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Objective: Some studies have hypothesized that atypical neural synchronization at the delta frequency band in the auditory cortex is associated with phonological and language skills in children with Autism Spectrum Disorder (ASD), but it is still poorly understood. This study investigated this neural activity and addressed the relationships between auditory response and behavioral measures of children with ASD., Methods: We used magnetoencephalography and individual brain models to investigate 2 Hz Auditory Steady-State Response (ASSR) in 20 primary-school-aged children with ASD and 20 age-matched typically developing (TD) controls., Results: First, we found a between-group difference in the localization of the auditory response, so as the topology of 2 Hz ASSR was more superior and posterior in TD children when comparing to children with ASD. Second, the power of 2 Hz ASSR was reduced in the ASD group. Finally, we observed a significant association between the amplitude of neural response and language skills in children with ASD., Conclusions: The study provided the evidence of reduced neural response in children with ASD and its relation to language skills., Significance: These findings may inform future interventions targeting auditory and language impairments in ASD population., Competing Interests: Declaration of competing interest The authors have no conflict to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

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.

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, M age = 10.03, SD = 1.7) and 20 typically developing controls (9 girls, M age = 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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis., Methods and Results: A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; P =0.01), noncalcified burden (rho=0.286; P =0.02), fibro-fatty burden (rho=0.346; P =0.004), and necrotic burden (rho=0.394; P =0.002). A strong relationship between sLOX-1, noncalcified burden ( β =0.19; P =0.03), and fibro-fatty burden ( β =0.29; P =0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1., Conclusions: Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.

Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; P  = .006). Importantly, ox-mtDNA was positively associated with IL-17a (β = 0.25; P  = .03) and low-density granulocytes (β = 0.37; P  = .005) but negatively associated with high-density lipoprotein-cholesterol (β = -0.29; P = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (β = 0.19; P  = .003). Biologic-naïve patients with PSO receiving anti-IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; P  = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; P  = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature., (© 2023 The Authors. Published by Elsevier Inc. on behalf of the Society for Investigative Dermatology.)

Background: Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing., Methods: In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA., Results: Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; β = 0.20; P < 0.0001) and fibrofatty burden (FFB; β = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (β = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL., Conclusion: Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD., Clinicaltrials: gov NCT01621594., Funding: National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.

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., (© 2023. Springer Nature Limited.)

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis., Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA., Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (β = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001)., Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Sorokin is a full-time US government employee., (© 2023 The Authors. Published by Elsevier Ltd.)

APOA-1 is central to the high-density lipoprotein function of reverse cholesterol transport measured by cholesterol efflux capacity. Psoriasis is a systemic inflammatory disease associated with poor cholesterol efflux capacity and accelerated noncalcified coronary burden (NCB) as measured by coronary computed tomographic angiography. In this study, we characterized the relationship between APOA-1, cholesterol efflux capacity, and progression of NCB over 4 years. Consecutively recruited participants with psoriasis underwent coronary computed tomographic angiography for NCB quantification (Medis QAngio, Leiden, The Netherlands) at baseline (n = 310) and at four years (n = 124). Blood was assessed for cardiometabolic biomarkers. The lowest quartile of APOA-1 was associated with cardiometabolic blood markers (insulin, homeostatic model assessment for insulin resistance, and cholesterol efflux capacity) and higher NCB (P < 0.001). The low APOA-1 quartile had higher NCB at 4 years (β = -0.36, P = 0.02) in fully adjusted models. Finally, a 10-unit decrease of APOA-1 was associated with a 16% increase in NCB progression over 4 years (OR = 0.83, 95% confidence interval = 0.70-0.99, P = 0.04). In addition to being associated with cardiometabolic disease, low APOA-1 was associated with more NCB over time. These findings show that low APOA-1 is correlated with initiation and progression of coronary artery disease and may have clinical utility in identifying high-risk populations for development of cardiovascular disease., (Published by Elsevier Inc.)

BACKGROUNDCellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODSWe developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels.RESULTSReceiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001).CONCLUSIONHDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATIONClinicalTrials.gov NCT01621594.FUNDINGNHLBI Intramural Research Program, NIH (HL006095-06).

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.

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 (M age ) = 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, M age  = 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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Persistent skin inflammation and impaired resolution are the main contributors to psoriasis and associated cardiometabolic complications. Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are known to exert beneficial effects on inflammatory response and lipid function. However, a specific role of omega-3 PUFAs in psoriasis and accompanied pathologies are still a matter of debate. Here, we carried out a direct comparison between EPA and DHA 12 weeks diet intervention treatment of psoriasis-like skin inflammation in the K14-Rac1V12 mouse model. By utilizing sensitive techniques, we targeted EPA- and DHA-derived specialized pro-resolving lipid mediators and identified tightly connected signaling pathways by RNA sequencing. Treatment with experimental diets significantly decreased circulating pro-inflammatory cytokines and bioactive lipid mediators, altered psoriasis macrophage phenotypes and genes of lipid oxidation. The superficial role of these changes was related to DHA treatment and included increased levels of resolvin D5, protectin DX and maresin 2 in the skin. EPA treated mice had less pronounced effects but demonstrated a decreased skin accumulation of prostaglandin E 2 and thromboxane B 2 . These results indicate that modulating psoriasis skin inflammation with the omega-3 PUFAs may have clinical significance and DHA treatment might be considered over EPA in this specific disease., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest Dr Mehta is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. Dr González- Cantero has served as a consultant for AbbVie, Janssen, Novartis, Almirall, Celgene, and Leo Pharma receiving grants/other payments. All other authors have no disclosures to report.

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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.

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.

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD), but its neural mechanisms are still poorly understood. Some studies hypothesize that the atypical low-level sensory perception in the auditory cortex accounts for the abnormal language development in these children. One of the potential non-invasive measures of such low-level perception can be the cortical gamma-band oscillations registered with magnetoencephalography (MEG), and 40 Hz Auditory Steady-State Response (40 Hz ASSR) is a reliable paradigm for eliciting auditory gamma response. Although there is research in children with and without ASD using 40 Hz ASSR, nothing is known about the relationship between this auditory response in children with ASD and their language abilities measured directly in formal assessment. In the present study, we used MEG and individual brain models to investigate 40 Hz ASSR in primary-school-aged children with and without ASD. It was also used to assess how the strength of the auditory response is related to language abilities of children with ASD, their non-verbal IQ, and social functioning. A total of 40 children were included in the study. The results demonstrated that 40 Hz ASSR was reduced in the right auditory cortex in children with ASD when comparing them to typically developing controls. Importantly, our study provides the first evidence of the association between 40 Hz ASSR in the language-dominant left auditory cortex and language comprehension in children with ASD. This link was domain-specific because the other brain-behavior correlations were non-significant., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objective: Psoriasis is a systemic inflammatory condition with poor cholesterol transport measured by cholesterol efflux capacity (CEC) that is associated with a heightened risk of cardiovascular disease (CVD). In psoriasis patients, we sought to characterize the lipoprotein profile by size using a novel nuclear magnetic resonance algorithm in patients with low CEC compared to normal CEC., Methods: Lipoprotein profile was assessed using the novel nuclear magnetic resonance LipoProfile-4 deconvolution algorithm. Aortic vascular inflammation (VI) and non-calcified burden (NCB) were characterized via positron emission tomography-computed tomography and coronary computed tomography angiography. To understand the relationship between lipoprotein size and markers of subclinical atherosclerosis, linear regression models controlling for confounders were constructed., Results: Psoriasis patients with low CEC had higher more severe psoriasis ( p = 0.04), VI ( p = 0.04) and NCB ( p = 0.001), concomitant with smaller high-density lipoprotein (HDL) ( p < 0.001) and low-density lipoprotein (LDL) particles ( p < 0.001). In adjusted models HDL size ( β = -0.19; p = 0.02) and LDL size ( β = -0.31; p < 0.001) associated with VI and NCB. Lastly, HDL size strongly associated with LDL size in fully adjusted models ( β = -0.27; p < 0.001)., Conclusion: These findings demonstrate that in psoriasis, low CEC associates with a lipoprotein profile comprised of smaller HDL and LDL particles which correlates with vascular health and may be driving early onset atherogenesis. Further, these results demonstrate a relationship between HDL and LDL size and provide novel insights into the complexities of HDL and LDL as biomarkers of vascular health., Competing Interests: NM has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc., and Novartis receiving grants and/or research funding. AG-C has served as a consultant for Abbie, Janssen, Novartis, Almirall, Celgene and Leo Pharma receiving grants/other payments. TThe remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Berg, Petrole, Li, Sorokin, Gonzalez-Cantero, Playford, Mehta and Teague.)

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., (© 2023. The Author(s).)

Ruthenium phthalocyanine complexes bearing n -OBu substituents in the peripheral or non-peripheral positions are efficient catalysts for the selective double or single carbene insertion to the amine N-H bonds. This complementary reactivity of two Ru complexes can be used for the synthesis of asymmetric tertiary amines and diamines bearing different substituents and has been demonstrated by two examples of readily available primary amines using different carbene precursors in successive reactions.

Psoriasis is a systemic inflammatory disease with an increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (β = 0.27, P = 0.009; n = 125 patients with psoriasis with available coronary computed tomography angiography scans; LRNC analyses; and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At 1 year, in patients receiving biologic therapy (36 of 73 patients had 1-year coronary computed tomography angiography scans available), a 79% reduction in S100A8/A9 levels (‒172 [‒291.7 to 26.4] vs. ‒29.9 [‒137.9 to 50.5]; P = 0.04) and a 0.6 mm 2 reduction in average LRNC area (0.04 [‒0.48 to 0.77] vs. ‒0.56 [‒1.8 to 0.13]; P = 0.02) were noted. These results highlight the potential role of S100A8/A9 in the development of high-risk coronary plaque in psoriasis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). 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-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003)., Interpretation: Together, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA., Competing Interests: NM has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants and other payments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwartz, Parel, Li, Sorokin, Berg, Chen, Dey, Hong, Playford, Sylvester, Teague, Siegel and Mehta.)

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 mm 2 [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., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

BackgroundAlthough traditional lipid parameters and coronary imaging techniques are valuable for cardiovascular disease (CVD) risk prediction, better diagnostic tests are still needed.MethodsIn a prospective, observational study, 795 individuals had extensive cardiometabolic profiling, including emerging biomarkers, such as apolipoprotein E-containing HDL-cholesterol (ApoE-HDL-C). Coronary artery calcium (CAC) score was assessed in the entire cohort, and quantitative coronary computed tomography angiography (CCTA) characterization of total burden, noncalcified burden (NCB), and fibrous plaque burden (FB) was performed in a subcohort (n = 300) of patients stratified by concentration of ApoE-HDL-C. Total and HDL-containing apolipoprotein C-III (ApoC-III) were also measured.ResultsMost patients had a clinical diagnosis of coronary artery disease (CAD) (n = 80.4% of 795), with mean age of 59 years, a majority being male (57%), and about half on statin treatment. The low ApoE-HDL-C group had more severe stenosis (11% vs. 2%, overall P < 0.001), with higher CAC as compared with high ApoE-HDL-C. On quantitative CCTA, the high ApoE-HDL-C group had lower NCB (β = -0.24, P = 0.0001), which tended to be significant in a fully adjusted model (β = -0.32, P = 0.001) and altered by ApoC-III in HDL levels. Low ApoE-HDL-C was significantly associated with LDL particle number (β = 0.31; P = 0.0001). Finally, when stratified by FB, ApoC-III in HDL showed a more robust predictive value of CAD over ApoE-HDL-C (AUC: 0.705, P = 0.0001) in a fully adjusted model.ConclusionApoE-containing HDL-C showed a significant association with early coronary plaque characteristics and is affected by the presence of ApoC-III, indicating that low ApoE-HDL-C and high ApoC-III may be important markers of CVD severity.Trial RegistrationClinicalTrials.gov: NCT01621594.FundingThis work was supported by the NHLBI at the NIH Intramural Research Program.

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. 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., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

DPCAR’s short- and long-term outcomes are highly diverse, while the causes and prevention of ischemic complications are unclear. To assess oncological, surgical, and hemodynamic outcomes of 40 consecutive DPCARs for pancreatic (n37) and gastric tumors (n3) (2009−2021), retrospective analyses of mortality, morbidity, survival, and hemodynamic consequences after DPCAR were undertaken using case history data, IOUS, and pre- and postoperative CT measurements. In postoperative complications (42.5%), the pancreatic fistula was the most frequent event (27%), 90-day mortality was 7.5. With 27 months median follow-up, median overall (OS) and progression-free survival (PFS) for PDAC were 29 and 18 months, respectively; with 1-, 3-, and 5-years, the OS were 90, 60, and 28%, with an R0-resection rate of 92.5%. Liver and gastric ischemia developed in 0 and 5 (12.5%) cases. Comparison of clinical and vascular geometry data revealed fast adaptation of collateral circulation, insignificant changes in proper hepatic artery diameter, and high risk of ischemic gastropathy if the preoperative diameter of pancreaticoduodenal artery was <2 mm. DP CAR can be performed with acceptable morbidity and survival. OS and RFS in this super-selective cohort were compared to those for resectable cancer. The changes in the postoperative arterial geometry could explain the causes of ischemic complications and determine directions for their prevention.

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm 2 ] vs. 1.0 [0.40 mm 2 ]), fibrofatty (0.23 [0.15 mm 2 ] vs. 0.11 [0.087 mm 2 ]), and lipid-rich necrotic core (4.3 [2.3 mm 2 ] vs. 3.0 [1.7 mm 2 ]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (β = 0.28; P < 0.001), fibrofatty (β = 0.49; P < 0.001), and lipid-rich necrotic core (β = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis., (Published by Elsevier Inc.)

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states., Competing Interests: Declaration of competing interest, (Published by Elsevier Inc.)

Background and Aims: Psoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort., Methods: Multimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18 F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA)., Results: Splenic and BM 18 F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18 F-FDG uptake associated with higher total coronary burden (β = 0.37; p<0.001), NCB (β = 0.39; p<0.001), and LRNC (β = 0.32; p<0.001) in fully adjusted models. Similar associations were seen for BM 18 F-FDG uptake in adjusted models (β = 0.38; β = 0.41; β = 0.24; respectively, all p<0.001)., Conclusions: Heightened splenic and BM uptake of 18 F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis., (Published by Elsevier B.V.)

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Abnormal language development in both expressive and receptive domains occurs in most children with Autism Spectrum Disorder (ASD), although the language deficit is not a core symptom of ASD. However, previous studies disagree on the difference in the degree of impairment between expressive and receptive language in ASD. Existing research has concentrated on vocabulary and 'global expressive and receptive language', often using parental reports for language assessment. Moreover, most of these studies have focused on toddlers and preschoolers with ASD, whereas data from school-aged children with ASD are very limited. At the same time, the age of children might account for the inconsistencies across publications on expressive-receptive language difference in children with ASD., Aims: The goal of the study was to directly compare the expressive and receptive language abilities of Russian primary-school-aged children with ASD (7-11 years old) at the levels of vocabulary, morphosyntax, and discourse., Methods: 82 children with ASD participated in language testing. We used tests from the Russian Child Language Assessment Battery in order to assess vocabulary, morphosyntax, and discourse in expressive and receptive domains., Results: Our results revealed different expressive and receptive patterns, depending on the linguistic level and tests complexity. Importantly, we showed that children's non-verbal IQ partly accounted for the difference between production and comprehension abilities., Conclusions: The expressive-better-than-receptive pattern in language has been considered by some authors as the unique hallmark of ASD. However, several studies, including our own, show that this is not a universal characteristic of ASD. We also revealed that expressive and receptive language patterns differed depending on the linguistic level, children's non-verbal IQ, and assessment tools., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Understand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis., Methods: We performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASAT adjBMI )., Results: In women, there was a positive correlation between ASAT adjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASAT adjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASAT adjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (β= -0.17; p=.03, β= -0.20; p=.03, respectively), but not women (β= -0.06; p=.57, β= 0.09; p=.49, respectively) with psoriasis., Conclusions: For a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation., (© 2021 Published by Elsevier B.V.)

Plant molecular farming, that is, using plants as hosts for production of therapeutic proteins and high-value compounds, has gained substantial interest in recent years. Chloroplasts in particular are an attractive subcellular compartment for expression of foreign genes. Here, we present a new method for transgene introduction and expression in chloroplasts that, unlike classically used approaches, does not require transgene insertion into the chloroplast genome. Instead, the transgene is amplified as a physically independent entity termed a 'minichromosome'. Amplification occurs in the presence of a helper protein that initiates the replication process via recognition of specific sequences flanking the transgene, resulting in accumulation of extremely high levels of transgene DNA. Importantly, we demonstrate that such amplified transgenes serve as a template for foreign protein expression, are maintained stably during plant development and are maternally transmitted to the progeny. These findings indicate that the minichromosome-based approach is an attractive tool for transgene expression in chloroplasts and for organelle genome engineering., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB)., Methods: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA., Results: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m 2.7 (3.8), 2nd tertile:25.5 g/m 2.7 (3.8), 3rd tertile:27.7 g/m 2.7 (5.5), p <0.001]. Both GlycA (β=0.24, p  = 0.001) and NCB (β=0.50, p <0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (β=0.25, p  = 0.002)., Conclusions: Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass., Competing Interests: Dr. Mehta is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc., and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institutes of Health receiving grants and/or research funding. All other authors declare no conflicts of interests in relation to the work presented in this manuscript., (Published by Elsevier B.V.)

Background: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome., Objective: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis., Methods: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria., Results: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (β = .31; P < .001) and its individual factors of waist circumference (β = .33; P < .001), triglyceride levels (β = .17; P = .005), blood pressure (β = .18; P = .005), and fasting glucose (β = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden., Limitations: Observational nature with limited ability to control for confounders., Conclusions: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk., Competing Interests: Conflicts of interest Dr Siegel reports personal fees from AbbVie, Janssen, and Lilly outside the submitted work. Dr Gelfand reports personal fees from Abcentra, BMS, Boehringer Ingelheim, Cara (data safety monitoring board [DSMB]), GSK, Lilly (data monitoring committee), Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), Dr. Reddy’s Labs, Happify, Inc, Mindera Dx, Pfizer Inc, and Sun Pharma and grants from AbbVie, Boehringer Ingelheim, Janssen, Novartis Corp, Celgene, Ortho Dermatologics, and Pfizer Inc outside the submitted work. Dr Mehta is a full-time US government employee and has received research grants from AbbVie, Janssen, Novartis Corp, and Celgene outside the submitted work. Drs Zhou, Dey, Sorokin, Teague, Sajja, Shanbhag, Chen, Bluemke, and Playford, and Authors Teklu, Kapoor, Patel, Manyak, Erb-Alvarez, Abdelrahman, Reddy, Uceda, Lateef, Scott, Prakash, Svirydava, Parel, Rodante, and Keel have no conflicts of interest to declare., (Published by Elsevier Inc.)

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.

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (β = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (β = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (β = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increased development of metabolic abnormalities including obesity and dyslipidemia, as well as increased cardiovascular disease (CVD) risk. Shared pathophysiological mechanisms linking psoriasis to CVD include altered immune activation, elevated chronic systemic inflammation, and lipoprotein dysfunction characterized by oxidative damage to lipids and apolipoproteins., Objective: This review aims to provide evidence-based proof for existing relationships between psoriatic inflammation, lipid oxidation, and increased CVD risk., Methods: We included review articles and original research papers, published between 1980 and 2020, using the following key words: psoriasis, oxidized lipids, oxidation, dyslipidemia, and inflammation., Results: Systemic inflammation underlying psoriasis leads to increased skin accumulation of pro-inflammatory oxidized lipids, derived from the omega-6 fatty acids, along with counteracting anti-inflammatory lipid mediators, products of the omega-3 polyunsaturated fatty acids. Imbalance in these metabolites culminates in impaired inflammation resolution and results in multisystemic biological alterations. Sustained systemic inflammation results in excessive lipid oxidation, generating proatherogenic oxidized low- and high-density lipoproteins. Together, these pathophysiological mechanisms contribute to increased CVD risk associated with psoriasis disease., Conclusion: Available anti-inflammatory treatment showed promising clinical results in treating psoriasis, although further research is warranted on managing associated dyslipidemia and establishing novel cardiometabolic markers specific for both skin and vascular pathology., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.