Increasing body mass index, blood pressure, and Acanthosis Nigricans abnormalities in school-age children.

This retrospective quantitative study examined the relationships among gender, Acanthosis Nigricans (AN), body mass index (BMI), and blood pressure (BP) in children attending school Grades 1-9 in Southwest Texas. Of the 34,897 health screening records obtained for the secondary analysis, 32,788 were included for the study. A logistic regression analysis was carried out with AN as the dependent variable, with year, gender, BMI, and BP as independent variables. The results indicate that the rate of children in each grade with three positive markers increased 2% during a 3-year period between 2008 and 2010. In the 5-year period between 2005 and 2010, a clear trend of significantly higher numbers of children with both AN and BMI markers was apparent. Gender played a significant role as females were more likely to have the AN marker than males. Further study is indicated based on the increasing trend of school-age children in Texas with positive markers for AN, increased BMI and BP.

Efficacy of Flossing and Mouthrinsing Regimens on Plaque and Gingivitis: A randomized clinical trial.

Purpose:Flossing is a well-known component of daily recommended oral care regimens, but patients often find it challenging to perform effectively on a regular basis. The purpose of this 12-week supervised clinical trial was to investigate the effects of twice daily rinsing with a mouthrinse containing a fixed combination of four essential oils (4EO) and supervised daily dental flossing regimens as compared to a negative control 5% hydroalcohol rinse (NC) on the prevention and reduction of plaque, gingivitis, and gingival bleeding.Methods:Volunteer participants who met the inclusion criteria were randomized into the following groups for the 12- week trial: 1) NC; 2) mouthrinse containing 4EO; 3) professional flossing performed by a dental hygienist (FBH); 4) supervised self-flossing (FUS). All participants received a professional dental prophylaxis prior to beginning the trial. On weekday mornings, all participants brushed on site. After brushing, the rinse groups used their products under supervision, and the floss groups had their teeth flossed by a dental hygienist or self-flossed under supervision. Participants performed their assigned regimen in the evenings and the twice-daily weekend use at home. Each individual assessment of oral hard and soft tissue, plaque, gingivitis, and gingival bleeding at weeks 4 and 12, probing depth and bleeding on probing at week 12 was made by the same calibrated examiner.Results:Of 156 randomized participants, 149 completed the trial. Use of the 4EO mouthrinse statistically significantly reduced plaque, gingivitis, and gingival bleeding on probing after 12 weeks as compared to the NC rinse. Both flossing interventions statistically significantly reduced interproximal gingivitis and gingival bleeding at 12 weeks compared to the NC rinse; neither flossing intervention significantly reduced interproximal plaque after 12 weeks compared to the NC rinse.Conclusions:Rinsing with a 4EO mouthrinse statistically significantly improved all oral health outcome measures at all time points compared to a NC rinse in this 12-week clinical trial. While professional and supervised flossing improved gingival health compared to use of the NC rinse, statistically significant plaque reduction with dental flossing was not attained at the end of the 12-week trial.

Predicting algal blooms: Are we overlooking groundwater?

Significant advances in understanding and predicting freshwater algal bloom dynamics have emerged in response to both increased occurrence and financial burden of nuisance and harmful blooms. Several factors have been highlighted as key controls of bloom occurrence, including nutrient dynamics, local hydrology, climatic perturbations, watershed geomorphology, biogeochemistry, food-web control, and algal competition. However, a major research gap continues to be the degree to which groundwater inputs modulate microbial biomass production and food-web dynamics at the terrestrial-aquatic interface. We present a synthesis of groundwater related algal bloom literature, upon which we derive a foundational hypothesis: long residence times cause groundwater to be geochemically and biologically distinct from surface water, allowing groundwater inputs to modulate algal bloom dynamics (growth, decline, toxicity) through its control over in-stream water chemistry. Distinct groundwater chemistry can support or prevent algal blooms, depending on specific local conditions. We highlight three mechanisms that influence the impact of groundwater discharge on algal growth: 1) redox state of the subsurface, 2) extent of water-rock interactions, and 3) stability of groundwater discharge. We underscore that in testing hypotheses related to groundwater control over algal blooms, it is critical to understand how changes in land use, water management, and climate will influence groundwater dynamics and, thus, algal bloom probabilities. Given this challenge, we argue that advances in both modeling and data integration, including genomics data and integrated process-based models that capture groundwater dynamics, are needed to illuminate mechanistic controls and improve predictions of algal blooms.

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5-1.0 mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.

Metabolic disposition of [14C]bazedoxifene in healthy postmenopausal women.

Bazedoxifene is a selective estrogen receptor modulator under development for the prevention and treatment of osteoporosis. The disposition of [(14)C]bazedoxifene was determined in six healthy postmenopausal women after administration of a single oral dose of 20 mg (200 microCi). After dosing, blood was collected at frequent intervals, and urine and fecal samples were collected for up to 10 days. Aliquots of plasma, blood, urine, and fecal homogenates were analyzed for concentrations of radioactivity. Bazedoxifene metabolite profiles in plasma and feces were determined by high-performance liquid chromatography with radioactivity flow detection; metabolite structures were confirmed by liquid chromatography-mass spectrometry. Bazedoxifene was rapidly absorbed, exhibiting a mean peak plasma concentration of 3.43 ng/ml at 1.2 h postdose. The total mean recovery of the radioactive dose in excreta was 85.6%, with the majority recovered in feces (84.7%) and only a small fraction (0.81%) in urine. Radiochromatograms of plasma revealed that glucuronidation was the major metabolic pathway; little or no cytochrome P450-mediated metabolism was evident. The majority of circulating radioactivity was constituted by metabolites, with bazedoxifene-5-glucuronide being the predominant metabolite (up to 95%). Bazedoxifene-4'-glucuronide was a minor metabolite (up to 20%), and unchanged bazedoxifene represented 0 to 13% of the radioactivity in most plasma samples. Unchanged bazedoxifene was the major radioactive component in feces, however, reflecting unabsorbed drug and/or glucuronides that were hydrolyzed by intestinal bacterial enzymes. [(14)C]Bazedoxifene was generally well tolerated. These findings demonstrated that, after oral administration in healthy postmenopausal women, bazedoxifene was rapidly absorbed, metabolized via glucuronidation, and excreted predominantly in feces.

Maintenance of tolerance by regulation of anti-myeloperoxidase B cells.

Anti-neutrophil cytoplasmic autoantibodies directed toward myeloperoxidase or proteinase 3 are detected in sera of patients with small vessel vasculitis and participate in the pathogenesis of this disease. Autoantibodies develop when self-reactive B cells escape the regulation that ensures self-tolerance. In this study, regulation of anti-myeloperoxidase B cells was examined in mice that express an anti-myeloperoxidase Vkappa1C-Jkappa5 light-chain transgene, which confers anti-myeloperoxidase specificity when combined with a variety of heavy chains. Vkappa1C-Jkappa5 transgenic mice have splenic anti-myeloperoxidase B cells but do not produce circulating anti-myeloperoxidase antibodies. Two groups of transgenic mice that differed by their relative dosage of the transgene were compared; high-copy mice had a mean relative transgene dosage of 1.92 compared with 1.02 in the low-copy mice. These mice exhibited a 90 and 60% decrease in mature follicular B cells, respectively. High-copy mice were characterized by a large population of anti-myeloperoxidase B cells, a preponderance of B-1 cells, and an increased percentage of apoptotic myeloperoxidase-binding B cells. Low-copy mice had similar changes in B cell phenotype with the exception of an expanded marginal zone population. B cells from low-copy mice but not high-copy mice produced anti-myeloperoxidase antibodies after stimulation with lipopolysaccharide. These results indicate that tolerance to myeloperoxidase is maintained by central and peripheral deletion and that some myeloperoxidase-binding B cells are positively selected into the marginal zone and B-1 B cell subsets. A defect in these regulatory pathways could result in autoimmune disease.

The effects of age and sex on electroconvulsive therapy using remifentanil as the sole anesthetic agent.

OBJECTIVE: This study examines electroencephalographic (EEG) and motor seizure duration and dynamic energy according to age and sex using remifentanil anesthesia in standard electroconvulsive therapy (ECT). BACKGROUND: In an earlier study, we showed that remifentanil provides superior anesthesia for ECT in terms of providing adequate seizure duration with lower stimulus doses in patients refractory to maximal ECT settings with methohexital. METHODS: Patients, refractory to maximal ECT settings with methohexital, received remifentanil as the sole anesthetic agent. Stimulus dose was determined by the dose-titration method. Electroencephalographic seizure duration, motor seizure duration, and dynamic energy in joules (j) were compared between male and female subjects and among patients aged 40 years or younger, older than 40 years but aged 65 years or younger, and older than 65 years. RESULTS: Seventy-two patients were included in the study. There was no significant difference in remifentanil doses between female and male subjects. There was no significant statistical difference between female and male subjects regarding motor seizure duration, EEG seizure duration, or dynamic energy (P > 0.05). There were significant statistical differences among different groups in terms of motor seizure duration, EEG seizure duration, and dynamic energy (P< 0.05). The younger age group had longer motor and EEG seizure durations and required lower dynamic energy. CONCLUSIONS: There is no significant effect of sex on ECT with remifentanil anesthesia regarding EEG or motor seizure durations or dynamic energy; however, statistically significant differences were observed based upon age. Younger patients had both increased motor and EEG seizure duration compared with older patients who may require higher stimulus doses than younger patients for comparable motor and EEG seizure durations.

Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads.

OBJECTIVE: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system. MEASUREMENTS AND MAIN RESULTS: Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent. CONCLUSIONS: This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

A retrospective comparison of remifentanil versus methohexital for anesthesia in electroconvulsive therapy.

The electroconvulsive therapy (ECT) service at West Virginia University conducted a retrospective analysis of 24 patients who received bilateral ECT between November 1998 and December 2003. Patients were treated with a standard methohexital-based anesthetic. Twenty-four patients became completely or relatively refractory to maximum settings on the ECT device and were then switched to remifentanil as the sole induction agent. Seizure threshold was established by stimulus dose retitration. Stimulus dose in total charge (mC) and dynamic energy (J) was significantly lower with the remifentanil anesthetic versus methohexital. (P < 0.0001) Resulting motor and EEG seizure duration in patients was significantly longer receiving the remifentanil anesthetic versus methohexital. (P < 0.0001) Previous reports describe a rise in seizure threshold in patients for repeated ECT. Although this rise occurred during the treatment course using a methohexital anesthetic, this effect was greatly diminished when remifentanil was used as the sole anesthetic agent. We conclude that remifentanil can provide improved seizure response to ECT in patients who are refractory to seizure induction after a standard methohexital anesthetic. We also conclude that the increase in stimulus dose typically required with repeated treatments is related to the anesthetic regimen.

Microarray studies of gene expression in circulating leukocytes in kidney diseases.

The molecular characterization of changes in mRNA expression in renal tissue during disease is hampered by the acquisition of sufficient mRNA to do genomewide expression profiling. In many renal diseases, such as systemic lupus erythematosus, IgA nephropathy, antineutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis, and small-vessel vasculitis (ANCA disease), circulating leukocytes play a role in onset, progression, and severity of the condition. Circulating leukocytes are readily isolated and supply sufficient mRNA for analysis, allowing molecular investigation into their involvement in the disease process. Our laboratory has undertaken a systematic study of the genomewide expression profiles of the circulating leukocytes from patients with a variety of renal diseases (ANCA disease, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis), using the Affymetrix high-density gene chip array technology. Analysis of the data showed clustering of expressed genes unique for each individual disease group. These results imply that significant gene expression changes occur in leukocytes that are circulating in patients with renal diseases. In addition, gene expression has been studied in leukocytes activated in vitro by mechanisms that mimic pathogenic events in vivo. The expression levels of genes identified in in vitro studies were compared with the patient leukocyte gene expression to determine whether similar pathological events were occurring in vivo.

Gene expression profiles of circulating leukocytes correlate with renal disease activity in IgA nephropathy.

BACKGROUND: The goal of these studies was to explore the possibility of using gene expression profiles of circulating leukocytes as a functional fingerprint of nephritic disease activity. METHODS: This feasibility study utilized IgA nephropathy (IgAN) as a model system. Genes differentially expressed in IgAN patients were identified by Affymetrix GeneChip microarrays, and compared with gene expression of focal segmental glomerulosclerosis (FSGS), minimal change disease, antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, and with healthy volunteers. Of the genes identified, 15 transcriptionally up-regulated were validated in a larger cohort of patients using TaqMan polymerase chain reaction (PCR). To test whether increased expression of these genes correlated with disease activity, cluster analyses were performed utilizing the TaqMan PCR values. Taking a mathematical approach, we tested whether gene expression values were correlative with kidney function, as reflected by serum creatinine and creatinine clearance values. RESULTS: We identified 15 genes significantly correlative with disease activity in IgAN. This gene signature of IgAN patients' leukocytes reflected kidney function. This was demonstrated in that mathematically generated theoretical values of serum creatinine and creatinine clearance correlated significantly with actual IgAN patient values of serum creatinine and creatinine clearance. There was no apparent correlation with hematuria and proteinuria. The expression levels of this same gene set in ANCA glomerulonephritis or Lupus nephritis patients were not correlative with serum creatinine or creatinine clearance values. CONCLUSION: These data indicate that leukocytes carry informative disease-specific markers of pathogenic changes in renal tissue.

Circumvention of normal constraints on granule protein gene expression in peripheral blood neutrophils and monocytes of patients with antineutrophil cytoplasmic autoantibody-associated glomerulonephritis.

Granulopoiesis-related genes are distinctively upregulated in peripheral leukocytes of patients with antineutrophil cytoplasmic autoantibodies (ANCA)-associated glomerulonephritis. Affymetrix microarrays identified the upregulation of nine neutrophilic primary granule genes, including myeloperoxidase (MPO) and proteinase 3 (PR3), plus five secondary granule genes. Coordinate expression of granulocyte maturation marker CD35, measured by TaqMan PCR, and positive in situ staining for PR3 transcripts in polymorphic neutrophils and monocytes indicate that these genes are expressed in "mature" cells. Increased transcripts correlated with disease activity and absolute neutrophil values but not with "left shift," drug regimen, cytokine levels, hematuria, proteinuria, ANCA titer, serum creatinine, gender, or age. Upregulation of PR3 and MPO transcripts was specifically associated with ANCA disease (n = 56) as these changes were not detected in patients with ESRD (n = 25) or systemic lupus erythematosus (n = 17), as determined by TaqMan PCR. This is the first report of this phenomenon in nonneoplastic cells. The data raise the hypothesis that, in addition to the presence of anti-MPO or anti-PR3 autoantibodies, a second critical component in the cause of this disease is the reactivation of once-silenced genes leading to increased antigen availability.