Efficacy of first-line ART regimens based on tenofovir in HIV-infected patients with pre-existing A62V mutation in reverse transcriptase.

INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 ‒ patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 ‒ patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.

Cognitive flexibility is associated with sickness resilience.

Psychological constructs related to health outcomes and well-being, such as metacognitive beliefs, have been linked to executive functions in general, and cognitive flexibility more specifically. However, such effects have previously only been discussed on a theoretical level and behavioral flexibility has most often been measured through self-report, only approximating information processing capacities. Objectively measured executive functions may be a more potent predictor of health outcomes. We set out to test whether cognitive flexibility capacity was associated with sick leave in a medium sized company. We included 111 subjects of widely different occupations and assessed their executive functions using Delis-Kaplan Executive Function System test battery (D-KEFS). To assess cognitive flexibility capacity, we included Design Fluency (DF) and Verbal Fluency (VF) and computed these into an index of cognitive flexibility (DFVF). Detailed information on sick leave for the last 5 years was gathered from the company. Our results showed that there was a significant negative correlation between DFVF and sick leave [rs(109) = -0.23, p = 0.015] in the full group as well as in the group that had at least 1 day of sick leave [rs(72) = -0.25, p = 0.03]. The results withstood adjustment for sex, age, occupation, and several core executive functions as well as autistic and ADHD-traits. The results remained for separate analyses using DF or VF. Our main findings were conceptually replicated in a group of bipolar disorder patients. This study shows that objectively measured capacity of cognitive flexibility is associated with key health outcomes such as sick leave.

[Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation].

INTRODUCTION: The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors. MATERIALS AND METHODS: The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients. RESULTS AND DISCUSSION: The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely. CONCLUSION: Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

[Relationship between vitamin D level and lipid profile in young adults].

Vitamin D deficiency, like cardiovascular disease, is widespread throughout the world. Researches indicate a number of potential mechanisms for the relationship between vitamin D deficiency and cardiometabolic risk factors. The results of studying the relationship between 25-hydroxyvitamin D [25(OH)D] in blood serum and lipid profile indicators are contradictory, studies were mainly carried out among the adult and elderly population. The aim of the research was to study the relationship between the level of 25(OH)D and lipid spectrum indicators in young people. Material and methods. The cross-sectional study included 278 young adults (aged from 18 to 24 years), of which 64 (23%) were boys, 214 (77%) were girls. The assessment of lipid spectrum indicators included total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, calculation of the atherogenic index; vitamin D status was evaluated by 25(OH)D blood serum level determination. Results. The levels of 25(OH)D below the criterion of insufficiency (30 ng/ml) were found in 81% of participants. A weak positive correlation was found between the level of triglycerides and 25(OH)D concentration (ρ=0.181, p=0.003). Gender differences were found in the association of 25(OH)D level with lipid profile parameters. In young men, a negative correlation was found between 25(OH)D level and indicators of total cholesterol (ρ=-0.316, p=0.014) and LDL cholesterol (ρ=-0.348, p=0.007), as well as significantly lower concentrations of 25(OH)D in the group with elevated LDL cholesterol levels. Conclusion. The results of the study indicate the existence of the relationships between 25(OH)D concentration and various parameters of the lipid spectrum of blood serum. Vitamin D deficiency may be associated with an increased risk of dyslipidemia, especially in males. The relationship between 25(OH)D level and lipid profile scores may differ depending on gender.

COVID-19 conspiracy ideation is associated with the delusion proneness trait and resistance to update of beliefs.

The rapid spread of conspiracy ideas associated with the recent COVID-19 pandemic represents a major threat to the ongoing and coming vaccination programs. Yet, the cognitive factors underlying the pandemic-related conspiracy beliefs are not well described. We hypothesized that such cognitive style is driven by delusion proneness, a trait phenotype associated with formation of delusion-like beliefs that exists on a continuum in the normal population. To probe this hypothesis, we developed a COVID-19 conspiracy questionnaire (CCQ) and assessed 577 subjects online. Their responses clustered into three factors that included Conspiracy, Distrust and Fear/Action as identified using principal component analysis. We then showed that CCQ (in particular the Conspiracy and Distrust factors) related both to general delusion proneness assessed with Peter's Delusion Inventory (PDI) as well as resistance to belief update using a Bias Against Disconfirmatory Evidence (BADE) task. Further, linear regression and pathway analyses suggested a specific contribution of BADE to CCQ not directly explained by PDI. Importantly, the main results remained significant when using a truncated version of the PDI where questions on paranoia were removed (in order to avoid circular evidence), and when adjusting for ADHD- and autistic traits (that are known to be substantially related to delusion proneness). Altogether, our results strongly suggest that pandemic-related conspiracy ideation is associated with delusion proneness trait phenotype.

[Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)].

INTRODUCTION: Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B. MATERIAL AND METHODS: The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database. RESULTS AND DISCUSSION: Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B. CONCLUSION: Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.

[Vitamin D deficiency and carbohydrate metabolism in obese children and adolescents].

Obesity in childhood and adolescence is an important clinical and social problem in all countries, due to its extremely adverse long-term health effects. Vitamin D deficiency is extremely widespread in the world. Obesity and metabolic syndrome are often associated with vitamin D deficit. The role of vitamin D deficiency in obesity and metabolic syndrome in childhood is not well understood. Aims - to study the relationship of vitamin D deficiency and carbohydrate metabolism parameters in school children with obesity. Material and methods. The cross-sectional study included 71 patients of the Arkhangelsk Children's Clinical Hospital named after P.G. Vyhletsova (32 boys, 39 girls, aged 10 to 15 years, all children live in Arkhangelsk) with abdominal obesity. An anthropometric study was conducted: height (cm), body weight (kg), waist circumference (cm), body mass index (BMI). Serum 25(ОН)D level, fasting glycemia, insulin level and HOMA-IR index were assessed. Results. It has been revealed that 98,6% of children have vitamin D deficiency of varying severity. 25(OH)D level in severely obese children (BMI>3SDS) was significantly lower than in other obese children (BMI<3SDS): 12.8 [7.3-14.9] vs 13.5 [8.9-18.2] ng/ml, (p=0.039). In children with hyperglycemia and insulin resistance, 25(OH)D levels were significantly lower compared with those who had normal glycemic parameters and HOMA-IR index. Conclusions. The high prevalence of vitamin D deficiency in children and adolescents with overweight and obesity, progressing with increasing obesity severity, has been demonstrated. The association of glucose metabolism disorders with vitamin D deficiency has been shown.

Renormalization flow of a weak extended backscattering Hamiltonian in a non-chiral Tomonaga-Luttinger liquid.

We consider a non-chiral Luttinger liquid in the presence of a backscattering Hamiltonian which has an extended range. Right/left moving fermions at a given location can thus be converted as left/right moving fermions at a different location, within a specific range. We perform a momentum shell renormalization group treatment which gives the evolution of the relative degrees of freedom of this Hamiltonian contribution under the renormalization flow, and we study a few realistic examples of this extended backscattering Hamiltonian. We find that, for repulsive Coulomb interaction in the Luttinger liquid, any such Hamiltonian contribution evolves into a delta-like scalar potential upon renormalization to a zero temperature cutoff. On the opposite, for attractive couplings, the amplitude of this kinetic Hamiltonian is suppressed, rendering the junction fully transparent. As the renormalization procedure may have to be stopped because of experimental constraints such as finite temperature, we predict the actual spatial shape of the kinetic Hamiltonian at different stages of the renormalization procedure, as a function of the position and the Luttinger interaction parameter, and show that it undergoes structural changes. This renormalized kinetic Hamiltonian has thus to be used as an input for the perturbative calculation of the current, for which we provide analytic expressions in imaginary time. We discuss the experimental relevance of this work by looking at one-dimensional systems consisting of carbon nanotubes or semiconductor nanowires.

Arrow of time and its reversal on the IBM quantum computer.

Uncovering the origin of the "arrow of time" remains a fundamental scientific challenge. Within the framework of statistical physics, this problem was inextricably associated with the Second Law of Thermodynamics, which declares that entropy growth proceeds from the system's entanglement with the environment. This poses a question of whether it is possible to develop protocols for circumventing the irreversibility of time and if so to practically implement these protocols. Here we show that, while in nature the complex conjugation needed for time reversal may appear exponentially improbable, one can design a quantum algorithm that includes complex conjugation and thus reverses a given quantum state. Using this algorithm on an IBM quantum computer enables us to experimentally demonstrate a backward time dynamics for an electron scattered on a two-level impurity.

[Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015]. / Molekuliarno-épidemiologicheskii analiz variantov VICh-1, tsirkulirovavshikh v Rossii v 1987-2015 gg.

AIM: To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. SUBJECTS AND METHODS: The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987-2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. RESULTS: The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988-1989. CONCLUSION: The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

H-theorem in quantum physics.

Remarkable progress of quantum information theory (QIT) allowed to formulate mathematical theorems for conditions that data-transmitting or data-processing occurs with a non-negative entropy gain. However, relation of these results formulated in terms of entropy gain in quantum channels to temporal evolution of real physical systems is not thoroughly understood. Here we build on the mathematical formalism provided by QIT to formulate the quantum H-theorem in terms of physical observables. We discuss the manifestation of the second law of thermodynamics in quantum physics and uncover special situations where the second law can be violated. We further demonstrate that the typical evolution of energy-isolated quantum systems occurs with non-diminishing entropy.

LSD-induced entropic brain activity predicts subsequent personality change.

Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc.

[Comparative analysis of genetic variants of the HIV-1 circulating in the Irkutsk region in 1999 and 2012].

The pol and env genome regions of the HIV-1 genetic variants circulating in the irkutsk region of russia in 1999 and 2012 were compared. The results of this work showed the dominance of the HIV-1 subtype a IDU-A genetic variant (100%) in this region. No primary resistance mutations in the pol gene in the treatment-naive patients were found. The heterogeneity of the viral population was found to be significantly increased based on the pol and env analysis among HIV-variants isolated in 2012 (12.88% and 2.16%) from the intravenous drug users as compared to HIV-variants that caused the outbreak of the HIV infection in 1999 (1.64% and 0.47%). In addition, the comparison of genetic distances of the pol and env gene sequences in the viruses isolated in 2012 from the HIV-positive persons infected through heterosexual intercourse and intravenous drug use demonstrated that the transmission route influenced the variability of the virus population. Among the viruses of IDU-A variant circulating in the area in 2012 the prevalence of X4-tropic variants was 24.7%.

Random Forest ensembles for detection and prediction of Alzheimer's disease with a good between-cohort robustness.

Computer-aided diagnosis of Alzheimer's disease (AD) is a rapidly developing field of neuroimaging with strong potential to be used in practice. In this context, assessment of models' robustness to noise and imaging protocol differences together with post-processing and tuning strategies are key tasks to be addressed in order to move towards successful clinical applications. In this study, we investigated the efficacy of Random Forest classifiers trained using different structural MRI measures, with and without neuroanatomical constraints in the detection and prediction of AD in terms of accuracy and between-cohort robustness. From The ADNI database, 185 AD, and 225 healthy controls (HC) were randomly split into training and testing datasets. 165 subjects with mild cognitive impairment (MCI) were distributed according to the month of conversion to dementia (4-year follow-up). Structural 1.5-T MRI-scans were processed using Freesurfer segmentation and cortical reconstruction. Using the resulting output, AD/HC classifiers were trained. Training included model tuning and performance assessment using out-of-bag estimation. Subsequently the classifiers were validated on the AD/HC test set and for the ability to predict MCI-to-AD conversion. Models' between-cohort robustness was additionally assessed using the AddNeuroMed dataset acquired with harmonized clinical and imaging protocols. In the ADNI set, the best AD/HC sensitivity/specificity (88.6%/92.0% - test set) was achieved by combining cortical thickness and volumetric measures. The Random Forest model resulted in significantly higher accuracy compared to the reference classifier (linear Support Vector Machine). The models trained using parcelled and high-dimensional (HD) input demonstrated equivalent performance, but the former was more effective in terms of computation/memory and time costs. The sensitivity/specificity for detecting MCI-to-AD conversion (but not AD/HC classification performance) was further improved from 79.5%/75%-83.3%/81.3% by a combination of morphometric measurements with ApoE-genotype and demographics (age, sex, education). When applied to the independent AddNeuroMed cohort, the best ADNI models produced equivalent performance without substantial accuracy drop, suggesting good robustness sufficient for future clinical implementation.

Simultaneous dual-wavelength stimulated Raman scattering in Ba(MoO4)x(WO4)(1-x) solid solution single crystals.

The simultaneous dual-wavelength stimulated Raman scattering (SRS) of the same order Stokes with 532 nm nanosecond laser pulse excitation was found for the first time to the best of our knowledge in Ba(MoO4)x(WO4)1-x single crystals. The results of studies of some peculiarities of this phenomenon were reported.

[Paramagnetic calcium melanins].

Treatment of catechol, pyrogallol, DOPA, dopamine, norepinephrine, and natural polyhydroxy-1,4-naphthoquinone echinochrome by aqueous solution of potassium superoxide (KO2) in the presence of CaCl2 leads to the formation of water-insoluble dark pigments with stable paramagnetic properties ("calcium melanins"). In control experiments in the same procedure without Ca2+, the pigments were not formed. EPR spectra of the calcium melanins had little difference from each other and from known melanins in shape, line width, and the g factor about 2,004. Addition of EDTA water solution to dried paramagnetic pigments leads to their fast dissolving and disappearing of EPR signal. Formation of similar polymers is also observed during autoxidation of o-diphenols in Ca(2+)-containing alkaline buffer solution, however, this process takes a few days instead of few seconds in the presence of KO2. Thus, calcium (and other divalent cation M2+) can consider as a key structural element in formation of M(2+)-catecholate paramagnetic Polymer. We assume the existence of two types of paramagnetic centers in melanin-like polymer: M(2+)-stabilized o-semiquinone radical or bi-radical complex containing o-semiquinone and superoxide anion radicals, stabilized by M2+.

[Diagnosis and treatment of anxiety-depressive disorders in patients with myocardial infarction].

The results of the study of psychopathological, somatic and functional characteristics of anxiety-depressive disorders in patients with acute myocardial infarction are presented. The authors confirmed the wide prevalence of these disorders in acute myocardial infarction and described the features of their diagnostics, dynamics and response to complex treatment. The impact of anxiety-depressive disorders on the clinical and functional state of the cardiovascular system and the dynamics of the patient's status due the concomitant anxiety-depressive disorder are considered.

[Primary percutaneous coronary angioplasty in patients with acute coronary syndrome and concomitant cancer].

The paper gives the results of X-ray surgical treatment in patients with acute coronary syndrome who have been ascertained to have concomitant cancer during their examination. Cancer was found in 11 patients in their medical history and diagnosed in 2 patients during examination after surgical treatment and 1 patient one year after his hospital discharge. The results of combination treatment showed the high efficiency of X-ray surgical treatment for acute coronary syndrome. Recovery of TIMI-III blood flow through the infarct-related coronary artery was achieved in 100% of cases; immediate clinical efficiency was 97.4%. In the concomitant cancer group, the therapeutic efficacy was 100%; there were no complications during X-ray surgery. All the patients from this group were discharged from hospital in a satisfactory state to be followed up by a cardiologist and oncologist for further treatment. The study performed suggests that concomitant cancer is not a contraindication to primary coronary angioplasty in patients with acute coronary syndrome. Primary coronary angioplasty with stenting is a safe effective treatment for acute coronary syndrome in this category of patients.

Dynamical resurrection of the visibility in a Mach-Zehnder interferometer.

We study a single-electron pulse injected into the chiral edge state of a quantum Hall device and subject it to a capacitive Coulomb interaction. We find that the scattered multiparticle state remains unentangled and hence can be created itself by a suitable classical voltage pulse. The application of an appropriate inverse pulse corrects for the shakeup due to the interaction and resurrects the original injected wave packet. We suggest an experiment with an asymmetric Mach-Zehnder interferometer where the application of such pulses manifests itself in an improved visibility.

[Calcium-dioxolene complexes: rate constants of pyrocatechol oxidation in the presence of Ca2+].

The effect of calcium ions on the rate of pyrocatechol autoxidation at pH 9.0 has been studied by mathematical modeling. The effect of Ca2+ on the oxygen absorption rate has been studied, and a kinetic model has been suggested, which takes different stages of interaction of pyrocatechol and its radical form with oxygen into account. It has been shown that the prooxidant action of Ca2+ is related to an abrupt increase (approximately by three orders of magnitude) in the rate constant of comproportionation (reaction of chain branching and formation of o-semiquinonates) and a marked decrease (by two orders of magnitude, from 1.4 10(7) to 0.6 10(5) M(-1)s(-1)) in the rate constant of disproportionation of o-semiquinones. The system can be used as a model for studying the prooxidant action of calcium ions.