1,211 research outputs found
Isolation of Acanthamoeba isolates belonging to T2, T3, T4 and T7 genotypes from environmental samples in Ankara, Turkey
Acanthamoeba keratitis is a blinding infection that is becoming increasingly important in human health. Early diagnosis is a prerequisite for successful treatment and requires identification of Acanthamoeba at the genotypic level. The genus Acanthamoeba consists of both pathogenic and non-pathogenic species and has been recently classified into 13 different genotypes, T1-T12 and T14. More importantly, 95% of Acanthamoeba isolates that produce keratitis belong to T4 genotypes. In this study, we attempted to determine whether predominance of T4 isolates in Acanthamoeba keratitis is due to greater virulence or greater prevalence. We isolated 18 Acanthamoeba isolates from environmental samples in Ankara, Turkey and determined their pathogenic potential by means osmotolerance, temperature tolerance and in vitro cytotoxicity assays using corneal epithelial cells. Ribosomal DNA sequencing revealed that 10 isolates belong to T2, 5 belong to T3, 2 belong to T4 and one belongs to T7 genotype. As expected, T3 and T4 isolates exhibited the most pathogenic traits and were osmotolerant, temperature tolerant and exhibited severe corneal epithelial cell cytotoxicity indicating their pathogenic potential. Overall these data indicate that high frequency of T4 isolates in keratitis cases may well be due to their greater virulence. This is the first report presenting environmental distribution of Acanthamoeba in Ankara, Turkey
Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3-kinase-dependent mechanism
Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious human infection with fatal consequences, but it is not clear how the circulating amoebae interact with the blood-brain barrier and transmigrate into the central nervous system. We studied the effects of an Acanthamoeba encephalitis isolate belonging to the T1 genotype on human brain microvascular endothelial cells, which constitute the blood-brain barrier. Using an apoptosis-specific enzyme-linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell death in brain microvascular endothelial cells. Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba-mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase
Escherichia coli K1 RS218 Interacts with Human Brain Microvascular Endothelial Cells via Type 1 Fimbria Bacteria in the Fimbriated State
Escherichia coli K1 is a major gram-negative organism causing neonatal meningitis. E. coli K1 binding to and invasion of human brain microvascular endothelial cells (HBMEC) are a prerequisite for E. coli penetration into the central nervous system in vivo. In the present study, we showed using DNA microarray analysis that E. coli K1 associated with HBMEC expressed significantly higher levels of the fim genes compared to nonassociated bacteria. We also showed that E. coli K1 binding to and invasion of HBMEC were significantly decreased with its fimH deletion mutant and type 1 fimbria locked-off mutant, while they were significantly increased with its type 1 fimbria locked-on mutant. E. coli K1 strains associated with HBMEC were predominantly type 1 fimbria phase-on (i.e., fimbriated) bacteria. Taken together, we showed for the first time that type 1 fimbriae play an important role in E. coli K1 binding to and invasion of HBMEC and that type 1 fimbria phase-on E. coli is the major population interacting with HBMEC
Maternal thyroid function and child educational attainment: prospective cohort study
Objective: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment.
Design: Prospective cohort study.
Setting: Avon Longitudinal Study of Parents and Children cohort in the UK.
Participants: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12).
Exposures: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function.
Main outcome measures: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15.
Results: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism.
Conclusions: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement
Osmopriming combined with Boron-Tolerant Bacteria (Bacillus sp. MN54) improved the productivity of Desi Chickpea under rainfed and irrigated conditions
Chickpeas are rich source of protein and predominantly grown in boron (B)-deficient sandy-loam soils in Pakistan. Boron-tolerant bacteria (BTB) could tolerate higher B levels in soil and increase B availability to the plants. Field trials were conducted under irrigated (district Layyah) and rainfed (district Chakwal) conditions to evaluate the interactive effects of pre-optimized B application methods and BTB (Bacillus sp. MN54) on the nodule’s population, grain quality, productivity, and grain-B concentration in desi chickpea during 2019–2020 and 2020–2021. Boron was applied as soil application (1 kg B ha−1), foliar application (0.025% B), osmopriming (0.001% B), and seed coating (1.5 g B kg−1 seed) with or without BTB inoculation. Untreated seeds receiving no B through any of the methods were regarded as control. The individual and interactive effects (up to three-way interaction of location × BTB inoculation × B application methods) of year, location, B application methods and BTB inoculation significantly altered the growth and yield-related traits of desi chickpea. The four-way interaction of year × location × BTB inoculation × B application methods was non-significant for all recorded growth and yield-related traits. Regarding individual effects, the higher values of growth and yield-related traits were noted for 2020–2021, rainfed location, BTB inoculation and B application through seed priming. Similarly, in two-way interactions 2020–2021 with rainfed location and BTB inoculation, rainfed location with BTB inoculation and osmopriming and osmopriming with BTB inoculation recorded higher values of the growth and yield-related traits. Osmopriming combined with BTB inoculation significantly improved dry matter accumulation and leaf area index in both locations. Boron application through all the methods significantly improved grain quality, yield grain B concentration. The highest grain and biological yields, and nodules’ population were recorded with osmopriming followed by soil application of B combined with BTB inoculation. The highest plant B concentration (75.05%) was recorded with foliar application of B followed by osmopriming (68.73%) combined with BTB inoculation. Moreover, the highest economic returns (USD 2068.5 ha−1) and benefit–cost ratio (3.7%) were recorded with osmopriming + BTB inoculation in 2020–2021 under rainfed conditions. Overall, B application through osmopriming and soil application combined with BTB inoculation could be used to increase productivity and profitability of desi chickpea, whereas foliar application is a better method to enhance grain and plant B concentration
An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy
Objective:
To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab‐treated patients with RA.
Methods:
In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup.
Results:
We identified 50 independently adjudicated cases of MACE during 14,683 patient‐years of followup (0.34 MACE cases/100 patient‐years). At baseline, age, a history of cardiac disorders, the Disease Activity Score in 28 joints (DAS28), and the total cholesterol:high‐density lipoprotein cholesterol ratio were independently associated with MACE in multivariable models (P < 0.05 for all). During treatment, a higher DAS28 and higher swollen and tender joint counts at week 24 were associated with future MACE. In separate models, greater reductions in the DAS28 and joint counts from baseline to week 24 were inversely associated with future MACE; changes in lipid parameters were not statistically significantly associated with the risk of MACE.
Conclusion:
In this population of patients treated with tocilizumab, an association was observed between the baseline total cholesterol:high‐density lipoprotein cholesterol ratio and an increased risk of MACE. The risk of MACE while receiving treatment, however, was associated with control of disease activity but not lipid changes. Larger studies are needed to confirm these findings
Screen time is associated with adiposity and insulin resistance in children
Higher screen time is associated with type 2 diabetes (T2D) risk in adults, but the association with T2D risk markers in children is unclear. We examined associations between self-reported screen time and T2D risk markers in children. Survey of 4495 children aged 9-10 years who had fasting cardiometabolic risk marker assessments, anthropometry measurements and reported daily screen time; objective physical activity was measured in a subset of 2031 children. Compared with an hour or less screen time daily, those reporting screen time over 3 hours had higher ponderal index (1.9%, 95% CI 0.5% to 3.4%), skinfold thickness (4.5%, 0.2% to 8.8%), fat mass index (3.3%, 0.0% to 6.7%), leptin (9.2%, 1.1% to 18.0%) and insulin resistance (10.5%, 4.9% to 16.4%); associations with glucose, HbA1c, physical activity and cardiovascular risk markers were weak or absent. Associations with insulin resistance remained after adjustment for adiposity, socioeconomic markers and physical activity. Strong graded associations between screen time, adiposity and insulin resistance suggest that reducing screen time could facilitate early T2D prevention. While these observations are of considerable public health interest, evidence from randomised controlled trials is needed to suggest causality. [Abstract copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Progressive Class-Wise Attention (PCA) Approach for Diagnosing Skin Lesions
Skin cancer holds the highest incidence rate among all cancers globally. The
importance of early detection cannot be overstated, as late-stage cases can be
lethal. Classifying skin lesions, however, presents several challenges due to
the many variations they can exhibit, such as differences in colour, shape, and
size, significant variation within the same class, and notable similarities
between different classes. This paper introduces a novel class-wise attention
technique that equally regards each class while unearthing more specific
details about skin lesions. This attention mechanism is progressively used to
amalgamate discriminative feature details from multiple scales. The introduced
technique demonstrated impressive performance, surpassing more than 15
cutting-edge methods including the winners of HAM1000 and ISIC 2019
leaderboards. It achieved an impressive accuracy rate of 97.40% on the HAM10000
dataset and 94.9% on the ISIC 2019 dataset
Assessing Safety Against Floods for an Ashpond Garlanded by Two Natural Streams
Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv
Pre-text Representation Transfer for Deep Learning with Limited Imbalanced Data : Application to CT-based COVID-19 Detection
Annotating medical images for disease detection is often tedious and
expensive. Moreover, the available training samples for a given task are
generally scarce and imbalanced. These conditions are not conducive for
learning effective deep neural models. Hence, it is common to 'transfer' neural
networks trained on natural images to the medical image domain. However, this
paradigm lacks in performance due to the large domain gap between the natural
and medical image data. To address that, we propose a novel concept of Pre-text
Representation Transfer (PRT). In contrast to the conventional transfer
learning, which fine-tunes a source model after replacing its classification
layers, PRT retains the original classification layers and updates the
representation layers through an unsupervised pre-text task. The task is
performed with (original, not synthetic) medical images, without utilizing any
annotations. This enables representation transfer with a large amount of
training data. This high-fidelity representation transfer allows us to use the
resulting model as a more effective feature extractor. Moreover, we can also
subsequently perform the traditional transfer learning with this model. We
devise a collaborative representation based classification layer for the case
when we leverage the model as a feature extractor. We fuse the output of this
layer with the predictions of a model induced with the traditional transfer
learning performed over our pre-text transferred model. The utility of our
technique for limited and imbalanced data classification problem is
demonstrated with an extensive five-fold evaluation for three large-scale
models, tested for five different class-imbalance ratios for CT based COVID-19
detection. Our results show a consistent gain over the conventional transfer
learning with the proposed method.Comment: Best paper at IVCN
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