Peripheral Structure Research Articles

Effect of omalizumab treatment on peripheral nerves in patients with chronic spontaneous urticaria

Aim: Chronic spontaneous urticaria (CSU) is characterised by itchy, red and raised lesions that appear as an attack without any cause and last for six weeks or longer. Omalizumab is a humanised monoclonal antibody that selectively binds to the Ce3 moiety of circulating IgE and is indicated for the treatment of resistant CSU. In this study, we aimed to investigate whether there was peripheral nervous system involvement in patients with chronic urticaria receiving omalizumab treatment. Methods: Forty-seven patients who were treated with omalizumab for CSU were included in the study. Electrophysiological measurements were performed following a neurological examination before treatment and at three months after omalizumab treatment. In nerve conduction tests, eight different nerves were studied in four extremities (total 16 nerves). During these studies, two motor and two sensory nerves (median and ulnar) in the upper extremities, and two motor (tibial and common peroneal) and two sensory nerves (sural and superficial peroneal) in the lower extremities were analysed. Results: No pathological electrophysiological findings supporting neuropathy were detected in any of the measurements performed before and after treatment. When the nerve conduction velocity, amplitude and latency values ​​of all examined nerves were compared, no significant difference was found between the pre- and post-treatment values. Conclusions: It can be considered that omalizumab has no effect on peripheral nerves, and it is a safe and well tolerated agent in terms of both peripheral nerves and neurological structure.

Oxaliplatin Neuropathy: Predictive Values of Skin Biopsy, QST and Nerve Conduction.

Oxaliplatin-induced peripheral neuropathy negatively affects the quality of life for patients with gastrointestinal cancers and may cause neuropathic pain. Measures of peripheral nerve structure or function, such as intraepidermal nerve fiber density (IENFD) during treatment could reduce neuropathy severity through individualized dose reduction. The aim was to evaluate the predictive values of IENFD, quantitative sensory testing (QST), and nerve conduction studies (NCS) for significant neuropathy and neuropathic pain. Fifty-five patients were examined prospectively before, during, and six months following treatment using skin biopsies, QST and NCS. Clinically significant neuropathy six months after treatment was defined as reduced Total Neuropathy Score of more than five and neuropathic pain was assessed according to International Association for the Study of Pain criteria. Thirty patients had a clinically significant neuropathy, and 14 had neuropathic pain. Vibration detection threshold (VDT) before treatment was correlated with clinically significant neuropathy six months after treatment (OR 0.54, p = 0.01) and reductions in cold detection threshold (CDT) after 25% of treatment (OR 1.38, p = 0.04) and heat pain threshold (HPT) after 50% of treatment (OR 1.91, p = 0.03) with neuropathic pain. Cut off values of 5 for baseline VDT and changes of more than -0.05 °C and -0.85 °C in CDT and HPT were estimated. Sensitivity and specificity was low to moderate. There was no correlation between changes in IENFD or NCS and significant neuropathy or neuropathic pain. Vibration detection thresholds and thermal detection thresholds may be useful for prediction of clinically significant and painful neuropathy, respectively. However, low to moderate sensitivity and specificity may limit the predictive value in clinical practice.

Impact of the metabolic syndrome on peripheral nerve structure and function in type 2 diabetes.

There is a strong association between the metabolic syndrome in diabetes and the development of peripheral neuropathy; however, the pathophysiological mechanisms remain unknown. Participants with type 2 diabetes and metabolic syndrome (T2DM/MetS, n=89) and type 2 diabetes alone (T2DM; n=59) underwent median nerve ultrasound and excitability studies to assess peripheral nerve structure and function. A subset of T2DM/MetS (n=24) and T2DM (n=22) participants underwent confocal microscopy to assess central and inferior whorl corneal nerve structure. Neuropathy severity was assessed using the modified Toronto Clinical Neuropathy Score (mTCNS). Diabetes groups were similar for age, sex distribution, diabetes duration, hemoglobin A1c , insulin treatment, and renal function. Sixty healthy controls similar for age and sex distribution were recruited for comparison. Participants with T2DM/MetS manifested with a greater mTCNS compared to T2DM (p<0.05). Median nerve cross-sectional area was larger in the T2DM/MetS group compared to the T2DM cohort (p<0.05). Participants with T2DM/MetS had reductions in central (all p<0.01) and inferior whorl (all p<0.05) nerve measures. Compared to T2DM, the T2DM/MetS group demonstrated more severe changes in nerve excitability measures, which was due to reduced sodium channel permeability and sodium-potassium pump function. In comparison, only sodium channel permeability was reduced in the T2DM group. Compared to participants with type 2 diabetes alone, those with diabetes and metabolic syndrome manifested greater alterations in peripheral nerve structure and function, which may be due to reduced function of the sodium-potassium pump.

Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population.

Aims Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of non-invasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality.Methods and results In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N=12 599) and fingertip peripheral arterial tonometry (N=11 125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank <0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality [hazard ratio (HR) per standard deviation increase, 0.86, 95% confidence interval (95% CI), 0.79–0.94; P=0.0009]. After exclusion of individuals with prevalent CVD the association was no longer statistically significant in multivariable-adjusted models (HR 0.91, 95% CI 0.81–1.02; P=0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors.Conclusions In our cohort, non-invasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident CVD or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.

The hyperbolic geometry of financial networks

Based on data from the European banking stress tests of 2014, 2016 and the transparency exercise of 2018 we construct networks of European banks and demonstrate that the latent geometry of these financial networks can be well-represented by geometry of negative curvature, i.e., by hyperbolic geometry. Using two different hyperbolic embedding methods, hydra+ and Mercator, this allows us to connect the network structure to the popularity-vs-similarity model of Papdopoulos et al., which is based on the Poincaré disc model of hyperbolic geometry. We show that the latent dimensions of ‘popularity’ and ‘similarity’ in this model are strongly associated to systemic importance and to geographic subdivisions of the banking system, independent of the embedding method that is used. In a longitudinal analysis over the time span from 2014 to 2018 we find that the systemic importance of individual banks has remained rather stable, while the peripheral community structure exhibits more (but still moderate) variability. Based on our analysis we argue that embeddings into hyperbolic geometry can be used to monitor structural change in financial networks and are able to distinguish between changes in systemic relevance and other (peripheral) structural changes.

Integrated model for energy consumption information of complex building based on BIM technology

In order to solve the problem of poor accuracy of energy consumption test in traditional complex building energy consumption information synthesis model, a BIM-based complex building energy consumption information synthesis model is proposed. The dynamic visual programming method is used to set and select the parameters of the complex building's peripheral structure. According to the network terminal, the basic data of energy consumption of the comprehensive architecture are obtained. The basic data of cloud computing are simulated, quantitative research and regression analysis are carried out. BIM technology is used to complete the construction of comprehensive model of energy expenditure information for complex buildings. The experimental results show that the root mean square error of the model is small, only 2.5%. The variation range of the measured coefficients is 0.6-0.8, which shows that the model has high test accuracy.

Integrated model for energy consumption information of complex building based on BIM technology

In order to solve the problem of poor accuracy of energy consumption test in traditional complex building energy consumption information synthesis model, a BIM-based complex building energy consumption information synthesis model is proposed. The dynamic visual programming method is used to set and select the parameters of the complex building's peripheral structure. According to the network terminal, the basic data of energy consumption of the comprehensive architecture are obtained. The basic data of cloud computing are simulated, quantitative research and regression analysis are carried out. BIM technology is used to complete the construction of comprehensive model of energy expenditure information for complex buildings. The experimental results show that the root mean square error of the model is small, only 2.5%. The variation range of the measured coefficients is 0.6-0.8, which shows that the model has high test accuracy.

Effect of sensory nerve conduction studies of median and ulnar nerve: Height and body mass index

Background: Nerve conduction studies (NCSs) have been contributed to a better understanding of normal peripheral nerve structure and function and understanding of various peripheral neuropathies. Height and body mass index (BMI) are influencing activity on nerve conduction velocities (NCVs). Median and ulnar nerves in upper limb were tested commonly for sensory NCSs (SNCSs). Multiple variables such as age; gender; BMI; and height influence NCS parameters. Therefore, this present study was assessing effect of height and BMI on SNCS of median and ulnar nerves among healthy subjects. Aim and Objective: This study aims to study and correlate SNCS of median and ulnar nerve with height and BMI. Materials and Methods: After taking permission from Human Ethics Committee, Government Medical College, Bhavnagar, 91 normal healthy subjects of both genders, age 15–65 years, were participated for SNCS of median and ulnar nerve of both hands using RMS Aleron electromyography/NCV EPII Mark 401, 4-Channels instrument. SNCSs of different parameters were taken out and analyzed for statistical significance. Results: P value is not statistically significant in all groups divided on the basis of height except I versus III and II versus III height group in the left ulnar nerve. P value is not statistically significant in all groups divided on the basis of BMI group. Positive correlation is seen in height with latency and negative correlation is seen in height with sensory NCV (SNCV) and amplitude which was similar to other study 3, 6, 13 and no uniform correlation in height with duration. A positive correlation is seen in BMI with SNCV and negative correlation is seen in BMI with duration. There is no uniform correlation in BMI with latency and amplitude. Conclusion: SNCV is slowing as height and BMI increases.

INFORMATION AND LIBRARY RESOURCES ON ISSUES OF PEDAGOGY AND EDUCATION (ON THE MATERIALS OF LIBRARY SITES OF UNIVERSITIES OF GERMANY)

The Results of the information review of the materials of the Websites of the Libraries of German Universities are presented. A sample of eleven libraries was formed, the selection criteria for which were the following indicators: The Universality of the acquisition of the fund; the presence in the structure of information resources of collections of rare, handwritten and old printed publications; participation in the network of library institutions located on campuses (libraries), library funds are completed with documents of a narrow-specialized direction. The practical problems of creating Information and library resources on education and pedagogy are highlighted; the defining components of the content and composition of the sites of these libraries are described. The Directions of formation of resources of the researched segment of libraries of universities with single - circuit and double – circuit structure are revealed and generalized. In universities of the first type, libraries perform the functions of the central and peripheral library structure, as a rule, information and library resources on pedagogy and education are exported from OPAC (Online public access Catalog) and KVK (Karlsruher Virtuelle Katalog). In universities with a two-circuit structure of libraries, the site presents resources for educational and pedagogical purposes, in library departments, resources of specialized direction are reflected. The qualitative characteristics of the portals of educational and pedagogical issues, placed on the basis of the DBIS information System, are given. features of the formed information resources on the basis of various information sources, according to needs of users, minimizing information overload by optional («superfluous») information flows are revealed. The directions of content formation, prospects of development of the portal «Pädagogik» are covered.

Меркантилизм, мир-системная гегемония и протоанализ национальной конкурентоспособности

The article represents in a world-system retrospect the European mercantilist discourse versus William Petty’s “Political Arithmetic”. It is revealed that the elevation of the Dutch Republic (the United Provinces of the Northern Netherlands) as the first hegemonic power of the emerging capitalist world-system during 17th century, made this land the “reference area” of the balance-of-trade doctrine. It is demonstrated that W. Petty gave the most insightful and profound explanations of the commercial success and industrial competitiveness of Holland, including various structural and institutional aspects. It is exposed that, unlike other proponents of the doctrine of an active trade balance, Petty did not limit himself to characterizing the Dutch leadership in shipbuilding and navigation and transit trade. He recorded the advanced development in Holland of diversified agriculture (rotation of crops, dairy farming and industrial crops), energy (wind mechanization) and the manufacturing industry (especially on far-delivered raw materials). It is explained in the context of world-systems approach that Petty reflected the core–peripheral structure of the emerging system of the international division of labor and noted that the fastening of the specialization of European countries East of the Elbe in laborious agriculture was the seamy side of the Dutch domination in oversea trade and their specialization in highly profitable industries. In comparison with M. Porter’s “diamond of national competitive advantages”, it was explicated that W. Petty in “Political Arithmetic”, using the example of Holland, actually analyzed three of the four main elements of national competitiveness: 1) parameters of production factors; 2) segment structure and other demand conditions; 3) the presence in the country of related or supporting industries that are competitive in the international market. The foresight of Petty as a forecaster is noted, which allowed him to discern the essential signs of the rise of England as a new hegemonic power in the next systemic cycle of capitalist accumulation. The distinctive features of England as the reference area of Physiocracy and classical political economy are briefly characterized, in contrast to the Dutch reference area of the trade balance doctrine.

Enhanced Fenton-like efficiency by the synergistic effect of oxygen vacancies and organics adsorption on FexOy-d-g-C3N4 with Fe‒N complexation

d-g-C3N4-Fe composites was prepared via a self-assembly and calcination process. According to measurements and density functional theory (DFT) computations, the complexation of iron and pyridinic N of g-C3N4 (Fe‒N) occurred with Fe(III)-π interaction, causing more oxygen vacancies (OVs) with more electrons in iron oxides. In the catalyst air-saturated suspension, the adsorbed pollutants complexed surface Fe(III) through their hydroxyl group donated electrons to around OVs, reducing the surface Fe(III) to Fe(II) and were destructed by Fe(III)-π interaction of the complexation. The addition of H2O2 mainly acted as acceptor being reduced •OH at the OV centers, causing higher degradation rate of pollutants due to both •OH and the surface reaction. However, for the adsorbed hydrophobic pollutants onto the sites of peripheral structure in g-C3N4, H2O2 was mainly decomposed into O2 by the synergistic effect of iron species and OVs. Therefore, the catalyst exhibited high Fenton-like efficiency for the degradation of hydroxyl-containing pollutants and hydrophobic pollutants mixing with the former. Our results demonstrate that the Fe(III)-π interaction could carry out the oxidation of pollutants on the catalyst surface, decreasing the consumption of H2O2, and the role of OVs depends on pollutant adsorption patterns.

Comprehensive assessment of cardiovascular structure and function and disease risk in middle-aged ultra-endurance athletes

Background and aimsRecent studies suggest that long-term endurance training may be damaging to the heart, thus increasing cardiovascular disease (CVD) risk. However, studies utilizing cardiac imaging are conflicting and lack measures of central and peripheral vascular structure and function, which are also independently predictive of CVD events. MethodsWe performed a comprehensive assessment of cardiovascular structure and function in long-term (≥ 10 years) ultra-endurance athletes (ATH, 14 M/11 F, 50 ± 1 y) and physically active controls (CON, 9 M/9 F, 49 ± 2 y). ResultsAs expected, left ventricular mass and end-diastolic volume (echocardiography) were greater in ATH vs CON, whereas there was no difference in cardiac function at rest. Coronary artery calcium scores (computed tomography) were not statistically different between groups. There was no evidence of myocardial fibrosis (contrast magnetic resonance imaging) in any subject. Aortic stiffness (carotid-femoral pulse wave velocity) was lower in ATH vs CON (6.2 ± 0.2 vs 6.9 ± 0.2 m/s, p < 0.05), whereas carotid intima-media thickness (ultrasound) was not different between groups. Peripheral vascular endothelial function (flow-mediated vasodilation of the brachial artery) and microvascular function (peak blood velocity) in response to 5 min of forearm ischemia were not different between groups. Furthermore, there was no difference in 10-year coronary heart disease risk (ATH; 2.3 ± 0.5 vs CON; 1.6 ± 0.2%, p > 0.05). ConclusionsOur data indicate that middle-aged ultra-endurance ATH do not have marked signs of widespread cardiovascular dysfunction or elevated CHD risk compared to CON meeting physical activity guidelines.

Initiator or Intermediary? A Case Study on Network Relation of Environmental Regulatory Capture in China.

Behind the environmental regulatory capture (ERC) lies a complex network of interactions and interests. Identifying the roles of stakeholders in the ERC network and their behavioral motives can illuminate the mechanism of ERC incidents, and provide policy recommendations for reducing other types of regulatory capture. Drawing on the regulatory capture and principal-agent theories, this study develops a triple-layer principal-agent model of environmental regulation practices in China. We further conduct a social network analysis (SNA) on the ERC case in the Environmental Protection Bureau (EPB) of Bobai County, Guangxi Province, China to illustrate the hidden interactions and interest transmission structure among stakeholders in ERC. The results show that the ERC presents obvious characteristics of concealment and complexity, and individual capture often evolves into collective capture. Different stakeholders are in different positions and play different roles in the network. The environmental regulatory authority, the commissioned regulatory agency, and the agency of enterprises form the core power circle of the ERC network, in which the first two play the role of intermediary and the latter acts as an initiator. They together occupy the structural hole position and dominate the evolution of the ERC network. Peripheral structure stakeholders play the role of “bridge” and profit from the expanding ERC network. It is recommended that the principle of decentralization and the balance of power must be taken into consideration. Quantitative analysis methods such as SNA should be applied to clarify accountability when punishing responsible persons. More subjects are also encouraged to participate in environmental regulations and report illegal acts actively. Finally, a blacklist system should be established in the field of environmental protection for regulating the professional and social morality of all parties.

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers.Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; NMDD cases = 271, Ncontrols = 609).Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, PFDR = 6 × 10−4) and energy levels (β = 0.101, PFDR = 0.027), along with reduced entorhinal cortex thickness (β = −0.095, PFDR = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, βFA= −0.12 to −0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = −0.15 versus βaverage = 0.01 respectively).These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.

A case study of the pyramid scheme in China based on communication network

This paper discusses the structure and endogenous process of a pyramid scheme organization. While most previous studies focus on the operation mode of pyramid scheme and its destruction to social economy, we investigate the non-trivial microstructure and endogenous interaction within the pyramid scheme. By using the motif analysis and the exponential random graph model (ERGM), we conducted an in-depth study on the communication network of a specific pyramid scheme organizations. Through integration of the communication networks with the organizational hierarchical structure, we explore what is the typical structure of a pyramid scheme organization and how do people interact with each other in the organization. The results show that the pyramid scheme communication network is a sparse network and obeys a core–peripheral structure. In terms of personnel interactions, pyramid scheme communication network presents significant homogeneity, with minimal cross-community and cross-hierarchy interactions.

Influence of hormonal contraceptives on peripheral vascular function and structure in premenopausal females: a review.

Hormonal contraceptives are one of the most widely used prescriptions for premenopausal women worldwide. Although the risk of venous and arterial cardiovascular events (e.g., deep vein thrombosis, arterial clotting) with hormonal contraceptives, specifically oral contraceptive pills, has been established, the literature on early risk indicators, such as peripheral vascular structure and function has yet to be consolidated. The purpose of this review is to summarize literature examining the impact of different hormonal contraceptives on vascular function and structure, including consideration of phasic differences within a contraceptive cycle, and to propose future directions for research. It is evident that hormonal contraceptive use appears to impact both macrovascular and microvascular endothelial function, with phasic differences in some contraceptive types dependent on progestin type, the ratio of ethinyl estradiol-to-progestin, and route of administration. However, hormonal contraceptives do not appear to impact smooth muscle function in the macrovasculature or microvasculature, arterial stiffness, or vascular structure. Underlying mechanisms for observed impacts and areas of future research are discussed. This review provides timely consolidation of research examining hormonal contraceptives and peripheral vascular function and structure and provides guidance on considerations for hormonal contraceptive use in study design.

Effect of different volumes of 0.375% ropivacaine on diaphragmatic paralysis by supraclavicular brachial plexus block under ultrasound guidance

Supraclavicular brachial plexus block (SCBPB) is a traditional anesthesia technique widely used in upper limb surgery. Ultrasound-guided SCBPB shows the peripheral structure and dynamic local anesthetic diffusion and can greatly shorten the anesthesia operation time, increase the success rate of anesthesia, and reduce the incidence of complications. However, it can still block the phrenic nerve and paralyze the diaphragm, which can be difficult to avoid. This study investigated two different volumes of the same concentration of ropivacaine used in ultrasound-guided SCBPB, and compared the effects on the incidence of diaphragmatic paralysis, pulse oxygen saturation (SpO2) and lung function in patients. The study group comprised 103 patients who were to undergo surgery on the right forearm or right hand. They were randomly divided into two groups: group A were given 20 mL 0.375% ropivacaine, and group B were given 30 mL 0.375% ropivacaine. We recorded the SpO2, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) before and 30 min after the block, and evaluated whether the patient had combined respiratory dysfunction according to the lung function indicators. We also recorded the maintenance time of anesthesia, the recovery time of motor block, and evaluated the effect of anesthesia. The time to onset of motor block in group B was significantly shorter than in group A (P<0.05). After 30 min of blockade, the rate of diaphragmatic paralysis in group B under different breathing states was significantly higher than that of group A (P<0.05); after 30 min of blockade, the rate of partial paralysis of the diaphragm with forced breathing was significantly higher than the rate of partial paralysis of the diaphragm with calm breathing (P<0.05). Both 20 and 30 mL of 0.375% ropivacaine can achieve the ideal brachial plexus block with ultrasound-guided SCBPB, but compared with 20 mL of 0.375% ropivacaine, 30 mL of 0.375% ropivacaine is more likely to cause diaphragmatic paralysis.

SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.

BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe.MethodsSTZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV).FindingsSP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice.InterpretationOur work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN.FundingPlease see funding sources.

Multivariate relationships between peripheral inflammatory marker subtypes and cognitive and brain structural measures in psychosis.

Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n=79; Psychotic Bipolar disorder, n=61) and matched healthy controls (HC, n=60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.

Simulation of peripheral coarse grain structure during hot extrusion of AA7020 aluminum alloy

In this investigation, microstructural evolution during hot extrusion of AA7020 aluminum alloy has been simulated using multiscale physical models, finite element and Monte Carlo simulation. In addition to predicting the evolution of grain structure in different regions during and after hot extrusion, the framework was capable of indicating the origin of the nucleation of recrystallized grains, which is of fundamental importance for the understanding of the effects of various types of dynamic and static recrystallization events on the resultant microstructure after hot extrusion. To validate the framework, model predictions for peripheral coarse grain (PCG) structure was compared with experimental results. It was found that the operating mechanism of PCG formation depends mainly on the local deformation history. As a result of moderate deformation, the PCG structure was mostly composed of grains nucleated in the static mode after the extrudate left the die orifice and only a few grains in the PCG structure originated from dynamic recrystallization. Local large deformation could, however lead to a fully dynamically recrystallized grain structure and the PCG structure resulted from normal grain growth of dynamically recrystallized grains.