183 research outputs found

    Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds

    Get PDF
    CONTEXT: Active surveillance of primary congenital hypothyroidism (CH) in a multi-ethnic population with established newborn bloodspot screening. OBJECTIVE: To estimate performance of newborn screening for CH at different test thresholds; to calculate incidence of primary CH. DESIGN: Prospective surveillance undertaken from June 2011 to June 2012 with three-year follow-up of outcomes. Relative likelihood ratios (rLRs) estimated to compare bloodspot thyroid-stimulating hormone (TSH) test thresholds of 6mU/L and 8mU/L, with the nationally recommended standard of 10mU/L for a presumptive positive result. SETTING: UK National Health Service. PATIENTS: Clinician notification of children aged under five years investigated following clinical presentation or presumptive positive screening result. MAIN OUTCOME MEASURE(S): Permanent primary CH status determined by clinician report of continuing thyroxine requirement at three-year follow-up. RESULTS: 629 newborns (58.3% girls; 58.7% white ethnicity) were investigated following presumptive positive screening result and 21 children (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment at three-year follow-up. Permanent CH incidence was 5.3 (95%CI 4.8, 5.8) per 10,000 infants. Using locally-applied thresholds, sensitivity, specificity and positive predictive value were 96.76%, 99.97% and 66.88% respectively. Compared with TSH threshold of 10mU/L, positive rLRs for 8mU/L and 6mU/L were 1.20 (95%CI 0.82, 1.75) and 0.52 (95%CI 0.38, 0.72), and negative rLRs 0.11 (95%CI 0.03, 0.36) and 0.11 (95%CI 0.06, 0.20) respectively. CONCLUSIONS: Screening programme performance is good, however a TSH threshold of 8mU/L appears superior to the current national standard (10mU/L) and requires further evaluation. Further research should explore the implications of transient CH for screening policy

    Antimicrobial activity of graphene oxide-metal hybrids.

    Get PDF
    With resistant bacteria on the increase, there is a need for new combinations of antimicrobials/biocidal agents to help control the transmission of such microorganisms. Particulate forms of graphite, graphene oxide (GO) and metal-hybrid compounds (silver-graphene oxide (AgGO) and zinc oxide graphene oxide (ZnOGO)) were fabricated and characterised. X-Ray diffraction and Diffuse Reflectance Infrared Fourier Transform Spectroscopy demonstrated the composition of the compounds. Scanning Electron Microscopy and Energy Dispersive X-Ray Spectroscopy determined the compounds were heterogeneous and irregular in shape and size and that the level of silver in the AgGO sample was 57.9 wt% and the ZnOGO contained 72.65 wt % zinc. The compounds were tested for their antimicrobial activity against four prominent bacteria; Escherichia coli, Staphylococcus aureus, Enterococcus faecium and Klebsiella pneumoniae. AgGO was the most effective antimicrobial (Minimum inhibitory concentration E. coli/Enterococcus faecium 0.125 mg mL−1; S. aureus/K. pneumoniae 0.25 mg mL−1). The addition of Ag enhanced the activity of GO against the bacteria tested, including the generally recalcitrant K. pneumoniae and Enterococcus faecium. These findings demonstrated that GO-metal hybrids have the potential to be utilised as novel antimicrobials or biocides in liquid formulations, biomaterials or coatings for use in the treatment of wounds where medically relevant bacteria are becoming increasingly resistant

    25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

    Get PDF
    BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor

    Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

    Get PDF
    We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing αVβ3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and αVβ3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0–60%) expressed LH39, while αVβ3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5–90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed

    Millicurrent stimulation of human articular chondrocytes cultivated in a collagen type-I gel and of human osteochondral explants

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Here we investigate the effect of millicurrent treatment on human chondrocytes cultivated in a collagen gel matrix and on human osteochondral explants.</p> <p>Methods</p> <p>Human chondrocytes from osteoarthritic knee joints were enzymatically released and transferred into a collagen type-I gel. Osteochondral explants and cell-seeded gel samples were cultivated in-vitro for three weeks. Samples of the verum groups were stimulated every two days by millicurrent treatment (3 mA, sinusoidal signal of 312 Hz amplitude modulated by two super-imposed signals of 0.28 Hz), while control samples remained unaffected. After recovery, collagen type-I, type-II, aggrecan, interleukin-1β, IL-6, TNFα and MMP13 were examined by immunohistochemistry and by real time PCR.</p> <p>Results</p> <p>With regard to the immunostainings 3 D gel samples and osteochondral explants did not show any differences between treatment and control group. The expression of all investigated genes of the 3 D gel samples was elevated following millicurrent treatment. While osteochondral explant gene expression of col-I, col-II and Il-1β was nearly unaffected, aggrecan gene expression was elevated. Following millicurrent treatment, IL-6, TNFα, and MMP13 gene expression decreased. In general, the standard deviations of the gene expression data were high, resulting in rarely significant results.</p> <p>Conclusions</p> <p>We conclude that millicurrent stimulation of human osteoarthritic chondrocytes cultivated in a 3 D collagen gel and of osteochondral explants directly influences cell metabolism.</p

    25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

    Get PDF
    BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (&lt;15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (&lt;15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor
    corecore