Blood alcohol level tests in nightlife recreational settings as a preventive tool.
Getting drunk is a common practice in the nightlife context and is related to risk behaviors. One potentially preventive strategy would be to conduct breathalyzer (blood alcohol content level-BAC) tests in situ, encouraging the young people to take responsibility. The aim of this study is to evaluate the efficacy of such a measure. A sample of 555 young people were interviewed in the most popular nightlife recreational areas in three Spanish cities. After they answered to a brief questionnaire, the breathalyzer test was done and they were then informed of the results and also informed about the results, telling them what the maximum authorized rate of alcohol in expired air was for driving. After, they were asked about their drinking intentions for the rest of the night, and if they we going to be driving. Only 21.6% stated that they would stop drinking or drink less, while a similar percentage (21.5%) said they would drink even more than they had intended after finding out their BAC. The logistic regression indicated that the decision to drink more or less was influenced by the BAC level, the amount they had planned to drink prior to the test and high scores on "sensation seeking." Those who decided to drive had lower BAC levels and had planned to drink less prior to the interview. Prevention strategies involving attempts to change behavior through informing drinkers of their own BAC are controversial, since although for some it leads to their drinking less, in other cases the young people end up drinking more than they had planned.


Inter-population Differences in Retrogene Loss and Expression in Humans.
Gene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression.


Dynamic expression of cell surface hydrophobicity during initial yeast cell growth and before germ tube formation of Candida albicans.
Expression of cell surface hydrophobicity (CSH) during initial growth of Candida albicans was monitored. CSH of hydrophobic and hydrophilic yeast cells changed within 30 min upon subculture into fresh medium. Morphologic evidence of germination was preceded by expression of CSH. These results indicate that CSH expression is important in C. albicans growth.


Serum complements and immunoglobulin profiles in systemic lupus erythematosus patients: An observational study at a teaching hospital.
Serum complement proteins and autoantibodies play an important role in the pathogenesis and diagnosis of systemic lupus erythematosus (SLE). Abnormalities in various immunoglobulin levels are described in patients of SLE. To study the spectrum of clinical manifestations and measure the serum levels of complement C3, complement C4, autoantibodies and immunoglobulin G (IgG) in patients of SLE and compare with healthy controls. The present study is a prospective hospital-based observational study conducted between May 2014 and December 2018. Unpaired t-test was used to compare the mean values between the SLE patients and healthy controls. A total of 100 cases of SLE and 100 healthy controls were included in the study. The clinical data were retrieved. Serum antinuclear antibody, anti-ds DNA antibody, and anti-Smith antibody levels, and complements C3, C4 and IgG were measured. Arthritis (89%) and anaemia (65%) were two common clinical presentations. The low complement C3 levels and C4 were detected in 64 and 62% of the SLE patients. Serum IgG was increased in 41% of the patients. A reduced level of IgG was detected in 6% of the patients. Primary care physicians should be aware of the clinical and serological manifestations of SLE as early detection will reduce end-organ damage. Autoantibody testing and complement testing should be done in all suspected cases. This study showed a significantly reduced C3 and C4 and elevated IgG in many cases of SLE as compared to control. Hypogammaglobulinemia was also present in a minority of the cases.


Effect of immunosuppression and amphotericin B on Aspergillus antigenemia in an experimental model.
A modified enzyme-linked immunosorbent assay (ELISA) for crude carbohydrate antigen was used to evaluate the kinetics of aspergillus antigenemia and to determine the effect of therapy on circulating antigen levels in an experimental model. The ELISA was rapid, simple to perform, and able to detect less than 10 ng of antigen/mL of serum. The model was also used to evaluate the effect of temporary and persistent immunosuppression on experimental disease. Antigen levels rose progressively in untreated control rabbits; all 15 animals had significant antigenemia. Treated animals had markedly reduced antigen levels, but nine of 13 rabbits had detectable antigen after 72 h of therapy, a result that correlated with persistent disease. Therapy begun 24 h after challenge in temporarily immunosuppressed animals was more likely to sterilize tissues than was therapy begun 48 h after challenge. Therapy in persistently immunosuppressed rabbits was less effective and may require improved antifungal regimens to be successful.


Directed Evolution of FLS2 towards Novel Flagellin Peptide Recognition.
Microbe-associated molecular patterns (MAMPs) are molecules, or domains within molecules, that are conserved across microbial taxa and can be recognized by a plant or animal immune system. Although MAMP receptors have evolved to recognize conserved epitopes, the MAMPs in some microbial species or strains have diverged sufficiently to render them unrecognizable by some host immune systems. In this study, we carried out in vitro evolution of the Arabidopsis thaliana flagellin receptor FLAGELLIN-SENSING 2 (FLS2) to isolate derivatives that recognize one or more flagellin peptides from bacteria for which the wild-type Arabidopsis FLS2 confers little or no response. A targeted approach generated amino acid variation at FLS2 residues in a region previously implicated in flagellin recognition. The primary screen tested for elevated response to the canonical flagellin peptide from Pseudomonas aeruginosa, flg22. From this pool, we then identified five alleles of FLS2 that confer modest (quantitatively partial) recognition of an Erwinia amylovora flagellin peptide. Use of this Erwinia-based flagellin peptide to stimulate Arabidopsis plants expressing the resulting FLS2 alleles did not lead to a detectable reduction of virulent P. syringae pv. tomato growth. However, combination of two identified mutations into a single allele further increased FLS2-mediated responses to the E. amylovora flagellin peptide. These studies demonstrate the potential to raise the sensitivity of MAMP receptors toward particular targets.


Risk factors for childhood diarrhea incidence: dynamic analysis of a longitudinal study.
Several longitudinal studies have investigated factors associated with childhood diarrhea in developing countries. However, most studies have neglected important dynamic features of the longitudinal design and hierarchical interrelationships among the potential risk factors. We conducted a longitudinal study of 902 children, age 0 to 36 months at baseline, in a large urban center in northeastern Brazil. Diarrhea data were collected by following children from October 2000 until January 2002 with biweekly home visits. We used a dynamic time-to-event analysis to account for several longitudinal features. We applied an effect-decomposition strategy to quantify direct and indirect effects of risk factors grouped in different blocks. Child's age and an autoregressive effect of past diarrhea episodes explained some of the decline of diarrhea incidence observed throughout the study (from more than 14 episodes to 2 episodes per child-year), a phenomenon already observed but not explained in other longitudinal diarrhea studies. We identified the following major diarrhea determinants: low socioeconomic status, poor sanitation conditions, presence of intestinal parasites, and absence of prenatal examination. The effect of socioeconomic status was mediated mostly by living and sanitation conditions. Our study shows important advantages of applying a dynamic analysis approach to longitudinal observational studies of diarrhea or other acute diseases and highlights the complex interrelationships of diarrhea determinants. Our results confirm the importance of sanitation as a major determinant of child health in urban settings of developing countries.


Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.
Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. LSC-targeting therapies may thus improve outcome of patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens that induce T-cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LSCs and identified AML- and AML/LSC-associated HLA-presented antigens absent from normal tissues comprising nonmutated peptides, cryptic neoepitopes, and neoepitopes of common AML driver mutations of NPM1 and IDH2. Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. Together, these antigens shared among AML and LSCs represent prime targets for T cell-based therapies with potential of eliminating residual LSCs in patients with AML. The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. This study identifies and functionally validates LSC-associated HLA class I and HLA class II-presented antigens, paving the way to the development of LSC-directed T cell-based immunotherapeutic approaches for patients with AML. See related commentary by Ritz, p. 430 . This article is featured in Selected Articles from This Issue, p. 419.


Team identification relates to lower burnout-Emotional and instrumental support as two different social cure mechanisms.
Team identification is associated with less exhaustion and disengagement through more social support and higher collective self-efficacy. However, previous studies did not distinguish between emotional and instrumental support, even though both forms of support may relate differently to collective self-efficacy. By distinguishing between both support forms, we expected an indirect effect-the 'supportive structure' mechanism-of team identification on burnout mediated via emotional support. For a second mechanism-the 'supportive action' mechanism-we expected an indirect effect serially mediated by instrumental support and collective self-efficacy. We tested our hypotheses among NT1 = 567 employees in a four-wave study with 3-month time lags between measurement points. Partially in line with our expectations, emotional support (T2) mediated the relation between team identification (T1) and disengagement (T4), but not emotional exhaustion (T4). Moreover, as expected, the results showed an indirect association between team identification (T1) and emotional exhaustion and disengagement (T4) via instrumental support (T2) and collective self-efficacy (T3). Accordingly, employees benefit from both support forms but through different mechanisms. We discuss our findings and implications for future research.


Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations.
Chylous pleural effusion (chylothorax) frequently accompanies lymphatic vessel malformations and other conditions with lymphatic defects. Although retrograde flow of chyle from the thoracic duct is considered a potential mechanism underlying chylothorax in patients and mouse models, the path chyle takes to reach the thoracic cavity is unclear. Herein, we use a novel transgenic mouse model, where doxycycline-induced overexpression of vascular endothelial growth factor (VEGF)-C was driven by the adipocyte-specific promoter adiponectin (ADN), to determine how chylothorax forms. Surprisingly, 100% of adult ADN-VEGF-C mice developed chylothorax within 7 days. Rapid, consistent appearance of chylothorax enabled us to examine the step-by-step development in otherwise normal adult mice. Dynamic imaging with a fluorescent tracer revealed that lymph in the thoracic duct of these mice could enter the thoracic cavity by retrograde flow into enlarged paravertebral lymphatics and subpleural lymphatic plexuses that had incompetent lymphatic valves. Pleural mesothelium overlying the lymphatic plexuses underwent exfoliation that increased during doxycycline exposure. Together, the findings indicate that chylothorax in ADN-VEGF-C mice results from retrograde flow of chyle from the thoracic duct into lymphatic tributaries with defective valves. Chyle extravasates from these plexuses and enters the thoracic cavity through exfoliated regions of the pleural mesothelium.


Haemangiopericytoma with no dural attachment.
The authors describe a case of a gentleman in his 40s who presented with a space-occupying lesion in the right precentral gyrus which showed no dural attachment and was well circumscribed, both on imaging and at surgery. This lesion was histologically challenging to diagnose but favoured to be a haemangiopericytoma. The lack of dural attachment is unusual for this tumour type but is typically associated with metastases to the brain, and less commonly a solid primary central nervous system tumour. The authors propose that haemangiopericytoma should be regularly considered as a differential diagnosis of cerebral metastases so that inadequate preoperative anticipation and planning is not encountered.


Disease burden and antimicrobial resistance of invasive group B streptococcus among infants in China: a protocol for a national prospective observational study.
Group B Streptococcus (GBS) is a cause of neonatal sepsis, pneumonia, and meningitis that can lead to neurological sequelae in infants less than 3 months of age. The GBS disease burden is not known in China, therefore it cannot receive major attention. The main objectives of this study are the evaluation of the incidence of neonatal GBS infection, GBS case-fatality ratio, its serotypes and genotypes, bacterial resistance, clinical treatment and outcomes in China. We are conducting a nation-wide, population-based, multi-center, prospective, observational cohort study in China from May 2016 to December 2017. Eighteen large urban tertiary care hospitals from 16 provinces were selected that cover the eastern, southern, western, northern and central regions of China. Meanwhile, we retrospectively collected data and GBS strains from January 2015 to April 2016 from selected hospitals. The incidence rate per 1000 live births will be defined as the total number of confirmed GBS cases born in the selected hospitals divided by the number of live births in the hospitals during the study period. All GBS cases detected in selected hospitals will be used to calculate the case-fatality ratio and for the typing analysis. GBS isolates will be serotyped using the Strep-B-Latex® rapid latex agglutination test for serotyping of Group B streptococci. Multi-locus sequence typing (MLST) will be performed by sequencing the internal fragments of seven house-keeping genes. Antimicrobial susceptibility will be tested per interpretive standards established by the Clinical and Laboratory Standards Institute. The presence of the common resistance genes ermA, ermB, mefA, tetI, tetO and tetM will be tested by PCR. We are conducting the first national study to estimate the invasive GBS disease burden and antimicrobial resistance of GBS among infants in China. Study findings will provide important evidence for improving clinical practice to ensure timely diagnosis of GBS disease and decisions for preventive measures. Surveillance of antimicrobial resistance will promote the rational use of antimicrobials. The study was retrospectively registered at http://clinicaltrials.gov on June 13, 2016. It was granted a registration number of "NCT02812576".


Intraneural perineurioma: a systematic review with illustrative cases.
Intraneural perineurioma may be confused with other "onion bulb" Schwann cell entities (localized hypertrophic neuropathy, reactive/demyelinating processes, or inherited polyneuropathies of Charcot-Marie-Tooth/Dejerine Sottas) due to similar clinical, radiologic, and histologic features. Perineurial and Schwann cells can only be differentiated by ultrastructure and immunohistochemsitry. To identify and summarize the clinicopathologic features of true cases of intraneural perineurioma from the English language literature. A systematic review was performed on definitive intraneural perineuriomas identified through Medline. Baylor College of Medicine-affiliated hospitals' anatomic pathology databases yielded 2 illustrative intraneural perineurioma cases. Intraneural perineurioma inclusion criteria consisted of characteristic histology and confirmation of perineurial cell lineage by either immunohistochemistry (epithelial membrane antigen positive, S100 protein negative) and/or ultrastructural analysis (thin cytoplasmic processes with an incomplete basal lamina, poorly formed tight junctions, and pinocytotic vesicles). Clinicopathologic data were extracted from all identified articles, with subsequent statistical analysis of the following parameters: age, sex, race, tumor location, tumor size, duration of symptoms prior to diagnosis, treatment modalities and outcomes measures, follow-up assessment for tumor recurrence and metastasis, clinical features (history of trauma, motor/sensory abnormalities, clinical/family history), and diagnostic workup (routine histology, immunohistochemistry, ultrastructural analysis, and molecular/cytogenetic characteristics). Intraneural perineurioma is a neoplastic proliferation of perineurial cells with unique immunohistochemistry and ultrastructural features, and it is distinct from other onion bulb Schwann cell-derived entities. Despite harboring molecular abnormalities of the long arm of chromosome 22, intraneural perineurioma has not been associated with neurofibromatosis. Intraneural perineurioma is a benign peripheral nerve sheath tumor that does not recur or metastasize.


Clinical Approach to Incidental Pancreatic Cystic Neoplasm in Outpatient Clinics.
Cystic lesions of the pancreas are increasingly observed due to increased use of abdominal images. The malignant rate of pancreas cystic lesion varies widely between various types. Identification of malignant or high-risk lesions is important when determining the appropriate course of management. Using these image findings, including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines provide a rationale in identifying higher risk patients requiring further workups using an endoscopic ultrasound (EUS). EUS with fine needle aspiration and cytology allows confirmation of the cyst type and determines the risk of malignancy. Small cysts with no suspicious features may undergo the regular imaging study for regular surveillance due to low risk for malignancy. In this review, the differences between the 2012 IAP and 2015 AGA guidelines are presented, In addition to possible recommendations for management and surveillance.


Structures and dynamics of Drosophila Tpr inconsistent with a static, filamentous structure.
Here we report immunofluorescence localizations of the Drosophila Tpr protein which are inconsistent with a filament-forming protein statically associated with nuclear pore complex-associated intranuclear filaments. Using tissues from throughout the Drosophila life cycle, we observe that Tpr is often localized to discontinuous, likely granular or particulate structures in the deep nuclear interior. These apparent granules have no obvious connectivity to pore complexes in the nuclear periphery, and are often localized on the surfaces of chromosomes and to the perinucleolar region. Most strikingly, after 1 h of heat shock, the great majority of the Tpr in the deep nuclear interior accumulates at a single heat shock puff, while Tpr in the nuclear periphery appears unchanged. This heat shock puff, 93D, is a known repository for many components of pre-mRNA metabolism during heat shock. Although we do not observe Tpr at sites of transcription under normal conditions, the 93D heat shock result leads us to favor a role for Tpr in mRNA metabolism, such as the transport of mRNA through the nuclear interior to nuclear pore complexes. Consistent with this, we observe networks of Tpr containing granules spanning between the nucleolus and the nuclear periphery which are also decorated by an anti-SR protein antibody. Since we also observe Drosophila Tpr in reticular or fibrous structures in other nuclei, such as salivary gland polytene nuclei, these results indicate that Tpr can exist in at least two structural forms, and suggest that Tpr may relocalize or even change structural forms in response to cellular needs.


5-aza-2',2'-Difluoro Deoxycytidine (NUC013): A Novel Nucleoside DNA Methyl Transferase Inhibitor and Ribonucleotide Reductase Inhibitor for the Treatment of Cancer.
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0.0025). The maximum tolerated dose in mice of NUC013 is greater than 120 mg/kg administered intravenously for three consecutive days a week for three weeks. With this regimen and a dose of 20 mg/kg in a human leukemia HL-60 (p53-null) NCr-nu/nu mouse xenograft model (n = 10/group), NUC013 demonstrated a survival benefit (saline median survival (MS) = 26.5 days, NUC013 MS = 32 days and hazard ratio (HR) = 0.26 (p = 0.032)). In a colon cancer LoVo (TP53 WT) xenograft, mice treated with decitabine at 5 mg/kg had worse survival than saline controls (decitabine MS = 31 days, saline MS > 60 days and HR = 26.89 (p < 0.0001)). At a dose of 20 mg/kg NUC013, mean tumor volume in the LoVo xenografts was lower than controls by 50.9% and at 40 mg/kg by 53.7% (both p < 0.0001).


Sequential statistical optimization of a positively-charged submicron emulsion of miconazole.
A positively charged oil/water (O/W) emulsion containing an antifungal agent was developed for ophthalmic use. An attempt was made using a sequential statistical methodology to optimize the O/W emulsion by varying both formulation and process parameters to obtain the smallest droplet size emulsion that can remain stable for a long period of time. During the first step of the study, not less than 7 parameters were found to be important--drug content, amount of lipophilic phase, poloxamer concentration, quantity of the phospholipids-stearylamine couple, pH adjustment, time of coarse emulsification and time of high pressure homogenization. A screening approach based on Hadamard's matrix was used to select the parameters displaying the most significant effects on response parameters. A first set of 8 experiments proved efficient enough to define the concentration of poloxamer and the quantity of the couple phospholipids-stearylamine, which confer the overall positive charge to the emulsified droplet, as the most significant parameters affecting the final droplet size of the emulsions formed. A 2k-type experimental design was then built with the two main factors in order to evaluate a first-order polynomial model with interaction. Poor analysis of variance results after an additional center experiment was performed revealed the lack of fit of the linear model as well as the importance of the response surface curvature due to a close optimum location. To find the optimal operating conditions the design was sequentially completed with 4 more experiments according to the Box and Wilson method. The response surfaces in 3-dimensional representation and their corresponding contour plots proved helpful in analyzing the validated models and in highlighting the precise optimum location. The optimized positive submicron emulsion is now under in vivo investigation.


[Effect of SIN-1 on the synthesis of leukotrienes in human polymorphonuclear cells].
Leukotriene (LT) synthesis triggered with ionophore A23187 or inflammatory stimuli (PAF, fMLP) in human polymorphonuclear leukocytes (PMNL) was markedly decreased by SIN-1, an active metabolite of molsidomine. This inhibition occurred in the absence or in the presence of exogenous arachidonic acid (AA). These results suggest that SIN-1 inhibited both the release of AA from membrane phospholipids and the 5-lipoxygenase activity in human PMNL. Molsidomine was without any effect on LT formation.


Biochemical markers of possible immunodepression in military training in harsh environments.
Prolonged, exhaustive exercise frequently leads to an increased incidence of upper respiratory tract illness (URTI) which is linked to transient immunodepression. We investigated potential biochemical markers of stress and fatigue, and URTI symptoms as a surrogate of immunodepression, in US Marines undergoing intensive winter training at altitude. Selected plasma amino acids and leptin (p[Lep]) were measured as possible markers of fatigue and immunodepression, together with nonesterified fatty acids (p[NEFA]) and total antioxidant capacity (p[TAC]). Changes were observed in plasma free tryptophan (p[FT]), p[Gln], p[Lep], p[NEFA], p[TAC] but not branched chain amino acids (p[BCAA]). p[FT] decreased markedly. Resting p[Gln] decreased overall after one month at altitude. p[Gln] routinely decreases 1-2 hrs after prolonged exercise. Importantly, we observed early morning decreases in p[Gln], suggesting a cumulative effect of prolonged activity, stress, and fatigue. Concomitantly, individuals with highest illness scores had the greatest p[Gln] decrease: low p[Gln] may therefore be associated with a diminished stress tolerance.


Sexually dimorphic morphology and swimming performance relationships in wild-type zebrafish Danio rerio.
This study compared prolonged swimming performance (Ucrit ) between male and female Danio rerio, and characterized how body shape was associated with this performance measure in each sex. When swimming in small (n = 6) mixed-sex groups at 28 °C, males swam, on average, over 10 cm s(-1) faster than females despite being significantly smaller. Body shape was sexually dimorphic, with males and females exhibiting small, but statistically significant differences in most aspects of body shape. Body shape explained 18 and 43% of the variation in Ucrit among males and females. In general, effects of body shape on swimming performance appeared to be sex limited, whereby different aspects of body shape affected performance in each sex, although the contribution of the distance between pelvic and anal fins to swimming performance was weakly sexually antagonistic.


Air-cooled cold trap channel integrated in a microfluidic device for monitoring airborne BTEX with an improved detection limit.
We integrated an air-cooled cold trap (CT) channel in a microfluidic device for monitoring airborne benzene, toluene, ethylbenzene, and xylene (BTEX) gases and demonstrated its effect on improving the detection limit of the microfluidic device. The device consists of concentration and detection cells formed of 3 x 1 cm Pyrex plates. We first introduced a sample gas into the concentration cell, and the gas was adsorbed onto an adsorbent in the channel. We then raised the temperature using a thin-film heater and introduced the desorbed gas into the detection cell. To prevent dilution of the gas before detection, we propose an improvement to the concentration cell structure that involves the integration of the CT channel. We examined the CT effect by comparing three types of concentration cell with different channel structures. We found that we could detect a gas concentration about 2 orders of magnitude lower than in our previous work by optimizing the channel structure and integrating a CT channel. As an example of BTEX detection,we obtained a 0.05 ppm detection limit for toluene gas with a sampling time of 30 min.


Big lessons in revalidation.
A huge revalidation pilot at Aneurin Bevan Health Board in Wales – more than 800 staff embarked on the process in February – has delivered important lessons for other organisations and individual registrants about what to expect when they begin the process.


Structure-based molecular simulations reveal the enhancement of biased Brownian motions in single-headed kinesin.
Kinesin is a family of molecular motors that move unidirectionally along microtubules (MT) using ATP hydrolysis free energy. In the family, the conventional two-headed kinesin was experimentally characterized to move unidirectionally through "walking" in a hand-over-hand fashion by coordinated motions of the two heads. Interestingly a single-headed kinesin, a truncated KIF1A, still can generate a biased Brownian movement along MT, as observed by in vitro single molecule experiments. Thus, KIF1A must use a different mechanism from the conventional kinesin to achieve the unidirectional motions. Based on the energy landscape view of proteins, for the first time, we conducted a set of molecular simulations of the truncated KIF1A movements over an ATP hydrolysis cycle and found a mechanism exhibiting and enhancing stochastic forward-biased movements in a similar way to those in experiments. First, simulating stand-alone KIF1A, we did not find any biased movements, while we found that KIF1A with a large friction cargo-analog attached to the C-terminus can generate clearly biased Brownian movements upon an ATP hydrolysis cycle. The linked cargo-analog enhanced the detachment of the KIF1A from MT. Once detached, diffusion of the KIF1A head was restricted around the large cargo which was located in front of the head at the time of detachment, thus generating a forward bias of the diffusion. The cargo plays the role of a diffusional anchor, or cane, in KIF1A "walking."


Thyroid-associated orbitopathy in patients with thyroid carcinoma: A case report of 5 cases.
Thyroid-associated orbitopathy (TAO) is most often seen in patients with autoimmune thyroid disease. Data about TAO occurred in patients with thyroid carcinoma are rare. We give a report of 5 patients to present the clinical characteristics, treatment, and prognosis of this type of case. Five thyroid carcinoma patients presented with orbitopathy. Among them, two patients (patient 1 and 4) were hyperthyroid and TSH receptor antibody (TRAb) positive, two patients (patient 3 and 5) were euthyroid and displayed slightly elevated TRAb titres, one patient (patient 2) was euthyroid and TRAb negative. They were diagnosed as thyroid carcinoma and TAO. Patient 1 underwent total thyroidectomy, intravenous glucocorticoids (GCs) therapy, orbital decompression surgery and oral GCs therapy. Patient 2 and 3 only received total thyroidectomy. Patient 4 received sub-total thyroidectomy and oral GCs therapy. patient 5 didn't received thyroidectomy and underwent intravenous GCs therapy for 2 courses. Patient 1,2,3 showed an improvement of TAO at the final follow-up. Patient 4,5 showed no improvement of TAO at the final follow-up. When TAO present in patients with thyroid nodules, the possibility of thyroid carcinoma should be considered, and the nature of these nodules should be carefully evaluated. In some patients with thyroid carcinoma and TAO, the remission of TAO can be seen post total thyroidectomy. But for other patients, besides thyroidectomy, an adequate dose and course of intravenous GCs treatment and even ocular surgery are also needed.


[Effects of different type urban forest plantations on soil fertility].
Aimed to study the effects of different urban forest plantations on soil fertility, soil samples were collected from eight mono-cultured plantations (Larix gmelinii, Pinus sylvestris var. mongolica, Pinus tabulaeformis var. mukdensis, Phellodendron amurense, Juglans mandshurica, Fraxinus mandshurica, Betula platyphylla, and Quercus mongolica) and one mixed plantation (P. sylvestris var. mongolica + F. mandshurica + Picea koraiensis + P. amurense + B. platyphylla) established in Northeast Forestry University's Urban Forestry Demonstration Research Base in the 1950s, with two sites of neighboring farmland and abandoned farmland as the control. The soils in broadleaved forest plantations except Q. mongolica were near neutral, those in mixed plantation, L. gmelinii, P. sylvestris var. mongolica, and P. tabulaeformis var. mukdensis were slightly acidic, and that in Q. mongolica was acidic. The contents of soil organic matter, total N and P, available P and K, and hydrolysable N tended to decrease with soil depth. There existed significant differences in the chemical indices of the same soil layers among different plantations. The soil fertility was decreased in the order of F. mandshurica > P. amurense > mixed plantation > J. mandshurica > B. platyphylla > abandoned farmland > farmland > P. sylvestris var. mongolica > L. gmelinii > Q. mongolica > P. tabulaeformis var. mukdensis, suggesting that the soil fertility in broadleaved forest plantations except Q. mongolica and in mixed plantation increased, while that in needle-leaved forest plantations tended to decrease.


Cost of discarded medication in Indiana long-term care facilities.
The cost of discarded medication was studied in 17 Indiana intermediate-care and skilled-nursing facilities with varying bed capacities and drug-distribution systems. During visits to each facility, one or two pharmacists collected data on patients' drug regimens and the quantities of medication dispensed and discarded over periods of one to seven months. A total of $ 5,620 worth of medication ($ 4,472 excluding topical medications) was destroyed in the facilities during the study period. The projected annual cost of discarded medication was approximately $ 15,800 ($ 12,460 excluding topical medications). In the 13 facilities using some type of unit dose drug distribution system, the mean projected annual cost of discarded medication per patient ($ 4.07) was significantly less than for the four facilities using traditional drug-distribution systems ($ 23.54). There was an inverse relationship between bed capacity and mean projected annual cost of discarded medication per patient. The use of unit dose drug distribution systems in all long-term care facilities would be expected to result in substantial savings in the costs of discarded medications.


The Epidemiology of Zoonotic Brucellosis in Bahr el Ghazal Region of South Sudan.
Background: In this study, we focused on three zoonotic brucellosis risk groups; abattoir workers, febrile cases at Wau hospital and cattle herders, in Bahr el Ghazal region, South Sudan. Competitive c-ELISA was used to detect anti-Brucella antibodies in 725 individuals between December 2015 and May 2016. In addition, questionnaire metadata, focus group discussions and key informant interviews were used to characterize the epidemiology of zoonotic brucellosis in this region. Results: Overall, we estimate 27.2 % (95% CI = 23.9-30.6) brucellosis sero-prevalence; 32.1% (95% CI = 26.2-38.4), 23.0% (95% CI = 19.1-27.4) and 34.6% (95% CI = 24.4-46.3) among abattoir workers, febrile cases, and herders, respectively. Marital status (Single, OR = 0.58, 95%CI: 0.36-0.91, P = 0.02) and ethnicity (Kerash OR = 6.01, 95%CI: 1.97-21.10, P = 0.003 and Balanda, OR = 3.78, 95%CI: 1.42-12.02, P = 0.01) were associated with brucellosis. While gender and ethnicity were important factors for general awareness of zoonotic diseases. Highly ranked occupations at risk included veterinarian, butchers and milk handlers. We also identified covariate patterns for clinical diagnostics and public health interventions. Conclusion: We report the highest sero-prevalence of zoonotic brucellosis in three risk groups in the East African region. All this is not only occurring in a population with limited awareness that brucellosis is a zoonotic disease but also where one in nine health workers tested was sero-positive. We identified social demographic associations with brucellosis, however, the qualitative analysis suggests these are more complex and nuanced. Therefore, future studies could benefit from the use of the mixed methods approach to add extensiveness and depth to our understanding of zoonotic disease drivers, in order to implement mitigating measures such as cattle vaccination.


'Run, hide, tell' applies to nurses too.
Nursing student Rhiannon Owen was at a cash machine in a busy area of London on a Saturday night when a taxi swerved towards her and the driver screamed at her to run. Looking up, she saw a man three metres away holding a knife with a 12-inch blade.


Agreement between histological subtype on punch biopsy and surgical excision in primary basal cell carcinoma.
Diagnosis of clinically suspected basal cell carcinoma (BCC) by histological confirmation with punch biopsy has been recommended before treatment. Even shave biopsy has been proposed as useful to predict the correct subtype in primary BCC in 76-81%, whereas the agreement between histological BCC subtype on punch biopsy and subsequent excision specimens in recurrent BCC is 67.1%. However, no large studies on the agreement between histological BCC subtype seen on punch biopsy and the following surgical excision are performed in primary BCC. The aims of this study were (i) to establish the agreement between histological BCC subtype on punch biopsy and the subsequent surgical excision of primary BCC and; (ii) to investigate the proportion of primary BCCs in which punch biopsy enables identification of the most aggressive growth pattern. Retrospective analyses of 243 primary BCCs with both punch biopsy and subsequent surgical excision. Analyses were based on the most aggressive histological subtype of the tumour. The agreement between BCC subtype on punch biopsy and the subsequent surgical excision of primary BCCs was 60.9%. A punch biopsy can predict the most aggressive growth pattern of primary BCCs in 84.4%. Seventy-four percentage of all primary BCCs consisted of more than one histological subtype. Dermatologists and other physicians have to be aware of the limited diagnostic value of a punch biopsy to determine the histological BCC subtype of the whole lesion. Misdiagnosis of the subtype will lead to undertreatment in one of six primary BCCs.


Comparative Lysine Acetylome Analysis of Y. pestis YfiQ/CobB Mutants Reveals that Acetylation of SlyA Lys73 Significantly Promotes Biofilm Formation of Y. pestis.
Increasing evidence shows that protein lysine acetylation is involved in almost every aspect of cellular physiology in bacteria. Yersinia pestis is a flea-borne pathogen responsible for millions of human deaths in three global pandemics. However, the functional role of lysine acetylation in this pathogen remains unclear. Here, we found more acetylated proteins and a higher degree of acetylation in Y. pestis grown under mammalian host (Mh) conditions than under flea vector (Fv) conditions, suggesting that protein acetylation could significantly change during fleabite transmission. Comparative acetylome analysis of mutants of YfiQ and CobB, the major acetyltransferase and deacetylase of Y. pestis, respectively, identified 23 YfiQ-dependent and 315 CobB-dependent acetylated proteins. Further results demonstrated that acetylation of Lys73 of the SlyA protein, a MarR-family transcriptional regulator, inhibits its binding to the promoter of target genes, including hmsT that encodes diguanylate cyclase responsible for the synthesis of c-di-GMP, and significantly enhances biofilm formation of Y. pestis. Our study presents the first extensive acetylome data of Y. pestis and a critical resource for the functional study of lysine acetylation in this pathogen. IMPORTANCE Yersinia pestis is the etiological agent of plague, historically responsible for three global pandemics. The 2017 plague epidemic in Madagascar was a reminder that Y. pestis remains a real threat in many parts of the world. Plague is a zoonotic disease that primarily infects rodents via fleabite, and transmission of Y. pestis from infected fleas to mammals requires rapid adaptive responses to adverse host environments to establish infection. Our study provides the first global profiling of lysine acetylation derived from mass spectrometry analysis in Y. pestis. Our data set can serve as a critical resource for the functional study of lysine acetylation in Y. pestis and provides new molecular insight into the physiological role of lysine acetylation in proteins. More importantly, we found that acetylation of Lys73 of SlyA significantly promotes biofilm formation of Y. pestis, indicating that bacteria can use lysine acetylation to fine-tune the expression of genes to improve adaptation.


Central Retinal Artery Occlusion after Rhinoplasty Surgery: A Case Report and Literature Review.
This study was aimed at reporting a case of central retinal artery occlusion (CRAO) after rhinoplasty. Case Report. Unilateral blindness occurred in a 22-year-old woman after rhinoplasty with a history of transient visual loss due to migraine aura and vasospasm. The physical examination of the patient revealed a visual acuity of no light perception in the right eye, a 4+ relative afferent pupillary defect, disc swelling, cherry-red spot in the macula, and ischemic retina in the right eye. Based on the diagnosis of CRAO, the patient underwent anterior chamber paracentesis (AC tap) along with treatment with mannitol and intravenous hydrocortisone. Visual acuity improved to 1/10 after a two-month follow-up. Taking history is very important in rhinoplasty surgery, and vasoconstrictors should be limited in the patients with a suspected history of vasospasm.


Extradural spinal cord compression by rheumatoid nodule.
Rheumatoid disease is a systemic disorder affecting multiple organs. It is known to affect the nervous system in a variety of ways, but its presentation with spinal cord compression by a rheumatoid nodule is rare. We report two cases presenting with cord compression by a rheumatoid nodule who underwent surgical decompression with good recovery.


Patient-satisfaction in an outpatient vein surgery office: A comparison of English- and Spanish-speaking patients.
In spite of an increasing Latino population and accompanying rise in demand for health care, not much is known about patient-satisfaction in Spanish-speaking patients and how to improve patient-satisfaction when using interpreters. We sought to compare patient-satisfaction with vein surgery office visits between English-speaking and Spanish-speaking patients. Directly before and after the office visit, 126 patients completed a socio-demographic survey, a five-point ordinal rating survey of physician and interpreter satisfaction with the encounter. Measures were satisfaction with the provider's friendliness, respectfulness, concern, ability to make the patient comfortable, and time spent for the exam. When the provider was fluent in the language that the patient spoke, patients ( M = 4.954, SD = 0.21) were significantly more satisfied with their visit at VVHC than patients who required an interpreter ( M = 4.762, SD = 0.71), z = 2.230, p = 0.012. Spanish speaking patients were more likely to be satisfied with the visit when they felt their interpreter was friendly ( n = 58, p = 0.049). There was no difference found with regard to the provider being thoughtful and comforting. Spanish-speaking patients are less satisfied with the care provided in a vein surgery office. Patients who communicated through an interpreter were less satisfied with the patient-provider relationship. In light of the growing diversity of the US population and the fact that patient-satisfaction is increasingly tied to reimbursement, additional research might identify potential areas of improvement for the surgeon, interpreter, and patient perspectives.


Correlating enzyme density, conformation and activity on nanoparticle surfaces in highly functional bio-nanocomposites.
The biological activity of the immobilized enzyme is crucial for the performance of different nanoparticle mediated enzymatic assays, where enzymatic conversion can be used for label-free analyte detection. In this article we have addressed two significant aspects of enzyme-nanoparticle interactions. First, we have developed copper sulfide (CuS) nanoparticles with an average diameter of 25 nm as a potential enzyme-interface using trypsin protease as a model enzyme. CuS nanoparticles showed high trypsin immobilization capacity of about 14.0 mg m(-2) with the significant retention of native enzymatic activity (75-98%) at room temperature, even beyond the calculated tightly packed monolayer coverage (which is around 4.1 mg m(-2)). Second, we report a quantitative correlation between the structure-functional relationship and the density of immobilized trypsin on a nanoparticle surface. The in situ conformation of immobilized trypsin could be efficiently analyzed by fluorescence, circular dichroism and FT-IR spectroscopic measurements because of the small size of the nanoparticles. Trypsin molecules appear to retain their close-native tertiary and secondary structural features (with a small loss of 1-2% of helical content) in the entire surface density range (2.0-14.0 mg m(-2)) on the CuS nanoparticles. However, interestingly, at a low surface coverage (2.0 mg m(-2)), immobilized trypsin retains almost 98% of its native enzymatic activity, leading to a highly functional bio-nanocomposite. However, at higher surface coverages, the enzyme activity decreases to 77%, indicating the influence of steric crowding. Furthermore, the high functionality of the immobilized trypsin at low surface density on CuS nanoparticle was also confirmed by determining the kinetic parameters of enzymatic activity.


Metabolic Complications and Kidney Transplantation: Focus on Glycaemia and Dyslipidaemia.
Post-transplant diabetes mellitus (PTDM) and dyslipidaemia are the most common metabolic complications in kidney transplant recipients (KTR). They are associated with a higher risk of lower graft function and survival, as well as an increased risk of cardiovascular disease (CVD). The aim of this review is to provide current data on the epidemiology, pathophysiology and optimal management of these two principal metabolic complications in KTR. Several risk factors in this metabolic milieu are either already present or emerge after renal transplantation, such as those due to immunosuppressive therapy. However, the exact pathogenic mechanisms have not been fully elucidated. Awareness of these disorders is crucial to estimate CVD risk in KTR and optimize screening and therapeutic strategies. These include lifestyle (preferably according to the Mediterranean pattern) and immunosuppressive regimen modification, as well as the best available anti-diabetic (insulin or oral hypoglycaemic agents) and hypolipidaemic (e.g. statins) regimen according to an individual's metabolic profile and medical history.


Malignant eccrine acrospiroma with metastasis to the parotid.
Malignant eccrine acrospiromas are rare. Clinically, they resemble other cutaneous lesions. A high index of suspicion must be maintained in cases of histologically benign eccrine acrospiromas for three reasons: (1) malignant transformation can occur, (2) the presence of both benign and malignant tissue can lead to a false-negative diagnosis if only the benign component is obtained in the biopsy specimen, and (3) benign-appearing tumors can recur locally or metastasize. The primary treatment is wide local excision with or without lymph node dissection. The efficacy of adjuvant chemotherapy and radiation therapy requires further investigation. We describe a case of malignant eccrine acrospiroma in an 80-year-old man, and we review the literature on this tumor, with emphasis on the differential diagnosis.


Aplastic anemia presenting as hemophagocytic lymphohistiocytosis.
Two unusual cases of hemophagocytic lymphohistiocytosis (HLH) complicating aplastic anemia (AA) are described. Each patient had a history of preexisting acute hepatitis of unknown cause at the time of HLH diagnosis and infection-associated secondary HLH. They developed high fever and pancytopenia. Hemophagocytes were seen in the bone marrow. With steroid (in combination with etoposide and CyA in 1 patient), high fever disappeared and the patients' liver function gradually recovered. As severe pancytopenia persisted, bone marrow became acellular and AA was diagnosed. Since HLH is known to be able to cause an aplastic bone marrow if untreated for a prolonged time, it is therefore in line that hepatitis-associated AA may also be associated with HLH. Aplastic anemia-associated HLH has been reported rarely, and problems in the diagnostic procedure are discussed.


Down-regulation of angiotensin II by shRNA reduces collagen synthesis in hepatic stellate cells.
The angiotensin-converting enzyme 2 (ACE-2), angiotensin II type I receptor (ATIR) antagonists and angiotensin-converting enzyme inhibitors (ACEI) were explored to block the renin-angiotensin-aldosterone system (RAAS). The experimental results were still not satisfactory, mainly due to excessive level of angiotensin II (AngII) in gene expression. RNA interference (RNAi) is a mature gene blocking technique, able to block target gene expression efficiently, specifically and continuously. In this study, we observed the effect of short hairpin RNA (shRNA) expression vectors targeting rat AngII on collagen synthesis in hepatic stellate cells (HSCs). According to rat AngII gene sequences, three AngII targeted shRNA expression vectors were designed and constructed. Using liposomes as transfection reagents, they were transfected into HSC-T6 cells. Enzyme digestion confirmed that the transfected shRNA target gene segment was successfully cloned to the vectors. Compared with the control group, AngII mRNA expression examined in shRNA1, shRNA2 and shRNA3 groups was inhibited by about 37, 30 and 61%, respectively. AngII protein expression in all three groups was also reduced by about 21, 24 and 59%, respectively. Furthermore, we revealed that the inhibitory effect exhibited a dose- and time-dependent relationship. In shRNA3 group, TGF-beta1 mRNA expression was reduced by about 51%. The levels of PIIIP, HA and LN were decreased by about 53, 47 and 58%, respectively. In conclusion, shRNA expression vectors targeting rat AngII can decrease collagen synthesis, which would hopefully serve as a foundation for RNAi study of liver fibrosis in vivo.


Regulation of Multiple Resonance Delayed Fluorescence via Through-Space Charge Transfer Excited State towards High-Efficiency and Stable Narrowband Electroluminescence.
B- and N-embedded multiple resonance (MR) type thermally activated delayed fluorescence (TADF) emitters usually suffer from slow reverse intersystem crossing (RISC) process and aggregation-caused emission quenching. Here, we report the design of a sandwich structure by placing the B-N MR core between two electron-donating moieties, inducing through-space charge transfer (TSCT) states. The proper adjusting of the energy levels brings about a 10-fold higher RISC rate in comparison with the parent B-N molecule. In the meantime, a high photoluminescence quantum yield of 91 % and a good color purity were maintained. Organic light-emitting diodes based on the new MR emitter achieved a maximum external quantum efficiency of 31.7 % and small roll-offs at high brightness. High device efficiencies were also obtained for a wide range of doping concentrations of up to 20 wt % thanks to the steric shielding of the B-N core. A good operational stability with LT95 of 85.2 h has also been revealed. The dual steric and electronic effects resulting from the introduction of a TSCT state offer an effective molecular design to address the critical challenges of MR-TADF emitters.


Sensitivity to Audiovisual Temporal Asynchrony in Children With a History of Specific Language Impairment and Their Peers With Typical Development: A Replication and Follow-Up Study.
Earlier, my colleagues and I showed that children with a history of specific language impairment (H-SLI) are significantly less able to detect audiovisual asynchrony compared with children with typical development (TD; Kaganovich & Schumaker, 2014). Here, I first replicate this finding in a new group of children with H-SLI and TD and then examine a relationship among audiovisual function, attention skills, and language in a combined pool of children. The stimuli were a pure tone and an explosion-shaped figure. Stimulus onset asynchrony (SOA) varied from 0-500 ms. Children pressed 1 button for perceived synchrony and another for asynchrony. I measured the number of synchronous perceptions at each SOA and calculated children's temporal binding windows. I, then, conducted multiple regressions to determine if audiovisual processing and attention can predict language skills. As in the earlier study, children with H-SLI perceived asynchrony significantly less frequently than children with TD at SOAs of 400-500 ms. Their temporal binding windows were also larger. Temporal precision and attention predicted 23%-37% of children's language ability. Audiovisual temporal processing is impaired in children with H-SLI. The degree of this impairment is a predictor of language skills. Once understood, the mechanisms underlying this deficit may become a new focus for language remediation.


Combined chemotherapy and local treatment in the management of intraocular retinoblastoma.
To assess the efficacy of chemotherapy (chemoreduction) plus local treatments as an alternative to external beam and enucleation for intraocular retinoblastoma. A prospective study was performed on 21 patients with retinoblastoma treated in our institution from September 1997 to December 2000 to study the ocular outcome of those 33 eyes. There were 9 unilateral and 12 bilateral retinoblastoma cases. There were 12 eyes with Reese-Ellsworth group I-IV and 21 eyes with group V. Among 33 eyes, nine eyes (27%) were initially managed by enucleation. The remaining 24 eyes (73%) were initially treated with chemoreduction (maximum of six cycles of carboplatin, vincristine, etoposide) or chemothermotherapy. Among those 24 eyes, 20 were successfully treated with local treatments (thermotherapy plus cryotherapy in 16 eyes and thermotherapy plus cryotherapy plus (125)I plaque radiotherapy in 4 eyes), enucleation eventually underwent in two eyes and was proposed but refused in one child with bilateral group V retinoblastoma. With a median follow-up of 21 months, conservative management without external beam radiation was successful in all 12 eyes with group I-IV and in a total of 20/33 eyes (60%). Among the nine cases of unilateral retinoblastoma, eight were enucleated but among the 24 eyes with bilateral retinoblastoma, 19 (79%) were successfully treated with conservative therapy. It may be possible to eradicate viable tumor in all eyes with Reese-Ellsworth group I-IV retinoblastoma by chemoreduction followed by local treatments. Although 8 out of 21 eyes (38%) with group V retinoblastoma may be salvaged after chemoreduction and local therapies, enucleation remained the treatment of choice in those eyes with total retinal detachment and diffuse vitreous seeding.


Transforming nonselective into chemoselective metal catalysts for the hydrogenation of substituted nitroaromatics.
It is generally accepted that good hydrogenation noble and nonnoble metal catalysts such as Pt, Ru, or Ni are not chemoselective for hydrogenation of nitro groups in substituted aromatic molecules. We have found that it is possible to transform nonchemoselective into highly chemoselective metal catalysts by controlling the coordination of metal surface atoms while introducing a cooperative effect between the metal and a properly selected support. Thus, highly chemoselective and general hydrogenation Pt, Ru, and Ni catalysts can be prepared by generating nanosized crystals of the metals on the surface of a TiO 2 support and decorating the exposed (111) and (100) crystal faces by means of a simple catalyst activation procedure. By doing this, it has been possible to change the relative rate for hydrogenating competitive groups present in the molecule by almost 2 orders of magnitude, increasing the chemoselectivity from less than 1% to more than 95%.


Evidence for obligate migratory flight behavior in young European corn borer (Lepidoptera: Crambidae) females.
European corn borer, Ostrinia nubilalis, flight behavior was examined in laboratory experiments. Adults were each tethered to 1 of 16 round-about flight mills in an environmental chamber, and the data were relayed to a computer. Parameters analyzed included duration, distance, and speed of the longest continuous flight and total flight time during an 8-h night. Comparisons were made between unmated and mated adults of both sexes at different ages up to 5 d after emergence. For unmated females, duration of the longest flight was highest the first night after emergence, declining significantly by 5 d of age. In contrast, duration of the longest flight for males was lowest at 1 d of age, increasing significantly by 3 d of age. Flight speed of females was roughly twice that of males at all ages. Mating did not affect flight behavior of either sex at any age tested, but mated adults could not be tested before 2 d of age because the first night was needed for mating. The pattern of age-specific flight behavior suggests that unmated females engage in obligate migratory flight the first full night after emergence. The median duration of this flight was approximately 2 h in our experiments, with some adults flying continuously for the full 8 h of darkness. Females of other ages and males of all ages tested were capable of long-duration flights, but they more likely represent foraging flight. These results help explain the high dispersal rate of newly emerged adults from release sites in field experiments.


Ranking competitors using degree-neutralized random walks.
Competition is ubiquitous in many complex biological, social, and technological systems, playing an integral role in the evolutionary dynamics of the systems. It is often useful to determine the dominance hierarchy or the rankings of the components of the system that compete for survival and success based on the outcomes of the competitions between them. Here we propose a ranking method based on the random walk on the network representing the competitors as nodes and competitions as directed edges with asymmetric weights. We use the edge weights and node degrees to define the gradient on each edge that guides the random walker towards the weaker (or the stronger) node, which enables us to interpret the steady-state occupancy as the measure of the node's weakness (or strength) that is free of unwarranted degree-induced bias. We apply our method to two real-world competition networks and explore the issues of ranking stabilization and prediction accuracy, finding that our method outperforms other methods including the baseline win-loss differential method in sparse networks.


A network coding based routing protocol for underwater sensor networks.
Due to the particularities of the underwater environment, some negative factors will seriously interfere with data transmission rates, reliability of data communication, communication range, and network throughput and energy consumption of underwater sensor networks (UWSNs). Thus, full consideration of node energy savings, while maintaining a quick, correct and effective data transmission, extending the network life cycle are essential when routing protocols for underwater sensor networks are studied. In this paper, we have proposed a novel routing algorithm for UWSNs. To increase energy consumption efficiency and extend network lifetime, we propose a time-slot based routing algorithm (TSR).We designed a probability balanced mechanism and applied it to TSR. The theory of network coding is introduced to TSBR to meet the requirement of further reducing node energy consumption and extending network lifetime. Hence, time-slot based balanced network coding (TSBNC) comes into being. We evaluated the proposed time-slot based balancing routing algorithm and compared it with other classical underwater routing protocols. The simulation results show that the proposed protocol can reduce the probability of node conflicts, shorten the process of routing construction, balance energy consumption of each node and effectively prolong the network lifetime.


Morphological evidence of an altered bone marrow microenvironment in patients with acute nonlymphoblastic leukemia and myelodysplastic disorders.
Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of type IV nuclear bodies in the in vitro bone marrow fibroblastic cells (FC) derived from eight nonleukemic subjects and 13 patients with acute nonlymphoblastic leukemia (ANLL) and myelodysplastic disorders (MDD). Patients with ANLL, MDD, and myelofibrosis, as a group, had four times as many type IV nuclear bodies as nonleukemic subjects. The mean frequency of type IV nuclear bodies for patients with ANLL and MDD was 2.68% +/- 3.27% as compared with 0.63% +/- 1.06% for the nonleukemic subjects (p less than 0.05). The mean maximum type IV nuclear body area of the ANLL and chronic myelomonocytic leukemia (CMML) patients as a group was 2.08 +/- 1.10 micron2, compared with a mean maximum area of 0.93 +/- 0.10 micron2 from nonleukemic subjects (p less than 0.05). The FC were otherwise morphologically indistinguishable and displayed the typical ultrastructural features of fibroblasts. These findings have provided the first morphologic evidence that supports the concept of an altered bone marrow microenvironment in patients with ANLL and MDD. Since type IV nuclear bodies are found in high frequency in virally infected tissues, our quantitative ultrastructural findings raise the possibility of a local viral infection that affects the bone marrow microenvironment of patients with ANLL and some MDD disorders.


Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles.
Asymmetric cascade double Michael additions to construct 2'-substituted 3,3'-spirooxindoles by using a chiral guanidine organocatalyst has been developed. A series of spirooxindole derivatives containing dihydrofuran or pyrrolidine subunits were obtained with good to excellent diastereo- and enantioselectivities. The method showed great tolerance of a number of aromatic and aliphatic alkynones. The strategy gave access to the asymmetric synthesis of (-)-salacin for the first time.


[Changes in percutaneous coronary intervention over the last 20 years: demographic, epidemiologic and clinical characteristics, techniques, and outcomes].
The aim of this study was to describe the changes observed in clinical practice in our interventional cardiology unit over the last 20 years. Between January 1, 1986 and December 31, 2005, >or=17,204 percutaneous transluminal coronary angioplasties (PTCAs) were performed at our center. They were analyzed in four periods of 5 years each. After each procedure, prospective data on patient, procedural, and outcome variables were recorded. The data were analyzed with regard to when the procedure was performed, and the patients' sex and age (i.e., < or >or=75 years). Data from 2006 were used as a reference, but were not included in the analysis. The number of PTCAs increased significantly. Over the time period, mean patient age increased (from 57[10] years to 62[12] years for males and from 66[10] years to 70[11] years for females), and there were significant increases in the proportions of women (from 16% to 22%) and patients aged >75 years (from 7% to 22%). Among men, the incidence of smoking decreased while that of hypertension, diabetes and hyperlipemia increased. Among women, however, there was no change in risk factors. The numbers of urgent and emergent procedures (17% of PTCAs were for acute myocardial infarction in 2006) increased in both sexes and age groups, more ad hoc procedures were carried out, and more lesions were treated, usually with a stent. Over time, the success rate increased and the complication rate decreased in both sexes and age groups. In-hospital mortality for all procedures, except those for acute myocardial infarction, was 0.7% in males and 1.4% in females (P=.012). Significant changes were observed over the last 20 years in the baseline characteristics of, the techniques used in, and the outcomes obtained in patients undergoing percutaneous coronary intervention.


Clinical significance of T cell clonality and expression levels of immune-related genes in endometrial cancer.
Immune microenvironment characterized by T cell clonality as well as expression signatures of immune-related genes in endometrial cancer tissues may play significant roles in clinical outcome of patients. We aimed to investigate the clinical significance of immune-related gene expression and TCR repertoire in endometrial cancer. Using total RNAs extracted from 32 endometrioid endometrial cancer cases, we performed quantitative real-time PCR to measure mRNA expression levels of immune-related genes including TRB, CD8, GZMA, HLA-A, CD11c and PD-L1. Higher mRNA expression levels of CD8 (P=0.039) and CD11c (P=0.046) in the 32 tissue samples were significantly associated with longer progression-free survival (PFS). Expression levels of CD8 (P<0.001) and CD11c (P=0.048) were also significantly associated with longer PFS in 540 cases in TCGA database. We also performed T cell receptor β (TCRβ) sequencing of tumor-infiltrating lymphocytes (TILs) on an Illumina MiSeq platform. To evaluate clonal expansion of TCRβ clonotypes, we adjusted the number of abundant TCRβ clonotypes by TRB mRNA expression levels and examined TCR clonality with the expression levels of immune-related genes and clinicopathological factors. The cases with high clonal T cell expansion along with high PD-L1 expression in cancer tissues was related to higher mRNA expression levels of CD8 (P<0.001), GZMA (P<0.001) and HLA-A (P=0.027), showed a significantly longer PFS (P=0.015), indicating a possibility that these parameters may serve as faborable prognostic factors. Considering clinical stage, mRNA expression of CD8 (P=0.037), GZMA (P=0.027) and HLA-A (P=0.022) was significantly higher in tumors at an early stage. Thus, we identified clinical and prognostic significance of immune microenvironment including the T cell clonality of TILs as well as PD-L1 and CD11c mRNA expression levels in endometrial cancer tissues.


Identification of Potential Diagnostic Biomarkers From Circulating Cells During the Course of Sleep Deprivation-Related Myocardial Infarction Based on Bioinformatics Analyses.
Myocardial infarction (MI) is the leading cause of death from non-infectious diseases worldwide and results in rapid deterioration due to the sudden rupture of plaques associated with atherosclerosis, a chronic inflammatory disease. Sleep is a key factor that regulates immune homeostasis of the body. The imbalance in circulating immune cells caused by sleep deprivation (SD) may represent a risk factor leading to the rapid deterioration of plaques and MI. Therefore, it is of profound significance to identify diagnostic biomarkers for preventing SD-related MI. In the present study, we identified coexpressed differentially expressed genes (co-DEGs) between peripheral blood mononuclear cells from MI and SD samples (compared to controls) from a public database. LASSO regression analysis was applied to identify significant diagnostic biomarkers from co-DEGs. Moreover, receiver operating characteristic (ROC) curve analysis was performed to test biomarker accuracy and diagnostic ability. We further analyzed immune cell enrichment in MI and SD samples using the CIBERSORT algorithm, and the correlation between biomarkers and immune cell composition was assessed. We also investigated whether diagnostic biomarkers are involved in immune cell signaling pathways in SD-related MI processes. A total of 10 downregulated co-DEGs from the sets of MI-DEGs and SD-DEGs were overlapped. After applying LASSO regression analysis, SYTL2, KLRD1, and C12orf75 were selected and validated as diagnostic biomarkers using ROC analysis. Next, we found that resting NK cells were downregulated in both the MI samples and SD samples, which is similar to the changes noted for SYTL2. Importantly, SYTL2 was strongly positively correlated not only with resting NK cells but also with most genes related to NK cell markers in the MI and SD datasets. Moreover, SYTL2 was highly associated with genes in NK cell signaling pathways, including the MAPK signaling pathway, cytotoxic granule movement and exocytosis, and NK cell activation. Furthermore, GSEA and KEGG analyses provided evidence that the DEGs identified from MI samples with low vs. high SYTL2 expression exhibited a strong association with the regulation of the immune response and NK cell-mediated cytotoxicity. In conclusion, SYTL2, KLRD1, and C12orf75 represent potential diagnostic biomarkers of MI. The association between SYTL2 and resting NK cells may be critically involved in SD-related MI development and occurrence.


The clinical investigation and management of chest pain in an emergency department: quality assessment by criteria mapping.
Criteria Mapping, a recently developed chart review method, was tested for its ability to assess the quality of symptom investigation and management for the presenting complaint of chest pain in an emergency department. A criteria map, which is based on decision making logic and permits use of criteria relevant to individual patients, was used to review the records of 137 patients who were examined for chest pain and subsequently discharged from the emergency department. All 111 patients assessed as receiving adequate process had positive outcomes. Twenty-six charts (19 per cent) were determined to have inadequate process, having failed at least one relevant and critical criterion; 23 of these 26 patients had positive outcomes. Review of the unmet criteria in these 23 charts revealed their uncertain predictive validity regarding immediate risk of death. We conclude that the Criteria Mapping method--the first reported technique for evaluating care for patient problems (as opposed to diagnoses)--provides an effective and feasible means for assessing the quality of symptom investigation and management.


Renal and Hepatic Functions after A Week of Controlled Ovarian Hyperstimulation during In Vitro Fertilization Cycles.
One the main aspects of in vitro fertilization (IVF) cycle is to avoid any possible systemic damage on women undergoing a controlled ovarian hyperstimulation (COH). The aim of this work is to evaluate renal and hepatic function blood tests in patients undergoing controlled ovarian hyperstimulation during IVF cycles. We performed a prospective cohort analysis. All patients re- ceived a long stimulation protocol with gonadotropin-releasing hormone (GnRH) analogues by daily administration, since the twenty-first day of the previous ovarian cycle followed by COH with recombinant follicle-stimulating hormone (FSH). The daily dose of exogenous gonadotropins for every single patient was modified according to her follicular growth. The oocytes were retrieved during the oocyte pick up and fertilized by standard procedures of intracytoplasmic sperm injection (ICSI). The blood samples to evaluate renal and hepatic functions were taken at the 7th day of ovarian stimulation. We enrolled 426 women aged between 19 and 44 years, with a mean body mass index (BMI) of 24.68 Kg/m2. The mean value of blood urea nitrogen was 14 ± 3.16 mg/ dl, creatinine: 1 ± 0.45 mg/dl, uric acid: 4 ± 1.95 mg/dl, total proteins: 7 ± 3.93 mg/dl, aspartate aminotransferase: 18 ± 6.29 mU/ml, alanine aminotransferase: 19 ± 10.41 mU/ ml, alkaline phosphatase: 81 ± 45.25 mU/ml, total bilirubin 1 ± 0.35 mg/dL. All of the results were considered as a normal range following the Medical Council of Canada. Our data suggest that, unlike ovarian hyperstimulation syndrome (OHSS), COH patients did not show any alteration to renal and hepatic functions.


Quantifying spatiotemporal chaos in Rayleigh-Bénard convection.
Using large-scale parallel numerical simulations we explore spatiotemporal chaos in Rayleigh-Bénard convection in a cylindrical domain with experimentally relevant boundary conditions. We use the variation of the spectrum of Lyapunov exponents and the leading-order Lyapunov vector with system parameters to quantify states of high-dimensional chaos in fluid convection. We explore the relationship between the time dynamics of the spectrum of Lyapunov exponents and the pattern dynamics. For chaotic dynamics we find that all of the Lyapunov exponents are positively correlated with the leading-order Lyapunov exponent, and we quantify the details of their response to the dynamics of defects. The leading-order Lyapunov vector is used to identify topological features of the fluid patterns that contribute significantly to the chaotic dynamics. Our results show a transition from boundary-dominated dynamics to bulk-dominated dynamics as the system size is increased. The spectrum of Lyapunov exponents is used to compute the variation of the fractal dimension with system parameters to quantify how the underlying high-dimensional strange attractor accommodates a range of different chaotic dynamics.


An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart.
Glufosfamide (β-D-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-D-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model. Cytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay. Glufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide. The current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.


1,n-Bisborylalkanes via Radical Boron Migration.
A systematic study of radical boron migration in diboronate complexes to form synthetically valuable 1,n-bisborylalkanes is reported. The boronate complexes are readily generated by reaction of commercial bis(pinacolato)diboron with alkyl Grignard compounds. C-radical generation at a defined position with respect to the diboron moiety is achieved either via intermolecular H-abstraction with a CF3-radical or via alkene perfluoroalkyl radical addition. It is shown that radical 1,2- and 1,4-boron migrations to provide geminal and 1,3-bisborylalkanes are efficient transformations. The 1,5-boron migration in the homologous series leading to 1,4-bisborylalkanes is also occurring, albeit with lower efficiency. Experimental results are supported by DFT calculations which also reveal the corresponding 1,3-boron migration in such diboronate complexes to be feasible.


Acute aortic dissection with tear in ascending aorta not diagnosed until necropsy or operation (for another condition) and comparison to similar cases receiving proper operative therapy.
Acute aortic dissection (AD) with a tear in ascending aorta (AA) is recognized to masquerade occasionally as another condition, and therefore the proper diagnosis is never made or made too late. During a recent 3-year period (2009 to 2011) at Baylor University Medical Center at Dallas, 30 patients with acute AD with tear in AA were diagnosed: 23 (77%) were diagnosed clinically and underwent proper urgent operative therapy; the remaining 7 (23%) with AD with tear in AA were not diagnosed until operation (for another condition) or necropsy or retrospectively by review of antemortem computed tomographic scan after death. The number of patients with AD from tear in AA whose cardiac condition was not diagnosed clinically and who died in the hospital but did not have an autopsy is unclear. Because the autopsy rate in most United States hospitals, including Baylor University Medical Center, is now <5%, many cases of AD are probably not diagnosed and thus its frequency is being underestimated. In conclusion, ≥ 7 of 30 patients (23%) with acute AD with a tear in AA were not diagnosed until necropsy or operation (for another condition) or retrospectively by computed tomography during a 3-year period at a large tertiary medical center showing that this condition continues to be underdiagnosed, and when not diagnosed correctly is usually rapidly fatal. Because the autopsy rate today is so low, the percentage not diagnosed clinically is probably >23%.


Ventricular dysfunction and pulmonary function in OSA syndrome.
Patients with obstructive sleep apnea (OSA) have increased cardiovascular morbidity and death as a result of myocardial ischemia and both pulmonary and systemic hypertension. Early detection allows for proper risk stratification and treatment.


Telecardiology application in jordan: its impact on diagnosis and disease management, patients' quality of life, and time- and cost-savings.
Objectives. To assess the impact of live interactive telecardiology on diagnosis and disease management, patients' quality of life, and time- and cost-savings. Methods. All consecutive patients who attended or were referred to the teleclinics for suspected cardiac problems in two hospitals in remote areas of Jordan during the study period were included in the study. Patients were interviewed for relevant information and their quality of life was assessed during the first visit and 8 weeks after the last visit. Results. A total of 76 patients were included in this study. Final diagnosis and treatment plan were established as part of the telecardiology consultations in 71.1% and 77.3% of patients, respectively. Patients' travel was avoided for 38 (50.0%) who were managed locally. The majority of patients perceived that the visit to the telecardiology clinic results in less travel time (96.1%), less waiting time (98.1%), and lower cost (100.0%). Telecardiology consultations resulted in an improvement in the quality of life after two months of the first visit. Conclusions. Telecardiology care in remote areas of Jordan would improve the access to health care, help to reach proper diagnosis and establish the treatment plan, and improve the quality of life.


Combination of inhibitors for two glycolytic enzymes portrays high synergistic efficacy against Cryptosporidium parvum.
Cryptosporidium is an intracellular protozoan parasite that causes serious enteric disease in humans and in a wide range of animals worldwide. Despite its high prevalence, no effective therapeutic drugs are available against life-threatening cryptosporidiosis in at-risk populations including malnourished children, immunocompromised patients, and neonatal calves. Thus, new efficacious drugs are urgently needed to treat all susceptible populations with cryptosporidiosis. Unlike other apicomplexans, Cryptosporidium parvum lacks the tricarboxylic acid cycle and the oxidative phosphorylation steps, making it solely dependent on glycolysis for metabolic energy production. We have previously reported that individual inhibitors of two unique glycolytic enzymes, the plant-like pyruvate kinase (CpPyK) and the bacterial-type lactate dehydrogenase (CpLDH), are effective against C. parvum, both in vitro and in vivo. Herein, we have derived combinations of CpPyK and CpLDH inhibitors with strong synergistic effects against the growth and survival of C. parvum, both in vitro and in an infection mouse model. In infected immunocompromised mice, compound combinations of NSC303244 + NSC158011 and NSC252172 + NSC158011 depicted enhanced efficacy against C. parvum reproduction and ameliorated intestinal lesions of cryptosporidiosis at doses fourfold lower than the total effective doses of individual compounds. Importantly, unlike individual compounds, NSC303244 + NSC158011 combination was effective in clearing the infection completely without relapse in immunocompromised mice. Collectively, our study has unveiled compound combinations that simultaneously block two essential catalytic steps for metabolic energy production in C. parvum to achieve improved efficacy against the parasite. These combinations are, therefore, lead compounds for the development of a new generation of efficacious anti-cryptosporidial drugs.


Endometrial stromal sarcomas and related high-grade sarcomas: immunohistochemical and molecular genetic study of 31 cases.
Classification and terminology of non-low-grade endometrial sarcomas, which show significant nuclear atypia, have been controversial. Currently, these tumors seem to be classified all together into "undifferentiated endometrial sarcoma (UES)." However, it remains unclear whether these non-low-grade sarcomas are universally "undifferentiated." We divided these sarcomas morphologically into undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P), and compared their molecular genetic and immunohistochemical profiles. Eighteen low-grade endometrial stromal sarcomas (ESS-LG), 7 UES-U, and 6 UES-P were examined. All the patients with ESS-LG were still alive, either with or without disease, whereas 4 of the 5 patients with advanced stage UES-U and all 3 of the patients with advanced stage UES-P had died of the disease. JAZF1-JJAZ1 fusion transcript was detected in 6 (50%) out of 12 ESS-LG and in 1 (33%) of 3 UES-U, whereas it was not detected in any of the cases of UES-P. ESS-LG and UES-U frequently showed positive immunoreaction for estrogen receptor (ESS-LG: 94%, UES-U: 57%) and progesterone receptor (ESS-LG: 94%, UES-U: 57%), whereas all the UES-P were negative for these receptors. Nuclear beta-catenin expression was more frequently recognized in ESS-LG (47%) and UES-U (85%), compared with UES-P (33%). Moreover, nuclear accumulation of p53 and TP53 gene missense mutations were limited to 3 UES-P cases. Our data suggest that UES-U shares some molecular genetic and immunohistochemical characteristics with ESS-LG, but UES-P considerably differs from ESS-LG.


Identification of novel cancer fusion genes using chromosome breakpoint screening.
Gene fusion due to rearrangement or translocation of chromosomes is a powerful mutational mechanism during tumorigenesis. Several new high-resolution technologies have recently been developed to evaluate large numbers of small aberrations as candidate loci for fusion gene screening. In our previous whole-genome screening study using 500K SNP arrays, we identified more than 700 homozygous deletions (HDs) and amplicons in 23 cancer cell lines. To explore novel fusion genes in cancer, we established stringent criteria for defining HD and amplicon breakpoints. Then genomic PCR and sequencing analyses identified a fusion gene, FNDC3B-PRKCI, that resulted from chromosome intra-rearrangement. Western blotting and 3'-RACE analyses revealed that the chimeric transcript was an in-frame fusion between FNDC3B and PRKCI. Finally, cell migration and colony formation assays suggested that FNDC3B-PRKCI is a potential oncogene.


Poly[(μ(2)-nitrato-κO:O')(μ(2)-pyrimidin-ium-2-carboxyl-ato-κO:O')lithium(I)].
In the structure of the title compound, [Li(C(5)H(4)N(2)O(2))(NO(3))](n), the Li(I) ion is coordinated by two carboxyl-ate O atoms donated by two ligands and two nitrate O atoms in a distorted tetrahedral geometry. Li(I) ions, bridged by carboxyl-ate O atoms, form mol-ecular ribbons composed of dimeric units. Two nitrate O atoms link the ribbons into mol-ecular layers parallel to (001). Hydrogen bonds are active between protonated heterocyclic N atoms as donors and carboxyl-ate O atoms as acceptors. The layers are held together by van der Waals inter-actions.


Total serum immunoglobulin E level and specific allergens in adults with skin diseases.
Immunoglobulin E (IgE) plays an important role in allergic diseases. Although several studies have shown the association of serum total IgE and allergen-specific IgE levels with allergic dermatological diseases such as atopic dermatitis, there are few studies addressing this association for skin diseases in general. We sought to evaluate IgE levels in skin diseases and investigate the differences based on the disease type and clinical factors such as gender and age. Data from 2836 patients who visited the dermatologic clinic of the Konkuk University Hospital, Seoul, Republic of Korea for 4 years were reviewed to document IgE levels and clinical information. IgE levels were collated with the type of skin disease, gender, and age. Patients with atopic dermatitis had a much higher total IgE level and were more susceptible to allergens as compared to other disease groups. Patients in other disease groups showed no significant differences in IgE levels. Men showed higher total IgE levels but the gender differences decreased with increasing age. The data were collected from patients at a referral centre and thus may not represent the general population of dermatologic patients. There was a lack of information regarding factors that could potentially influence IgE levels such as smoking history and disease severity. The results suggest that there are physiological or environmental differences in IgE-mediated immune responses between males and females. Also, except for atopic dermatitis, there were no clinical differences in the IgE levels among various skin diseases.


CALCR knockdown inhibits the development and progression of non-small-cell lung cancer.
G-protein-coupled receptors (GPCRs) have been reported to participate in the occurrence and development of a variety of human cancers. CALCR is one of the hundreds of GPCRs, but its expression level and functional importance have never been investigated in non-small-cell lung cancer (NSCLC). In the present study, the protein expression level of CALCR was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound-healing assay and the transwell assay were performed to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed to conduct the in vivo experiments. The results indicated that the CALCR expression was abundantly up-regulated in NSCLC and positively related to tumor infiltrate. Besides, CALCR knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study verified the inhibitory effects of CALCR knockdown on NSCLC tumorigenesis. The abovementioned results provided a reference for the treatment of NSCLC, that was, CALCR knockdown might be a considerable therapeutic strategy.


Genome-wide association study of lung lesions and pleurisy in New Zealand lambs.
Pneumonia is an important issue for sheep production, leading to reduced growth rate and a predisposition to pleurisy. The objective of this study was to identify loci associated with pneumonic lesions and pleurisy in New Zealand progeny test lambs. The lungs from 3,572 progeny-test lambs were scored for presence and severity of pneumonic lesions and pleurisy at slaughter. Animals were genotyped using the Illumina Ovine Infinium HD SNP BeadChip (606,006 markers). The heritability of lung lesion score and pleurisy were calculated using the genomic relationship matrix, and genome-wide association analyses were conducted using EMMAX and haplotype trend regression. At slaughter, 35% of lambs had pneumonic lesions, with 9% showing lesions on more than half of any individual lobe. The number of lambs recorded as having pleurisy by the processing plants was 9%. Heritability estimates for pneumonic lesions and pleurisy scores adjusted for heteroscedasticity (CPSa and PLEURa) were 0.16 (± 0.03) and 0.05 (± 0.02), respectively. Five single-nucleotide polymorphisms (SNPs) were significantly associated with pneumonic lesions at the genome-wide level, and additional 37 SNPs were suggestively significant. Four SNPs were significantly associated with pleurisy, with an additional 11 SNPs reaching the suggestive level of significance. There were no regions that overlapped between the 2 traits. Multiple SNPs were in regions that contained genes involved in either the DNA damage response or the innate immune response, including several that had previously been reported to have associations with respiratory disease. Both EMMAX and HTR analyses of pleurisy data showed a significant peak on chromosome 2, located downstream from the transcription factor SP3. SP3 activates or suppresses the expression of numerous genes, including several genes with known functions in the immune system. This study identified several SNPs associated with genes involved in both the innate immune response and the response to DNA damage that are associated with pneumonic lesions and pleurisy in lambs at slaughter. Additionally, the identification in sheep of several SNPs within genes that have previously been associated with the respiratory system in cattle, pigs, rats, and mice indicates that there may be common pathways that underlie the response to invasion by respiratory pathogens in multiple species.


(AuAg)144(SR)60 alloy nanomolecules.
(Au-Ag)(144)(SR)(60) alloy nanomolecules were synthesized and characterized by ESI mass spectrometry to atomic precision. The number of Ag atoms can be varied by changing the incoming metal ratio and plateaus at ∼60. UV-vis data demonstrates that the electronic structure of the nanomolecules can be tuned by incorporation of silver atoms. Based on the proposed 3-shell structure of Au(144)(SR)(60), we hypothesize that the Ag atoms are selectively incorporated in to the symmetry equivalent 60-atom shell-having Au(12), Au(42), Ag(60) concentric shells with 30 -SR-Au-SR- protecting units.


Construction and characterization of a BAC library for functional genomics in Xenopus tropicalis.
Large insert genomic DNA libraries are useful resources for genomic studies. Although the genome of Xenopus tropicalis stands as the amphibian reference genome because it benefitted from large-scale sequencing studies, physical mapping resources such as BAC libraries are lagging behind. Here we present the construction and characterization of a BAC library that covers the whole X. tropicalis genome. We prepared this BAC library from the genomic DNA of X. tropicalis females of the Adiopodoume strain. We characterized BAC clones by screening for specific loci, by chromosomal localization using FISH and by systematic BAC end sequencing. The median insert size is about 110kbp and the library coverage is around six genome equivalents. We obtained a total of 163,787 BAC end sequences with mate pairs for 77,711 BAC clones. We mapped all BAC end sequences to the reference X. tropicalis genome assembly to enable the identification of BAC clones covering specific loci. Overall, this BAC library resource complements the knowledge of the X. tropicalis genome and should further promote its use as a reference genome for developmental biology studies and amphibian comparative genomics.


Continuous Venovenous Hemofiltration (CVVH) Versus Conventional Treatment for Acute Severe Hypernatremia in Critically Ill Patients: A Retrospective Study.
Patients with severe hypernatremia who receive conventional treatment are often undertreated. Data on the management of acute hypernatremia using continuous venovenous hemofiltration (CVVH) are limited to anecdotes. This study aimed to evaluate the efficacy and safety of CVVH treatment for acute severe hypernatremia in critically ill patients in a retrospective cohort. A total of 95 patients who were admitted to our ICU between January 2009 and January 2014 were analyzed as the original cohort. These patients were divided into CVVH and conventional treatment groups. The patients in the conventional and CVVH groups were then matched by age, reason for ICU admission, vasopressor dependency, basic serum sodium concentration, and Glasgow scores. A Cox regression model was used to adjust the confounding variables. In the original cohort, the 28-day survival rates were 41.9% and 25.0% for the CVVH and conventional treatment groups, respectively. Conventional treatment (HR = 2.1, 95% CI 1.1-3.8, P = 0.019) was an independent predictor of patient mortality in the multivariate Cox regression model. In the matched cohort, the two groups were not significantly different in baseline characteristics. The CVVH group had a significantly greater reduction in the serum sodium concentration (0.78 [0.63-1.0] mmol/L/h versus 0.13 [0.009-0.33] mmol/L/h), P < 0.001) and an improved 28-day survival rate (34.8% vs. 8.7%, P = 0.002) compared with the conventional treatment group. The two groups did not differ significantly in treatment-related complications. CVVH treatment is possibly more effective than conventional treatment for the management of acute severe hypernatremia in critically ill patients.


Cytochrome aa3 in facultatively aerobic and hyperthermophilic archaeon Pyrobaculum oguniense.
We partially purified and characterized the cytochrome aa3 from the facultatively aerobic and hyperthermophilic archaeon Pyrobaculum oguniense. This cytochrome aa3 showed oxygen consumption activity with N, N, N', N'-tetramethyl-1,4-phenylenediamine and ascorbate as substrates, and also displayed bovine cytochrome c oxidase activity. These enzymatic activities of cytochrome aa3 were inhibited by cyanide and azide. This cytochrome contained heme As, but not typical heme A. An analysis of trypsin-digested fragments indicated that 1 subunit of this cytochrome was identical to the gene product of subunit I of the SoxM-type heme--copper oxidase (poxC). This is the first report of a terminal oxidase in hyperthermophilic crenarchaeon belonging to the order Thermoproteales.


Endoscopical segmental piecemeal tumorectomy for nodular elevation of colorectal tumor: applicability and patient's quality of life.
Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.