Optical determination of lithium therapeutic levels in micro-volumes of interstitial fluid.

BACKGROUND: Long-term management of bipolar disorder (BD), characterized by mood fluctuating between episodes of mania and depression, involves the regular taking of lithium preparations as the most reliable mood stabilizer for bipolar patients. However, despite its effectiveness in preventing and reducing mood swings and suicidality, lithium has a very narrow therapeutic index and it is crucial to carefully monitor lithium plasma levels as concentrations >1.2 mmol/L are potentially toxic and can be fatal. Current methods of lithium therapeutic monitoring involve frequent blood tests, which have several drawbacks related to the invasiveness of the technique, comfort, cost and reliability. Dermal interstitial fluid (ISF) is an accessible and information-rich biofluid, and correlations have been found between blood and ISF levels of lithium medication. METHODS: In the current study, we sought to investigate the optical determination of lithium therapeutic concentrations in samples of ISF extracted from porcine skin utilizing a microneedle-based approach. Monitoring of lithium levels in porcine ISF was achieved by employing a spectrophotometric method based on the reaction between the chromogenic agent Quinizarin and lithium. RESULTS: The resulting spectra show spectral variations which relate to lithium concentrations of lithium in samples of porcine ISF with a coefficient of determination (R2 ) of 0.9. This study has demonstrated successfully that therapeutic levels of lithium in micro-volumes of porcine ISF can be measured with a high level of accuracy utilizing spectroscopic techniques. CONCLUSIONS: The results support the future development of a miniaturized and minimally-invasive device for lithium monitoring in bipolar patients.

Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder.

Since the mid-20th century, lithium continues to be prescribed as a first-line mood stabilizer for the management of bipolar disorder (BD). However, lithium has a very narrow therapeutic index, and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The quantification of lithium in clinical laboratories is performed by atomic absorption spectrometry, flame emission photometry, or conventional ion-selective electrodes. All these techniques are cumbersome and require frequent blood tests with consequent discomfort which results in patients evading treatment. Furthermore, the current techniques for lithium monitoring require highly qualified personnel and expensive equipment; hence, it is crucial to develop low-cost and easy-to-use devices for decentralized monitoring of lithium. The current paper seeks to review the pertinent literature rigorously and critically with a focus on different lithium-monitoring techniques which could lead towards the development of automatic and point-of-care analytical devices for lithium determination.

Nutrient Therapy for the Improvement of Fatigue Symptoms.

Fatigue, characterised by lack of energy, mental exhaustion and poor muscle endurance which do not recover following a period of rest, is a common characteristic symptom of several conditions and negatively impacts the quality of life of those affected. Fatigue is often a symptom of concern for people suffering from conditions such as fibromyalgia, chronic fatigue syndrome, cancer, and multiple sclerosis. Vitamins and minerals, playing essential roles in a variety of basic metabolic pathways that support fundamental cellular functions, may be important in mitigating physical and mental fatigue. Several studies have examined the potential benefits of nutrients on fatigue in various populations. The current review aimed to gather the existing literature exploring different nutrients' effects on fatigue. From the searches of the literature conducted in PubMed, Ovid, Web of Science, and Google scholar, 60 articles met the inclusion criteria and were included in the review. Among the included studies, 50 showed significant beneficial effects (p < 0.05) of vitamin and mineral supplementation on fatigue. Altogether, the included studies investigated oral or parenteral administration of nutrients including Coenzyme Q10, L-carnitine, zinc, methionine, nicotinamide adenine dinucleotide (NAD), and vitamins C, D and B. In conclusion, the results of the literature review suggest that these nutrients have potentially significant benefits in reducing fatigue in healthy individuals as well as those with chronic illness, both when taken orally and parenterally. Further studies should explore these novel therapies, both as adjunctive treatments and as sole interventions.

A paper-based colorimetric method for monitoring of lithium therapeutic levels.

Lithium remains the "gold standard" for both acute and maintenance treatment of bipolar disorder (BD), a serious life-long condition characterised by recurrent episodes of depressed and manic mood states. However, lithium has a very narrow therapeutic range (0.4-1.2 mmol L-1) and despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. While it is crucial to carefully monitor lithium plasma levels, the current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Therefore, development of low-cost and facile lithium detection techniques that can be translated into point-of-care devices for personal monitoring will be a major advance in the management of BD. In the current study, we present colorimetric determination of lithium therapeutic levels utilizing test paper strips, based on its reaction with the chromogenic agent Quinizarin. Exposure of Quinizarin-dipped test papers to samples of interstitial fluid (ISF) or dH2O spiked with therapeutic concentrations of lithium resulted in colour changes that were monitored using optical spectroscopy. The acquired spectra from the test papers show spectral variations which are related to lithium concentrations in spiked samples of dh2O and artificial ISF with a coefficient of determination (R2) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.

Identification of biomarkers for glycaemic deterioration in type 2 diabetes.

We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.

Simultaneous extraction and analysis of clozapine and lorazepam from human plasma using dual solvent-stir bar microextraction with different acceptor phases followed by high-performance liquid chromatography ultra-violet detection.

A new design of dual solvent stir bar microextraction (DSSBME) was developed and combined with HPLC-UV for the simultaneous extraction of clozapine (CLZ) and lorazepam (LRP) from human plasma with different acceptor phases. Two short hollow fibers immobilized with an organic extraction solvent were used as the solvent bars for microextraction of CLZ and LRP from the sample solution. The solvent bars were fixed with a staple pin which served as the stirrer. The target analytes were simultaneously and selectively extracted from the sample solution into their corresponding solvent bar. Extraction parameters such as organic solvent type, pH of the sample solution, the acceptor phase concentration, salt incorporation into the solution, stirring rate, and extraction time were optimized to achieve the best extraction results. Under the optimum conditions (1-undecanol as extraction solvent, pH of sample solution = 9.0, 10% w/v NaCl, concentration of HCl = 10 mM, concentration of NaOH = 100 mM, stirring rate of 1400 rpm and extraction time of 30 min at ambient temperature) the limit of detection for CLZ was 0.4 ng mL-1 and for LRP it was 1.1 ng mL-1. The linear range for CLZ was 1.3-1000.0 ng mL-1 (R2 = 0.9991) and for LRP it was 3.6-800.0 ng mL-1 (R2 = 0.9993). Extraction recovery and the enrichment factor for CLZ were 95.4% and 343 and for LRP they were 74.3% and 263, respectively. Finally, the method developed was successfully applied for the simultaneous determination of CLZ and LRP in human plasma samples.

Wearable, Environmental, and Smartphone-Based Passive Sensing for Mental Health Monitoring.

Collecting and analyzing data from sensors embedded in the context of daily life has been widely employed for the monitoring of mental health. Variations in parameters such as movement, sleep duration, heart rate, electrocardiogram, skin temperature, etc., are often associated with psychiatric disorders. Namely, accelerometer data, microphone, and call logs can be utilized to identify voice features and social activities indicative of depressive symptoms, and physiological factors such as heart rate and skin conductance can be used to detect stress and anxiety disorders. Therefore, a wide range of devices comprising a variety of sensors have been developed to capture these physiological and behavioral data and translate them into phenotypes and states related to mental health. Such systems aim to identify behaviors that are the consequence of an underlying physiological alteration, and hence, the raw sensor data are captured and converted into features that are used to define behavioral markers, often through machine learning. However, due to the complexity of passive data, these relationships are not simple and need to be well-established. Furthermore, parameters such as intrapersonal and interpersonal differences need to be considered when interpreting the data. Altogether, combining practical mobile and wearable systems with the right data analysis algorithms can provide a useful tool for the monitoring and management of mental disorders. The current review aims to comprehensively present and critically discuss all available smartphone-based, wearable, and environmental sensors for detecting such parameters in relation to the treatment and/or management of the most common mental health conditions.