Evaluation of four disease management programs: evidence from blue cross blue shield of Louisiana.

Aims: Chronic diseases impose a substantial healthcare burden. This study sought to evaluate the clinical and economic impact of new disease management (DM) programs, targeting four major chronic disease groups: diabetes, coronary heart disease (CHD)/hypertension (HTN), asthma/chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF)/chronic kidney disease (CKD).Materials and methods: Between March 1, 2015, and February 28, 2018, members with Blue Cross Blue Shield of Louisiana insurance were contacted and enrolled in a DM program if they were aged 18 years through 64 years, eligible for a DM program, and had not been previously enrolled in a DM program. Active enrollees of a DM program ("IN" group) were compared to members who were not yet enrolled ("OUT" group). Average per member per month (PMPM) costs were aggregated annually to document any descriptive trends. Multivariable model estimates were used to compare PMPM costs for all IN subjects and all OUT subjects. Total medical savings were evaluated for the following time intervals: 1-12 months, 13-24 months, and 25-36 months.Results: For all four DM programs, average costs PMPM trended upward over time for the OUT cohort, while they remained relatively stable for the IN cohort. Some evidence also showed that DM programs improved clinical outcomes, such as hemoglobin A1c values. A difference in difference analysis showed PMPM savings for all four programs combined of $31.61, $50.45, and $53.72 after 1, 2, and 3 years, respectively. Multivariable modeling results showed total savings after 3 years of $14,460,174 for all DM programs combined.Limitations: Although multivariable models adjusted for several clinical, demographic, and economic characteristics; it is possible that some important confounders were missing due to lack of data.Conclusions: DM programs implemented to control diabetes, CHD/HTN, CHF/CKD, and asthma/COPD are cost-effective and show some evidence of improved clinical outcomes.

Vehicular traffic noise prediction using soft computing approach.

A new approach for the development of vehicular traffic noise prediction models is presented. Four different soft computing methods, namely, Generalized Linear Model, Decision Trees, Random Forests and Neural Networks, have been used to develop models to predict the hourly equivalent continuous sound pressure level, Leq, at different locations in the Patiala city in India. The input variables include the traffic volume per hour, percentage of heavy vehicles and average speed of vehicles. The performance of the four models is compared on the basis of performance criteria of coefficient of determination, mean square error and accuracy. 10-fold cross validation is done to check the stability of the Random Forest model, which gave the best results. A t-test is performed to check the fit of the model with the field data.

Alveolar proteinosis associated with aluminium dust inhalation.

Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries.

Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group.

The critical importance of membrane-bound transporters in pharmacotherapy is widely recognized, but little is known about drug transporter activity in children. In this white paper, the Pediatric Transporter Working Group presents a systematic review of the ontogeny of clinically relevant membrane transporters (e.g., SLC, ABC superfamilies) in intestine, liver, and kidney. Different developmental patterns for individual transporters emerge, but much remains unknown. Recommendations to increase our understanding of membrane transporters in pediatric pharmacotherapy are presented.

Modal analysis of human body vibration model for Indian subjects under sitting posture.

Need and importance of modelling in human body vibration research studies are well established. The study of biodynamic responses of human beings can be classified into experimental and analytical methods. In the past few decades, plenty of mathematical models have been developed based on the diverse field measurements to describe the biodynamic responses of human beings. In this paper, a complete study on lumped parameter model derived from 50th percentile anthropometric data for a seated 54- kg Indian male subject without backrest support under free un-damped conditions has been carried out considering human body segments to be of ellipsoidal shape. Conventional lumped parameter modelling considers the human body as several rigid masses interconnected by springs and dampers. In this study, concept of mass of interconnecting springs has been incorporated and eigenvalues thus obtained are found to be closer to the values reported in the literature. Results obtained clearly establish decoupling of vertical and fore-and-aft oscillations. PRACTITIONER SUMMARY: The mathematical modelling of human body vibration studies help in validating the experimental investigations for ride comfort of a sitting subject. This study clearly establishes the decoupling of vertical and fore-and-aft vibrations and helps in better understanding of possible human response to single and multi-axial excitations.

Status of iodine deficiency in district Kangra, Himachal Pradesh after 60 years of salt iodization.

BACKGROUND/OBJECTIVES: District Kangra, Himachal Pradesh(HP), India is a known endemic area for iodine deficiency disorders (IDD) since 1956. The present study was conducted in district Kangra, Himachal Pradesh with the objective to assess the prevalence of iodine deficiency in school-age children. SUBJECTS/METHODS: A total of 1864 children in the age group of 6-12 years were included. Clinical examination of thyroid of all children was undertaken. 'On the spot' urine samples were collected from 463 children. The salt samples were collected from 327 children. RESULTS: The total goiter prevalence of 15.8% was found. The proportion of children with urinary iodine excretion (UIE) levels <50.0, 50.0-99.9 and ≥ 100 µg/l was 2.2, 14.3 and 83.5%, respectively. The median UIE level was 200 µg/l. About 82.3% of the families were consuming salt with iodine content ≥ 15 ppm. CONCLUSION: The population in district Kangra is possibly in a transition phase from iodine deficient (as revealed by total goiter rate of 15.8%) to iodine sufficiency (as revealed by median UIE levels of 200 µg/l).

How much do we know about drug handling by SLC and ABC drug transporters in children?

Although solute carrier (SLC) and ATP-binding cassette (ABC) transporters are critical to the absorption, distribution, and elimination of many small-molecule drugs in children, how these transporters regulate pediatric drug handling remains unclear. For proper dosing and to diminish toxicity, we need a better understanding of how organ development and functional maturation, as well as developmental changes in systemic physiology, impact transporter-mediated drug handling at pediatric developmental stages from the preterm infant through adolescence.

Prevalence of left heart contrast in healthy, young, asymptomatic humans at rest breathing room air.

Our purpose was to report the prevalence of healthy, young, asymptomatic humans who demonstrate left heart contrast at rest, breathing room air. We evaluated 176 subjects (18-41 years old) using transthoracic saline contrast echocardiography. Left heart contrast appearing ≤3 cardiac cycles, consistent with a patent foramen ovale (PFO), was detected in 67 (38%) subjects. Left heart contrast appearing >3 cardiac cycles, consistent with the transpulmonary passage of contrast, was detected in 49 (28%) subjects. Of these 49 subjects, 31 were re-evaluated after breathing 100% O2 for 10-15min and 6 (19%) continued to demonstrate the transpulmonary passage of contrast. Additionally, 18 of these 49 subjects were re-evaluated in the upright position and 1 (5%) continued to demonstrate the transpulmonary passage of contrast. These data suggest that ~30% of healthy, young, asymptomatic subjects demonstrate the transpulmonary passage of contrast at rest which is reduced by breathing 100% O2 and assuming an upright body position.

Groundnut improvement: use of genetic and genomic tools.

Groundnut (Arachis hypogaea L.), a self-pollinated legume is an important crop cultivated in 24 million ha world over for extraction of edible oil and food uses. The kernels are rich in oil (48-50%) and protein (25-28%), and are source of several vitamins, minerals, antioxidants, biologically active polyphenols, flavonoids, and isoflavones. Improved varieties of groundnut with high yield potential were developed and released for cultivation world over. The improved varieties belong to different maturity durations and possess resistance to diseases, tolerance to drought, enhanced oil content, and improved quality traits for food uses. Conventional breeding procedures along with the tools for phenotyping were largely used in groundnut improvement programs. Mutations were used to induce variability and wide hybridization was attempted to tap variability from wild species. Low genetic variability has been a bottleneck for groundnut improvement. The vast potential of wild species, reservoir of new alleles remains under-utilized. Development of linkage maps of groundnut during the last decade was followed by identification of markers and quantitative trait loci for the target traits. Consequently, the last decade has witnessed the deployment of molecular breeding approaches to complement the ongoing groundnut improvement programs in USA, China, India, and Japan. The other potential advantages of molecular breeding are the feasibility to target multiple traits for improvement and provide tools to tap new alleles from wild species. The first groundnut variety developed through marker-assisted back-crossing is a root-knot nematode-resistant variety, NemaTAM in USA. The uptake of molecular breeding approaches in groundnut improvement programs by NARS partners in India and many African countries is slow or needs to be initiated in part due to inadequate infrastructure, high genotyping costs, and human capacities. Availability of draft genome sequence for diploid (AA and BB) and tetraploid, AABB genome species of Arachis in coming years is expected to bring low-cost genotyping to the groundnut community that will facilitate use of modern genetics and breeding approaches such as genome-wide association studies for trait mapping and genomic selection for crop improvement.

Quantitative trait locus analysis and construction of consensus genetic map for drought tolerance traits based on three recombinant inbred line populations in cultivated groundnut (Arachis hypogaea L.).

Groundnut (Arachis hypogaea L.) is an important food and cash crop grown mainly in semi-arid tropics (SAT) regions of the world where drought is the major constraint on productivity. With the aim of understanding the genetic basis and identification of quantitative trait loci (QTL) for drought tolerance, two new recombinant inbred line (RIL) mapping populations, namely ICGS 76 × CSMG 84-1 (RIL-2) and ICGS 44 × ICGS 76 (RIL-3), were used. After screening of 3,215 simple sequence repeat (SSR) markers on the parental genotypes of these populations, two new genetic maps were developed with 119 (RIL-2) and 82 (RIL-3) SSR loci. Together with these maps and the reference map with 191 SSR loci based on TAG 24 × ICGV 86031 (RIL-1), a consensus map was constructed with 293 SSR loci distributed over 20 linkage groups, spanning 2,840.8 cM. As all these three populations segregate for drought-tolerance-related traits, a comprehensive QTL analysis identified 153 main effect QTL (M-QTL) and 25 epistatic QTL (E-QTL) for drought-tolerance-related traits. Localization of these QTL on the consensus map provided 16 genomic regions that contained 125 QTL. A few key genomic regions were selected on the basis of the QTL identified in each region, and their expected role in drought adaptation is also discussed. Given that no major QTL for drought adaptation were identified, novel breeding approaches such as marker-assisted recurrent selection (MARS) and genomic selection (GS) approaches are likely to be the preferred approaches for introgression of a larger number of QTL in order to breed drought-tolerant groundnut genotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11032-011-9660-0) contains supplementary material, which is available to authorized users.

A diagnostic system for electrical faults in a high current discharge plasma setup.

A diagnostic system to detect electrical faults inside a coaxial high current discharge device is presented here. This technique utilizes two biconical antennas picking up electromagnetic radiation from the discharge device, a voltage divider sensing input voltage, and a Rogowski coil measuring the main discharge current. A computer program then analyses frequency components in these signals and provides information as to whether the discharge event was normal or any breakdown fault occurred inside the coaxial device. The diagnostic system is developed for a 450 kV and 50 kA capillary discharge plasma setup. For the setup various possible faults are analyzed by electrical simulation, followed by experimental results. In the case of normal discharge through the capillary load the dominant frequency is ∼4 MHz. Under faulty conditions, the peak in magnitude versus frequency plot of the antenna signal changes according to the fault position which involves different paths causing variation in the equivalent circuit elements.

Identification of several small main-effect QTLs and a large number of epistatic QTLs for drought tolerance related traits in groundnut (Arachis hypogaea L.).

Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2n = 4x = 40), is a self pollinated and widely grown crop in the semi-arid regions of the world. Improvement of drought tolerance is an important area of research for groundnut breeding programmes. Therefore, for the identification of candidate QTLs for drought tolerance, a comprehensive and refined genetic map containing 191 SSR loci based on a single mapping population (TAG 24 x ICGV 86031), segregating for drought and surrogate traits was developed. Genotyping data and phenotyping data collected for more than ten drought related traits in 2-3 seasons were analyzed in detail for identification of main effect QTLs (M-QTLs) and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48-33.36% phenotypic variation explained (PVE) were identified using QTL Cartographer, while only 65 M-QTLs with 1.3-15.01% PVE were identified using QTLNetwork. A total of 53 M-QTLs were such which were identified using both programmes. On the other hand, GMM identified 186 (8.54-44.72% PVE) and 63 (7.11-21.13% PVE), three and two loci interactions, whereas only 8 E-QTL interactions with 1.7-8.34% PVE were identified through QTLNetwork. Interestingly a number of co-localized QTLs controlling 2-9 traits were also identified. The identification of few major, many minor M-QTLs and QTL × QTL interactions during the present study confirmed the complex and quantitative nature of drought tolerance in groundnut. This study suggests deployment of modern approaches like marker-assisted recurrent selection or genomic selection instead of marker-assisted backcrossing approach for breeding for drought tolerance in groundnut.

Assessment of transpiration efficiency in peanut (Arachis hypogaea L.) under drought using a lysimetric system.

Transpiration efficiency (TE) is an important trait for drought tolerance in peanut (Arachis hypogaea L.). The variation in TE was assessed gravimetrically using a long time interval in nine peanut genotypes (Chico, ICGS 44, ICGV 00350, ICGV 86015, ICGV 86031, ICGV 91114, JL 24, TAG 24 and TMV 2) grown in lysimeters under well-watered or drought conditions. Transpiration was measured by regularly weighing the lysimeters, in which the soil surface was mulched with a 2-cm layer of polythene beads. TE in the nine genotypes used varied from 1.4 to 2.9 g kg(-1) under well-watered and 1.7 to 2.9 g kg(-1) under drought conditions, showing consistent variation in TE among genotypes. A higher TE was found in ICGV 86031 in both well-watered and drought conditions and lower TE was found in TAG-24 under both water regimes. Although total water extraction differed little across genotypes, the pattern of water extraction from the soil profile varied among genotypes. High water extraction within 24 days following stress imposition was negatively related to pod yield (r(2) = 0.36), and negatively related to water extraction during a subsequent period of 32 days (r(2) = 0.73). By contrast, the latter, i.e. water extraction during a period corresponding to grain filling (24 to 56 days after flowering) was positively related to pod yield (r(2) = 0.36). TE was positively correlated with pod weight (r(2) = 0.30) under drought condition. Our data show that under an intermittent drought regime, TE and water extraction from the soil profile during a period corresponding to pod filling were the most important components.

The first SSR-based genetic linkage map for cultivated groundnut (Arachis hypogaea L.).

Molecular markers and genetic linkage maps are pre-requisites for molecular breeding in any crop species. In case of peanut or groundnut (Arachis hypogaea L.), an amphidiploid (4X) species, not a single genetic map is, however, available based on a mapping population derived from cultivated genotypes. In order to develop a genetic linkage map for tetraploid cultivated groundnut, a total of 1,145 microsatellite or simple sequence repeat (SSR) markers available in public domain as well as unpublished markers from several sources were screened on two genotypes, TAG 24 and ICGV 86031 that are parents of a recombinant inbred line mapping population. As a result, 144 (12.6%) polymorphic markers were identified and these amplified a total of 150 loci. A total of 135 SSR loci could be mapped into 22 linkage groups (LGs). While six LGs had only two SSR loci, the other LGs contained 3 (LG_AhXV) to 15 (LG_AhVIII) loci. As the mapping population used for developing the genetic map segregates for drought tolerance traits, phenotyping data obtained for transpiration, transpiration efficiency, specific leaf area and SPAD chlorophyll meter reading (SCMR) for 2 years were analyzed together with genotyping data. Although, 2-5 QTLs for each trait mentioned above were identified, the phenotypic variation explained by these QTLs was in the range of 3.5-14.1%. In addition, alignment of two linkage groups (LGs) (LG_AhIII and LG_AhVI) of the developed genetic map was shown with available genetic maps of AA diploid genome of groundnut and Lotus and Medicago. The present study reports the construction of the first genetic map for cultivated groundnut and demonstrates its utility for molecular mapping of QTLs controlling drought tolerance related traits as well as establishing relationships with diploid AA genome of groundnut and model legume genome species. Therefore, the map should be useful for the community for a variety of applications.

Chemical synthesis, pharmacological characterization, and possible formation in unicellular fungi of 3-hydroxy-anandamide.

The fungal pathogen Candida albicans transforms arachidonic acid (AA) into 3-hydroxyarachidonic acid [3R-HETE], and we investigated if its nonpathogenic and 3R-HETE-producing close relative, Dipodascopsis uninucleata, could similarly transform the endocannabinoid/endovanilloid anandamide into 3-hydroxyanandamide (3-HAEA). We found that D. uninucleata converts anandamide into 3-HAEA, and we therefore developed an enantiodivergent synthesis for this compound to study its pharmacological activity. Both enantiomers of 3-HAEA were as active as anandamide at elevating intracellular Ca2+ via TRPV1 receptors overexpressed in HEK-293 cells, while a approximately 70-90-fold and approximately 45-60-fold lower affinity at cannabinoid CB1 and CB2 receptors was instead observed. Patch clamp recordings showed that 3R-HAEA activates a TRPV1-like current in TRPV1-expressing HEK-293 cells. Thus, 3R-HETE-producing yeasts might convert anandamide released by host cells at the site of infection into 3R-HAEA, and this event might contribute to the inflammatory and algogenous responses associated to fungal diseases.

Tubercular and chronic pyogenic osteomyelitis of cranio-facial bones: a retrospective analysis.

AIM: To analyse current trends in our population with respect to the presentation, diagnosis and management of tubercular and chronic pyogenic osteomyelitis of the cranio-facial bones. DESIGN: Retrospective study. SETTING: Tertiary healthcare centre. PATIENTS AND METHODS: The study population comprised 14 patients with tubercular and chronic pyogenic osteomyelitis who were managed in the otorhinolaryngology department between May 2002 and December 2005. RESULTS: Odontogenic infections, sinus infections and aural infections were the most commonly identified aetiological factors. Most of the patients presented with swelling, pain and discharging sinus. The diagnosis was established on the basis of clinical evaluation, radiological investigations and histopathological analysis, with six cases diagnosed with tubercular osteomyelitis and eight cases with chronic pyogenic osteomyelitis. All the patients were initially commenced on oral antibiotics, which were continued for two weeks in all cases with chronic pyogenic osteomyelitis. All the patients with pyogenic osteomyelitis underwent surgical management, with one patient requiring repeated surgical interventions. All the patients with tubercular osteomyelitis received anti-tubercular chemotherapy, with complete cure. CONCLUSIONS: Osteomyelitis of the cranio-facial bones is an uncommon entity which requires a high index of clinical suspicion along with radiological and histopathological investigations in order to establish the diagnosis. Tubercular osteomyelitis is clinically and radiologically indistinguishable from pyogenic osteomyelitis, and the two conditions can be differentiated only on the basis of histopathological evaluation of involved tissue.

Staged in vitro reconstitution and implantation of engineered rat kidney tissue.

A major hurdle for current xenogenic-based and other approaches aimed at engineering kidney tissues is reproducing the complex three-dimensional structure of the kidney. Here, a stepwise, in vitro method of engineering rat kidney-like tissue capable of being implanted is described. Based on the fact that the stages of kidney development are separable into in vitro modules, an approach was devised that sequentially induces an epithelial tubule (the Wolffian duct) to undergo in vitro budding, followed by branching of a single isolated bud and its recombination with metanephric mesenchyme. Implantation of the recombined tissue results in apparent early vascularization. Thus, in principle, an unbranched epithelial tubular structure (potentially constructed from cultured cells) can be induced to form kidney tissue such that this in vitro engineered tissue is capable of being implanted in host rats and developing glomeruli with evidence of early vascularization. Optimization studies (of growth factor and matrix) indicate multiple suitable combinations and suggest both a most robust and a minimal system. A whole-genome microarray analysis suggested that recombined tissue recapitulated gene expression changes that occur in vivo during later stages of kidney development, and a functional assay demonstrated that the recombined tissue was capable of transport characteristic of the differentiating nephron. The approach includes several points where tissue can be propagated. The data also show how functional, 3D kidney tissue can assemble by means of interactions of independent modules separable in vitro, potentially facilitating systems-level analyses of kidney development.

Biological role of hepoxilins: upregulation of phospholipid hydroperoxide glutathione peroxidase as a cellular response to oxidative stress?

The 12S-lipoxygenase (12S-LOX) pathway of arachidonic acid (AA) metabolism is bifurcated at 12(S)-hydroperoxy-5Z,8Z,10E (12S-HpETE) in the reduction route to form 12S-hydroxy-eicosatetraenoic acid (12S-HETE) and in 8(S/R)-hydroxy-11(S),12S-trans-epoxyeicosa-5Z,9E,14Z-trienoic acid (HXA3) synthase pathway, previously known as isomerization route, to form hepoxilins. Earlier we showed that the HXA3 formation is restricted to cellular systems devoid of hydroperoxide reducing enzymes, e.g. GPxs, thus causing a persistent oxidative stress situation. Here, we show that HXA3 at as low as 100 nM concentration upregulates phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA and protein expressions, whereas other metabolites of AA metabolism 12S-HpETE and 12S-HETE failed to stimulate the PHGPx. Moreover, the decrease in 12S-HpETE below a threshold value of the hydroperoxide tone causes both suppression of the overall 12S-LOX activity and a shift from HXA3 formation towards 12S-HETE formation. We therefore propose that under persistent oxidative stress the formation of HXA3 and the HXA3-induced upregulation of PHGPx constitute a compensatory defense response to protect the vitality and functionality of the cell.

Acetylsalicylic acid as antifungal in Eremothecium and other yeasts.

Interesting distribution patterns of acetylsalicylic acid (ASA, aspirin) sensitive 3-hydroxy (OH) oxylipins were previously reported in some representatives of the yeast genus Eremothecium--an important group of plant pathogens. Using immunofluorescence microscopy and 3-OH oxylipin specific antibodies in this study, we were able to map the presence of these compounds also in other Eremothecium species. In Eremothecium cymbalariae, these oxylipins were found to cover mostly the spiky tips of narrowly triangular ascospores while in Eremothecium gossypii, oxylipins covered the whole spindle-shaped ascospore with terminal appendages. The presence of these oxylipins was confirmed by chemical analysis. When ASA, a 3-OH oxylipin inhibitor, was added to these yeasts in increasing concentrations, the sexual stage was found to be the most sensitive. Our results suggest that 3-OH oxylipins, produced by mitochondria through incomplete beta-oxidation, are associated with the development of the sexual stages in both yeasts. Strikingly, preliminary studies on yeast growth suggest that yeasts, characterized by mainly an aerobic respiration rather than a fermentative pathway, are more sensitive to ASA than yeasts characterized by both pathways. These data further support the role of mitochondria in sexual as well as asexual reproduction of yeasts and its role to serve as a target for ASA antifungal action.