Breastfeeding; food sensitization; gene-environment interaction
Indian health system is characterized by a vast public health infrastructure which lies underutilized, and a largely unregulated private market which caters to greater need for curative treatment. High out-of-pocket (OOP) health expenditures poses barrier to access for healthcare. Among those who get hospitalized, nearly 25% are pushed below poverty line by catastrophic impact of OOP healthcare expenditure. Moreover, healthcare costs are spiraling due to epidemiologic, demographic, and social transition. Hence, the need for risk pooling is imperative. The present article applies economic theories to various possibilities for providing risk pooling mechanism with the objective of ensuring equity, efficiency, and quality care. Asymmetry of information leads to failure of actuarially administered private health insurance (PHI). Large proportion of informal sector labor in India's workforce prevents major upscaling of social health insurance (SHI). Community health insurance schemes are difficult to replicate on a large scale. We strongly recommend institutionalization of tax-funded Universal Health Insurance Scheme (UHIS), with complementary role of PHI. The contextual factors for development of UHIS are favorable. SHI schemes should be merged with UHIS. Benefit package of this scheme should include preventive and in-patient curative care to begin with, and gradually include out-patient care. State-specific priorities should be incorporated in benefit package. Application of such an insurance system besides being essential to the goals of an effective health system provides opportunity to regulate private market, negotiate costs, and plan health services efficiently. Purchaser-provider split provides an opportunity to strengthen public sector by allowing providers to compete.
Equity; health insurance; health financing; India; universal healthcare
Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.
We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA.
African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.
Heart failure (HF) is accompanied by diminished cognitive, motor, learning, emotional, and planning deficits, which are associated with increased morbidity and mortality. A basal ganglia structure, the putamen, serves many functions that are affected in HF, but its global or localized structural integrity is unknown. Our aim was to evaluate global and regional putamen volume differences in HF over control subjects.
Methods and results
We collected two high-resolution T1-weighted scans from 16 HF patients (age, 54.1 ± 8.3 years; 12 males; left ventricular ejection fraction, 27.8 ± 6.8%) and 32 control subjects (52.4 ± 7.3 years; 24 males) using a 3.0 T magnetic resonance imaging scanner. After realigning, averaging, and reorienting the T1-weighted volumes into a common space, the structures were manually outlined, tracings were normalized for head size, volumes calculated, and surface models generated. Demographic data were compared between groups with χ2 and independent samples t-tests, global putamen volumes were evaluated using independent samples t-tests, and regional differences were examined with surface morphometry. No significant differences in age or sex appeared between groups, but body mass index differed significantly (P = 0.008). Heart failure patients showed significantly lower left (controls vs. HF; 4842.1 ± 740.0 vs. 4224.1 ± 894.4 mm3, P = 0.014) and right (4769.3 ± 651.9 vs. 4193.7 ± 876.2 mm3, P = 0.014) global putamen volumes than controls, with localized reductions in bilateral rostral, mid-dorsal, and medial-caudal regions (left, P < 0.003; right, P < 0.0002).
Putamen structures showed global and localized volume reductions in HF over controls. The localized volume losses suggest deficits in motor and neuropsychological functions, which are evident in HF subjects, and may be due to hypoxic and ischaemic processes targeting these areas.
Magnetic resonance imaging; Brain; Heart failure; Three-dimensional surface morphometry; Basal ganglia