In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.
Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. None.


Prevalence and recovery of aspiration poststroke: a retrospective analysis.
This retrospective study was undertaken to review aspiration documented by videofluoroscopic modified barium swallow (VMBS) examination in a group of patients admitted to a stroke rehabilitation unit. Forty-two of 54 patients tested demonstrated evidence of aspiration of thin liquids on VMBS performed an average of over 5 weeks following the onset of stroke. However, only patients in whom there was clinical concern of aspiration (54 of 255 stroke patients admitted to the rehab unit) were tested with VMBS evaluation. With this limitation in mind, aspiration was demonstrated in at least 9.9% of all unilateral right hemispheric patients, 12.1% of unilateral left hemispheric, 24% of bilateral hemispheric, and 39.5% of brainstem stroke patients. Of the 42 patients in whom aspiration of thin liquids was demonstrated, 31 underwent repeat VMBS studies an average of 6 weeks after the initial VMBS. 7 of these 31 (22.6%) no longer showed aspiration on VMBS. Eighteen of the 42 patients (43%) clinically stopped aspirating over this 6-week period.


Regulation of epidermal growth factor (EGF) receptor activity during the modulation of protein synthesis.
The capacity of cultured human fibroblasts to bind 125I-labeled epidermal growth factor (EGF) was measured during protein synthesis inhibition and reinitiation. Protein synthesis was inhibited by incubation of human fibroblasts in histidine-free medium supplemented with L-histidinol to produce a stringent amino acid starvation. Under these conditions 125 I-EGF binding activity decreased with a half-life of 14.5 hours. Protein synthesis could be rapidly reinitiated by the addition of L-histidine to human fibroblasts which had been preincubated in histidinol containing media for 36 to 48 hours. 125I-EGF binding activity rapidly increased upon the reinitiation of protein synthesis. In the presence of serum 100% of the original binding capacity was recovered ten hours after the reinitiation or protein synthesis, while 70% of the binding capacity was recovered in 12 hours in serum-free media. The recovery of 125I-EGF binding activity after the reinitiation of protein synthesis, was not blocked by the presence of Actinomycin D, indicating that the messenger RNA for the EGF receptor may accumulate during the period of histidinol-mediated inhibition of protein synthesis. The time course of recovery of 125I-EGF binding activity after the reinitiation of protein synthesis is very similar to that observed during the recovery of receptor activity following "down regulation" of EGF receptor activity. Recovery from down regulation, however, was markedly sensitive to Actinomycin D.


Aortic valve disease and gamma-glutamyltransferase: accumulation in tissue and relationships with calcific degeneration.
Degenerative aortic valve disease is characterized by some of the histological features of atherosclerotic lesions. Gamma-glutamyltransferase (GGT) has been recently implicated in pathogenesis of atherosclerosis, as well as in modulation of cells involved in calcium metabolism. We aimed to evaluate the possible implication of this enzyme activity in aortic valve disease. GGT immunohistochemistry was performed on valve leaflets of 64 patients with aortic valve stenosis undergoing valve replacement. Fractional GGT activity in plasma and tissue was analysed in a subgroup of cases by molecular exclusion chromatography. A close association was found between tissue extracellular GGT staining and lipid deposits (p<0.0001). GGT was expressed by CD68-positive cells around neovessels, as well as by MMP-9- and TRAP-positive multinucleated cells in the vicinity of bone metaplasia areas. Total plasma GGT levels were associated with low HDL-c (p=0.028) and high triglycerides (p=0.017). Total GGT activity in tissue was negatively correlated with the extent of valves calcification (p=0.03). Both serum and tissue GGT levels were negatively associated with severity of valve stenosis, as judged by peak transvalvular pressure gradients (p<0.0003 and p<0.002, respectively). Accumulation of GGT activity inside the lipid component of valves leaflets suggests a common mechanism of lesion shaping underlying both atherosclerosis and degenerative aortic valve disease. Moreover, the finding of GGT expression in cells with an osteoclast-like phenotype, and its negative correlation with both valves calcification and degree of valvular stenosis lend additional support to the recently envisaged involvement of GGT in the homeostasis of calcified tissues.


[Construction of eukaryotic expression vectors for different domains of the extracellular region of RAGE and their expression in prostate cancer cells].
To construct eukaryotic expression vectors for different domains (V and VC1) of the extracellular region of the receptor of advanced glycation end products (RAGE) and investigate the roles of these domains in prostate cancer. The coding sequence of V and VC1 domains was amplified from the plasmid pcDNA3-HA-RAGE by PCR and cloned into the pcDNA3-HA vector following routine procedures. After identification by PCR and sequencing, the vectors including V and VC1 domains were transfected into PC-3 cells. Western blotting and immunofluorescence were used to detect the expression and distribution of the expressed products in transfected PC-3 cells. The expression vectors containing V and VC1 domains of RAGE were successfully constructed as confirmed by PCR and DNA sequence analysis. The V and VC1 domains of RAGE were highly expressed and showed a cytoplasmic distribution in transfected PC-3 cells. The constructed eukaryotic expression vectors for V and VC1 domains of RAGE can be efficiently expressed in prostate cancer cells.


TDDFT screening auxiliary withdrawing group and design the novel D-A-π-A organic dyes based on indoline dye for highly efficient dye-sensitized solar cells.
Based on the experimentally synthesized dye JZ145, we designed a series of novel D-A-π-A dyes SPL201-SPL211 with different π-conjugated bridges and a new auxiliary withdrawing group for highly efficient dye-sensitized solar cells (DSSCs) using density functional theory (DFT) and time-dependent DFT(TDDFT). The molecular structures, energy levels, absorption spectra, light-harvesting efficiency (LHE), driving force of injection(ΔGinj) and regeneration(ΔGreg), electron dipole moment (μnormal) and lifetime of the first excited state(τ) were all scrutinized in details. Results reveal that the additional withdrawing group A2 and the π-conjugated group di-η-hexyl-substituted cyclopentadithiophene (CPDT) are more promising functional groups for the organic dyes with D-A-π-A structure. We further designed SPL212 and SPL213 by employing indoline group as donor, the above screened functional groups as π-conjugated bridge and additional withdrawing group, biscarbodithiolic acid and dicyanovinyl sulfonic acid groups as acceptor group. We found that SPL212 exhibits not only a higher molar extinction coefficient with an increment of 30.8%, larger excited state lifetime and an obvious redshift of 201nm but also a broader absorption spectrum covering the entire visible range even up to near-IR of 1200nm compared to JZ145. So, SPL212 can be used as a promising candidate for DSSCs. In addition, the results also prove that biscarbodithiolic acid may be more favorable than dicyanovinylsulfonic acid as acceptor group in DSSCs.


Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study.
Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording provides information on both intracortical reorganization and networking, and that information could yield new insights into post-stroke neuroplasticity. However, a comprehensive investigation using both concurrent TMS-EEG and motor-evoked potential-based outcomes has not been carried out in patients with chronic stroke. Therefore, this study sought to investigate the intracortical and network neurophysiological features of patients with chronic stroke, using concurrent TMS-EEG and motor-evoked potential-based outcomes. A battery of motor-evoked potential-based measures and concurrent TMS-EEG recording were performed in 23 patients with chronic stroke and 21 age-matched healthy controls. The ipsilesional primary motor cortex (M1) of the patients with stroke showed significantly higher resting motor threshold (P = 0.002), reduced active motor-evoked potential amplitudes (P = 0.001) and a prolonged cortical silent period (P = 0.007), compared with their contralesional M1. The ipsilesional stimulation also produced a reduction in N100 amplitude of TMS-evoked potentials around the stimulated M1 (P = 0.007), which was significantly correlated with the ipsilesional resting motor threshold (P = 0.011) and motor-evoked potential amplitudes (P = 0.020). In addition, TMS-related oscillatory power was significantly reduced over the ipsilesional midline-prefrontal and parietal regions. Both intra/interhemispheric connectivity and network measures in the theta band were significantly reduced in the ipsilesional hemisphere compared with those in the contralesional hemisphere. The ipsilesional M1 demonstrated impaired GABA-B receptor-mediated intracortical inhibition characterized by reduced duration, but reduced magnitude. The N100 of TMS-evoked potentials appears to be a useful biomarker of post-stroke recovery.


Polyelectrolyte complex templated synthesis of monodisperse, sub-100 nm porous silica nanoparticles for cancer targeted and stimuli-responsive drug delivery.
Porous silica nanoparticles (PSiNPs) have long attracted interest in drug delivery research. However, conventional synthesis methods for sub-100 nm, functionalised PSiNPs typically give poor monodispersity, reproducibility, or involve complex synthetic protocols. We report a facile, reproducible, and cost-effective one-pot method for the synthesis of cancer targeting and pH responsive PSiNPs in this size range, without the need for post-synthetic modification. This was achieved by using monodisperse l-arginine (Arg)/ poly(acrylic acid) (PAA) polyelectrolyte complexes (PECs) as soft templates for silane hydrolysis and condensation. Highly uniform PSiNPs with tunable size control between 42 and 178 nm and disordered pore structure (1.1-2.7 nm) were obtained. Both PAA and Arg were retained within the PSiNPs, which enabled a high doxorubicin hydrochloride (Dox) loading capacity (22% w/w) and a 4-fold increase in drug release under weakly acidic pH compared to physiological pH. The surface presentation of Arg conferred significantly higher intracellular accumulation of Arg/PAA-PSiNPs in patient-derived glioblastoma cells compared to non-tumorigenic neural progenitor cells, which effectively translated to lower IC50 values for Dox-loaded Arg/PAA-PSiNPs than non-functionalised PSiNPs. This work brings forward new insights for the development of monodisperse PSiNPs with highly desirable built-in functionalities for biomedical applications.


A prospective comparative study of the relationship between different types of ring and microbial hand colonization among pediatric intensive care unit nurses.
The aim of the study is to assess the effect of ring wearing and ring types on hand contamination and efficacy of alcohol-based hand disinfection among nurses working in intensive care settings. Hand cultures were obtained from 84 nurses providing direct patient care in intensive care units of a pediatric hospital. Colony counts were compared depending on ring wearing and the type of ring worn. Twenty-eight nurses were asked to a wear plain wedding ring, 28 to wear rings with stones and 28 not to wear any rings, starting 15 days before and continuing throughout the study. Cultures were obtained by using sterile gloves containing phosphate-buffered-saline solution (PBS) after an alcohol-based hand disinfectant was used and bacteria were identified with standard laboratory tests. The nurses wearing rings had more Gram-positive, Gram-negative and total bacterial colonization on their hands than the nurses without rings despite using an alcohol-based rub (p=0.001). When comparing the two groups with rings (plain wedding rings and rings with stones), colony counts of Gram-positive, Gram-negative and total bacteria did not differ (p>0.05). Ring wearing increases the bacterial colonization of hands and alcohol-based hand disinfection might not significantly reduce contamination of the ring-wearing hands. The type of ring did not cause any significant difference on the bacterial load. Wearing rings could increase the frequency of transmission of potential nosocomial pathogens.


Immunohistochemical identification of gamma-aminobutyric acid-containing neurons in the rat basolateral amygdala.
The peroxidase-antiperoxidase immunohistochemical technique was used together with an antiserum to gamma-aminobutyric acid (GABA) to identify GABA-containing structures in the rat basolateral amygdala (ABL). Morphological characteristics of GABA-positive neurons in ABL indicate that they correspond to class II, and perhaps class III, local circuit neurons observed in previous Golgi studies. GABA-positive punctate structures resembling axon terminals were observed both in the neuropil and forming peri-cellular baskets around large unlabeled perikarya in ABL. These results suggest that the strong intrinsic inhibition noted in electrophysiological studies of ABL is due primarily to synapses of GABAergic class II neurons with class I projection neurons.


The #MeToo Movement and Perceptions of Sexual Assault: College Students' Recognition of Sexual Assault Experiences Over Time.
On October 15, 2017, Alyssa Milano encouraged anyone who had been sexually harassed or assaulted to respond on Twitter with the phrase, #MeToo. Millions responded and a cultural reckoning ensued. Anecdotally, the #MeToo movement appears to have affected survivors' acceptance and acknowledgment of their own sexual assault experiences, but empirical evidence is lacking. To address this gap, the aim of this study was to examine associations between behavioral and labeled reports of sexual assault and time since the #MeToo movement began. Participants were 2,566 college students who completed a sexual assault survey over the course of three years, overlapping with the onset of the #MeToo movement. Regarding our hypothesis that the prevalence of sexual assault - indicated by standardized behaviorally specific questions - would be relatively constant over time after controlling for demographics, a Bayesian logistic regression model yielded inconclusive results. However, among the 596 students who endorsed behaviorally specific screeners for sexual assault, a Bayesian linear regression model revealed that, after controlling for demographics and characteristics of the assault, participants were increasingly likely to label the experience a "sexual assault" with more time post #MeToo. Overall, findings revealed no evidence for or against changes in prevalence of sexual assault, but suggested there were associations between the #MeToo movement and greater recognition of past unwanted sexual experiences as "sexual assault" over time. These findings highlight the importance of considering social context in research examining sexual assault survivors' cognitions.


Disruption of the Clock Component Bmal1 in Mice Promotes Cancer Metastasis through the PAI-1-TGF-β-myoCAF-Dependent Mechanism.
The circadian clock in animals and humans plays crucial roles in multiple physiological processes. Disruption of circadian homeostasis causes detrimental effects. Here, it is demonstrated that the disruption of the circadian rhythm by genetic deletion of mouse brain and muscle ARNT-like 1 (Bmal1) gene, coding for the key clock transcription factor, augments an exacerbated fibrotic phenotype in various tumors. Accretion of cancer-associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive myoCAFs, accelerates tumor growth rates and metastatic potentials. Mechanistically, deletion of Bmal1 abrogates expression of its transcriptionally targeted plasminogen activator inhibitor-1 (PAI-1). Consequently, decreased levels of PAI-1 in the tumor microenvironment instigate plasmin activation through upregulation of tissue plasminogen activator and urokinase plasminogen activator. The activated plasmin converts latent TGF-β into its activated form, which potently induces tumor fibrosis and the transition of CAFs into myoCAFs, the latter promoting cancer metastasis. Pharmacological inhibition of the TGF-β signaling largely ablates the metastatic potentials of colorectal cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Together, these data provide novel mechanistic insights into disruption of the circadian clock in tumor growth and metastasis. It is reasonably speculated that normalization of the circadian rhythm in patients provides a novel paradigm for cancer therapy.


The analysis of the function, diversity, and evolution of the Bacillus phage genome.
Phages play a pivotal role in the evolution of microbial populations. The interactions between phages and their hosts are complex and may vary in response to host physiology and environmental conditions. Here, we have selected the genomes of some representative Bacillus prophages and lysosomes from the NCBI database for evolutionary analysis. We explored their evolutionary relationships and analyzed the protein information encoded by hundreds of Bacillus phages. We obtained the following conclusions: First, Bacillus phages carried some known functional gene fragments and a large number of unknown functional gene fragments, which might have an important impact on Bacillus populations, such as the formation of spores and biofilms and the transmission of virulence factors. Secondly, the Bacillus phage genome showed diversity, with a clear genome boundary between Bacillus prophages and Bacillus lytic phages. Furthermore, genetic mutations, sequence losses, duplications, and host-switching have occurred during the evolution of the Bacillus phage, resulting in low genome similarity between the Bacillus phages. Finally, the lysis module played an important influence on the process of Bacillus phage cross-species infestation. This study systematically described their protein function, diversity, and genome evolution, and the results of this study provide a basis for evolutionary diversity, horizontal gene transfer and co-evolution with the host in Bacillus phages.


Deficit of theory of mind after temporal lobe cerebral infarction.
Previous studies have indicated that the temporal lobe is involved in theory of mind (ToM). However, little attention has been paid to ToM in patients with cerebral infarction. In this study, we investigated the ability of ToM in patients with temporal lobe cerebral infarction (TLCI) using a variety of tests. In the study, 19 patients with TLCI and 20 healthy controls (HC) were examined using the Recognition of faux pas and the Reading the Mind in the Eyes (RME) tasks, to assess their ability of ToM. The results of the study indicated that the TLCI group performed significantly worse compared with the HC group as revealed in the total faux pas-related score and in emotion recognition (Mind Reading). Our results implied that patients with TLCI had difficulty in ToM. Our data provided new evidence that the temporal lobe may be involved in processing ToM inferences.


pH-sensitive diamond field-effect transistors (FETs) with directly aminated channel surface.
We have introduced pH sensors fabricated on diamond thin films through modification of the surface-terminated atom. We directly modified the diamond surface from hydrogen to amine or oxygen with ultraviolet (UV) irradiation under ammonia gas. The quantified amine site based on the spectra obtained by X-ray photoelectron spectroscopy (XPS) is 26% (2.6 x 10(14) cm(-2)) with UV irradiation for 8h and its coverage is dependent on the UV irradiation time. This directly aminated diamond surface is stable with long-term exposure in air and electrolyte solution. We fabricated diamond solution-gate field-effect transistors (SGFETs) without insulating layers on the channel surface. These diamond SGFETs with amine modified by direct amination are sensitive to pH (45 mV/pH) over a wide range from pH 2 to 12 and their sensitivity is dependent on the density of binding sites corresponding to UV irradiation time on the channel surface.


Neuronal intermediate filament α-internexin is expressed by neuronal lineages in the developing chicken retina.
α-Internexin, a neuronal intermediate filament (IF) protein that is expressed in most neurons at the beginning of differentiation, has been studied in the developing vertebrate retina. It has been suggested that α-internexin plays a role in neuroplasticity during development. However, the expression of α-internexin in the chicken retina has not been investigated. In this study, we identified the expression patterns of the chicken α-internexin (chkINA) and neurofilament (NF) proteins in the developing chicken retina. These proteins exhibited dynamic patterns of expression with the progression of retinal development. Expression of chkINA was detected in the processes of ganglion, amacrine, and horizontal cells throughout development. chkINA was also transiently expressed in photoreceptor and bipolar cell lineages. NF triplet proteins exhibited more restricted expression patterns than did chkINA during development. Our observations suggest the coexpression of chkINA and NF triplet proteins in ganglion and amacrine cells in the developing retina, as well as in horizontal cell processes in the adult chicken retina. Our results indicate that chkINA is transiently expressed in all neuronal lineages in the developing chicken retina. These findings provide novel information on chicken retinal cell development and suggest that chkINA is a good neuronal marker for the study of retinal differentiation.


miR-382-3p Overexpression attenuates N-methyl-D-aspartate-induced HT22 cell apoptosis via the regulation of the RhoC/ROCK1 signaling pathway.
miR-382-3p can regulate apoptosis through multiple pathways, but the mechanism remains unknown. In this experiment, we explored whether miR-382-3p can modulate the N-methyL-D-aspartate (NMDA)- induced HT22 cell apoptosis by regulating the RhoC/ROCK1 signaling pathway. An excitatory neurotoxicity model of HT22 cells was induced in vitro with 2 mmol/L NMDA. The cells were divided into normal control, NMDA-induced, NMDA + miR-382-3p mimic, and NMDA + miR-382-3p inhibitor groups. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, Real-time PCR, Western blot, and flow cytometry were performed to investigate the mechanisms. The results found that NMDA can increase the oxidative stress of HT22 cells in a dose-dependent manner, downregulate the expression of miR-382-3p, upregulate the expression of mRNA and protein abundance of ROCK1 and RhoC, increase the expression levels of proapoptotic proteins Bax, Caspase-3, and Caspase-9, increase the apoptosis of HT22 cells, and reduce the activity and survival rate of HT22 cells. Compared with the NMDA-induced group, the miR-382-3p mimic-transfected HT22 cells increased the expression of miR- 382-3p, reduced the expression of the mRNA and protein abundance of ROCK1 and RhoC, inhibited the expression of proapoptotic proteins Bax, Caspase-3, and Caspase-9, reduced the apoptosis of HT22 cells, and increased the activity and survival rate of HT22 cells. The results suggest that increasing the expression of miR-382-3p can inhibit the activity of the RhoC/ROCK1 signaling pathway, reduce the expression of proapoptotic proteins, reduce the oxidative stress and apoptosis of HT22 cells, and increase the activity and survival rate of HT22 cells.


Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources.
In this work, we identified glucose and glycerol as tacrolimus repressing carbon sources in the important species Streptomyces tsukubaensis. A genome-wide analysis of the transcriptomic response to glucose and glycerol additions was performed using microarray technology. The transcriptional time series obtained allowed us to compare the transcriptomic profiling of S. tsukubaensis growing under tacrolimus producing and non-producing conditions. The analysis revealed important and different metabolic changes after the additions and a lack of transcriptional activation of the fkb cluster. In addition, we detected important differences in the transcriptional response to glucose between S. tsukubaensis and the model species Streptomyces coelicolor. A number of genes encoding key players of morphological and biochemical differentiation were strongly and permanently downregulated by the carbon sources. Finally, we identified several genes showing transcriptional profiles highly correlated to that of the tacrolimus biosynthetic pathway regulator FkbN that might be potential candidates for the improvement of tacrolimus production.


New concepts in the surgical treatment of actual and impending pathological fractures in metastatic disease.
Long bone metastases are a disease of high social importance. The goals of surgical treatment are to relieve pain, maintain or restore joint function, and prevent or treat pathological fractures. "Oligometastases" is a disease with a limited number (3-5) of metastatic lesions in the same body district, where an aggressive treatment can be carried out with "curative" intent. This study aimed to evaluate patients with bone metastases surgically treated to determine how surgical treatment can influence prognosis and quality of life, comparing solitary metastasis, oligometastases, and multiple metastases. This is a retrospective analysis of 130 patients with long bone metastases surgically treated between October 2015 and August 2019: 40 patients had solitary metastasis; 38 had less than three metastases (oligometastases), and 52 had multiple metastases. Surgery was resection and reconstruction with a cemented prosthesis (95) or nailing (35). Overall survival was significantly better in patients with solitary metastasis or oligometastases than in those with multiple metastases (p <0.0001). Patients treated with resection and prosthesis had significantly better survival than those treated with nailing (p <0.0001). Implant complications requiring surgical revision occurred in 20 patients treated with prostheses, while no complications occurred in patients treated with nailing. Survival of cancer patients has improved in the last two decades, leading to an increase of diagnosed metastases. Patients with oligometastases have a survival similar to those with a single metastasis. Optimal implants survival curves should stay above the curves of patients survival. Since there are no differences in survival, patients with oligometastases should be treated as patients with a solitary lesion, with more aggressive surgery (wide resection and reconstruction with prosthesis). Intramedullary nailing is still indicated in metaphyseal or diaphyseal metastases in patients with advanced disease or poor prognosis when the life expectancy does not overcome the expected survival of the nail, avoiding the need for further surgery.


Analysis of microRNA expression in rat kidneys after VEGF inhibitor treatment under different degrees of hypoxia.
Previously, we found that the incidence of kidney injury in patients with chronic hypoxia was related to the partial pressure of arterial oxygen. However, at oxygen concentrations that contribute to kidney injury, the changes in the relationship between microRNAs (miRNAs) and the hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) axis and the key miRNAs involved in this process have not been elucidated. Therefore, we elucidated the relationship between VEGF and kidney injury at different oxygen concentrations and the mechanisms mediated by miRNAs. Sprague-Dawley rats were exposed to normobaric hypoxia and categorized into six groups based on the concentration of the oxygen inhaled and injection of the angiogenesis inhibitor bevacizumab, a humanized anti-VEGF monoclonal antibody. Renal tissue samples were processed to determine pathological and morphological changes and HIF-1α, VEGF, and miRNA expression. We performed a clustering analysis of high-risk pathways and key hub genes. The results were validated using two Gene Expression Omnibus datasets (GSE94717 and GSE30718). As inhaled oxygen concentration decreased, destructive changes in the kidney tissues became more severe. Although the kidney possesses a self-protective mechanism under an intermediate degree of hypoxia (10% O2), bevacizumab injections disrupted this mechanism, and VEGF expression was associated with the ability of the kidney to repair itself. rno-miR-124-3p was identified as a crucial miRNA; a key gene target, Mapk14, was identified during this process. VEGF plays an important role in kidney protection from injury under different hypoxia levels. Specific miRNAs and their target genes may serve as biomarkers that provide new insights into kidney injury treatment.NEW & NOTEWORTHY Renal tolerance to hypoxic environments is limited, and the degree of hypoxia does not show a linear relationship with angiogenesis. VEGF plays an important role in the kidney's self-protective mechanism under different levels of hypoxia. miR-124-3p may be particularly important in kidney repair, and it may modulate VEGF expression through the miR-124-3p/Mapk14 signaling pathway. These microRNAs may serve as biomarkers that provide new insights into kidney injury treatment.


Detection of long terminal repeat loci derived from endogenous retrovirus in junglefowl using whole-genome sequencing.
Endogenous retroviruses (ERVs) are genetic elements present in the genome that retain traces of past viral infections. Characterization of ERVs can provide crucial insights into avian evolution. This study aimed to identify novel long terminal repeat (LTR) loci derived from ERVs (ERV-LTRs) absent in the reference genome using whole-genome sequencing data of red junglefowl, gray junglefowl, Ceylon junglefowl, and green junglefowl. In total, 835 ERV-LTR loci were identified across the four Gallus species. The numbers of ERV-LTRs loci detected in red junglefowl and its subspecies gray junglefowl, Ceylon junglefowl, and green junglefowl were 362, 216, 193, and 128, respectively. The phylogenetic tree was congruent with previously reported trees, suggesting the potential for inferring relationships among past junglefowl populations from the identified ERV-LTR loci. Of the detected loci, 306 ERV-LTRs were identified near or within the genes, and some were associated with cell adhesion. The detected ERV-LTR sequences were classified as endogenous avian retrovirus family, avian leukosis virus subgroup E, Ovex-1, and murine leukemia virus-related ERVs. In addition, the sequence of the EAV family was divided into four patterns by combining the U3, R, and U5 regions. These findings contribute to a more comprehensive understanding of the characteristics of junglefowl ERVs.


Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia.
Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.


Hemofiltration modifies complement activation after extracorporeal circulation in infants.
Complement and fibrinolytic factors were measured in 9 infants undergoing hemofiltration immediately after cardiopulmonary bypass in an attempt to reduce activation of these systems. Plasma levels of C3a, C5a, and terminal complement complexes increased during bypass by 460%, 85%, and 745%. Plasma levels were reduced after hemofiltration in 8 of the 9 infants, and C3a and C5a fractions were recovered in the ultrafiltrate. The observed activation of the fibrinolytic system seemed to be unaltered by hemofiltration. Fibrinolytic factors were not filtered. Our study shows that increased concentrations of complement factors in the plasma after bypass in infants may be reduced by hemofiltration.


Survey of young women with breast cancer to identify rates of fertility preservation (FP) discussion and barriers to FP care.
To identify the proportion of reproductive age women with breast cancer that engaged in a fertility preservation discussion and reproductive endocrinology and infertility (REI) consultation. This cross-sectional survey recruited women 18-42 years who were diagnosed with breast cancer from 2006 to 2016 by phone or email and asked them to complete an online survey. Demographic characteristics, barriers to FP, utilization of FP consultation, and FP procedures (oocyte and embryo cryopreservation) were analyzed. A majority of women (64%) did not have FP discussed by any provider. Older women and those who were parents at the time of diagnosis were less likely to engage in a FP discussion. However, there were no significant differences in partner status or cancer stage between women with or without FP discussions. Of the women who desired future children prior to the cancer diagnosis, 93% received chemotherapy; however, only 34% of these women had a consultation with an REI. The most common reasons for declining FP consultation were already having their desired number of children (41%), financial barriers (14%), and concern about delaying cancer treatment and cancer recurrence (12%). Forty percent of women who desired future children and met with an REI pursued FP procedures. Younger women were more likely to receive FP counseling. FP consultations and procedures were low even in women who desired future fertility, with the predominant barriers being cost, fears concerning a delay in cancer treatment, and future cancer recurrence.


Production of antibody against saikosaponin a, an active component of bupleuri radix.
High titer rabbit polyclonal antibodies (pAbs) which show a specificity for saikosaponin a (SSA), have been generated. The immunogen used was a conjugate of SSA linked through its glucose moiety to bovine serum albumin by periodate oxidation method. The antibody titers obtained from two rabbits, inoculated with the immunogen, reached a plateau after the fourth and third booster injection, respectively. The specificity of the pAbs was determined by hapten inhibition assays using several SSA-like structures. SSA competitively inhibited the binding of the rabbit anti-SSA pAbs to SSA-ovalbumin on solid phase, a coated antigen on the well. The antibodies showed high specificity to SSA, exhibiting no significant cross-reactivity with any of SSA analogues tested.


Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.
Chronic pain affects 19% of adults in the United States, with increasing prevalence in active and aging populations. Pain can limit physical activity and activities of daily living (ADLs), resulting in declined mental and social health. Nutritional interventions for pain currently target inflammation or joint health, but few influence both. Collagen, the most abundant protein in the human body and constituent of the extra cellular matrix, is such a nutraceutical. While there have been reports of reductions in pain with short-term collagen peptide (CP) supplementation, there are no long-term studies specifically in healthy middle-aged active adults. To determine the effects of daily CP consumption over 3, 6, and 9 months on survey measures of pain, function, and physical and mental health using The Knee Injury & Osteoarthritis Outcomes Score (KOOS) and Veterans Rand 12 (VR-12) in middle-aged active adults. This study was a double-blind randomized control trial with three treatment groups (Placebo, 10 g/d CP, and 20 g/d CP). Improvements in ADLs (p = .031, ηp2 = .096) and pain (p = .037, ηp2 = .164) were observed with 10 g/d CP over 6 months, although pain only improved in high frequency exercisers (>180 min/week). Additionally, VR-12 mental component scores (MCS) improved with 10 g/d of CP over 3-9 months (p = .017, ηp2 = .309), while physical component scores (PCS) improved with 20 g/d of CP over 3-9 months, but only in females (p = .013, ηp2= .582). These findings suggest 10 to 20 g/d of CP supplementation over 6 to 9 months may improve ADLs, pain, MCS, and PCS in middle-aged active adults.


Role of MDR1 C3435T and GABRG2 C588T gene polymorphisms in seizure occurrence and MDR1 effect on anti-epileptic drug (phenytoin) absorption.
To assess the role of MDR1 and gamma-aminobutyric acid receptor-gamma 2 sub unit (GABRG2) gene polymorphism in seizure susceptibility in generalized seizure (GS) and febrile seizure (FS) patients and to evaluate MDR1 C3435T gene polymorphism's role in absorption of the anti-epileptic drug, phenytoin (PHT) in a cohort of patients. One hundred twenty-seven cases of seizure (86 GS and 41 FS) patients were analyzed for MDR1 C3435T and GABRG2 C588T gene polymorphisms using restriction fragment length polymorphism-polymerase chain reaction. Serum PHT levels were analyzed. The T allele of MDR1 C3435T and GABRG2 C588T gene polymorphism was higher in GS in the Indian population compared with controls. From the data in GS, CT and TT genotype carriers of the MDR1 gene and TT genotype carriers of the GABRG2 gene had more recurrent seizures compared with others. MDR1 T allele carriers in the seizure reoccurrence (SR) group of GS and FS were high compared with the well-controlled seizure group (with no seizures after treatment). TT genotype carriers in SR group were high in FS (with regard to MDR1 gene polymorphism) and GS (with regard to GABRG2 gene polymorphism) compared with a well-controlled seizure group. MDR1 C3435T gene polymorphism affects serum PHT levels (p<0.015). Association of dose PHT ratio and genotype groups of MDR1 C3435T gene polymorphism showed a significant association (p<0.05). MDR1*CC genotype was more common in cases with low serum PHT levels.In addition, it is evident that CT and TT genotype carriers have a high percentage of SR with elevated serum PHT levels. Our results show that the MDR1 3435T and GABRG2 588T alleles play a role in seizure occurrence. Moreover, the MDR1 3435T allele also affects PHT absorption. We suggest MDR1 C3435T and GABRG2 C588T genotyping would be of value in order to lower the risk of concentration-dependent drug toxicity and for better patient management.


Circulating vascular endothelial growth factor concentrations in a case of pulmonary hypertrophic osteoarthropathy. Correlation with disease activity.
Vascular endothelial growth factor (VEGF) is a cytokine overexpressed in hypoxic and malignant pathologies. VEGF induces vascular hyperplasia, new bone formation, and edema. These histological abnormalities characterize hypertrophic osteoarthropathy. We describe a case of pulmonary hypertrophic osteoarthropathy with high circulating VEGF levels. Removal of the lung tumor led to a dramatic disappearance of the skeletal abnormalities and to reduction of circulating VEGF levels. Histochemical studies of the excised tumor confirmed abnormal VEGF production.


Asking About Pets Enhances Patient Communication and Care: A Pilot Study.
This research explored whether asking patients about their pets would enable better environmental/social history taking, and improve patient communication/care. Primary health care providers (PHPs) were surveyed about prevalence of patients living with pets, the health impact of pets, and influences on patient communication. Following an educational intervention, they committed to asking patients about their pets. A follow-up survey was conducted electronically. PHPs were recruited at a continuing medical education (CME) conference and at CME workshops. All 225 participants were PHPs. At the conference, participants were educated one-on-one about the clinical relevance of pets in the family. CME sessions were large or small group teaching. Baseline and final surveys measured awareness of pets in patients' families, assessment of determinants of health, impact on rapport with patients, and patient care. A sign test assessed difference in scores using repeated-measures analysis. Binomial outcomes were assessed using Fisher's exact test. Comments were themed. Ninety-four PHPs (42%) completed the study. Pet-related discussions opened communication with patients. Two-thirds of participants identified positive effects on practice and on relationships with patients. PHPs were able to leverage the health benefits of pets (zooeyia) and mitigate zoonotic risk. Asking patients about pets in the family reveals clinically relevant information, improves communication, and strengthens the therapeutic alliance.


Comparison of early and delayed inpatient dexamethasone suppression tests.
Ninety-five inpatients completed a dexamethasone suppression test (DST) within 72 hours after admission and again after at least 1 week of medication-free hospital care. The frequency of cortisol nonsuppression in patients with endogenous depression (ED) was high and not significantly different at both tests. In patients with diagnoses other than ED, the higher rate of cortisol nonsuppression at the first DST was associated with a significant decrease in test specificity. Change in postdexamethasone cortisol levels at repeat testing was associated with a decrease in depressive symptomatology, but was not related to weight change during hospitalization.


Ultrastructural and functional development of macrophages in the dermal tissue of rat fetuses.
After about 12 days of gestation, fetal macrophages begin to appear in the subepidermal mesenchyme of rat fetuses. The macrophages are ultrastructurally characterized by cytoplasmic vacuoles, abundant polyribosomes and long filopodia. Immunocytologically, they possess Fc and complement (C3) receptors on the cell surface and are capable of immune phagocytosis, Latex or carbon phagocytosis, and glass adherence. From 15 days of gestation, lysosomal granules and micropinocytic vesicles gradually develop, together with an enlargement of Golgi complexes, whereas the number of polysomes and the number and size of cytoplasmic vacuoles are gradually reduced when gestation ends. Finally, the macrophages become amoeboid. Non-specific esterase and endogenous peroxidase activities are always absent in these macrophages. In culture experiments with cell suspensions prepared from the mesenchyme, fetal macrophages show a similar maturation process. Autoradiography with 3H-thymidine demonstrates a high proliferative capacity of the macrophages, particularly during the fetal stage.


Role of Avastin in management of central serous chorioretinopathy.
To evaluate the short-term safety and efficacy of intravitreal bevacizumab for the treatment of intraretinal or subretinal fluid accumulation secondary to central serous chorioretinopathy (CSC). Prospective interventional series non-comparative study. Department of Ophthalmology, Al-Minya University Faculty of Medicine, Egypt. The study included 20 eyes of 20 patients with central serous chorioretinopathy (CSC), Out of them 10 eyes with acute CSC (group I), 6 eyes with chronic CSC (defined as symptoms present for longer than 6 months) and four eyes with recurrent (defined as more than one episode of the disease) chronic and recurrent cases are considered in one group (group II), all patients were injected with intravitreal Avastin (IVA) 1.25 mg (0.05 mL) of commercially available bevacizumab [Avastin; Genentech, Inc., San Francisco, CA] as a primary treatment. At baseline and follow up visits patients had best corrected visual acuity (BCVA), IOP assessment, dilated fundus examination, fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT) imaging is used for measurement of central retinal thickness (CRT). Main outcome measures were the resolution of neurosensory detachment, improvement in visual symptoms and visual acuity, and resolution of leakage in FA. Secondary outcome and measures were the need for re-injection and the adverse effects. The mean number of injections was 2 (range 1-3 injections) 6-8 weeks intervals and follow up for 6 months (range 5-7 months). All finding at baseline and each follow up visit were reported and compared. The mean age of all patients was 40.3 years ± 6.5 (range 25-50 years), 15 males and five females patients. In acute CSC group, the mean baseline BCVA was 20/60 (log MAR 0.48) and improved to 20/30 (log MAR 0.18) with statistically significance difference change (P < 0.003) and in (chronic and recurrent group), the mean baseline VA was 20/80 (log MAR 0.60) and improved to 20/40 (log MAR 0.30) with statistically significance difference change (P < 0.002). The mean baseline CRT for all patients was 486 ± 86 μm (range, 386-580), decreased to 316 ± 56 μm (range, 276-368) after 1 months with statistically significance difference change (P < 0.02) and to 272 ± 52 μm (range 220-338) at last follow up with statistically significance difference change from the baseline (P < 0.001). Intravitreal Avastin (IVA) injection was associated with visual improvement and reduced neurosensory detachment without adverse events in patients with CSC. Although these results are promising, further randomized controlled studies would be helpful to understand this therapy for patients with CSC.


Use of discretionary protective equipment in high school athletes: prevalence and determinants.
We sought to describe the use of discretionary protective equipment among high school athletes and to examine social and behavioral determinants contributing to equipment usage. We analyzed data from a 3-year (1996-1999), stratified, 2-stage cluster sample of athletes engaged in 12 organized sports in 100 North Carolina high schools (n=19728 athlete-seasons) (an athlete-season represents an individual student who participates in a particular sport in a particular season). We used generalized logistic regression to model the association of social and behavioral determinants and demographic variables with discretionary protective equipment use. About one third of high school athletes self-reported using lower extremity discretionary protective equipment. Girls, seniors, those who played limited-contact sports, and those who played multiple sports reported higher usage. Small school size, low player/coach ratio, high proportion of team usage, and history of previous lower extremity injury were important predictors of usage. Coaches' experience, qualifications, and training, however, were not predictive of usage. Intervention efforts to promote use of discretionary protective equipment need to target school-level factors and should consider both team requirements and the role of peers in setting and reinforcing norms.


Osteoid osteoma of the patella: a case report.
Though osteoid osteoma is a common primary benign lesion of the bones, intra-articular involvement is rare and poses diagnostic difficulties when it affects middle-aged patients. We present the case of a 51-year-old woman with a 2.5 year history of anterior knee pain that was misdiagnosed as osteochondritis dissecans. Radiological findings were absent, whereas MRI showed a well-circumscribed lesion. A local excisional biopsy was performed and microscopic appearance confirmed diagnosis.


Diazoxide preconditioning of endothelial progenitor cells from streptozotocin-induced type 1 diabetic rats improves their ability to repair diabetic cardiomyopathy.
Type 1 diabetes mellitus (DM) is a strong risk factor for the development of diabetic cardiomyopathy (DCM) which is the leading cause of morbidity and mortality in the type 1 diabetic patients. Stem cells may act as a therapeutic agent for the repair of DCM. However, deteriorated functional abilities and survival of stem cells derived from type 1 diabetic subjects need to be overcome for obtaining potential outcome of the stem cell therapy. Diazoxide (DZ) a highly selective mitochondrial ATP-sensitive K(+) channel opener has been previously shown to improve the ability of mesenchymal stem cells for the repair of heart failure. In the present study, we evaluated the effects of DZ preconditioning in improving the ability of streptozotocin-induced type 1 diabetes affected bone marrow-derived endothelial progenitor cells (DM-EPCs) for the repair of DCM in the type 1 diabetic rats. DM-EPCs were characterized by immunocytochemistry, flow cytometry, and reverse transcriptase PCR for endothelial cell-specific markers like vWF, VE cadherin, VEGFR2, PECAM, CD34, and eNOS. In vitro studies included preconditioning of DM-EPCs with 200 μM DZ for 30 min followed by exposure to either 200 μM H2O2 for 2 h (for oxidative stress induction) or 30 mM glucose media (for induction of hyperglycemic stress) for 48 h. Non-preconditioned EPCs with and without exposure to H2O2 and 30 mM high glucose served as controls. These cells were then evaluated for survival (by MTT and XTT cell viability assays), senescence, paracrine potential (by ELISA for VEGF), and alteration in gene expression [VEGF, stromal derived factor-1α (SDF-1α), HGF, bFGF, Bcl2, and Caspase-3]. DZ preconditioned DM-EPCs demonstrated significantly increased survival and VEGF release while reduced cell injury and senescence. Furthermore, DZ preconditioned DM-EPCs exhibited up-regulated expression of prosurvival genes (VEGF, SDF-1α, HGF, bFGF, and Bcl2) on exposure to H2O2, and VEGF and Bcl2 on exposure to hyperglycemia while down regulation of Caspase-3 gene. Eight weeks after type 1 diabetes induction, DZ preconditioned, and non-preconditioned DM-EPCs were transplanted into left ventricle of diabetic rats (at a dose of 2 × 10(6) DM-EPCs/70 μl serum free medium). After 4 weeks, DZ preconditioned DM-EPCs transplantation improved cardiac function as assessed by Millar's apparatus. There was decrease in collagen content estimated by Masson's trichrome and sirius red staining. Furthermore, reduced cell injury was observed as evidenced by decreased expression of Caspase-3 and increased expression of prosurvival genes Bcl2, VEGF, and bFGF by semi-quantitative real-time PCR. In conclusion, the present study demonstrated that DZ preconditioning enhanced EPCs survival under oxidative and hyperglycemic stress and their ability to treat DCM.


Phospholipid metabolism of 3T3 mouse fibroblasts after serum stimulation and through the G1 and S cell cycle phases : incorporation and disappearance of 32P.
Phospholipid metabolism of 3T3 mouse fibroblasts has been studied after serum stimulation of arrested cells. The study of [32Pi] incorporation shows : a) in the case of PE and PC an early peak of incorporation in the G1 phase of the cell cycle, 6 hours after serum addition; b) in the case of PI an intense initial increasing of the incorporation which continues up to a S phase peak. The study of the disappearance of [32P] Phosphate from the different phospholipids points out: a) at the beginning of serum stimulation, an intense breakdown of PI, that continues through the G1 and S phases. Except at the onset, the breakdown of PI, is at any time exactly compensated for by synthesis : the two phenomena are closely linked; b) a synthesis of PE, from PC probably, at the G1 phase, 4 hours after the serum addition and the beginning of the chase experiment.


A new species of clearwing moth (Lepidoptera: Sesiidae: Osminiini) from Peninsular Malaysia, exhibiting bee-like morphology and behaviour.
A new species of Sesiidae, tribe Osminiini from Peninsular Malaysia, Heterosphecia pahangensis Skowron, displaying numerous bee-mimicking features, is described. DNA barcodes showed significant differences with related taxa. However, the paucity of Sesiidae barcodes from Southeast Asia prevents meaningful taxonomic comparisons. The closest match out of published data on Sesiidae barcodes is Heterosphecia bantanakai, Arita & Gorbunov (2000a) from the tribe Osminiini, which has 9.98% sequence divergence from Heterosphecia pahangensis. Photographs of the moth in its natural habitat are shown. Behavioural aspects, such as mud-puddling and mode of flight, are described and presented in a video.


Contact urticaria and its mechanisms.
This paper reviews the syndrome of contact urticaria in terms of current knowledge regarding pathophysiological mechanisms. The three mechanistic categories into which contact urticants are grouped include: (1) immunological contact urticaria, (2) non-immunological contact urticaria and (3) uncertain-mechanism-mediated contact urticaria. Within this schema, the clinical manifestations, diagnosis and therapy of contact urticaria are presented.


Does blue dye contribute to success of sentinel node mapping for breast cancer?
We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node (SLN) mapping at a high-volume institution. Using a prospectively maintained database, 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified. Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review. Statistical analysis was performed with Student t test and chi-square analysis. 2,049 (60.2%) patients underwent mapping with dual technique, and 1,353 (39.8%) with radioisotope only. Blue dye use decreased gradually over time (69.8% in 2002 to 48.3% in 2006, p < 0.0001). Blue dye was used significantly more frequently in patients with lower axillary counts, higher body mass index (BMI), African-American race, and higher T stage, and in patients not undergoing skin-sparing mastectomy. There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone (both 98.4%). Four (0.8%) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN. None of these four had significant counts detected in the axilla intraoperatively. Nine (0.4%) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye. Blue dye use has decreased with increasing institutional experience with SLN mapping. In patients with adequate radioactive counts in the axilla, blue dye is unlikely to improve the success of sentinel node mapping.


Aluminium and fluoride concentrations of three tea varieties growing at Lantau Island, Hong Kong.
The present project aims to investigate aluminium (Al) and fluoride (F) contents in teas (Camellia sinensis (L.) O. Kuntze). Three different commercial tea varieties: Assam variety and two China sub-varieties, a large leafed variety and small leafed variety, were collected in two tea gardens of Lantau Island tea plantation of Hong Kong. In general, high concentrations of Al and F were accumulated in the mature leaves (15.3 and of 2.07 g kg-1 respectively). Among the three varieties, 'the small leafed' variety exhibited the highest Al and F contents followed by the 'large leafed' variety whereas the Assam variety had the lowest Al and F concentrations in its tea bushes. Tea products from a plantation were also analysed and it was noted that black tea had higher Al and F concentrations than green tea. The amount of Al and F released into tea liquor was also tested and the results showed that higher concentrations of Al and F were released into tea liquor under repeated infusion method than continuous infusion method.


The Role of Italy's Ministero della Cultura in the Process of Improving Accessibility to Cultural Heritage: National Lines of Action and Prospects for Protection in the Territory of the Soprintendenza di Cremona, Lodi e Mantova.
Improving the accessibility of Italy's cultural heritage is one of the essential conditions for ensuring its qualitative fruition and, therefore, one of the main tasks of the Ministero della Cultura. Recent renewed interest in this issue has led to the launch of a series of important ministerial initiatives, both at the central and peripheral levels, with the main objective of seeking that delicate balance between the demands for conservation and protection and the improvement of the level and quality of accessibility.


Detection and Characterization of Flat Aberrant Crypt Foci (Flat ACF) in the Novel A/J Min/+ Mouse.
Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) have previously been described as preneoplastic colonic lesions. We used the novel A/J Min/+ mouse model, that demonstrates extensive spontaneous colon carcinogenesis to refine the method of detection of flat ACF and further characterize and define them as early lesions by histological examination and comparison with MDF. Colons were stained with methylene blue (MB) for flat ACF detection and restained with high-iron diamine-alcian blue (HID-AB) for MDF detection. Optimal flat ACF recognition required at least 24 h of storage post-MB staining and adherence to a set of characteristics. The fraction of flat ACF corresponding with MDF was 93%. Flat ACF/MDF displayed the same picture of severe dysplasia, lack of mucus and goblet cells and accumulation of cytoplasmic β-catenin. The easily detectable flat ACF are reliable surface biomarkers of Apc-driven colon carcinogenesis.


Ocular symptoms associated with digital device use in contact lens and non-contact lens groups.
Previous reports indicate that "eye fatigue" occurs in roughly 60 % of the adult population using digital devices and may negatively impact quality of life. However, the construct of eye fatigue remains poorly understood. The goal of this study was to quantify the relationship among symptoms most frequently associated with eye fatigue in those using digital devices. Six hundred and two soft contact lens (SCL) wearers and 127 non-contact lens (non-CL) wearers who reported using digital devices at least 4 hours per day completed a questionnaire assessing the frequency and severity of ten symptoms commonly associated with digital device-related eye fatigue. Subjective ratings were made separately for each symptom using unipolar, five-point Likert scales. From the initial pool of respondents, 89 % of the SCL wearers reported experiencing eye fatigue more than once per month, while over 60 % reported more than once per week. Notably, eye fatigue frequency did not differ between the soft contact and non-contact lens groups. Although eye strain/pain, dryness, and tired eyes were the most frequently endorsed symptoms by both groups, only dryness and eye irritation were significant factors that discriminated the SCL from the non-CL wearers on the basis of frequency and severity. Principal component analysis indicated that eye strain/pain, soreness, tired eyes, and headaches may comprise a "primary sensations" factor, whereas burning, eye irritation, tearing and dryness comprise a "secondary or surface sensations" factor, and blurred/double vision and words move/float comprise a "visual sensations" factor. Confirmatory factor analysis (CFA) of frequency and severity ratings for SCL wearers yielded excellent fits (RMSEA = 0.046 and 0.050, respectively) with construct reliabilities ranging from 0.729 to 0.824. Frequent and severe eye fatigue is highly prevalent among both soft contact lens and non-contact lens wearers. Those utilizing SCL do not experience symptoms at higher frequency or severity. Key descriptors of digital eye fatigue have been identified and may then be used to help identify and evaluate specific causative, palliative, or ameliorating factors.


[Hormonal homeostasis (somatotropin, thyrotropin, triiodothyronine and cortisol) and the histomorphologic indicators of the gastric mucosa during treatment with preparations enhancing protein synthesis (alvesin-new and retabolyl)].
The paper is devoted to a study of hormonal homeostasis and indices of histomorphological and endoscopic examination of the gastric mucosa in 96 patients with stomach ulcer with ulcerative defect of different site using the combination of an anabolic steroid nandrolene and alvezine-new. The incorporation of anabolic steroids and alvezine in multiple modality therapy was accompanied by a rise of epithelial mitotic activity, faster disappearance of inflammatory and dystrophic processes in the gastric mucosa and improved differentiation of cells of the main glands. A positive time course of histochemical indices was accompanied by favorable shifts in clinical signs of disease and hormonal homeostasis.


Arterial and venous signs of tumors within the fourth ventricle.
A positive diagnosis of tumors located within the fourth ventricle should be based on specific signs therby excluding other space occupying lesions in the posterior fossa. These are a typical omega form of the hemispheric cerebellar branches on the lateral projection, and an also typical inverted 3 form of the PICA in the semiaxial projection. Alteration of the veins of the lateral recess of the fourth ventricle and of the precentral cerebellar vein are important venous signs. Indirect signs are found in the absence of tonsillar herniation with arterial and venous signs of AP stretching of the cerebellar tonsils.


Ages and stages questionnaires: adaptation to an Arabic speaking population and cultural sensitivity.
Early detection of developmental delay is essential to initiate early intervention. The Ages and Stages Questionnaires (ASQ) correlate well with physician's assessment and have high predictive value. No such tool exists in Arabic. Translate and test the applicability and reliability of Arabic translated Ages and Stages Questionnaires (A-ASQ) in an Arabic speaking population. 733 healthy children were assessed. ASQ-II for 10 age groups (4-60 months) were translated to Arabic, back translations and cultural adaptation were performed. Test-retest reliability and internal consistency were evaluated using Pearson Correlation Coefficient (CC) and Cronbach's alpha (Cα). Mean scores per domain were compared to US normative scores using t-test. A-ASQ, after culturally relevant adaptations, was easily administered for 4-36 months age groups but not for 4-5 year old due to numerous cultural differences in the later. For the 4-36 month age groups Pearson CC ranged from 0.345 to 0.833. The internal consistency coefficients Cα scores ranged from 0.111 to 0.816. Significant differences were found in the mean domain scores of all age groups between Lebanese and US normative sample (p-value <0.001) with some exceptions in gross motor, fine motor and personal social domains. A-ASQ was easily translated and administered with acceptable internal consistency and reliability in the younger age groups. It proved to be culturally sensitive, which should be taken into consideration when adapting such tool to non-western populations.


Correction: Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway.
[This corrects the article DOI: 10.1371/journal.ppat.1005589.].


Risk-reduction surgery in BRCA mutation carriers in a Spanish population: adherence and results.
To analyse the level of adherence to prophylactic surgery of breast and/or ovarian cancer in female carriers of the BRCA1 or BRCA2 mutation in a referential genetic counselling unit in Spain. Between January 1998 and November 2006, a total of 684 families with several cases of breast and/or ovarian cancer were selected by the Genetic Counselling Unit at the Hospital Clínico Universitario San Carlos. Some of them opted for prophylactic surgery after genetic counselling and genetic testing. The pathogenic mutation was found in 57 families out of a total of 449 families who fulfilled the hereditary breast/ovarian cancer criteria. Out of a total of 238 individuals who were carriers of the mutation, 136 (57%) were offered risk-reducing prophylactic surgery. Prophylactic surgery was chosen by 58 (43%) women out of a total of 136 who were offered this possibility; the histological findings observed 7% malignant lesions in the breast and, in the ovarian-fallopian complex, 2 cases (8%) of a borderline tumour and one case (4%) of papillary adenocarcinoma. This is the first study published on the role of prophylactic surgery in BRCA mutation carriers in the Spanish population. The incidence of occult carcinoma in these cases is lower than in other series.


Patterns of antibiotic use and administration in hospitalized patients in Jordan.
Inappropriate use of antibiotics is the leading cause of emergence of resistance. It has been estimated that two million people in the United States had infection with resistant bacteria, resulting in 23,000 deaths annually. In Jordan, more than 50% of physicians prescribe antibiotics for inappropriate indication such as common cold, and approximately 67% of adult Jordanians believe that antibiotics should be used for this purpose. It is essential to follow antibiotics prescription guidelines in order to maximize effectiveness and enhance patient safety. The study aim was to describe patterns of antibiotics prescription and adherence to guidelines of IV to oral antibiotic conversion in elderly patients visiting King Abdullah University Hospital (KAUH). A retrospective cross sectional study was conducted on hospitalized patients who were prescribed IV antibiotics. Sociodemographic and clinical data in addition to a list of IV prescribed antibiotics was collected by referring to information technology department at KAUH. Patients' eligibility for antibiotic conversion from IV to oral route was then evaluated based on Society for Healthcare Epidemiology of America criteria. A total of 110 antibiotics were dispensed for 80 patients, imipenem/cilastatin was the most prescribed antibiotic (41.25%), followed by cephalosporines which were prescribed for 27.5% of the participants. Approximately half of the study patients (47.5%) were prescribed IV antibiotics despite their eligibility for oral conversion. This study shows a shortage in the implementation of guidelines which are important to decrease antibiotic resistance and improving clinical outcomes. The clinical Pharmacist needs to be more involved in antibiotics prescription with the aim of improving effectiveness and decreasing potential antimicrobial resistance in hospital settings.


Domain organization of Bacillus thuringiensis CryIIIA delta-endotoxin studied by denaturation in guanidine hydrochloride solutions and limited proteolysis.
Denaturation of Bacillus thuringiensis CryIIIA delta-endotoxin--an insecticidal protein, active against Coleoptera larvae--in concentrated guanidine hydrochloride solutions was pursued by fluorescence and circular dichroism spectroscopy and limited proteolysis. It was found that the protein consists of two fragments that differ by their stability to denaturation by guanidine hydrochloride at pH 3. The less stable fragment corresponds to the N-terminal alpha-helical domain limited by Leu-279; the more stable one starts with Ile-280, contains about 330 amino acid residues, and corresponds to the molecule C-terminal moiety that consist of its two beta-structural domains forming a superdomain.


On the choice of laser dyes for use in exciting tyrosine fluorescence decays.
The choice of laser dyes for exciting tyrosine fluorescence using synchronously pumped cavity-dumped dye laser systems is discussed. Rhodamine 560 was found to be optimal for a system based on an argon-ion pumping laser, whereas rhodamine 575 was preferred using a frequency-doubled Nd:YAG laser. Modifications of our fluorescence decay instrument to permit rejection of multiphoton events using a microchannel plate photomultiplier are described. An example of a four-component resolution of tyrosine decays illustrates the dramatic resolution capabilities attainable.


Confocal optical system: a novel noninvasive sensor to study mixing.
A novel confocal optical system to study mixing time in small-scale bioreactors is presented. The system is designed to monitor fluorescence upon tracer addition from a localized confocal volume of 0.21 mL within a glass vessel. The key elements of the fluorescence-based confocal system are a pinhole, a lens, an APD (Avalanche photodiode) detector, and light filters. The optical technique was validated by comparison with a pH-based technique. Finally, the optical sensor was tested and a real cultivation media (i.e., spent mammalian cell media) was used to measure mixing time in a 12.5-mL stirred transparent vessel. High accuracy, easy results interpretation, and low costs are the three most attractive characteristics of the sensor. Because of its noninvasive nature and versatility, the results suggest that the confocal system is a promising tool to perform mixing time studies in stirred vessels.


Controlled trial of universal neonatal screening for early identification of permanent childhood hearing impairment. Wessex Universal Neonatal Hearing Screening Trial Group.
Congenital permanent childhood hearing impairment (PCHI) impairs communication skills and, possibly, mental health and employment prospects. Management within 1 year of birth can alleviate most of its adverse effects. Neonatal screening for this disorder is feasible but its benefit for all babies is disputed. We investigated whether neonatal screening of all babies born in hospital, in addition to the standard health visitor distraction test, would increase the rates of early referral, confirmation, and management. Between 1993 and 1996, two teams of four part-time testers and equipment moved between two pairs of hospitals to achieve four periods with neonatal screening and four without neonatal screening, each of 4-6 months' duration. Babies did or did not undergo neonatal screening dependent on during which periods they were born. We used a transient evoked otoacoustic emissions test and, in babies who failed this test, an automated auditory brainstem response test on the same day. We referred babies with positive results for audiological assessment. 53,781 babies were included in the trial, and 25,609 were born during periods with neonatal screening. Neonatal screening achieved 87% coverage of births, with a false-alarm rate of 1.5%, and an overall yield of 90 cases of bilateral PCHI of 40 dB or more relative to hearing threshold level per 100,000 target population, equivalent to 80% of the expected prevalence of the disorder in the population. 71 more babies with moderate or severe PCHI per 100,000 target population were referred before age 6 months during periods with neonatal screening than during periods without. Early confirmation and management of PCHI were significantly increased. The rate of false-negative results from neonatal screening was significantly lower than that for the distraction test (4 vs 27% p=0.041). Neonatal screening is effective in identification of congenital PCHI early and may be particularly useful for babies with moderate and severe PCHI for whom early management may have the most benefit.


Molecular phylogenetic analysis of "pirate spiders" (Araneae, Mimetidae) with the description of a new African genus and the first report of maternal care in the family.
We investigate the phylogeny of "pirate spiders" (Mimetidae), a family of araneophagic spiders known for their use of aggressive mimicry as a foraging strategy, but poorly understood phylogenetically. Relationships are inferred by including molecular data from six loci for 92 mimetid terminals spanning four genera, and 119 outgroups representing 12 families. Phylogenetic analyses based on parsimony, maximum-likelihood and Bayesian approaches, as well as static and dynamic homology, robustly support monophyly of Mimetidae and a sister-group relationship to a clade comprising Tetragnathidae + Arkyidae. Relationships among the mimetid genera are largely congruent across methods, as follows: (Gelanor (Ero (Anansi n. gen. (Australomimetus, Mimetus)))). Diversification of Mimetidae is estimated to be around 114 Ma, in the Early Cretaceous. In light of the results of our phylogenetic analyses, we erect Anansi n. gen. to include a clade of mimetids from West Africa that contains at least four species, including the newly described A. luki n. sp. We present the first report of maternal care in Mimetidae based on novel field observations.


Nrp2 deficiency leads to trabecular bone loss and is accompanied by enhanced osteoclast and reduced osteoblast numbers.
Neuropilin 1 (Nrp1) and Nrp2 are transmembrane receptors that can bind class 3 semaphorins (Sema3A-G) in addition to VEGF family members to play important roles in axonal guidance, vascularization and angiogenesis, as well as immune responses. Moreover, recent evidence implicates Sema3A/Nrp-mediated signaling in bone regulation. However, to date the expression of Nrp2 in bone has not been investigated and a possible role for Nrp2 in the maintenance of bone homeostasis in vivo remains unexplored. Here we show that Nrp2, together with its possible coreceptors (Plexin A family members and Plexin D1) and class 3 semaphorin ligands, were expressed during in vitro osteogenic differentiation of bone marrow stromal cells. Moreover, Nrp2 transcript and protein levels were highly induced in hematopoietic bone marrow cell-derived osteoclast cultures. Osteoblastic as well as osteoclastic Nrp2 expression was confirmed by immunohistochemistry of the long bones of mice. Interestingly, Nrp2 knockout mice were characterized by a low bone mass phenotype which was accompanied by an increased number of osteoclasts and a decreased osteoblast count. Collectively, these data point to a physiological role for Nrp2 in bone homeostasis.


Cutaneous silent period in ulnar neuropathy at the elbow.
The cutaneous silent period (CSP) reflects the function of A-delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small-diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP. We consecutively evaluated UNE patients at one electrodiagnostic laboratory. The CSP was obtained upon stimulating the fifth (D5) and third digits, recording from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. We enrolled 37 UNE patients (mean age 55.4 ± 11.2 y) and 30 controls (mean age 51.2 ± 11.1 y). The combinations of the D5-APB and D5-FDI mean onset latencies of CSP were significantly more prolonged in patients (83.7 ± 6.8 and 84.5 ± 8 ms, respectively) than in controls (78.2 ± 8.1 and 79.4 ± 7.6 ms, respectively). The D5-FDI duration of CSP was shorter in patients (52.2 ± 8.3 ms) than in controls (55.8 ± 7 ms). The mean of the onset latencies of D5-FDI and D5-APB was related to the clinical severity (P = .013 and .0025, respectively). D5-APB and D5-FDI onset latencies were more prolonged and the duration was shorter in the UNE group with absent ulnar sensory nerve action potentials (SNAPs) and axonal motor damage than in patients with preserved SNAPs and with demyelinating damage. CSP was able to demonstrate abnormalities of small-diameter myelinated sensory fibers. This damage was directly related to UNE severity and to axonal damage of motor fibers. Absence of a sensory large-diameter fiber response did not exclude preserved residual small fiber conduction.


VCMM: a visual tool for continuum molecular modeling.
This paper describes the design and function of a visualization tool, VCMM, for visualizing and analyzing data, and interfacing solvers for generic continuum molecular modeling. In particular, an emphasis of the program is to treat the data set based on unstructured mesh as used in finite/boundary element simulations, which largely enhances the capabilities of current visualization tools in this area that only support structured mesh. VCMM is segmented into molecular, meshing and numerical modules. The capabilities of molecular module include molecular visualization and force field assignment. Meshing module contains mesh generation, analysis and visualization tools. Numerical module currently provides a few finite/boundary element solvers of continuum molecular modeling, and contains several common visualization tools for the numerical result such as line and plane interpolations, surface probing, volume rendering and stream rendering. Three modules can exchange data with each other and carry out a complete process of modeling. Interfaces are also designed in order to facilitate usage of other mesh generation tools and numerical solvers. We develop a technique to accelerate data retrieval and have combined many graphical techniques in visualization. VCMM is highly extensible, and users can obtain more powerful functions by introducing relevant plug-ins. VCMM can also be useful in other fields such as computational quantum chemistry, image processing, and material science.


Nonionic versus ionic contrast media in intravenous urography: clinical trial in 1,000 consecutive patients.
A double-blind clinical trial was performed in 1,000 consecutive patients to compare the safety and efficacy of intravenously administered nonionic (iohexol) and ionic (metrizoate) urographic contrast media. The patients ranged in age from 10 to 80 years. The incidence of mild to moderate adverse effects was 7.7% with iohexol and 31.2% with metrizoate. No serious reactions were recorded with either of the contrast media. Urography with iohexol was found to give better parenchymal opacification, pelvocalyceal opacification, and overall quality. The sum of examinations with good and excellent overall quality was 97.8% with iohexol and 91.1% with metrizoate. The frequency of poor overall quality urograms was 1.6% with iohexol and 7.5% with metrizoate. The data suggest that iohexol is safer and more frequently produces urograms of better quality.


Crystal structure of reducing-end xylose-releasing exoxylanase in subfamily 7 of glycoside hydrolase family 30.
TcXyn30A from Talaromyces cellulolyticus, which belongs to subfamily 7 of the glycoside hydrolase family 30 (GH30-7), releases xylose from the reducing end of xylan and xylooligosaccharides (XOSs), the so-called reducing-end xylose-releasing exoxylanase (ReX). In this study, the crystal structures of TcXyn30A with and without xylose at subsite +1 (the binding site of the xylose residue at the reducing end) were determined. This is the first report on the structure of ReX in the family GH30-7. TcXyn30A forms a dimer. The complex structure of TcXyn30A with xylose revealed that subsite +1 is located at the dimer interface. TcXyn30A recognizes xylose at subsite +1 composed of amino acid residues from each monomer and blocks substrate binding to subsite +2 by dimer formation. Thus, the dimeric conformation is responsible for ReX activity. The structural comparison between TcXyn30A and the homologous enzyme indicated that subsite -2 is composed of assembled three stacked Trp residues, Trp49, Trp333, and Trp334, allowing TcXyn30A to accommodate xylan and any branched XOSs decorated with a substitution such as α-1,2-linked 4-O-methyl-d-glucuronic acid or α-1,2- and/or -1,3-linked L-arabinofuranose. These findings provide an insight into the structural determinants for ReX activity of TcXyn30A.


The effects of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue.
The effect of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue has been investigated. Synovial explants were maintained in tissue culture for periods up to six days and PGE2 concentrations in culture were determined by radioimmunoassay. The more potent nonsteroidal inhibitors of PGE2 production and their IC50 (micrometer) values were indomethacin 0.005, flufenamic acid 0.2, flurbiprofen 0.6, ibuprofen 2.0 , naproxen 6.0, phenylbutazone 10.0, and aspirin 20.0. Drugs with weak or insignificant effects were hydroxychloroquin, acetaminophen, azathioprine, chloroquin, penicillamine, gold Na thiomalate, and Na salicylate. Glucocorticoids were potent inhibitors; dexamethasone 0.003, prednisolone 0.01, hydrocortisone 0.03; while mineralocorticoids deoxycorticosterone and aldosterone were inactive at 1.0 micrometer. There is a reasonably good correlation between the IC50 concentrations of the nonsteroidal inhibitors and their peak free plasma concentration achieved during therapy in man. Inhibition of prostaglandin synthesis may contribute to the effects of many but not all anti-inflammatory drugs.


Adrenergic neurons in human brain demonstrated by immunohistochemistry with antibodies to phenylethanolamine-N-methyltransferase (PNMT): discovery of a new group in the nucleus tractus solitarius.
Adrenaline neurons in human brain were demonstrated by immunohistochemistry using antibody to phenylethanolamine-N-methyltransferase (PNMT), the final enzyme in the pathway of adrenaline synthesis, using fixed frozen sections and a highly sensitive free floating technique which utilizes metallization. Small densely packed PNMT-immunoreactive neurons were observed to form a nucleus lying just ventrolateral to the area postrema and in the dorsal part of the nucleus tractus solitarius. Larger adrenergic neurons were also present in and around the lateral reticular nucleus and in relationship with the dorsal motor nucleus of the vagus in regions equivalent to the C1 and C2 groups in rats. Longitudinally oriented PNMT-positive axons constitute a subset of tyrosine hydroxylase-immunoreactive axons in the dorsomedial reticular formation.


Fiftyfold amplification of the Lowry protein assay.
The blue product of the Lowry et al. (1951, J. Biol. Chem. 193, 265-275) reaction interacts with malachite green (MG), inducing a change in the visible light spectrum. At A690 nm the absorbance of malachite green solutions increases 10-fold in the presence of Lowry blue (LB). Under the optimum conditions, 0.01 A700 nm unit of Lowry blue produces a change in A690 nm unit of malachite green of 0.5 and the delta A690 nm is a linear function of Lowry blue concentration. Conditions under which this 50-fold amplification can be exploited to detect less than 100 ng of protein (or 4 micrograms X ml-1) are described. A number of chemicals including sodium dodecyl sulfate can interfere with the assay but a strategy has been devised to overcome these problems. Amplification of the Lowry assay appears to involve a cooperative interaction between malachite green and the Lowry blue product such that about 23 molecules of malachite green undergo a spectral shift per molecule of a model reactant such as tyrosine. Malachite green can be used to amplify the molybdenum blue signal obtained in other assays. Less than 10 pmol of tyrosine can be detected using this procedure. Lowry blue also interacts with auramine O, giving a large increase in A500 nm and a 40-fold amplification of the LB signal. As with malachite green, there is a cooperative interaction between auramine O and LB. About 72 molecules of auramine O undergo a spectral shift per molecule of tyrosine. The product of this reaction is also fluorescent and could be exploited in a protein assay.(ABSTRACT TRUNCATED AT 250 WORDS)


Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV.
Hepatitis B Virus (HBV) constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing were conducted on a recently established HBV replication system, through which we identified multiomic differentially expressed genes (DEGs) that HBV orchestrated to remodel host proteostasis networks. Our multiomics interrogation revealed that HBV induced significant changes in both transcription and translation of 35 canonical genes including PPP1R15A, PGAM5 and SIRT6, as well as the expression of at least 15 non-canonical open reading frames (ncORFs) including ncPON2 and ncGRWD1, thus revealing an extra coding potential of human genome. Overexpression of these five genes but not the enzymatically deficient SIRT6 mutants suppressed HBV replication while knockdown of SIRT6 had opposite effect. Furthermore, the expression of SIRT6 was down-regulated in patients, cells or animal models of HBV infection. Mechanistic study further indicated that SIRT6 directly binds to mini-chromosome and deacetylates histone H3 lysine 9 (H3K9ac) and histone H3 lysine 56 (H3K56ac), and chemical activation of endogenous SIRT6 with MDL800 suppressed HBV infection in vitro and in vivo. By generating the first multiomics landscape of host-HBV interaction, our work is thus opening a new avenue to facilitate therapeutic development against HBV infection.


Amiodarone-induced cutaneous leukocytoclastic vasculitis: a case report and a review of the literature.
Amiodarone can be used in a variety of arrhythmias. Given its widespread use, the probability of clinicians encountering its cutaneous adverse effects is high. A few cases of amiodarone-induced cutaneous vasculitis were reported in the literature, probably because it is underdiagnosed in clinical practice. Indeed, amiodarone-related cutaneous reactions may present a wide range of manifestations and are sometimes difficult to diagnose. Herein, we report a case with a sizeable necrotic ulcer on the left lower leg shortly after amiodarone exposure. A rigorous diagnostic study was performed before concluding the diagnosis of amiodarone-induced cutaneous vasculitis, which showed the histopathological features of leukocytoclastic vasculitis. The lesion was almost completely healed by the third month of discontinuation of amiodarone. We did a literature search and found seven cases which were reported as leukocytoclastic or lymphocytic vasculitis. We reviewed previous cases and presented our case in comparison to prior cases.


Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1β in the Lung Tissue and Blood Serum of Mice with Experimental Influenza.
We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1β levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 μg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. The results of studying the dynamics of the cytokine levels in the infected animals in general support the previous hypothesis that, in repeated dosing, tilorone enhances the IFN response (compensates for its deficiency) at the early stages of acute respiratory viral infections and suppresses (damps) excessive production of IFN and proinflammatory cytokines at the later stages.


Application of unmanned aerial vehicle (UAV) thermal infrared remote sensing to identify coal fires in the Huojitu coal mine in Shenmu city, China.
China is a major coal-producing country that consumes large amounts of coal every year. Due to the existence of many small coal kilns using backward mining methods, numerous worked-out areas have been formed. The coal mines were abandoned with no mitigation, so air penetrates into the roadways and contacts the coal seams; as a result, the residual coal seams spontaneously ignite to form coal fires. These coal fires have burned millions of tons of valuable coal resources and caused serious environmental problems. To implement fire suppression more effectively, coal fire detection is a key technology. In this paper, thermal infrared remote sensing from unmanned aerial vehicle combined with a surface survey is used to identify the range of coal fires in the Huojitu coal mine in Shenmu city. The scopes and locations of the fire zones are preliminarily delineated, which provides an accurate basis for the development of fire suppression projects.


Magnetic responses of the trigeminal nerve system of the bobolink (Dolichonyx oryzivorus).
Extracellular recordings using glass microelectrodes were made from the ophthalmic and supraorbital nerves of a transequatorial migratory bird, the bobolink. The rate of electrical activity was modified in 15% of the spontaneously active units by earth-strength alterations of the horizontal or vertical component of the ambient magnetic field using box coils. Responses to magnetic stimulation included augmentation or inhibition of spontaneous activity, or an ON-OFF or OFF response. Responses to magnetic stimulation were also recorded from the optic tectum and the pineal gland. The responses of the trigeminal system are probably independent of the visual system and indicate the presence of two separate magnetic receptor systems in one avian species. The responses from the trigeminal receptor may involve magnetite for transduction of magnetic field information.


Morphometric characteristics of preantral and antral follicles and expression of factors involved in folliculogenesis in ovaries of adult baboons (Papio anubis).
Baboons are commonly utilized as an animal model for studies of human reproduction. However, folliculogenesis in this species has not been fully documented. The aim of this study was to assess follicle morphometry and expression of essential proteins involved in folliculogenesis in baboons. Ovaries were recovered from four adult baboons and processed for histological evaluation and immunohistochemical analyses. Follicle proportion, follicle and oocyte diameter, theca layer thickness, number of granulosa cells, and follicle density were calculated. Immunohistochemical staining was also carried out for connexin 43 (Cx43), aromatase, and zona pellucida 3 (ZP3). A total of 2221 follicles were counted and measured. Proportions of primordial, primary, secondary, small antral, and large antral follicles were 49, 26, 23, 1, and 1 %, respectively. The increase in follicle diameter was due not only to the increase in oocyte diameter but also to granulosa cell proliferation. Almost all antral follicles were positive for Cx43 (89.8 %), aromatase (84.8 %), and ZP3 (100 %). Most secondary follicles were positive for Cx43 (65 %) and ZP3 (64.5 %), and some primary follicles were positive only for Cx43. No primordial follicles stained positive in any of these immunohistochemical analyses. Only antral follicles showed aromatase activity. On the basis of these results, we can conclude that folliculogenesis in baboons appears to be similar to that in humans, and this animal therefore constitutes a valuable model.


A systematic review of published literature describing factors associated with tuberculosis recurrence in people living with HIV in Africa.
A summary of factors associated with recurrent tuberculosis (TB) in the African HIV-infected population is lacking. We performed a systematic review to address this. We performed a literature search within PubMed and The WHO Global Library with specific inclusion and exclusion criteria to identify manuscripts emanating from the African continent which potentially described factors associated with recurrent TB in persons living with HIV. The literature search yielded 52 unique manuscripts, of which only 4 manuscripts were included in the final systematic review following application of the inclusion and exclusion criteria. Baseline CD4 count, baseline HIV viral load, a positive tuberculin skin test, prior active TB disease, cutaneous hypersensitivity reaction to treatment, having < 3 lung zones affected by prior TB disease, and anaemia were associated with recurrent TB in HIV-infected individuals, whilst age and antiretroviral status were not. The lack of studies describing recurrent TB in Africa which stratify results by HIV-status is a hindrance to understanding risk factors for recurrent TB in this population. This might be overcome by implementing guidelines related to the publishing of data from observational studies in peer-reviewed medical journals reporting recurrent TB in populations with a high-burden of HIV infection.


Weight and weddings: expectations about wedding-specific body weight and shape ideals and dieting and exercise behavior among university students.
Weddings are significant life events when brides and grooms often seek a culturally-defined ideal appearance. A cross-sectional survey of 275 unmarried university students assessed current weight and shape, general ideal weight and shape, desired wedding weight and shape, and expectations to diet and/or exercise when contemplating their future wedding. Results indicated that men and women conceptualize the size and scope of their wedding similarly, but wedding appearance (including weight) was more important among women than men. Few men and women idealized a wedding-specific weight and shape that differed from their general ideal weight and shape. When contemplating their future wedding day, expectations about engaging in weight control behaviors were more common among women, and exercise was preferred over dieting among both genders. These findings suggest that although weddings focus attention on body weight and shape, young adults do not have overly unrealistic body weight and shape expectations when contemplating their future wedding and generally do not construct a specific body weight and shape for their future wedding. These relationships may change as marriage becomes more salient.