Multi-Parametric Rigid and Flexible, Low-Cost, Disposable Sensing Platforms for Biomedical Applications

The measurement of Na+, K+ and H+ is essential in medicine and plays an important role in the assessment of tissue ischemia. Microfabrication, inkjet- and screen-printing can be used for solid contact ion selective electrodes (ISE) realization; these, however, can be non-standardized, costly and time consuming processes. We present the realization of ISEs on post-processed electrodes fabricated via standardized printed circuit board (PCB) manufacturing techniques. In vitro results are presented from two rigid platforms (32 ISEs) for liquid sample dip-stick measurements and two flexible platforms (6 and 32 ISEs) for post-surgical intestinal tissue monitoring, each with a common reference electrode (RE). These are combined with optimized tetrapolar bioimpedance sensors for tissue ischemia detection. Both electroless and hard gold PCB finishes are examined. Apart from the electroless rigid platform, the rest demonstrated comparable and superior performance, with the pH sensors demonstrating the greatest deviation; the flexible hard gold platform achieved a sensitivity 4.6 mV/pH and 49.2 mV/pH greater than the electroless flexible and rigid platforms, respectively. The best overall performance was achieved with the hard gold flexible platform with sensitivities as large as 73.4 mV/pH, 56.3 mV/log [Na+], and 57.4 mV/log [K+] vs. custom REs on the same substrate. Simultaneous measurements of target analytes is demonstrated with test solutions and saliva samples. The results exhibit superior performance to other PCB-based pH sensors, demonstration of Na+ and K+ PCB-based sensors with comparable performance to potentiometric sensors fabricated with other techniques, paving the way towards mass-produced, low-cost, disposable, multi-parametric chemical sensing diagnostic platforms

Development of chitosan, pullulan, and alginate based drug-loaded nano-emulsions as a potential malignant melanoma delivery platform

Melanoma is the most aggressive form of skin cancer and various treatments have been investigated to treat this disease, but drug resistance remains an important factor in the failure of conventional therapeutics. Here we describe the development, optimisation and characterisation of alginate, chitosan, pullulan, and their combined nano-emulsions as drug delivery platforms for potential application for melanoma. A novel nano-emulsion delivery system was designed and assessed by determining in vitro drug release, cell viability (MTT), cellular apoptosis (ELISA) and confocal microscopy. A comparative analysis of the effect of the nano-emulsions on BRAF-mutant melanoma (A375) and keratinocyte (HaCaT) cells was conducted, with the “pullulan-chitosan” nano-emulsion chosen as an approach for melanoma drug delivery. Increased apoptosis induction of melanoma cells was recorded as 90% after 72 h of treatment with doxorubicin-loaded optimal nano-emulsion. Similarly, in the same treatment, the viability of melanoma cells was decreased by 70%. More importantly, A375 cells treated with naïve doxorubicin were 100% viable compared to cells treated with doxorubicin-loaded nano-emulsion which were only 30%viable. Achieved results are indicating the importance of the drug carrier’s polymeric combination and the impact of the drug release pattern on the efficiency of the treatment. This offers potential for the abrogation of drug- efflux-related chemo-resistance

COMT gene polymorphism and antipsychotic-induced hyperprolactinemia in schizophrenia patients

Hyperprolactinemia (HPRL) is considered to be a frequent and typical adverse drug reaction caused by antipsychotic medications first and foremost due to excessive dopamine D2 receptors blockade. The aim is to study the set of polymorphisms of genes encoding neurotransmitter synthesis and metabolism enzymes COMT, TPH1 and TPH2 in schizophrenia inpatients. A comprehensive examination of 446 schizophrenia inpatients, aged 18-75 years, was conducted. Genotyping of DNA samples in patients with or without HPRL was carried out for 14 polymorphisms of COMT, TPH1, and TPH2 genes. We revealed an association between carriership of the COMT rs165774* G allele and HPRL. As a result of the study, a regression model was designed to predict the risk of developing HPRL in schizophrenia inpatients, taking into account age, gender, and treatment duration, the dosage of drugs in chlorpromazine equivalents as independent covariates and genotypes of the studied polymorphisms

Polymorphisms in the adrenergic neurotransmission pathway impact antidepressant response in depressed patients

Mood disorders are a prevalent mental health disorder. The adrenergic neurotransmission pathway presents an opportunity to determine whether genetic mutations impact antidepressant response. For this study, 163 patients with major depressive disorders were enrolled to measure treatment response using the Hamilton Depression Rating Scale (HAMD-17). More than half of the patients had never been treated with antidepressants previously. Patients were genotyped for 14 SNPs within ADRA1A, SLC6A2, ADRβ1, MAOA and COMT to determine the impact of adrenergic neurotransmission polymorphisms related in antidepressant response. Patients were treated mainly with SSRIs and TCAs. The difference in HAMD-17 scores between the measurement periods were defined as the outcome measure. Multiple linear regression was conducted to determine the association between the genotypes and difference in HAMD-17 across the study period. Covariates of age, sex, antidepressant medication and depression diagnoses were included in the regression. Throughout the study HAMD-17 scores were measured at initiation, at two weeks and at four weeks for each patient. The difference in HAMD-17 scores was found to be 11.2 ​± ​4.4 between initiation and two weeks, 7.8 ​± ​5.3 between two week and four week, and 19.0 ​± ​5.3 throughout the entire study. SLC6A2 rs1532701 homozygous G/G Patients were associated with improved ΔHAMD-17 across week 2–4 and the entire study (B ​= ​7.1, p ​= ​0.002; B ​= ​6.7, p ​= ​0.013) compared to homozygous A/A patients. SLC6A2 rs1532701 homozygous A/G patients were further associated with improved ΔHAMD-17 compared to homozygous A/A patients at week 2–4 (B ​= ​2.8, p ​= ​0.023). Through our investigation, we were able to determine the genes within the adrenergic pathway to investigate further. To further elucidate these findings, replication and combination with other neurotransmitter pathways to better map the mechanism of actions of antidepressant for tailored treatment would be suggested

Environmental and Technological Problems of Rational Use of Secondary Resources for Processing Grapes

Rational use of grapes processing resources is among environmental problems of AIC of Republics of the North Caucasus and Krasnodar Territory. Currently, waste from grapes processing is not practically used and worsen the ecological state of environment. The research subject is a technology based on the production of cryo-powder from pulp, squeeze, seeds and grapes skin grown in the foothill and mountainous regions. The prerequisites for research were previously performed author works on related topics. The data on vacuum SHF-drying of grape raw materials and subsequent grinding in a cryomiller are given. Modes of preparation of grape raw materials and its subsequent dehydration and cryo-grinding, which provide the possibility of successful use in the dried state in the production technology of wine beverages, are proposed. The principal feature is the use of whole grapes as a raw material, with skin and seeds. Physico-chemical parameters, the content of phenolic substances and organoleptic characteristics of wine beverages made according to the traditional technology and the beverage made from grape cryo-powders are studied. A comparative assessment is made. It is established that vacuum SHF-drying contributes to better preservation of the properties of raw materials and finished products. The organoleptic assessment has shown that wine beverages developed according to the proposed technology had a more intense color and a more pronounced taste of sweetness and acid than traditional wine beverages. The advantage of this technology is the ability to transport grape cryo-powders in unregulated temperature conditions to any point close to the consumer and carry out the production of nutritional food there

Group Analysis of Variable Coefficient Diffusion-Convection Equations. I. Enhanced Group Classification

We discuss the classical statement of group classification problem and some its extensions in the general case. After that, we carry out the complete extended group classification for a class of (1+1)-dimensional nonlinear diffusion--convection equations with coefficients depending on the space variable. At first, we construct the usual equivalence group and the extended one including transformations which are nonlocal with respect to arbitrary elements. The extended equivalence group has interesting structure since it contains a non-trivial subgroup of non-local gauge equivalence transformations. The complete group classification of the class under consideration is carried out with respect to the extended equivalence group and with respect to the set of all point transformations. Usage of extended equivalence and correct choice of gauges of arbitrary elements play the major role for simple and clear formulation of the final results. The set of admissible transformations of this class is preliminary investigated.Comment: 25 page

5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia

Background Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia. Methods A set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4. Results Statistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results. Conclusion We found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia

Objective: Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic-induced HPRL. Methods: We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test. Results: A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p =.05; odds ratio [OR] = 1.30 [0.99–1.69]). Conclusion: The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia

Group classification of (1+1)-Dimensional Schr\"odinger Equations with Potentials and Power Nonlinearities

We perform the complete group classification in the class of nonlinear Schr\"odinger equations of the form $i\psi_t+\psi_{xx}+|\psi|^\gamma\psi+V(t,x)\psi=0$ where $V$ is an arbitrary complex-valued potential depending on $t$ and $x,$ $\gamma$ is a real non-zero constant. We construct all the possible inequivalent potentials for which these equations have non-trivial Lie symmetries using a combination of algebraic and compatibility methods. The proposed approach can be applied to solving group classification problems for a number of important classes of differential equations arising in mathematical physics.Comment: 10 page