Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Preanalytical stability of antibodies to pathogenic antigens

Background: Serologic testing for antibodies against epitopes from pathogens is a valuable tool for investigating the relationship between infection and disease. This study comprehensively evaluates the impact of preanalytic variation on antibody seropositivities to a selected set of antigens arising from delays in processing of blood samples, preprocessing storage temperature, and vacutainer type. Methods: We assessed peripheral blood collected from 29 volunteers in four different Vacutainer types [ethylenediaminoetetraacetic acid (EDTA), acid-citrate-dextrose (ACD), lithium heparin (LH), serum separator tubes (SST)], and stored at 4°C or room temperature for 0, 1, 2, 3, 4, 5, and 6 days before processing. Multiplex serology was used to determine antibody reactivity against 35 antigens derived from human papillomaviruses, human polyomaviruses, Epstein- Barr virus, and Helicobacter pylori. Cohen's k statistic was used to measure agreement on seropositivity status between samples exposed to standard and nonstandard clinical practice conditions. Results: For samples processed without delay, k was not associated with storage-temperature (P value range 0.23 to 0.95) or vacutainer type (P value range, 0.35-0.89). Kappa did not significantly decline with increasing delays in processing for any vacutainer-type storage temperature combination (P slope range, 0.06-1.00). Conclusions: Antibodies to epitopes from various pathogenic infectious agents can be measured reliably from samples stored in SST, EDTA, ACD, or LH vacutainers at either room temperature or 4°C for up to 6 days before processing. Impact: Serologic testing is robust to several preanalytic options. These findings are particularly important for epidemiologic studies recruiting participants from remote settings where sample exposure to preanalytic conditions can vary considerably. Cancer Epidemiol Biomarkers Prev; 26(8); 1337-44

Standard Peripheral Blood Mononuclear Cell Cryopreservation Selectively Decreases Detection of Nine Clinically Relevant T Cell Markers

Biobanking is an operational component of various epidemiological studies and clinical trials. Although peripheral blood is routinely acquired and stored in biobanks, the effects of specimen processing on cell composition and clinically relevant functional markers of T cells still require a systematic evaluation. In this study, we assessed 25 relevant T cell markers in human PBMCs and showed that the detection of nine membrane markers (e.g., PD-1, CTLA4, KLRG1, CD25, CD122, CD127, CCR7, and others reflecting exhaustion, senescence, and other functions) was reduced among at least one T cell subset following standard processing, although the frequency of CD4, CD8, and regulatory T cells was unaffected. Nevertheless, a 6-mo-long cryopreservation did not impair the percentages of cells expressing many other membrane and all the eight tested intracellular lineage or functional T cell markers. Our findings uncover that several clinically relevant markers are particularly affected by processing and the interpretation of those results in clinical trials and translational research should be done with caution.</p

Prirodni i proizvedeni radionuklidi u uzorcima mahovina iz regiona Severne Grčke

Terrestrial mosses obtain most of their nutrients directly from precipitation and dry deposition, and they can be used for monitoring of airborne radionuclide depositions. Ninetyfive samples of Hypnum Cupressiforme were collected in Northern Greece during the end of summer 2016. After the preparation, mosses were measured in a low-background HPGe detector with relative efficiency 32%. The activity concentrations of 7 Be ranged from 69 to 1280 Bq kg-1, and the concentrations of 137Cs ranged from 0 to 425 Bq kg-1. The concentrations of 210Pb were between 147 and 1920 Bq kg-1 and for 40K were between 120 and 750 Bq kg-1. Differences have been observed in the activity concentrations between the mosses collected from ground surface, rocks, branches and near roots. Finally, no correlation between the concentrations of 7 Be and 210Pb has been found.Mahovine svoje nutrijente direktno dobijaju iz padavina i suvom depozicijom i mogu se koristiti za monitoring depozicije radionuklida iz vazduha. Devedesetpet uzoraka mahovina (Hypnum Cupressiforme) je sakupljeno u regionu Severne Grčke tokom kraja leta 2016. godine. Posle pripreme, mahovine su merene na niskofonskom HPGe detektoru relativne efikasnosti 32%. Izmerene koncentracije aktivnosti 7 Be su bile od 69 do 1280 Bq kg-1, aktivnosti 137Cs od 0 do 425 Bq kg-1, aktivnosti 210Pb od 147 do 1920 Bq kg-1 , a 40K od 120 do 750 Bq kg-1. Primećene su razlike u koncentracijama aktivnosti radionuklida u mahovinama koje su sakupljene sa zemlje, kamena, grana stabala i blizu korena stabla. Između 7 Be i 210Pb nije pronađena nikakva korelacija

Towards norms for accreditation of biobanks for human health and medical research:Compilation of existing guidelines into an ISO certification/accreditation norm-compatible format

In recent years, biobanks have evolved into professional infrastructures that acquire, validate, process, store, manage and distribute biological material of human origin to public or private end-users/researchers. This article (a) highlights the importance of quality assurance for both the biobank basic processes and sample annotation in order to ensure reliable results of research based on these samples, (b) suggests that certification according to international standards can contribute to the organization of the biobanking processes while accreditation can contribute to the organization of sample characterization/validation, and (c) provides a compilation of all existing guidelines against an International Organization for Standardization (ISO) format.</p

Prirodni i proizvedeni radionuklidi u uzorcima mahovina iz regiona Severne Grčke

Terrestrial mosses obtain most of their nutrients directly from precipitation and dry deposition, and they can be used for monitoring of airborne radionuclide depositions. Ninetyfive samples of Hypnum Cupressiforme were collected in Northern Greece during the end of summer 2016. After the preparation, mosses were measured in a low-background HPGe detector with relative efficiency 32%. The activity concentrations of 7 Be ranged from 69 to 1280 Bq kg-1, and the concentrations of 137Cs ranged from 0 to 425 Bq kg-1. The concentrations of 210Pb were between 147 and 1920 Bq kg-1 and for 40K were between 120 and 750 Bq kg-1. Differences have been observed in the activity concentrations between the mosses collected from ground surface, rocks, branches and near roots. Finally, no correlation between the concentrations of 7 Be and 210Pb has been found.Mahovine svoje nutrijente direktno dobijaju iz padavina i suvom depozicijom i mogu se koristiti za monitoring depozicije radionuklida iz vazduha. Devedesetpet uzoraka mahovina (Hypnum Cupressiforme) je sakupljeno u regionu Severne Grčke tokom kraja leta 2016. godine. Posle pripreme, mahovine su merene na niskofonskom HPGe detektoru relativne efikasnosti 32%. Izmerene koncentracije aktivnosti 7 Be su bile od 69 do 1280 Bq kg-1, aktivnosti 137Cs od 0 do 425 Bq kg-1, aktivnosti 210Pb od 147 do 1920 Bq kg-1 , a 40K od 120 do 750 Bq kg-1. Primećene su razlike u koncentracijama aktivnosti radionuklida u mahovinama koje su sakupljene sa zemlje, kamena, grana stabala i blizu korena stabla. Između 7 Be i 210Pb nije pronađena nikakva korelacija

Protocol for a prospective, longitudinal cohort of people with COVID-19 and their household members to study factors associated with disease severity:the Predi-COVID study

INTRODUCTION: A few major clinical factors such as sex, obesity or comorbidities have already been associated with COVID-19 severity, but there is a need to identify new epidemiological, clinical, digital and biological characteristics associated with severity and perform deep phenotyping of patients according to severity. The objectives of the Predi-COVID study are (1) to identify new determinants of COVID-19 severity and (2) to conduct deep phenotyping of patients by stratifying them according to risk of complications, as well as risk factors for infection among household members of Predi-COVID participants (the Predi-COVID-H ancillary study). METHODS AND ANALYSIS: Predi-COVID is a prospective, hybrid cohort study composed of laboratory-confirmed COVID-19 cases in Luxembourg who will be followed up remotely for 1 year to monitor their health status and symptoms. Predi-COVID-H is an ancillary cohort study on household members of index cases included in Predi-COVID to monitor symptoms and household clusters in this high-risk population. A subcohort of up to 200 Predi-COVID and 300 Predi-COVID-H participants with biological samples will be included. Severity of infection will be evaluated by occurrence and duration of hospitalisation, admission and duration of stay in intensive care units or equivalent structures, provision of and duration of supplemental oxygen and ventilation therapy, transfer to another hospital, as well as the impact of infection on daily activities following hospital discharge. ETHICS AND DISSEMINATION: The study has been approved by the National Research Ethics Committee of Luxembourg (study number 202003/07) in April 2020. An informed consent is signed by study participants. Scientific articles will be submitted to international peer-reviewed journals, along with press releases for lay audience for major results. TRIAL REGISTRATION NUMBER: NCT04380987.</p

Prostorna distribucija prirodnih radionuklida merena u Srbiji upotrebom biomonitora

Активност природних радионуклида је мерена у 217 узорака маховина Hypnum cupressiforme које су сакупљене крајем лета 2015. године на комплетној територији Републике Србије са циљем да се установи просторна дистрибуција радионуклида. Мерења су вршена NaI детектором облика јаме. Посебна пажња је посвећена 7Be који се већ деценијама користи као природни обележивач у изучавању транспортних процеса у атмосфери. Добијено је да је дистрибуција атмосферске депозиције 7Be неуниформна и да се најмања и највећа измерена вредност разликују девет пута. Просторна дистрибуција 7Be не показује корелацију са рељефом терена за разлику од 137Cs кога има више у планинским и шумовитим пределима. Присутност радионуклида из урановог и торијумовог низа у доброј мери зависи од структуре и састава тла на локацијама са којих су узимани узорци.The activities of natural radionuclide were measured in 217 moss samples that were collected at the entire territory of Serbia. Measurements were taken by well-type NaI detector in order to establish the spatial distribution of radionuclides. Special attention was paid to 7Be. It is obtained that the distribution of atmospheric deposition of 7Be is non-uniform; the minimum and maximum measured value differs nine times. No coincidence of the spatial distribution of 7Be with the relief was observed. It was noticed that higher values of 137Cs were detected in mountain and wooded areas. The presence of radionuclides from the Uranium and Thorium chains in the large extent depends on the structure of the soil at the sampling site

Recommandations préanalytiques pour les analyses de protéomique clinique des fluides biologiques

International audienc

LacaScore: a novel plasma sample quality control tool based on ascorbic acid and lactic acid levels

Introduction Metabolome analysis is complicated by the continuous dynamic changes of metabolites in vivo and ex vivo. One of the main challenges in metabolomics is the robustness and reproducibility of results, partially driven by pre-analytical variations. Objectives The objective of this study was to analyse the impact of pre-centrifugation time and temperature, and to determine a quality control marker in plasma samples. Methods Plasma metabolites were measured by gas chromatography-mass spectrometry (GC–MS) and analysed with the MetaboliteDetector software. The metabolites, which were the most labile to pre-analytical variations, were further measured by enzymatic assays. A score was calculated for their use as quality control markers. Results The pre-centrifugation temperature was shown to be critical in the stability of plasma samples and had a significant impact on metabolite concentration profiles. In contrast, pre-centrifugation delay had only a minor impact. Based on the results of this study, whole blood should be kept on wet ice and centrifuged within maximum 3 h as a prerequisite for preparing EDTA plasma samples fit for the purpose of metabolome analysis. Conclusions We have established a novel blood sample quality control marker, the LacaScore, based on the ascorbic acid to lactic acid ratio in plasma, which can be used as an indicator of the blood pre-centrifugation conditions, and hence the suitability of the sample for metabolome analyses. This method can be applied in research institutes and biobanks, enabling assessment of the quality of their plasma sample collections