Numerical Simulation of the Microtron Electron Beam Absorption by the Modified ABS-Plastic

Each specific task of the electron beam application imposes requirements for the beam profile and shape. One of the methods allows achieving high accuracy and low cost of the filters production is the 3D print method. The required properties of the electron beam interaction with the material can be achieved by using the modified plastic filaments. In this paper, the results of the model creation of the electron beams interaction with the ABS-plastic doped with different concentrations are presented. The depth dose distributions of the electron beam in the modified ABS-plastic are sown. The electron beam profiles and the electron beam distribution in the modified ABS-plastic are illustrated

CONCOMITANT CARDIOVASCULAR DISEASES AND ANTIHYPERTENSIVE TREATMENT IN OUTPATIENT PRACTICE (BY THE RECVASA REGISTRY DATA)

Aim. To study a pattern of concomitant cardiovascular diseases (CVDs) and to estimate particularities and quality of medical antihypertensive therapy in hypertensive patients in real outpatient practice with a help of the Registry in Ryazan region.Material and methods. A total of 3690 patients with hypertension, ischemic heart disease, chronic heart failure and atrial fibrillation, who had attended general practitioners and cardiologists of 3 outpatient clinics in Ryazan city, were enrolled in the outpatient Registry of cardiovascular diseases (RECVASA). The diagnosis of hypertension was recorded in 3648 of 3690 (98.9%) outpatient charts, 28.1% of the subjects were men and 71.9% - women.Results. A total of 2907 (79.7%) of 3648 patients had combination of hypertension with other CVDs. Combination of 3-4 cardiovascular diagnoses was registered in 63.8% of the cases. 11.5% and 9.5% of the patients had a history of myocardial infarction and cerebral stroke, respectively. Diagnosis of hypertension was verified in 448 of 450 randomized hypertensive patients (99.6%). The incidence of prescription of one and two antihypertensive drugs (AHDs) was 25% and 39%, respectively, of 3 AHDs – 21%, 4 and more – 2%. AHDs were not prescribed in 13% of hypertensive patients. The mean number of prescribed AHDs was 1.73. The mean incidence rate of target blood pressure achievement was 26.1%. We have noted insufficient ACE inhibitors/angiotensin receptor blockers (ARB) and beta-blockers prescription in different concomitant CVDs. Patients with 3-4 cardiovascular diagnoses were more often prescribed combined antihypertensive treatment. Prescription of ACE inhibitors/ARB, beta-blockers and thiazide diuretics combination was preferable in 74.1% of the cases, when taking into account absolute and relative contraindications for betablockers use – in 64.0%. 15.2% of the hypertensive patients used reimbursed drugs for CVDs at the moment of the Registry enrollment as compared with 39.2% in previous years (p<0.05).Conclusion. The RECVASA study data allowed revealing high incidence of concomitant CVDs in hypertensive patients, insufficient use of combined antihypertensive treatment, including AHDs with proved favorable influence on prognosis. Achievement of concordance of medical treatment to national and international guidelines, taking into account concomitant CVDs, and optimization of patients’ coverage with reimbursed drugs are the main reserves for antihypertensive treatment quality improvement

Characterization of Leishmania donovani MCM4: Expression Patterns and Interaction with PCNA

Events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. Nuclear DNA replication in trypanosomatids has thus far remained a largely uninvestigated area. While several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms. Here, we characterize the expression of Leishmania donovani MCM4, and find that while it broadly resembles other eukaryotes, noteworthy differences exist. MCM4 is constitutively nuclear, signifying that, unlike what is seen in S.cerevisiae, varying subcellular localization of MCM4 is not a mode of replication regulation in Leishmania. Overexpression of MCM4 in Leishmania promastigotes causes progress through S phase faster than usual, implicating a role for MCM4 in the modulation of cell cycle progression. We find for the first time in eukaryotes, an interaction between any of the proteins of the MCM2-7 (MCM4) and PCNA. MCM4 colocalizes with PCNA in S phase cells, in keeping with the MCM2-7 complex being involved not only in replication initiation, but fork elongation as well. Analysis of a LdMCM4 mutant indicates that MCM4 interacts with PCNA via the PIP box motif of MCM4 - perhaps as an integral component of the MCM2-7 complex, although we have no direct evidence that MCM4 harboring a PIP box mutation can still functionally associate with the other members of the MCM2-7 complex- and the PIP box motif is important for cell survival and viability. In Leishmania, MCM4 may possibly help in recruiting PCNA to chromatin, a role assigned to MCM10 in other eukaryotes

Combination of Atrial Fibrillation and Coronary Heart Disease in Patients in Clinical Practice: Comorbidities, Pharmacotherapy and Outcomes (Data from the REСVASA Registries)

Aim. Assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) included in the outpatient and hospital RECVASA registries.Materials and methods. 3169 patients with AF were enrolled in outpatient RECVASA (Ryazan), RECVASA AF-Yaroslavl registries and hospital RECVASA AF (Moscow, Kursk, Tula). 2497 (78.8%) registries of patients with AF had CAD and 703 (28.2%) of them had a previous myocardial infarction (MI).Results. There were 2,497 patients with a combination of AF and CAD (age was 72.2±9.9 years; 43.1% of men; CHA2DS2-VASc – 4.57±1.61 points; HAS-BLED – 1.60±0,75 points), and the group with AF without CAD included 672 patients (age was 66.0±12.3 years; 43.2% of men; CHA2DS2-VASc – 3.26±1.67 points; HAS-BLED – 1,11±0.74 points). Patients with CAD were on average 6.2 years older and had a higher risk of thromboembolic and hemorrhagic complications (p<0.05). 703 patients with a combination of AF and CAD had the previous myocardial infarction (MI; age was 72.3±9.5 years; 55.2% of men; CHA2DS2-VASc – 4.57±1.61; HAS-BLED – 1.65±0.76), and 1794 patients didn't have previous MI (age was 72.2±10.0 years; 38.4% of men; CHA2DS2-VASc – 4.30±1.50; HAS-BLED – 1.58±0.78). The proportion of men was 1.4 times higher among those with the previous MI. Patients with a combination of AF and CAD significantly more often (p <0.0001) than in the absence of CAD received a diagnosis of hypertension (93.8% and 78.6%), chronic heart failure (90.1% and 51.2%), diabetes mellitus (21.4% and 13.8%), chronic kidney disease (24.8% and 17.7%), as well as anemia (7.0% and 3.0%; p=0.001). Patients with and without the previous MI had the only significant difference in the form of a diabetes mellitus higher incidence having the previous MI (27% versus 19.2%, p=0.0008). The frequency of proper cardiovascular pharmacotherapy was insufficient, mainly in the presence of CAD (67.8%) than in its absence (74.5%), especially the prescription of anticoagulants (39.1% and 66.2%; p <0.0001), as well as in the presence of the previous MI (63.3%) than in its absence (74.3%). The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death (risk ratio [RR]=1.58; 95% confidence interval [CI] was 1.33-1.88; p <0.001 and RR=1.59; 95% CI was 1.33-1.90; p <0.001), as well as with a higher risk of developing a combined cardiovascular endpoint (RR=1.88; 95% CI was 1.17-3 , 00; p <0.001 and RR=1.75; 95% CI was 1.44-2.12; p<0.001, respectively).Conclusion. 78.8% of patients from AF registries in 5 regions of Russia were diagnosed with CAD, of which 28.2% had previously suffered myocardial infarction. Patients with a combination of AF and CAD more often than in the absence of CAD had hypertension, chronic heart failure, diabetes, chronic kidney disease and anemia. Patients with the previous MI had higher incidence of diabetes than those without the previous MI. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CAD and the previous MI than in their absence. All-cause mortality was recorded in patients with a combination of AF and CAD more often than in the absence of CAD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and the previous MI than in those without the previous MI. The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death, as well as a higher risk of developing a combined cardiovascular endpoint

Patients with a Combination of Atrial Fibrillation and Chronic Heart Failure in Clinical Practice: Comorbidities, Drug Treatment and Outcomes

Aim. To assess in clinical practice the structure of multimorbidity, cardiovascular pharmacotherapy and outcomes in patients with a combination of atrial fibrillation (AF) and chronic heart failure (CHF) based on prospective registries of patients with cardiovascular diseases (CVD).Materials and Methods. The data of 3795 patients with atrial fibrillation (AF) were analyzed within the registries RECVASA (Ryazan), RECVASA FP (Moscow, Kursk, Tula, Yaroslavl), REGION-PO and REGION-LD (Ryazan), REGION-Moscow, REGATA (Ryazan). The comparison groups consisted of 3016 (79.5%) patients with AF in combination with CHF and 779 (29.5%) patients with AF without CHF. The duration of prospective observation is from 2 to 6 years.Results. Patients with a combination of AF and CHF (n=3016, age was 72.0±10.3 years; 41.8% of men) compared with patients with AF without CHF (n=779, age was 70.3±12.0 years; 43.5% of men) had a higher risk of thromboembolic complications (CHA2DS2-VASc – 4.68±1.59 and 3.10±1.50; p<0.001) and hemorrhagic complications (HAS-BLED – 1.59±0.77 and 1.33±0.76; p<0.05). Patients with a combination of AF and CHF significantly more often (p<0.001) than in the absence of CHF were diagnosed with arterial hypertension (93.9% and 83.8%), coronary heart disease (87.9% and 53,5%), myocardial infarction (28.4% and 14.0%), diabetes mellitus (22.4% and 7.7%), chronic kidney disease (24.8% and 16.2%), as well as respiratory diseases (20.1% and 15.3%; p=0.002). Patients with AF in the presence of CHF, compared with patients without CHF, were more often diagnosed with a permanent form of arrhythmia (49.3% and 32.9%; p<0.001) and less often paroxysmal (22.5% and 46.2%; p<0.001) form  of  arrhythmia.  Ejection  fraction  ≤40%  (9.3%  and  1.2%;  p<0.001),  heart  rate  ≥90/min  (23.7% and 19.3%; p=0.008) and blood pressure ≥140/90 mm Hg (59.9% and 52.2%; p<0.001) were recorded with AF in the presence of CHF more often than in the absence of CHF. The frequency of proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF (64.9%) than in the absence of it (56.1%), but anticoagulants were prescribed less frequently when AF and CHF were combined (38.8% and  49, 0%; p<0.001). The frequency of unreasonable prescription of antiplatelet agents instead of anticoagulants was 52.5% and 33.3% (p<0.001) in the combination of AF, CHF and coronary heart disease, as well as in the combination of AF with coronary heart disease but without CHF. Patients with AF and CHF during the observation period compared with those without CHF had higher mortality from all causes (37.6% and 30.3%; p=0.001), the frequency of non-fatal cerebral stroke (8.2% and 5.4%; p=0.032) and myocardial infarction (4.7% and 2.5%; p=0.036), hospitalizations for CVD (22.8% and 15.5%; p<0.001).Conclusion. Patients with a combination of AF and CHF, compared with the group of patients with AF without CHF, were older, had a higher risk of thromboembolic and hemorrhagic complications, they were more often diagnosed with other concomitant cardiovascular and chronic noncardiac diseases, decreased left ventricular ejection fraction, tachysystole, failure to achieve the target blood pressure level in the presence of arterial hypertension. The frequency of prescribing proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF, while the frequency of prescribing anticoagulants was less. The  incidence of mortality from all causes, the development of non-fatal myocardial infarction   and cerebral stroke, as well as the incidence of hospitalizations for CVDs were higher in AF associated with CHF

СРАВНИТЕЛЬНАЯ ХАРАКТЕРИСТИКА МУЛЬТИМОРБИДНОСТИ, МЕДИКАМЕНТОЗНОГО ЛЕЧЕНИЯ И ИСХОДОВ У БОЛЬНЫХ С СОЧЕТАНИЕМ ПЕРЕНЕСЕННОГО ОСТРОГО НАРУШЕНИЯ МОЗГОВОГО КРОВООБРАЩЕНИЯ И ФИБРИЛЛЯЦИИ ПРЕДСЕРДИЙ ПРИ НАЛИЧИИ ИЛИ ОТСУТСТВИИ АНАМНЕЗА ИНФАРКТА МИОКАРДА (ДАННЫЕ РЕГИСТРОВ РЕГИОН)

AIM. Within the framework of outpatient and hospital registers of REGION (REGIster of patients who have undergone acute cerebrovascular accident) to carry out a comparative assessment of demographic and clinical-anamnestical characteristics, medical treatment and outcomes in clinical practice in patients with a combination of undergone acute cerebrovascular accident (ACVA) and atrial fibrillation (AF) in the presence or absence of myocardial infarction (MI) in the medical history.MATERIAL AND METHODS. Outpatient registers REGION (Ryazan) and hospital register REGION (Moscow) included 1886 patients who have undergone ACVA (age 70.6 ± 12.5 years, 41.9% of men), of them 516 (27.4%) people with AF. Comparison groups included 152 (8.1%) patients with a combination of ACVA, AF and MI in medical history (ACVA + AF + MI group) and 364 (19.3%) patients with ACVA, AF without MI (ACVA + AF without MI group). The presence of cardiovascular diseases (CVD), concomitant diseases, drug therapy and outcomes were analyzed.RESULTS. In the group of ACVA + AF + MI patients, compared to the ACVA + AF without MI group, the share of patients with AH (100% and 97.2%), IHD (100% and 87.1%), CHD (68.4% and 57.1%), repeated ACVA (36.9% and 23.9%), diabetes mellitus in women (39.5% and 20.4%) was statistically significantly higher. In the comparison groups, the share of smokers (13.3% and 15.5%), patients with burdened heredity of early development of CVDs (2.1% and 1.1%) and hypercholesterolemia (41.1% and 50.0%) did not differ significantly, however, in the group of ACVA + AF + MI, in comparison with the group of ACVA + AF without MI, there was a higher risk on the CHA2DS2-VASc scale (5.26 ± 1.32 and 4.09 ± 1.44; p < 0.001) and HAS-BLED scale (1.91 ± 0.76 and 1.62 ± 0.79; p < 0.01). Patients with AF of REGION register, both with and without MI, had insufficient frequency of proper medical prescriptions for CVDs (46.6% and 38.9% on average), especially prescription of anticoagulants (19.1% and 21.4%), statins in case of IHD (33.6% and 27.4%) and beta-adrenoblockers in case of CHD (39.4% and 35.6%).  During the four-year period of observation, in comparison with post-stroke patients without a history of MI, the mortality rate for all causes was 1.5 times higher (56.6% and 37.6%, p = 0.0001), the incidence of non-fatal MI was higher (2.0% and 0.3%,p = 0.04). CONCLUSION. Patients with a combination of ACVA, AF and MI history are a very high risk group for adverse outcomes observed on an outpatient stage. For these patients it is very important to improve the quality of drug therapy and the effectiveness of secondary prophylaxis.ЦЕЛЬ. В рамках амбулаторных и госпитального регистров РЕГИОН (РЕГИстр больных, перенесших Острое Нарушение мозгового кровообращения) провести сравнительную оценку демографических и клинико-анамнестических характеристик, медикаментозного лечения и исходов в клинической практике у больных с сочетанием перенесенного острого нарушения мозгового кровообращения (ОНМК) и фибрилляции предсердий (ФП) при наличии или отсутствии инфаркта миокарда (ИМ) в анамнезе.МАТЕРИАЛ И МЕТОДЫ. В амбулаторные регистры РЕГИОН (Рязань) и в госпитальный регистр РЕГИОН (Москва) включено 1886 пациентов, перенесших ОНМК (возраст 70,6 ± 12,5 лет, 41,9% мужчин), из них с ФП 516 (27,4%) человек. Группы сравнения составили 152 (8,1%) пациента с сочетанием перенесенного ОНМК, ФП и ИМ в анамнезе (группа ОНМК + ФП + ИМ) и 364 (19,3%) больных с ОНМК, ФП без анамнеза ИМ (группа ОНМК + ФП без ИМ). Проанализированы наличие сердечно-сосудистых заболеваний (ССЗ), сопутствующих заболеваний, медикаментозная терапия и исходы.РЕЗУЛЬТАТЫ. В группе пациентов ОНМК + ФП + ИМ, по сравнению с пациентами группы ОНМК + ФП без ИМ, была статистически значимо выше доля лиц с АГ (100% и 97,2%), ИБС (100% и 87,1%), ХСН (68,4% и 57,1%), повторного ОНМК (36,9% и 23,9%), сахарного диабета у женщин (39,5% и 20,4%). В группах сравнения доля курящих (13,3% и 15,5%), пациентов с отягощенной наследственностью раннего развития ССЗ (2,1% и 1,1%) и гиперхолестеринемией (41,1% и 50,0%) существенно не различалась, однако в группе ОНМК + ФП + ИМ, по сравнению с группой ОНМК + ФП без ИМ, был выше риск по шкале СHA 2DS2–VASc (5,26 ± 1,32 и 4,09 ± 1,44; p < 0,001) и шкале HAS-BLED (1,91 ± 0,76 и 1,62 ± 0,79; p < 0,01). У больных с ФП регистра РЕГИОН, как с перенесенным ИМ, так и без ИМ, частота должных медикаментозных назначений по поводу ССЗ была недостаточной (в среднем 46,6% и 38,9%), особенно назначения антикоагулянтов (19,1% и 21,4%), статинов при ИБС (33,6% и 27,4%) и бета-адреноблокаторов при ХСН (39,4% и 35,6%). За четырехлетний период наблюдения у больных группы ОНМК + ФП + ИМ, по сравнению с постинсультными пациентами без анамнеза ИМ, смертность от всех причин была в 1,5 раза выше (56,6% и 37,6%, p = 0,0001), чаще развивался нефатальный ИМ (2,0% и 0,3%, р = 0,04).ЗАКЛЮЧЕНИЕ. Больные с сочетанием перенесенных ОНМК, ФП и анамнеза ИМ являются группой очень высокого риска неблагоприятного исхода при наблюдении на амбулаторном этапе. Для данных пациентов крайне важным является повышение качества медикаментозной терапии и эффективности вторичной профилактики

Attention to Bright Surfaces Enhances the Pupillary Light Reflex

One longstanding question is how early in the visual system attention exerts its influence. Here we show that an effect of attention can be measured at the earliest possible stage of visual information processing, as a change in the optics of the eye. We tested human subjects and found that covertly attending to bright surfaces results in an enhanced pupillary light reflex (PLR)—the pupillary constriction that occurs in response to light increments. The PLR optimizes the optical quality of the retinal image across illumination conditions, increasing sensitivity by modulating retinal illumination, and improving acuity by reducing spherical aberrations. The attentional modulation of the PLR that we describe constitutes a new mechanism through which vision is affected by attention; we discuss three alternatives for the neural substrates of this effect, including the possibility that attention might act indirectly, via its well established effects in early visual cortex