Recovery of microbially mediated processes in soil augmented with a pentachlorophenol-mineralizing bacterium.
Specific physiological groups can be used to evaluate the recovery of soil microbial communities following disturbance. In this study, soil was contaminated with pentachlorophenol (PCP) to assess the resiliency of microorganisms responsible for carbon and nitrogen cycling. Methane fluxes were monitored in soil microcosms to evaluate the effects of contamination and augmentation on microbial populations involved in carbon cycling. The addition of a PCP-mineralizing bacterium, Sphingomonas chlorophenolica strain RA2, enhanced the recovery of methane-oxidizing capacity relative to uninoculated treatments when soil was contaminated with low concentrations of PCP (10 and 50 microg/g soil, ppm). At the highest level of PCP contamination tested (300 ppm), there was no recovery of methane-oxidizing capacity whether or not the PCP-mineralizing bacterium was added to soil. The nitrogen-cycling capacity of contaminated and augmented soil was tested by measuring nitrification potentials. The addition of PCP resulted in a concentration-dependent reduction in nitrification rates. After three months of incubation, all augmented soils had nitrification rates equivalent to the uncontaminated control, and the uninoculated soils contaminated with 100 and 300 ppm PCP still were impaired in their nitrification potentials. These results indicate that biological removal of a contaminant has the potential to restore microbially mediated processes to levels observed prior to contamination.


Evaluating Lightning-Caused Fire Occurrence Using Spatial Generalized Additive Models: A Case Study in Central Spain.
It is widely accepted that the relationship between lightning wildfire occurrence and its influencing factors vary depending on the spatial scale of analysis, making the development of models at the regional scale advisable. In this study, we analyze the effects of different biophysical variables and lightning characteristics on lightning-caused forest wildfires in Castilla y León region (Central Spain). The presence/absence of at least one lightning-caused fire in any 4 × 4-km grid cell was used as a dependent variable and vegetation type and structure, terrain, climate, and lightning characteristics were used as possible covariates. Five prediction methods were compared: a generalized linear model (GLM), a random forest model (RFM), a generalized additive model (GAM), a GAM that includes a spatial trend function (GAMs) and a spatial autoregressive model (AUREG). A GAMs with just one covariate, apart from longitude and latitude for each observation included as a combined effect, was considered the most appropriate model in terms of both predictive ability and simplicity. According to our results, the probability of a forest being affected by a lightning-caused fire is positively and nonlinearly associated with the percentage of coniferous woodlands in the landscape, suggesting that occurrence is more closely associated with vegetation type than with topography, climate, or lightning characteristics. The selected GAMs is intended to inform the Regional Government of Castilla y León (the fire and fuel agency in the region) regarding identification of areas at greatest risk so it can design long-term forest fuel and fire management strategies.


A rare case of myocardial infarction by myocardial bridging of circumflex artery.
Myocardial Bridging (MB) is a benign condition that may be considered as a possible cause of ischaemic cardiopathy up to myocardial infarction. The authors describe the autopsy case of an MB of circumflex artery in a person with a myocardial infarction of the posterior wall of the left ventricle. In this case, the chronic ischemic heart disease can be explained by the congenital anomaly and in the literature there is scientific evidence to support the thesis. The MB is a benign condition that in combination with other risk factors can cause ischemic heart disease.


Extracellular vesicles derived from small intestinal lamina propria reduce antigen-specific immune response.
Extracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs. LpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance. The isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner. EVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.


Concentration of herpesviruses.
A method has been developed for the concentration of herpesviruses by negative pressure ultrafiltration through dialysis tubing. The procedure results in high titer concentrates of unaggregated, morphologically intact viral particles with a virtually quantitative recovery of infectivity.


Nanoparticle Density: A Critical Biophysical Regulator of Endothelial Permeability.
The integrity of the vasculature system is intrinsically sensitive to a short list of biophysical cues spanning from nano to micro scales. We have earlier found that certain nanomaterials could induce endothelial leakiness (nanoparticle induced endothelial leakiness, nanoEL). In this study, we report that the density of the nanomaterial, a basic intrinsic material property not implicated in many nanoparticle-mediated biological effects, predominantly dictates the nanoEL effect. We demonstrated that the impinging force exerted by a library of increasing effective densities but consistently sized silica nanoparticles (SiNPs) could directly increase endothelial permeability. The crossover effective particle density that induced nanoEL was determined to be between 1.57 g/cm3 to 1.72 g/cm3. It was also found that a cumulative gravitational-mediated force of around 1.8 nN/μm along the boundaries of the vascular endothelial cadherin (VE-cad) adherens junctions appeared to be a critical threshold force required to perturb endothelial cell-cell adhesion. The net result is the "snapping" of the mechanically pretensed VE-cad (Nanosnap), leading to the formation of micron-sized gaps that would dramatically increase endothelial leakiness.


Time-action profile of zinc human insulin (recombinant DNA) in young volunteers as compared with zinc porcine insulin (Monotard).
Zinc human insulin (recombinant DNA) or zinc PPI (Monotard) 20 U was injected subcutaneously to study the time-action profile in six healthy volunteers. During the test period they received a 10-g biscuit containing 3% moisture, 7% protein, 10% fat, 80% carbohydrate, and 30 ml of water every hour. The onset of action with zinc human insulin occurred earlier than with zinc PPI. Also, the intensity of the blood sugar-lowering effect was more pronounced 3 and 4 h after administration of insulin. No other statistically significant differences were detected between the two blood glucose curves. The results show that it is possible to develop a zinc human insulin formulation with a duration of the blood sugar-lowering effect equal to a zinc PPI formulation.


[Prevalence of Actinobacillus actinomycetemcomitans in saliva of different types of periodontitis].
To investigate the prevalence of Actinobacillus actinomycetemcomitans (Aa) in whole saliva of different types of periodontitis and compare the detections of Aa between saliva and pooled subgingival plaque sample, and analyze the relationship between Aa and clinical conditions. Unstimulated whole saliva samples and pooled subgingival samples were collected from 50 aggressive periodontitis (AgP) patients, 48 chronic periodontitis (CP) patients and 25 subjects with no periodontitis, and Aa was detected in these samples by PCR method. The prevalence of Aa in whole saliva of AgP patients was significantly higher than in subjects with no periodontitis (32% vs. 4%, P<0.01) and CP patients (32% vs. 15%, P<0.05). Aa was also more frequently detected in whole saliva sample than in pooled subgingival sample of AgP patients (32% vs. 16%, P<0.05). Subjects younger than 30 years old were more likely to present Aa in whole saliva ( OR = 3.23, P<0.05) and percentage of sites with bleeding index (BI) > or = 3 over 70% was a risk indicator for the presence of Aa in whole saliva The detection of Aa in whole saliva sample of AgP patients was more frequent than in pooled subgingival plaque samples, and also more frequent than in CP patients and subjects with no periodontitis, which suggest that Aa may participate in the initiation and progression of aggressive periodontitis.


In Vitro Antibacterial Activity of Propyl-Propane-Thiosulfinate and Propyl-Propane-Thiosulfonate Derived from Allium spp. against Gram-Negative and Gram-Positive Multidrug-Resistant Bacteria Isolated from Human Samples.
The aim of this study was to compare the in vitro antibacterial activity of two compounds derived from Alliaceae, PTS (propyl-propane-thiosulfinate), and PTSO (propyl-propane-thiosulfonate), with that of other antibiotics commonly used against bacteria isolated from humans. A total of 212 gram-negative bacilli and 267 gram-positive cocci isolated from human clinical samples and resistant to at least one group of antibiotics were selected. In order to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) to various antibiotics as well as PTS and PTSO, all isolates underwent broth microdilution assay. PTS showed moderate activity against Enterobacteriaceae with MIC50 (and MBC50) and MIC90 (and MBC90) values of 256-512 mg/L, while PTSO showed greater activity with MIC50 and MIC90 values of 64-128 mg/L and MBC50 and MBC90 values of 128-512 mg/L. These data show the bactericidal activity of both compounds and indicate that PTSO was more active than PTS against this group of bacteria. Both compounds showed lower activity against P. aeruginosa (MIC50 = 1024 mg/L, MIC90 = 2048 mg/L, MBC50 = 2048 mg/L, and MBC90 = 2048 mg/L, for PTS; MIC50 = 512 mg/L, MIC90 = 1024 mg/L, MBC50 = 512 mg/L, and MBC90 = 2048 mg/L, for PTSO) compared to those obtained in others nonfermenting gram-negative bacilli (MIC50 = 128 mg/L, MIC90 = 512 mg/L, MBC50 = 128 mg/L, and MBC90 = 512 mg/L, for PTS; MIC50 = 64 mg/L, MIC90 = 256 mg/L, MBC50 = 64 mg/L, and MBC90 = 256 mg/L, for PTSO) and also indicate the bactericidal activity of both compounds against these groups of bacteria. Finally, the activity against S. aureus, E. faecalis, and S. agalactiae was higher than that observed against enterobacteria, especially in the case of PTSO (MIC50 = 8 mg/L, MIC90 = 8 mg/L, MBC50 = 32 mg/L, and MBC90 = 64 mg/L, in S. aureus; MIC50 = 4 mg/L, MIC90 = 8 mg/L, MBC50 = 8 mg/L, and MBC90 = 16 mg/L, in E. faecalis and S. agalactiae). PTS and PTSO have a significant broad spectrum antibacterial activity against multiresistant bacteria isolated from human clinical samples. Preliminary results in present work provide basic and useful information for development and potential use of these compounds in the treatment of human infections.


Biomechanical studies of the anterior spinal fixators after corpectomy in pigs.
An unstable corpectomy porcine spinal model was created for the testing of anterior spinal fixators including: Kaneda device (KD), combination of Polster-Brinckmann prosthesis and Zielke implant (PBZ), and a new prototype device (CH). These spinal implants were examined in a one above/one below corpectomy model to determine the relative stiffness of each construct and the deformation of the adjacent discs under loading. The results indicated that the relative torsion and flexion stiffness were higher for the tested spines fixed with KD and CH. However, the relative compression stiffness of the tested spines was the same for all devices. The rigidity of the spinal constructs, which were measured around the corpectomy region showed the same tendency as above. However, the stiffness of CH and KD constructs were significantly higher than that of the PBZ construct under flexion and torsion. The difference in deformation of the upper and lower adjacent discs was not obvious among the intact spine and the spinal constructs with different devices. Clinical relevances: The corpectomy model represents a "worst case" scenario of spinal instability. In many conditions, spinal reconstructive surgery can restore axial compressive, torsional, and flexural rigidity to normal levels. These experimental conclusions apply to acute restoration of stability, rather than to rigidity after long-term cyclical loading. These three anterior fixators extended to only one cephalad level and one caudal level beyond the corpectomy defect. The new prototype device (CH) has a stability to the Kaneda device. The superior mechanical strength and simpler operative procedure of the new device provide for a potential clinical advantage in restoration of unstable spinal conditions.


Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals.
Colorectal cancer is one of the most common types of cancer in the world and its morbidity and mortality rates are increasing due to alterations to human lifestyle and dietary habits. The relationship between human gut flora and colorectal cancer has attracted increasing attention. In the present study, a metabolic fingerprinting technique that combined pyrosequencing with gas chromatography-mass spectrometry was utilized to compare the differences in gut flora profiling and fecal metabolites between healthy individuals and patients with colorectal cancer. The results demonstrated that there were no significant differences in the abundance and diversity of gut flora between healthy individuals and patients with colorectal cancer (P>0.05) and the dominant bacterial phyla present in the gut of both groups included Firmicutes, Bacteroidetes and Verrucomicrobia. At the bacterial strain/genus level, significant differences were observed in the relative abundance of 18 species of bacteria (P<0.05). Analysis of fecal metabolites demonstrated that the metabolic profiles of healthy individuals and patients with colorectal cancer were distinct. The levels of short-chain fatty acid metabolites, including acetic acid, valeric acid, isobutyric acid and isovaleric acid, and of nine amino acids in patients with colorectal cancer were significantly higher than those in healthy individuals (P<0.05). However, the levels of butyrate, oleic acid, trans-oleic acid, linoleic acid, glycerol, monoacyl glycerol, myristic acid, ursodesoxycholic acid and pantothenic acid in patients with colorectal cancer were significantly lower than those in healthy individuals (P<0.05). Pearson rank correlation analysis demonstrated that there was a correlation between gut flora profiling and metabolite composition. These findings suggest that gut flora disorder results in the alteration of bacterial metabolism, which may be associated with the pathogenesis of colorectal cancer. The results of the present study are useful as a foundation for further studies to elucidate a potential colorectal cancer diagnostic index and therapeutic targets.


Assessment of inhaled corticosteroids use and associated factors among asthmatic patients attending Tikur Anbessa Specialized Hospital, Ethiopia.
Inhaled corticosteroids (ICSs) are cornerstone therapy for persistent asthma. However, underutilization of ICSs is common and little is known about factors contributing toward this undesirable use. A cross-sectional study was conducted through interview and chart review among persistent asthmatic patients attending chest clinic of Tikur Anbessa Specialized Hospital from 1 May to 31 September 2014. A total of 131 eligible patients who attended the clinic during study period were included in the study. A multivariate logistic regression was used to examine the association between independent and dependent variables. Overall, extent of underutilization of ICSs was found to be 68%. Monthly income, comorbidity and types of ICSs products prescribed showed significant association with reported underutilization. Patients' reported reasons for underutilization includes; unaffordability (44%), using only when symptoms exacerbate (21%), fear of side effects (10%), practitioners' recommendation (10%) and unavailability of ICSs in the local market (7%). Physicians also stated unaffordability, fear of side effects and dependency, lack of local guideline for asthma management and unavailability of ICSs as the contributing factors. In this setting, extent of underutilization of ICSs was found to be high and seems the result of complex interaction of various factors. Financial problem combined with inconsistent availability of ICSs in the local market, patients' poor knowledge of asthma and ICSs, negative attitude toward ICSs, absence of local guidelines for asthma management are found to be essential elements dictating an extent of ICSs use.


Exploring public sentiment and vaccination uptake of COVID-19 vaccines in England: a spatiotemporal and sociodemographic analysis of Twitter data.
Vaccination is widely regarded as the paramount approach for safeguarding individuals against the repercussions of COVID-19. Nonetheless, concerns surrounding the efficacy and potential adverse effects of these vaccines have become prevalent among the public. To date, there has been a paucity of research investigating public perceptions and the adoption of COVID-19 vaccines. Therefore, the present study endeavours to address this lacuna by undertaking a spatiotemporal analysis of sentiments towards vaccination and its uptake in England at the local authority level, while concurrently examining the sociodemographic attributes at the national level. A sentiment analysis of Twitter data was undertaken to delineate the distribution of positive sentiments and their demographic correlates. Positive sentiments were categorized into clusters to streamline comparison across different age and gender demographics. The relationship between positive sentiment and vaccination uptake was evaluated using Spearman's correlation coefficient. Additionally, a bivariate analysis was carried out to further probe public sentiment towards COVID-19 vaccines and their local adoption rates. The results indicated that the majority of positive tweets were posted by males, although females expressed higher levels of positive sentiment. The age group over 40 dominated the positive tweets and exhibited the highest sentiment polarity. Additionally, vaccination uptake was positively correlated with the number of positive tweets and the age group at the local authority level. Overall, public opinions on COVID-19 vaccines are predominantly positive. The number of individuals receiving vaccinations at the local authority level is positively correlated with the prevalence of positive attitudes towards vaccines, particularly among the population aged over 40. These findings suggest that targeted efforts to increase vaccination uptake among younger populations, particularly males, are necessary to achieve widespread vaccination coverage.


Visual attention and driving behaviors among community-living older persons.
Older drivers have higher rates of crashes per mile driven compared with most other drivers, and these crashes result in greater morbidity and mortality. Various aspects of cognition, particularly visual attention, have been linked with crash risk among older individuals. The current study was designed to specify those cognitive variables associated with specific on-road driving behaviors in a sample of older, nonclinic-referred individuals. 35 community-residing active drivers aged 72 years and older (M = 80) underwent a standardized, on-road driving evaluation involving parking lot maneuvers, and urban, suburban, and highway driving. They were also administered tests of visual attention, executive function, visuospatial cognition, and memory. Driving score was significantly correlated with visual attention, visual memory, and executive function. Visual attention was associated with 25 of 36 driving behaviors, including those involving scanning the environment, interaction with traffic or pedestrians, and distance judgments. Executive function and visual memory were associated with fewer maneuvers, most of which were a subset of maneuvers that correlated with visual attention. Visual attention, a cognitive function involving search, selection, and switching, plays an important role in driving risk among older drivers. In the current study, key driving maneuvers involving interaction with other vehicles/pedestrians, such as yielding right of way and negotiating safe turns or merges, have the greatest association with visual attention. Specification of both the cognitive risk factors and their impact on problematic driving maneuvers may provide guidelines for developing targeted interventions to reduce risk among older adults.


Chemical probes for the recognition of cannabinoid receptors in native systems.
Receptors made visible: The described biotin-tagged small-molecule probes with excellent affinities for the CB(1) and CB(2) cannabinoid receptors (CB(1)R and CB(2)R) enable direct visualization of these receptors in native cellular systems, including neurons, microglia, and immune cells. This method could overcome some of the limitations of current methodologies and may help to dissect the complexity of the endogenous cannabinoid system.


Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation.
The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.


Engineering Bacillus thuringiensis Cyt1Aa toxin specificity from dipteran to lepidopteran toxicity.
The Cyt and Cry toxins are different pore-forming proteins produced by Bacillus thuringiensis bacteria, and used in insect-pests control. Cry-toxins have a complex mechanism involving interaction with several proteins in the insect gut such as aminopeptidase N (APN), alkaline phosphatase (ALP) and cadherin (CAD). It was shown that the loop regions of domain II of Cry toxins participate in receptor binding. Cyt-toxins are dipteran specific and interact with membrane lipids. We show that Cry1Ab domain II loop3 is involved in binding to APN, ALP and CAD receptors since point mutation Cry1Ab-G439D affected binding to these proteins. We hypothesized that construction of Cyt1A-hybrid proteins providing a binding site that recognizes gut proteins in lepidopteran larvae could result in improved Cyt1Aa toxin toward lepidopteran larvae. We constructed hybrid Cyt1Aa-loop3 proteins with increased binding interaction to Manduca sexta receptors and increased toxicity against two Lepidopteran pests, M. sexta and Plutella xylostella. The hybrid Cyt1Aa-loop3 proteins were severely affected in mosquitocidal activity and showed partial hemolytic activity but retained their capacity to synergize Cry11Aa toxicity against mosquitos. Our data show that insect specificity of Cyt1Aa toxin can be modified by introduction of loop regions from another non-related toxin with different insect specificity.


A Review of the Biological Mechanisms of Dexmedetomidine for Postoperative Neurocognitive Disorders.
Postoperative neurocognitive disorders are common neurological complications following surgery that are generally characterized by varying degrees of cognitive impairment. Postoperative neurocognitive disorders can exhibit as short-term postoperative delirium and/or long-term postoperative cognitive dysfunction. In addition, postoperative neurocognitive disorders may result in poor outcomes in patients, and are a leading cause of postoperative morbidity and mortality, particularly in elderly patients. Recently, there has been a heightened interest in mechanisms and clinical treatments for postoperative neurocognitive disorders. Though some influencing factors and mechanisms of postoperative neurocognitive disorders have been revealed, they remain troublesome problems in clinical departments. Dexmedetomidine is a commonly used anesthetic adjuvant that may help improve postoperative cognitive impairment, especially the conditions of a postoperative acute event (postoperative delirium, within 1 week after operation) and delayed neurocognitive recovery (postoperative cognitive dysfunction, up to 30 days). In the recent literature, dexmedetomidine has been shown to exert positive effects on cognitive impairment in clinical and animal studies, especially for postoperative neurocognitive disorders. However, not all clinical findings support this efficacy. Though some mechanisms of dexmedetomidine on postoperative neurocognitive disorders have been proposed, such as signaling pathways associated with inflammation and apoptosis, this evidence is fragmentary and disputed in the literature. Therefore, this article aims to review the potential biological mechanisms underlying dexmedetomidine's effects on postoperative neurocognitive disorders, providing a reference for future studies.


Update on pathogenesis of cystic fibrosis lung disease.
It has been an ongoing challenge to translate knowledge pertaining to the molecular basis of cystic fibrosis (CF) into a clear understanding of the development of CF lung disease. Various hypotheses have attempted to explain the apparent breach of innate defenses in CF, although a definitive explanation has been elusive. Recent data suggest that altered ion transport functions--namely sodium hyperabsorption and reduced chloride secretion--lead to a depletion of airway surface liquid. As a result, the overlying mucus layer may encroach upon cell surfaces and become adherent, thus interfering with cilia-dependent and cough clearance. These static, and ultimately anaerobic, niches provide a favorable environment for the development of bacterial biofilms and persistent infection with Pseudomonas aeruginosa. With a better understanding of pathogenic steps leading to CF lung disease, we may now be able to direct the development of therapies that will substantially improve disease outcomes.


Gene expression profiling in Werner syndrome closely resembles that of normal aging.
Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial to the development of the syndrome. We used cDNA microarrays to characterize the expression of 6,912 genes and ESTs across a panel of 15 primary human fibroblast cell lines derived from young donors, old donors, and WS patients. Of the analyzed genes, 6.3% displayed significant differences in expression when either WS or old donor cells were compared with young donor cells. This result demonstrates that the WS transcription defect is specific to certain genes. Transcription alterations in WS were strikingly similar to those in normal aging: 91% of annotated genes displayed similar expression changes in WS and in normal aging, 3% were unique to WS, and 6% were unique to normal aging. We propose that a defect in the transcription of the genes as identified in this study could produce many of the complex clinical features of WS. The remarkable similarity between WS and normal aging suggests that WS causes the acceleration of a normal aging mechanism. This finding supports the use of WS as an aging model and implies that the transcription alterations common to WS and normal aging represent general events in the aging process.


The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas.
Glioblastoma (GBM) is a common and refractory subtype of high-grade glioma with a poor prognosis. The epithelial-mesenchymal transition (EMT) is an important cause of enhanced glioblastoma invasiveness and tumor recurrence. Our previous study found that retinoic acid receptor-related orphan receptor A (RORA) is a nuclear receptor and plays an important role in inhibiting proliferation and tumorigenesis of glioma. We further confirmed RORA was downregulated in GBM. Thus, we determined whether RORA was involved in the migration, invasion, and EMT of GBM. Human GBM cell lines, U87 and T98G, and patient-derived glioma stem cells (GSCs), GSC2C and GSC4D, were used for in vitro and in vivo experiments. The expressions of RORA, CASC2, and EIF4A3 in GBM cells and GSCs were detected by RT-qPCR and western blotting. The biological effects of RORA, CASC2, and EIF4A3 on GBM migration, invasion, and EMT were evaluated using the migration assay, transwell assay, immunofluorescence staining, and xenograft experiments. We found that RORA inhibited the migration, invasion, and EMT of GBM. CASC2 could bind to, maintain the stability, and promote the nuclear translocation of RORA protein. EIF4A3 could downregulate CASC2 expression via inducing its cleavage, while RORA transcriptionally inhibited EIF4A3 expression, which formed a feedback loop among EIF4A3/CASC2/RORA. Moreover, gene set enrichment analysis (GSEA) and in vitro and in vivo experiments showed RORA inhibited the aggressiveness of GBM by negatively regulating the TGF-β1/Smad signaling pathway. Therefore, The EIF4A3/CASC2/RORA feedback loop regulated TGF-β1/Smad signaling pathway might become a promising therapeutic strategy for GBM treatment.


Treatment of adults with lingual orthodontic appliances.
With the advent of lingual orthodontic treatment, an alternative became available to the adult patient who preferred to avoid the unesthetic appearance of conventional orthodontic appliances. The newer brackets and archwires described in this article, in combination with the proven technique developed by the author and others, has made lingual orthodontic treatment a practical reality. The appliance has been shown to be as effective as labial counterparts in correcting all types of malocclusions. New laboratory and indirect bonding techniques have eliminated the need for intricate wire bending and have reduced patient chair time and overall treatment time. Because of the premature introduction of early lingual appliances, many dental practitioners mistakenly believe that lingual treatment is less effective than labial treatment. As more examples of successful treatment are seen, dental practitioners will be more apt to refer patients to orthodontists proficient in this technique. Many graduate orthodontic programs now are teaching this technique to their residents. About 3000 patients currently are starting treatment with lingual appliances each year. This represents only about 1 per cent of adult patients. It is projected that this slowly will climb to about 10 per cent of adult orthodontic treatment over the next 5 years. The increased cost of this treatment, coupled with the resistance on the part of many orthodontists to learn the new technique, seem to be the limiting factors.


Single-dose extended-release epidural morphine for pain following hip arthroplasty.
This open-label, serial-cohort pilot study evaluated DepoDur, a new, single-dose, extended-release epidural morphine (EREM) for pain control after hip arthroplasty. Single-dose EREM (10-30 mg) or a single dose of standard morphine sulfate (MS) (5 mg) was administered before surgery and spinal anesthesia. Among the 39 patients enrolled, total 48-hour supplemental fentanyl use was lower (P = 0.011 overall treatment) and median time to first postoperative fentanyl use was three- to six-fold longer (P < 0.001 overall treatment), among 10-, 20-, and 30-mg single-dose EREM patients versus MS patients. EREM patients reported higher levels of satisfaction with pain intensity scores comparable to MS patients. Safety results were similar between groups. Single-dose EREM was generally safe and effective for treating postoperative pain and reduced the need for supplemental analgesia.


[Physiology of cardiac performance].
We previously proposed i) Emax (end-systolic maximum elastance of the ventricle) as an index of contractility independent of preload and afterload and ii) PVA (systolic pressure-volume area of the ventricle) as a measure of the total mechanical energy generated by the ventricular contraction. Emax is defined as the slope of the end-systolic pressure-volume relation, which is relatively linear within the normal working range of the left ventricle. A working pressure-volume point starts from the end-diastolic pressure-volume curve, comes close to or slightly exceeds the end-systolic pressure-volume line, and returns to the end-diastolic curve. Thus, the end-diastolic and end-systolic pressure-volume curves envelop a family of pressure-volume trajectories of variously loaded contractions in a stable contractility. Emax increases with enhanced contractility and decreases with depressed contractility. PVA is an area between the end-diastolic and end-systolic pressure-volume curves on the origin side of the systolic pressure-volume trajectory. PVA linearly correlates with myocardial oxygen consumption regardless of ventricular loading conditions in a given Emax and this load-independent oxygen consumption-PVA relation is elevated with an enhanced Emax. Consequently, Emax and PVA have proved to be key measures and concepts in the physiology of cardiac performance.


Higher myonuclei density in muscle fibers persists among former users of anabolic androgenic steroids.
No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AAS) usage on the myocellular properties of human skeletal muscle in previous AAS users. We hypothesized former AAS users would demonstrate smaller myonuclei domains (i.e., higher myonuclei density) compared to matched controls. A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = 0.482). Geometric mean (95%CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA-to-cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = 0.013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users, beta-coefficient (95%CI), -94 (-169; -18), P = 0.024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = 0.031) compared to controls. Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA-to-cytoplasm ratio four years after AAS cessation suggestive of enhanced retraining capacity.


Shifts in the evolutionary rate and intensity of purifying selection between two Brassica genomes revealed by analyses of orthologous transposons and relics of a whole genome triplication.
Recent sequencing of the Brassica rapa and Brassica oleracea genomes revealed extremely contrasting genomic features such as the abundance and distribution of transposable elements between the two genomes. However, whether and how these structural differentiations may have influenced the evolutionary rates of the two genomes since their split from a common ancestor are unknown. Here, we investigated and compared the rates of nucleotide substitution between two long terminal repeats (LTRs) of individual orthologous LTR-retrotransposons, the rates of synonymous and non-synonymous substitution among triplicated genes retained in both genomes from a shared whole genome triplication event, and the rates of genetic recombination estimated/deduced by the comparison of physical and genetic distances along chromosomes and ratios of solo LTRs to intact elements. Overall, LTR sequences and genic sequences showed more rapid nucleotide substitution in B. rapa than in B. oleracea. Synonymous substitution of triplicated genes retained from a shared whole genome triplication was detected at higher rates in B. rapa than in B. oleracea. Interestingly, non-synonymous substitution was observed at lower rates in the former than in the latter, indicating shifted densities of purifying selection between the two genomes. In addition to evolutionary asymmetry, orthologous genes differentially regulated and/or disrupted by transposable elements between the two genomes were also characterized. Our analyses suggest that local genomic and epigenomic features, such as recombination rates and chromatin dynamics reshaped by independent proliferation of transposable elements and elimination between the two genomes, are perhaps partially the causes and partially the outcomes of the observed inter-specific asymmetric evolution.


Effects of ELF magnetic field in combination with Iron(III) chloride (FeCl3) on cellular growth and surface morphology of Escherichia coli (E. coli).
This study investigated the effects of extremely low frequency (ELF) magnetic field with/without iron(III) chloride (FeCl3) on bacterial growth and morphology. The ELF exposures were carried out using a pair of Helmholtz coil-based ELF exposure system which was designed to generate 50 Hz sinusoidal magnetic field. The field was approximately uniform throughout the axis of the coil pair. The samples which were treated or non-treated with different concentrations FeCl3 were exposed to 50 Hz, 2 millitesla (mT) magnetic field for 24 h. ELF effect on viability was assessed in terms of viable colony counts (in colony-forming unit per milliliter) with the standard plate count technique. Scanning electron microscopy was used to investigate the magnetic field effect on surface morphology of Escherichia coli. No significant results were seen in terms of cell viability between ELF and sham-exposed bacterial strains. Similarly, FeCl3 treatment did not change cell viability of E. coli samples. However, we observed some morphological changes on E. coli cell surfaces. Pore formations and membrane destruction were seen on the surface of 24 h ELF field-exposed cells. We concluded that ELF magnetic field exposure at 2 mT does not affect cell viability; however, it may affect bacterial surface morphology.


Colonic cell proliferation in normal mucosa of patients with colon cancer.
Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), 3H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt.


Prospective study comparing multislice CT colonography with colonoscopy in the detection of colorectal cancer and polyps.
Multislice CT colonography is an alternative to colonoscopy. The purpose of this study was to compare multislice CT colonography with colonoscopy in the detection of colorectal polyps and cancers. Between June 2000 and December 2001, 45 males and 35 females (median age, 68 (29-83) years) with symptoms of colorectal disease were studied prospectively. All patients underwent multislice CT colonography and colonoscopy, and the findings were compared. Colonoscopy was incomplete in 18 (22 percent) patients because of obstructing lesions or technical difficulty, and multislice CT colonography was unsuccessful in 4 (5 percent) because of fecal residue. Colonoscopy was normal in 26 patients and detected 29 colorectal cancers and 33 polyps in 35 patients, diverticulosis in 16 patients, and colitis in 3 patients. Multislice CT colonography identified 28 of 29 colorectal cancers with one false negative and one false positive (sensitivity, 97 percent; specificity, 98 percent; positive predictive value, 96 percent; negative predictive value, 98 percent). Multislice CT colonography identified all 12 polyps measuring >or=10 mm in diameter (sensitivity, 100 percent), 5 of 6 measuring 6 to 9 mm in diameter (sensitivity, 83 percent), 8 of 15 polyps <or=5 mm (sensitivity, 53 percent), and false-positive for 8 polyps. The overall sensitivity was 74 percent and specificity 96 percent. The positive predictive value for polyps was 88 percent, and the negative predictive value was 90 percent. Multislice CT colonography also detected 5 of 16 patients with diverticulosis (sensitivity, 31 percent; specificity, 98 percent) and colitis in 2 of 3 patients (sensitivity, 67 percent; specificity, 100 percent). In ten (13 percent) patients, extracolonic findings on multislice CT colonography altered management and included five patients with colorectal liver metastases. In 15 (19 percent) patients, there were incidental findings that did not demand further investigation. The results from this study indicate that the efficacy of multislice CT colonography in the detection of colorectal cancers and polyps >or=6 mm is similar to colonoscopy. Multislice CT colonography allows clinical staging of colorectal cancers, outlines the whole length of the colon in obstructing carcinoma when colonoscopy fails, and can identify extracolonic causes of abdominal symptoms.


Human Tissue Kallikreins-Related Peptidases Are Targets for the Treatment of Skin Desquamation Diseases.
Human tissue Kallikrein-related peptidases (hKLKs) are serine proteases distributed in several tissues that are involved in several biological processes. In skin, many are responsible for skin desquamation in the Stratum Corneum (SC) of the epidermis, specially hKLK5, hKLK7, hKLK6, hKLK8, and hKLK14. In SC, hKLKs cleave proteins of corneodesmosomes, an important structure responsible to maintain corneocytes attached. As part of skin desquamation, hKLKs are also involved in skin diseases with abnormal desquamation and inflammation, such as Atopic Dermatitis (AD), psoriasis, and the rare disease Netherton Syndrome (NS). Many studies point to hKLK overexpression or overactive in skin diseases, and they are also part of the natural skin inflammation process, through the PAR2 cleavage pathway. Therefore, the control of hKLK activity may offer successful treatments for skin diseases, improving the quality of life in patients. Diseases like AD, Psoriasis, and NS have an impact on social life, causing pain, itchy and mental disorders. In this review, we address the molecular mechanisms of skin desquamation, emphasizing the roles of human tissue Kallikrein-related peptidases, and the promising therapies targeting the inhibition of hKLKs.


Complete Revascularization and Angina-Related Health Status in the ISCHEMIA Trial.
The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied. Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON. Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization. Propensity-weighted modeling was then performed to estimate the treatment effect had CR or ICR been achieved in all INV patients, compared with CON. Anatomic and functional CR were achieved in 43.3% and 57.8% of 1,641 INV patients, respectively. Among revascularized patients, CR was associated with improved Seattle Angina Questionnaire Angina Frequency compared with ICR after adjustment for baseline differences. After modeling CR and ICR in all INV patients, patients with CR and ICR each had greater improvements in health status than CON, with better health status with CR than ICR. The projected benefits of CR were most pronounced in patients with baseline daily/weekly angina and not seen in those with no angina. Among patients with CCD in ISCHEMIA, health status improved more with CR compared with ICR or CON, particularly in those with frequent angina. Anatomic and functional CR provided comparable improvements in quality of life. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).


Light-driven formation and rupture of droplet bilayers.
We demonstrate the optical manipulation of nanoliter aqueous droplets containing surfactant or lipid molecules and immersed in an organic liquid using near-infrared light. The resulting emulsion droplets are manipulated using both the thermocapillary effect and convective fluid motion. Droplet-pair interactions induced in the emulsion upon optical initiation and control provide direct observations of the coalescence steps in intricate detail. Droplet-droplet adhesion (bilayer formation) is observed under several conditions. Selective bilayer rupture is also realized using the same infrared laser. The technique provides a novel approach to studying thin film drainage and interface stability in emulsion dynamics. The formation of stable lipid bilayers at the adhesion interface between interacting water droplets can provide an optical platform on which to build droplet-based lipid bilayer assays. The technique also has relevance to understanding and improving microfluidics applications by devising Petri dish-based droplet assays requiring no substrate fabrication.


Newer antibiotics for the treatment of peritoneal dialysis-related peritonitis.
Peritonitis is a debilitating infectious complication of peritoneal dialysis (PD). Drug-resistant bacterial peritonitis typically has a lower response rate to antibiotics. In the past 15 years, newer antibiotics with activities against drug-resistant Gram-positive bacteria have been developed. In most circumstances, peritonitis due to methicillin-resistant staphylococci responds to vancomycin. If vancomycin cannot be used due to allergy and/or non-susceptibility, there is increasing evidence that linezolid and daptomycin are the drugs of choice. It is reasonable to start linezolid orally or intravenously, but subsequent dose reduction may be necessary in case of myelosuppression. Daptomycin can be given intravenously or intraperitoneally and has excellent anti-biofilm activity. Other treatment options for drug-resistant Gram-positive bacterial peritonitis include teicoplanin, tigecycline and quinupristin/dalfopristin. Teicoplanin is not available in some countries (e.g. the USA). Tigecycline can only be given intravenously. Quinupristin/dalfopristin is ineffective against Enterococcus faecalis and there is only low-quality evidence to support its efficacy in the treatment of peritonitis. Effective newer antibiotics against drug-resistant Gram-negative bacteria are lacking. Polymyxins can be considered, but evidence on its efficacy is limited. In this review, we will discuss the potential use of newer antibiotics in the treatment of drug-resistant bacterial peritonitis in PD patients.


The political discourse on quota immigration in Germany.
"Since the late 1980s many professional politicians and social interest associations/organisations have been arguing for the creation of an immigration law which would allow and organise limited and legal new immigration to Germany on the basis of annual or two-three year quotas. This political discourse on immigration policy contains proposals which go beyond pure self-interest and aim to contribute to the stated goals of ¿citizenship in Europe' and ¿open, transnational citizenship'. This position is so far only held by a minority. More dominant are the proponents of quota immigration policy and of political asylum and civil refugee policies, directly or indirectly exclusionist in relation to ¿old' and/or ¿new' immigrants and refugees. This article presents the argument for rethinking and restructuring the notion of quota immigration rather than rejecting it altogether."


Balancing Type I and Type II error concerns in fMRI through compartmentalized analysis.
We seek to balance the need to minimize false positives with the need to maximize power. We propose a compartmentalized series of analyses that a priori selects regions of voxels that have different degrees of predicted involvement. Alpha thresholds are allocated based on the strength of expected theoretical relationships. For example, confirmatory studies might allocate most of the error to the regions predicted from the literature and thus use a relatively more liberal threshold on these voxels. Simulations reveal that this technique increases power for hypothesized regions, while maintaining a constant false-positive rate and allowing exploratory analysis.


Aquaporin-4 and traumatic brain edema.
Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.


Case Report: Whole Exome Sequencing Revealed Two Novel Mutations of PIEZO1 Implicated in Nonimmune Hydrops Fetalis.
Nonimmune hydrops fetalis (NIHF) is a serious and complex fetal condition. Prenatal diagnosis of hydrops fetalis is not difficult by ultrasound. However, determining the underlying etiology of NIHF remains a challenge which is essential to address for prenatal counseling. We extracted DNA from a proband prenatally diagnosed unexplained NIHF. Trio-whole exome sequencing (WES) was performed to filter candidate causative variants. Two gene mutations were identified as a compound heterozygous state in the proband. Both variants located on the PIEZO1 gene: c.3895C > T, a missense mutation in exon 27 paternally inherited; c.4030_4032del, a maternally inherited in-frame deletion in exon 28. Both variants were first reported to be related to NIHF. PIEZO1 gene mutations, leading to an autosomal recessive congenital lymphatic dysplasia, which can present as NIHF and partial or complete resolution postnatally. In conclusion, WES can aid in the elucidation of the genetic cause of NIHF and has a positive effect on the assessment of prognosis.


What respondents really expect from researchers.
This article addresses the issue of falling response rates in telephone surveys. To better understand and maintain respondent goodwill, concepts of psychological contract and respondent expectations are introduced and explored. Results of the qualitative study show that respondent expectations are not only socially contingent but also ego-expressive, utilitarian, pleasurable, and epistemic by nature. Although results are reassuring in terms of commercialization of the psychological contract, they indicate some radical changes that are needed for the respondents to accept its continuation. The article discusses several practical and theoretical implications of such changes and suggests a series of corresponding propositions aimed at facilitating and inspiring future developments in this field.


Radiofrequency Ablation Combined with Radioactive Seed Implantation for Nonsmall Cell Lung Cancer.
The aim of this study is to investigate the value of radiofrequency ablation combined with radioactive seed implantation in nonsmall cell lung cancer treatment. 30 patients with primary nonsmall cell lung cancer were randomly divided into two groups. Group A was treated with radiofrequency ablation combined with radiation seed implantation, and group B was treated with radiofrequency ablation only. We compared the incidence of complications in the two groups and reviewed the effective percentage every 3 months. All patients were treated successfully, and there were no deaths during treatment. There were no deaths and no cases of distant organ metastasis in nine months of follow-up. There were no significant differences in treatment-related complications between the two groups. The early postoperative (three and six months) effective percentage was not significantly different (P > 0.05). After 9 months, the postoperative effective rate for group A (9/15) was significantly different from that for group B (radiofrequency ablation) (6/15) (P < 0.05). Radiofrequency ablation combined with radiation 125I seed implantation can complement each other in the treatment of nonsmall cell lung cancer.


The sludge loading rate regulates the growth and release of heterotrophic bacteria resistant to six types of antibiotics in wastewater activated sludge.
Wastewater treatment plants are considered as hot reservoirs of antimicrobial resistance. However, the fates of antibiotic-resistant bacteria during biological treatment processes and relevant influencing factors have not been fully understood. This study evaluated the effects of the sludge loading rate on the growth and release of six kinds of antibiotic-resistant bacteria in an activated sludge system. The results indicated that higher sludge loading rates amplified the growth of all six types of antibiotic resistant bacteria. The release of most antibiotic-resistant bacteria through both the effluent and biosolids was amplified with increased sludge loading rate. Biosolids were the main pattern for all antibiotic-resistant bacteria release in an activated sludge system, which was determined primarily by their growth in the activated sludge. A higher sludge loading rate reactor tended to retain more antibiotic resistance. An activated sludge system with lower sludge loading rates was considered more conducive to the control of antibiotic resistance.


Molecular cloning and sequence analysis of the X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. cremoris.
Lactococcus lactis subsp. cremoris P8-2-47 contains an X-prolyl dipeptidyl aminopeptidase (X-PDAP; EC 22.214.171.124). A mixed-oligonucleotide probe prepared on the basis of the N-terminal amino acid sequence of the purified protein was made and used to screen a partial chromosomal DNA bank in Escherichia coli. A partial XbaI fragment cloned in pUC18 specified X-PDAP activity in E. coli clones. The fragment was also able to confer X-PDAP activity on Bacillus subtilis. The fact that none of these organisms contain this enzymatic activity indicated that the structural gene for X-PDAP had been cloned. The cloned fragment fully restored X-PDAP activity in X-PDAP-deficient mutants of L. lactis. We have sequenced a 3.8-kb fragment that includes the X-PDAP gene and its expression signals. The X-PDAP gene, designated pepXP, comprises 2,289 nucleotide residues encoding a protein of 763 amino acids with a predicted molecular weight of 87,787. No homology was detected between pepXP and genes that had been previously sequenced. A second open reading frame, divergently transcribed, was present in the sequenced fragment; the function or relationship to pepXP of this open reading frame is unknown.


Exploring dual inhibitors for STAT1 and STAT5 receptors utilizing virtual screening and dynamics simulation validation.
Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that transduce signals from cytokines and growth factors to the nucleus and thereby regulate the expression of a variety of target genes. Although mutations of STATs have not been reported in human tumors but the activity of several members of the family, such as STAT1 and STAT5, is deregulated in a variety of human carcinoma. STAT1 and STAT5 share a structural similarity with a highly conserved SH2 domain which is responsible for the activation of STAT proteins on interaction with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The purpose of this study is to identify domain-specific dual inhibitors for both STAT1 and STAT5 proteins from a database of natural products and natural product-like compounds comprising of over 90,000 compounds. Virtual screening-based molecular docking was performed in order to find novel natural dual inhibitors. Further, the study was supported by the 50-ns molecular dynamics simulation for receptor-ligand complexes (STAT1-STOCK-1N-69677 and STAT5-STOCK-1N-69677). Analysis of molecular interactions in the SH2 domains of both STAT1 and STAT5 proteins with the ligand revealed few conserved amino acid residues which are responsible to stabilize the ligands within the binding pocket through bonded and non-bonded interactions. This study suggested that compound STOCK-1N-69677 might putatively act as a dual inhibitor of STAT1 and STAT5 receptors, through its binding to the SH2 domain.


Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature.
Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms. We found that the increase in urinary output and urinary sodium excretion in response to systemic infusion of GLP-1 for 30min in SHRs was much less pronounced than in normotensive rats. The diuretic and natriuretic actions of GLP-1 in normotensive rats were accompanied by increases in GFR and RBF and a reduction in RVR through activation of the cAMP signaling pathway. However, no changes in renal hemodynamics were observed in SHRs. Similarly, GLP-1 induced an endothelium-independent relaxation effect in the renal arteries of normotensive rats, whereas the renal vasculature of SHRs was unresponsive to this vasodilator. The absence of a GLP-1-induced renal artery vasodilator effect in SHRs was associated with lower expression of the GLP-1 receptor, blunted GLP-1-induced increases in cAMP production and higher activity and expression of the GLP-1 inactivating enzyme dipeptidyl peptidase IV relative to the renal arteries of normotensive rats. Collectively, these results demonstrate that the renal acute responses to GLP-1 are attenuated in SHRs. Thus, chronic treatment with incretin-based agents may rely upon the upregulation of GLP-1/GLP-1 receptor signaling in the kidneys of hypertensive patients and experimental models.


PDK1-WNK1 signaling is affected by HBx and involved in the viability and metastasis of hepatic cells.
Hepatitis B virus (HBV)-encoded X antigen (HBx) contributes to the development of hepatocellular carcinoma (HCC). Although HBx has been implicated in the progression of HCC, its precise function in HBV-associated HCC remains unclear. In the present study, HBx affected 3-phosphoinositide-dependent protein kinase-1 (PDK1) and with-no-lysine (K) kinase (WNK1) signaling, which was identified to be involved in the viability and metastasis of hepatic cells. The phosphorylation of WNK1 was decreased when the hepatic cells were treated with a PDK1 inhibitor. The inhibition of PDK1 activity inhibited the viability and migration of hepatic cells. To the best of our knowledge, the present study is the first to identify the activation of PDK1 in HCC tissues, confirmed using western blot analysis. PDK1-WNK1 signaling may be a potential therapeutic target in HBV-associated liver cancer.


A test of the equal-loudness-ratio hypothesis using cross-modality matching functions.
This study tests the Equal-Loudness-Ratio hypothesis [Florentine et al., J. Acoust. Soc. Am. 99, 1633-1644 (1996)], which states that the loudness ratio between equal-SPL long and short tones is independent of SPL. The amount of temporal integration (i.e., the level difference between equally loud short and long sounds) is maximal at moderate levels. Therefore, the Equal-Loudness-Ratio hypothesis predicts that the loudness function is shallower at moderate levels than at low and high levels. Equal-loudness matches and cross-modality string-length matches were used to assess the form of the loudness function for 5 and 200 ms tones at 1 kHz and the loudness ratio between them. Results from nine normal listeners show that (1) the amount of temporal integration is largest at moderate levels, in agreement with previous studies, and (2) the loudness functions are shallowest at moderate levels. For eight of the nine listeners, the loudness ratio between the 200 and 5 ms tones is approximately constant, except at low levels where it tends to increase. The average data show good agreement between the two methods, but discrepancies are apparent for some individuals. These findings support the Equal-Loudness-Ratio hypothesis, except at low levels.


First report on the presence of huanglongbing vectors (Diaphorina citri and Trioza erytreae) in Ghana.
As significant threats to global citrus production, Diaphorina citri (Kuwayama; Hemiptera: Psyllidae) and Trioza erytreae (Del Guercio; Hemiptera: Triozidae) have caused considerable losses to citrus trees globally. Diaphorina citri vectors "Candidatus Liberibacter asiaticus" and "Ca. L. americanus", whereas T. erytreae transmits "Ca. L. africanus" and "Ca. L. asiaticus", the pathogens responsible for citrus greening disease or Huanglongbing (HLB). Though HLB is a destructive disease of citrus wherever it occurs, information on the occurrence and geographical distribution of its vectors in Africa is limited. In recent surveys to determine if HLB vectors are present in Ghana, we observed eggs, nymphs, and adults of insects suspected to be D. citri and T. erytreae. Using morphological traits and DNA analyses, the identity of the suspected insects was confirmed to be D. citri and T. erytreae. Individuals of D. citri and T. erytreae were examined using qPCR for CLaf, CLam, and CLas, but none of them tested positive for any of the Liberibacter species. Herein we report, for the first time, the presence of D. citri and T. erytreae in Ghana (West Africa). We discuss the implications of this new threat to the citrus industry to formulate appropriate management strategies.


Innervation of the adrenal cortex, its physiological relevance, with primary focus on the noradrenergic transmission.
The current knowledge of the catecholaminergic innervation of the mammalian adrenal cortex is summarized, and macro- and microscopic neuromorphology, including the central nervous system connections of the adrenal cortex, is briefly discussed. Morphological and functional data on the catecholaminergic (i.e., noradrenergic) innervation of the adrenal cortex are reviewed. Experimental data suggest that in addition to the regulation of adrenal blood flow, the noradrenergic innervation has a primary influence on zona glomerulosa cells possibly via beta 1 adrenergic and dopaminergic receptors (DA2 subtype via inhibiting T-type Ca2+ channels) It is concluded that the local, modulatory effect of noradrenergic nerve fibres, terminating in the close vicinity of the zona glomerulosa cells, on the systemic renin-angiotensin-aldosterone and other peptide cascade may be influenced by neuropeptides, particularly neuropeptide Y and vasoactive intestinal peptide.


[Effect of insulin on brain pyruvate dehydrogenase in the rat. (Preliminary note)].
The activity of both active and total pyruvate dehydrogenase (E.C.22.214.171.124) is substantially reduced in the rat brain 24h after alloxan administration. Effects are partially removed by insulin administration. Ca++ and Mg++ produce: a) a considerable conversion of the inactive form of pyruvate dehydrogenase into its active form in a preparation from the brain of normal rats and of rats treated with insulin; b) no conversion in a preparation from the brain of rats treated with alloxan; c) some conversion in a preparation from the brain of rats treated with both alloxan and insulin. Active and total pyruvate dehydrogenase from the brain of rats treated with alloxan are activated by a preparation obtained from a mixture of entire plasma membranes-mitochondria from normal and from alloxan-treated rats, or from insulin-treated and alloxan treated rats. The oxygen uptake, the respiratory control index and the ADP/O ratio in mitochondrial preparations obtained from the brain of rats treated with alloxan show no modification at all.


Blood Concentrations of Designer Benzodiazepines: Relation to Impairment and Findings in Forensic Cases.
The use of designer benzodiazepines appears to be increasing in many countries, but data concerning blood concentrations are scarce, making interpretation of concentrations difficult. The aim of this study was to report blood concentrations of clonazolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam and phenazepam and to investigate the relationship between blood concentrations and impairment. The concentration data are from blood samples collected from living cases (apprehended drivers and other drug offences) and medico-legal autopsies. The blood samples were analysed for the seven designer benzodiazepines mentioned above by ultra high performance liquid chromatography-tandem mass spectrometry. Positive cases from between 1 June 2016 and 30 September 2019 were included. Blood concentrations and the conclusion from a clinical test of impairment (when available) are reported. The presented seven benzodiazepines were detected in a total of 575 cases, where 554 of these cases concerned apprehended drivers or other criminal offenders. The number of findings and the median (range) concentrations were as follows: clonazolam, n = 22, 0.0041 mg/L (0.0017-0.053 mg/L); diclazepam, n = 334, 0.0096 mg/L (0.0016-0.25 mg/L); etizolam, n = 40, 0.054 mg/L (0.015-0.30 mg/L); flualprazolam, n = 10, 0.0080 mg/L (0.0033-0.056 mg/L); flubromazepam, n = 5, 0.037 mg/L (0.0070-0.70 mg/L); flubromazolam, n = 20, 0.0056 mg/L (0.0004-0.036 mg/L); and phenazepam, n = 138, 0.022 mg/L (0.0018-0.85 mg/L). A designer benzodiazepine was the only drug detected with relevance for impairment in 25 of the 554 living cases. The physician concluded with impairment in 19 of the 25 cases. Most of the concentrations in these cases were relatively similar to or higher than the median reported concentrations. The most frequent other drugs detected were amphetamine, tetrahydrocannabinol, clonazepam and methamphetamine. The presented blood concentrations can be helpful with the interpretation of cases involving one or more of these seven benzodiazepines. The results indicate that concentrations commonly observed in forensic cases are associated with impairment.


Instability versus equilibrium propagation of a laser beam in plasma.
We obtain, for the first time, an analytic theory of the forward stimulated Brillouin scattering instability of a spatially and temporally incoherent laser beam that controls the transition between statistical equilibrium and nonequilibrium (unstable) self-focusing regimes of beam propagation. The stability boundary may be used as a comprehensive guide for inertial confinement fusion designs. Well into the stable regime, an analytic expression for the angular diffusion coefficient is obtained, which provides an essential correction to a geometric optic approximation for beam propagation.


[Research Advances in the Association between Inflammasome and Abdominal Aortic Aneurysm].
The inflammasome is a multiprotein complex localized in the cytoplasm.It can mediate the expressions of various inflammatory cytokines such as interleukin(IL)-1β and IL-18 and plays a key role in regulating inflammatory response.As sterile inflammation,abdominal aortic aneurysm currently can only be treated by surgery.This article reviews the research advances in the role of inflammasomes in abdominal aortic aneurysm.


Phase separation as a tool to control dispersion of multiwall carbon nanotubes in polymeric blends.
Conducting polymeric materials with stable phase microstructures have a range of potential applications. In this work, it is investigated whether phase separation in polymer blends can be used as a tool to create well dispersed conducting filler rich domains in 3D with controlled morphology, potentially resulting in more effective percolation. The effect of amine functionalized multiwall carbon nanotubes (NH(2)-MWCNTs) on the thermally induced phase separation processes in poly[(alpha-methyl styrene)-co-acrylonitrile]/poly(methyl methacrylate) (PalphaMSAN/PMMA) blends was monitored by melt rheology, conductivity spectroscopy, and microscopic techniques. Electron microscopic images revealed that the phase separation resulted in a heterogeneous distribution of NH(2)-MWCNTs in the blends. The migration of NH(2)-MWCNTs is controlled by the thermodynamic forces that drive phase separation and led to an increase in their local concentration in a specific phase resulting in percolative "network-like" structure. Conductivity spectroscopy measurements demonstrated that the blends with 2 wt % NH(2)-MWCNTs that showed insulating properties for a one phasic system revealed highly conducting material in the melt state (two phasic) as a result of phase separation. By quenching this morphology, a highly conducting material with controlled dispersion of MWCNTs can be achieved. Furthermore, the role of NH(2)-MWCNTs in stabilizing the PMMA droplets against flow induced coalescence in 85/15 PalphaMSAN/PMMA blends was also established for the first time. It was observed that at a typical loading of 1.25 wt % NH(2)-MWCNTs the coalescence was completely suppressed on a practical time scale.


Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons.
An understanding of the diversity of cortical GABAergic interneurons is critical to understand the function of the cerebral cortex. Recent data suggest that neurons expressing three markers, the Ca2+-binding protein parvalbumin (PV), the neuropeptide somatostatin (SST), and the ionotropic serotonin receptor 5HT3a (5HT3aR) account for nearly 100% of neocortical interneurons. Interneurons expressing each of these markers have a different embryological origin. Each group includes several types of interneurons that differ in morphological and electrophysiological properties and likely have different functions in the cortical circuit. The PV group accounts for ∼40% of GABAergic neurons and includes fast spiking basket cells and chandelier cells. The SST group, which represents ∼30% of GABAergic neurons, includes the Martinotti cells and a set of neurons that specifically target layerIV. The 5HT3aR group, which also accounts for ∼30% of the total interneuronal population, is heterogeneous and includes all of the neurons that express the neuropeptide VIP, as well as an equally numerous subgroup of neurons that do not express VIP and includes neurogliaform cells. The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states and behavioral contexts.


Efficacy of rivastigmine in comparison to ginkgo for treating Alzheimer's dementia.
To assess the efficacy of the Ginkgo biloba in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with rivastigmine. Total 56 patients aged 50-75 years, suffering from dementia, were allocated into one of the two treatments: group 1) Ginkgo biloba (120 mg daily dose); group 2) rivastigmine (4.5 mg daily dose) in a 24-week randomized double blind study. The degree of severity of dementia was assessed by the Seven Minute test and the Mini-Mental State Examination. Our results confirm the clinical efficacy of rivastigmine in the dementia of the Alzheimer type, comparing to Ginkgo biloba. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type. Our study suggests that there are differences in the efficacy of Ginkgo biloba and rivastigmine in the treatment of Alzheimer's dementia. In addition, this study suggested that cholinesterase inhibitors should be used in preference to Ginkgo biloba in patients with mild to moderate AD.


Impact of coexisting multivessel coronary artery disease on short-term outcomes and long-term survival of patients treated with carotid stenting.
Systemic atherosclerosis can result in both coronary artery disease (CAD) and carotid artery disease. Recently it has been shown that patients with CAD have a higher incidence of microembolization during carotid artery stenting (CAS), and it has been hypothesized that they could be at higher risk in this intervention. We retrospectively evaluated an institutional registry with 437 consecutive patients who underwent coronary angiography and CAS to evaluate their short-term outcomes and long-term survival with regard to the presence of coexisting multivessel coronary artery disease (MVD). We performed 220 CAS procedures in MVD patients and 318 CAS procedures in non-MVD patients. The incidence of in-hospital CAS-related adverse events was 2.7% and 2.5% in the MVD and non-MVD groups, respectively (p = 0.88). At 30 days, there was no significant difference between the groups in terms of the number of patients with adverse events (hierarchically death/stroke/myocardial infarction; 8.8% vs. 5.5%; p = 0.18). The median duration of follow-up was 4.23 years. Survival free of all-cause mortality at 1, 3 and 5 years was 90% (95% CI: 86-94%), 79% (95% CI: 73-85%) and 70% (95% CI: 64-77%), and 92% (95% CI: 89-95%), 85% (95% CI: 80-90%) and 76% (95% CI: 70-82%) for the MVD and non-MVD groups (p = 0.02), respectively. These results suggest that patients with MVD combined with carotid artery disease are probably not at higher risk of early post-CAS adverse clinical events, but they have significantly worse long-term survival rates.


Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D-Printed Mesoreactors.
3D-printed flow reactors were designed, fabricated from different materials (PLA, HIPS, nylon), and used for a catalytic stereoselective Henry reaction. The use of readily prepared and tunable 3D-printed reactors enabled the rapid screening of devices with different sizes, shapes, and channel dimensions, aimed at the identification of the best-performing reactor setup. The optimized process afforded the products in high yields, moderate diastereoselectivity, and up to 90 % ee. The method was applied to the continuous-flow synthesis of biologically active chiral 1,2-amino alcohols (norephedrine, metaraminol, and methoxamine) through a two-step sequence combining the nitroaldol reaction with a hydrogenation. To highlight potential industrial applications of this method, a multistep continuous synthesis of norephedrine has been realized. The product was isolated without any intermediate purifications or solvent switches.


Long-Term Outcomes and Quality of Life in Patients after Soave Pull-Through Operation for Hirschsprung's Disease: An Observational Retrospective Study.
Patients after pull-through operation for Hirschsprung's disease (HD) are at high risk of defecation disorders. This study aimed at investigating their long-term outcomes and quality of life (QoL) in comparison with controls. Patients older than 5 years operated on for HD were interviewed to complete detailed questionnaires on bowel function. Patients without neurologic impairment were enrolled in a QoL survey to compare with controls matched for sex and age and selected randomly from the general population using sampling set in a ratio of four controls to one case of HD. In total, 53 operated patients were enrolled. Mean age of the patients was 16 ± 8 years, with 68% boys. Rectosigmoid aganglionosis was the most seen form of HD in 38 (72%) cases. Open Soave was performed in 40 (75.5%) cases, and minimally invasive surgery Soave (MIS Soave) in 13 (24.5%) cases. At investigation, prevalence of fecal incontinence and constipation were 22.6 and 13.2%, respectively. Regarding QoL survey, 45 patients and 180 controls were enrolled, excluding 8 patients with neurologic impairment. Thirty-seven (82.2%) patients were classified as having a good QoL (score ≥ 9 points); whereas six had a fair QoL (5-8 points) and two had a poor QoL (< 5 points). QoL score in the cases and the controls were 10.2 ± 2.5 and 11.9 ± 0.4 points, respectively. Long aganglionosis form of HD was significantly associated with a low QoL (score < 8 points), adjusted odds ratio = 9, 95% confidence interval [1.3; 64.1] (p < 0.05). In subscales analyses, the prevalence of each dimension including fecal continence, school absenteeism, unhappiness or anxiety, food restriction, and peer rejection was significantly higher in operated patients than in controls (p <0.001). Although the QoL of patients operated on for HD in general was with good outcomes, fecal incontinence and constipation still are problematic issues and challenges in a high percentage of patients. Therefore, a long-term and multidisciplinary follow-up is essentially required for these patients.


Enhancing the Therapy Experience Using Principles of Video Game Design.
This article considers the potential benefits that applying design principles from contemporary video games may have on enhancing therapy experiences. Six principles of video game design are presented, and their relevance for enriching clinical experiences is discussed. The motivational and learning benefits of each design principle have been discussed in the education literature as having positive impacts on student motivation and learning and are related here to aspects of clinical practice. The essential experience principle suggests connecting all aspects of the experience around a central emotion or cognitive connection. The discovery principle promotes indirect learning in focused environments. The risk-taking principle addresses the uncertainties clients face when attempting newly learned skills in novel situations. The generalization principle encourages multiple opportunities for skill transfer. The reward system principle directly relates to the scaffolding of frequent and varied feedback in treatment. Last, the identity principle can assist clients in using their newly learned communication skills to redefine self-perceptions. These principles highlight areas for research and interventions that may be used to reinforce or advance current practice.


Axelrod models of social influence with cultural repulsion.
Since both attractive and repulsive effects among agents are important in social systems, we present simulations of two models based on Axelrod's homogenization mechanism that includes repulsion. These models are the repulsive model, where all individuals can repel, and the partially repulsive model where only a fraction of repelling agents are considered. In these two models, attractive dynamics is implemented for agents with the ability to repel each other only if the number of features shared by them is greater than a threshold parameter. Otherwise, repelling dynamics is used. In the repulsive model, the transition from a monocultural state to a fragmented one often occurs abruptly from one cultural-variability value to the next one and a second transition emerges. For the partially repulsive model, there are also two different transitions present: the initial one being as abrupt as the one found for the repulsive model, whereas the second one follows a less abrupt behavior and resembles that of the original Axelrod model. However, the second transition for this model occurrs from a partially fragmented state and not from a monocultural one.


Brucella haemorrhagic pleural effusion.
Brucella melitensis (BM) is a rare respiratory pathogen. The lungs are usually affected in the subacute and chronic course of the disease, when pleurisy, empyema, hilar adenopathy, pneumonia and lung abscess have been described. We present a patient with BM haemorrhagic pleural effusion, with low pH, low glucose and positive pleural fluid cultures. Brucellosis should be considered in the differential diagnosis of patients with long-standing pleural effusions of unknown aetiology.


Separation of beta-galactosidases and beta-glucosidases from human liver.
Various fractions obtained from normal human liver homogenates by gel chromatography and selective adsorption and elution from insolubilized concanavalin A were compared as to their beta-galactosidase and beta-glucosidase activities. The high-molecular-weight acidic beta-galactosidase form was converted into the smaller major form by sodium dodecyl sulfate treatment. Electrophoresis and electrofocusing on acrylamide slabs revealed, in addition to the two major isoenzyme forms (acid and neutral), another five minor bands with enzymatic activity.


DNA Barcoding studies on Thrips in India: Cryptic species and Species complexes.
Thrips are one of the major sucking pest and vector of plant viruses causing huge economic loss in agriculture. The accurate identification of thrips is crucial for effective pest management strategies. However, morphology based identification has limitations and warrants integration of molecular data. We attempted the largest DNA barcoding initiative on 370 sequences of 89 thrips morphospecies including 104 novel sequences from 39 morphospecies, including the type specimens of four species. The results of multiple species delimitation methods (BIN, ABGD, GMYC and bPTP) were consistent for 73 species (82%) with their morphological identifications. A total of 107 molecular operational taxonomic units (MOTUs) was recovered for 89 morphospecies by superimposing multiple methods and applying a three level nomenclature system. We detected more than one MOTU in 14 morphospecies indicating to have cryptic diversity including, two major vector species (Frankliniella schultzei and Thrips palmi). However, four morphospecies (Thrips moundi, Thrips carthami, Haplothrips andersi and Haplothrips gowdeyi) showed low genetic distances between them with overlapping in barcode gap that requires further analysis with multiple molecular markers and more specimens from wide geographical areas for better taxonomic judgment. We also presented the advantage of simultaneous use of multiple delimitation methods for detection and identification of cryptic species.


Automated breast ultrasound system (ABUS): reproducibility of mass localization, size measurement, and characterization on serial examinations.
Automated breast ultrasound (ABUS) is gaining popularity for breast cancer detection and diagnosis with its high reproducibility. Consistent recognition of breast lesions on serial exams is critical, and high reproducibility for lesion characterization is expected with ABUS, but not well reported. To retrospectively evaluate the reproducibility of ABUS for mass localization, size measurement, and characterization. Bilateral whole breast US images were obtained twice using a commercially available ABUS within a mean interval of 1.3 days. In total, 24 patients were imaged before biopsy or surgery. There were 24 breast cancers and nine benign diagnoses. Two breast radiologists reviewed every paired three-dimensional dataset with regard to lesion visibility, reproducibility of documented location (clockface location, distance from nipple, and lesion depth), size of the lesions, and similarity for lesion characteristics. Lesion similarity was classified as being identical, similar, or different by consensus reading using the SomoVu workstation. Intraclass correlation coefficients (ICCs) and the Bland-Altman method were used to determine the amount of agreement between assessments of lesion location and size. Among 33 breast lesions, 31 lesions were depicted in both serial examinations. ICCs for the displayed lesion location (clock face location, distance from nipple), and the individual size of detected lesions were 0.994, 0.926, and 0.980, indicating excellent reliability. However, the ICC for lesion depth from the skin was 0.342 showing low reliability. For lesion similarity, 16 cancers and five benign lesions were classified as being identical, and six cancers and two benign lesions were classified as being similar. Two benign lesions were assessed to have different lesion characteristics and final assessment categories. The ABUS provided reproducible images for mass localization, size measurement, and characterization, which may be useful for follow-up studies.


[The progress of clinical research and treatment of monocular elevation deficiency].
Monocular elevation deficiency (MED) is a functional defect in upward eye movement caused by paralysis, restriction, or a combination of factors. The affected eye experiences limited movement in the upward, nasal, and temporal directions, often accompanied by downward deviation and ptosis. Previously known as double elevator palsy (DEP), MED can result from muscle paralysis responsible for upward movement, restriction of the inferior rectus muscle, or lesions in the supranuclear pathway. The Knapp procedure was once the most commonly used surgical approach for MED. However, in cases involving restriction of the inferior rectus muscle, a staged approach combining inferior rectus muscle weakening and subsequent Knapp procedure is necessary to avoid anterior segment ischemia. This has led to the development of alternative surgical techniques, such as single-rectus muscle transposition, partial tendon transposition, and muscle belly transposition. Differentiating MED subtypes based on the underlying paralysis or restriction etiology is crucial for determining the appropriate surgical plan. This review article summarizes the clinical features, classification, and available surgical options for MED, aiming to provide valuable insights for clinical research and treatment.


The effect of the extent of A1 pulley release on the force required to flex the digits. A cadaver study on the thumb, middle and ring fingers.
The A1 pulley was released distally in consecutive stages by 25%, 50%, 75% and 100% of its length. The force required to fully flex the digit at each stage was recorded. The force decreased with more extensive A1 pulley release and this became significant when more than 50% of the pulley was released. These changes were probably due to loss of friction force rather than bowstringing of the tendon.


Nonequilibrium fluctuation relations in a quantum coherent conductor.
We experimentally demonstrate the validity of nonequilibrium fluctuation relations by using a quantum coherent conductor. In equilibrium the fluctuation-dissipation relation leads to the correlation between current and current noise at the conductor, namely, the Johnson-Nyquist relation. When the conductor is voltage biased so that the nonlinear regime is entered, the fluctuation theorem has predicted similar nonequilibrium fluctuation relations, which hold true even when the Onsager-Casmir relations are broken in magnetic fields. Our experiments qualitatively validate the predictions as the first evidence of this theorem in the nonequilibrium quantum regime.


Understanding Glaucomatous Optic Neuropathy: The Synergy Between Clinical Observation and Investigation.
Glaucoma is a complex disorder of aging defined by the death of retinal ganglion cells and remodeling of connective tissues at the optic nerve head. Intraocular pressure-induced axonal injury at the optic nerve head leads to apoptosis. Loss of retinal ganglion cells follows a slowly progressive sequence. Clinical features of the disease have suggested and corroborated pathological events. The death of retinal ganglion cells causes secondary loss of neurons in the brain, but only as a by-product of injury to the retinal ganglion cells. Although therapy to lower intraocular pressure is moderately effective, new treatments are being developed to alter the remodeling of ocular connective tissue, to interrupt the injury signal from axon to soma, and to upregulate a variety of survival mechanisms.


Effect of land use history and pattern on soil carbon storage in arid region of Central Asia.
The purpose of this study is to investigate variations in soil organic carbon (SOC) in arid areas due to differences in the cultivation history, land use, and soil salinization. The study area is the lower Sangong River basin on the piedmont of the northern TianShan mountains, which experiences heavy land-use activities. In 1982 and 2005,127(152) and 74 (161) samples in old (new) oasis were collected from each site at the surface soil (i.e., 0-20 cm). The data reveal that the mean value of the surface soil organic carbon content of the old oasis was higher than that of the new oasis by 4.01 g/kg in 1982 and 3.79 g/kg in 2005. Additionally, the soil organic carbon content decreased more rapidly in the newly reclaimed oasis than in the old oasis from 1982 to 2005. The spatial pattern of the SOC content was correlated with the exploitation time in the new oasis, the agricultural land use history, and the SOC content. The decreasing trend is clearer in the high SOC content area than in the low SOC content area. Farmland is the largest carbon pool in both the new and old oases. The carbon density of the old oasis was higher than that of the new oasis by 4.01 and 3.79 g/kg in 1982 and 2005 respectively. The loss of SOC in the agricultural watershed of the arid region in NW China is obvious. Improvements of land management practices, such as no tillage, straw returning to soil, and balanced fertilization techniques, should be adopted to increase the SOC content.


Effects of joint stabilizers on proprioception and stability: A systematic review and meta-analysis.
The current review and meta-analysis systematically investigated the effect of joint stabilizers on proprioception, postural stability, and neurological activity. Systematic identification of published literature was performed on online databases; Scopus, PEDro, SportDiscus, and EMBASE, followed by a critical PEDro methodological quality appraisal. Data from the studies were extracted and summarized in a tabular format. Of 2954 records, 50 studies, involving 1443 participants met our inclusion criteria. In the included studies, 60% of studies reported significant enhancements (p < 0.05), 19% of studies reported enhancements (p > 0.05) and 21% of studies reported no effects of joint stabilizers on proprioception and/or postural stability. Meta-analysis of pooled studies demonstrated beneficial effects of joint stabilizers on the knee (95% CI: 0.35°-0.61°) and ankle (at 10: 0.1°-0.65°) joint proprioception, and negligible effects on postural stability (-0.28°-0.19°). The pooled evidence suggests that application of joint stabilizers enhances joint proprioception and stability by not merely altering the mechanical stability of the underlying musculoskeletal structures but by also causing subtle changes in cerebral haemodynamics and musculoskeletal activation. These findings support clinical implications of joint stabilizers as a prophylactic and rehabilitation measure in modern sports and rehabilitation settings.


Metabolic engineering of Escherichia coli to minimize byproduct formate and improving succinate productivity through increasing NADH availability by heterologous expression of NAD(+)-dependent formate dehydrogenase.
Succinic acid is a specialty chemical having numerous applications in industrial, pharmaceutical and food uses. One of the major challenges in the succinate fermentation process is eliminating the formation of byproducts. In this study, we describe eliminating byproduct formate and improving succinate productivity by reengineering a high succinate producing E. coli strain SBS550MG-Cms243(pHL413Km). The NAD(+)-dependent formate dehydrogenase gene (fdh1) of Candida boidinii was coexpressed with Lactococcus lactis pyruvate carboxylase (pycA) under the control of Ptrc and PpycA promoters in plasmid pHL413KF1. The newly introduced fdh1 converts 1 mol of formate into 1 mol of NADH and CO2. The reengineered strain SBS550MG-Cms243(pHL413KF1) retains the reducing power of formate through an increase in NADH availability. In anaerobic shake flask fermentations, the parent strain SBS550MG-Cms243(pHL413Km) consumed 99.86 mM glucose and produced 172.38 mM succinate, 16.16 mM formate and 4.42 mM acetate. The FDH bearing strain, SBS550MG-Cms243(pHL413KF1) consumed 98.43 mM glucose and produced 171.80 mM succinate, 1mM formate and 5.78 mM acetate. Furthermore, external formate supplementation to SBS550MG(pHL413KF1) fermentations resulted in about 6% increase in succinate yields as compared to SBS550MG(pHL413Km). In an anaerobic fed-batch bioreactor process, the average glucose consumption rate, succinate productivity, and byproduct formate concentration of SBS550MG(pHL413Km) was 1.40 g/L/h, 1g/L/h, and 17 mM, respectively. Whereas, the average glucose consumption rate, succinate productivity and byproduct formate concentration of SBS550MG(pHL413KF1) was 2 g/L/h, 2 g/L/h, 0-3 mM respectively. A high cell density culture of SBS550MG(pHL413KF1) showed further improvement in succinate productivity with a higher glucose consumption rate. Reduced levels of byproduct formate in succinate fermentation broth would provide an opportunity for reducing the cost associated with downstream processing, purification, and waste disposal.


Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage.
Asymmetric divisions allow a precursor to produce four distinct cells of a Drosophila sensory organ lineage (SOL). Whereas this process requires cell-cell communication via Notch (N) receptor, mitotic recombination that removes the N ligand Delta (Dl) or Serrate (Ser) in the SOL had mild or no effect. Removal of both Dl and Ser, however, led to cell fate transformations similar to the N phenotype. Cell fate transformation occurred even when a single SOL cell lost both Dl and Ser. Thus, Dl and Ser are redundant in mediating signaling between daughter cells to specify their distinct cell fates.