Showing papers by "University of Maryland, Baltimore published in 2009"

CHARMM: the biomolecular simulation program.

Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.

Abstract: The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3-phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform "all-CHARMM" simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems.

Mammalian nicotinic acetylcholine receptors: from structure to function.

Abstract: The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a “receptive substance,” from which the idea of a “receptor” came to light. Subsequent studies...

Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy

Abstract: Context Clopidogrel therapy improves cardiovascular outcomes in patients with acute coronary syndromes and following percutaneous coronary intervention by inhibiting adenosine diphosphate (ADP)–dependent platelet activation. However, nonresponsiveness is widely recognized and is related to recurrent ischemic events. Objective To identify gene variants that influence clopidogrel response. Design, Setting, and Participants In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 healthy Amish persons and measured response by ex vivo platelet aggregometry. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention. Main Outcome Measure ADP-stimulated platelet aggregation in response to clopidogrel treatment and cardiovascular events. Results Platelet response to clopidogrel was highly heritable (h 2 = 0.73; P −13 for rs12777823, additive model). The rs12777823 polymorphism was in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished clopidogrel response, accounting for 12% of the variation in platelet aggregation to ADP (P = 4.3 × 10 −11 ). The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention (P = .02). Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death during 1 year of follow-up (hazard ratio, 2.42; 95% confidence interval, 1.18-4.99; P = .02). Conclusion CYP2C19*2 genotype was associated with diminished platelet response to clopidogrel treatment and poorer cardiovascular outcomes.

Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.

Abstract: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

The genome of the blood fluke Schistosoma mansoni

Abstract: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

Development and Characterization of a High Density SNP Genotyping Assay for Cattle

Abstract: The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle.

A Novel Androgen Receptor Splice Variant Is Up-regulated during Prostate Cancer Progression and Promotes Androgen Depletion–Resistant Growth

Abstract: The androgen receptor (AR) plays a key role in progression to incurable androgen ablation–resistant prostate cancer (PCA). We have identified three novel AR splice variants lacking the ligand-binding domain (designated as AR3, AR4, and AR5) in hormone-insensitive PCA cells. AR3, one of the major splice variants expressed in human prostate tissues, is constitutively active, and its transcriptional activity is not regulated by androgens or antiandrogens. Immunohistochemistry analysis on tissue microarrays containing 429 human prostate tissue samples shows that AR3 is significantly up-regulated during PCA progression and AR3 expression level is correlated with the risk of tumor recurrence after radical prostatectomy. Overexpression of AR3 confers ablation-independent growth of PCA cells, whereas specific knockdown of AR3 expression (without altering AR level) in hormone-resistant PCA cells attenuates their growth under androgen-depleted conditions in both cell culture and xenograft models, suggesting an indispensable role of AR3 in ablation-independent growth of PCA cells. Furthermore, AR3 may play a distinct, yet essential, role in ablation-independent growth through the regulation of a unique set of genes, including AKT1 , which are not regulated by the prototype AR. Our data suggest that aberrant expression of AR splice variants may be a novel mechanism underlying ablation independence during PCA progression, and AR3 may serve as a prognostic marker to predict patient outcome in response to hormonal therapy. Given that these novel AR splice variants are not inhibited by currently available antiandrogen drugs, development of new drugs targeting these AR isoforms may potentially be effective for treatment of ablation-resistant PCA. [Cancer Res 2009;69(6):2305–13]

Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease

Abstract: Background— Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD. Methods and Results— In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increas...

Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.

Abstract: Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features of CSCs, including capacities for proliferation, self-renewal, and differentiation, resistance to chemotherapy, and expressing CSC surface marker CD133. In vivo experiments show that the ALDH1-positive cells could generate tumors that recapitulate the heterogeneity of the parental cancer cells. Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer. ALDH1 is therefore a lung tumor stem cell-associated marker. These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer. (Mol Cancer Res 2009;7(3):330–8)

The genomic basis of trophic strategy in marine bacteria.

Abstract: Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis RB2256, that serve as useful model organisms for copiotrophic and oligotrophic modes of life and specifically relate the genomic features to trophic strategy for these organisms and define their molecular mechanisms of adaptation. We developed a model for predicting trophic lifestyle from genome sequence data and tested >400,000 proteins representing >500 million nucleotides of sequence data from 126 genome sequences with metagenome data of whole environmental samples. When applied to available oceanic metagenome data (e.g., the Global Ocean Survey data) the model demonstrated that oligotrophs, and not the more readily isolatable copiotrophs, dominate the ocean's free-living microbial populations. Using our model, it is now possible to define the types of bacteria that specific ocean niches are capable of sustaining.

Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project.

Abstract: OBJECTIVE: To report contemporary estimates of the prevalence of knee-related osteoarthritis (OA) outcomes in African Americans and Caucasians aged > or = 45 years. METHODS: Weighted prevalence estimates for knee symptoms, radiographic knee OA, symptomatic knee OA, and severe radiographic knee OA were calculated for age, ethnic, and sex subgroups, in 3018 participants (33% African Americans, 38% men) in the baseline examination (1991-97) of The Johnston County Osteoarthritis Project, a population-based study of OA in North Carolina. Radiographic knee OA was defined as Kellgren-Lawrence radiographic grade > or = 2, severe radiographic knee OA as grades 3 and 4, and symptomatic knee OA as knee symptoms in a knee with radiographic OA. RESULTS: Knee symptoms were present in 43%, 28% had radiographic knee OA, 16% had symptomatic knee OA, and 8% had severe radiographic knee OA. Prevalence was higher in older individuals and women. African Americans had slightly higher prevalence of knee symptoms, radiographic knee OA, and symptomatic knee OA, but significantly higher prevalence of severe radiographic knee OA compared to Caucasians. CONCLUSION: Policy should be directed to increasing education of the public and the medical community about the high prevalence of these conditions, especially in these subgroups, to decrease their impact and ultimately prevent them.

The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness.

Abstract: Objectives Poor adherence to medication treatment can have devastating consequences for patients with mental illness. The goal of this project was to develop recommendations for addressing adherence problems to improve patient outcomes. Methods The editors identified important topics and questions concerning medication adherence problems in serious mental illness that are not fully addressed in the literature. A survey was developed containing 39 questions (521 options) asking about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. Results of the literature review and survey were used to develop recommendations for assessing and improving adherence in patients with serious mental illness. Results ASSESSING ADHERENCE: The experts endorsed percentage of medication not taken as the preferred method of defining adherence, with 80% or more of medication taken endorsed as an appropriate cut-off for adherence in bipolar disorder and schizophrenia. Although self- and physician report are the most common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. The experts recommend that, if possible, clinicians also use more objective measures (e.g., pill counts, pharmacy records, and, when appropriate, serum levels such as are used for lithium). Use of a validated self-report scale may help improve accuracy. Scope of the problem The majority of the experts believed the average patient with schizophrenia or bipolar disorder in their practices takes only 51%-70% of prescribed medication. FACTORS ASSOCIATED WITH NONADHERENCE: The experts endorsed poor insight and lack of illness awareness, distress associated with specific side effects or a general fear of side effects, inadequate efficacy with persistent symptoms, and believing medications are no longer needed as the most important factors leading to adherence problems in schizophrenia and bipolar disorder. The experts considered weight gain a side effect that is very likely to lead to adherence problems in patients with schizophrenia and bipolar disorder; sedation was considered a more important contributor to adherence problems in bipolar disorder than schizophrenia. The experts rated persistent positive or negative symptoms in schizophrenia and persistent grandiosity and manic symptoms in bipolar disorder as the most important symptomatic contributors to adherence problems in these illnesses. Interventions It is important to identify the specific factors that may be contributing to a patient's adherence problems in order to customize interventions to target those problems. Multiple problems may be involved, requiring a combination of interventions. Conclusions Adherence problems are complex and multidetermined. The experts recommended customized interventions focused on the underlying causes.

Detection of functional haematopoietic stem cell niche using real-time imaging

Abstract: Haematopoietic stem cells are found in a specialized regulatory environment or niche in bone marrow. The precise location and characteristics of this niche are now made clearer by two sophisticated imaging studies. Lo Celso et al. performed live-animal tracking of individual haematopoietic cells and find that osteoblasts are enmeshed in microvessels and that different haematopoietic cell populations are localized in different areas according to their stage of differentiation. Xie et al. used newly developed ex vivo real-time imaging technology and immunoassays to trace the homing of fluorescently labelled haematopoietic stem cells in response to irradiation. They report that the membrane lining the medullary cavity of bone forms a special zone that normally maintains haematopoietic stem cells, but promotes their expansion in response to bone marrow damage. Recently haematopoietic stem cell niches have been shown to comprise osteoblastic and vascular microenvironments. This study describes a newly developed ex vivo real-time imaging technology and immunoassaying to trace the homing of highly purified GFP-expressing haematopoietic stem cells in response to irradiation. Haematopoietic stem cell (HSC) niches, although proposed decades ago1, have only recently been identified as separate osteoblastic and vascular microenvironments2,3,4,5,6. Their interrelationships and interactions with HSCs in vivo remain largely unknown. Here we report the use of a newly developed ex vivo real-time imaging technology and immunoassaying to trace the homing of purified green-fluorescent-protein-expressing (GFP+) HSCs. We found that transplanted HSCs tended to home to the endosteum (an inner bone surface) in irradiated mice, but were randomly distributed and unstable in non-irradiated mice. Moreover, GFP+ HSCs were more frequently detected in the trabecular bone area compared with compact bone area, and this was validated by live imaging bioluminescence driven by the stem-cell-leukaemia (Scl) promoter–enhancer7. HSCs home to bone marrow through the vascular system. We found that the endosteum is well vascularized and that vasculature is frequently localized near N-cadherin+ pre-osteoblastic cells, a known niche component. By monitoring individual HSC behaviour using real-time imaging, we found that a portion of the homed HSCs underwent active division in the irradiated mice, coinciding with their expansion as measured by flow assay. Thus, in contrast to central marrow, the endosteum formed a special zone, which normally maintains HSCs but promotes their expansion in response to bone marrow damage.

CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses

Abstract: We present an extension of the CHARMM hexopyranose monosaccharide additive all-atom force field to enable modeling of glycosidic-linked hexopyranose polysaccharides. The new force field parameters encompass 1→1, 1→2, 1→3, 1→4, and 1→6 hexopyranose glycosidic linkages, as well as O-methylation at the C1 anomeric carbon, and are developed to be consistent with the CHARMM all-atom biomolecular force fields for proteins, nucleic acids, and lipids. The parameters are developed in a hierarchical fashion using model compounds containing the key atoms in the full carbohydrates, in particular O-methyl-tetrahydropyran and glycosidic-linked dimers consisting of two molecules of tetrahyropyran or one molecule of tetrahydropyran and one of cyclohexane. Target data for parameter optimization include full two-dimensional energy surfaces defined by the Φ/Ψ glycosidic dihedral angles in the disaccharide analogs, as determined by quantum mechanical MP2/cc-pVTZ single point energies on MP2/6-31G(d) optimized structures (MP2...

A new perspective on the role of the orbitofrontal cortex in adaptive behaviour

Abstract: The orbitofrontal cortex (OFC) is crucial for changing established behaviour in the face of unexpected outcomes. This function has been attributed to the role of the OFC in response inhibition or to the idea that the OFC is a rapidly flexible associative-learning area. However, recent data contradict these accounts, and instead suggest that the OFC is crucial for signalling outcome expectancies. We suggest that this function--signalling of expected outcomes--can also explain the crucial role of the OFC in changing behaviour in the face of unexpected outcomes.

The Frequency of Hyperkalemia and Its Significance in Chronic Kidney Disease

Abstract: Background Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality. Methods This retrospective analysis of a national cohort comprised 2 103 422 records from 245 808 veterans with at least 1 hospitalization and at least 1 inpatient or outpatient serum potassium record during the fiscal year 2005. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers (blockers of the renin-angiotensin-aldosterone system [RAAS]) were the key predictors of hyperkalemia. Death within 1 day of a hyperkalemic event was the principal outcome. Results Of the 66 259 hyperkalemic events (3.2% of records), more occurred as inpatient events (n = 34 937 [52.7%]) than as outpatient events (n = 31 322 [47.3%]). The adjusted rate of hyperkalemia was higher in patients with CKD than in those without CKD among individuals treated with RAAS blockers (7.67 vs 2.30 per 100 patient-months; P P P Conclusions The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within 1 day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.

Chronic Renal Insufficiency Cohort (CRIC) Study: Baseline Characteristics and Associations with Kidney Function

Abstract: Background and objectives: The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with CKD. We examined baseline demographic and clinical characteristics. Design, setting, participants, & measurements: Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR (eGFR) inclusion criteria. At baseline, blood and urine specimens were collected and information regarding health behaviors, diet, quality of life, and functional status was obtained. GFR was measured using radiolabeled iothalamate in one third of participants. Results: A total of 3612 participants were enrolled with mean age ± SD of 58.2 ± 11.0 yr; 46% were women, and 47% had diabetes. Overall, 45% were non-Hispanic white, 46% were non-Hispanic black, and 5% were Hispanic. Eighty-six percent reported hypertension, 22% coronary disease, and 10% heart failure. Mean body mass index was 32.1 ± 7.9 kg/m2, and 47% had a BP >130/80 mmHg. Mean eGFR was 43.4 ± 13.5 ml/min per 1.73 m2, and median (interquartile range) protein excretion was 0.17 g/24 h (0.07 to 0.81 g/24 h). Lower eGFR was associated with older age, lower socioeconomic and educational level, cigarette smoking, self-reported CVD, peripheral arterial disease, and elevated BP. Conclusions: Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status. Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes.

The Hispanic-White Achievement Gap in Math and Reading in the Elementary Grades:

Abstract: This article describes the developmental patterns of Hispanic-White math and reading achievement gaps in elementary school, paying attention to variation in these patterns among Hispanic subgroups. Compared to non-Hispanic White students, Hispanic students enter kindergarten with much lower average math and reading skills. The gaps narrow by roughly a third in the first 2 years of schooling but remain relatively stable for the next 4 years. The development of achievement gaps varies considerably among Hispanic subgroups. Students with Mexican and Central American origins—particularly first- and second-generation immigrants—and those from homes where English is not spoken have the lowest math and reading skill levels at kindergarten entry but show the greatest achievement gains in the early years of schooling.

Remote sensing of particulate pollution from space: have we reached the promised land?

Abstract: The recent literature on satellite remote sensing of air quality is reviewed. 2009 is the 50th anniversary of the first satellite atmospheric observations. For the first 40 of those years, atmospheric composition measurements, meteorology, and atmospheric structure and dynamics dominated the missions launched. Since 1995, 42 instruments relevant to air quality measurements have been put into orbit. Trace gases such as ozone, nitric oxide, nitrogen dioxide, water, oxygen/tetraoxygen, bromine oxide, sulfur dioxide, formaldehyde, glyoxal, chlorine dioxide, chlorine monoxide, and nitrate radical have been measured in the stratosphere and troposphere in column measurements. Aerosol optical depth (AOD) is a focus of this review and a significant body of literature exists that shows that ground-level fine particulate matter (PM2.5) can be estimated from columnar AOD. Precision of the measurement of AOD is +/-20% and the prediction of PM2.5 from AOD is order +/-30% in the most careful studies. The air quality needs that can use such predictions are examined. Satellite measurements are important to event detection, transport and model prediction, and emission estimation. It is suggested that ground-based measurements, models, and satellite measurements should be viewed as a system, each component of which is necessary to better understand air quality.

Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.

Abstract: Objective: We sought to determine if an oral disposition index (DIO) predicts the development of diabetes over a 10 year period. First, we assessed the validity of DIO by demonstrating that a hyperbolic relationship exists between oral indices of insulin sensitivity and β-cell function. Research design and methods: 613 Japanese American subjects (322M/291F) underwent a 75-gram oral glucose tolerance test (OGTT) at baseline, 5 and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or HOMA-S. Insulin response was estimated as the change in insulin divided by change in glucose from 0-30 minutes (ΔI0-30/ΔG0-30). Results: ΔI0-30/ΔG0-30 demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the loge-transformed estimates included -1 for ΔI0-30/ΔG0-30 vs. 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with NGT or IFG/IGT, but not diabetes. Based on this hyperbolic relationship, the product of ΔI0-30/ΔG0-30 and 1/fasting insulin was calculated (oral disposition index: DIO) and decreased from NGT to IFG/IGT to diabetes (p<0.001). Among non-diabetic subjects at baseline, baseline DIO predicted cumulative diabetes at 10-years (p<0.001) independent of age, sex, BMI, family history of diabetes and baseline fasting and 2-hour glucose. Conclusions: DIO provides a measure of β-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

Acupuncture for migraine prophylaxis

Abstract: BACKGROUND: Acupuncture is often used for migraine prophylaxis but its effectiveness is still controversial. This review (along with a companion review on'Acupuncture for tension-type headache') represents an updated version of a Cochrane review originally published in Issue 1, 2001, of The Cochrane Library. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than'sham' (placebo) acupuncture; and c) as effective as other interventions in reducing headache frequency in patients with migraine. SEARCH STRATEGY: The Cochrane Pain, Palliative& Supportive Care Trials Register, CENTRAL, MEDLINE, EMBASE and the Cochrane Complementary Medicine Field Trials Register were searched to January 2008. SELECTION CRITERIA: We included randomized trials with a post-randomization observation period of at least 8 weeks that compared the clinical effects of an acupuncture intervention with a control (no prophylactic treatment or routine care only), a sham acupuncture intervention or another intervention in patients with migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility; extracted information on patients, interventions, methods and results; and assessed risk of bias and quality of the acupuncture intervention. Outcomes extracted included response (outcome of primary interest), migraine attacks, migraine days, headache days and analgesic use. Pooled effect size estimates were calculated using a random-effects model. MAIN RESULTS: Twenty-two trials with 4419 participants (mean 201, median 42, range 27 to 1715) met the inclusion criteria. Sixtrials (including two large trials with 401 and 1715 patients) compared acupuncture to no prophylactic treatment or routine care only. After 3 to 4 months patients receiving acupuncture had higher response rates and fewer headaches. The only study with long-term follow up saw no evidence that effects dissipated up to 9 months after cessation of treatment. Fourteen trials compared a'true' acupuncture intervention with a variety of sham interventions. Pooled analyses did not show a statistically significant superiority for true acupuncture for any outcome in any of the time windows, but the results of single trials varied considerably. Four trials compared acupuncture to proven prophylactic drug treatment. Overall in these trials acupuncture was associated with slightly better outcomes and fewer adverse effects than prophylactic drug treatment. Two small low-quality trials comparing acupuncture with relaxation (alone or in combination with massage) could not be interpreted reliably. AUTHORS' CONCLUSIONS: In the previous version of this review, evidence in support of acupuncture for migraine prophylaxis was considered promising but insufficient. Now, with 12 additional trials, there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of'true' acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment.