Copper and Zinc as Potential Biomarkers of Mood Disorders and Pandemic Syndrome

The diagnosis of affective disorders has been the subject of constant research by clinicians from all over the world for many years. Making an appropriate diagnosis among patients suffering from mood disorders is sometimes problematic due to the personality-changing nature of patients and the similarity in the clinical picture of episodes in affective disorders. For this reason, there is a need to develop rapid and effective methods of determining biological markers that differentiate these diseases. The research was carried out with blood taken from 15 patients and 15 volunteers. The analysis of biological material for trace concentrations of zinc and copper was carried out with the use of ultrasensitive triple-quadrupole inductively coupled plasma mass spectrometry (TQ ICP-MS). The obtained results prove that the concentration of copper in the test group was lower than in the control group. For the zinc concentrations, the inverse relationship was observed. The group of patients was characterized by a higher concentration of this element than the group of healthy volunteers. Summarizing the obtained results and comparing them with the results of studies by other authors, it was found that zinc and copper may be potential biomarkers of affective disorders and pandemic syndrome.     

Preparation and Performance of Thickened Liquids for Patients with Konjac Glucomannan-Mediated Dysphagia

The present study sought to characterize the rheological and thickening properties of Konjac glucomannan (KGM) and prepare thickening components for special medical purposes using KGM and maltodextrin as the primary raw materials and guar gum (GG), xanthan gum (XG), locust bean gum (LBG), and carrageenan (KC) as the supplemented materials. The formulation and preparation processes were optimized through single factor experiments taking sensory evaluation as an indicator. The results confirm that KGM had excellent thickening performance, reaching about 90 times its own mass. The optimal formulation process of the thickening components based on KGM was as follows: the mass concentration of the compound thickener (KGM/GG/XG/LBG/KC = 13:2:2:2:1) was 5.0–7.0 mg/mL; the maltodextrin concentration was 10.0 mg/mL; the brewing temperature of the thickening component was 60 °C with no restriction on consumption time. The rheology test results revealed that the thickening components had shear thinning characteristics, which could provide three different thickening effects of nectar-thick level (350 mPa·s), honey-thick level (1250 mPa·s), and pudding-thick level (1810 mPa·s) suitable for people with different degrees of chewing disorders. Overall, this study provides a theoretical basis and technical reference for KGM as a dietary nutrition support for patients with dysphagia.     

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.     

Development and validation of a reversed‐phase HPLC method for licarbazepine monitoring in serum of patients under oxcarbazepine treatment

Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders. Several HPLC methods have been developed thus far but there is lack of control for interferences from antipsychotic drugs. The aim of the present study was to develop a simple, low‐cost and reliable HPLC‐UV method for the determination of licarbazepine in human serum in the presence of co‐administered antiepileptic, antipsychotic and commonly prescribed drugs. Sample preparation consisted of a single protein precipitation step with methanol. Separation lasted ~9 min on a reversed‐phase C₁₈ column using a mobile phase composed of 50 mm sodium‐dihydrogen‐phosphate‐monohydrate/acetonitrile (70:30, v/v) delivered isocratically at 0.9 mL/min and 30°C. Wavelength was 210 nm and calibration curve was linear with r ² 0.998 over the range 0.2–50.0 μg/mL. Coefficient of variation was <5.03% and bias <−4.92%. Recovery ranged from 99.49 to 104.52% and the limit of detection was 0.0182 μg/mL. No interferences from the matrix or from antiepileptic, antipsychotic and commonly prescribed drugs were observed. The method was applied to serum samples of patients under oxcarbazepine treatment and proved to be a useful tool for the therapeutic drug monitoring of licarbazepine during monotherapy or adjunctive treatment of seizures or affective disorders.     

Classification of chromatographic data using multidimensional polynomials

Summary A pattern recognition methodology has been developed for analysis of chromatographic data. The method uses a new class of multidimensional orthogonal polynomials developed by Cohen in conjunction with a supervised learning technique. The method is applicable to any chromatographic data for which classification into two or more categories is desired. The algorithm analyzes both elution times and peak areas. An application is shown for the analysis of organic acids in ascitic fluid obtained from patients with liver disorders. Classification of these patients for presence or absence of bacterial infection shows over ninety percent correct classification.     

Acid reflux and hoarseness

The aim of this study was to investigate the prevalence of acid reflux in patients complaining of hoarseness where no organic disease or functional dysphonia could be found. We also aimed to determine whether anti-reflux treatment improved their symptoms. Patients were not selected on the basis of symptoms of reflux. Fifty patients with hoarseness took part in a prospective study that sought to establish objectively whether acid reflux was present. All patients were given a 6-week course of ranitidine and Gaviscon. Patients were asked to score their voice quality before and after treatment. Although 72% of patients complained of heartburn more than once a week, only 40% proved to have acid reflux. Although subjective improvement after anti-reflux treatment was found in a larger proportion of those with than without proven reflux, the conclusions that can be drawn are limited as there were no satisfactory objective measurements of voice or controls.     

Evaluation of comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry for the diagnosis of inherited metabolic disorders using an automated data processing strategy

Organic acidurias are a large group of inherited metabolic disorders (IMDs), commonly diagnosed by GC-MS analysis of organic acids in urine after acidic extraction and trimethylsilylation. In this study, a GC×GC-ToF-MS method has been optimized for the analysis of pathological metabolites in urine. An automated data processing strategy based on the use of mass spectra and GC retention times for the target search and quantification of pathological metabolites has been developed. Using this procedure, each unknown sample is automatically examined for the presence of markers of several diseases at the same time. The method has been applied for the analysis of 6 challenging proficiency testing samples from patients with IMDs (thymidine phosphorylase deficiency, mevalonic aciduria, hawkinsinuria, aromatic l-amino acid decarboxylase deficiency, propionic acidemia and medium-chain acyl-CoA dehydrogenase deficiency). Using the GC×GC-ToF-MS method, we were able to determine complete sets of markers for all the IMDs. The quality of the mass spectral matches for the pathological markers was higher than 800 (out of 1000).     

The Impact of Voice Disorders Among Teachers: Vocal Complaints, Treatment-Seeking Behavior, Knowledge of Vocal Care, and Voice-Related Absenteeism

Objectives

Teachers are at increased risk for developing voice disorders. Occupational risk factors have been extensively examined; however, little attention has been paid to the consequences of the vocal complaints. The objective of this study was to investigate the knowledge that teachers have about vocal care, treatment-seeking behavior, and voice-related absenteeism.

Methods

The study group comprised 994 teachers and 290 controls whose jobs did not involve vocal effort. All participants completed a questionnaire inquiring about vocal complaints, treatment-seeking behavior, voice-related absenteeism, and knowledge about vocal care. Comparisons were made between teachers with and without vocal complaints and with the control group.

Results

Teachers reported significantly more voice problems than the control population (51.2% vs 27.4%) (χ² = 50.45, df = 1, P < 0.001). Female teachers reported significantly higher levels of voice disorders than their male colleagues (38% vs 13.2%, χ² = 22.34, df = 1, P < 0.001). Teachers (25.4%) sought medical care and eventually 20.6% had missed at least 1 day of work because of voice problems. Female teachers were significantly more likely to seek medical help (χ² = 7.24, df = 1, P = 0.007) and to stay at home (χ² = 7.10, df = 1, P = 0.008) in comparison with their male colleagues. Only 13.5% of all teachers received information during their education.

Conclusions

Voice disorders have an impact on teachers' personal and professional life and imply a major financial burden for society. A substantial number of teachers needed medical help and was obligated to stay at home because of voice problems. This study strongly recommends the implementation of vocal education during the training of teacher students to prepare the vocal professional user.     

Parsing disease‐relevant protein modifications from epiphenomena: perspective on the structural basis of SOD1‐mediated ALS

Conformational change and modification of proteins are involved in many cellular functions. However, they can also have adverse effects that are implicated in numerous diseases. How structural change promotes disease is generally not well‐understood. This perspective illustrates how mass spectrometry (MS), followed by toxicological and epidemiological validation, can discover disease‐relevant structural changes and therapeutic strategies. We (with our collaborators) set out to characterize the structural and toxic consequences of disease‐associated mutations and post‐translational modifications (PTMs) of the cytosolic antioxidant protein Cu/Zn‐superoxide dismutase (SOD1). Previous genetic studies discovered >180 different mutations in the SOD1 gene that caused familial (inherited) amyotrophic lateral sclerosis (fALS). Using hydrogen–deuterium exchange with mass spectrometry, we determined that diverse disease‐associated SOD1 mutations cause a common structural defect – perturbation of the SOD1 electrostatic loop. X‐ray crystallographic studies had demonstrated that this leads to protein aggregation through a specific interaction between the electrostatic loop and an exposed beta‐barrel edge strand. Using epidemiology methods, we then determined that decreased SOD1 stability and increased protein aggregation are powerful risk factors for fALS progression, with a combined hazard ratio > 300 (for comparison, a lifetime of smoking is associated with a hazard ratio of ~15 for lung cancer). The resulting structural model of fALS etiology supported the hypothesis that some sporadic ALS (sALS, ~80% of ALS is not associated with a gene defect) could be caused by post‐translational protein modification of wild‐type SOD1. We developed immunocapture antibodies and high sensitivity top‐down MS methods and characterized PTMs of wild‐type SOD1 using human tissue samples. Using global hydrogen–deuterium exchange, X‐ray crystallography and neurotoxicology, we then characterized toxic and protective subsets of SOD1 PTMs. To cap this perspective, we present proof‐of‐concept that post‐translational modification can cause disease. We show that numerous mutations (N➔D; Q➔E), which result in the same chemical structure as the PTM deamidation, cause multiple diseases. Copyright © 2017 John Wiley & Sons, Ltd.     

Protonation sites and dissociation mechanisms of t-butylcarbamates in tandem mass spectrometric assays for newborn screening

Structures of tert-butylcarbamate ions in the gas-phase and methanol solution were studied for simple secondary and tertiary carbamates as well as for carbamate-containing products and internal standards for lysosomal enzyme assays used in newborn screening of a α-galactosidase A deficiency (Fabry disease), mucopolysaccharidosis I (Hurler disease), and mucopolysaccharidosis II (Hunter disease). The protonation of simple t-butylcarbamates can occur at the carbonyl group, which is the preferred site in the gas phase. Protonation in methanol solution is more favorable if occurring at the carbamate nitrogen atom. The protonation of more complex t-butylcarbamates occurs at amide and carbamate carbonyl groups, and the ions are stabilized by intramolecular hydrogen bonding, which is affected by solvation. Tertiary carbamates containing aminophenol amide groups were calculated to have substantially greater gas-phase basicities than secondary carbamates containing coumarin amide groups. The main diagnostically important ion dissociation by elimination of 2-methylpropene (isobutylene, i-C(4)H(8)) and carbon dioxide is shown by experiment and theory to proceed in two steps. Energy-resolved collision-induced dissociation of the Hurler's disease enzymatic product ion, which is a coumarin-diamine linker-t-butylcarbamate conjugate (3a(+)), indicated separate energy thresholds for the loss of i-C(4)H(8) and CO(2). Computational investigation of the potential energy surface along two presumed reaction pathways indicated kinetic preference for the migration of a t-butyl hydrogen atom to the carbamate carbonyl resulting in the isobutylene loss. The consequent loss of CO(2) required further proton migrations that had to overcome energy barriers.