Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows.

Therapeutic drug monitoring is essential for dosing pharmaceuticals with narrow therapeutic windows. Nevertheless, standard methods are imprecise and involve invasive/resource-intensive procedures with long turnaround times. Overcoming these limitations, we present a microneedle-based electrochemical aptamer biosensing patch (µNEAB-patch) that minimally invasively probes the interstitial fluid (ISF) and renders correlated, continuous, and real-time measurements of the circulating drugs' pharmacokinetics. The µNEAB-patch is created following an introduced low-cost fabrication scheme, which transforms a shortened clinical-grade needle into a high-quality gold nanoparticle-based substrate for robust aptamer immobilization and efficient electrochemical signal retrieval. This enables the reliable in vivo detection of a wide library of ISF analytes-especially those with nonexistent natural recognition elements. Accordingly, we developed µNEABs targeting various drugs, including antibiotics with narrow therapeutic windows (tobramycin and vancomycin). Through in vivo animal studies, we demonstrated the strong correlation between the ISF/circulating drug levels and the device's potential clinical use for timely prediction of total drug exposure.

Measurement of Hepatic Lipids.

Liver plays a central role in lipid metabolism, uptake of lipoproteins and lipids from the circulation (e.g., chylomicron remnant), and secretions of very low-density lipoproteins (VLDL). Therefore, measurements of lipid levels in the liver have been broadly used to check hepatic function, especially in subjects who have chronic liver diseases, such as nonalcoholic steatohepatitis (NASH), in which there is accumulation of fat, inflammation, and damage to liver cells. In this chapter, we describe the processes of extracting hepatic lipids by the method of Folch et al., and measuring the levels of cholesterol, triglycerides, phospholipids, and non-esterified fatty acids using enzymatic assays.

The epidemiology of hypernatraemia in hospitalised children in Lothian: a 10-year study showing differences between dehydration, osmoregulatory dysfunction and salt poisoning.

INTRODUCTION: The relative frequencies of the causes of hypernatraemia in children after the neonatal period are unknown. Salt poisoning and osmoregulatory dysfunction are extremely rare and potentially fatal. In this retrospective 10-year study, the incidence, causes and differential biochemistry of hypernatraemia in children is examined. METHODS: Children with hypernatraemia (sodium ≥ 150 mmol/litre) aged >2 weeks to 17 years were identified from laboratory data of two paediatric departments serving the Lothian region of Scotland. A review of patient notes established time of onset and cause. Denominator data were available from the Scottish Health Service. RESULTS: On admission to hospital, 1 in 2288 children (1:1535 admitted as an emergency) had hypernatraemia. This is 1 in 30 563 Lothian children <17 years. Overall 0.04% hospital stays had an episode of hypernatraemia. In 45 children admitted with 64 separate episodes (11 from a case of salt poisoning), the commonest cause was dehydration secondary to either gastroenteritis or systemic infection; 31% had an underlying chronic neurological disorder. A total of 177 further cases developed hypernatraemia after admission. The commonest causes were dehydration secondary to severe systemic infection and postoperative cardiac surgery. Urine sodium:creatinine ratio and fractional excretion of sodium were both much higher in the salt poisoning case than in a child with osmoregulatory dysfunction or children with simple dehydration. CONCLUSIONS: Hypernatraemia after 2 weeks of age is uncommon, and on admission is usually associated with dehydration. Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission will differentiate these rare causes.

Self-assembled monolayers of alkylphosphonic acid on GaN substrates.

In this paper we describe the formation and characterization of self-assembled monolayers of octadecylphosphonic acid (ODPA) on epitaxial (0001) GaN films on sapphire. By immersing the substrate in its toluene solution, ODPA strongly adsorbed onto UV/O 3-treated GaN to give a hydrophobic surface. Spectroscopic ellipsometry verified the formation of a well-packed monolayer of ODPA on the GaN substrate. In contrast, adsorption of other primarily substituted hydrocarbons (C n H 2 n+1 X; n = 16-18; X = -COOH, -NH 2, -SH, and -OH) offered less hydrophobic surfaces, reflecting their weaker interaction with the GaN substrate surfaces. A UV/O 3-treated N-polar GaN had a high affinity to the -COOH group in addition to ODPA, possibly reflecting the basic properties of the surface. These observations suggested that the molecular adsorption was primarily based on hydrogen bond interactions between the surface oxide layer on the GaN substrate and the polar functional groups of the molecules. The as-prepared ODPA monolayers were desorbed from the GaN substrates by soaking in an aqueous solution, particularly in a basic solution. However, ODPA monolayers heated at 160 degrees C exhibited suppressed desorption in acidic and neutral aqueous solution maybe due to covalent bond formation between ODPA and the surface. X-ray photoelectron spectroscopy provided insight into the effect of the UV/O 3 treatment on the surface composition of the GaN substrate and also the ODPA monolayer formation. These results demonstrate that the surface of a GaN substrate can be tailored with organic molecules having an alkylphosphonic acid moiety for future sensor and device applications.