Do cerebrospinal fluid transfer methods affect measured amyloid β42, total tau, and phosphorylated tau in clinical practice?

Introduction Cerebrospinal fluid (CSF) neurodegenerative markers are measured clinically to support a diagnosis of Alzheimer's disease. Several preanalytical factors may alter the CSF concentrations of amyloid β 1–42 (Aβ1–42) in particular with the potential to influence diagnosis. We aimed to determine whether routine handling of samples alters measured biomarker concentration compared with that of prompt delivery to the laboratory. Methods Forty individuals with suspected neurodegenerative diseases underwent diagnostic lumbar punctures using a standardized technique. A sample of each patient's CSF was sent to the laboratory by four different delivery methods: (1) by courier at room temperature; (2) by courier, on ice; (3) using standard hospital portering; and (4) after quarantining for >24 hours. Aβ1–42, total tau (t‐tau), and phosphorylated tau (p‐tau) levels measured using standard enzyme‐linked immunosorbent assay techniques were compared between transfer methods. Results There were no significant differences in Aβ1–42, t‐tau, or p‐tau concentrations measured in samples transported via the different delivery methods despite significant differences in time taken to deliver samples. Discussion When CSF is collected in appropriate tubes, transferred at room temperature, and processed within 24 hours, neurodegenerative markers can be reliably determined

The complete digital workflow in fixed prosthodontics: a systematic review

Background The continuous development in dental processing ensures new opportunities in the field of fixed prosthodontics in a complete virtual environment without any physical model situations. The aim was to compare fully digitalized workflows to conventional and/or mixed analog-digital workflows for the treatment with tooth-borne or implant-supported fixed reconstructions. Methods A PICO strategy was executed using an electronic (MEDLINE, EMBASE, Google Scholar) plus manual search up to 2016–09-16 focusing on RCTs investigating complete digital workflows in fixed prosthodontics with regard to economics or esthetics or patient-centered outcomes with or without follow-up or survival/success rate analysis as well as complication assessment of at least 1 year under function. The search strategy was assembled from MeSH-Terms and unspecific free-text words: {((“Dental Prosthesis” [MeSH]) OR (“Crowns” [MeSH]) OR (“Dental Prosthesis, Implant-Supported” [MeSH])) OR ((crown) OR (fixed dental prosthesis) OR (fixed reconstruction) OR (dental bridge) OR (implant crown) OR (implant prosthesis) OR (implant restoration) OR (implant reconstruction))} AND {(“Computer-Aided Design” [MeSH]) OR ((digital workflow) OR (digital technology) OR (computerized dentistry) OR (intraoral scan) OR (digital impression) OR (scanbody) OR (virtual design) OR (digital design) OR (cad/cam) OR (rapid prototyping) OR (monolithic) OR (full-contour))} AND {(“Dental Technology” [MeSH) OR ((conventional workflow) OR (lost-wax-technique) OR (porcelain-fused-to-metal) OR (PFM) OR (implant impression) OR (hand-layering) OR (veneering) OR (framework))} AND {((“Study, Feasibility” [MeSH]) OR (“Survival” [MeSH]) OR (“Success” [MeSH]) OR (“Economics” [MeSH]) OR (“Costs, Cost Analysis” [MeSH]) OR (“Esthetics, Dental” [MeSH]) OR (“Patient Satisfaction” [MeSH])) OR ((feasibility) OR (efficiency) OR (patient-centered outcome))}. Assessment of risk of bias in selected studies was done at a ‘trial level’ including random sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other bias using the Cochrane Collaboration tool. A judgment of risk of bias was assigned if one or more key domains had a high or unclear risk of bias. An official registration of the systematic review was not performed. Results The systematic search identified 67 titles, 32 abstracts thereof were screened, and subsequently, three full-texts included for data extraction. Analysed RCTs were heterogeneous without follow-up. One study demonstrated that fully digitally produced dental crowns revealed the feasibility of the process itself; however, the marginal precision was lower for lithium disilicate (LS2) restorations (113.8 μm) compared to conventional metal-ceramic (92.4 μm) and zirconium dioxide (ZrO2) crowns (68.5 μm) (p < 0.05). Another study showed that leucite-reinforced glass ceramic crowns were esthetically favoured by the patients (8/2 crowns) and clinicians (7/3 crowns) (p < 0.05). The third study investigated implant crowns. The complete digital workflow was more than twofold faster (75.3 min) in comparison to the mixed analog-digital workflow (156.6 min) (p < 0.05). No RCTs could be found investigating multi-unit fixed dental prostheses (FDP). Conclusions The number of RCTs testing complete digital workflows in fixed prosthodontics is low. Scientifically proven recommendations for clinical routine cannot be given at this time. Research with high-quality trials seems to be slower than the industrial progress of available digital applications. Future research with well-designed RCTs including follow-up observation is compellingly necessary in the field of complete digital processing

The contribution of inherited genotype to breast cancer

The etiology of breast cancer is complex, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. These inherited genotypes include those that affect the propensity to be exposed to breast carcinogens, and those associated with breast tumorigenesis directly. In addition, inherited genotypes may influence response to breast cancer chemoprevention and treatment. Studies relating inherited genotypes with breast cancer incidence and mortality should consider a broader spectrum of genes and their potential roles in multistage carcinogenesis than have been typically evaluated to date. Understanding the role of inherited genotype at different stages of carcinogenesis could improve our understanding of cancer biology, may identify specific exposures or events that correlate with carcinogenesis, or target relevant biochemical pathways for the development of preventive or therapeutic interventions

Surgical reconstruction of the left main coronary artery with patch-angioplasty

<p>Abstract</p> <p>Background</p> <p>Conventional coronary artery bypass grafting (CABG) has been established as the treatment of choice for left main coronary artery (LMCA) stenosis However, the conventional grafting provides a retrograde perfusion to extensive myocardial area and leads prospectively to competitive flow of the non-occluded coronaries thus consuming the grafts. Surgical reconstruction of the LMCA with patch-angioplasty is an alternative method that eliminates these drawbacks.</p> <p>Methods</p> <p>Between February 1997 and July 2007, 37 patients with isolated LMCA stenosis were referred for surgical ostial reconstruction. In 27 patients (73%) surgical angioplasties have been performed. All patients were followed up clinically and with transesophageal echocardiography (TEE) and coronary angiography when required.</p> <p>Results</p> <p>In 10 patients (27%) a LMCA stenosis could not be confirmed. There were no early mortality or perioperative myocardial infarctions. The postoperative course was uneventful in all patients. In 25 patients, TEE demonstrated a wide open main stem flow pattern one to six months after reconstruction of the left main coronary artery with one patch mild aneurysmal dilated.</p> <p>Conclusions</p> <p>The surgical reconstruction with patch-angioplasty is a safe and effective method for the treatment of proximal and middle LMCA stenosis. Almost one third of the study group had no really LMCA stenosis: antegrade flow pattern remained sustained and the arterial grafts have been spared. In the cases of unclear or suspected LMCA stenosis, cardio-CT can be performed to unmask catheter-induced coronary spasm as the underlying reason for isolated LMCA stenosis.</p

Mutagenicity of comfrey (Symphytum Officinale) in rat liver

Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. METHODS: We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n = 156), DLB (n = 20), behavioural variant frontotemporal dementia (bvFTD; n = 45), progressive non-fluent aphasia (PNFA; n = 17), and semantic dementia (SD; n = 7); approximately 10% were pathology/genetically confirmed (n = 26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n = 104), DLB (n = 5), bvFTD (n = 12), PNFA (n = 3), SD (n = 9), and controls (n = 10). RESULTS: There were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity > 50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort. CONCLUSIONS: CSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA

Nine-year comparison of presentation and management of acute coronary syndromes in Ireland: a national cross-sectional survey

BACKGROUND: Shorter time to treatment is associated with lower mortality in acute coronary syndromes (ACS). A previous (1994) survey showed substantial delays for acute myocardial infarction (AMI) in Ireland. The present study compared current practice with 1994 and surveyed acute coronary syndromes as a more complete contemporary evaluation of critical cardiac care than assessing AMI alone. METHODS: Following ethics committee approval, all centres (N = 39) admitting acute cardiac patients to intensive/coronary care unit provided information on 1365 episodes. A cross-sectional survey design was employed. RESULTS: Since 1994, median hospital arrival to thrombolysis time was reduced by 41% (76 to 45 minutes). Thrombolysis was delivered more often in the emergency department in 2003 (48% vs 2%). Thrombolysis when delivered in the emergency department was achieved faster than thrombolysis delivered in intensive/coronary care (35 mins v 60 mins; z = 5.62, p < .0001). Suspected AMI patients who did not subsequently receive thrombolysis took longer to present to hospital (5 h vs 2 h 34 mins; z = 7.33, p < .0001) and had longer transfer times to the intensive/coronary care unit following arrival (2 h 17 mins vs 1 h 10 mins; z = 8.92, p < .0001). Fewer confirmed AMI cases received thrombolysis in 2003 (43% vs 58%). There was an increase in confirmed cases of AMI from 1994 (70% to 87%). CONCLUSIONS: Substantial improvements in time to thrombolysis have occurred since 1994, probably relating to treatment provision in emergency departments. Patient delay pre-hospital is still the principal impediment to effective treatment of ACS. A recent change of definition of AMI may have precluded an exact comparison between 1994 and 2003 data

Gene selection for classification of microarray data based on the Bayes error

<p>Abstract</p> <p>Background</p> <p>With DNA microarray data, selecting a compact subset of discriminative genes from thousands of genes is a critical step for accurate classification of phenotypes for, e.g., disease diagnosis. Several widely used gene selection methods often select top-ranked genes according to their individual discriminative power in classifying samples into distinct categories, without considering correlations among genes. A limitation of these gene selection methods is that they may result in gene sets with some redundancy and yield an unnecessary large number of candidate genes for classification analyses. Some latest studies show that incorporating gene to gene correlations into gene selection can remove redundant genes and improve classification accuracy.</p> <p>Results</p> <p>In this study, we propose a new method, Based Bayes error Filter (BBF), to select relevant genes and remove redundant genes in classification analyses of microarray data. The effectiveness and accuracy of this method is demonstrated through analyses of five publicly available microarray datasets. The results show that our gene selection method is capable of achieving better accuracies than previous studies, while being able to effectively select relevant genes, remove redundant genes and obtain efficient and small gene sets for sample classification purposes.</p> <p>Conclusion</p> <p>The proposed method can effectively identify a compact set of genes with high classification accuracy. This study also indicates that application of the Bayes error is a feasible and effective wayfor removing redundant genes in gene selection.</p