Seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential “universal” vaccine.

Author Summary

Influenza virus continues to pose a significant risk to global health and is responsible for thousands of deaths each year in the United States. This threat is largely due to the ability of the influenza virus to undergo rapid changes, allowing it to escape from immune responses elicited by previous infections or vaccinations. Certain internal determinants of the influenza virus are largely conserved across different viral strains and represent attractive targets for potential “universal” influenza vaccines. Here, we demonstrated that cross-subtype protection against the influenza virus could be obtained through simultaneous priming of multiple arms of the immune response against conserved elements of the influenza virus. These results suggest a novel strategy that could potentially form a primary component of a universal influenza vaccine capable of providing long-lasting protection.

Background

Biofilms are organized communities of microorganisms embedded in a self-produced extracellular polymeric matrix (EPM), often with great phylogenetic variety. Bacteria in the subgingival biofilm are key factors that cause periodontal diseases; among these are the Gram-negative bacteria Fusobacterium nucleatum and Porphyromonas gingivalis. The objectives of this study were to characterize the major components of the EPM and to test the effect of deoxyribonuclease I (DNase I) and proteinase K.

Methods

F. nucleatum and P. gingivalis bacterial cells were grown in dynamic and static biofilm models. The effects of DNase I and proteinase K enzymes on the major components of the EPM were tested during biofilm formation and on mature biofilm. Confocal laser scanning microscopy was used in observing biofilm structure.

Results

Proteins and carbohydrates were the major components of the biofilm matrix, and extracellular DNA (eDNA) was also present. DNase I and proteinase K enzymes had little effect on biofilms in the conditions used. In the flow cell, F. nucleatum was able to grow in partially oxygenated conditions while P. gingivalis failed to form biofilm alone in similar conditions. F. nucleatum supported the growth of P. gingivalis when they were grown together as dual species biofilm.

Conclusion

DNase I and proteinase K had little effect on the biofilm matrix in the conditions used. F. nucleatum formed biofilm easily and supported the growth of P. gingivalis, which preferred anaerobic conditions.

Knowledge of the variations of the renal artery has grown in importance with increasing of renal transplants, vascular reconstructions and various surgical and radiologic techniques performing in recent years. We report the presence of unilateral doubled renal vessels, discovered on routine dissection of a male cadaver, on the right side; additional renal artery originated from the abdominal aorta. In addition the right suprarenal gland received arteries from right renal and inferior phrenic arteries only. The right inferior phrenic originated from the right renal artery.

Purpose:

Phenylephrine hydrochloride (PHCl), a commonly used mydriatic agent, causes a small but significant deterioration of accommodation. The relative roles of pharmacology and optics in this deterioration, however, remain unascertained. The study determined the combined impact of PHCl concentration (pharmacology) and pupil size (optics) on the static and dynamic characteristics of accommodation.

Materials and Methods:

A total of 16 emmetropic Indian adults viewed a high-contrast visual target that switched between 67 and 33 cm viewing distance (1.5D stimulus) with their right eye (left eye occluded using infrared transmitting filter) through natural pupils and through 8, 6, 4, and 1 mm diameter artificial pupils. This protocol was repeated once without PHCl and once each with 2.5%, 5%, and 10% PHCl. Consensual accommodation of the left eye was recorded using infrared photorefraction (60 Hz).

Results:

Relative to no PHCl, the horizontal pupil diameter of left eye was significantly larger (P < 0.001) and the response magnitude and peak velocity of accommodation and disaccommodation were modestly but significantly smaller (P < 0.02 for all) for all concentrations of PHCl tested. There was no significant difference in these parameters across the three drug concentrations (P > 0.4 for all). The response magnitude and peak velocity also decreased significantly with pupil diameter, at similar rates for the no PHCl and the three PHCl conditions (P < 0.001 for all).

Conclusion:

The reduction in accommodative performance with all drug concentrations and with pupil diameter suggests independent roles of pharmacology and optics in determining accommodative performance with PHCl. The reduction in accommodative performance is, however, modest and may be clinically irrelevant in Indian eyes.

OBJECTIVE

To assess the cardiovascular risk profile of youths across socioeconomic groups in the U.S.

RESEARCH DESIGN AND METHODS

Analysis of 1999–2008 National Health and Nutrition Examination Surveys (NHANES) including 16,085 nonpregnant 6- to 24-year-olds to estimate race/ethnicity-adjusted prevalence of obesity, central obesity, sedentary behaviors, tobacco exposure, elevated systolic blood pressure, glycated hemoglobin, non-HDL cholesterol (non–HDL-C), and high-sensitivity C-reactive protein according to age-group, sex, and poverty-income ratio (PIR) tertiles.

RESULTS

Among boys aged 6–11 years, 19.9% in the lowest PIR tertile were obese and 30.0% were centrally obese compared with 13.2 and 21.6%, respectively, in the highest-income tertile households (Pobesity < 0.05 and Pcentral obesity < 0.01). Boys aged 12–17 years in lowest-income households were more likely than their wealthiest family peers to be obese (20.6 vs. 15.6%, P < 0.05), sedentary (14.8 vs. 9.3%, P < 0.05), and exposed to tobacco (19.0 vs. 6.5%, P < 0.01). Compared with girls aged 12–17 years in highest-income households, lowest-income household girls had higher prevalence of obesity (17.9 vs. 13.1%, P < 0.05), central obesity (41.5 vs. 29.2%, P < 0.01), sedentary behaviors (20.4 vs. 9.4%, P < 0.01), and tobacco exposure (14.1 vs. 5.9%, P < 0.01). Apart from higher prevalence of elevated non–HDL-C among low-income women aged 18–24 years (23.4 vs. 15.8%, P < 0.05), no other cardiovascular disease risk factor prevalence differences were observed between lowest- and highest-income background young adults.

CONCLUSIONS

Independent of race/ethnicity, 6- to 17-year-olds from low-income families have higher prevalence of obesity, central obesity, sedentary behavior, and tobacco exposure. Multifaceted cardiovascular health promotion policies are needed to reduce health disparities between income groups.

Background

Cardio-metabolic diseases (CMDs) are a growing public health problem, but data on incidence, trends, and costs in developing countries is scarce. Comprehensive and standardised surveillance for non-communicable diseases was recommended at the United Nations High-level meeting in 2011.

Aims: To develop a model surveillance system for CMDs and risk factors that could be adopted for continued assessment of burdens from multiple perspectives in South-Asian countries.

Methods

Design: Hybrid model with two cross-sectional serial surveys three years apart to monitor trend, with a three-year prospective follow-up of the first cohort.

Sites: Three urban settings (Chennai and New Delhi in India; Karachi in Pakistan), 4000 participants in each site stratified by gender and age.

Sampling methodology: Multi-stage cluster random sampling; followed by within-household participant selection through a combination of Health Information National Trends Study (HINTS) and Kish methods.

Culturally-appropriate and methodologically-relevant data collection instruments were developed to gather information on CMDs and their risk factors; quality of life, health-care utilisation and costs, along with objective measures of anthropometric, clinical and biochemical parameters. The cohort follow-up is designed as a pilot study to understand the feasibility of estimating incidence of risk factors, disease events, morbidity, and mortality.

Results

The overall participant response rate in the first cross-sectional survey was 94.1% (Chennai 92.4%, n = 4943; Delhi 95.7%, n = 4425; Karachi 94.3%, n = 4016). 51.8% of the participants were females, 61.6% < 45years, 27.5% 45–60years and 10.9% >60 years.

Discussion

This surveillance model will generate data on prevalence and trends; help study the complex life-course patterns of CMDs, and provide a platform for developing and testing interventions and tools for prevention and control of CMDs in South-Asia. It will also help understanding the challenges and opportunities in establishing a surveillance system across countries.

Background

The present paper describes the isolation and characterization of two new aliphatic δ-lactones along with three glycerides and n-nonadecanyl cetoleate from the fruits of Coriandrum sativum L. (Apiaceae). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions.

Results

Phytochemical investigation of the methanolic extract of C. sativum L. (Apiaceae) fruits resulted in the isolation of two new aliphatic δ-lactones characterized as 2α-n-heptatriacont-(Z)-3-en-1,5-olide (1) (coriander lactone) and 2α-n-tetracont-(Z,Z)-3,26-dien-18α-ol-1,5-olide (2) (hydroxy coriander lactone) together with glyceryl-1,2-dioctadec-9,12-dienoate-3-octadec-9-enoate (3); glyceryl-1,2,3-trioctadecanoate (4); n-nonadecanyl-n-docos-11-enoate (5) and oleiyl glucoside (6).

Conclusions

Phytochemical investigation of the methanolic extract of C. sativum gave coriander lactone and hydroxy coriander lactone as the new phytoconstituents.

Background

Currently available estimates of diabetes prevalence in India are based on published data derived from very few studies. The Indian Council of Medical Research–India Diabetes (ICMR–INDIAB) study is a community-based survey conceived with the aim of obtaining the prevalence rates of diabetes in India as a whole, covering all 28 states, the National Capital Territory of Delhi, and two of the union territories in the mainland of India, with a total sample size of 124,000 individuals.

Methods

A stratified multistage sampling design has been used. In all study subjects, a structured questionnaire was administered and anthropometric parameters and blood pressure were measured. Fasting capillary blood glucose was first determined using a glucose meter. An oral glucose load was then administered to all subjects except those with self-reported diabetes, and the 2 h post-load capillary blood glucose was estimated. In every fifth subject, a fasting venous sample was collected for measurement of lipids and creatinine, a resting 12-lead electrocardiogram was performed, and dietary assessment questionnaire was administered. In all diabetic subjects, an additional diabetes questionnaire was used and a fasting venous sample drawn for glycated hemoglobin.

Results

All biological samples collected were analyzed in a central laboratory. All data collected were stored electronically. Quality control was achieved through multiple tiers of checks.

Conclusions

The ICMR–INDIAB study is the first of its kind attempting to provide accurate and comprehensive state- and national-level data on diabetes prevalence in India.

Context:

Diabetes care is complex, requiring motivated patients, providers, and systems that enable guideline-based preventative care processes, intensive risk-factor control, and positive lifestyle choices. However, care delivery in low- and middle-income countries (LMIC) is hindered by a compendium of systemic and personal factors. While electronic medical records (EMR) and computerized clinical decision-support systems (CDSS) have held great promise as interventions that will overcome system-level challenges to improving evidence-based health care delivery, evaluation of these quality improvement interventions for diabetes care in LMICs is lacking.

Objective and Data Sources:

We reviewed the published medical literature (systematic search of MEDLINE database supplemented by manual searches) to assess the quantifiable and qualitative impacts of combined EMR–CDSS tools on physician performance and patient outcomes and their applicability in LMICs.

Study Selection and Data Extraction:

Inclusion criteria prespecified the population (type 1 or 2 diabetes patients), intervention (clinical EMR–CDSS tools with enhanced functionalities), and outcomes (any process, self-care, or patient-level data) of interest. Case, review, or methods reports and studies focused on nondiabetes, nonclinical, or in-patient uses of EMR–CDSS were excluded. Quantitative and qualitative data were extracted from studies by separate single reviewers, respectively, and relevant data were synthesized.

Results:

Thirty-three studies met inclusion criteria, originating exclusively from high-income country settings. Among predominantly experimental study designs, process improvements were consistently observed along with small, variable improvements in risk-factor control, compared with baseline and/or control groups (where applicable). Intervention benefits varied by baseline patient characteristics, features of the EMR–CDSS interventions, motivation and access to technology among patients and providers, and whether EMR–CDSS tools were combined with other quality improvement strategies (e.g., workflow changes, case managers, algorithms, incentives). Patients shared experiences of feeling empowered and benefiting from increased provider attention and feedback but also frustration with technical difficulties of EMR–CDSS tools. Providers reported more efficient and standardized processes plus continuity of care but also role tensions and “mechanization” of care.

Conclusions:

This narrative review supports EMR–CDSS tools as innovative conduits for structuring and standardizing care processes but also highlights setting and selection limitations of the evidence reviewed. In the context of limited resources, individual economic hardships, and lack of structured systems or trained human capital, this review reinforces the need for well-designed investigations evaluating the role and feasibility of technological interventions (customized to each LMIC's locality) in clinical decision making for diabetes care.

Patients with trivial blunt abdominal trauma may present with isolated jejunal blow out (IJBO). A high index of suspicion is required as delayed presentation or delayed diagnosis may increase morbidity. Presentation with frank perforation peritonitis can be diagnosed by abdominal X-rays. We report the case of a patient who presented with features of peritonitis 10 days after being injured by a knee kick trauma. An erect abdominal X-ray showed extraluminal air-fluid levels, suggesting a hollow viscous injury which on exploration was found to be IJBO.

Introduction

Twin pregnancy with complete hydatidiform mole represents a very rare obstetric problem. Management of such cases is always problematic because the possibility of fetal survival should always be weighed against the risk of complications of molar pregnancy.

Case presentation

A 34-year-old Caucasian woman presented to our center with mild vaginal bleeding. Our patient was 16 weeks pregnant after a seven-year period of primary infertility. She became pregnant following a non-prescribed regimen of clomiphene citrate extending from the second day to the 13th day of her last cycle. A transabdominal ultrasound examination revealed a twin pregnancy with complete hydatidiform mole and a coexisting fetus. Serum β human chorionic gonadotropin was falsely low as identified by serial dilution of the sample (the 'hook effect'). Our patient refused termination of pregnancy and she was hospitalized for strict observation and follow-up. Unfortunately, she developed an attack of severe vaginal bleeding and a hysterotomy was performed. The fetus died shortly after birth.

Conclusions

Twin pregnancy with complete hydatidiform mole represents a matter of controversy. We suggest that conservation should always be considered whenever tertiary care services and strict observation are available.

OBJECTIVE

To compare the effect of intensive versus standard glycemic control strategies on health-related quality of life (HRQL) in a substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

RESEARCH DESIGN AND METHODS

A randomly selected subsample of 2,053 ACCORD participants enrolled in the HRQL substudy was assessed at baseline and 12-, 36-, and 48-month visits. HRQL assessment included general health status (the 36-Item Short Form Health Survey [SF-36]), diabetes symptoms (the Diabetes Symptom Distress Checklist), depression (Patient Health Questionnaire [PHQ]-9), and treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Repeated-measures ANOVA models were used to estimate change in HRQL outcomes by treatment group over 48 months adjusting for model covariates. The effects of early discontinuation of the ACCORD intensive glycemic control arm on study results were explored.

RESULTS

A total of 1,956 (95%) completed the self-report HRQL instrument(s) at baseline. The intensive arm had a larger decrease in SF-36 physical health component score than the standard arm (−1.6 vs. −1.1, P = 0.0345). Treatment satisfaction (DTSQ) showed larger improvement with intensive than standard (P = 0.0004). There were no differences in mean scores of the Diabetes Symptom Checklist and PHQ-9. Effects of participant transition following discontinuation of the intensive arm on HRQL were not significant.

CONCLUSIONS

The ACCORD trial strategy of intensive glycemic control did not lead to benefits in HRQL and was associated with modest improvement in diabetes treatment satisfaction. Thus patient acceptability was apparently not compromised with intensive and complex interventions such as those used in ACCORD.

T cell exhaustion plays a major role in failure to control chronic infections. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the transcription factor T-bet regulates CD8+ T cell exhaustion and inhibitory receptor expression. T-bet directly repressed Pdcd1 transcription and decreased the expression of other inhibitory receptors. While elevated T-bet promoted terminal differentiation following acute infection, high T-bet expression sustained exhausted CD8+ T cells and repressed inhibitory receptor expression during chronic viral infection. Persisting antigenic stimulation caused T-bet downregulation, which resulted in more severe exhaustion of CD8+ T cells. These observations suggest therapeutic opportunities involving increasing T-bet expression during chronic infection.

2,3-Butanediol (23BD) is a high-value chemical usually produced petrochemically but which can also be synthesized by some bacteria. To date, the best microbial 23BD production rates have been observed using pathogenic bacteria in fermentation systems that depend on sugars as the carbon and energy sources for product synthesis. Here we present evidence of 23BD production by three nonpathogenic acetogenic Clostridium species—Clostridium autoethanogenum, C. ljungdahlii, and C. ragsdalei—using carbon monoxide-containing industrial waste gases or syngas as the sole source of carbon and energy. Through an analysis of the C. ljungdahlii genome, the complete pathway from carbon monoxide to 23BD has been proposed. Homologues of the genes involved in this pathway were also confirmed for the other two species investigated. A gene expression study demonstrates a correlation between mRNA accumulation from 23BD biosynthetic genes and the onset of 23BD production, while a broader expression study of Wood-Ljungdahl pathway genes provides a transcription-level view of one of the oldest existing biochemical pathways.

Background

Poor neonatal health is a major contributor to under-five mortality in developing countries. A major constraint to effective neonatal survival programme has been the lack of population level data in developing countries. This study investigated the consultation patterns of caregivers during neonatal fatal illness episodes in the rural Matlab sub-district of eastern Bangladesh.

Methods

Neonatal deaths were identified through a population-based demographic surveillance system in Matlab ICDDR,B maternal and child health (MCH) project area and an adjoining government service area. Trained project staff administered a structured questionnaire on care seeking to mothers at home who had experienced a neonatal death. Univariate, bivariate and binary multivariate logistic regressions were performed to describe care seeking during the fatal illness episode.

Results

Of the 365 deaths recorded during 2003 and 2004, 84% died in the early (0-7 days) neonatal period, with the remaining deaths occurring over the subsequent 8 to 28 days. The first resort of care by parents was a qualified doctor or paramedic in 37% of cases, followed by traditional and unqualified health care providers in 25%, while 38% sought no care. Thus, almost two thirds (63%) of neonates who died received only traditional and unqualified care or no care at all during their final illness episode. About 22% sought care from more than one provider, including 6% from 3 or more providers. Such plurality in care seeking was more likely among male infants, in the late neonatal period, and in the MCH project area.

Conclusions

The high proportion of neonatal deaths that had received traditional care or no medical care in a rural area of Bangladesh highlights the need to develop community awareness about prompt medical care seeking for neonatal illnesses and to improve access to effective health care. Integration of traditional care providers into mainstream health programs should also be considered.

Background

Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known.

Methods

In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status - new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing).

Results

Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined.

Conclusions

We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem.

Catechol estrogens, especially 4-hydroxylated metabolites of 17β-estradiol (E2), are responsible for estrogen-induced carcinogenesis. 4-Hydroxyestradiol (4-OHE2), a major metabolite of E2 formed preferentially by cytochrome P-450 1B1, is oxidized to E2-3,4-quinone, which can react with DNA to yield the depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua. The apurinic sites generated by the loss of these depurinating adducts induce mutations that could lead to cancer initiation. In the present study, we have evaluated the effects of N-acetycysteine (NAcCys) on the metabolism of two cell lines, MCF-10F (a normal human breast epithelial cell line) and E6 (a normal mouse mammary epithelial cell line), treated with 4-OHE2 or its reactive metabolite, E2-3,4-quinone. Extensive HPLC with electrochemical detection and UPLC-MS/MS analyses of the cell media demonstrated that the presence of NAcCys very efficiently shifted the estrogen metabolism towards protective methoxylation and conjugation pathways in multiple ways, while formation of depurinating DNA adducts was inhibited. Protection by NAcCys appears to be similar in both cell lines irrespective of their origin (human or mouse) or the presence of estrogen receptor-alpha. This finding suggests that NAcCys, a common dietary supplement, could be used as a potential chemopreventive agent to block the initial step in the genotoxicity caused by catechol estrogen quinones.

Background

In developed countries, perinatal death is known to cause major emotional and social effects on mothers. However, little is known about these effects in low income countries which bear the brunt of perinatal mortality burden. This paper reports the impact of perinatal death on psychological status and social consequences among mothers in a rural area of Bangladesh.

Methods

A total of 476 women including 122 women with perinatal deaths were assessed with the Edinburgh Postnatal Depression Scale (EPDS-B) at 6 weeks and 6 months postpartum, and followed up for negative social consequences at 6 months postpartum. Trained female interviewers carried out structured interviews at women's home.

Results

Overall 43% (95% CI: 33.7-51.8%) of women with a perinatal loss at 6 weeks postpartum were depressed compared to 17% (95% CI: 13.7-21.9%) with healthy babies (p = < 0.001). Depression status were significantly associated with women reporting negative life changes such as worse relationships with their husband (adjusted OR = 3.89, 95% CI: 1.37-11.04) and feeling guilty (adjusted OR = 2.61, 95% CI: 1.22-5.63) following the results of their last pregnancy outcome after 6 months of childbirth.

Conclusions

This study highlights the greatly increased vulnerability of women with perinatal death to experience negative psychological and social consequences. There is an urgent need to develop appropriate mental health care services for mothers with perinatal deaths in Bangladesh, including interventions to develop positive family support.

The title compound, C20H16O6, which contains one chiral centre, crystallizes as a racemate. The mean planes of the two coumarin units make a dihedral angle of 88.07 (2)°. The pyrone ring containing the chiral centre adopts a sofa conformation. In the crystal, four mol­ecules are linked by O—H⋯O hydrogen bonds, forming a tetrameric ring with graph-set motif R 4 4(32). These tetramers are further linked by O—H⋯O hydrogen bonds into a three-dimensional network.

Coronary heart disease (CHD) is currently the leading cause of death worldwide and together with diabetes, poses a serious health threat, particularly in the Indian Asian population. Risk factor management has evolved considerably with the continued emergence of new and thought-provoking evidence. The stream of laboratory- and population-based research findings as well as unresolved controversies may pose dilemmas and conflicting impulses in most clinicians, and even in our more well-informed patients. As results of the most recent clinical trials on glycaemic control for macrovascular risk reduction are woven into concrete clinical practice guidelines, this paper seeks to sort through unwieldy evidence, keeping these findings in perspective, to deliver a clearer message for the context of South Asia and cardio-metabolic risk management.

OBJECTIVE

To compare diabetes prevalence among Asian Americans by World Health Organization and U.S. BMI classifications.

RESEARCH DESIGN AND METHODS

Data on Asian American adults (n = 7,414) from the National Health Interview Survey for 1997–2005 were analyzed. Diabetes prevalence was estimated across weight and ethnic group strata.

RESULTS

Regardless of BMI classification, Asian Indians and Filipinos had the highest prevalence of overweight (34–47 and 35–47%, respectively, compared with 20–38% in Chinese; P < 0.05). Asian Indians also had the highest ethnic-specific diabetes prevalence (ranging from 6–7% among the normal weight to 19–33% among the obese) compared with non-Hispanic whites: odds ratio (95% CI) for Asian Indians 2.0 (1.5–2.6), adjusted for age and sex, and 3.1 (2.4–4.0) with additional adjustment for BMI.

CONCLUSIONS

Asian Indian ethnicity, but not other Asian ethnicities, was strongly associated with diabetes. Weight classification as a marker of diabetes risk may need to accommodate differences across Asian subgroups.

Objective

This study assessed the agreement between medical physicians in their interpretation of verbal autopsy (VA) interview data for identifying causes of neonatal deaths in rural Bangladesh.

Methods

The study was carried out in Matlab, a rural sub-district in eastern Bangladesh. Trained persons conducted the VA interview with the mother or another family member at the home of the deceased. Three physicians and a medical assistant independently reviewed the VA interviews to assign causes of death using the International Classification of Diseases - Tenth Revision (ICD-10) codes. A physician assigned cause was decided when at least two physicians agreed on a cause of death. Cause-specific mortality fraction (CSMF), kappa (k) statistic, sensitivity, specificity, and positive predictive values were applied to compare agreement between the reviewers.

Results

Of the 365 neonatal deaths reviewed, agreement on a direct cause of death was reached by at least two physicians in 339 (93%) of cases. Physician and medical assistant reviews of causes of death demonstrated the following levels of diagnostic agreement for the main causes of deaths: for birth asphyxia the sensitivity was 84%, specificity 93%, and kappa 0.77. For prematurity/low birth weight, the sensitivity, specificity, and kappa statistics were, respectively, 53%, 96%, and 0.55, for sepsis/meningitis they were 48%, 98%, and 0.53, and for pneumonia they were 75%, 94%, and 0.51.

Conclusion

This study revealed a moderate to strong agreement between physician- assigned and medical assistant- assigned major causes of neonatal death. A well-trained medical assistant could be considered an alternative for assigning major causes of neonatal deaths in rural Bangladesh and in similar settings where physicians are scarce and their time costs more. A validation study with medically confirmed diagnosis will improve the performance of VA for assigning cause of neonatal death.

The study assessed the timing and causes of neonatal deaths in a rural area of Bangladesh. A population-based demographic surveillance system, run by the International Centre for Diarrhoeal Disease Research, Bangladesh, recorded livebirths and neonatal deaths during 2003-2004 among a population of 224,000 living in Matlab, a rural subdistrict of eastern Bangladesh. Deaths were investigated using the INDEPTH/World Health Organization verbal autopsy. Three physicians independently reviewed data from verbal autopsy interview to assign the cause of death. There were 11,291 livebirths and 365 neonatal deaths during the two-year period. The neonatal mortality rate was 32.3 per 1,000 livebirths. Thirty-seven percent of the neonatal deaths occurred within 24 hours, 76% within 0-3 days, 84% within 0-7 days, and the remaining 16% within 8-28 days. Birth asphyxia (45%), prematurity/low birthweight (15%), sepsis/meningitis (12%), respiratory distress syndrome (7%), and pneumonia (6%) were the major direct causes of death. Birth asphyxia (52.8%) was the single largest category of cause of death in the early neonatal period while meningitis/sepsis (48.3%) was the single largest category in the late neonatal period. The high proportion of deaths during the early neonatal period and the far-higher proportion of neonatal deaths caused by birth asphyxia compared to the global average (45% vs 23-29%) indicate the lack of skilled birth attendance and newborn care for the large majority of births that occur in the home in rural Bangladesh. Resuscitation of newborns and management of low-birthweight/premature babies need to be at the core of neonatal interventional packages in rural Bangladesh.

Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of “individually tailored” donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.

Background

Tetherin/BST-2 is a recently-identified potent restriction factor in human cells that restricts HIV particle release following particle formation and budding at the plasma membrane. Vpu counteracts tetherin's restriction of particle release in a manner that has not yet been fully defined. We recently identified calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting protein that also restricts particle release. We hypothesized that CAML may act to enhance tetherin-mediated restriction of particle release and thereby explain how two distinct factors could be responsible for Vpu-responsive restriction.

Methodology/Principal Findings

Endogenous levels of tetherin in human cells correlated well with their restriction pattern and responsiveness to Vpu, while levels of cellular CAML protein did not. Tetherin but not CAML was inducible by interferon in a wide variety of human cells. Stable depletion of human CAML in restrictive HeLa cells had no effect on cell surface levels of tetherin, and failed to relieve tetherin-mediated restriction. Stable depletion of tetherin from HeLa cells, in contrast, rendered HeLa cells permissive and Vpu-unresponsive. Tetherin but not CAML expression in permissive human cells rendered them restrictive and Vpu responsive. Depletion of CAML had no influence on cell surface levels of tetherin.

Conclusions/Significance

We conclude that tetherin restricts particle release and does not require CAML for this effect. Furthermore, these results do not support a major role for CAML in restricting HIV particle release in human cells.