138 research outputs found

    Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study

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    The immune response involved in each phase of type 2 diabetes (T2D) development might be different. We aimed to identify novel inflammatory markers that predict progression from normoglycemia to pre-diabetes, incident T2D and insulin therapy. We used plasma levels of 26 inflammatory markers in 971 subjects from the Rotterdam Study. Among them 17 are novel and 9 previously studied. Cox regression models were built to perform survival analysis. Main Outcome Measures: During a follow-up of up to 14.7 years (between April 1, 1997, and Jan 1, 2012) 139 cases of pre-diabetes, 110 cases of T2D and 26 cases of insulin initiation were identified. In age and sex adjusted Cox models, IL13 (HR = 0.78), EN-RAGE (1.30), CFH (1.24), IL18 (1.22) and CRP (1.32) were associated with incident pre-diabetes. IL13 (0.62), IL17 (0.75), EN-RAGE (1.25), complement 3 (1.44), IL18 (1.35), TNFRII (1.27), IL1ra (1.24) and CRP (1.64) were associated with incident T2D. In multivariate models, IL13 (0.77), EN-RAGE (1.23) and CRP (1.26) remained associated with pre-diabetes. IL13 (0.67), IL17 (0.76) and CRP (1.32) remained associated with T2D. IL13 (0.55) was the only marker associated with initiation of insulin therapy in diabetics. Various inflammatory markers are associated with progression from normoglycemia to pre-diabetes (IL13, EN-RAGE, CRP), T2D (IL13, IL17, CRP) or insulin therapy start (IL13). Among them, EN-RAGE is a novel inflammatory marker for pre-diabetes, IL17 for incident T2D and IL13 for pre-diabetes, incident T2D and insulin therapy start

    A genome-wide scan for microrna-related genetic variants associated with primary open-angle glaucoma

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    PURPOSE: To identify microRNAs (miRNAs) involved in primary open-angle glaucoma (POAG), using genetic data. MiRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Genetic variants in miRNAs or miRNA-binding sites within gene 3’-untranslated regions (3’UTRs) are expected to affect miRNA function and con

    Gait patterns associated with thyroid function: The Rotterdam Study

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    Gait is an important health indicator and poor gait is strongly associated with disability and risk of falls. Thyroid dysfunction is suggested as a potential determinant of gait deterioration, but this has not been explored in a population-based study. We therefore investigated the association of thyroid function with gait patterns in 2645 participants from the Rotterdam Study with data available on TSH (thyroid-stimulating hormone), FT4 (free thyroxine) and gait, without known thyroid disease or dementia. The primary outcome was Global gait (standardized Z-score), while secondary outcomes included gait domains (Rhythm, Variability, Phases, Pace, Base of support, Tandem, Turning) and velocity. Gait was assessed by electronic walkway. Multivariable regression models revealed an inverted U-shaped association of TSH (p < 0.001), but no association of FT4 concentrations with Global gait (p = 0.2). TSH levels were positively associated with Base of support (p = 0.01) and followed an inverted U-shaped curve with Tandem (p = 0.002) and velocity (p = 0.02). Clinical and subclinical hypothyroidism were associated with worse Global gait than euthyroidism (β =-0.61; CI =-1.03,-0.18; p = 0.004 and β =-0.13; CI =-0.26,-0.00; p = 0.04, respectively). In euthyroid participants, higher thyroid function was associated with worse gait patterns. In conclusion, both low and high thyroid function are associated with alterations in Global gait, Tandem, Base of support and velocity

    Molecular detection of Strongyloides sp. in Australian thoroughbred foals

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    Background Strongyloides westeri is found in the small intestine of young horses, mainly in foals up to about 16 weeks of age. The main source of infection for foals is through transmammary transmission, and foals can develop acute diarrhoea, weakness, dermatitis and respiratory signs. The epidemiology of S. westeri in Australia is largely unknown. Further, molecular techniques have never been employed for detection of S. westeri in horses. This pilot study aimed to assess the utility of a molecular phylogenetic method for the detection of S. westeri in the faeces of foals. Methods Faecal samples were collected from a foal of less than 2 months of age, and eggs of Strongyloides sp. were detected using the modified McMaster technique. DNA was extracted from purified eggs, and a partial fragment of the small subunit of the nuclear ribosomal DNA (18S) was characterised using polymerase chain reaction, DNA sequencing and phylogenetic methods. Results Microscopic examination of faeces revealed small ellipsoidal eggs typical of Strongyloides sp. The 18S sequence generated by PCR in this study revealed 98.4% identity with that of a reference sequence of S. westeri available from GenBank. Phylogenetic analyses revealed a polyphyletic clustering of S. westeri sequences. Conclusion This is the first study reporting the detection of DNA of Strongyloides sp. in faeces of a foal using a molecular phylogenetic approach targeting the variable region of 18S rDNA. It is anticipated that this study will allow future molecular epidemiological studies on S. westeri in horses

    Comparative studies on faecal egg counting techniques used for the detection of gastrointestinal parasites of equines: A systematic review

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    Faecal egg counting techniques (FECT) form the cornerstone for the detection of gastrointestinal parasites in equines. For this purpose, several flotation, centrifugation, image- and artificial intelligence-based techniques are used, with varying levels of performance. This review aimed to critically appraise the literature on the assessment and comparison of various coprological techniques and/or modifications of these techniques used for equines and to identify the knowledge gaps and future research directions. We searched three databases for published scientific studies on the assessment and comparison of FECT in equines and included 27 studies in the final synthesis. Overall, the performance parameters of McMaster (81.5%), Mini-FLOTAC® (33.3%) and simple flotation (25.5%) techniques were assessed in most of the studies, with 77.8% of them comparing the performance of at least two or three methods. The detection of strongyle, Parascaris spp. and cestode eggs was assessed for various FECT in 70.4%, 18.5% and 18.5% studies, respectively. A sugar-based flotation solution with a specific gravity of ≥1.2 was found to be the optimal flotation solution for parasitic eggs in the majority of FECT. No uniform or standardised protocol was followed for the comparison of various FECT, and the tested sample size (i.e. equine population and faecal samples) also varied substantially across all studies. To the best of our knowledge, this is the first systematic review to evaluate studies on the comparison of FECT in equines and it highlights important knowledge gaps in the evaluation and comparison of such techniques

    Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation:discovering causal pathways

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    Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.</p

    CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images

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    Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70�75. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80�98, but similar accuracy of 70. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95 compared to radiologists (70). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership. © 2021, The Author(s)

    Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

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    Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders

    City branding as economic necessity

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    Kvalitetno brendiranje grada je preduvjet za njihovu prepoznatljivost, kvalitetno pozicioniranje i stvaranje dodatne vrijednosti. Praksa i mnogobrojni primjeri potvrđuju ispravnost ove teze. Brendiranje gradova je nužno kako bi se pojačala konkurentnost, ostvarila veća dobit i osigurao razvoj mjesta. No ne radi se samo o ekonomskim kategorijama jer se pod razvojem mjesta podrazumijevaju i pozitivna demografska kretanja, obogaćivanje kulturnih sadržaja kao i drugih činitelja koji podižu ukupnu kvalitetu života. Izazov je to i nužnost i za gradove u Hrvatskoj kako bi bili konkurentni u oštroj tržišnoj konkurenciji.Quality city branding is a precondition for their recognazibility, quality positionig and creating of added value. Practice and numerous examples confirm correction of this theses. City branding is necessary to enhance concurence, gain bigger profit and ensure place development. But this is not only about economic categories because under place development it is understandable alsto positive demographic movement, enrichment of cultural contens as well as other factors which raise total quality of life. This is as well a challenge as it is a necessity for cities in Croatia so they could be concurente in harsh economy concurence
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