A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. ...For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk.
In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-β-1 HDL subclass that participates in macrophage cholesterol efflux.
We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions.
The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge
. ...Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment. Vibrationally excited molecules emit a coherent electric field following few-cycle infrared laser excitation
, and this field is specific to the sample's molecular composition. Employing electro-optic sampling
, we directly measure this global molecular fingerprint down to field strengths 10
times weaker than that of the excitation. This enables transillumination of intact living systems with thicknesses of the order of 0.1 millimetres, permitting broadband infrared spectroscopic probing of human cells and plant leaves. In a proof-of-concept analysis of human blood serum, temporal isolation of the infrared electric-field fingerprint from its excitation along with its sampling with attosecond timing precision results in detection sensitivity of submicrograms per millilitre of blood serum and a detectable dynamic range of molecular concentration exceeding 10
. This technique promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings.
Abstract
Objective
To update the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline published in 2010.
Participants
The participants include an Endocrine Society–appointed ...task force of 10 medical content experts and a clinical practice guideline methodologist.
Evidence
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
Consensus Process
One group meeting, several conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline.
Conclusions
We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone–binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.
This update to the Endocrine Society’s 2010 testosterone guideline, prepared by an expert panel, describes the diagnosis, screening, treatment, and monitoring of hypogonadal men.
Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers ...insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
Purpose: Current modalities for glucose monitoring are invasive and inconvenient. The search for a noninvasive technique is still ongoing, without a clinically viable product. The aim of our study ...was to evaluate the safety and accuracy of a novel non-invasive continuous glucometer - the Wizmi™ device.
Methods: Prospective, observational, controlled clinical trial. We included healthy pregnant women designated to undergo a 3-hour oral glucose tolerance test. Each participant underwent synchronous and simultaneous glucose measurement by venous sampling of plasma glucose and non-invasive glucose by Wizmi device. Primary outcome was the accuracy of the Wizmi device as assessed by comparing between paired measurements, i.e. non-invasive glucose measurements by Wizmi versus standard plasma glucose levels, which were taken at the exact same time.
Results: Thirty-two women underwent oral glucose tolerance test (OGTT), contributing 224 paired glucose measurements. Of the 224 paired measurements, all were within the clinically appropriate zones of the Clarke error grid analysis zones −208 (93%) in Zone A and 16 (7%) in zone B. Mean absolute relative difference of the Wizmi non-invasive glucose versus plasma glucose laboratory reference was 7.23% or 9.66 mg/dl. Overall, for all 224 paired measurements, across all Wizmi glucose ranges, the agreement was 86.6, 92.0, 97.8 and 99.5% for deviations within ±15, 20, 30, 40% (if glucose >80 mg/dl) or mg/dl (if glucose ≤80 mg/dl).
Conclusions: Wizmi device is novel non-invasive continuous glucose monitor, safe to use, with overall high accuracy compared to a gold standard reference of plasma glucose.
Ascorbic acid, dopamine, and uric acid are important electroactive biomolecules for health monitoring and they coexist in serum or urine. Their quantitative determination by electrochemistry could ...provide the accurate reference for diseases diagnosis and treatment. However, the traditional electrochemical workstations are too large for on-field inspection. Hence, the design of handheld electrochemical system for the detection of biomolecules is significant for point-of-care testing (POCT). In this paper, a smartphone-based integrated voltammetry system using modified electrode was developed for simultaneous detection of biomolecules. The system contained a disposable sensor, a coin-size detector, and a smartphone equipped with application program. Screen-printed electrodes were used as sensors for the detection, on which reduced graphene oxide and gold nanoparticles were electrochemically deposited by the system. The detector was used with voltammetric methods, in which excitation voltage was applied on the sensors and subsequent current responses were detected. The smartphone is the core component to communicate with the detector, calculate data, and plot voltammograms in real-time. Then, the system was applied to detect standard solutions of the biomolecules and their mixtures as examples. The results showed that the peak currents of each substance increased with higher concentration and the method allowed the discrimination of the different potentials of the studied species. Finally, the practical applications of the system were tested through detections of the biomolecules in artificial urine. The results exhibited that the system could be used to detect electrochemical activity of biomolecules with linear, high sensitivity, and specific responses in point-of-care testing.
•A smartphone-based integrated voltammetry system was successfully constructed.•The system can perform both cyclic voltammetry and differential pulse voltammetry.•The system could be used to modify the electrodes with graphene and gold nanoparticles simultaneously.•The system could be used for simultaneous detection of DA, AA, and UA in urine and phosphate buffer solution.•The system with screen printed electrodes showed great potentials in POCT.
We report a fully integrated device that can perform both multiple biochemical analysis and sandwich type immunoassay simultaneously on a disc. The whole blood is applied directly to the disposable ..."lab-on-a-disc" containing different kinds of freeze-dried reagents for the blood chemistry analysis as well as reagents required for the immunoassay. The concentrations of different kinds of analytes are reported within 22 min by simply inserting a disc to a portable device. Using the innovative laser irradiated ferrowax microvalves together with the centrifugal microfluidics, the total process of plasma separation, metering, mixing, incubation, washing, and detection is fully automated. The analyzer is equipped with an optical detection module to measure absorbances at 10 different wavelengths to accommodate the various kinds of reaction protocols. Compared to the conventional blood analysis done in clinical laboratories, it is advantageous for point-of-care applications because it requires a smaller amount of blood (350 μL vs. 3 mL), takes less time (22 min vs. several days), does not require specially trained operators or expensive instruments to run biochemical analysis and immunoassay separately.
•Improved electrospray ionization in SFC-MS by post-column make-up.•Enhanced sensitivity for protease inhibitors plasma analysis.•DMSO adducts to simplify full scan spectrum.
In supercritical fluid ...chromatography coupled to atmospheric pressure ionization mass spectrometry (SFC-MS), the use of a make-up post-column is almost mandatory to avoid analyte precipitation, especially when using low percentage of modifier (<5%) in the mobile phase. Due to the specific nature of gaseous CO2, the tuning of the make-up conditions in electrospray becomes an important factor and can be used to tune analyte sensitivity. Neither a dilution effect (loss of signal) nor a relevant degradation of chromatographic performances is observed with the addition of a make-up at various flow-rates, up to 0.7mL/min. From supercritical conditions (1mL/min 40°C, 150bar) to gaseous state (room temperature, atmospheric pressure), the CO2 expands around 430 times, contributing to almost 5% of the nebulizing process. In positive mode, the presence of ammonium ions either in the mobile phase or in the make-up did significantly increase the MS signal, even at basic apparent pH. The ionization performance of electrospray is influenced by the acidic buffer power of the carbon dioxide, and was found to be restricted in the apparent pH range of 3.8–7.2 in the various conditions investigated. This may challenge sensitive detection in negative mode, as illustrated for bosentan. The use of DMSO as make-up additive (up to 30%) showed a simplification of the full scan spectrum regarding the adducts. Finally, the optimization of make-up composition leads to an enhancement up to a factor of 69 on the electrospray MS response signal, for the SFC-SRM/MS analysis of HIV protease inhibitors in plasma extracted from Dried Plasma Spots.
Non-specific symptoms, as well as the lack of a cost-effective test to triage patients in primary care, has resulted in increased time-to-diagnosis and a poor prognosis for brain cancer patients. A ...rapid, cost-effective, triage test could significantly improve this patient pathway. A blood test using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy for the detection of brain cancer, alongside machine learning technology, is advancing towards clinical translation. However, whilst the methodology is simple and does not require extensive sample preparation, the throughput of such an approach is limited. Here we describe the development of instrumentation for the analysis of serum that is able to differentiate cancer and control patients at a sensitivity and specificity of 93.2% and 92.8%. Furthermore, preliminary data from the first prospective clinical validation study of its kind are presented, demonstrating how this innovative technology can triage patients and allow rapid access to imaging.
Coronavirus disease 2019 (COVID-19) represents a new pandemic caused by severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2). A previous pooled analysis clearly identified elevated ...D-dimer levels as being associated with severity of COVID-19. Since then, several other studies have provided clearer support for this initial evidence. However, potentially under-recognized by those reporting on D-dimer is the considerable variation in reporting units for D-dimer, and thus also the potential for misreporting of D-dimer data based on poor or incomplete reporting. A PubMed search was used to identify recent papers reporting on D-dimers in COVID-19-based studies. We report that: (1) most publications did not identify either the manufacturer or D-dimer product used; (2) most did not identify whether D-dimer values were reported as D-dimer units (DDU) or fibrinogen equivalent units (FEU) (~2 × differences); (3) nearly half did not identify normal cut-off values; (4) some did not report numerical findings or units for D-dimer; (5) where reported, most identified units as either mg/L or μg/mL; (6) we identified at least four errors in reporting from 21 papers. It may not be possible to truly standardize D-dimer assays, but it should be feasible to harmonize D-dimer assays to a single unit of measurement.
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