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107 patients (34 female and 73 male) diagnosed with “generalized psoriasis vulgaris, exudative form, progressive stage” were evaluated for the levels of anxiety and depression. These measurements were carried out along with psychiatrist interview, taking into consideration anamnestic and status information. 67,3% of patients unhesitatingly marked that a previous psychological trauma had caused the current exacerbation of psoriasis. The study reveals interrelationship between the psychiatric and somatic components of psoriasis. We managed to reach marked remission in 19 patients using low doses of psychotropic drugs along with primary dermatological treatment.

1AbstractThe testing of pharmacological hypotheses becomes faster and more accurate, but at the same time more difficult than even two decades ago. It takes more time to collect and analyse disease mechanisms and experimental facts in various specialized resources. We discuss a new approach to aggregating individual pieces of information about a single disease using Elsevier’s automated text mining technology. Developed algorithm allows for the collection of published facts in a unified format starting only with the name of the disease. The special template, which combines research and clinical descriptions of diseases was developed. The approach was tested, and information was collected for 55 rare monogenic diseases. Clinical, molecular, and pharmacological characteristics of diseases with supporting references from the literature are available in the form of tables and files. Manually curated templates for 10 rare diseases, including top ranked Cystic Fibrosis and Huntington’s disease, were published to demonstrate the results of the described approach.

Impulsive–compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson’s disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.

Increased content of monounsaturated fatty acids with low melting points in cattle milk and meat known to strongly affect their taste and nutritional value. Steroyl-CoA-desaturase (SCD) is a key enzyme in the biosynthesis of monounsaturated fatty acids. The gene encoding SCD in cattle is located on chromosome 26 and consists of 6 exons and 5 introns and is expressed in the cells of cow udder, adipose, muscles and other tissues. To date, several SNPs in cattle SCD gene have been found. For SNP rs41255693 (g.10329T > C), a correlation was shown between the content of monounsaturated fatty acids in cattle milk/meat and milk productivity. This article describes the development of a real-time PCR assay for genotyping SNP rs41255693 in cattle SCD gene with allele-specific TaqMan probes. The use of this assay allows to significantly reduce the time needed for cattle genotyping compared to the commonly used PCR-RFLP method.

Aims: To establish the common rules of exon combinatorics during RNA splicing. Study Design: Inferring a plausible statistical model of exon combinatorics from the annotated models of human genes during RNA splicing. Place and Duration of Study: Department of Genetics (Belarusian State University), Proteome and Genome Research Unit (Luxembourg Institute of Health), Department of Genetics (Lomonosov Moscow State University) and Moscow Center of Experimental Embryology and Reproductive Biotechnologies, between January 2017 and July 2019. Methodology: We used human mRNA and EST sequences from GenBank (1093522 unique records in total) and linear models of the human genes from Ensembl (58051 genes), AceView (72384 genes), ECgene (57172 genes), NCBI RefSeq (54262 genes), UCSC Genome Browser (58037 genes) and VEGA (54950 genes) to calculate a combinatorial index of human exons. We inferred the most plausible statistical model describing the distribution of combinatorial index of human exons using Clauset’s mathematical formalism. Predictors of the combinatorial index values and functional outcomes of the predefined behavior of exons during splicing were also determined. Results: Power-law is the most plausible statistical model describing the combinatorics of exons during RNA splicing. The combinatorial index of human exons is defined by more than 90% by the 138 features that have different importance. The most important of these features are the abundance of exon in transcripts, the strength of splice sites, the rank of exon in transcripts and the type of exon. Analysis of the marginal effects shows that different values of the same feature have unequal influence on the combinatorial index of human exons. Power-law behavior of exons during RNA splicing pre-determines structural diversity of transcripts, low sensitivity of splicing process to random perturbations and its high vulnerability to manipulation with highly combinative exons. Conclusion: Exons widely involved in alternative splicing are a part of the common power-law phenomenon in human cells. The power-law behavior of exons during RNA splicing gives the unique characteristics to human genes.

Aims: Caseins are among the main milk proteins that determine many of its properties. Bovine kappa-casein (CSN3) is associated with the qualitative composition of milk, as well as with the quality of cheese obtained from this milk. The rs43703016 single-nucleotide substitution (g.88532332A>C; Asp148Ala) in exon 4 of the bovine CSN3 gene plays an important role in the production of quality hard cheeses. Various methods for the DNA testing of this substitution have been developed in the last three decades. Emergent DNA technologies provide an opportunity to modernize methods of genotyping single-nucleotide polymorphisms. Results: We have developed and verified a method to differentiate A/C alleles of the rs43703016 substitution in the bovine CSN3 gene by real-time PCR using allele-specific fluorescent probes. Conclusion: Our new method allows fast genotyping of animals, and may be used for selection of cows carrying the CC genotype, which determines good cheese-making properties of milk.

Psoriasis is a multigene and multifactorial skin disease with heterogeneous genetic inheritance. Mental disorders participate in the development of psoriasis as predisposing factors; a correlation of dermatological diseases with pathological anxiety and stress was shown. Meanwhile, there are no studies describing molecular mechanisms of the linkages between psycho-emotional disorders and skin diseases. The aim of this study is to find the associations between SNP in genes COMT (rs4680), DBH (rs141116007), CCKAR (rs1800857) and CCKBR (rs1805002), and psoriasis. Patients were selected according to the 10th revision of International Classification of Diseases (L-40). The sample size was 88 patients. The size of the control sample (population control) was 365 people. Genotyping was performed using PCR-RFLP and real-time PCR. Statistical analysis was performed using WinPepi software. Identification of complex genotypes was performed by the Monte Carlo method using APSampler 3.6.1 algorithm. Among the studied genes, only GA genotype of COMT gene is significantly associated with psoriasis [χ2 = 19.163 (p = 1.3E−5), F (p) = 1.2E−5, OR 3.47 (CI 99% = 1.61–7.91)]. At the moment, the functional significance of this phenomenon is difficult to explain.

Peroxisome proliferator-activated receptor (PPAR) group includes three isoforms encoded by PPARG, PPARA, and PPARD genes. High concentrations of PPARs are found in parts of the brain linked to anxiety development, including hippocampus and amygdala. Among three PPAR isoforms, PPARG demonstrates the highest expression in CNS, where it can be found in neurons, astrocytes, and glial cells. Herein, the highest PPARG expression occurs in amygdala. However, little is known considering possible connections between PPARs and anxiety behavior. We reviewed possible connections between PPARs and anxiety. We used the Pathway Studio software (Elsevier). Signal pathways were created according to previously developed algorithms. SNEA was performed in Pathway Studio. Current study revealed 14 PPAR-regulated proteins linked to anxiety. Possible mechanism of PPAR involvement in neuroinflammation protection is proposed. Signal pathway reconstruction and reviewing aimed to reveal possible connection between PPARG and CCK-ergic system was conducted. Said analysis revealed that PPARG-dependent regulation of MME and ACE peptidase expression may affect levels of nonhydrolysed, i.e., active CCK-4. Impairments in PPARG regulation and following MME and ACE peptidase expression impairments in amygdala may be the possible mechanism leading to pathological anxiety development, with brain CCK-4 accumulation being a key link. Literature data analysis and signal pathway reconstruction and reviewing revealed two possible mechanisms of peroxisome proliferator-activated receptors involvement in pathological anxiety: (1) cytokine expression and neuroinflammation mechanism and (2) regulation of peptidases targeted to anxiety-associated neuropeptides, primarily CCK-4, mechanism.

(1) Background: Although panic disorder (PD) is one of the most common anxiety disorders severely impacting quality of life, no effective genetic testing exists; known data on possible genetic biomarkers is often scattered and unsystematic which complicates further studies. (2) Methods: We used PathwayStudio 12.3 (Elsevier, The Netherlands) to acquire literature data for further manual review and analysis. 229 articles were extracted, 55 articles reporting associations, and 32 articles reporting no associations were finally selected. (3) Results: We provide exhaustive information on genetic biomarkers associated with PD known in the scientific literature. Data is presented in two tables. Genes COMT and SLC6A4 may be considered the most promising for PD diagnostic to date. (4) Conclusions: This review illustrates current progress in association studies of PD and may indicate possible molecular mechanisms of its pathogenesis. This is a possible basis for data analysis, novel experimental studies, or developing test systems and personalized treatment approaches.

The review is devoted to the analysis of proteins, protein complexes and microRNAs involved in papillomavirus infection. The papilloma viruses belong to the family of DNA-containing papovaviruses (Papovaviridae) and infect the basal layers of the epithelium. Human papillomaviruses (HPV) have an oncogenic potential, which varies significantly. The ring genome HPV encodes 6 early proteins and 2 later proteins (envelope proteins), and uses the host cell proteins for its own replication. For infection the membrane proteins that bind to the host cell membrane are especially important. In this paper we analyzed the arrays of literature data on proteins and microRNAs involved in binding, internalization, transport of HPV virions, and virus multiplication. The analysis of literature data was carried out using the program PathwayStudio9 ® and the database ResNet13 ® of Elsivier (USA), as well as online services. Total was revealed 69 infection-related proteins and protein complexes and 3 microRNAs (72 in total). As a result of the subsequent detailed analysis of the literature, 17 proteins and microRNAs involved in the following processes were selected: penetration of virus particles into the cell (7), transport of the virus in the cytoplasm of the host cell (5), transfer of the virus DNA into the core of the host cell (1) and regulation of gene transcription HPV (4). These proteins and microRNAs are potential targets for drugs that can prevent and suppress HPV infection.

Allele frequencies of three substitutions in the CCK (rs42891945 and rs42891946) and CCKBR (rs42670352) genes were identified in three Russian cattle breeds: Holstein (dairy), Bestuzhev (dual-purpose), and Kalmyk (beef). The most promising for further associative studies is the rs42670352 substitution in the CCKBR gene.

The comprehensive list of various eye disorders includes congenital malformations, eye infections, and other acquired pathologies. If inherited and infectious diseases are excluded from the list, the most common causes of blindness are glaucoma, age-related macular degeneration, cataract, and diabetic retinopathy. Among these, cataract is the one most easily diagnosed and treatable by surgery. Diabetic retinopathy is the late complication of diabetes mellitus. Early detection and the timely treatment of diabetes mellitus help prevent diabetic retinopathy. The following chapter focuses on glaucoma, cataract, and age-related macular degeneration as the most common eye disorders with no effective treatment yet.

Our modern lifestyle and low air quality provoke disorders of the respiratory system, which are often chronic. This chapter focuses on two major chronic respiratory illnesses: asthma and chronic obstructive pulmonary disease (COPD). Hyperstimulation of the immune response leads to asthma progression, while the inflammation-mediated destruction of the pulmonary tissues is a critical element in the development of COPD.

In children with normal hearing, inflammatory disorders caused by infections of the middle ear (otitis media) are the most common ear illnesses. Many of older adults experience some level of hearing loss. Several factors can lead to either a partial loss or the total inability to hear (deafness) including exposure to noise, a hereditary predisposition, chronic infections, traumas, medications, and aging.

Despite the efforts of researchers all over the world, the mechanisms underlying the pathology of neurological diseases remain unclear. In this chapter, we review the molecular pathogenesis of Alzheimer’s disease and amyotrophic lateral sclerosis because these disorders are among the most challenging. Familial hemiplegic migraine is also reviewed in this chapter as an example of a disease with known mutations in genes regulating neuronal function.

Background Migraine is a multifactorial socially significant disease affecting the peripheral and central nervous system. The diagnosis of “migraine” is still the only clinical, and additional methods of inspection are only required to avoid secondary headaches if certain “signs of danger”. Accordingly, the search for biomarkers of migraine, confirming the diagnosis, rather than refuting others, is the leading vector in this scientific field. Aim In this paper we have analyzed the literature data on the genetic markers associated with migraine. Methods List of genes was compiled using Pathway Studio 10® software and abstract database ResNet12 ® made by Elsevier. Addition search (last time on 15 March 2016) was performed by using PubMed or TargetInsights. Information about 185 polymorphic loci in 98 genes associated with migraine was extracted and described. Results The genes associated with migraine could be classified into 8 major groups: homeostasis of blood vessels - 26.5%, metabolism of neurotransmitters - 11.2%, transport and reception of neurotransmitters - 24.5%, neurogenesis - 5.1%, inflammation - 8.2%, sex hormones - 5.1%, ion channels and membrane potential - 11.2%, other - 8.2%. Conclusion These findings parallel the range of mechanisms implicated in migraine pathogenesis.

The term, glaucoma, describes a group of conditions that are characterised by progressive optic nerve damage. Untreated glaucoma causes progressive visual field loss and eventually blindness. There are four main types: primary open angle glaucoma, acute angle closure glaucoma, secondary glaucoma, and congenital glaucoma. Primary open angle glaucoma is a common condition; it affects 2.1% of the UK population and is the second-most-common cause of blindness in the UK. Incidence and prevalence increase with age. Intraocular pressure is the only modifiable risk factor for progression of glaucoma; treatment to reduce intraocular pressure can prevent progression of optic nerve damage and preserve vision. Acute angle closure glaucoma is an ophthalmic emergency and prompt recognition and treatment of the condition is sight-saving. This article will discuss the aetiology, diagnosis and management of primary open angle and acute angle closure glaucoma, the role of GPs in supporting patients with glaucoma, and summarise the Driver and Vehicle Licensing Agency guidance relevant to these patients.

This article describes premises for the development of psychodermatology. An analysis of research literature and data is presented based on the example of psoriasis and anxiety disorder. Protein molecules with altered concentrations in patients with psoriasis and anxiety disorder compared to controls are identified (chemokine [C-C motif] ligand 2, corticotropin-release hormone, growth hormone 1, leptin, and tumor necrosis factor with increased concentration and brain-derived neurotrophic factor with decreased concentration). All molecules are secretory peptides. In the future, the information obtained may make it possible to pursue an in-depth study of the molecular mechanisms underlying psychodermatology.

To evaluate the frequency and spectrum of impulsive-compulsive disorders (ICDs) in patients with Parkinson's disease (PD) without dopaminergic medication and among patients receiving dopaminergic replacement therapy, depending on personality type, genetic factors, and to determine the influence of ICDs on the development of other non-motor manifestations of the disease.Three hundred and eighty-six consecutive patients with idiopathic PD, including untreated patients with PD (de novo) and patients receiving dopaminergic replacement therapy during one year, were examined. ICDs were evaluated with QUIP and diagnostic criteria. Personality type and temperament features were assessed by the Eysenck personality inventory. Genotyping for the single nucleotide polymorphism rs141116007 in the DBH gene involved in the pathogenesis of PD and ICDs was performed.ICDs were identified in 20.2% patients with PD and in 4% patients of the de novo group. The most common (10.36%) behavioral disorder was a binge eating. The frequency of ICDs among patients with PD before the onset of dopamine replacement therapy increased by 1.03 times after one year treatment. Smoking and young age were risk factors for ICDs (p0.05). The results of the study allowed the determination of social and neuropsychological risk factors for ICDs in patients with PD. The account of these features, as well as early detection of ICDs using screening questionnaires may help to personalize treatment of patients with PD and to prevent the risk of developing comorbid non-motor manifestations of the disease.Цель исследования. Оценить частоту и спектр импульсивно-компульсивных расстройств (ИКР) у пациентов с болезнью Паркинсона (БП) как в начальной стадии (de novo), так и у больных, получающих дофаминергическую терапию, в зависимости от типа личности, генетических особенностей, а также определить влияние ИКР на развитие других немоторных проявлений заболевания. Материал и методы. Обследовали 386 больных с идиопатической формой БП: пациентов с БП de novo без лечения и больных, получающих дофаминергическую терапию в течение года. Симптомы ИКР оценивали с помощью QUIP-опросников и диагностических критериев. Для определения типа личности и особенностей темперамента использовался личностный опросник Айзенка. Определялась частота генотипов замены rs141116007 в гене DBH, вовлеченном в патогенез БП и ИКР. Результаты и заключение. ИКР выявлены у 20,2% пациентов с БП, в группе de novo - у 4%. Самым распространенным (10,36%) поведенческим расстройством оказалось патологическое переедание. Дофаминергическая терапия в течение года увеличивала вероятность развития ИКР в 1,03 раза, также факторами риска являлись курение и молодой возраст (р0,05). У пациентов с БП и ИКР наблюдалось увеличение выраженности депрессии, личностной тревожности и нарушений сна (р0,05). Выявили, что особую роль в развитии ИКР играют определенные личностные характеристики и тип темперамента. Ассоциаций между развитием ИКР и заменой rs141116007 в гене DBH обнаружено не было (p0,05). Результаты проведенного исследования позволили определить социальные и нейропсихологические факторы риска развития ИКР у пациентов с БП. Учет этих особенностей, а также раннее выявление ИКР с помощью скрининговых опросников позволяют персонифицировать подход к терапии пациентов с БП и предотвратить риск развития немоторных проявлений заболевания.

The chapter on alpha-1 antitrypsin deficiency describes the genetics and the pathogenesis of this disorder as well as the clinical features of the homozygous PiZ alpha-1 antitrypsin deficiency and its management.

Aims: Alice-in-Wonderland syndrome (AIWS) is a rare neuropsychological syndrome that includes paroxysmal distortion of the body schema, depersonalization, derealization, visual hallucinations, distorted sense of time, and deja vu and jamais vu experiences. Alice-in-Wonderland syndrome may be an equivalent of a migraine attack. The objective of this study was to evaluate the clinical particulars of Alice-in-Wonderland syndrome in patients suffering from migraine. Place and Duration of Study: University Headache Clinic between June 2012 and November 2015. Methodology: The study sample involved 14 subjects with migraine as defined in the

This article describes premises for the development of psychodermatology. An analysis of research literature and data is presented based on the example of psoriasis and anxiety disorder. Protein molecules with altered concentrations in patients with psoriasis and anxiety disorder compared to controls are identified (chemokine [C-C motif] ligand 2, corticotropin-release hormone, growth hormone 1, leptin, and tumor necrosis factor with increased concentration and brain-derived neurotrophic factor with decreased concentration). All molecules are secretory peptides. In the future, the information obtained may make it possible to pursue an in-depth study of the molecular mechanisms underlying psychodermatology.

Hypertrophic cardiomyopathy is a myocardial disease characterized by myocardial hypertrophy, disorganization of cardiac myocytes, and fibrosis. Twenty-five percent of patients have a dynamic left ventricular outflow tract gradient caused by the combined effects of rapid ventricular ejection, a narrowed outflow tract, and systolic anterior motion of the mitral valve. Most cases are caused by mutations in genes that encode cardiac sarcomeric proteins. Patients present at all ages with chest pain, dyspnea, palpitations, and syncope. The most important complications of the disease are sudden cardiac death, heart failure, and thromboembolism. The principal aims of management are the alleviation of symptoms and the prevention of sudden death. In patients with substantial left ventricular outflow tract obstruction, interventions that reduce the magnitude of the outflow tract gradient (disopyramide, verapamil, β-blockade, alcohol ablation of the interventricular septum, dual-chamber pacing, and surgery) often improve symptoms. Therapeutic options in patients without left ventricular outflow tract obstruction are more limited. Clinical risk stratification is used to estimate the risk of sudden death and to target effective prophylactic treatment with an implantable cardioverter defibrillator.

Background:Jugular paraganlioma is a slow-growing tumor originating from the paraganglion cells. The diagnosis of a jugular paraganglioma may be delayed due to its atypical symptoms. We report a case of jugular paraganglioma presented as temporomandibular joint (TMJ) disorder. Clinical presentation: 29-years old woman with preliminary diagnosis probable atypical face pain. She experienced her pain for the first time 2 months prior to reference. Pain intensity was seven to eight out of ten points on Visual Analogue Scale, simple and combined analgetics and NSAIDs were ineffective. Pain was dull, aching, localized in the right temporal area with irradiation to the ipsilateral maxillar and periauricular areas. Pain was more intensive in the nighttime. Temporomandibular joint movement (maximum unassisted and assisted opening, right to left movements) also increased pain. Significant dilatation of right foramen jugularis with its right side destruction was detected by computed tomography with contrast. The radiological findings were consistent with those of a jugular paraganglioma. Conclusion:This case confirms that in refractory headache and TMJ pain other reasons should be considered with rigorous investigation including neuroimaging

To study an influence of depression on the course of migraine and the efficacy of antidepressants in treatment of depression associated with migraine.The study consisted of 544 patients with migraine including 240 patients with depression. Patients were examined at the first visit, after 6 months (visit 2) and one year (visit 3). Then patients were interviewed by phone once a year (visits 5, 6, 7, 8), they were asked about a number of days with migraine. Patients with depression were treated with antidepressants. Results and сonclusion. Six types of migraine course were determined: persistent episodic migraine, migraine remission, episodic migraine chronification, chronic migraine regress to episodic migraine, persistent chronic migraine, remitted or wavelike chronic migraine. The presence of depression and skin allodynia predicted the development of persistent and remitted chronic migraine. The effect of antidepressants of different groups was noted in treatment of patients with the combination of chronic migraine and depression. The most pronounced effect was observed with tricyclic antidepressants, the smallest one when selective serotonin reuptake inhibitors were used.Цель исследования. Изучение влияния депрессии на течение мигрени и на эффективность терапии ассоциированной с мигренью депрессии антидепрессантами. Материал и методы. Наблюдали 544 пациента с мигренью, в числе которых были 240 пациентов с депрессией. Оценка их состояния проводилась при обращении пациента с основной жалобой на головную боль (визит 1), через 6 мес (визит 2), через 1год (визит 3). Затем проводились телефонные интервью 1 раз в год (визит 5, 6, 7, 8), при которых выяснялось количество дней с головной болью. Пациентам с депрессией была назначена терапия антидепрессантами. Результаты и заключение. Выделены 6 типов течения мигрени: персистирующая эпизодическая мигрень, ремиссия мигрени, хронизация эпизодической мигрени, регресс хронической мигрени в эпизодическую, персистирующая хроническая мигрень, ремиттирующая или волнообразная хроническая мигрень. Наличие депрессии и кожной аллодинии были предикторами развития персистирующей и ремиттирующей хронической мигрени. При лечении случаев сочетания хронической мигрени и депрессии был отмечен эффект антидепрессантов разных групп. Наибольший эффект наблюдался при использовании трициклических антидепрессантов, наименьший - при лечении селективными ингибиторами обратного захвата серотонина.Цель исследования. Изучение влияния депрессии на течение мигрени и на эффективность терапии ассоциированной с мигренью депрессии антидепрессантами. Материал и методы. Наблюдали 544 пациента с мигренью, в числе которых были 240 пациентов с депрессией. Оценка их состояния проводилась при обращении пациента с основной жалобой на головную боль (визит 1), через 6 мес (визит 2), через 1год (визит 3). Затем проводились телефонные интервью 1 раз в год (визит 5, 6, 7, 8), при которых выяснялось количество дней с головной болью. Пациентам с депрессией была назначена терапия антидепрессантами. Результаты и заключение. Выделены 6 типов течения мигрени: персистирующая эпизодическая мигрень, ремиссия мигрени, хронизация эпизодической мигрени, регресс хронической мигрени в эпизодическую, персистирующая хроническая мигрень, ремиттирующая или волнообразная хроническая мигрень. Наличие депрессии и кожной аллодинии были предикторами развития персистирующей и ремиттирующей хронической мигрени. При лечении случаев сочетания хронической мигрени и депрессии был отмечен эффект антидепрессантов разных групп. Наибольший эффект наблюдался при использовании трициклических антидепрессантов, наименьший - при лечении селективными ингибиторами обратного захвата серотонина.