Veni, Vidi, Vici: Immobilized Peptide-Based Conjugates as Tools for Capture, Analysis, and Transformation

Analysis of peptide biomarkers of pathological states of the organism is often a serious challenge, due to a very complex composition of the cell and insufficient sensitivity of the current analytical methods (including mass spectrometry). One of the possible ways to overcome this problem is sample enrichment by capturing the selected components using a specific solid support. Another option is increasing the detectability of the desired compound by its selective tagging. Appropriately modified and immobilized peptides can be used for these purposes. In addition, they find application in studying the specificity and activity of proteolytic enzymes. Immobilized heterocyclic peptide conjugates may serve as metal ligands, to form complexes used as catalysts or analytical markers. In this review, we describe various applications of immobilized peptides, including selective capturing of cysteine-containing peptides, tagging of the carbonyl compounds to increase the sensitivity of their detection, enrichment of biological samples in deoxyfructosylated peptides, and fishing out of tyrosine–containing peptides by the formation of azo bond. Moreover, the use of the one-bead-one-compound peptide library for the analysis of substrate specificity and activity of caspases is described. Furthermore, the evolution of immobilization from the solid support used in peptide synthesis to nanocarriers is presented. Taken together, the examples presented here demonstrate immobilized peptides as a multifunctional tool, which can be successfully used to solve multiple analytical problems.

Highly sensitive biomarker biosensor for early detection of cancer biomarkers

Biomarkers are emerging as potentially important diagnostic tools for cancer and many other diseases. However, many current detection systems for suffer from insufficient sensitivity. To address this concern, we developed a highly sensitive biosensor, featuring monoclonal antibody-coated polystyrene nanobeads assembled in the trenches of a microchip, for the detection of cancer biomarkers. These biosensors detected nucleosomes and carcinoembryonic antigen in serum at concentrations of 62.5 and 15.6 pg/mL, respectively. Very low detection limits that suggest such devices might be beneficial for the early detection of tumors and for monitoring of patients in remission.

Yersiniosis in New Zealand

The rate of yersiniosis in New Zealand (NZ) is high compared with other developed countries, and rates have been increasing over recent years. Typically, >99% of human cases in NZ are attributed to Yersinia enterocolitica (YE), although in 2014, a large outbreak of 220 cases was caused by Yersinia pseudotuberculosis. Up until 2012, the most common NZ strain was YE biotype 4. The emergent strain since this time is YE biotype 2/3 serotype O:9. The pathogenic potential of some YE biotypes remains unclear. Most human cases of yersiniosis are considered sporadic without an identifiable source. Key restrictions in previous investigations included insufficient sensitivity for the isolation of Yersinia spp. from foods, although foodborne transmission is the most likely route of infection. In NZ, YE has been isolated from a variety of sick and healthy domestic and farm animals but the pathways from zoonotic reservoir to human remain unproven. Whole-genome sequencing provides unprecedented discriminatory power for typing Yersinia and is now being applied to NZ epidemiological investigations. A “One-Health” approach is necessary to elucidate the routes of transmission of Yersinia and consequently inform targeted interventions for the prevention and management of yersiniosis in NZ

Clinical diagnosis of COVID-19: a prompt, feasible, and sensitive diagnostic tool for COVID-19 based on a 1,757-patient cohort (The AndroCoV Clinical Scoring for COVID-19 diagnosis)

ImportanceIn the COVID-19 pandemic, a limiting barrier for more successful approaches to COVID-19 is the lack of appropriate timing for its diagnosis, during the viral replication stage, when antiviral approaches could demonstrate efficacy, precluding progression to severe stages. Three major reasons that hamper the diagnosis earlier in the disease are the unspecific and mild symptoms in the first stage, the cost- and time-limitations of the rtPCR-SARS-CoV-2, and the insufficient sensitivity of this test as desired for screening purposes during the pandemic. More sensitive and earlier methods of COVID-19 detection should be considered as key for breakthrough changes in the disease course and response to specific therapeutic strategies. Our objective was to propose a clinical scoring for the diagnosis of COVID-19 (The AndroCoV Clinical Scoring for COVID-19 Diagnosis) that has been validated in a large population sample, aiming to encourage the management of patients with high pre-clinical likelihood of presenting COVID-19, at least during the pandemics, independent of a rtPCR-SARS-COV-2 test.Materials and methodsThis is a compounded retrospective and prospective analysis of clinical data prospectively collected from the Pre-AndroCoV and AndroCov Trials that resulted in a clinical scoring for COVID-19 diagnosis based on likelihood of presenting COVID-19 according to the number of symptoms, presence of anosmia, and known positive household contact, in a variety of combinations of scoring criteria, aiming to the detect scorings that provided the highest pre-test probability and accuracy. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and accuracy were calculated for subjects screened in two different periods and altogether, for females, males, and both, in a total of nine different scenarios, for combinations between one, two, or three or more symptoms, or presence of anosmia in subjects without known positive household contacts, and no symptoms, one, two, or three or more symptoms, or presence of anosmia or ageusia in subjects with known positive household contacts.Results1,757 patients were screened for COVID-19. Among the multiple combinations, requiring two or more symptoms with or without anosmia or ageusia for subjects without known contact and one or more symptoms with or without anosmia or ageusia with known positive contacts presented the highest accuracy (80.4%), and higher pretest probability and accuracy than virtually all rtPCR-SARS-CoV-2 commercially available kit tests.ConclusionThe AndroCoV Clinical Scoring for COVID-19 Diagnosis was demonstrated to be a feasible, quick, inexpensive and sensitive diagnostic tool for clinical diagnosis of COVID-19. A clinical diagnosis of COVID-19 should avoid delays and missed diagnosis, and reduce costs, and should therefore be recommended as a first-line option for COVID-19 diagnosis for public health policies, at least while SARS-CoV-2 is the prevailing circulating virus.Key PointsQuestionIs a clinical diagnosis of COVID-19 sensitive, accurate, and feasible?FindingsThe present analysis of a 1,757-subject cohort of the AndroCoV trials demonstrated that clinical scoring for COVID-19 diagnosis can deliver a more sensitive and prompter diagnosis than the current gold-standard diagnostic method, rtPCR-SARS-CoV-2, with an accuracy above 80%.MeaningA clinical diagnosis of COVID-19 avoids missed diagnosis due to insufficient sensitivity or incorrect timing of the performance of rtPCR-SARS-CoV-2, reduces costs, avoid delays on specific managements, and allows the testing of potentially effective antiviral therapeutic approaches that should work if administered in the early stage of COVID-19

A Nonspecific Approach to Metacognitive Experiences: The Experimental Study of Control Sense and Confidence in Giving a Correct Answer

There are specific and nonspecific approaches to explaining diversity of metacognitive experiences in psychological testing. The study is concerned with verification of the effects of a nonspecific approach, according to which there is a nonspecific signal about the success of task performance behind metacognitive experiences. Unidirectional changes in experiencing confidence and control sense were expected to be revealed. The findings showed that correct answers were given with more confidence than wrong ones, confident correct answers were given faster than unconfident correct ones, straightforward cases were handled with a high level of confidence and more sense of control if long time was given to think them over. The study failed in demonstrating unidirectional character of control sense and confidence in other conditions, which can be explained by insufficient sensitivity of the technique chosen to measure control sense.

Synchronous Detection of Heavy Metal ions in Aqueous Solution by Gold Nanoparticles SurfaceEnhanced Laser-Induced Breakdown Spectroscopy

Heavy metal ion-induced water pollution has become a severe environmental problem in the world. Although providing a powerful technique for multi-element detection, laser-induced breakdown spectroscopy (LIBS) suffers from insufficient sensitivity...

Anxiety and Depression Related Abnormalities in Socio-affective Learning

High anxiety may be related insufficient sensitivity to changing reinforcement during operant learning. Whether such findings are specific to anxiety is unclear given a wider literature relating negative affect to abnormal learning and the possibility that relationships are not consistent across incentive types (i.e. punishment and reward) and outcomes (i.e., positive or negative). In two separate samples ( = 76; = 49), participants completed an operant learning task with positive, negative, and neutral socio-affective feedback, designed to assess adaptive responses to changing environmental volatility. Contrary to expectations, general affective distress, rather than anxiety or depression specifically, was related to an increase, rather than a decrease, in the rate of learning for negative outcomes in volatile, relative to stable, environments. Our results suggest an important but general role in anxiety and depression of overweighting negative feedback when the value of an action becomes uncertain, as when environmental volatility increases.

Why we should be looking for ear lobe creases. A systematic review and meta-analysis of diagonal ear lobe crease and coronary artery disease.

Objectives The association between diagonal ear lobe crease (DELC) and cardiovascular disease was first suggested in 1973 although some studies have attributed this to confounding cardiovascular factors. This review looked to see if there is a significant association between DELC and angiography-confirmed coronary artery disease (CAD) independent of other risk factors. Design Systematic review and meta-analysis of selected studies using the PRISMA checklist. Setting 12 different hospitals with angiography in eight countries. Participants 4960 adult patients undergoing coronary angiography. Main Outcome Measures • Presence/absence of diagonal ear lobe crease • Diagnostic Odds Ratio • Sensitivity/Specificity Results 12 studies were included in the meta-analysis. Findings from our study suggest: • Patients with DELC have a 4x increased likelihood of having CAD (OR 4.61 P<0.00001). • The relationship between DELC and CAD was independent of age and all other conventional cardiovascular risk factors. • Bilateral DELC has a stronger association with CAD than unilateral DELC. • Presence of DELC has insufficient sensitivity / specificity to be used as a diagnostic test for cardiovascular disease but instead should be used as a risk marker. Conclusions We found that DELC is associated with CAD independently of other known cardiovascular risk factors including age. Histology studies indicate that atherosclerosis is causing DELC and patients with DELC appear to have an increased risk of CAD. It has insufficient sensitivity or specificity to be used as a diagnostic test but should be used as a valuable risk marker to be aware of whilst examining ears.

Diagnostik und Therapie unklarer Gallengangsstenosen

Biliary stenoses represent a differential diagnostic challenge. Diagnostic methods to clarify the underlying dignity are often invasive, and provide high specificity beside insufficient sensitivity. In many cases, an accurate diagnosis is only possible over time, and therefore limits curative treatment options. This article provides an overview of the diagnostic challenges and treatment options for unclear biliary stenosis.

Insufficient Sensitivity of RNA Dependent RNA Polymerase Gene of SARS-CoV-2 Viral Genome as Confirmatory Test using Korean COVID-19 Cases

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. As of February 21, total 75,773 confirmed cases worldwide have spread to more than two dozen countries. Transmission of COVID-19 can occur early in the course of infection since SARS-CoV-2 viral loads in asymptomatic patients are similar to that in the symptomatic patients. Therefore, more sensitive diagnostic methods are needed to detect early phase of the infection to prevent secondary or tertiary spreads. Here, we compare the RT-PCR confirmatory test results using two different SARS-CoV-2 viral RNAs from two Korean COVID-19 confirmed cases.RT-PCR method targeting the RdRP gene, which was recommended by WHO guideline, was less sensitive than targeting N genes (as per CDC guideline). Because many countries follow the WHO guideline, our findings may contribute to the early diagnosis of COVID-19.