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Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD. [ABSTRACT FROM AUTHOR]

Simple Summary: Radical pancreatectomies with superior mesenteric vein (SMV) resection without portal-to-superior mesenteric vein (PV/SMV) reconstruction are scarcely discussed in the literature. The existing data contain around 15 cases published with unclear oncological results and algorithms of patients' selection. In the present report, we analyzed the short- and long-term results of 19 consecutive pancreatectomies with SMV resection without PV/SMV reconstruction for locally advanced pancreatic ductal adenocarcinoma, and discussed the role of CT-based preoperative reconstructions and selection criteria for radical and safe surgery in this highly specific group of patients. The "vein definition" for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies for "low" LA PDAC with SMV and all its tributaries resection without PV/SMV reconstruction has shown zero mortality; overall morbidity—56%; Dindo–Clavien—3–10.5%; R0—rate—82%; mean operative procedure time—355 ± 154 min; mean blood loss—330 ± 170 mL; delayed gastric emptying—25%; and clinically relevant postoperative pancreatic fistula—8%. In three cases, surgery was associated with superior mesenteric (n2) and common hepatic artery (n1) resection. Surgery was completed without vein reconstruction (n13) and with inferior mesenteric-to-splenic anastomosis (n6). There were no cases of liver, gastric, or intestinal ischemia. A specific complication of the SMV resection without reconstruction was 2–3 days-long intestinal edema (48%). Median overall survival was 25 months, and median progression-free survival was 18 months. All the relapses, except two, were distant. The possibility of successful SMV resection without PV/SMV reconstruction can be predicted before surgery by CT-based reconstructions. The mandatory anatomical conditions for the procedure were as follows: (1) preserved SMV-SV confluence; (2) occluded SMV for any reason (tumor or thrombus); (3) well-developed inferior mesenteric vein collaterals with dilated intestinal veins; (4) no right-sided vein collaterals; and (5) no varices in the upper abdomen. Conclusion: "Low" LA PDACs involving SMV with all its tributaries can be radically and safely resected in highly and specifically selected cases without PV/SMV reconstruction with an acceptable survival rate. [ABSTRACT FROM AUTHOR]

The neurobiology of Autism Spectrum Disorder (ASD) is hypothetically related to the imbalance between neural excitation (E) and inhibition (I). Different studies have revealed that alpha-band (8–12 Hz) activity in magneto- and electroencephalography (MEG and EEG) may reflect E and I processes and, thus, can be of particular interest in ASD research. Previous findings indicated alterations in event-related and baseline alpha activity in different cortical systems in individuals with ASD, and these abnormalities were associated with core and co-occurring conditions of ASD. However, the knowledge on auditory alpha oscillations in this population is limited. This MEG study investigated stimulus-induced (Event-Related Desynchronization, ERD) and baseline alpha-band activity (both periodic and aperiodic) in the auditory cortex and also the relationships between these neural activities and behavioral measures of children with ASD. Ninety amplitude-modulated tones were presented to two groups of children: 20 children with ASD (5 girls, Mage = 10.03, SD = 1.7) and 20 typically developing controls (9 girls, Mage = 9.11, SD = 1.3). Children with ASD had a bilateral reduction of alpha-band ERD, reduced baseline aperiodic-adjusted alpha power, and flattened aperiodic exponent in comparison to TD children. Moreover, lower raw baseline alpha power and aperiodic offset in the language-dominant left auditory cortex were associated with better language skills of children with ASD measured in formal assessment. The findings highlighted the alterations of E / I balance metrics in response to basic auditory stimuli in children with ASD and also provided evidence for the contribution of low-level processing to language difficulties in ASD. [ABSTRACT FROM AUTHOR]

Radiation hardening is studied for stainless austenitic and ferritic-martensitic chromium steels after ion and neutron irradiation at various temperatures. Austenitic and ferritic-martensitic steels irradiated up to 30 dpa in various nuclear reactors and ion accelerators are studied at various temperatures. A change in Vickers microhardness is used as the radiation hardening parameter. A methodology is developed that allows one to determine the ion irradiation parameters, which ensure the radiation hardening of ferritic-martensitic and austenitic steels, as close as possible to the radiation hardening of the same steels under neutron irradiation. A transferability function is introduced to connect the irradiation temperatures for ion and neutron irradiation that provides the same radiation hardening. On the basis of the obtained experimental data, after ion and neutron irradiation the transferability functions are determined for the investigated austenitic and ferritic-martensitic steels, which connect the temperatures for ion and neutron irradiation and provide the same radiation hardening at a given damage dose. [ABSTRACT FROM AUTHOR]

Objective: Assessment of diastolic function of the left ventricle (LVDF) makes it possible to detect chronic heart failure (CHF) at the preclinical stage of development, when its progression can still be prevented. Doppler echocardiography (echo) is the most accurate non-invasive diagnostic method for left ventricular diastolic dysfunction (LVDD), requiring expensive equipment and trained professionals. The development of an accessible screening method for the diagnosis of LVDD is an urgent and practically significant task. Purpose of the study was to evaluate the diagnostic value, sensitivity and specificity, positive predictive value and negative predictive value of the method of spectral analysis of a single-channel electrocardiogram (S-ch ECG) proposed by us for the diagnosis of LVDD in comparison with Doppler echo as a reference. Methods: The study involved 60 people (35 patients on program hemodialysis with arterial hypertension and 25 healthy individuals). Among the patients there were 19 men and 16 women aged 29 to 65 (45.9 (12.8)) years. Among the healthy were 15 men and 10 women aged 25 to 63 (43.2(11.8)). Doppler echo was performed on the SonoSite Micro Maxx Belse X2 apparatus. LVDF was determined according to the generally accepted method. S-ch ECG was taken with portable recorder DuoEK 118 from Lepu Medical. LVDD was determined by S-ch ECG spectral analysis as the ratio of the sum of harmonic power in the period of early diastolic filling to the sum of harmonic power during the period of atrial contraction. Results: The sensitivity of the method developed by us was 0.74, and the specificity was 0.84. Positive predictive value was 0.87 and negative predictive value was 0.70. Chi-square: 15.043, p<0.0001 - the presence of a relationship is statistically highly significant; Phi=0.514, p<0.0001 - the presence of a connection is highly significant. Area Under the Curve is 0.791 (0.061) with a confidence interval of 0.672 to 0.911. The obtained values indicate that S-ch ECG scores are fairly good predictors of LVDD. Conclusion: Spectral analysis of S-ch ECG has a high sensitivity and sufficient specificity for the diagnosis of LVDD. This method can be used for remote mass screening studies for the purpose of preclinical diagnosis of CHF. [ABSTRACT FROM AUTHOR]

The Altai falcon from Central Asia always attracted the attention of humans. Long considered a totemic bird in its native area, modern falconers still much appreciated this large-bodied and mighty bird of prey due to its rarity and unique look. The peculiar body characteristics halfway between the saker falcon (Falco cherrug) and the gyrfalcon (F. rusticolus) triggered debates about its contentious taxonomy. The weak phylogenetic signal associated with traditional genetic methods could not resolve this uncertainty. Here, we address the controversial evolutionary origin of Altai falcons by means of a genome-wide approach, Restriction-site Associated DNA sequencing, using sympatric eastern sakers falcons, allopatric western saker falcons and gyrfalcons as outgroup. This approach provided an unprecedented insight into the phylogenetic relationships of the studied populations by delivering 17,095 unlinked SNPs shedding light on the polyphyletic nature of Altai falcons within eastern sakers. Thus we concluded that the former must correspond to a low taxonomic rank, probably an ecotype or form of the latter. Also, we found that eastern sakers are paraphyletic without gyrfalcons, thus, these latter birds are best regarded as the direct sister lineage of the eastern sakers. This evolutionary relationship, corroborated also by re-analyzing the dataset with the inclusion of outgroup samples (F. biarmicus and F. peregrinus), put eastern sakers into a new light as the potential ancestral genetic source of high latitude and altitude adaptation in descendent populations. Finally, conservation genomic values hint at the stable genetic background of the studied saker populations. [ABSTRACT FROM AUTHOR]

The Altai falcon from Central Asia always attracted the attention of humans. Long considered a totemic bird in its native area, modern falconers still much appreciated this large-bodied and mighty bird of prey due to its rarity and unique look. The peculiar body characteristics halfway between the saker falcon (Falco cherrug) and the gyrfalcon (F. rusticolus) triggered debates about its contentious taxonomy. The weak phylogenetic signal associated with traditional genetic methods could not resolve this uncertainty. Here, we address the controversial evolutionary origin of Altai falcons by means of a genome-wide approach, Restriction-site Associated DNA sequencing, using sympatric eastern sakers falcons, allopatric western saker falcons and gyrfalcons as outgroup. This approach provided an unprecedented insight into the phylogenetic relationships of the studied populations by delivering 17,095 unlinked SNPs shedding light on the polyphyletic nature of Altai falcons within eastern sakers. Thus we concluded that the former must correspond to a low taxonomic rank, probably an ecotype or form of the latter. Also, we found that eastern sakers are paraphyletic without gyrfalcons, thus, these latter birds are best regarded as the direct sister lineage of the eastern sakers. This evolutionary relationship, corroborated also by re-analyzing the dataset with the inclusion of outgroup samples (F. biarmicus and F. peregrinus), put eastern sakers into a new light as the potential ancestral genetic source of high latitude and altitude adaptation in descendent populations. Finally, conservation genomic values hint at the stable genetic background of the studied saker populations. [ABSTRACT FROM AUTHOR]

Alpha-band (8–12 Hz) event-related desynchronization (ERD) or a decrease in alpha power in electro- and magnetoencephalography (EEG and MEG) reflects the involvement of a neural tissue in information processing. It is known that most children with autism spectrum disorder (ASD) have difficulties in information processing, and, thus, investigation of alpha oscillations is of particular interest in this population. Previous studies have demonstrated alterations in this neural activity in individuals with ASD; however, little is known about alpha ERD during simultaneous presentation of auditory and visual stimuli in children with and without ASD. As alpha oscillations are intimately related to attention, and attention deficit is one of the common co-occurring conditions of ASD, we predict that children with ASD can have altered alpha ERD in one of the sensory domains. In the present study, we used MEG to investigate alpha ERD in groups of 20 children with ASD and 20 age-matched typically developing controls. Simple amplitude-modulated tones were presented together with a fixation cross appearing on the screen. The results showed that children with ASD had a bilateral reduction in alpha-band ERD in the auditory but not visual cortex. Moreover, alterations in the auditory cortex were associated with a higher presence of autistic traits measured in behavioral assessment. [ABSTRACT FROM AUTHOR]

A study published in the British Journal of Dermatology suggests that there may be a link between psoriasis and cardiovascular risk through elevated plasma triglycerides. The study found that individuals with high plasma triglyceride levels had a higher probability of developing psoriasis compared to those with lower levels. The researchers also identified genetic variants associated with triglyceride metabolism that could potentially be targeted for treatment. Further research is needed to explore the impact of lowering triglyceride levels on psoriasis severity and the development of related conditions. [Extracted from the article]

The core symptoms of Autism Spectrum Disorder (ASD) are impairments in social interaction/communication and the presence of stereotyped and repetitive behaviour. The amygdala and hippocampus are involved in core functions in the "social brain" and, thus, may be of particular interest in ASD. Previous studies demonstrated inconsistent results, revealing both increased and reduced volume of these brain structures in individuals with ASD. In this study, we investigated the grey and white matter volumes of amygdala and hippocampus in primary-school-aged children with and without ASD. Also, we assessed the relationships between the volume of brain structures and behavioural measures in children with ASD. A total of 36 children participated in the study: 18 children with ASD (13 boys, age range 8.01–14.01 years, mean age (Mage) = 10.02, standard deviation (SD) = 1.76) and 18 age- and sex-matched typically developing controls (13 boys, age range 7.06–12.03 years, Mage = 10.00, SD = 1.38). The whole-brain structural magnetic resonance imaging (MRI) was applied to acquire T1 images for each child. The results showed a bilateral reduction in grey matter volume of amygdala and hippocampus in children with ASD, but no difference was found in white matter volume. Importantly, pathological reduction in grey matter volume of amygdala was associated with lower language skills and more severe autistic traits; also, a reduced grey matter volume of the left hippocampus was related to lower language skills in the ASD group. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is characterized by social interaction and communication deficits, repetitive behavior and often by co-occurring conditions such as language and non-verbal IQ development delays. Previous studies reported that those behavioral abnormalities can be associated with corpus callosum organization. However, little is known about the specific differences in white matter structure of the corpus callosum parts in children with ASD and TD peers and their relationships to core and co-occurring symptoms of ASD. The aim of the study was to investigate the volumetric and microstructural characteristics of the corpus callosum parts crucially involved in social, language, and non-verbal IQ behavior in primary-school-aged children with ASD and to assess the relationships between these characteristics and behavioral measures. 38 children (19 with ASD and 19 typically developing (TD) controls) were scanned using diffusion-weighted MRI and assessed with behavioral tests. The tractography of the corpus callosum parts were performed using Quantitative Imaging Toolkit software; diffusivity and volumetric measurements were extracted for the analysis. In the ASD group, fractional anisotropy (FA) was decreased across the supplementary motor area and the ventromedial prefrontal cortex, and axial diffusivity (AD) was reduced across each of the corpus callosum parts in comparison to the TD group. Importantly, the AD decrease was related to worse language skills and more severe autistic traits in individuals with ASD. The microstructure of the corpus callosum parts differs between children with and without ASD. Abnormalities in white matter organization of the corpus callosum parts are associated with core and co-occurring symptoms of ASD. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. Methods: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. Results: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (β = 0.37; P = 0.050) and LDL-C adjustment for FFB (β = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. Conclusions: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01778569 [ABSTRACT FROM AUTHOR]

The supercritical water-cooled reactors (SWCR) belong to Generation IV of reactors. These reactors have a number of advantages over currently operating WWERs and PWRs. These advantages include higher thermal efficiency, a more simplified unit design, and the possibility of incorporating it into a closed fuel cycle. It is therefore necessary to identify candidate materials for the SWCR and validate the safety and effectiveness of their use. 12Cr ferritic-martensitic (F/M) stainless steel is considered a candidate material for SWCR internals. Radiation embrittlement and corrosion cracking in the primary circuit coolant environment are the main mechanisms of F/M steels degradation during SWCR operation. Here, the stress corrosion cracking (SCC) in supercritical water at 390 and 550 °C of 12Cr F/M steel irradiated by neutrons to 12 dpa is investigated. Autoclave tests of specially designed disk specimens in supercritical water were performed. The tests were carried out under different constant load (CL), temperature 450 °C, and pressure in autoclave 25 MPa. The threshold stress, below which the SCC initiation of irradiated 12Cr F/M steel does not occur, was determined. [ABSTRACT FROM AUTHOR]

Increased oxidative/genotoxic stress is known to impact the pathophysiology of ASD (autism spectrum disorder). Clinical studies, however, reported limited, heterogeneous but promising responses to treatment with antioxidant remedies. We determined whether the functional polymorphism of the Nrf2 gene, master regulator of anti-oxidant adaptive reactions to genotoxic stress, links to the genotoxic stress responses and to an in vitro effect of a NRF2 inductor in ASD children. Oxidative stress biomarkers, adaptive responses to genotoxic/oxidative stress, levels of master antioxidant regulator Nrf2 and its active form pNrf2 before and after inducing by dimethyl fumarate (DMF), and promotor rs35652124 polymorphism of NFE2L2 gene encoding Nrf2 were studied in children with ASD (n = 179). Controls included healthy adults (n = 101). Adaptive responses to genotoxicity as indicated by H2AX and cytoprotection by NRF2 contents positively correlated in ASD children with a Spearman coefficient of R = 0.479 in T+, but not CC genotypes. ASD children with NRF2 rs35652124 CC genotype demonstrated significantly higher H2AX content (0.652 vs. 0.499 in T+) and pNrf2 induction by DMF, lowered 8-oxo-dG concentration in plasma and higher cfDNA/plasma nuclease activity ratio. Our pilot findings suggest that in ASD children the NEF2L2 rs35652124 polymorphism impacts adaptive responses that may potentially link to ASD severity. Our data warrant further studies to reveal the potential for NEF2L2 genotype-specific and age-dependent repurposing of DMF and/or other NRF2-inducing drugs. [ABSTRACT FROM AUTHOR]

Interaction of J-aggregates of two carbocyanine dyes, TDBC and TCC, with similar structures has been studied in aqueous solutions and thin polymer films. It has been revealed that despite the structure similarity these J-aggregates didn't interact explicitly when mixed both in aqueous solutions and polycation thin films. However, by placing the J-aggregates in different layers separated by polycation film spacer, efficient energy transfer can be achieved with TDBC J-aggregates as an energy donor and TCC J-aggregates as energy acceptor. [ABSTRACT FROM AUTHOR]

Atherosclerosis, autoimmune disease, cardiovascular disease, coronary artery disease, CT angiography (CTA), risk factors Keywords: atherosclerosis; autoimmune disease; cardiovascular disease; coronary artery disease; CT angiography (CTA); risk factors EN atherosclerosis autoimmune disease cardiovascular disease coronary artery disease CT angiography (CTA) risk factors 342 344 3 08/10/23 20230801 NES 230801 Atherosclerosis has significant inflammatory and lipid components that lead to adverse cardiovascular events, driven in part by high-risk, vulnerable coronary plaque rupture.[1],[2] Lipid-rich necrotic core (LRNC) is a rupture-prone plaque feature predictive of future cardiovascular events and linked with myocardial infarction.[3] We previously showed that psoriasis, a chronic inflammatory disease predisposing to accelerated atherosclerosis, had increased LRNC prevalence that attenuated with biologic therapy over 1 year.[4] These findings relied on statistical models that could only assess a few variables to predict complex outcomes. [Extracted from the article]

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD) but its neural basis is poorly understood. Using structural magnetic resonance imaging (MRI), the present study provides the whole-brain comparison of both volume- and surface-based characteristics between groups of children with and without ASD and investigates the relationships between these characteristics in language-related areas and the language abilities of children with ASD measured with standardized tools. A total of 36 school-aged children participated in the study: 18 children with ASD and 18 age- and sex-matched typically developing controls. The results revealed that multiple regions differed between groups of children in gray matter volume, gray matter thickness, gyrification, and cortical complexity (fractal dimension). White matter volume and sulcus depth did not differ between groups of children in any region. Importantly, gray matter thickness and gyrification of language-related areas were related to language functioning in children with ASD. Thus, the results of the present study shed some light on the structural brain abnormalities associated with language impairment in ASD. [ABSTRACT FROM AUTHOR]

Background: Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on the efficacy and safety of diazepam therapy. Objective: The objective of our study was to study the effect of CYP3A isoenzymes activity on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg / day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP3A4 C>T intron 6 (rs35599367) genotypes: (CC) −9.0 [−13.0; −5.0], (CT+TT) −13.5 [−15.0; −10.0], p = 0.014. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 7.5 [6.0; 11.0], (CT+TT) 11.0 [8.0; 12.0], p = 0.003. Conclusion: Possible relationship between the CYP3A activity, evaluated by the content of the urinary endogenous substrate of the given isoenzyme and its metabolite, the 6-beta-hydroxy cortisol (6-β-HC) / cortisol ratio, and the efficacy of diazepam was demonstrated. This possible relationship was also supported by the genotyping results. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of pharmacoresistance. [ABSTRACT FROM AUTHOR]

Background and Objectives: Psoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies. Methods: In this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1b, IL-6, IL-12/IL-23, IL-17A, TNF-a, IFN-g). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity. Results: Compared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-g (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized b = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized b = 0.488, p = 0.008), liver (standardized b = 0.619, p < 0.001), spleen (standardized b = 0.523, p = 0.004), and subcutaneous adipose (standardized b = 0.524, p = 0.003). [ABSTRACT FROM AUTHOR]

Background: Statin treatment is a potent lipid‐lowering therapy associated with decreased cardiovascular risk and mortality. Recent studies including the PARADIGM trial have demonstrated the impact of statins on promoting calcified coronary plaque. Hypothesis: The degree of systemic inflammation impacts the amount of increase in coronary plaque calcification over 2 years of statin treatment. Methods: A subgroup of 142 participants was analyzed from the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study (NCT01212900), who were on statin treatment and underwent cardiac computed tomography angiography (CCTA) at baseline and 2‐year follow‐up. This cohort was stratified by baseline median levels of high‐sensitivity hs‐CRP and analyzed with linear regressions using Stata‐17 (StataCorp). Results: In the high versus low hs‐CRP group, patients with higher baseline median hs‐CRP had increased BMI (median [IQR]; 29 [27–31] vs. 27 [24–28]; p <.001), hypertension (59% vs. 41%; p =.03), and LDL‐C levels (97 [77–113] vs. 87 [75–97] mg/dl; p =.01). After 2 years of statin treatment, the high hs‐CRP group had significant increase in dense‐calcified coronary burden versus the low hs‐CRP group (1.27 vs. 0.32 mm2 [100×]; p =.02), beyond adjustment (β =.2; p =.03). Conclusions: Statin treatment over 2 years associated with a significant increase in coronary calcification in patients with higher systemic inflammation, as measured by hs‐CRP. These findings suggest that systemic inflammation plays a role in coronary calcification and further studies should be performed to better elucidate these findings. [ABSTRACT FROM AUTHOR]

Purpose of Review: In this review, we focus on the clinical and epidemiological studies pertaining to systemic and vascular inflammation by positron emission tomography (PET) in patients with chronic inflammatory conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and psoriasis to highlight the importance of chronic systemic inflammation on vascular inflammation by PET in these disease states. Recent Findings: Recent clinical and translation advancements have demonstrated the durable relationship between chronic systemic inflammation and cardiovascular disease (CVD). In chronic inflammatory states, this relationship is robustly evident in the form of increased vascular inflammation, yet traditional risk estimates often underestimate the subclinical cardiovascular risk conferred by chronic inflammation. PET has emerged as a novel, non-invasive imaging modality capable of both quantifying the degree of systemic and vascular inflammation and detecting residual inflammation prior to cardiovascular events. Summary: We begin by demonstrating the role of inflammation in the pathogenesis of atherosclerosis, discussing how PET has been utilized to measure systemic and vascular inflammation and their effect on subclinical atherosclerosis, and finally reviewing recent applications of PET in constructing improved risk stratification for patients at high risk for stroke and CVD. [ABSTRACT FROM AUTHOR]

The purpose of the present research was to comprehensively assess the language abilities of Russian primary-school-aged children with Autism Spectrum Disorder (ASD), varying in non-verbal IQ, at all linguistic levels (phonology, lexicon, morphosyntax, and discourse) in production and comprehension. Yet, the influence of such non-language factors as children's age, the severity of autistic traits, and non-verbal IQ on language functioning was studied. Our results indicate a high variability of language skills in children with ASD (from normal to impaired) which is in line with the previous studies. Interestingly, the number of children with normal language abilities was related to the linguistic levels: according to more complex morphosyntax and discourse tests, fewer children with ASD were within the normal range unlike the results in simpler phonological and lexical tests. Importantly, we found that language abilities were best predicted by non-verbal IQ but were independent from age and the severity of autistic traits. The findings support the claim that formal language assessment of children with ASD needs to include all linguistic levels, from phonology to discourse, for helping speech-language therapists to choose an appropriate therapy target. [ABSTRACT FROM AUTHOR]

Nonlinear feedback shift registers (NFSR) are widely used in cryptography as the source of pseudo-random sequences used in ciphers. The nature of the feedback in a given NFSR affects its output sequence and its statistical quality. The complexity of the problem of restoring the initial state of an NFSR by partially known values of the output is one of the signs of a "good" NFSR. In this regard, we note that the presence of the output affine functions lowers the quality of an NFSR since the corresponding problem is reduced to the solution of a system of linear equations. This paper is concerned with the conditions providing the absence of nontrivial affine functions among NFSR output functions. The obtained theoretical results can be used to improve the effectiveness of experimental methods of finding NFSRs with no affine output functions. [ABSTRACT FROM AUTHOR]

The article analyses Russian peasants' differentiation in the late 19th to early 20th centuries, addressing issues related to transformation of the peasantry's socio-economic standing during the market economy formation period. Combining statistical data analysis and using a multilevel model on peasants' welfare in the province of Simbirsk, we find that a high level of inequality existed in the region at the time of the census; that inequality within a county contributes more toward income inequality than inequality between counties. Based on different statistical resources, we also plot the graphs and calculate the Gini indices for provinces for which data on the distribution of land, horses, and cows by individual farms are available. Our results do not support Chayanov's hypothesis on the correlation between the number of peasant family members and the amount of land in their possession. Our results indicate that communes were losing their 'equalising' function. For most provinces, the Gini index had been rising over time, indicating increasing inequality. Most importantly, this increase occurred in a relatively short period—much faster than in other countries—thereby making Russia more socially and politically vulnerable. [ABSTRACT FROM AUTHOR]

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 − 806C>T genotypes: (*1/*1) −12.0 [−15.0; −8.0], (*1/*17+*17/*17) −7.0 [−14.0; −5.0], P <.001, as well as the results of TDM: (CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P <.001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes. [ABSTRACT FROM AUTHOR]

Electron-rich ruthenium phthalocyanine complexes were evaluated in carbene transfer reactions from ethyl diazoacetate (EDA) to aromatic and aliphatic olefins as well as to a wide range of aromatic, heterocyclic and aliphatic amines for the first time. It was revealed that the ruthenium octabutoxyphthalocyanine carbonyl complex [(BuO)8Pc]Ru(CO) is the most efficient catalyst converting electron-rich and electron-poor aromatic olefins to cyclopropane derivatives with high yields (typically 80–100%) and high TON (up to 1000) under low catalyst loading and nearly equimolar substrate/EDA ratio. This catalyst shows a rare efficiency in the carbene insertion into amine N–H bonds. Using a 0.05 mol% catalyst loading, a high amine concentration (1 M) and 1.1 eq. of EDA, a number of structurally divergent amines were selectively converted to mono-substituted glycine derivatives with up to quantitative yields and turnover numbers reaching 2000. High selectivity, large substrate scope, low catalyst loading and practical reaction conditions place [(BuO)8Pc]Ru(CO) among the most efficient catalysts for the carbene insertion into amines. [ABSTRACT FROM AUTHOR]

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Objectives: Although pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests do not themselves provide the interpretation of data for a physician. Currently, there are approximately two dozen pharmacogenomic clinical decision support systems (CDSSs) used in psychiatry. Implementation of the CDSSs forming the recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects. Methods: The study included 118 male patients (48 in the main group and 70 in the control group) with affective disorders and comorbid alcohol use disorder. To evaluate the efficacy and safety of therapy, several international psychometric scales and rating scales to measure side effects were used. Genotyping was performed using the real-time polymerase chain reaction with allele-specific hybridization. Pharmacogenetic testing results were interpreted using free software PGX2 (LLE Medicine, Russian Federation, Biomedical Cluster of Skolkovo, Moscow Innovative Cluster; www.pgx2.com). Results: The statistically significant differences across the scores on psychometric scales were revealed. For instance, the total score on the Hamilton Rating Scale for Depression by day 9 was 9.0 [8.0; 10.0] for the main group and 11.0 [10.0; 12.0] (p<0.001) for the control group and by day 16 it was 4.0 [2.0; 6.0] for the main group and 14.0 [13.0; 14.0] (p<0.001) for the control group. The UKU Side-Effect Rating Scale (UKU) also revealed a statistically significant difference. The total score on the UKU scale by day 9 was 4.0 [4.0; 5.0] for the main group and 5.0 [5.0; 6.0] (p<0.001) for the control group and by day 16 this difference grew significantly: 3.0 [0.0; 4.2] for the main group and 9.0 [7.0; 11.0] (p<0.001) for the control group. Conclusions: Pharmacogenetic-guided personalization of the drug dose in patients with affective disorders and comorbid alcohol use disorder can reduce the risk of undesirable side effects and pharmacoresistance. It allows recommending the use of pharmacogenetic CDSSs for optimizing drug dosage. [ABSTRACT FROM AUTHOR]

This is a comment on the paper "Hovsgol earthquake 5 December 2014, MW = 4.9 seismic and acoustic effects" by Dobrynina, A.A., Sankov, V.A., Tcydypova, L.R., German, V.I., Chechelnitsky, V.V., and Munkhuu U. (JOSE, 2018, 22, 377–389). The model of infrasonic wave generation from the Mw = 4.9 Hovsgol earthquake of 5 December 2014 suggested by Dobrynina et al. was based on an incorrect traveltime which led to an error in the location of the infrasound source and to misinterpretation of its type. [ABSTRACT FROM AUTHOR]

Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves high-density lipoprotein cholesterol antioxidative capacity in rheumatoid arthritis patients. This editorial refers to 'TNF induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal by monoclonal TNF antibodies' by A. Akhmedov I et al. i , pp. 254-266. [Extracted from the article]

Background: Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) −8.5 [−15.0; −5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) −12.0 [−13.0; −9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 –806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions: Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated. [ABSTRACT FROM AUTHOR]

The biodegradation of compounds with C−F bonds is challenging due to the fact that these bonds are stronger than the C−H bond in methane. In this work, results on the unprecedented reactivity of a biomimetic model complex that contains an N‐bridged diiron‐phthalocyanine are presented; this model complex is shown to react with perfluorinated arenes under addition of H2O2 effectively. To get mechanistic insight into this unusual reactivity, detailed density functional theory calculations on the mechanism of C6F6 activation by an iron(IV)‐oxo active species of the N‐bridged diiron phthalocyanine system were performed. Our studies show that the reaction proceeds through a rate‐determining electrophilic C−O addition reaction followed by a 1,2‐fluoride shift to give the ketone product, which can further rearrange to the phenol. A thermochemical analysis shows that the weakest C−F bond is the aliphatic C−F bond in the ketone intermediate. The oxidative defluorination of perfluoroaromatics is demonstrated to proceed through a completely different mechanism compared to that of aromatic C−H hydroxylation by iron(IV)‐oxo intermediates such as cytochrome P450 Compound I. [ABSTRACT FROM AUTHOR]

Methane hydroxylation by metal-oxo oxidants is one of the Holy Grails in biomimetic and biotechnological chemistry. The only enzymes known to perform this reaction in Nature are iron-containing soluble methane monooxygenase and copper-containing particulate methane monooxygenase. Furthermore, few biomimetic iron-containing oxidants have been designed that can hydroxylate methane efficiently. Recent studies reported that μ-nitrido-bridged diiron(IV)-oxo porphyrin and phthalocyanine complexes hydroxylate methane to methanol efficiently. To find out whether the reaction rates are enhanced by replacing iron by ruthenium, we performed a detailed computational study. Our work shows that the μ-nitrido-bridged diruthenium(IV)-oxo reacts with methane via hydrogen atom abstraction barriers that are considerably lower in energy (by about 5 kcal mol‒1) as compared to the analogous diiron(IV)-oxo complex. An analysis of the electronic structure implicates similar spin and charge distributions for the diiron(IV)-oxo and diruthenium(IV)-oxo complexes, but the strength of the O‒H bond formed during the reaction is much stronger for the latter. As such a larger hydrogen atom abstraction driving force for the Ru complex than for the Fe complex is found, which should result in higher reactivity in the oxidation of methane. [ABSTRACT FROM AUTHOR]

Series of substituted µ‐carbido diruthenium(IV) bisphthalocyaninates [Pc*Ru]2(µ‐C) [where Pc* = tetra‐tert‐butyl‐, octa‐n‐butoxy‐, tetra‐15‐crown‐5‐ and hexa‐n‐butoxy‐mono‐(15‐crown‐5)‐substituted ligands] were synthesized using two alternative approaches – (i) direct metalation of phthalocyanines with Ru3(CO)12 in refluxing o‐dichlorobenzene where [Pc*Ru]2(µ‐C) are formed as by‐products together with monomeric complexes [Pc*Ru](CO) and (ii) dimerization of [Pc*Ru](CO) by dichlorocarbene generated in situ from chloroform and bases (KOH or NMe4OH), which affords target complexes in high yield. Application of the appropriate base – NMe4OH was found to be crucial in the case of synthesis of crown‐substituted µ‐carbido dimers. Reaction of Ru3(CO)12 with the phthalocyanine bearing bulky mesityloxy‐groups yielded solely monomeric complex which could not be dimerized under any studied conditions. Therefore, the influence of nature of peripheral substituents in phthalocyanines on their reactivity in metalation and dimerization reactions was revealed. [ABSTRACT FROM AUTHOR]

The catalytic properties of a chemically stable iron porphyrin MOF were evaluated in a reaction with ethyl diazoacetate. In contrast to its homogeneous counterpart, an Fe-porphyrin-MOF features a different reaction pathway leading to the formation of pyrazoline due to the confinement of catalytic sites within the MOF network. Unexpectedly, a sharp increase of the selectivity from 35% (run 1) to 86% (run 5) occurs upon catalyst recycling. [ABSTRACT FROM AUTHOR]

μ-Nitrido diiron tetrabutylphthalocyanine, (FePctBu4)2N, in combination with H2O2 can perform an efficient defluorination of heavily fluorinated aromatics via an oxidative pathway. To check whether hydroxyl radicals might be involved in this reaction we have compared catalytic activities of (FePctBu4)2N - H2O2 and FeSO4 - H2O2 systems in the transformation of five differently fluorinated benzenes, perfluoronaphthalene, pentafluoropyridine, and eight functionalized perfluorinated benzenes. In sharp contrast with (FePctBu4)2N - H2O2 system, all fluorinated benzene derivatives were completely stable in the presence of FeSO4 and H2O2 at 60 °C during 15 h. Perfluorinated aromatic compounds functionalized with electron-donating or electron-withdrawing groups as well as pentafluoropyridine exhibited very low conversions. These results unambiguously show that Fenton chemistry is not responsible for the oxidative defluorination of highly fluorinated aromatic compounds performed by the (FePctBu4)2N - H2O2 system. [ABSTRACT FROM AUTHOR]

A μ-carbido diruthenium(iv) phthalocyanine complex was prepared for the first time from the free-base octabutoxyphthalocyanine by direct metalation with Ru3(CO)12. The first examples of the catalytic activity of Ru(iv) binuclear phthalocyanines were demonstrated by the cyclopropanation of aromatic olefins and carbene insertion into the N–H bonds of aromatic or aliphatic amines with turnover numbers of 680–1000 and 580–1000, respectively. [ABSTRACT FROM AUTHOR]