Search

The ability to monitor protein biomarkers continuously and in real-time would significantly advance the precision of medicine. Current protein-detection techniques, however, including ELISA and lateral flow assays, provide only time-delayed, single-time-point measurements, limiting their ability to guide prompt responses to rapidly evolving, life-threatening conditions. In response, here we present an electrochemical aptamer-based sensor (EAB) that supports high-frequency, real-time biomarker measurements. Specifically, we have developed an electrochemical, aptamer-based (EAB) sensor against Neutrophil Gelatinase-Associated Lipocalin (NGAL), a protein that, if present in urine at levels above a threshold value, is indicative of acute renal/kidney injury (AKI). When deployed inside a urinary catheter, the resulting reagentless, wash-free sensor supports real-time, high-frequency monitoring of clinically relevant NGAL concentrations over the course of hours. By providing an "early warning system", the ability to measure levels of diagnostically relevant proteins such as NGAL in real-time could fundamentally change how we detect, monitor, and treat many important diseases.

Objective Methods Results Conclusions We aimed to evaluate how urine specific gravity (USG) and rates of supposed hypohydration vary by race/ethnicity, and to examine how adjustment for several important factors impacts estimated USG.Using the National Health and Nutrition Examination Survey, this cross‐sectional study evaluated a total of 4195 (2098 female, 2097 male) Americans and categorized them as supposedly hypohydrated (USG≥1.020) or not using spot urine samples. USG and prevalence of supposed hypohydration were compared across racial/ethnic groups, separately by gender. The analyses considered the impact of urine creatinine, body composition, age, dietary nutrients, and physical activity.Differences in supposed hypohydration prevalence were observed by race/ethnicity in men (p = .030) and women (p < .001). In unadjusted models, Black women's USG (1.0189) was higher (p < .05) than all the other race/ethnicity groups' USG (1.0142–1.0171). In men, Blacks' USG (1.0197) was higher (p < .05) than the USG of Whites (1.0177) and other/multi‐racial (1.0176) but not Mexican Americans (1.0196) or other Hispanics (1.0192). Adjustments for age, arm circumference, nutrients (protein, sodium, potassium, and moisture), and physical activity minimally influenced USG estimates. Further adjustment for urine creatinine lowered USG for Black women and men by 0.003 and 0.0023, respectively, with no notable lowering of USG in the other races/ethnicities. Supplemental analyses matching Whites and Blacks on age, moisture intake, and poverty‐to‐income ratio confirmed racial differences in urine creatinine and USG, though the effects were most pronounced in women.Using a USG≥1.020 to identify hypohydration in all races/ethnicities may be inappropriate due to, among other factors, differences in urinary creatinine. [ABSTRACT FROM AUTHOR]

Oxygen uptake kinetics (τVO2) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q) kinetics is unclear. This study determined τVO2 in canine muscle in situ, with experimental control over muscle activation and Q during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. Muscle VO2 was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τVO2/TTI and τQ were less in S1SPON (mean ± s.d.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2SPON (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τVO2/TTI was unchanged by pump-perfusion (S1PUMP, 12 ± 4 s; S2PUMP, 24 ± 6 s; P < 0.001) despite increased O2 delivery; at S2 onset, venous O2 saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively. VO2 kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O2 delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscle VO2 control is more complex than previously suggested.

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients' health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at subminute temporal resolution. We show that MEDIC can also obtain pharmacokinetic parameters for individual animals in real time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe that MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters.

Aberrations in glucose, insulin, and other postprandial (PP) markers are common in obesity and cardiometabolic disorders. One potentially simple lifestyle/dietary modification to manage these issues is to change the order in which foods are consumed within meals. Carbohydrate exerts the largest effect on PP glucose, and there is some evidence that ingesting dietary fat or protein before carbohydrate delays gastric emptying of carbohydrate and reduces PP glucose. Additionally, certain dietary proteins may augment insulin release if ingested with carbohydrate, thereby improving blood glucose clearance. This review aimed to systematically evaluate evidence from acute experiments that modified the order in which foods were consumed in isocaloric meals. Outcomes of interest were PP glucose and insulin (including area under the curve for both), C-peptide, gut hormones, and perceptual responses. Three databases were searched (PubMed, Cochrane CENTRAL, Web of Science) in February 2022. Additionally, reference lists of identified reports were searched, and an author of several studies was consulted to verify that relevant literature was included. The review included acute interventions that administered isocaloric meals of the same foods but with foods eaten in different orders. Studies were not excluded based on participant characteristics. Eleven reports were identified. All reports that assessed glucose and insulin showed a tendency toward lower levels, at least over parts of the PP period, by consuming carbohydrates last. GLP-1 tended to be higher in carbohydrate-last conditions, though this was only measured in a few studies. Perceptual responses (hunger, fullness, etc.) were not consistently different between conditions in two studies, but the certainty of evidence was very low. Findings indicate that, at least acutely, there may be benefits to eating carbohydrate after vegetable and/or protein-rich foods. The most consistent effect (judged as moderate certainty) is that carbohydrate-last meal orders tend to lower blood glucose and insulin excursions. [ABSTRACT FROM AUTHOR]