Screening Method For Selection Research Articles

Comparative genomics of quinolone-resistant Escherichia coli from broilers and humans in Norway

BackgroundThe usage of fluoroquinolones in Norwegian livestock production is very low, including in broiler production. Historically, quinolone-resistant Escherichia coli (QREC) isolated from Norwegian production animals rarely occur. However, with the introduction of a selective screening method for QREC in the Norwegian monitoring programme for antimicrobial resistance in the veterinary sector in 2014; 89.5% of broiler caecal samples and 70.7% of broiler meat samples were positive. This triggered the concern if there could be possible links between broiler and human reservoirs of QREC. We are addressing this by characterizing genomes of QREC from humans (healthy carriers and patients) and broiler isolates (meat and caecum).ResultsThe most frequent mechanism for quinolone resistance in both broiler and human E. coli isolates were mutations in the chromosomally located gyrA and parC genes, although plasmid mediated quinolone resistance (PMQR) was also identified. There was some relatedness of the isolates within human and broiler groups, but little between these two groups. Further, some overlap was seen for isolates with the same sequence type isolated from broiler and humans, but overall, the SNP distance was high.ConclusionBased on data from this study, QREC from broiler makes a limited contribution to the incidence of QREC in humans in Norway.

Short-Term Energy Consumption Prediction of Large Public Buildings Combined with Data Feature Engineering and Bilstm-Attention

Accurate building energy consumption prediction is a crucial condition for the sustainable development of building energy management systems. However, the highly nonlinear nature of data and complex influencing factors in the energy consumption of large public buildings often pose challenges in improving prediction accuracy. In this study, we propose a combined prediction model that combines signal decomposition, feature screening, and deep learning. First, we employ the Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) to decompose energy consumption data. Next, we propose the Maximum Mutual Information Coefficient (MIC)-Fast Correlation Based Filter (FCBF) combined feature screening method for feature selection on the decomposed components. Finally, the selected input features and corresponding components are fed into the Bi-directional Long Short-Term Memory Attention Mechanism (BiLSTMAM) model for prediction, and the aggregated results yield the energy consumption forecast. The proposed approach is validated using energy consumption data from a large public building in Shaanxi Province, China. Compared with the other five comparison methods, the RMSE reduction of the CEEMDAN-MIC-FCBF-BiLSTMAM model proposed in this study ranged from 57.23% to 82.49%. Experimental results demonstrate that the combination of CEEMDAN, MIC-FCBF, and BiLSTMAM modeling markedly improves the accuracy of energy consumption predictions in buildings, offering a potent method for optimizing energy management and promoting sustainability in large-scale facilities.

Development of a Potential-Modulated Electrochemiluminescence Measurement System for Selective and Sensitive Determination of the Controlled Drug Codeine.

Codeine is a common analgesic drug that is a pro-drug of morphine. It also has a high risk of abuse as a recreational drug because of its extensive distribution as an OTC drug. Therefore, sensitive and selective screening methods for codeine are crucial in forensic analytical chemistry. To date, a commercial analytical kit has not been developed for dedicated codeine determination, and there is a need for an analytical method to quantify codeine in the field. In the present work, potential modulation was combined with electrochemiluminescence (ECL) for sensitive determination of codeine. The potential modulated technique involved applying a signal to electrodes by superimposing an AC potential on the DC potential. When tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) was used as an ECL emitter, ECL activity was confirmed for codeine. A detailed investigation of the electrochemical reaction mechanism suggested a characteristic ECL reaction mechanism involving electrochemical oxidation of the opioid framework. Besides the usual ECL reaction derived from the amine framework, selective detection of codeine was possible under the measurement conditions, with clear luminescence observed in an acidic solution. The sensitivity of codeine detection by potential modulated-ECL was one order of magnitude higher than that obtained with the conventional potential sweep method. The proposed method was applied to codeine determination in actual prescription medications and OTC drug samples. Codeine was selectively determined from other compounds in medications and showed good linearity with a low detection limit (150 ng mL-1).

SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function.

The importance of CD11b/CD18 expression in neutrophil effector functions is well known. Beyond KINDLIN3 and TALIN1, which are involvedinthe induction of the high-affinity binding CD11b/CD18 conformation,thesignaling pathways that orchestrate this response remain incompletely understood. We performed an unbiased screening method for protein selection by biotin identification (BioID) and investigated the KINDLIN3 interactome. We used liquid chromatography with tandem mass spectrometry as a powerful analytical tool. Generation of NB4 CD18, KINDLIN3, or SKAP2 knockout neutrophils was achieved using CRISPR-Cas9 technology, and the cells were examined for their effector function using flow cytometry, live cell imaging, microscopy, adhesion, or antibody-dependent cellular cytotoxicity (ADCC). Among the 325 proteins significantly enriched, we identified Src kinase-associated phosphoprotein 2 (SKAP2), a protein involved in actin polymerization and integrin-mediated outside-in signaling. CD18 immunoprecipitation in primary or NB4 neutrophils demonstrated the presence of SKAP2 in the CD11b/CD18 complex at a steady state. Under this condition, adhesion to plastic, ICAM-1, or fibronectin was observed in the absence of SKAP2, which could be abrogated by blocking the actin rearrangements with latrunculin B. Upon stimulation of NB4 SKAP2-deficient neutrophils, adhesion to fibronectin was enhanced whereas CD18 clustering was strongly reduced. This response corresponded with significantly impaired CD11b/CD18-dependent NADPH oxidase activity, phagocytosis, and cytotoxicity against tumor cells. Our results suggest that SKAP2 has a dual role. It may restrict CD11b/CD18-mediated adhesion only under resting conditions, but its major contribution lies in the regulation of dynamic CD11b/CD18-mediated actin rearrangements and clustering as required for cellular effector functions of human neutrophils.

Assessing the Current and Future Potential Distribution of Solanum rostratum Dunal in China Using Multisource Remote Sensing Data and Principal Component Analysis

Accurate information concerning the spatial distribution of invasive alien species’ habitats is essential for invasive species prevention and management, and ecological sustainability. Currently, nationwide identification of suitable habitats for the highly destructive and potentially invasive weed, Solanum rostratum Dunal (S. rostratum), poses a series of challenges. Simultaneously, research on potential future invasion areas and likely directions of spread has not received adequate attention. This study, based on species occurrence data and multi-dimensional environmental variables constructed from multi-source remote sensing data, utilized Principal Component Analysis (PCA) in combination with the Maxent model to effectively model the current and future potential habitat distribution of S. rostratum in China, while quantitatively assessing the various factors influencing its distribution. Research findings indicate that the current suitable habitat area of S. rostratum covers 1.3952 million km2, all of which is located in northern China. As the trend of climate warming persists, the potential habitat suitability range of S. rostratum is projected to shift southward and expand in the future; while still predominantly located in northern China, it will have varying degrees of expansion at different time frames. Notably, during the period from 2040 to 2061, under the SSP1-2.6 scenario, the habitat area exhibits the most significant increase, surpassing the current scenario by 19.23%. Furthermore, attribution analysis based on PCA inverse transformation reveals that a combination of soil, climate, spatial, humanistic, and topographic variables collectively influence the suitability of S. rostratum habitats, with soil factors, in particular, playing a dominant role and contributing up to 75.85%. This study identifies target areas for the management and control of S. rostratum, providing valuable insights into factor selection and variable screening methods in species distribution modeling (SDM).

Simple and selective screening method for the synthetic cathinone MDPT in forensic samples using carbon nanofiber screen-printed electrodes

3′,4′-Methylenedioxy-N-tert-butylcathinone (MDPT), also known as tBuONE or D-Tertylone, is a synthetic cathinone (SC) frequently abused for recreational purposes due to its potent stimulant effects and similarity to illegal substances like methamphetamine and ecstasy. The structural diversity and rapid introduction of new SC analogs to the market poses significant challenges for law enforcement and analytical methods for preliminary screening of illicit drugs. In this work, we present, for the first time, the electrochemical detection of MDPT using screen-printed electrodes modified with carbon nanofibers (SPE-CNF). MDPT exhibited three electrochemical processes (two oxidations and one reduction) on SPE-CNF. The proposed method for MDPT detection was optimized in 0.2 mol L−1 Britton-Robinson buffer solution at pH 10.0 using differential pulse voltammetry (DPV). The SPE-CNF showed a high stability for electrochemical responses of all redox processes of MDPT using the same or different electrodes, with relative standard deviations less than 4.7% and 1.5% (N = 3) for peak currents and peak potentials, respectively. Moreover, the proposed method provided a wide linear range for MDPT determination (0.90–112 μmol L−1) with low LOD (0.26 μmol L−1). Interference studies for two common adulterants, caffeine and paracetamol, and ten other illicit drugs, including amphetamine-like compounds and different SCs, showed that the proposed sensor is highly selective for the preliminarily identification of MDPT in seized forensic samples. Therefore, SPE-CNF with DPV can be successfully applied as a fast and simple screening method for MDPT identification in forensic analysis, addressing the significant challenges posed by the structural diversity of SCs.

Microbial Biosurfactant Screening: Diversity in Assessment Methods

Abstract Biosurfactants are a group of surface-active agents mainly produced by microorganisms and have a wide range of applications in industries as well as agriculture. Global usage of such biologically active compounds as detergents, bioremediation agents, cosmetic products is hugely dependent on their high production. New avenues of research have opened up due to this increased interest, most of which are focused on identifying specialized microorganisms capable of biosurfactant production. Screening methods for selection of biosurfactant producing bacteria are, therefore, of utmost importance in this endeavor. The aim of this review was to discuss various conventional and novel methods that can overcome the hurdles encountered in time effective, economical microbial biosurfactant screening. This review lists several important biosurfactant screening methods based on supernatant, biomass as well as culture media. New methods devised for biosurfactant screening in the last half decade such as surfactant dependent dye solubilization, metagenomic studies etc. are also explained in detail. A thorough grasp of both contemporary and anachronistic screening methodologies will not only lead to discoveries of novel native strains capable of biosurfactant production but also form the basis on which new screening methods can be devised.

Electrochemistry of the synthetic tryptamine 5-MeO-MiPT at glassy carbon and screen-printed electrodes: A rapid and simple screening method for application in forensic analysis

5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT), also known as moxy, is a synthetic tryptamine analogue used recreationally as a hallucinogenic drug. This work investigates the electrochemical behaviour of 5-MeO-MiPT using carbon electrodes for the first time. Although 5-MeO-MiPT showed only one irreversible oxidation process at a glassy carbon electrode, many electrochemical processes were exhibited on a graphite screen-printed electrode (SPE-Gr). The oxidation reaction of 5-MeO-MiPT on both carbon electrode surfaces involves an adsorption-controlled process with the loss of one electron and one proton. A voltammetric screening method for 5-MeO-MiPT was performed in 0.1 mol L−1 phosphate buffer solution at pH 7.0 on the SPE-Gr using differential pulse adsorptive stripping voltammetry (DPAdSV). The proposed method showed a wide linear range (0.05–30.0 µmol L−1) and a sufficiently low limit of detection (0.015 µmol L−1) for application to seized forensic samples containing 5-MeO-MiPT. Good stability of the electrochemical responses for 5-MeO-MiPT detection on SPE-Gr was obtained, using the same or different electrodes (N = 3) with a relative standard deviation of less than 4.0%. Interference studies with other drugs demonstrated that the proposed sensor is selective for electrochemical screening of 5-MeO-MiPT. In addition, 5-MeO-MiPT was identified in a biological sample of synthetic urine and in real seized samples by the proposed method and confirmed by GC-MS. The analytical performance of SPE-Gr with DPAdSV for 5-MeO-MiPT detection shows great potential as a simple, fast, and selective screening method in forensic scenarios.

Isolation and characterization of fungi and bacteria able to grow on media containing gasoline and diesel fuel

Petroleum products are significant environmental pollutants. This study aimed to isolate microorganisms able to grow on media containing gasoline and diesel fuel. Microorganisms were isolated from soils sampled near gasoline and diesel pumps. Bacterial isolates were characterized and tested on media containing concentrations ranging from 10 to 100 % gasoline and diesel fuel and combinations of both 50/50 % and 25/25/50 % (gasoline/ diesel/ Mueller Hinton broth). Results showed that microbial isolates belong to the genera Pseudomonas, Bacillus, Staphylococcus, Micrococcus, Flavobacterium, Actinobacteria, Penicillium, Hansfordia and Alternaria. Pseudomonas spp. and Bacillus spp. showed the ability to grow on both products up to the concentration of 80 %. However, no growth was noticed above that concentration and on both mixtures. Throughout this study, it has been shown that using a selective screening method for microorganisms able to grow on pollutants can present a significant advantage for bioremediation. Keywords: Pollution; gasoline; diesel; microorganisms.

Blastomere movement correlates with ploidy and mosaicism in early-stage human embryos after in vitro fertilization.

Embryos undergo chaotic division and decrease in quality on day 3 with a reduction in the rates of subsequent blastocyst formation. Disordered cleavage causes a deterioration in embryonic quality, here we assessed the relationship between an cleavage model in first mitosis and the chromosomal status of human embryos, and discuss the potential biological and clinical implications for the cleavage model as a single parameter that can be used to assess embryonic quality. Thirty-two infertile couples, with normal karyotypes and who underwent their first IVF cycle were recruited to donate one normal two-cell-stage embryo each for this study between 2019 and 2020. Twenty-eight two-cell embryos underwent preimplantation genetic testing of each blastomere, and four chaotic-division embryos were stained with Hoechst and cultured in a confocal laser-scanning microscopy incubator system. This system showed high specificity and PPV but low sensitivity and NPV using the CM in the prediction of euploidy, indicating that CM could be considered a screening method for embryo selection; additional observational studies using the CM to select transferable embryos are needed before it can be used in clinical practice.

Rapid and simple voltammetric screening method for Lysergic Acid Diethylamide (LSD) detection in seized samples using a boron-doped diamond electrode

We present a new approach for the screening method of Lysergic Acid Diethylamide (LSD) in blotter papers using square wave voltammetry with a Boron-Doped Diamond Electrode (BDDE). The LSD electrochemical detection is based on an oxidation process at the BDDE in 0.1 mol L−1 acetate buffer pH 4.0. The BDDE exhibited a highly stable response for LSD oxidation (peak current and peak potential) with a relative standard deviation lower than 1.6 % (N = 10). The linear range for LSD determination spans over two orders of magnitude (5.0–100 μmol L−1) with an excellent linear regression coefficient (r2 > 0.999) and a LOD of 0.5 μmol L−1, which is sufficiently low to detect this drug in seized samples. An interference study for LSD detection in seized blotter papers was performed for twenty (20) synthetic drugs belonging to the phenethylamines derivative groups. The analytical performance of the proposed approach revealed itself as an easy, rapid, and selective screening method for the detection of LSD in blotter papers and other presentation formats.

Predicting quality, texture and chemical content of yam (Dioscorea alataL.) tubers using near infrared spectroscopy

Despite the importance of yam ( Dioscorea spp.) tuber quality traits, and more precisely texture attributes, high-throughput screening methods for varietal selection are still lacking. This study sets out to define the profile of good quality pounded yam and provide screening tools based on predictive models using near infrared reflectance spectroscopy. Seventy-four out of 216 studied samples proved to be moldable, i.e. suitable for pounded yam. While samples with low dry matter (<25%), high sugar (>4%) and high protein (>6%) contents, low hardness (<5 N), high springiness (>0.5) and high cohesiveness (>0.5) grouped mostly non-moldable genotypes, the opposite was not true. This outline definition of a desirable chemotype may allow breeders to choose screening thresholds to support their choice. Moreover, traditional near infrared reflectance spectroscopy quantitative prediction models provided good prediction for chemical aspects (R2 > 0.85 for dry matter, starch, protein and sugar content), but not for texture attributes (R2 < 0.58). Conversely, convolutional neural network classification models enabled good qualitative prediction for all texture parameters but hardness (i.e. an accuracy of 80, 95, 100 and 55%, respectively, for moldability, cohesiveness, springiness and hardness). This study demonstrated the usefulness of near infrared reflectance spectroscopy as a high-throughput way of phenotyping pounded yam quality. Altogether, these results allow for an efficient screening toolbox for quality traits in yams.

Rapid Self-Selecting and Clone-Free Integration of Transgenes into Engineered CRISPR Safe Harbor Locations in Caenorhabditis elegans.

Precision genome editing for model organisms has revolutionized functional analysis and validation of a wide variety of molecular systems. To date, the capacity to insert single-copy transgenes into the model nematode Caenorhabditis elegans has focused on utilizing either transposable elements or CRISPR-based safe harbor strategies. These methods require plate-level screening processes to avoid selecting heritable extrachromosomal arrays or rely on co-CRISPR markers to identify knock-in events. As a result, verification of transgene insertion requires anti-array selection screening methods and PCR genotyping. These approaches also rely on cloning plasmids for the addition of transgenes. Here, we present a novel safe harbor CRISPR-based integration strategy that utilizes engineered insertion locations containing a synthetic guide RNA target and a split-selection system to eliminate false positives from array formation, thereby providing integration-specific selection. This approach allows the experimenter to confirm an integration event has taken place without molecular validation or anti-array screening methods and is capable of producing integrated transgenic lines in as little as five days post-injection. To further increase the speed of generating transgenic lines, we also utilized the C. elegans native microhomology-based recombination, to assemble transgenes in-situ, removing the cloning step. We show that complete transgenes can be made and inserted into our split-selection safe harbor locations starting from PCR products, providing a clone-free and molecular-validation-free strategy for single-copy transgene integration. Overall, this combination of approaches provides an economical and rapid system for generating highly reproducible complex transgenics in C. elegans.

A normal screening ultrasound does not provide complete reassurance in infants at risk of hip dysplasia; further follow-up is required.

Screening for developmental hip dysplasia (DDH) continues to evolve with the use of ultrasound (US) in either selective or universal screening methods. The possibility of delayed evidence of DDH, and thus the need for radiographic follow-up at a later stage of development have been suggested by some authors. The aim of this review was to evaluate the number of patients in our hospital network with a normal screening US at 6weeks with evidence of DDH at the time of radiographic review at 6months. Secondary aim; to determine the outcomes for these patients. A retrospective review was done to infants undergoing DDH ultrasound screening between January and December 2015. Initial US and radiographs at 6months were reviewed. Patients with normal screening US who had subsequent radiographs were included for analysis. In total, there were 829 patients included for analysis. Sixty-three patients (8%) had evidence of DDH at 6months, representing 34% of all DDH diagnoses for the study period. Five of the 63 patients were lost to follow-up. The remaining 58 babies were treated in Boston bracing. Four patients with evidence of persistent DDH were referred for tertiary review. The osteotomy rate in the radiograph diagnosed group was 2%, versus 6% and 3% in the unstable and US diagnosed groups, respectively. Eight percent of patients with a normal screening US had evidence of DDH at time of radiograph at 6months, reflecting 34% of all our DDH cases for the year. Based on these findings, patients in our hospital network undergo radiographic evaluation at 6months even if the initial screening US is normal.

A first-phase screening method for site selection of large-scale solar plants with an application to Italy

Increasing the exploitation of renewable energy sources (RES) is a key element for reducing the detrimental consequences of greenhouse-gases emissions and for satisfying the growing demand for energy. Solar power plays a central role having the potential to completely satisfy the world energetic needs. Locating optimal sites for installing solar plants is therefore an important task deeply affecting the long term profitability of such plants. The present paper proposes a filtering method to select a subset of efficient locations in order to reduce the dimensionality of the original problem when a large territory is screened for locating optimal sites for large-scale solar plants. It is based on the idea of preference relations and Pareto dominance and, avoiding to operate an inter-comparison of different locations’ attributes, it can be considered assumptions-free. Moreover, the paper applies such filtering method, together with an analysis of economic viability, to Italy, a country with relatively high potentials in terms of solar energy that currently lacks an optimal site selection analysis. Once applied, the filter reduces the original set of feasible locations by more than 99%. The resulting Pareto efficient locations, evaluated through five selected criteria, are concentrated in the southern part of Italy and, particularly, in the islands of Sicily and Sardinia, where also the economic viable locations are mostly found.

COMPUTATIONAL DESIGN OF NOVEL ORAL INSULIN CONJUGATES FOR THE DEVELOPMENT OF SOLID ORAL INSULIN DOSAGE FORMS

Objective: Insulin is used to manage diabetes mellitus by subcutaneous injections regulary, that has become a part of patients life and is distressing for patients. Hence, we anticipate to get rid of the usage of subcutaneous injections completely from the medicine world and would make the diabetic people to say as “farewell to painful injections.”
 Methods: Virtual screening method (for selection of carriers), Toxtree tool (for toxicity evaluation of carriers), and discovery studio tool (for pharmacophore designing, absorption, distribution, metabolism, excretion, and toxicity [ADMET] analysis, designing oral insulin conjugates (OICs), and interaction studies between insulin receptor and OICs) were used for proposed study.
 Results: We have screened 14 competent drug delivering molecules (DDMs) from seven chemical compound databases. The ADMET and pharmacophoric properties of DDMs were analyzed by drug-informatics’ tools. Consequently, the DDMs were mono, di, and poly conjugated by covalent bonding with various binding sites of monomeric and hexameric form of human insulin and insulin-lispro (Humalog®) individually; and novel OICs were generated. Its binding efficiency and biological activity with insulin-receptor were determined.
 Conclusion: Inulin and Vitamin-B1 are the novel, safe, and proficient carriers for oral delivery of insulin. Insulin lispro is the remarkable option for oral delivery than other insulin forms.

Incorporating immunohistochemical markers into screening methods for BRCA1-mutated breast cancer.

BRCA1-mutated breast cancer (BC) is responsible for approximately 25% of hereditary breast cancer cases. BRCA1 is a tumor suppressor protein regulating the cell cycle and DNA repair; therefore its dysfunctions play a significant role in carcinogenesis. BRCA1-mutated BC is associated with basal-like phenotype, lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in addition to frequent TP53 mutations and poor prognosis. Currently used criteria for genetic evaluation of BC for the risk of hereditary mutations are based on patients' age and family history, and therefore are prone to be imprecise or incomplete. This review discusses recently developed sets of immunohistochemical markers, promising independent markers (nestin, ALDH1, FOXO3, claudins, topoisomerase 1, EGFR) and their potential to be incorporated into clinical practice as a support tool in oncological counseling. This approach could be applied as a screening method for cost-effective selection of cases requiring genetic testing or adapted in pathology laboratories with limited access to molecular techniques. Although not all of the described predictor models have been validated yet, they could further improve the performance of BRCA1 screening methods in BC in the near future via increasing the accuracy of criteria for further genetic evaluation.

Prevalence of Transfusion Transmitted Infections from Eastern Part of India

Background: Blood transfusion saves millions of lives everyday across the world. However, transmission of infections along with blood transfusion though can be minimized but cannot be completely avoided. The chance of transmitting infections is higher in underdeveloped laboratories with limited resources. Transfusion transmitted infections (TTI’s) can cause significant morbidity and mortality as well. Methods: A retrospective data analysis was carried out in SMIMS, Gangtok, in the far eastern part of India to estimate the incidence of transfusion transmitted infections (TTI’s) in the last five years, from January, 2013 to December, 2017. 5 ml of venous blood was collected from each donor and blood was screened for HBsAg, HIV, HCV, Syphilis and Malaria using card tests. The reactive cases were confirmed with third generation ELISA, TrueLISATM. Result: A total of 10,011 blood donors were screened from January, 2013 to December, 2017. Male voluntary donors were more compared to female donors. Among the 135 seropositive cases 92 donors (0.91%) were positive for HBsAg, 23 donors (0.22%) were positive for anti HCV, 16 donors (0.15%) were positive for HIV while 4 donors(0.04%) were positive for syphilis. No case of malaria was noted in our study. The overall prevalence of HBsAg, HCV, HIV and syphilis was 0.91%, 0.15%, 0.22%, and 0.04% respectively. Conclusion: The goal of routine blood transfusion should be to decrease the seroprevalance of TTI’s. Strict blood donor selection and proper screening methods along with nucleic acid detection can help in reducing the seroprevalance of TTI’s.

Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population.

The prevalence of Lynch syndrome and the use of universal tumor screening to identify Lynch syndrome among unselected patients with upper urinary tract urothelial carcinoma, which is associated with Lynch syndrome, have not been closely investigated yet. A total of 166 tumors from 164 upper urinary tract urothelial carcinoma patients were tested for microsatellite instability and expression of mismatch repair proteins (MLH1, MHS2, MSH6 and PMS2) by immunohistochemistry. Genetic testing was performed for patients suspected of having Lynch syndrome. Clinicopathological factors, including familial and personal cancer history associated with mismatch repair deficiency, were evaluated. The frequency of high-level microsatellite instability and loss of at least one mismatch repair protein was 2.4% (4/164); the microsatellite instability and immunohistochemistry results showed complete concordance. Of these four patients, three were genetically proven to have Lynch syndrome, while the remaining one was highly suggestive for Lynch syndrome based on their personal cancer history. Univariate analysis showed that age<70years (P=0.04), ureter as the tumor location (P=0.052), previous history/synchronous diagnosis of colorectal cancer (P<0.01) and fulfillment of the criteria per the revised Bethesda guideline (P<0.01) tended to be or were significantly associated with high-level microsatellite instability/mismatch repair loss. The prevalence of Lynch syndrome among unselected upper urinary tract urothelial carcinoma patients was at least 1.8% in our study population. The screening efficacies of the microsatellite instability test and immunohistochemistry appear equivalent. Universal tumor screening may be a valid approach; however, selective screening methods that consider factors associated with mismatch repair loss/high-level microsatellite instability tumors require further investigation.

Selective screening for familial hypercholesterolemia in Austrian children - first year results

BackgroundFamilial hypercholesterolemia (FH), the most frequent monogenetic hereditary disorder, is underdiagnosed and undertreated. Early identification of FH is essential because of the increased risk for premature cardiovascular diseases and childhood might be the optimal period for cholesterol screening. Aim of this selective screening was to detect familial hypercholesterolemia, the most frequent monogenetic hereditary disorder in children to guarantee early detection and treatment. The Austrian strategy for primary schools, to perform a pre-school examination by school physicians, allows to reach all children aged 5–7 years.MethodsThe screening was conducted within the school enrolment examinations in all 215 public primary schools in Vienna between January to May 2017. Positive cholesterol screening was defined by non-HDL-C > 160 mg/dL and/or LDL-C > 130 mg/dL.ResultsIn total, 18,152 children had their school enrolment examination. From 133 tested pre-school children, nine individuals were positive-screened with a mean LDL-C of 161 ± 26 mg/dL, non-HDL-C of 181 ± 24 mg/dL and total cholesterol (TC) of 239 ± 23 mg/dL. From 85 siblings, four individuals were positively screened with a mean LDL-C of 150 ± 7 mg/dL, non-HDL-C of 184 ± 8 mg/dL and TC of 231 ± 10 mg/dL. Patients did not have any xanthomas, xanthelasms, arcus lipoides, or any cardiovascular comorbidities.ConclusionsScreening at early childhood by school physicians seems to be a successful strategy and possible. With this Austrian selective screening method, FH Kids Austria, we could find nine patients with positive raised level LDL-cholesterol and/or non-HDL cholesterol out of 133 blood tests. Prevention of cardiovascular diseases is essential and it is our duty to increase the awareness of this disease. Limitations of the FH Kids project were reduced participation of school physicians and refusal of the parents.