Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands.
Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia.


Multilocus genetic analyses differentiate between widespread and spatially restricted cryptic species in a model ascidian.
Elucidating the factors that shape species distributions has long been a fundamental goal in ecology and evolutionary biology. In spite of significant theoretical advancements, empirical studies of range limits have lagged behind. Specifically, little is known about how the attributes that allow species to expand their ranges and become widespread vary across phylogenies. Here, we studied the ascidian Botryllus schlosseri, a worldwide invasive species that is also characterized by marked genetic subdivision. Our study includes phylogenetic and population genetic data based on mitochondrial and nuclear genes, as well as polymorphic microsatellites for B. schlosseri colonies sampled from the southern and northern coasts of Europe and the eastern and western coasts of North America. We demonstrate that this well-known model organism comprises three highly divergent and probably reproductively isolated cryptic species (A, D and E), with two more (B and C) being suggested by data retrieved from GenBank. Among these, species A, recovered in all of the surveyed regions, is by far the most common and widespread. By contrast, species B-E, occurring mostly in sites from northern Europe, are considerably more geographically restricted. These findings, along with inferences made on transport opportunity, suggest that divergent evolutionary histories promoted differences in invasive potential between B. schlosseri sibling species, indicating that attributes that facilitate dramatic shifts in range limits can evolve more easily and frequently than previously thought. We propose environmental disturbance as a selective force that could have shaped the evolution of invasiveness in the B. schlosseri complex.


Leveraging smart technologies to improve the management of diabetic foot ulcers and extend ulcer-free days in remission.
The prevalent and long neglected diabetic foot ulcer (DFU) and its related complications rank among the most debilitating and costly sequelae of diabetes. Management of the DFU is multifaceted and requires constant monitoring from patients, caregivers, and healthcare providers. The alarmingly high rates of recurrence of ulcerations in the diabetic foot requires a change in our approach to care and to the vernacular in the medical literature. Our efforts should be directed not only on healing of open wounds, but also on maximizing ulcer-free days for the patient in diabetic foot remission. The increasing development and use of technology within every aspect of our lives represents an opportunity for creative solutions to prevent or better manage this devastating condition. In particular, recent advances in wearable and mobile health technologies appear to show promise in measuring and modulating dangerous foot pressure and inflammation to extend remission and improve the quality of life for these most complex patients. This review article discusses how harnessing wearables and digital technologies may improve the management and optimize prevention of DFUs by identifying high-risk patients for triage and timely intervention, personalizing prescription of offloading, and improving adherence to protective footwear. While still in their infancy, we envisage a future network of skin-worn, jewellery-worn, and implantable sensors that, if allowed to effectively communicate with one another and the patient, could dramatically impact measuring, personalizing, and managing how we and the patients we serve move through our collective world.


Semantic annotation of mutable data.
Electronic annotation of scientific data is very similar to annotation of documents. Both types of annotation amplify the original object, add related knowledge to it, and dispute or support assertions in it. In each case, annotation is a framework for discourse about the original object, and, in each case, an annotation needs to clearly identify its scope and its own terminology. However, electronic annotation of data differs from annotation of documents: the content of the annotations, including expectations and supporting evidence, is more often shared among members of networks. Any consequent actions taken by the holders of the annotated data could be shared as well. But even those current annotation systems that admit data as their subject often make it difficult or impossible to annotate at fine-enough granularity to use the results in this way for data quality control. We address these kinds of issues by offering simple extensions to an existing annotation ontology and describe how the results support an interest-based distribution of annotations. We are using the result to design and deploy a platform that supports annotation services overlaid on networks of distributed data, with particular application to data quality control. Our initial instance supports a set of natural science collection metadata services. An important application is the support for data quality control and provision of missing data. A previous proof of concept demonstrated such use based on data annotations modeled with XML-Schema.


Childhood enuresis. Epidemiology, pathophysiology and management.
The goal of this article is to review childhood enuresis, which is a common behavioral condition reported in millions of children worldwide. An online computer search was made, and the literature up to 1997 was screened in order to include relevant data for this review. The prevalence of childhood enuresis varies across reviewed studies. This was attributed to a variety of sociodemographic and cultural dynamics of societies. Similarly, the pathophysiology of this ubiquitous symptom is determined by multiple risk factors including biological, psychological, social, and cultural, but the developmental/maturational delay influenced by genetics remains the most plausible explanation. Although a variety of pharmacological and non-pharmacological treatment modalities are traced in the literature, there is yet no agreement on a single strategy. A general agreement about behavioral therapy as the first choice of treatment of this minor malady began to emerge. Additionally, tricyclic antidepressants are the most frequently prescribed drugs for the treatment of childhood enuresis. Enuresis is a pediatric public health problem and concerted efforts at all levels, ie, professional, promotional, educational and public should be made to address its multiple domains such as preventive, etiological and curative.


Role of nutritional status and intervention in oesophageal cancer treated with definitive chemoradiotherapy: outcomes from SCOPE1.
Malnutrition is common in oesophageal cancer. We aimed to identify nutritional prognostic factors and survival outcomes associated with nutritional intervention in the SCOPE1 (Study of Chemoradiotherapy in OesoPhageal Cancer with or without Erbitux) trial. Two hundred and fifty eight patients were randomly allocated to definitive chemoradiotherapy (dCRT) +/- cetuximab. Nutritional Risk Index (NRI) scores were calculated; NRI<100 identified patients at risk of malnutrition. Nutritional intervention included dietary advice, oral supplementation or major intervention (enteral feeding/tube placement). Univariable and multivariable analyses using Cox proportional hazard modelling were conducted. At baseline NRI<100 strongly predicted for reduced overall survival (hazard ratio (HR) 12.45, 95% CI 5.24-29.57; P<0.001). Nutritional intervention improved survival if provided at baseline (dietary advice (HR 0.12, P=0.004), oral supplementation (HR 0.13, P<0.001) or major intervention (HR 0.13, P=0.003)), but not if provided later in the treatment course. Cetuximab patients receiving major nutritional intervention had worse outcomes compared with controls (13 vs 28 months, P=0.003). Pre-treatment assessment and correction of malnutrition may improve survival outcomes in oesophageal cancer patients treated with dCRT. Nutritional Risk Index is a simple and objective screening tool to identify patients at risk of malnutrition.


Immune complexes regulate bone metabolism through FcRγ signalling.
Autoantibody production and immune complex (IC) formation are frequently observed in autoimmune diseases associated with bone loss. However, it has been poorly understood whether ICs regulate bone metabolism directly. Here we show that the level of osteoclastogenesis is determined by the strength of FcRγ signalling, which is dependent on the relative expression of positive and negative FcγRs (FcγRI/III/IV and IIB, respectively) as well as the availability of their ligands, ICs. Under physiological conditions, unexpectedly, FcγRIII inhibits osteoclastogenesis by depriving other osteoclastogenic Ig-like receptors of FcRγ. Fcgr2b(-/-) mice lose bone upon the onset of a hypergammaglobulinemia or the administration of IgG1 ICs, which act mainly through FcγRIII. The IgG2 IC activates osteoclastogenesis by binding to FcγRI and FcγRIV, which is induced under inflammatory conditions. These results demonstrate a link between the adaptive immunity and bone, suggesting a regulatory role for ICs in bone resorption in general, and not only in inflammatory diseases.


Distinct Transcriptomic Features are Associated with Transitional and Mature B-Cell Populations in the Mouse Spleen.
Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II. FO-II may be an intermediate in FO-I differentiation and may also become MZ B-cells as suggested by principle component analysis. MZ B-cells possessed the most distinct transcriptome including down-regulation of CD45 phosphatase-associated protein (CD45-AP/PTPRC-AP), as well as upregulation of IL-9R and innate molecules TLR3, TLR7, and bactericidal Perforin-2 (MPEG1). Among the endosomal TLRs, stimulation via TLR3 further enhanced Perforin-2 expression exclusively in MZ B-cells. Using gene-deleted and overexpressing transgenic mice we show that IL-9/IL-9R interaction resulted in rapid activation of STAT1, 3, and 5, primarily in MZ B-cells. Importantly, CD45-AP mutant mice had reduced transitional and increased mature MZ and FO B-cells, suggesting that it prevents premature entry of transitional B-cells to the mature B-cell pool or their survival and proliferation. Together, these findings suggest, developmental plasticity among splenic B-cell subsets, potential for receptor revision in peripheral tolerance whereas enhanced metabolism coincides with T2 to mature B-cell differentiation. Further, unique core transcriptional signatures in MZ B-cells may control their innate features.


Priority determines Tribolium competitive outcome in a food-limited environment.
Flour beetles are a classic model system for studying competitive dynamics between species occupying the same ecological niche. Competitive performance is often interpreted in terms of biological species traits such as fecundity, resource use, and predation. However, many studies only measure competitive ability when species enter an environment simultaneously, and thus do not consider how the relative timing of species' arrival may determine competitive outcome (i.e., priority effects). Whether priority effects may influence competition in Tribolium remains to be tested. The present study examined the importance of priority effects in competitions between two common species of flour beetle (Coleoptera: Tenebrionidae): Tribolium castaneum and T. confusum. To investigate whether priority effects confer competitive advantages to Tribolium beetles, relative introduction times of T. castaneum and T. confusum to competitive arenas were manipulated, and adult populations were measured for seven months. Four important patterns were noted: (1) Tribolium species given two-weeks priority access to experimental arenas attained larger populations than their late-arriving competitor, (2) when founding adults were introduced simultaneously, T. castaneum was competitively dominant, (3) T. castaneum benefited more from priority arrival than T. confusum, and (4) available bran resources largely predicted population decline in adult beetles toward the end of the experiment. These results suggest competitive outcome in Tribolium is not always predicted by species' identity, and that performance could instead be determined by the timing of species' arrivals and available resources.


Short, synthetic and selectively 13C-labeled RNA sequences for the NMR structure determination of protein-RNA complexes.
We report an optimized synthesis of all canonical 2'-O-TOM protected ribonucleoside phosphoramidites and solid supports containing [13C5]-labeled ribose moieties, their sequence-specific introduction into very short RNA sequences and their use for the structure determination of two protein-RNA complexes. These specifically labeled sequences facilitate RNA resonance assignments and are essential to assign a high number of sugar-sugar and intermolecular NOEs, which ultimately improve the precision and accuracy of the resulting structures. This labeling strategy is particularly useful for the study of protein-RNA complexes with single-stranded RNA in solution, which is rapidly an increasingly relevant research area in biology.


The Impact of Left Atrium Appendage Morphology on Stroke Risk Assessment in Atrial Fibrillation: A Computational Fluid Dynamics Study.
Atrial fibrillation (AF) carries out a 5-fold increase in stroke risk, related to embolization of thrombi clotting in left atrium (LA). Left atrial appendage (LAA) is the site with the highest blood stasis which causes thrombus formation. About 90 % of the intracardiac thrombi in patients with cardioembolic events originally develop in the LAA. Recent studies have been focused on the association between LAA anatomical features and stroke risk and provided conflicting results. Haemodynamic and fluid dynamic information on the LA and mostly on the LAA may improve stroke risk stratification. Therefore, the aim of this study was the design and development of a workflow to quantitatively define the influence of the LAA morphology on LA hemodynamics. Five 3D LA anatomical models, obtained from real clinical data, which were clearly different as regard to LAA morphology were used. For each LAA we identified and computed several parameters describing its geometry. Then, one LA chamber model was chosen and a framework was developed to connect the different LAAs belonging to the other four patients to this model. These new anatomical models represented the computational domain for the computational fluid dynamics (CFD) study; simulations of the hemodynamics within the LA and LAA were performed in order to evaluate the interplay of the LAA shape on the blood flow characteristics in AF condition. CFD simulations were carried out for five cardiac cycles. Blood velocity, vorticity, LAA orifice velocity, residence time computed in the five models were compared and correlated with LAA morphologies. Results showed that not only complex morphologies were characterized by low velocities, low vorticity and consequently could carry a higher thrombogenic risk; even qualitatively simple morphologies showed a thrombogenic risk equal, or even higher, than more complex auricles. CFD results supported the hypothesis that LAA geometric characteristics plays a key-role in defining thromboembolic risk. LAA geometric parameters could be considered, coupled with the morphological characteristics, for a comprehensive evaluation of the regional blood stasis. The proposed procedure might address the development of a tool for patient-specific stroke risk assessment and preventive treatment in AF patients, relying on morpho-functional defintion of each LAA type.


Extracting laboratory test information from biomedical text.
No previous study reported the efficacy of current natural language processing (NLP) methods for extracting laboratory test information from narrative documents. This study investigates the pathology informatics question of how accurately such information can be extracted from text with the current tools and techniques, especially machine learning and symbolic NLP methods. The study data came from a text corpus maintained by the U.S. Food and Drug Administration, containing a rich set of information on laboratory tests and test devices. THE AUTHORS DEVELOPED A SYMBOLIC INFORMATION EXTRACTION (SIE) SYSTEM TO EXTRACT DEVICE AND TEST SPECIFIC INFORMATION ABOUT FOUR TYPES OF LABORATORY TEST ENTITIES: Specimens, analytes, units of measures and detection limits. They compared the performance of SIE and three prominent machine learning based NLP systems, LingPipe, GATE and BANNER, each implementing a distinct supervised machine learning method, hidden Markov models, support vector machines and conditional random fields, respectively. Machine learning systems recognized laboratory test entities with moderately high recall, but low precision rates. Their recall rates were relatively higher when the number of distinct entity values (e.g., the spectrum of specimens) was very limited or when lexical morphology of the entity was distinctive (as in units of measures), yet SIE outperformed them with statistically significant margins on extracting specimen, analyte and detection limit information in both precision and F-measure. Its high recall performance was statistically significant on analyte information extraction. Despite its shortcomings against machine learning methods, a well-tailored symbolic system may better discern relevancy among a pile of information of the same type and may outperform a machine learning system by tapping into lexically non-local contextual information such as the document structure.


Effect of serotonin receptor 2A gene polymorphism on mirtazapine response in major depression.
The 5-HTR2A gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the -1438A/G polymorphism of the 5-HTR2A gene and the response to mirtazapine in a Korean population with major depressive disorder. Mirtazapine was administered for eight weeks to the 101 patients who completed the study, during which we evaluated the clinical outcome using repeated-measures ANCOVA. A main effect of genotype or an effect of genotype-time interactions on the decrease in HAMD score during the eight-week follow-up was not found, which suggests that the 5-HTR2A -1438A/G polymorphism does not affect the clinical outcome to mirtazapine administration. However, significant effects of genotype and allele carriers on the decrease in the sleep score over the eight weeks were found (genotype: F = 4.093, p = 0.017; allele: F = 4.371, p = 0.037), whereas no effect of genotype-time interactions on the decrease in the HAMD score over the eight-week follow-up was found. These observations suggest that the -1438A/G polymorphism on the sleep improvement at each time period revealed significant differences in the sleep scores after two weeks of mirtazapine administration. The sleep scores were lower for carriers of the A+ allele than of the A- allele after two weeks of mirtazapine administration (p = 0.041), which means that the -1438GG genotype is associated with less improvement in sleep, and suggests that the effect of mirtazapine on improving the sleep quality differs with the 5-HTR2A -1438A/G polymorphism within two weeks of mirtazapine treatment. In conclusion, although the -1438A/G polymorphism affects the sleep improvement resulting from the administration of mirtazapine to Korean patients with major depressive disorder, our results do not support the hypothesis that this polymorphism of the 5-HTR2A gene is involved in the therapeutic response to mirtazapine.


Vacuum ultraviolet excitation luminescence spectroscopy of few-layered MoS2.
We report on vacuum ultraviolet (VUV) excited photoluminescence (PL) spectra emitted from a chemical vapor deposited MoS2 few-layered film. The excitation spectrum was recorded by monitoring intensities of PL spectra at ~1.9 eV. A strong wide excitation band peaking at 7 eV was found in the excitation. The PL excitation band is most intensive at liquid helium temperature and completely quenched at 100 K. Through first-principles calculations of photoabsorption in MoS2, the excitation was explicated and attributed to transitions of electrons from p- and d- type states in the valence band to the d- and p-type states in the conduction band. The obtained photon-in/photon-out results clarify the excitation and emission behavior of the low dimensional MoS2 when interacting with the VUV light sources.


Pregnenolone can protect the brain from cannabis intoxication.
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.


Bone marrow is the preferred site of memory CD4+ T cell proliferation during recovery from sepsis.
Sepsis survivors suffer from increased vulnerability to infections, and lymphopenia presumably contributes to this problem. The mechanisms of the recovery of memory CD4+ T cells after sepsis remain elusive. We used the cecal ligation and puncture mouse model of sepsis to study the restoration of the memory CD4+ T cells during recovery from sepsis. Then, adoptive transfer of antigen-specific naive CD4+ T cells followed by immunization and BrdU labeling were performed to trace the proliferation and migration of memory CD4+ T cells. We revealed that the bone marrow (BM) is the primary site of CD4+ memory T cell homing and proliferation after sepsis-induced lymphopenia. Of interest, BM CD4+ T cells had a higher basal proliferation rate in comparison with splenic T cells. These cells also show features of resident memory T cells yet have the capacity to migrate outside the BM niche and engraft secondary lymphoid organs. The BM niche also sustains viability and functionality of CD4+ T cells. We also identified IL-7 as the major inducer of proliferation of the BM memory CD4+ T cells and showed that recombinant IL-7 improves the recovery of these cells. Taken together, we provide data on the mechanism and location of memory CD4+ T cell proliferation during recovery from septic lymphopenia, which are of relevance in studying immunostimulatory therapies in sepsis.


Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy.
Peritoneal surface malignancy usually results from implantation of gastrointestinal cancer. In the past, this clinical situation was treated with palliative intent. A definitive approach to peritoneal surface malignancy involves peritonectomy procedures, visceral resections, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The quantitative prognostic indicators necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 45% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. The definitive prognostic indicator was the complete cytoreduction. Oncologists must seek new knowledge regarding the management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies; in contrast all historical controls show 0% long-term survival. Additional adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.


Low flow anesthesia: Efficacy and outcome of laryngeal mask airway versus pressure-optimized cuffed-endotracheal tube.
Low flow anesthesia can lead to reduction of anesthetic gas and vapor consumption. Laryngeal mask airway (LMA) has proved to be an effective and safe airway device. The aim of this study is to assess the feasibility of laryngeal mask airway during controlled ventilation using low fresh gas flow (1.0 L/min) as compared to endotracheal tube (ETT). Fifty nine non-smoking adult patients; ASA I or II, being scheduled for elective surgical procedures, with an expected duration of anesthesia 60 minutes or more, were randomly allocated into two groups - Group I (29 patients) had been ventilated using LMA size 4 for females and 5 for males respectively; and Group II (30 patients) were intubated using ETT. After 10 minutes of high fresh gas flow, the flow was reduced to 1 L/min. Patients were monitored for airway leakage, end-tidal CO(2)(ETCO(2)), inspiratory and expiratory isoflurane and nitrous oxide fraction concentrations, and postoperative airway-related complications. Two patients in the LMA-group developed initial airway leakage (6.9%) versus no patient in ETT-group. Cough and sore throat were significantly higher in ETT patients. There were no evidences of differences between both groups regarding ETCO(2), uptake of gases, nor difficulty in swallowing. The laryngeal mask airway proved to be effective and safe in establishing an airtight seal during controlled ventilation under low fresh gas flow of 1 L/min, inducing less coughing and sore throat during the immediate postoperative period than did the ETT, with continuous measurement and readjustment of the tube cuff pressure.


Impact of Beta-Blocker Initiation Timing on Mortality Risk in Patients With Diabetes Mellitus Undergoing Noncardiac Surgery: A Nationwide Population-Based Cohort Study.
Relevant clinical studies have been small and have not convincingly demonstrated whether the perioperative initiation of beta-blockers should be considered in patients with diabetes mellitus undergoing noncardiac surgery. In this nationwide propensity score-matched study, we included patients with diabetes mellitus undergoing noncardiac surgery between 2000 and 2011 from Taiwan's National Health Insurance Research Database. Patients were classified as beta-blocker and non-beta-blocker cohorts. We further stratified beta-blocker users into cardioprotective beta-blocker (atenolol, bisoprolol, metoprolol, or carvedilol) and other beta-blocker users. To investigate time of initiation of beta-blocker use, initiation time was stratified into 2 periods (>30 and ≤30 days preoperatively). The outcomes of interest were in-hospital and 30-day mortality. After propensity score matching, we identified 50 952 beta-blocker users and 50 952 matched controls. Compared with non-beta-blocker users, cardioprotective beta-blocker users were associated with lower risks of in-hospital (odds ratio 0.75, 95% CI 0.68-0.82) and 30-day (odds ratio 0.75, 95% CI 0.70-0.81) mortality. Among initiation times, only the use of cardioprotective beta-blockers for >30 days was associated with decreased risk of in-hospital (odds ratio 0.72, 95% CI 0.65-0.78) and 30-day (odds ratio 0.72, 95% CI 0.66-0.78) mortality. Of note, use of other beta-blockers for ≤30 days before surgery was associated with increased risk of both in-hospital and 30-day mortality. The use of cardioprotective beta-blockers for >30 days before surgery was associated with reduced mortality risk, whereas short-term use of beta-blockers was not associated with differences in mortality in patients with diabetes mellitus.


Context-related vocalization rates of fallow bucks, Dama dama.
We studied the short-term vocalization rates of fallow bucks to determine the primary recipients of the signal conveyed by these rates. We used the contexts in which groans occurred to investigate whether the signal represented an intrasexual threat or an intersexual advertisement. We found that fallow buck groaning rates were highly variable and that this variation was associated with the contexts of groaning. Groaning rates were higher during the rut than during the prerut, and also higher when males were with females than when they were with other males. Males with females groaned at higher rates when other vocal males were nearby. We identified a postcopulation call that consisted of the highest groaning rates that males produced. The presence of a harem did not contribute to the variation in groaning rates, except to a minor extent in postcopulation rates. Our findings suggest that the signal transmitted by short-term vocalization rates is primarily a threat aimed at other males. Copyright 1999 The Association for the Study of Animal Behaviour.


Evaluating early repeat emergency department use in patients with atrial fibrillation: a population-based analysis.
Emergency department (ED) use by patients with atrial fibrillation is high and will accelerate with the aging of the population. In patients with atrial fibrillation who are discharged from the ED, we aimed to describe their subsequent outpatient care, return ED visits, and management strategies associated with early return. We conducted a retrospective cohort analysis of patients 65 years or older with a primary ED diagnosis of atrial fibrillation who were discharged home from an ED in the province of Ontario, Canada, between April 2007 and March 2010. We describe subsequent outpatient care and repeat ED visits within 14 days of the index visit. We assessed factors associated with a repeat visit, overall, as well as by repeat visit outcome (discharged or admitted). Among 12,772 index ED visits, the mean (SD) age was 77 (7.4) years, and 14-day mortality was 0.7% (95% CI 0.5%-0.8%). Within 14 days, 67.8% had no follow-up care, 19.4% saw solely a family physician, and 12.8% saw a specialist (internist or cardiologist). There were 1,310 (10.3%) repeat ED visits made by 1,146 (9.0%) patients. Management strategies associated with a lower hazard of a repeat visit included follow-up care with a specialist (hazard ratio 0.61; P = .003) and a digoxin prescription (vs a β-blocker; hazard ratio 0.69, P = .001). Among older patients with atrial fibrillation discharged from an ED in the province of Ontario, 9% make 1 or more repeat visits within 14 days. Reductions in repeat emergency visits by low-risk patients are associated with timely specialist follow-up care.


Increased plant sterol deposition in vascular tissue characterizes patients with severe aortic stenosis and concomitant coronary artery disease.
The aim of the study was to evaluate the relationship between phytosterols, oxyphytosterols, and other markers of cholesterol metabolism and concomitant coronary artery disease (CAD) in patients with severe aortic stenosis who were scheduled for elective aortic valve replacement. Markers of cholesterol metabolism (plant sterols and cholestanol as markers of cholesterol absorption and lathosterol as an indicator of cholesterol synthesis) and oxyphytosterols were determined in plasma and aortic valve tissue from 104 consecutive patients with severe aortic stenosis (n=68 statin treatment; n=36 no statin treatment) using gas chromatography-flame ionization and mass spectrometry. The extent of CAD was determined by coronary angiography prior to aortic valve replacement. Patients treated with statins were characterized by lower plasma cholesterol, cholestanol, and lathosterol concentrations. However, statin treatment did not affect the sterol concentrations in cardiovascular tissue. The ratio of campesterol-to-cholesterol was increased by 0.46±0.34μg/mg (26.0%) in plasma of patients with CAD. The absolute values for the cholesterol absorption markers sitosterol and campesterol were increased by 18.18±11.59ng/mg (38.8%) and 11.40±8.69ng/mg (30.4%) in the tissues from patients with documented CAD compared to those without concomitant CAD. Campesterol oxides were increased by 0.06±0.02ng/mg (17.1%) in the aortic valve cusps and oxidized sitosterol-to-cholesterol ratios were up-regulated by 0.35±0.2ng/mg (22.7%) in the plasma of patients with CAD. Of note, neither cholestanol nor the ratio of cholestanol-to-cholesterol was associated with CAD. Patients with concomitant CAD are characterized by increased deposition of plant sterols, but not cholestanol in aortic valve tissue. Moreover, patients with concomitant CAD were characterized by increased oxyphytosterol concentrations in plasma and aortic valve cusps.


Electrospun alginate nanofibres impregnated with silver nanoparticles: Preparation, morphology and antibacterial properties.
Silver nanoparticles are amongst the most valuable nanoparticles with interesting properties, such as a non-toxic nature and high antibacterial efficiency, making them applicable for tissue scaffold, protective clothing and wound dressing. In this study, silver nanoparticles (AgNPs) have been synthesized using chitosan as reducing and stabilizing agent. The formation of silver nanoparticles was confirmed by UV-vis, and the TEM showed that different shapes were obtained depending on the heating duration. The chitosan/AgNPs was coated onto an electrospun alginate membrane to produce stable polyelectrolyte complex (PEC) nanofibre composites with high antibacterial efficiency. These composites were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). AgNPs were successfully impregnated into the PEC nanofibre composite, while there was complexation between the electrospun alginate and the chitosan/AgNPs composite. PEC demonstrated a good antibacterial activity against both gram negative and gram positive bacteria with acceptable water vapour transmission within the range required for the treatment of injuries or wounds.


Naturally occurring lactococcal plasmid pAH90 links bacteriophage resistance and mobility functions to a food-grade selectable marker.
The bacteriophage resistance plasmid pAH90 (26,490 bp) is a natural cointegrate plasmid formed via homologous recombination between the type I restriction-modification specificity determinants (hsdS) of two smaller lactococcal plasmids, pAH33 (6,159 bp) and pAH82 (20,331 bp), giving rise to a bacteriophage-insensitive mutant following phage challenge (D. O'Sullivan, D. P. Twomey, A. Coffey, C. Hill, G. F. Fitzgerald, and R. P. Ross, Mol. Microbiol. 36:866-876; 2000). In this communication we provide evidence that the recombination event is favored by phage infection. The entire nucleotide sequence of plasmid pAH90 was determined and found to contain 24 open reading frames (ORFs) responsible for phenotypes which include restriction-modification, phage adsorption inhibition, plasmid replication, cadmium resistance, cobalt transport, and conjugative mobilization. The cadmium resistance property, encoded by the cadA gene, which has an associated regulatory gene (cadC), is of particular interest, as it facilitated the selection of pAH90 in other phage-sensitive lactococci after electroporation. In addition, we report the identification of a group II self-splicing intron bounded by two exons which have the capacity to encode a relaxase implicated in conjugation in gram-positive bacteria. The functionality of this intron was evident by demonstrating splicing in vivo. Given that pAH90 encodes potent phage defense systems which act at different stages in the phage lytic cycle, the linkage of these with a food-grade selectable marker on a replicon that can be mobilized among lactococci has significant potential for natural strain improvement for industrial dairy fermentations which are susceptible to phage inhibition.


Gating mechanisms of canonical transient receptor potential channel proteins: role of phosphoinositols and diacylglycerol.
Canonical transient receptor potential (TRPC) Ca(2+)-permeable channels are members of the mammalian TRP super-family of cation channels, and have the closest homology to the founding members, TRP and TRPL, discovered in Drosophila photoreceptors. The TRPC subfamily is composed of 7 subunits (C1-C7, with TRPC2 a pseudogene in humans), which can all combine with one another to form homomeric and heteromeric structures. This review focuses on mechanisms involved in opening TRPC channels (i.e. gating mechanisms). It initially describes work on the involvement of phosphatidylinositol-4,5-bisphosphate (PIP(2)) and diacylglycerol (DAG) in gating TRP and TRPL channels in Drosophila, and then discusses evidence that similar gating mechanisms are involved in opening mammalian TRPC channels. It concludes that there are two common activation pathways of mammalian TRPC channels. Non-TRPC1-containing channels are opened by interactions between DAG, the direct activating ligand, and PIP(2), which acts as a physiological antagonist at TRPC proteins. Competitive interactions between an excitatory effect of DAG and an inhibitory action of PIP(2) can also be modulated by IP(3) acting via an IP(3) receptor-independent mechanism. In contrast TRPC1-containing channels are gating by PIP(2), which requires PKC-dependent phosphorylation of TRPC1 proteins.


Men perceive their female partners, and themselves, as more attractive around ovulation.
The purpose of this study was to test whether men perceive changes in their female partner's attractiveness as a function of her fertility status. We further tested how both male and female self-perception varies in relation to female fertility status. This study benefits from the use of transvaginal ultrasonography to detect fertility during the regular cycle and the use of a within-subjects design in which romantic couples were followed both across the cycle and during hormonal contraceptive use. We find that men rated their female partner as more attractive near to ovulation (when fertile) as compared to during the luteal cycle phase or during hormonal contraceptive use. Moreover, our results point to a presently unrecognized negative consequence of hormonal contraceptive use on male self-perception, with men rating themselves lower in attractiveness when their partner was using hormonal contraceptives than when she was regularly cycling. In contrast, there was no difference across measures in female self-reported attractiveness. Results are discussed in terms of their potential impact on within-couple social dynamics.


Acute endovascular treatment by coil embolisation of ruptured intracranial aneurysms.
Over 5 years, 317 consecutive patients were treated by coil embolisation within 30 days of aneurysm rupture. Neurological deteriorations were recorded in 35 patients during the first 48 h after treatment. In 21 patients these were due to procedural complications, which occurred in 31 procedures (9.8%). The timing of treatment relative to the last subarachnoid haemorrhage (SAH) was compared in patients treated after 0-2, 3-7, 8-14 and 15-30 days. No correlation was found in the incidence of such deteriorations and treatment periods, nor with patient's outcomes at 6 months. However, patients treated within 6 days of SAH had better outcomes than those treated later. Patients should, therefore, be treated as soon as possible after presentation since the technique appears less susceptible to the adverse effects of vasospasm in the 3-10 day period after SAH.


Evaluation of the particle gel diffusion technique for the detection of haemoglobin S in Sudanese patients.
Sickle cell disease is a heterogenous disorder characterized by an abnormal haemoglobin and sickling phenomena of red cells. It is prevalent among certain nomadic tribes in Sudan. Painful, aplastic and haemolytic crises mark sickle cell anaemia. Haemoglobin S (HbS) is detected using haemoglobin electrophoresis, iso-electric focusing and/or high-performance liquid chromatography techniques with high sensitivity, but entails cost and expertise. This study aimed to determine the sensitivity, specificity and positive predictive values (PPV) of the ID-particle gel diffusion technique for screening, diagnosis and phenotyping of HbS in patients with a provisional diagnosis of abnormal haemoglobin. Following informed consent, 100 sequential individuals who reported to a central referral haemoglobinopathy clinic were enrolled. ID-particle gel diffusion technique was compared with cellulose acetate electrophoresis to determine haemoglobin phenotypes. The ID-particle gel test detected HbAA with 100% sensitivity and 100% specificity. Sensitivity for HbS was 100%, whether as HbSS or as a mixed pattern. HbSS was identified in all cases where this is the only haemoglobin present. Other patterns were detected with <100% specificity and these would require further testing by other means to definitively identify abnormal haemoglobins. Although the ID-particle technique is a simple and cheap technique with high sensitivity, specificity and PPV compared with cellulose acetate electrophoresis in detecting HbSS, it could not differentiate HbAS from HbSS with high levels of HbF. High environmental temperatures could melt the test microtubes. Cellulose acetate electrophoresis remains the technique of choice for the screening of abnormal haemoglobins in the Sudan.


A Mobile App (WhiteTeeth) to Promote Good Oral Health Behavior Among Dutch Adolescents with Fixed Orthodontic Appliances: Intervention Mapping Approach.
The insertion of fixed orthodontic appliances increases the risk of dental caries, particularly in adolescents. Caries can be prevented through good oral health behavior. To support adolescents with fixed orthodontic appliances and for promoting oral health behavior, we developed a theory- and evidence-based mHealth program, the WhiteTeeth app. The objective of our paper was to describe the systematic development and content of the WhiteTeeth app. For systematic development of the program, we used the intervention mapping (IM) approach. In this paper, we present the results of applying the first 5 steps of IM to the design of an mHealth program: (1) identifying target behaviors and determinants through problem analysis, including a literature search, a survey study, and semistructured interviews, to explore adolescent oral health behavior during orthodontic therapy; (2) defining program outcomes and objectives; (3) selecting theoretical methods and translating them into practical strategies for the program design; (4) producing the program, including a pilot test with 28 adolescents testing the acceptability and usability of the WhiteTeeth app; and (5) planning implementation and adoption. On the basis of our literature search, we identified fluoride use and control of dental plaque levels (eg, tooth brushing and proxy brush usage) as target behaviors for preventing caries. Next, we identified important and changeable determinants of oral health behavior that fitted the theoretical concepts of the Health Action Process Approach (HAPA) theory. The HAPA theory, the self-regulation theory, and the results of the semistructured interviews were used to define the program objectives, that is, the performance and change objectives. After defining the objectives, we identified multiple behavior change techniques that could be used to achieve these objectives, such as providing oral health information and feedback, prompting self-monitoring, coaching of set actions and coping plans, and sending reminders. We translated these methods into practical strategies, such as videos and a brushing timer. Next, we combined these strategies into a single program resulting in the WhiteTeeth app (which is available on both iTunes and Google Play stores as "Witgebit"). Adolescents with fixed orthodontic appliances and dental professionals were included in the development process to increase the success of implementation. The pilot test revealed that the app users appreciated and liked the app. The WhiteTeeth app can be integrated into current orthodontic care. IM allowed us to identify multiple techniques that have been shown to be the most effective in initiating behavior change, but have not yet been incorporated into existing orthodontic apps. The WhiteTeeth app contains all these techniques, which makes it a unique and promising home-based app for promoting oral health in adolescents with fixed orthodontic appliances.


Histopathologic findings in ascending aortas from individuals with Loeys-Dietz syndrome (LDS).
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from genetic mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized phenotypically by hypertelorism, bifid uvula, and/or cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has a much more rapid clinical course than Marfan syndrome (MFS) and thus those diagnosed with LDS are currently being recommended for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Aortic root tissue obtained at surgery was compared between 15 patients carrying a diagnosis of LDS, 11 patients with MFS and 11 control aortas to evaluate the range of histopathologic changes in LDS. Standard hematoxylin and eosin and Movat pentachrome stains were performed. LDS samples had increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition, referred to as diffuse medial degeneration. LDS samples had significantly more diffuse medial degeneration compared with MFS and control samples (P<0.05), significantly less medial degeneration of the "cystic" variety compared with MFS (P<0.01) and significantly more collagen deposition than control samples (P<0.01). Additionally, an immunohistochemical stain for pSmad2, a marker of TGFbeta activity, was significantly increased in LDS patients compared with controls (P<0.001). Overall, the histologic findings of LDS are best appreciated with special stains to evaluate fibrosis and elastic fiber fragmentation. The changes described, although not entirely specific for LDS, help differentiate this entity from other vascular diseases in the appropriate clinicopathologic setting.


Pharmacological modulation of responses of guinea-pig airways contracted with antigen and calcium ionophore A23187.
Ovalbumin (OA) and calcium ionophore A23187 were used to induce contractions of sensitized guinea-pig tracheal and lung parenchymal preparations in the presence and absence of indomethacin. This model was used to examine the properties of a series of compounds reported to inhibit 5-lipoxygenase or to antagonize lipoxygenase products at the receptor level. FPL55712 and piriprost appeared to act as pharmacological antagonists because they rapidly reduced tracheal tone established by OA. The prolonged phase (i.e. greater than 10 min post-challenge) of airways contractions induced by OA is assumed to be lipoxygenase-dependent and was inhibited by nordihydroguaiaretic acid (NDGA), FPL55712, nafazatrom and benoxaprofen, in order of potency. Piriprost had similar inhibitory effects on the trachea, but not on lung parenchyma. The inhibitory effects of NDGA and FPL55712 were reduced, and those of nafazatrom increased by indomethacin. Indomethacin decreased the inhibitory effect of piriprost on the trachea, but facilitated inhibition by this agent on the parenchyma. A roughly similar pattern was seen on A23187-induced contractions, but FPL55712 did not modify these contractions and benoxaprofen enhanced the response of the trachea. BW755C enhanced the overall contractile response of OA- and A23187-induced tracheal contractions (but not parenchymal contractions) in a bell-shaped manner, an effect not seen in the presence of indomethacin. This indicated that BW755C could be acting as a cyclo-oxygenase inhibitor. The results suggested that, although inhibitors of the lipoxygenase pathway were partially effective in inhibiting the contractions of the airways induced by OA or A23187, other mediators in addition to those of the lipoxygenase pathway contribute to these contractions.


Formation of multigradient porous surfaces for selective bacterial entrapment.
Herein we describe the preparation of multigradient porous platforms by using the breath figures approach. In a single and straightforward step, we prepared porous surfaces in which three different parameters vary gradually from the edge of the sample to the center in a radial manner. Thus, we evidenced the gradual variation of the pore size and the shape of the pores that can be varied, depending on the sample concentration, but also depending on their radial position within the same sample. In addition, we succeeded in the control over the chemical composition inside and outside the pores as well as the variation of the concentration of block copolymer inside the pores as a function of their radial position. Moreover, the chemical composition and the variable cavity size of porous surfaces have been evaluated to analyze the influence of these variables on the selective bacterial immobilization. To the best of our knowledge this is the first example in which, by using a simple one-step strategy, a multigradient surface can be obtained. These initial results can be the base to construct platforms for selective immobilization and isolation of bacteria.


Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis.
Epidemiological studies suggest that retarded growth in infancy is associated with low adult bone mass. The mechanism underlying this association is unknown, but the programming of GH secretion or sensitivity by environmental influences during early development may play a role. We examined this issue in a sample of 37 healthy men, aged 63-73 yr, whose weight gain in infancy had been recorded. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of the GH secretory profile, insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and GH-binding protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual energy x-ray absortiometry. There was a statistically significant association between peak GH concentration (r = 0.46; P < 0.01) and fasting IGF-I concentration (r = 0.46; P < 0.01) with femoral neck bone density. After allowing for the peak GH concentration, median GH was negatively (P < 0.05) associated with bone mineral density. Weight at 1 yr was not related to peak GH, but was strongly related to the median GH concentration (r = 0.42; P = 0.01). These observations are consistent with a dual effect of GH secretion on bone density. High peak GH values drive IGF-I production and maintain bone mineralization in adult life. However, integrated GH secretion, after adjusting for the effect of pulse amplitude, is negatively associated with bone density in adult life. This particular characteristic of the GH secretory profile correlates with growth during infancy and might be programmed by environmental factors during intrauterine or early postnatal life.


Phytohormone signaling pathway analysis method for comparing hormone responses in plant-pest interactions.
Phytohormones mediate plant defense responses to pests and pathogens. In particular, the hormones jasmonic acid, ethylene, salicylic acid, and abscisic acid have been shown to dictate and fine-tune defense responses, and identification of the phytohormone components of a particular defense response is commonly used to characterize it. Identification of phytohormone regulation is particularly important in transcriptome analyses. Currently there is no computational tool to determine the relative activity of these hormones that can be applied to transcriptome analyses in soybean. We developed a pathway analysis method that provides a broad measure of the activation or suppression of individual phytohormone pathways based on changes in transcript expression of pathway-related genes. The magnitude and significance of these changes are used to determine a pathway score for a phytohormone for a given comparison in a microarray experiment. Scores for individual hormones can then be compared to determine the dominant phytohormone in a given defense response. To validate this method, it was applied to publicly available data from previous microarray experiments that studied the response of soybean plants to Asian soybean rust and soybean cyst nematode. The results of the analyses for these experiments agreed with our current understanding of the role of phytohormones in these defense responses. This method is useful in providing a broad measure of the relative induction and suppression of soybean phytohormones during a defense response. This method could be used as part of microarray studies that include individual transcript analysis, gene set analysis, and other methods for a comprehensive defense response characterization.


Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta.
Following infection with Ostertagia circumcincta there was considerable variation in worm burdens, worm size and number of inhibited larvae even among sheep matched for age, sex, breed, farm of origin and history of parasite exposure. There was also substantial variation among sheep in the concentration of mast cells, globule leucocytes, eosinophils, IgA-positive plasma cells and parasite-specific IgA in the abomasal mucosa. With the exception of faecal egg counts over time, the parasitological and immunological traits were all continually distributed among animals and sheep did not fall into discrete high and low-responder categories. The responses were correlated. Sheep with more mast cells also had more globule leucocytes, more eosinophils, more IgA plasma cells and greater amounts of parasite-specific IgA in the abomasal mucosa. Female worm length was strongly and positively correlated with the number of eggs in utero. Faecal egg counts were associated with variation in worm number and with variation in the number of eggs in utero. The worm burden was negatively correlated with the number of globule leucocytes in the abomasal mucosa, suggesting that worm numbers are regulated by immediate hypersensitivity reactions. Decreased female worm length was associated with an increased local IgA response to fourth stage larvae. The number of inhibited larvae was positively associated with the size of the local IgA response and positively associated with the size of the worm burden. The results suggest that variation among mature sheep in faecal egg counts is due, at least in part, to variation in local IgA responses which regulate worm fecundity and to variation in local immediate hypersensitivity reactions which regulate worm burdens.


Density and morphology of coronary artery calcium for the prediction of cardiovascular events: insights from the Framingham Heart Study.
To investigate the association between directly measured density and morphology of coronary artery calcium (CAC) with cardiovascular disease (CVD) events, using computed tomography (CT). Framingham Heart Study (FHS) participants with CAC in noncontrast cardiac CT (2002-2005) were included and followed until 2016. Participants with known CVD or uninterpretable CT scans were excluded. We assessed and correlated (Spearman) CAC density, CAC volume, and the number of calcified segments. Moreover, we counted morphology features including shape (cylindrical, spherical, semi-tubular, and spotty), location (bifurcation, facing pericardium, or facing myocardium), and boundary regularity. In multivariate Cox regression analyses, we associated all CAC characteristics with CVD events (CVD-death, myocardial infarction, stroke). Among 1330 included participants (57.8 ± 11.7 years; 63% male), 73 (5.5%) experienced CVD events in a median follow-up of 9.1 (7.8-10.1) years. CAC density correlated strongly with CAC volume (Spearman's ρ = 0.75; p < 0.001) and lower number of calcified segments (ρ = - 0.86; p < 0.001; controlled for CAC volume). In the survival analysis, CAC density was associated with CVD events independent of Framingham risk score (HR (per SD) = 2.09; 95%CI, 1.30-3.34; p = 0.002) but not after adjustment for CAC volume (p = 0.648). The extent of spherically shaped and pericardially sided calcifications was associated with fewer CVD events accounting for the number of calcified segments (HR (per count) = 0.55; 95%CI, 0.31-0.98; p = 0.042 and HR = 0.66; 95%CI, 0.45-0.98; p = 0.039, respectively). Directly measured CAC density does not predict CVD events due to the strong correlation with CAC volume. The spherical shape and pericardial-sided location of CAC are associated with fewer CVD events and may represent morphological features related to stable coronary plaques. • Coronary calcium density may not be independently associated with cardiovascular events. • Coronary calcium density correlates strongly with calcium volume. • Spherical shape and pericardial-sided location of CAC are associated with fewer CVD events.


Effectiveness evaluation of existing noise controls in a deep shaft underground mine.
Noise exposures and hearing loss in the mining industry continue to be a major problem, despite advances in noise control technologies. This study evaluated the effectiveness of engineering, administrative, and personal noise controls using both traditional and in-ear dosimetry by job task, work shift, and five types of earplug. The noise exposures of 22 miners performing deep shaft-sinking tasks were evaluated during 56 rotating shifts in an underground mine. Miners were earplug-insertion trained, earplug fit-tested, and monitored utilizing traditional and in-ear dosimetry. The mean TWA8 noise exposure via traditional dosimetry was 90.1 ± 8.2 dBA, while the mean in-ear TWA8 was 79.6 ± 13.8 dBA. The latter was significantly lower (p < 0.05) than the Mine Safety and Health Administration (MSHA) personal exposure limit (PEL) of 90 dBA. Dosimetry mean TWA8 noise exposures for bench blowing (103.5 ± 0.9 dBA), jumbo drill operation (103.0 ± 0.8 dBA), and mucking tasks (99.6 ± 4.7 dBA) were significantly higher (p < 0.05) than other tasks. For bench blowing, cable pulling, grinding, and jumbo drill operation tasks, the mean in-ear TWA8 was greater than 85 dBA. Those working swing shift had a significantly higher (p < 0.001) mean TWA8 noise exposure (95.4 ± 7.3 dBA) than those working day shift. For percent difference between traditional vs. in-ear dosimetry, there was no significant difference among types of earplug used. Reflective of occupational hearing loss rate trends across the mining industry, this study found that, despite existing engineering and administrative controls, noise exposure levels exceeded regulatory limits, while the addition of personal hearing protection limited excessive exposures.


Biological monitoring and health effects of low-level exposure to N-methyl-2-pyrrolidone: a cross-sectional study.
To examine the value of urinary 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in a population of workers exposed to N-methyl-2-pyrrolidone (NMP) and to look for health effects of exposure to this organic solvent. Airborne NMP was determined according to the NIOSH method. Urinary 5-HNMP and 2-HMSI (after and before next shift) were determined by liquid chromatography with tandem mass spectrometry. Outcomes were effects on lung, kidney, skin and mucous membranes, nervous system, haematopoiesis and liver determined by clinical examination and laboratory measurements. Univariate statistical methods and multiple regressions were used to analyse results. Skin resorption, smoking and other potential confounders were taken into account. Three hundred twenty-seven workers were eligible out of which 207 workers (63%) participated. Ninety-one of these worked with NMP. Occupational exposure to NMP did often not occur daily and ranged from non-detectable to 25.8 mg/m3 (median = 0.18). Urinary 2-HMSI (mg/l; before next shift) was the best biomarker of exposure to NMP, explaining about 70% of the variance, but most likelihood ratios did not allow for ruling exposure in or out, at these low levels of exposure. Creatinine adjustment did not improve the results clearly. No clear and consistent health effects could be associated with NMP exposure. No indication for a bias due to non-participation was found. Biological monitoring, primarily urinary 2-HMSI (mg/l; before next shift), is of value to estimate exposure to NMP even when exposure is irregular and low. Likelihood ratios of urinary 5-HMNP or 2-HMSI are, however, not quite satisfactory at these low levels. No irritant or other health effects were found.


Accurate assessment of carotid artery stenosis in atherosclerotic mice using accelerated high-resolution 3D magnetic resonance angiography.
High-resolution magnetic resonance angiography (MRA) enables non-invasive detection and longitudinal monitoring of atherosclerosis in mouse models of human disease. However, MRA is hampered by long acquisition times putting high demands on the physiological stability of the animal. Therefore, we evaluated the feasibility of accelerated MRA using the parallel imaging technique SENSE with regard to both lesion detection and quantification. MRA acquisitions of supra-aortic vessels were performed in ApoE (-/-) mice that have been shown to develop atherosclerotic plaques. Findings obtained from accelerated data sets were compared to fully sampled reference data sets and histology. Our results revealed only minor differences in detecting vascular lesions for data collections accelerated by factors of up to 3.3 using a four-element coil array. For vessels with a mean lumen diameter of 500 μm, morphometry of stenotic lesions revealed no substantial deviations from reference (fully sampled) data for all investigated acceleration factors. For the highest acceleration factor of 3.3, an average deviation of the degree of stenosis of 4.9 ± 3.6% was found. Common carotid stenoses assessed by in vivo MRA displayed a good correlation with histological analyses (slope of linear regression = 0.97, R (2) = 0.98). According to the results of this work, we have demonstrated the feasibility and accuracy of accelerated high-resolution 3D ToF MRA in mice suitable for detailed depiction of mouse supra-aortic vessels and amenable to non-invasive quantification of small atherosclerotic lesions.


Socio-demographics of adult orthodontic visits in the United States.
Population-based studies in orthodontics have focused on differences between normative and perceived needs. However, information from national data on the prevalence of orthodontic visits and their associated factors in adults in the United States is scarce. We examined the demographic profile of likely adult users of orthodontic services and whether there is racial and ethnic disparity in orthodontic visits. We analyzed data from the Medical Expenditure Panel Survey, 2000-2004. Overall, about 1% of the population reported an orthodontic visit. Subjects who made a general dental visit during the current year were significantly more likely to also have an orthodontic visit. Single adults, women, people between 18 and 30 years of age, and those from high-income families were more likely to report an orthodontic visit. There were no indications of racial and ethnic disparity for either black or Hispanic adults compared with white adults after adjusting for other covariates. Substantial racial and ethnic disparity in adult orthodontic usage was not identified. Adults (ages 18-30 years), women, those with higher incomes, and single adults had significantly higher odds of reporting an orthodontic visit. However, additional studies specifically evaluating the association of treatment need among low-income families are required to evaluate whether these adults face significant barriers in accessing orthodontic care.


Psychiatric disorder in pregnancy and the first postnatal year.
We interviewed 128 women regularly during pregnancy and the first postnatal year. Psychiatric interviews identified eight 'cases' of psychiatric disorder (6 per cent) in early pregnancy and twenty 'cases' (16 per cent) at six weeks after birth. Postnatal affective disorder, which accounted for 15 of these cases, was significantly associated with dissatisfaction with the marital relationship and also with previous psychiatric history. The implications of the term 'postnatal depression' are considered in terms of the course of the disorder in the 29 women (23 per cent) who had episodes of affective disorder at some time during pregnancy and the postnatal year. We found that the majority of episodes of affective disorder could be understood in terms of previous psychiatric history and/or reaction to life-events, including the stress of childbirth itself.


Swallowing dysfunction in infants less than 1 year of age.
Gastroesophageal reflux (GER) occurs frequently in infants and children and is implicated as a trigger for reactive airways disease. While evaluating patients for GER by upper gastrointestinal studies (UGI), we frequently noticed laryngeal penetration or tracheal aspiration in infants < 1 year of age. We conducted this prospective study to assess the incidence of swallowing dysfunction in infants with vomiting or respiratory symptoms. Between February 1994 and August 1997, 1,003 UGI in infants < 1 year of age were performed by two experienced pediatric radiologists. Fluoroscopy of swallowing using an appropriate image intensifier was observed as part of the UGI in all patients. In addition to evaluating premature infants, former premature infants, and infants with underlying conditions such as bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), esophageal atresia and/or tracheoesophageal fistula (EA), and neurologic disorders, we assessed swallowing in 472 full-term infants in the general population who had respiratory symptoms or suspected GER, but no other apparent abnormalities. Swallowing was not assessed in patients with congenital bowel obstruction. The presence of normal swallowing or swallowing dysfunction was recorded immediately following the study. Chest radiographs obtained on the same day as the UGI were evaluated in the study. Forty-four videotaped modified barium-swallow studies (MBSS) were obtained in 25 general-population infants and reviewed frame-by-frame to determine the length of time that barium could be visualized in the subglottic trachea. The incidence of swallowing dysfunction is significant in premature and former premature infants, those with BPD, CHD, EA, various syndromes, and neurologic abnormality. In the general population of full-term infants referred for evaluation of vomiting or respiratory symptoms, 63 (13.4 % of 472) had swallowing dysfunction. Forty-four had tracheal aspiration (TA) and 19 had laryngeal penetration (LP). Gastroesophageal reflux was found in 79.5 % with TA and in 68.4 % with LP. The MBSS confirmed swallowing dysfunction in all patients shown to have vocal cord penetration or tracheal aspiration by UGI. Careful evaluation of swallowing during an UGI can identify swallowing dysfunction in full-term infants who have respiratory problems, as well as in infants with an abnormality that predisposes the patient to aspiration. Episodes of tracheal aspiration may be fleeting and overlooked if swallowing is not assessed carefully. An MBSS can confirm the observation of swallowing dysfunction found during an UGI and assist in planning appropriate dietary therapy that minimizes the likelihood of tracheal aspiration during feeding.


GLO1 overexpression in human malignant melanoma.
Glyoxalase I [lactoylglutathione lyase (EC 18.104.22.168) encoded by GLO1] is a ubiquitous cellular defense enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis. Accumulative evidence suggests an important role of GLO1 expression in protection against methylglyoxal-dependent protein adduction and cellular damage associated with diabetes, cancer, and chronological aging. On the basis of the hypothesis that GLO1 upregulation may play a functional role in glycolytic adaptations of cancer cells, we examined GLO1 expression status in human melanoma tissue. Quantitative reverse transcription polymerase chain reaction analysis of a cDNA tissue array containing 40 human melanoma tissues (stages III and IV) and 13 healthy controls revealed pronounced upregulation of GLO1 expression at the mRNA level. Immunohistochemical analysis of a melanoma tissue microarray confirmed upregulation of glyoxalase I protein levels in malignant melanoma tissue versus healthy human skin. Consistent with an essential role of GLO1 in melanoma cell defense against methylglyoxal cytotoxicity, siRNA interference targeting GLO1-expression (siGLO1) sensitized A375 and G361 human metastatic melanoma cells towards the antiproliferative, apoptogenic, and oxidative stress-inducing activity of exogenous methylglyoxal. Protein adduction by methylglyoxal was increased in siGLO1-transfected cells as revealed by immunodetection using a monoclonal antibody directed against the major methylglyoxal-derived epitope argpyrimidine that detected a single band of methylglyoxal-adducted protein in human LOX, G361, and A375 total cell lysates. Using two-dimensional proteomics followed by mass spectrometry the methylglyoxal-adducted protein was identified as heat shock protein 27 (Hsp27; HSPB1). Taken together, our data suggest a function of GLO1 in the regulation of detoxification and target adduction by the glycolytic byproduct methylglyoxal in malignant melanoma.


Predicting coral recruitment in Palau's complex reef archipelago.
Reproduction and recruitment are key processes that replenish marine populations. Here we use the Palau archipelago, in the western Pacific Ocean, as a case study to examine scales of connectivity and to determine whether an oceanographic model, incorporating the complex reef architecture, is a useful predictor of coral recruitment. We tested the hypothesis that the reefs with the highest retention also had the highest densities of juvenile coral density from 80 field sites. Field comparisons showed a significant correlation between the densities of juvenile Acropora colonies and total larval recruitment derived from the model (i.e., calculated as the sum of the densities of larvae that self-seeded and recruited from the other reefs in the archipelago). Long-distance larval imports may be too infrequent to sustain coral populations, but are critical for recovery in times of extreme local stress.


Improved prediction equations for estimating height in adults from ethnically diverse backgrounds.
When body height cannot be measured, it can be predicted from ulna length (UL). However, commonly used published prediction equations may not provide useful estimates in adults from all ethnicities. This study aimed to evaluate the relationship between UL and height in adults from diverse ethnic groups and to consider whether this can be used to provide useful prediction equations for height in practice. Standing height and UL were measured in 542 adults at seven UK locations. Ethnicity was self-defined using UK Census 2011 categories. Data were modelled to give two groups of height prediction equations based on UL, sex and ethnicity and these were tested against an independent dataset (n = 180). UL and height were significantly associated overall and in all groups except one with few participants (P = 0.059). The new equations yielded predicted height (Hp) that was closer to measured height in the Asian and Black subgroups of the independent population than the Malnutrition Universal Screening Tool (MUST) equations. For Asian men, (Hp (cm) = 3.26 UL (cm) + 83.58), mean difference from measured (95% confidence intervals) was -0.6 (-2.4, +1.2); Asian women, (Hp = 3.26 UL + 77.62), mean difference +0.5 (-1.4, 2.4) cm. For Black men, Hp = 3.14 UL + 85.80, -0.4 (-2.4, 1.7); Black women, Hp = 3.14 UL + 79.55, -0.8 (-2.8, 1.2). These differences were not statistically significant while predictions from MUST equations were significantly different from measured height. The new prediction equations provide an alternative for estimating height in adults from Asian and Black groups and give mean predicted values that are closer to measured height than MUST equations.


Balloon catheter hypoxic abdominal and pelvic perfusion with tumour necrosis factor-alpha, Melphalan and Mitomycin C: a pharmacokinetic study in pigs.
Addition of tumour necrosis factor-alpha (TNF) to hypoxic abdominal perfusion (HAP) and hypoxic pelvic perfusion (HPP) with chemotherapeutic agents for treatment of un-resectable malignancies may lead to similar enhanced anti-tumour effects as are observed when TNF is added to isolated limb perfusions (ILP) with Melphalan. Here, we validate the methodology of HAP and HPP using balloon catheter techniques, and investigate the distribution of TNF, Melphalan and Mitomycin C (MMC) over the regional and systemic blood compartments when applying these techniques. Twelve pigs underwent HAP or HPP with TNF, Melphalan and MMC for 20 min. Throughout and after the procedures blood samples were obtained from hepatic, portal and systemic blood compartments and plasma concentrations of perfused agents were determined. We demonstrated that HAP and HPP result in temporary loco-regional concentration advantages of all perfused agents, although from start of perfusion significant systemic leakage occurred. On basis of these results it seems that the advantage in terms of regional plasma concentration of TNF may be insufficient for TNF-mediated effects to occur, making future addition of this cytokine to these procedures in the clinical setting questionable. The observed regional concentration advantages of MMC and Melphalan, however, warrant further studies on clinical application of these agents in both settings.


Sweating: A Specific Predictor of ST-Segment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study Group.
Today, cardiologists seek to minimize time from symptom onset to interventional treatment for the most favorable results. In the acute coronary syndrome (ACS) symptom complex, sweating can differentiate ST-segment elevation myocardial infarction (STEMI) from non-ST-segment elevation ACS (NSTE-ACS) during early hours of infarction. This single-center, prospective, observational study compared symptoms of STEMI and NSTE-ACS patients admitted from August 2012 to July 2014. Of 12 913 patients, 90.56% met ACS criteria. Among these, 22.51% had STEMI. Typical angina was the most common symptom (83.82%). On stepwise multiple regression, sweating (odds ratio: 97.06, 95% confidence interval [CI]: 82.16-114.14, P < 0.0001) and typical angina (odds ratio: 2.72, 95% CI: 2.18-3.38, P < 0.001) had significant association with STEMI. For diagnosis of STEMI, positive likelihood ratio (LR) and positive predictive value (PPV) were highest for typical angina with sweating (LR: 11.17, 95% CI: 10.31-12.1; PPV: 76.09, 95% CI: 74.37-77.75), followed by sweating with atypical angina (LR: 3.6, 95% CI: 3.07-4.21; PPV: 50.61, 95% CI: 46.45-54.76), typical angina (LR: 1.05, 95% CI: 1.03-1.07; PPV: 22.97, 95% CI: 22.11-23.84), and atypical angina (LR: 0.77, 95% CI: 0.69-0.87; PPV: 18.09, 95% CI: 16.32-19.97). C statistic values of 0.859 for typical angina with sweating and 0.519 for typical angina alone reflected high discriminatory value of sweating for STEMI prediction. Presence of sweating with ACS symptoms predicts probability of STEMI, even before clinical confirmation. Sweating in association with typical or atypical angina is a much better predictor of STEMI than NSTE-ACS.


Impact of a chronic disease management program on hospital admissions and readmissions in an Australian population with heart disease or diabetes.
Chronic disease management programs (CDMPs) were introduced in Australia to reduce unnecessary health care utilization by the growing population with chronic conditions; however, evidence of effectiveness is needed. This study evaluated the impact of a comprehensive CDMP, My Health Guardian (MHG), on rate of hospital admissions, readmissions, and average length of hospital stay (ALOS) for insured individuals with heart disease or diabetes. Primary outcomes were assessed through retrospective comparison of members in MHG (treatment; n=5053) to similar nonparticipating members (comparison; n=23,077) using a difference-in-differences approach with the year before program commencement serving as baseline and the subsequent 12 or 18 months serving as the program periods. All outcomes were evaluated for the total study population and for disease-matched subgroups (heart disease and diabetes). Statistical tests were performed using multivariate regression controlling for age, sex, number of chronic diseases, and past hospitalization status. After both 12 and 18 months, treatment members displayed decreases in admissions (both, P≤0.001) and readmissions (both, P≤0.01), and ALOS after 18 months (P≤0.01) versus the comparison group; magnitude of impact increased over time for these 3 measures. All outcomes for both disease-matched subgroups directionally mirrored the total study group, but the diabetes subgroup did not achieve significance for readmissions or ALOS. Within the treatment group, admissions decreased with increasing care calls to members (12 and 18 months, P<0.0001). These results show that MHG successfully reduced the frequency and duration of hospital admissions and presents a promising approach to reduce the burden associated with hospitalizations in populations with chronic disease.


Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5.
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that has been implicated in learning, synaptic plasticity, neurotransmission, and numerous neurological disorders. We previously showed that conditional loss of Cdk5 in adult mice enhanced hippocampal learning and plasticity via modulation of calpain-mediated N-methyl-D-aspartic acid receptor (NMDAR) degradation. In the present study, we characterize the enhanced synaptic plasticity and examine the effects of long-term Cdk5 loss on hippocampal excitability in adult mice. Field excitatory post-synaptic potentials (fEPSPs) from the Schaffer collateral CA1 subregion of the hippocampus (SC/CA1) reveal that loss of Cdk5 altered theta burst topography and enhanced post-tetanic potentiation. Since Cdk5 governs NMDAR NR2B subunit levels, we investigated the effects of long-term Cdk5 knockout on hippocampal neuronal excitability by measuring NMDAR-mediated fEPSP magnitudes and population-spike thresholds. Long-term loss of Cdk5 led to increased Mg(2+)-sensitive potentials and a lower threshold for epileptiform activity and seizures. Biochemical analyses were performed to better understand the role of Cdk5 in seizures. Induced-seizures in wild-type animals led to elevated amounts of p25, the Cdk5-activating cofactor. Long-term, but not acute, loss of Cdk5 led to decreased p25 levels, suggesting that Cdk5/p25 may be activated as a homeostatic mechanism to attenuate epileptiform activity. These findings indicate that Cdk5 regulates synaptic plasticity, controls neuronal and behavioral stimulus-induced excitability and may be a novel pharmacological target for cognitive and anticonvulsant therapies.


Why Japanese workers show low work engagement: An item response theory analysis of the Utrecht Work Engagement scale.
With the globalization of occupational health psychology, more and more researchers are interested in applying employee well-being like work engagement (i.e., a positive, fulfilling, work-related state of mind that is characterized by vigor, dedication, and absorption) to diverse populations. Accurate measurement contributes to our further understanding and to the generalizability of the concept of work engagement across different cultures. The present study investigated the measurement accuracy of the Japanese and the original Dutch versions of the Utrecht Work Engagement Scale (9-item version, UWES-9) and the comparability of this scale between both countries. Item Response Theory (IRT) was applied to the data from Japan (N = 2,339) and the Netherlands (N = 13,406). Reliability of the scale was evaluated at various levels of the latent trait (i.e., work engagement) based the test information function (TIF) and the standard error of measurement (SEM). The Japanese version had difficulty in differentiating respondents with extremely low work engagement, whereas the original Dutch version had difficulty in differentiating respondents with high work engagement. The measurement accuracy of both versions was not similar. Suppression of positive affect among Japanese people and self-enhancement (the general sensitivity to positive self-relevant information) among Dutch people may have caused decreased measurement accuracy. Hence, we should be cautious when interpreting low engagement scores among Japanese as well as high engagement scores among western employees.


Diagnostic meta-analysis of the Pediatric Sleep Questionnaire, OSA-18, and pulse oximetry in detecting pediatric obstructive sleep apnea syndrome.
The aim of this meta-analysis was to compare the pooled sensitivity and specificity of the Pediatric Sleep Questionnaire (PSQ), Obstructive Sleep Apnea Questionnaire (OSA-18), and pulse oximetry (PO) according to OSAS severity. Three electronic databases were searched for studies evaluating sensitivity and specificity of the three tools against the apnea-hypopnea index measured using overnight in-laboratory or in-home polysomnography in children and adolescents from inception until January 11, 2020. A random-effects bivariate model was used to estimate the summary sensitivity and specificity of the tools. We identified 39 studies involving 6131 clinical and community children (aged 2.9-16.7 y). The PSQ exhibited the highest sensitivity (74%) for detecting symptoms of mild pediatric OSAS. The PSQ and PO had comparable sensitivity in screening moderate and severe pediatric OSAS (0.82 and 0.89 vs 0.83 and 0.83, respectively). PO yielded superior specificity in detecting mild, moderate, and severe pediatric OSAS (86%, 75%, and 83%, respectively) than did the PSQ and OSA-18 (all p < 0.05). Age, percentage of girls, index test criteria, methodology quality, and sample size significantly moderated sensitivity and specificity. For early detection of pediatric OSAS, the combined use of PSQ and PO is recommended when polysomnography is not available. PROSPERO REGISTRATION NUMBER: CRD42018090571.


A Transdiagnostic Perspective on Social Anhedonia.
Humans are highly social beings, yet people with social anhedonia experience reduced interest in or reward from social situations. Social anhedonia is a key facet of schizotypal personality, an important symptom of schizophrenia, and increasingly recognized as an important feature in a range of other psychological disorders. However, to date, there has been little examination of the similarities and differences in social anhedonia across diagnostic borders. Here, our goal was to conduct a selective review of social anhedonia in different psychological and life course contexts, including the psychosis continuum, depressive disorder, posttraumatic stress disorder, eating disorders, and autism spectrum disorders, along with developmental and neurobiological factors. Current evidence suggests that the nature and expression of social anhedonia vary across psychological disorders with some groups showing deficient learning about, enjoyment from, and anticipation of the pleasurable aspects of social interactions, while for others, some of these components appear to remain intact. However, study designs and methodologies are diverse, the roles of developmental and neurobiological factors are not routinely considered, and direct comparisons between diagnostic groups are rare-which prevents a more nuanced understanding of the underlying mechanisms involved. Future studies, parsing the wanting, liking, and learning components of social reward, will help to fill gaps in the current knowledge base. Consistent across disorders is diminished pleasure from social situations, subsequent withdrawal, and poorer social functioning in those who express social anhedonia. Nonetheless, feelings of loneliness often remain, which suggests the need for social connection is not entirely absent. Adolescence is a particularly important period of social and neural development and may provide a valuable window on the developmental origins of social anhedonia. Adaptive social functioning is key to recovery from mental health disorders; therefore, understanding the intricacies of social anhedonia will help to inform treatment and prevention strategies for a range of diagnostic categories.


Viewing speech modulates activity in the left SI mouth cortex.
The ability to internally simulate other persons' actions is important for social interaction. In monkeys, neurons in the premotor cortex are activated both when the monkey performs mouth or hand actions and when it views or listens to actions made by others. Neuronal circuits with similar "mirror-neuron" properties probably exist in the human Broca's area and primary motor cortex. Viewing other person's hand actions also modulates activity in the primary somatosensory cortex SI, suggesting that the SI cortex is related to the human mirror-neuron system. To study the selectivity of the SI activation during action viewing, we stimulated the lower lip (with tactile pulses) and the median nerves (with electric pulses) in eight subjects to activate their SI mouth and hand cortices while the subjects either rested, listened to other person's speech, viewed her articulatory gestures, or executed mouth movements. The 55-ms SI responses to lip stimuli were enhanced by 16% (P<0.01) in the left hemisphere during speech viewing whereas listening to speech did not modulate these responses. The 35-ms responses to median-nerve stimulation remained stable during speech viewing and listening. Own mouth movements suppressed responses to lip stimuli bilaterally by 74% (P<0.001), without any effect on responses to median-nerve stimuli. Our findings show that viewing another person's articulatory gestures activates the left SI cortex in a somatotopic manner. The results provide further evidence for the view that SI is involved in "mirroring" of other persons' actions.


Probing the invasiveness of prostate cancer cells in a 3D microfabricated landscape.
The metastatic invasion of cancer cells from primary tumors to distant ecological niches, rather than the primary tumors, is the cause of much cancer mortality [Zhang QB, et al. (2010) Int J Cancer 126:2534-2541; Chambers AF, Goss PE (2008) Breast Cancer Res 10:114]. Metastasis is a three-dimensional invasion process where cells spread from their site of origin and colonize distant microenvironmental niches. It is critical to be able to assess quantitatively the metastatic potential of cancer cells [Harma V, et al. (2010) PLoS ONE 5:e10431]. We have constructed a microfabricated chip with a three-dimensional topology consisting of lowlands and isolated square highlands (Tepuis), which stand hundreds of microns above the lowlands, in order to assess cancer cell metastatic potential as they invade the highlands. As a test case, the invasive ascents of the Tepui by highly metastatic PC-3 and noninvasive LNCaP prostate cancer cells were used. The vertical ascent by prostate cancer cells from the lowlands to the tops of the Tepui was imaged using confocal microscopy and used as a measure of the relative invasiveness. The less-metastatic cells (LNCaP) never populated all available tops, leaving about 15% of them unoccupied, whereas the more metastatic PC-3 cells occupied all available Tepuis. We argue that this distinct difference in invasiveness is due to contact inhibition.


Continuously spacing-tunable multiwavelength semiconductor-optical-amplifier-based fiber ring laser incorporating a superimposed chirped fiber Bragg grating.
We investigate a flexibly tunable multiwavelength semiconductor-optical-amplifier-based fiber ring laser with continuous wavelength spacing controllability incorporating a superimposed chirped fiber Bragg grating (CFBG). The wavelength spacing of a superimposed CFBG can be continuously controlled by symmetrically modifying the chirp bandwidth of the grating with the specially designed apparatus. We achieve a wide and continuous tuning range of the wavelength spacing from 0.35 to 0.78 nm. The continuous tunability of the wavelength spacing is measured to be ~ +/-0.033 nm/mm. By controlling the reflection bandwidth of the tunable CFBG, we can independently adjust the number of lasing channels from 2 to 23 at the wavelength spacing of 0.51 nm.


Internet-based videoconferencing coder/decoders and tools for telemedicine.
Alternative videoconferencing technologies for providing telemedicine via the Internet are described. Background information about how digital video applications have been instantiated using Internet protocols is presented. Specific methods for encoding and decoding video are discussed and video applications that have been tested at the National Library of Medicine are reviewed. This article suggests that no one technology is best and that the appropriateness of a method depends on specific applications. Some technologies, however, have lower, more flexible bandwidth requirements and are more standardized, making them more practical. Still, emerging, yet-to-be-standardized applications offer new capabilities warranting further investigation.


Even-skipped homeobox 1 is frequently hypermethylated in prostate cancer and predicts PSA recurrence.
DNA methylation is an important epigenetic mechanism in prostate cancer (PCa) progression. Given the role of even-skipped homeobox 1 (EVX1) in the regulation of multiple genes during embryogenesis, we postulated that EVX1 methylation is altered in PCa progression. Bisulphite sequencing and quantitative MethyLight were used to assess methylation in human prostate epithelial cells, four PCa cell lines, liver, lung, spleen, kidney, 35 paired tumour and tumour-associated benign tissues, and 11 normal prostate tissues. Prostate cancer cell lines were treated with 5-azacytidine (AzaC) or trichostatin A (TSA), and expression of EVX1 transcript and variants was assessed by qPCR. Hypermethylation was compared with clinicopathological features in a validation set of 58 patients using microarray. Even-skipped homeobox 1 hypermethylation was observed in all four PCa cell lines and 57% of tumours. High-grade tumours exhibited increased methylation compared with intermediate-grade tumours. Even-skipped homeobox 1 expression was induced in PCa cell lines after treatment with AzaC or TSA. In the validation set, 83% of tumours were hypermethylated and hypermethylation was associated with worse recurrence-free survival. In this first evaluation of EVX1 methylation in human cancer, EVX1 is one of the most commonly hypermethylated genes observed in PCa and predicted treatment failure in moderate risk patients.


Comparison of intestinal bacterial populations between two dairy cattle herds colonized or not by Campylobacter jejuni.
Campylobacter jejuni is an important foodborne pathogen. It can be isolated from bovine feces and its presence is influenced by farm characteristics and management practices. The impact of the bovine gut microbiota on the presence of C. jejuni is poorly documented. Two herds of lactating cows were selected: one where C. jejuni was not detected in 20 animals and the other where 55% of the sampled animals (11/20) were contaminated by C. jejuni. The bacterial diversity of bovine feces from these two herds was analyzed by terminal restriction fragment length polymorphism. The full-length 16S rRNA gene was amplified using fluorescently labeled primers and subsequently digested with HaeIII. Terminal restriction fragments profiles comparison showed a similarity level >79% between microbial populations from both herds. As profiles containing or not C. jejuni were clustered together, it is proposed that the presence of C. jejuni is not linked to a particular profile from the recovered intestinal bovine microbiota.


First Report of Anthracnose on Rohdea japonica Caused by Colletotrichum liriopes in Korea.
Lily of China (Rohdea japonica Roth) is a flowering plant native to eastern Asia. In the summers of 2010 and 2011, suspected anthracnose disease was observed on R. japonica plants in the exhibition field of Jinju Agriculture Technology Center, Jinju, South Korea. Symptoms began as yellow to brown spots on leaves and darkened as the spots expanded. The lesions subsequently became dark brown, and bristled acervuli were observed on the dark brown areas. Leaf spots led to leaf shriveling and eventual death. Fresh leaf specimens were collected from infected plants and the putative causal pathogen was isolated on potato dextrose agar (PDA). The fungus formed a dark brown colony, irregularly shaped black sclerotia, and abundant setae in PDA cultures. Conidia were colorless, falcate, fusiform, and 21 to 26 × 2 to 3 μm. Appressoria were clavate to circular and 8 to 12 × 6 to 8 μm. Amplification of the internal transcribed spacer was conducted as described previously (2) and generated a 577-bp sequence (GenBank Accession No. JQ677042) with 99% identity to sequences of C. liriopes strain CBS 119444 (GU227804), identified previously as C. dematium from Agavaceae (1). In the phylogenetic tree, the representative strain was placed within a clade comprising a reference strain of C. liriopes (data not shown). A representative isolate of the pathogen was used to inoculate R. japonica leaves for pathogenicity testing. Five 4-month-old R. japonica plants were sprayed to runoff with a conidial suspension (104 conidia/ml) and 0.025% Tween. Three plants were sprayed with sterilized distilled water and 0.025% Tween as a control. The plants were kept in a moist chamber with >90% relative humidity at 25°C for 48 h and then moved to a greenhouse. After 7 days of incubation, necrotic spot symptoms similar to those observed in the field developed on the inoculated leaves. Control plants remained asymptomatic. The pathogenicity test was repeated twice with similar results and the causal fungus was reisolated from the lesions of inoculated plants to satisfy Koch's postulates in each test. On the basis of observed symptoms, morphology, pathogenicity, and molecular characterization, this fungus was identified as Colletotrichum liriopes. The recent outbreak of leaf spot on R. japonica plants suggests that C. liriopes is spreading and poses a serious threat to these plants in Korea. References: (1) U. Damm et al. Fungal Diversity 39:45, 2009. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications, M. A. Innis et al., eds., Academic Press, Inc., New York, 1990.