[Change of transcription level of photoreceptor-specific CRX gene in the peripheral blood of the participants of an arctic world oceanic international flight]. / Izmenenie urovnya transkriptsii fotoretseptor-spetsifichnogo gena CRX u uchastnikov arkticheskogo krugosvetnogo pereleta.

The CRX gene encoding the cone-rod homeobox protein is a specific photoreceptor transcription factor crucial for retinal function. Persons temporarily residing in the Arctic zone during the polar summer may suffer from disturbances associated with extremely high ambient illumination. These environmental changes are mediated by retinal photoreceptors; therefore, it is important to study the expression of retinal genes in order to assess individual capacities of sensory adaptation to polar day conditions. PURPOSE: To reveal the dynamics of CRX expression level in humans after a prolonged temporary exposure to polar day conditions. MATERIAL AND METHODS: The study included 6 pilots (males from 39 to 69 y.o.) who participated in the Arctic World Oceanic International Flight Sever Vash (West to East, from 62°N 74°E to 72°N 114°E). Samples of peripheral blood for RNA isolation were collected at the start and at the end of the flight. The level of mRNA in the samples was evaluated based on the data of quantitative real-time PCR of the CRX gene, as well as the b2M and TBP housekeeping genes (reference). RESULTS: Expression of the CRX gene in the studied group (p<0.01) was revealed; the total average level of mRNA was about 3 times higher prior to, and approximately 7 times higher after normalization to the b2M gene. Five pilots had increased expression of the CRX gene within the range of -1.53 to -3.07 (Z-score of <0 before the flight and >0 after the flight). In one pilot, the level of CRX expression was higher at the start, but it reduced by the end of the circumnavigation flight. CONCLUSIONS: The results confirm the hypothesis that the CRX gene is expressed after a prolonged temporary exposure to polar day conditions. It was also revealed that during rapid adaptation, equal changes in the illumination of retinal photoreceptors lead to different individual dynamics of CRX expression.

[Disturbances of Autonomic Regulation of Cardiovascular System at Different Working Regimes with Night Shifts].

Aim        To study temporal and spectral characteristics of heart rhythm variability (HRV) in night shift workers.Materials and methods       Along with traditional risk factors, conditions of labor contribute to development of cardiovascular morbidity, including night shift work, which can be associated with disorders of the autonomic regulation detected by analysis of HRV. This study included 100 healthy men. 74 of them were engaged in shift work, including 53 men with rotating shift work, 21 men with fixed night shifts, and 26 men with day-time work. HRV was analyzed by data of 5-min electrocardiogram recording (background recording and orthostatic test).Results   Night-shift workers had decreases in total power of regulation (ТР, SDNN) and in the parasympathetic branch (HF, pNN50). Rotating night-shift workers displayed significant decreases in SDNN and pNN50 and pronounced changes in the VLF / LF / HF ratio in the orthostatic test.Conclusion            In work with night shifts, the type of autonomic regulation differs from the "standard" functioning of the autonomic nervous system (ANS). This study showed different effects of night work regimens on HRV indexes. With the rotating shift work, the ANS dysregulation was more profound and was evident by a significant decrease in the ANS total tone and parasympathetic activity (SDNN, pNN50) compared to night shifts with fixed working hours. The excessive weakening of the parasympathetic component in the passive orthostatic test can be considered as an early marker for ANS maladaptation.

Novel CAPN3 variant associated with an autosomal dominant calpainopathy.

AIMS: The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. The exclusively recessive inheritance of this disorder has been recently challenged by the description of the recurrent variants, c.643_663del21 [p.(Ser215_Gly221del)] and c.598_612del15 [p.(Phe200_Leu204del)], associated with autosomal dominant inheritance. Our objective was to confirm the existence of autosomal dominant calpainopathies. METHODS: Through our activity as one of the reference centres for genetic diagnosis of calpainopathies in France and the resulting collaborations through the French National Network for Rare Neuromuscular Diseases (FILNEMUS), we identified four families harbouring the same CAPN3 heterozygous variant with supposedly autosomal dominant inheritance. RESULTS: We identified a novel dominantly inherited CAPN3 variant, c.1333G>A [p.(Gly445Arg)] in 14 affected patients from four unrelated families. The complementary phenotypic, functional and genetic findings correlate with an autosomal dominant inheritance in these families, emphasizing the existence of this novel transmission mode for calpainopathies. The mild phenotype associated with these autosomal dominant cases widens the phenotypic spectrum of calpainopathies and should therefore be considered in clinical practice. CONCLUSIONS: We confirm the existence of autosomal dominant calpainopathies as an entity beyond the cases related to the in-frame deletions c.643_663del21 and c.598_612del15, with the identification of a novel dominantly inherited and well-documented CAPN3 missense variant, c.1333G>A [p.(Gly445Arg)]. In addition to the consequences for genetic counselling, the confirmation of an autosomal dominant transmission mode for calpainopathies underlines the importance of re-assessing other myopathies for which the inheritance is considered as strictly autosomal recessive.

[On evaluating occupational fitness in railway workers with ventricular arrhythmias after coronary arteries stenting].

The authors studied prospects of work capacity preserving after coronary stenting in IHD and cardiac arrhythmias. Examination covered 158 railway workers underwent complete endovascular revascularization of myocardium for coronary stenosis; all of them had ventricular arrhythmias before coronary surgery. Findings are that in long-term period (in 16 months in average) after coronary stenting, grade I and III ventricular extrasystoles disappeared in 77.8 and 54.5% of cases respectively, but only in 11.9% of grade IV ventricular extrasystoles cases. Ventricular extrasystoles remained unchanged in 44.3% of cases. Reliable relationships were seen between unchanged grade IV ventricular extrasystoles and body weight index (OR = 5.49, 95% CI: 0.87-34.67), general cholesterol level (OR = 1.69; 95% CI: 1.06-2.69), low density lipoproteins (OR = 1.66; 95% CI: 1.00-2.76) and left ventricular ejection function lower 45% (OR = 1.61; 95% CI: 1.14-2.27), exertion ventricular extrasystoles before myocardium revascularization (OR = 3.1; 95% CI: 1.78-5.41). That necessitates correction of the mentioned risk factors of cardiac arrhythmias for restored work capacity.

[Structure of allostatic load in railway workers].

The authors studied allostatic load in railway workers, as an indicator of stress effect. Analysis covered biomarkers that form allostatic load index, and their ratio for variable allostatic load index levels. Moderate allostatic load appeared to prevail in the examinees group. Findings are that systolic and diastolic blood pressure, general cholesterol and hemoglobin make major contribution into allostatic load index. Comparison covered models of allostatic load index calculation for variable biomarkers sets.

[Ethical problems of hygienic tests in occupational medicine].

The authors discuss bioethical problems appearing in usage of genetic tests as a technology of personalized medicine for prevention and early diagnosis of occupational diseases, and connected with question "Who has a right to know results of genetic test?". Analysis covered principles and legal norms, regulating human rights for security of health information, and causes of anxiety about workers' discrimination due to genetic test results. The authors necessitate differentiation between discrimination and reasonable restrictions favorable for workers in cases when work conditions can be a health hazard for person due to genetic predisposition.

[Occupational deafness in workers of locomotive crew and its association with risk factors].

The authors studied relationship between occupational neurosensory deafness and risk factors in locomotive crew workers. Examination covered 173 locomotive crew workers divided into 2 groups: group 1--with occupational neurosensory deafness (n = 85) and group 2--without occupational neurosensory deafness (n = 88). Study covered occupational factors and calculated effective dose connected to length of service for exposure assessment. Complex clinical and laboratory study was performed. For signs structure analysis, principal components method and chances ratio were used. Occupational neurosensory deafness appeared to be reliably connected with length of service, arterial hypertension, dyslipidemia--with OR equals 5.7 (95% CI: 2.98-11.00), 1.88 (95% CI: 1.03-3.43) and 2.79 (95% CI: 1.5-5.18) respectively. That necessitates correction of hypertension and dyslipidemia.

Clinical massively parallel sequencing for the diagnosis of myopathies.

Massively parallel sequencing, otherwise known as high-throughput or next-generation sequencing, is rapidly gaining wide use in clinical practice due to possibility of simultaneous exploration of multiple genomic regions. More than 300 genes have been implicated in neuromuscular disorders, meaning that many genes need to be considered in a differential diagnosis for a patient affected with myopathy. By providing sequencing information for numerous genes at the same time, massively parallel sequencing greatly accelerates the diagnostic processes of myopathies compared to the classical "gene-after-gene" approach by Sanger sequencing. In this review, we describe multiple advantages of this powerful sequencing method for applications in myopathy diagnosis. We also outline recent studies that used this approach to discover new myopathy-causing genes and to diagnose cohorts of patients with muscular disorders. Finally, we highlight the key aspects and limitations of massively parallel sequencing that a neurologist considering this test needs to know in order to interpret the results of the test and to deal with other issues concerning the test.

[On hi-tech cardiologic care model in medical support of train operation safety].

The article covers hi-tech cardiologic care model in system of medical support of train operation safety, with definition of structure blocks in this model. Discussion covers peculiarities of the model functioning in comparison with the governmental system of hi-tech medical care, including its closed cycle principle characteristics, wide patients selection among railway workers, continuous and close cooperation between various medical speicalities, with active involvement of occupational fitness specialists (medical examination committees of various levels, including Central Medical Examination Committee), major extent of interventional rentgenosurgical technologies applied in diseases without significant functional failure.

[ETACISIN-INDUCED BRUGADA SYNDROME IN A PATIENT WITH LONG-STANDING SUPRAVENTRICULAR EXTRASYSTOLE].

Brugada syndrome is a commonest cause of malignant disorders of cardiac rhythm associated with sudden death. It is diagnosed based on characteristic ECG signs and ventricular arrhythmia. This paper reports a 49 year-old patient with long-standing latent BS manifest as supraventricular and transient blockade of the right branch of the His bundle. The ECG pattern of BS became apparent in association with a 7 day treatment with class IC antiarrhythmic agent etacisin. Diagnostic difficulties account for the fact that the disease was initially described as myocardial infarction. Diagnosis of BS was confirmed by an electrophysiological study in which stable ventricular tachycardia and fibrillation were induced by etacisin. A cardioverter defibrillator was implanted to the patient.

[Use of fendivia transdermal therapeutic system in Russian patients with malignant neoplasms during palliative care: pharmacoeconomic aspects].

AIM: To make a comparative clinical and economic assessment of a transdermal therapeutic system (TTS) for fendivia and traditional opioid analgesics in patients with malignant neoplasms (MN) during palliative care. MATERIALS AND METHODS: Pharmacoeconomic analysis of opioid analgesics used in patients with MN during analgesic therapy was made using the cost-effectiveness analysis in the framework of a budget impact analysis (BIA). RESULTS: The assessment of the medical cost structure in the fendivia and morphine groups (100 patients in each group), which was made in the framework of BIA, demonstrated that the cost of pharmacotherapy in the fendivia group was comparable with that of an ambulance call for additional analgesia and correction of the side effects of performed therapy (615,804.00 and 645,337.60 rbl. monthly, respectively). At the same time, in the morphine group the cost of an ambulance call was more than 20 times that of pharmacotherapy (2,117,514.00 and 93,120.00 rbl. monthly, respectively). Thus, the total savings from applying the fendivia TTS in the group of 100 patients ranged up to 949,492.40 rbl. monthly. CONCLUSION: The application of the fendivia TTS is clinically and pharmacoeconomically valid and leads to a considerable reduction in public health care costs.

[Tissue Doppler imaging of physiological asynchrony in intracardiac myocardium].

Tissue Doppler imaging (TDI) is one of the most widely used methods of quantitative assessment of asynchrony of ventricular myocardium movements. To study the parameters physiological asynchrony using TDI, we examined 32 healthy subjects (18 male, 14 female, mean age of 35.8 +/- 11.0) with no history and signs of cardiovascular disease. The putative relative parameters of systolic and diastolic asynchrony (intra- and interventricular heterogeneity at basal and mid level of 8 myocardial segments) and traditional absolute values (septolateral S-L delay, QE, TsSD, TESD intervals) were measured and compared. We have established the range of normal values of the relative physiological myocardium asynchrony factors in healthy persons, and found that systolic and diastolic asynchrony is more evident at the midventricular level compared to basal level, and diastolic asynchrony is more apparent than systolic; this fact is discussed in terms of single-layer spiral myocardium theory.

[Microbiological evaluation of chicken meal "shaverma" as a factor for Salmonella transmission].

It has been established that the dish shawarma may be a factor for Salmonella transmission, by involving in sporadic and outbreak cases of Salmonella infection. Chicken fillet grilling when cooking the dish shawarma has been found to ensure its guaranteed freedom from Salmonella only in a piece less than 2 cm thick. Deeper layers of chicken and its juice that accumulates in the grill tray may remain be Salmonella-contaminated throughout the heat treatment. Obviously, for the epidemiological safety of the dish shawarma, it is necessary to cut a not more than 2-cm piece of fillet every time the latter is ready-made, i.e. a white color and a clear juice are produced. At the time one should not use the chicken juice as sauce to the ready-made fillet and to gather and crumble the latter in a separate container rather than in the tray.

[Systolic and diastolic intraventricular asynchrony of the left ventricular myocardium in patients with pacemaker].

AIM: To study intraventricular asynchrony and effects of pacemaker implantation on asynchrony severity in patients with rhythm and conduction disorders. MATERIAL AND METHODS: The study of 46 patients with cardiac arrhythmia (atrial fibrillation, sick sinus syndrome, AB-block of the third degree) included such examinations as echocardiography, tissue dopplerography (PWTDI) before pacemaker implantation and 7 days after it. Electromechanic systolic and diastolic myocardial asynchrony was assessed by intraventricular heterogeneity index (IHb, IHm, TSD) in 8 segments of the left ventricle (LV) at the basal and mean levels. Values obtained in examination of 32 healthy volunteers were considered normal. RESULTS: Parameters of systolic and diastolic asynchrony in patients with cardiac arrhythmia significantly differ from normal ones. Basal LV diastolic asynchrony was detected in 41-48% patients, systolic one--in 62-100%, systolodiastolic--in 41% cases. Pacemaker implantation into the right heart significantly reduces LV systolic asynchrony while diastolic one was unaffected in an early postoperative period. The best sensitivity in detection of systolic asynchrony is achieved with TsSD index. Informative value of diastolic asynchrony parameters is much less than of the systolic one. CONCLUSION: Indices of systolic asynchrony (TsSD, IhbS, IhmS) can be used for heart condition control after pacemaker implantation.

[Cardiovascular continuum: possibilities of coenzyme-q in correction of oxidative stress].

Great attention is devoted at present to oxidative stress, free radical reactions as leading mechanisms in the cardiovascular continuum. The strategy of correction of oxidative stress implies the use of antioxidants. In this work we consider problems of the use of coenzyme-Q as a component of complex therapy of arterial hypertension; atherosclerosis, chronic heart failure.

[Characteristics of erythrocytes and hemoglobin in patients with ischemic heart disease and type 2 diabetes mellitus].

AIM: To study characteristics of erythrocytes and hemoglobin in patients with ischemic heart disease in the presence or absence of concomitant type 2 diabetes mellitus (DM) with consideration of clinical symptoms and selective coronaroangiographic data. MATERIAL AND METHODS: 287 patients with various forms of ischemic heart disease (IHD) were divided into two groups: 226 non-diabetic patients (group 1) and 61 type 2 diabetic patients (group 2). The following blood parameters were studied: Hb, HCT, red cell count, MCV, MCH, MCHC. Electrocardiography, echocardiography, doppler-echocardiography, circadian Holter ECG monitoring, bicycle exercise test were made in all the patients, coronaroangiography--in 174 patients. RESULTS: Group 2 patients showed significantly lower indices of the red blood. Anemia was detected in 38.05 and 47.62% patients of groups 1 and 2. A highly significant correlation was found in both groups between Hb concentration and severity of IHD manifestations (chi-square 49.06, p < 0.01 and 18.94, p < 0.01 in group 1 and 2, respectively). The same correlation was established in group 1 between angina pectoris severity and HCT (chi-square 37.912, p < 0.01). ECG registered myocardial ischemia much more often in group 2 than in group 1 (52.46 versus 42.48%, respectively). Group 2 patients with depression of the ST segment had lower red cell level. Diabetic and anemic patients had ischemic changes on ECG more frequently, their exercise tolerance was less, ectopic activity high. Coronary angiography demonstrated more severe affection of the coronary circulation in diabetics. Hb level and the latter also correlated (chi-square 24.379, p < 0.01). CONCLUSION: Hemoglobin and red cells proved essential in regulation of coronary blood flow and saturation of the myocardium with oxygen.