Upregulation of Glutamate Receptors in Rat Cerebral Cortex with Neuronal Migration Disorders

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immunohistochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs

Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fi llers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specifi c degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fi bers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specifi c biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.  The research leading to this work has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS, and from QREN (ON.2 - NORTE-01-0124-FEDER-000016) cofinanced by North Portugal Regional Operational Program (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Robust People Tracking Using an Adaptive Sensor Fusion between a Laser Scanner and Video Camera

Robust detection and tracking in a smart environment have numerous valuable applications. In this paper, an adaptive sensor fusion method which automatically compensates for bias between a laser scanner and video camera is proposed for tracking multiple people. The proposed system comprises five components: blob extraction, object tracking, scan data clustering, a cluster selection, and updating the bias. Based on the position of object in an image, the proposed system determines the candidate scan region. Then, the laser scan data in the candidate region of an object is clustered into several clusters. A cluster which has maximum probability as an object is selected using a discriminant function. Finally, a horizontal bias between the laser scanner and video camera is updated based on the selected cluster information. To evaluate the performance of the proposed system, we show error analysis and two applications. The results confirm that the proposed system can be used for a real-time tracking system and interactive virtual environment

Translocation, Rejection and Trapping of Polyampholytes

Polyampholytes (PA) are a special class of polymers comprising both positive and negative monomers along their sequence. Most proteins have positive and negative residues and are PAs. Proteins have a well-defined sequence while synthetic PAs have a random charge sequence. We investigated the translocation behavior of random polyampholyte chains through a pore under the action of an electric field by means of Monte Carlo simulations. The simulations incorporated a realistic translocation potential profile along an extended asymmetric pore and translocation was studied for both directions of engagement. The study was conducted from the perspective of statistics for disordered systems. The translocation behavior (translocation vs. rejection) was recorded for all 220 sequences comprised of N = 20 charged monomers. The results were compared with those for 107 random sequences of N = 40 to better demonstrate asymptotic laws. At early times, rejection was mainly controlled by the charge sequence of the head part, but late translocation/rejection was governed by the escape from a trapped state over an antagonistic barrier built up along the sequence. The probability distribution of translocation times from all successful attempts revealed a power-law tail. At finite times, there was a population of trapped sequences that relaxed very slowly (logarithmically) with time. If a subensemble of sequences with prescribed net charge was considered the power-law decay was steeper for a more favorable net charge. Our findings were rationalized by theoretical arguments developed for long chains. We also provided operational criteria for the translocation behavior of a sequence, explaining the selection by the translocation process. From the perspective of protein translocation, our findings can help rationalize the behavior of intrinsically disordered proteins (IDPs), which can be modeled as polyampholytes. Most IDP sequences have a strong net charge favoring translocation. Even for sequences with those large net charges, the translocation times remained very dispersed and the translocation was highly sequence-selective

Longitudinal trajectories of sedation level and clinical outcomes in patients who are mechanically ventilated based on a group-based trajectory model: a prospective, multicentre, longitudinal and observational study in Korea

Objectives Changes in sedation levels over a long time in patients who are mechanically ventilated are unknown. Therefore, we investigated the long-term sedation levels of these patients by classifying them into different longitudinal patterns.Design This was a multicentre, prospective, longitudinal, and observational study.Setting Twenty intensive care units (ICUs) spanning several medical institutions in Korea.Participants Patients who received mechanical ventilation and sedatives in ICU within 48 hours of admission between April 2020 and July 2021.Primary and secondary outcome measures The primary objective of this study was to identify the pattern of sedation practice. Additionally, we analysed the associations of trajectory groups with clinical outcomes as the secondary outcome.Results Sedation depth was monitored using Richmond Agitation-Sedation Scale (RASS). A group-based trajectory model was used to classify 631 patients into four trajectories based on sedation depth: persistent suboptimal (13.2%, RASS ≤ −3 throughout the first 30 days), delayed lightening (13.9%, RASS ≥ −2 after the first 15 days), early lightening (38.4%, RASS ≥ −2 after the first 7 days) and persistent optimal (34.6%, RASS ≥ −2 during the first 30 days). ‘Persistent suboptimal’ trajectory was associated with delayed extubation (HR: 0.23, 95% CI: 0.16 to 0.32, p<0.001), longer ICU stay (HR: 0.36, 95% CI: 0.26 to 0.51, p<0.001) and hospital mortality (HR: 13.62, 95% CI: 5.99 to 30.95, p<0.001) compared with ‘persistent optimal’. The ‘delayed lightening’ and ‘early lightening’ trajectories showed lower extubation probability (HR: 0.30, 95% CI: 0.23 to 0.41, p<0.001; HR: 0.72, 95% CI: 0.59 to 0.87, p<0.001, respectively) and ICU discharge (HR: 0.44, 95% CI: 0.33 to 0.59, p<0.001 and HR: 0.80, 95% CI: 0.65 to 0.97, p=0.024) compared with ‘persistently optimal’.Conclusions Among the four trajectories, ‘persistent suboptimal’ trajectory was associated with higher mortality

Development of a Dual-Modality Gamma-ray/Fast Neutron Imaging System for Air Cargo Inspection

High-energy radiation sources have provided a strong security inspection capability using a non-invasive imaging system. The use of multiple radiation sources in one imaging system can also lead to a more powerful system that can classify various materials compared to using a single radiation source. The Advanced Radiation Technology Institute of Korea Atomic Energy Research Institute has developed an air cargo inspection system using multiple radiation sources such as fast neutrons and gamma-rays to classify the plastics, metals, and organics among various sample materials. The fast neutron beam with an energy of 14.1 MeV, generated using the D-T neutron generator, and the gamma-ray beam with an energy of 6 MeV, generated by an electron linear accelerator, are projected onto the vertically aligned scintillator-based radiation detectors. The neutron and gamma-ray images of a cargo container moved by a motorized linear translation stage are acquired, and the image data processing shows good material classification results. In this paper, we describe a multi-radiation imaging system for air cargo inspection and investigate its material classification capability using various sample materials

Evaluation of Radiation Resistance of Polystyrene Using Molecular Dynamics Simulation

The scission rates of polystyrene and fluorinated polystyrene irradiated in an irradiation facility with Co-60 γ-rays were determined using molecular dynamics simulation and gel permeation chromatography (GPC) molecular weight distributions. The prediction was based on the assumption that γ-ray energy is transferred to the initial velocity of the primary knock-on atom. We employed a molecular dynamics simulation procedure to compute the changes in bond length between the connections for selected values of the absorbed dose and compared the calculated values with measurements made on the irradiated samples. The samples were exposed to four different absorbed doses of 25, 50, 75, and 100 kGy. The scission process and scission ratio were simulated with LAMMPS with ReaxFF potential for each bond, and we compared the simulation results with the experimental data especially measuring average molecular weight to evaluate the effect of fluorination on radiation enhancement

Anti-Atopic Effect of <i>Scutellaria baicalensis</i> and <i>Raphanus sativus</i> on Atopic Dermatitis-like Lesions in Mice by Experimental Verification and Compound-Target Prediction

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms