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61.
Joseph Okebe Muna Affara Simon Correa Abdul Khalie Muhammad Davis Nwakanma Chris Drakeley Umberto D’Alessandro 《PloS one》2014,9(10)
Background
As the geographical distribution of malaria transmission becomes progressively clustered, identifying residual pockets of transmission is important for research and for targeting interventions. Malarial antibody-based surveillance is increasingly recognised as a valuable complement to classic methods for the detection of infection foci especially at low transmission levels. The study presents serological evidence for transmission heterogeneity among school children in The Gambia measured during the dry, non-transmission season.Methods
Healthy primary school children were randomly selected from 30 schools across the country and screened for malaria infection (microscopy) and antimalarial antibodies (MSP119). Antibody distribution was modelled using 2-component finite mixture model with cut-off for positivity from pooled sera set at 2-standard deviation from the mean of the first component. Factors associated with a positive serological status were identified in a univariate model and then combined in a multilevel mixed-effects logistic regression model, simultaneously adjusting for variations between individuals and school.Results
A total of 4140 children, 1897 (46%) boys, were enrolled with mean age of 10.2 years (SD 2.6, range 4–20 years). Microscopy results available for 3640 (87.9%) children showed that 1.9% (69) were positive for Plasmodium falciparum infections, most of them (97.1%, 67/69) asymptomatic. The overall seroprevalence was 12.7% (527/4140) with values for the schools ranging from 0.6% to 43.8%. Age (OR 1.12, 95% CI 1.07–1.16,) and parasite carriage (OR 3.36, 95% CI 1.95–5.79) were strongly associated with seropositivity.Conclusion
Serological responses to malaria parasites could identify individuals who were or had been infected, and clusters of residual transmission. Field-adapted antibody tests able to guide mass screening and treatment campaigns would be extremely useful. 相似文献62.
Jimenez Eulalia Astbury Carol Albayaty Muna Whlby-Hamrn Ulrika Seoane Beatriz Villarroel Cristina Pujol Helena Bermejo Maria Jesus Aggarwal Ajay Psallidas Ioannis 《Respiratory research》2020,21(1):1-11
Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression. In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (− 312.7 [SE 32.2] versus − 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups. In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not.
ClinicalTrials.gov
; Nos.
NCT01335464
and
NCT01335477
; URL:
www.clinicaltrials.gov
. 相似文献
63.
M.H.A. Mhareb Y.S.M. Alajerami Muna Alqahtani Fatimh Alshahri Noha Saleh N. Alonizan M. Maghrabi S. Hashim S.K. Ghoshal 《Luminescence》2020,35(4):525-533
Lithium borate (LB) glasses doped with dysprosium oxide (Dy2O3) have been prepared by utilizing the conventional melt‐quench technique. The prepared glass samples were exposed to 60Co to check their dosimetric features and kinetic parameters. These features involve glow curves, annealing, fading, reproducibility, minimum detectable dose (MDD), and effective atomic number (Zeff). Kinetic parameters including the frequency factors and activation energy were also determined using three methods (glow curve analysis, initial rise, and peak shape method) and were thoroughly interpreted. In addition, the incorporation of Dy impurities into LB enhanced the thermoluminescence sensitivity ~170 times. The glow from LB:Dy appeared as a single prominent peak at 190°C. The best annealing proceeding was obtained at 300°C for 30 min. Signal stability was reported for a period of 1 and 3 months with a reduction of 26% and 31%, respectively. The proposed glass samples showed promising dosimeter properties that can be recommended for personal radiation monitoring. 相似文献
64.
Muna H. Abdi Paul J. Beswick Andy Billinton Laura J. Chambers Andrew Charlton Sue D. Collins Katharine L. Collis David K. Dean Elena Fonfria Robert J. Gleave Clarisse L. Lejeune David G. Livermore Stephen J. Medhurst Anton D. Michel Andrew P. Moses Lee Page Sadhana Patel Shilina A. Roman Stefan Senger Brian Slingsby Daryl S. Walter 《Bioorganic & medicinal chemistry letters》2010,20(17):5080-5084
A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X7 receptor antagonist. Structure–activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X7 antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies. 相似文献
65.
Appia-Ayme C Patrick E Sullivan MJ Alston MJ Field SJ AbuOun M Anjum MF Rowley G 《PloS one》2011,6(8):e23713
The RpoE and CpxR regulated envelope stress responses are extremely important for Salmonella Typhimurium to cause infection in a range of hosts. Until now the role for BaeSR in both the Salmonella Typhimurium response to stress and its contribution to infection have not been fully elucidated. Here we demonstrate stationary phase growth, iron and sodium tungstate as novel inducers of the BaeRregulon, with BaeR critically required for Salmonella resistance to sodium tungstate. We show that functional overlap between the resistance nodulation-cell division (RND) multidrug transporters, MdtA, AcrD and AcrB exists for the waste disposal of tungstate from the cell. We also point to a role for enterobactinsiderophores in the protection of enteric organisms from tungstate, akin to the scenario in nitrogen fixing bacteria. Surprisingly, BaeR is the first envelope stress response pathway investigated in S. Typhimurium that is not required for murine typhoid in either ity(S) or ity(R) mouse backgrounds. BaeR is therefore either required for survival in larger mammals such as pigs or calves, an avian host such as chickens, or survival out with the host altogether where Salmonella and related enterics must survive in soil and water. 相似文献
66.
Conley SM Cai X Makkia R Wu Y Sparrow JR Naash MI 《Biochimica et biophysica acta》2012,1822(7):1169-1179
Autosomal recessive Stargardt macular dystrophy is caused by mutations in the photoreceptor disc rim protein ABCA4/ABCR. Key clinical features of Stargardt disease include relatively mild rod defects such as delayed dark adaptation, coupled with severe cone defects reflected in macular atrophy and central vision loss. In spite of this clinical divergence, there has been no biochemical study of the effects of ABCA4 deficiency on cones vs. rods. Here we utilize the cone-dominant Abca4(-/-)/Nrl(-/-) double knockout mouse to study this issue. We show that as early as post-natal day (P) 30, Abca4(-/-)/Nrl(-/-) retinas have significantly fewer rosettes than Abca4(+/+)/Nrl(-/-) retinas, a phenotype often associated with accelerated degeneration. Abca4-deficient mice in both the wild-type and cone-dominant background accumulate more of the toxic bisretinoid A2E than their ABCA4-competent counterparts, but Abca4(-/-)/Nrl(-/-) eyes generate significantly more A2E per mole of 11-cis-retinal (11-cisRAL) than Abca4(-/-) eyes. At P120, Abca4(-/-)/Nrl(-/-) produced 340 ± 121 pmoles A2E/nmol 11-cisRAL while Abca4(-/-) produced 50.4 ± 8.05 pmoles A2E/nmol 11-cisRAL. Nevertheless, the retinal pigment epithelium (RPE) of Abca4(-/-)/Nrl(-/-) eyes exhibits fewer lipofuscin granules than the RPE of Abca4(-/-) eyes; at P120: Abca4(-/-)/Nrl(-/-) exhibit 0.045 ± 0.013 lipofuscingranules/μm2 of RPE vs. Abca4(-/-) 0.17 ± 0.030 lipofuscingranules/μm2 of RPE. These data indicate that ABCA4-deficient cones simultaneously generate more A2E than rods and are less able to effectively clear it, and suggest that primary cone toxicity may contribute to Stargardt's-associated macular vision loss in addition to cone death secondary to RPE atrophy. 相似文献
67.
Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle 总被引:4,自引:1,他引:3
Taylor AH Guzail M Wahab M Thompson JR Al-Azzawi F 《Histochemistry and cell biology》2005,123(4-5):463-474
The aim of this study was to test the hypothesis that the distribution of oestrogen receptor beta (ER) and androgen receptor (AR) are related to cell proliferation or correlated with the expression of progesterone receptor (PR) or oestrogen receptor alpha (ER) in the normal human endometrium. Immunohistochemical distribution of immunoreactive ER in well-characterised menstrual cycle biopsy samples was lowest in proliferative endometrial glands, highest in early secretory phase glands and maintained at ~20% throughout the rest of the menstrual cycle and was closely correlated with stromal AR and stromal ER expression. Stromal ER was not significantly altered until the menstrual phase of the cycle and was not correlated with the expression of any other antigen in the stroma or endometrial glands except stromal AR. By contrast, glandular AR immunoreactivity was below 5% early in the cycle, increased during the secretory phase and showed strong expression just before menstruation. PR and Ki-67 expression showed strong positive correlations, indicating that PR may be a potent regulator of endometrial proliferation. These data suggest that glandular ER expression is closely associated with a functional secretory role whereas glandular ER and PR are associated with proliferation; glandular AR expression may be the switch required for menstruation. 相似文献
68.
Olubukola T. Adenubi Muna Ali Abdalla Aroke S. Ahmed Emmanuel M. Njoya Lyndy J. McGaw Jacobus N. Eloff Vinny Naidoo 《Experimental & applied acarology》2018,75(3):345-354
The menace caused by ticks and tick-borne diseases is a major limitation to the livestock industry in Africa. The high costs and non-availability of synthetic, chemical acaricides to resource-limited farmers, resistance of ticks to available acaricides and residue problems in meat and milk consumed by humans further complicate matters. The use of plant extracts as a possible source of new acaricides has received much interest in the last decade. In our endeavour to discover natural acaricidal compounds, tick toxicant bioassays were conducted and the chloroform fraction of Calpurnia aurea ethanol leaf extract had good acaricidal activity. Further purification of the fraction revealed two flavonoids, isolated from C. aurea for the first time. These flavonoids were characterized as apigenin-7-O-β-d-glycoside and isorhoifolin by means of NMR spectroscopic and mass spectrometry analysis. Isorhoifolin was the most potent compound (LC50?=?0.65 mg/ml), was not cytotoxic and should be further investigated for its potential as an acaricidal agent. 相似文献
69.
Christopher Faulk Jung H. Kim Olivia S. Anderson Muna S. Nahar Tamara R. Jones Maureen A. Sartor 《Epigenetics》2016,11(7):489-500
Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next-generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples. Mice were treated during gestation and lactation to BPA in chow at 0, 50, or 50,000 ng/g levels and total BPA was measured in stratified human fetal liver tissue samples as low (non-detect to 0.83 ng/g), medium (3.5 to 5.79 ng/g), or high (35.44 to 96.76 ng/g). Transposon methylation changes were evident in human classes, families, and subfamilies, with the medium group exhibiting hypomethylation compared to both high and low BPA groups. Mouse repeat classes, families, and subfamilies did not respond to BPA with significantly detectable differential DNA methylation. In human samples, 1251 individual transposon loci were detected as differentially methylated by BPA exposure, but only 19 were detected in mice. Of note, this approach recapitulated the discovery of a previously known mouse environmentally labile metastable epiallele, CabpIAP. Thus, by querying repetitive DNA in both mouse and humans, we report the first known transposons in humans that respond to perinatal BPA exposure. 相似文献
70.
Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial
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