Rheology of protic ionic liquids and their mixtures.
The rheological properties of five pure protic ionic liquids (ILs), ethylammonium nitrate (EAN), propylammonium nitrate (PAN), ethanolammonium nitrate (EtAN), ethylammonium formate (EAF), and dimethylethylammonium formate (DMEAF), are characterized and interpreted by considering the effects of both the H-bond network and the solvophobic nanostructure of the liquids. The results demonstrate that these effects are not, however, independent or simply additive. At 20 °C, EtAN has the highest zero shear viscosity of 156.1 mPa·s, followed by PAN (89.3 mPa·s), EAN (35.9 mPa·s), EAF (23.1 mPa·s), and DMEAF (9.8 mPa·s). The primary ammonium ILs behave as Newtonian fluids at low shear rates but shear thin at high shear. Fits to the Vogel-Fulcher-Tammann model reveal that nanostructure is not affected appreciably by temperature and that all the ILs studied are of intermediate fragility. The rheology of binary mixtures of these ILs was analyzed and used to demonstrate fundamental differences in the way IL cations and anions interact. IL mixtures containing both nitrate and formate anions resist flow more strongly than the pure liquids, which is a consequence of the difference in hydrogen bonding capacity of the anions. Mixing cations can give rise to complex behavior due to the offsetting effects of hydrogen bonding and solvophobic nanostructure formation.


Benzodiazepine Use Disorder and Cognitive Impairment in Older Patients: A Six-Month-Follow-Up Study in an Outpatient Unit in Barcelona.
Adverse health effects including cognitive impairment have been described in older adults with benzodiazepine misuse, although the literature about this issue is scarce. The present study aimed to assess cognitive decline in older adults with benzodiazepine use disorder and changes in cognitive state at the 6-month follow-up, as well as whether patients achieved abstinence. A 6-month follow-up longitudinal study was conducted in an outpatient drug center in Barcelona in a sample of older adults (≥65 years old) who had benzodiazepine use disorder. The sample was compared with an equivalent control group. A neuropsychological protocol was performed at baseline and after 6-month follow-up covering the most important cognitive domains. The final sample comprised 33 patients with an average age of 73.5 years. At baseline, patients presented impairment in several domains compared with the control group: visual immediate recall (p < .001), visual delayed recall (p < .001), copy (p < .001), working memory (p < .003), immediate verbal learning (p < .002), total words learned (p < .009), set switching (p < .001), verbal fluency (p < .007), speed processing (p < .002), solving problems (p < .006), nonverbal fluency (p < .004), and sustained attention in all three areas omissions (p < .001), variability (p < .001), and perseverance (p < .005). At 6-month follow-up, patients achieving abstinence showed improvement compared with patients in active consumption in visual delayed recall (p < .006), total words learned (p < .010), and verbal fluency (p < .013). Benzodiazepine misuse in older adults may produce negative effects on cognitive skills. Recovery of some of these cognitive deficits may be possible with benzodiazepine abstinence.


The Impact of Various Promotional Activities on Ebola Prevention Behaviors and Psychosocial Factors Predicting Ebola Prevention Behaviors in the Gambia Evaluation of Ebola Prevention Promotions.
The outbreak of the Ebola virus disease (EVD) from 2014 to 2016 is over. However, several outbreaks of contagious diseases have already arisen and will recur. This paper aims to evaluate the effectiveness of EVD prevention promotions in the Gambia and to assess the psychosocial factors that steer three behaviors: handwashing with soap, calling the Ebola Hotline, and not touching a person who might be suffering from EVD. In 2015, data were gathered from 498 primary care providers. The questionnaire was based on psychosocial factors from the risks, attitudes, norms, abilities, and self-regulation (RANAS) model. Three promotional activities were significantly associated with psychosocial factors of handwashing and, thus, with increased handwashing behavior: the home visit, posters, and info sheets. Norm factors, especially the perception of what other people do, had a great impact on handwashing with soap and on calling the Ebola Hotline. The perceived certainty that a behavior will prevent a disease was a predictor for all three protection behaviors. Commitment to the behavior emerged as especially relevant for the intention to call the Ebola Hotline and for not touching a person who might be suffering from EVD. Health behavior change programs should rely on evidence to target the right psychosocial factors and to maximize their effects on prevention behaviors, especially in emergency contexts.


Identification and characterization of a novel adhesin unique to oral fusobacteria.
Fusobacterium nucleatum is a gram-negative anaerobe that is prevalent in periodontal disease and infections of different parts of the body. The organism has remarkable adherence properties, binding to partners ranging from eukaryotic and prokaryotic cells to extracellular macromolecules. Understanding its adherence is important for understanding the pathogenesis of F. nucleatum. In this study, a novel adhesin, FadA (Fusobacterium adhesin A), was demonstrated to bind to the surface proteins of the oral mucosal KB cells. FadA is composed of 129 amino acid (aa) residues, including an 18-aa signal peptide, with calculated molecular masses of 13.6 kDa for the intact form and 12.6 kDa for the secreted form. It is highly conserved among F. nucleatum, Fusobacterium periodonticum, and Fusobacterium simiae, the three most closely related oral species, but is absent in the nonoral species, including Fusobacterium gonidiaformans, Fusobacterium mortiferum, Fusobacterium naviforme, Fusobacterium russii, and Fusobacterium ulcerans. In addition to FadA, F. nucleatum ATCC 25586 and ATCC 49256 also encode two paralogues, FN1529 and FNV2159, each sharing 31% identity with FadA. A double-crossover fadA deletion mutant, F. nucleatum 12230-US1, was constructed by utilizing a novel sonoporation procedure. The mutant had a slightly slower growth rate, yet its binding to KB and Chinese hamster ovarian cells was reduced by 70 to 80% compared to that of the wild type, indicating that FadA plays an important role in fusobacterial colonization in the host. Furthermore, due to its uniqueness to oral Fusobacterium species, fadA may be used as a marker to detect orally related fusobacteria. F. nucleatum isolated from other parts of the body may originate from the oral cavity.


The cardiac inotropic responses to insulin in the rat heart.
Insulin (5 to 40 I.U.) produced dose-dependent positive inotropic effect in the isolated rat heart. The responses to insulin were markedly inhibited in the presence of propranolol (1 . 1X10(-6) M). Insulin responses were markedly reduced in reserpine pretreated (5 mg/kg, i.p.) rats. Theophylline (4.4 mM), the phosphodiesterase inhibitor, potentiated the responses to insulin, whereas imidazole (20 mM), the phosphodiesterase stimulator inhibited the responses to insulin. The data suggest that the positive inotropic effects of insulin in rat heart is mediated through the release of cardiac catecholamines which stimulates beta-adrenoceptors. The final mediator of cardiac action seems to be cyclic-AMP.


AtLSG1-2 Regulates Leaf Growth by Affecting Cell Proliferation and the Onset of Endoreduplication and Synergistically Interacts with AtNMD3 during Cell Proliferation Process.
AtLSG1-2 is a circularly permuted GTPase required for ribosome biogenesis and recently shown to be involved in early leaf development, although it was unclear how AtLSG1-2 affects leaf growth. Here, we found that atlsg1-2 mutants had reduced leaf size as a result of decreased cell size and cell number. Leaf kinematic analysis and CYCB1;1::GUS expression pattern in atlsg1-2 mutant indicated that loss of function of AtLSG1-2 delays the transition from cell division to cell expansion. Decreases in ploidy levels and trichome branch number suggest that AtLSG1-2 deficiency suppresses endoreduplication. Real-time PCR analysis showed that genes specifically expressed in the proliferation stage were highly expressed and those involved in endoreduplication were differentially regulated. LSG1 is known to mediate the recruitment of nucleocytoplasmic shuttling protein NMD3 back to the nucleus in yeast, yet their relationship was unclear in plants. Our genetic analysis revealed that the atlsg1 atnmd3 double mutant displayed enhanced phenotypes as compared with the respective single mutant and that AtLSG1-2 and AtNMD3 synergistically affect the cell proliferation process.


CXCL12 alone is insufficient for gliomagenesis in Nf1 mutant mice.
Tumorigenesis requires interactions between tumor progenitors and their microenvironment. We found that low cAMP levels were sufficient for tumorigenesis in a mouse model of Neurofibromatosis-1 (NF1)-associated optic pathway glioma (OPG). We hypothesized that the distinct pattern of glioma in NF1 reflected spatiotemporal differences in CXCL12 effects on cAMP levels. Thus, we sought to alter the pattern of gliomagenesis through manipulation of CXCL12-CXCR4 pathway activation in Nf1 OPG mice. Forced CXCL12 expression induced glioma at a low frequency. Further, treatment of Nf1 OPG mice with AMD3100, a CXCR4 antagonist, did not attenuate glioma growth. Thus, it appears, CXCL12 alone cannot promote gliomagenesis in NF1 mice.


Testing alternatives: the use of adipose-derived mesenchymal stem cells to slow neurodegeneration in a rat model of Parkinson's disease.
Parkinson's disease (PD) is a chronic neurodegenerative disease. Unfortunately, the effectiveness of anti-Parkinson treatments gradually diminishes owing to the progressive degeneration of the dopaminergic terminals. The research described here investigated the effect of adipose-derived mesenchymal stem cells (AD-MSC) versus that of an anti-Parkinson drug in a rat model of Parkinsonism. Forty adult rats were divided into four equal groups, each group receiving a different treatment: vehicle, rotenone, rotenone + AD-MSC, or rotenone + carbidopa/levodopa. Behavioral tests were carried out before and at the end of the treatment and specimens harvested from the midbrain were processed for light and electron microscopy. Genetic expression of glial fibrillary acidic protein (GFAP) and Nestin mRNA was assessed. Expression of the Lamin-B1 and Vimentin genes was measured, along with plasma levels of Angiopoietin-2 and dopamine. Treatment with rotenone induced pronounced motor deficits, as well as neuronal and glial alterations. The AD-MSC group showed improvements in motor function in the live animals and in the microscopic picture presented by their tissues. The fold change of both genes (GFAP and Nestin) decreased significantly in the AD-MSC and carbidopa/levodopa groups compared to the group with Parkinson's disease. Plasma levels of Angiopoietin-2 and dopamine were significantly increased after treatment (P < 0.001) compared to levels in the rats with Parkinson's disease. AD-MSC reduced neuronal degeneration more efficiently than did the anti-Parkinson drug in a rat model of Parkinsonism.


[Mitotic activity changes in the corneal epithelium of rats of different ages following exposure to pain].
A study was made of pain stimulus (amputation of 1/3 of the tail) on the mitotic activity in the corneal epithelium of 21-day fetuses, 1-, 3-, 4-, 5-, 7-, 10-, 15-, 20- and 25-day rats. In 45 minutes after the infliction of trauma no significant change was seen in the cornea of the fetuses and of the one-day-old ratlings. A gradual establishment of the reactive inhibition of mitoses in response to pain occurred between the 3rd and the 10th day of postnatal development. This reaction became more intense after the 10th day, reaching the maximum by the 25th day. Reactive inhibition of the mitotic activity was connected with the inhibition of the entrance of cells into mitosis.


OTX Genes in Adult Tissues.
OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets.


Effect of a Smartphone-Based App on the Quality of Life of Patients With Heart Failure: Randomized Controlled Trial.
Patients with heart failure have low quality of life because of physical impairments and advanced clinical symptoms. One of the main goals of caring for patients with heart failure is to improve their quality of life. The aim of this study was to investigate the effect of the use of a smartphone-based app on the quality of life of patients with heart failure. This randomized controlled clinical trial with a control group was conducted from June to October 2018 in an urban hospital. In this study, 120 patients with heart failure hospitalized in cardiac care units were randomly allocated to control and intervention groups. Besides routine care, patients in the intervention group received a smartphone-based app and used it every day for 3 months. Both the groups completed the Minnesota Living with Heart Failure Questionnaire before entering the study and at 3 months after entering the study. Data were analyzed using the SPSS software V.16. The groups showed statistically significant differences in the mean scores of quality of life and its dimensions after the intervention, thereby indicating a better quality of life in the intervention group (P<.001). The effect size of the intervention on the quality of life was 1.85 (95% CI 1.41-2.3). Moreover, the groups showed statistically significant differences in the changes in the quality of life scores and its dimensions (P<.001). Use of a smartphone-based app can improve the quality of life in patients with heart failure. The results of our study recommend that digital apps be used for improving the management of patients with heart failure. Iranian Registry of Clinical Trials IRCT2017061934647N1; https://www.irct.ir/trial/26434.


Effects of egg size on the development time of non-feeding larvae.
The evolution of egg size in marine invertebrates remains a topic of central importance for life-history biologists, and the pioneering work of Vance has strongly influenced our current views. Vance's model and most models developed since have assumed that increases in egg size result in an increase in the prefeeding period of marine invertebrate larvae. For lecithotrophic species, this means that the entire development period should be correlated with egg size. Despite the importance of this assumption, it has not been tested at the appropriate scale-within species. We investigated the effects of egg size on development time for three lecithotrophic species from two phyla: the ascidians Phallusia obesa and Ciona intestinalis, and the echinoid Heliocidaris erythrogramma. We found that within individual broods of eggs, larger eggs took longer than smaller eggs to develop or become metamorphically competent larvae. It has long been recognized that producing larger eggs decreases fecundity, but our results show that increasing egg size also carries the extra cost of an extended planktonic period during which mortality can occur. The substantial variation in egg sizes observed within broods may represent a bet-hedging strategy by which offspring with variable dispersal potentials are produced.


A novel human hexameric DNA helicase: expression, purification and characterization.
We have cloned, expressed and purified a hexameric human DNA helicase (hHcsA) from HeLa cells. Sequence analysis demonstrated that the hHcsA has strong sequence homology with DNA helicase genes from Saccharomyces cerevisiae and Caenorhabditis elegans, indicating that this gene appears to be well conserved from yeast to human. The hHcsA gene was cloned and expressed in Escherichia coli and purified to homogeneity. The expressed protein had a subunit molecular mass of 116 kDa and analysis of its native molecular mass by size exclusion chromatography suggested that hHcsA is a hexameric protein. The hHcsA protein had a strong DNA-dependent ATPase activity that was stimulated >/=5-fold by single-stranded DNA (ssDNA). Human hHcsA unwinds duplex DNA and analysis of the polarity of translocation demonstrated that the polarity of DNA unwinding was in a 5'-->3' direction. The helicase activity was stimulated by human and yeast replication protein A, but not significantly by E.coli ssDNA-binding protein. We have analyzed expression levels of the hHcsA gene in HeLa cells during various phases of the cell cycle using in situ hybridization analysis. Our results indicated that the expression of the hHcsA gene, as evidenced from the mRNA levels, is cell cycle-dependent. The maximal level of hHcsA expression was observed in late G(1)/early S phase, suggesting a possible role for this protein during S phase and in DNA synthesis.


Acute radiodermatitis following radiotherapy for classic Kaposi's sarcoma.
There is a high incidence of radiation toxicity associated with Kaposi's sarcoma. The authors review acute radiodermatitis and present a case where it occurred in the foot following radiotherapy for classic Kaposi's sarcoma.


Partial purification and properties of an exonuclease inhibitor induced by bacteriophage Mu-1.
From an induced lysogen of bacteriophage Mu-1, we partially purified a substance of high molecular weight that blocks the action of several exonucleases on double-stranded DNA. The presence of the inhibitor in cell-free extracts is dependent on induction of a Mu prophage. The Mu-related inhibitor acts by binding to double-stranded DNA rather than by interacting with the DNase. The inhibitor protects linear duplex DNA of Mu, P22, and phi X174am3 from exonucleolytic degradation by recBC DNase and lambda exonuclease. Single-stranded DNA, however, is not protected by the inhibitor from degradation by either recBC DNase or exonuclease I. The inhibitor preparation contains a protein that binds to linear duplex DNA, but not to circular duplex DNA; ends are required for binding to occur. Single-stranded DNA is not a substrate for the binding protein. These and other results suggest that the binding protein and the inhibitor are the same activity.


Suicidal ideation and associated factors among school going adolescents in Swaziland.
Suicide among children has been a major issue and the statistics are considerably alarming. However, no studies have been conducted in Swaziland on suicidal ideation which is a starting point for committing suicide. The objective of the study was to determine the prevalence of suicidal ideation and its correlates. A secondary analysis of data was conducted using data collected in a Swaziland 2013 Global School-based Student Health Survey (GSHS). The survey assessed among other factors, mental health of the students using a self-administered questionnaire. We considered factors that have been reported to be associated with suicidal ideation in the literature. Unadjusted odds ratios (OR) and adjusted odds ratios (AOR) together with their 95 confidence intervals (CI) are reported. The overall proportions of students who considered suicide were 18.3% of 1866 females and 15.6% of 1672 males. In bivariate models the risk factors for suicidal ideation were feeling lonely, anxiety, using drugs and smoking marijuana. In multivariate model to include age, gender, food security, close friends, truancy, bullied, attacked, physical fight, drugs, marijuana, parental understanding anxiety and loneliness, all the considered factors were significantly associated with suicide except close friends. The rate of suicidal ideation was high among adolescents in Swaziland and intervention considering violence, social support from friends and parents, and drug abuse should be designed to prevent suicidal thoughts.


Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.
Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease.


Substance Use Among Transgender Students in California Public Middle and High Schools.
Transgender adolescents face tremendous social stress in families and schools, which often leads to behavioral health disparities. This study assessed whether rates of substance use were higher among transgender adolescents when compared to nontransgender adolescents. This study is a secondary data analysis of the 2013-2015 California Healthy Kids Survey (CHKS) that examines whether rates of substance use are higher among transgender youth when compared to nontransgender youth. Participants included 4778 transgender and 630,200 nontransgender students in middle and high schools in nearly all school districts in California. The study outcomes were lifetime, recent, and in-school use of cigarettes, tobacco, alcohol, marijuana, cocaine, and ecstasy as well as nonmedical use of prescription painkillers, diet pills, Ritalin or Adderall, and cold medicine. Transgender students were about 2-1/2 times more likely as nontransgender students to use cocaine/methamphetamine in their lifetime (odds ratio [OR] = 2.53; 95% confidence interval [CI] = 2.18-2.95) and about 2.8 times as likely to report past 30-day inhalant use (OR = 2.80; 95% CI = 2.41-3.26). Transgender students were more than twice as likely to report past 30-day prescription pain medication use (OR = 2.19; 95% CI = 1.90-2.53) and more than 3 times as likely to use cigarettes in school (OR = 3.37; 95% CI = 2.84-3.99). The study's findings indicate a need for community- and school-based interventions that reduce substance use among transgender youth.


Investigating the contribution of distance-based features to automatic sleep stage classification.
In this paper, the contribution of distance-based features to automatic sleep stage classification is investigated. The potency of these features is analyzed individually and in combination with 48 conventionally used features. The distance-based set consists of 32 features extracted by calculating Itakura, Itakura-Saito and COSH distances of autoregressive and spectral coefficients of Electrocardiography (EEG) (C3-A2), Left EOG, Chin EMG and ECG signals. All the evaluations are performed on three feature sets: distance-based, conventional and total (combined distance based and conventional). Six ranking methods were used to find the top features with the highest discrimination ability in each set. The ranked feature lists were evaluated using k-Nearest Neighbor (kNN), Artificial Neural Network (ANN), and Decision-tree-based multi-SVM (DSVM) classifiers for five sleep stages including Wake, REM, N1, N2 and N3. Furthermore, the ability of distance-based and conventional features to discriminate between each pair of sleep stages was evaluated using t-test, a hypothesis testing method. Distance-based features occupied 25% of top-ranked features. Simulation results showed that using distance-based features together with conventional features can lead to an enhancement of accuracy. The best classification accuracy (85.5%) was achieved by DSVM classifier and 13 features selected by mRMR-MID and normalized with Min-Max method for total feature set, where two of them were from the distance-based feature set. The t-test results show that distance-based features outperform conventional features in discriminating between N1 and REM stages that is usually a challenge for classification systems. Distance-based features have a positive contribution to sleep stage classification, including enhancement of accuracy and better REM-N1 discrimination ability. The main motivation for this work was to evaluate new features to characterize each sleep stage in such a way that extracted features were more powerful than conventional features, to distinguish sleep stages from each other, and to improve classifiers accuracy.


Low Variability and Stable Frequency of Common Haplotypes of the TP53 Gene Region in Colorectal Cancer Patients in a Slovak Population.
To test the association between common TP53 haplotypes and colorectal cancer (CRC) development. A total of 277 CRC patients and 167 healthy volunteers were included in the study. Common TP53 haplotypes were estimated from eight single-nucleotide polymorphisms (SNPs) (rs1614984, rs77697176, rs12947788, rs1800372, rs2909430, rs1042522, rs17878362 and rs11652704). Stepwise haplotype trend regression showed the haplotype-regressor cccgaRDa as a possible predictive marker. The rare haplotype cccgaRDa was identified in 10 CRC cases and 3 controls. Although it is approximately twice as common in CRC (odds ratio (OR)=2.068; 95% confidence interval (CI)=0.471-9.069), the cccgaRDa haplotype frequency is low in the studied groups. Results of our study suggest that the common TP53 variability is relatively low (only 3 haplotypes occurred above 10%). The haplotype background of TP53 gene is relative stable and despite low haplotype-regressor cccgaRDa frequency it shows to be a possible predictive parameter for CRC development.


Vascular assembly in natural and engineered tissues.
With the advent of molecular embryology and exploitation of genetic models systems, many genes necessary for normal blood vessel formation during early development have been identified. These genes include soluble effectors and their receptors, as well as components of cell-cell junctions and mediators of cell-matrix interactions. In vitro model systems (2-D and 3-D) to study paracrine and autocrine interactions of vascular cells and their progenitors have also been created. These systems are being combined to study the behavior of genetically altered cells to dissect and define the cellular role(s) of specific genes and gene families in directing the migration, proliferation, and differentiation needed for blood vessel assembly. It is clear that a complex spatial and temporal interplay of signals, including both genetic and environmental, modulates the assembly process. The development of real-time imaging and image analysis will enable us to gain further insights into this process. Collaborative efforts among vascular biologists, biomedical engineers, mathematicians, and physicists will allow us to bridge the gap between understanding vessel assembly in vivo and assembling vessels ex vivo.


An optimal global nearest neighbor metric.
A quadratic metric dAO (X, Y) =[(X - Y)T AO(X - Y)]¿ is proposed which minimizes the mean-squared error between the nearest neighbor asymptotic risk and the finite sample risk. Under linearity assumptions, a heuristic argument is given which indicates that this metric produces lower mean-squared error than the Euclidean metric. A nonparametric estimate of Ao is developed. If samples appear to come from a Gaussian mixture, an alternative, parametrically directed distance measure is suggested for nearness decisions within a limited region of space. Examples of some two-class Gaussian mixture distributions are included.


Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas with Unusually Low Mucin Production Mimicking Intraductal Tubulopapillary Neoplasm: A Report of a Case Diagnosed by a Preoperative Endoscopic Biopsy.
We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively.


The longitudinal effectiveness of lateral atlantoaxial intra-articular steroid injection in the treatment of cervicogenic headache.
The most accepted mechanism of cervicogenic headache is referred pain from cervical structures innervated by the upper three cervical spinal nerves. The lateral atlantoaxial joint is not an uncommon cause of cervicogenic headache. In this retrospective study, we examined the effect of lateral atlantoaxial intra-articular steroid injection in managing 32 patients with cervicogenic headache who have a clinical picture suggestive of atlantoaxial joint pain. The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires. A total of 115 patients with cervicogenic headache who were referred to our institute were identified. Of those patients, 32 had a clinical picture suggestive of atlantoaxial joint pain and subsequently underwent a diagnostic/therapeutic intra-articular block. Fifteen of the 32 patients (46.8%) had a postprocedure pain score of 0 (95% CI = 17.5-72.1%). Twenty-six of the 32 patients (81.2%) had a decrease in their postprocedure pain score of 50% or more (95% CI = 62.4-97.6%). The mean preprocedure pain score was 6.8 and postprocedure was 2.2 (Bonferroni-adjusted P < 0.001). At 1 and 3 months, the mean pain scores were 1.9 (P < 0.001) and 3.6 (P < 0.008), respectively. However, at 6 months, the mean pain score was 3.7, and this was not statistically significant (P = 0.208). Lateral atlantoaxial intra-articular corticosteroid injections may provide short-term analgesia for patients with pain originating from the lateral atlantoaxial joint.


Cardiac myocyte guanosine transport and metabolism.
Guanosine transport and metabolism were examined in adult rat cardiac myocytes. Myocytes transported guanosine via saturable [Km = 18 microM, maximum velocity (Vmax) = 3.61 pmol.mg-1.s-1] and nonsaturable (rate constant = 1.47 X 10(-2] processes. The saturable process was inhibited by nitrobenzyl-thioinosine, inosine [inhibition constant (Ki) = 180 microM], and adenosine (Ki = 112 microM). Extracellular guanosine taken up by myocytes was slowly phosphorylated to guanine nucleotides. The majority of guanosine (98%) existed as free intracellular guanosine after 60 s. Countertransport of nucleosides could not be demonstrated in these cells at physiological concentrations in the presence of up to a 10-fold gradient of nucleoside. These studies indicate that adult rat cardiac myocytes can be used to assess myocardial guanosine transport separate from its metabolism. Comparable inhibition of guanosine and adenosine transport by each other and by inosine support the hypothesis that guanosine and adenosine are transported by a common carrier.


[Effect of electroacupuncture of "Neiguan" (PC 6) and "Zusanli" (ST 36) on expression of cerebral cortical slit 2/Robo 1 in the focal cerebral infarction rats ].
To observe the effect of electroacupuncture (EA) intervention on expression of Slit 2 and its transmembrane receptor Robo 1 in the cortex tissue of cerebral infarction rats so as to study its mechanism underlying improvement of cerebral ischemia. Ninety male Sprague Dawley rats were randomly divided into control group (n = 10), model group (n = 40) and EA group (n = 40), and the latter two groups were further randomized into four subgroups: 1 d, 3 d, 7 d, and 14 d (n = 10 in each subgroup) according to the cerebral ischemia duration. Cerebral infarction model was established by occlusion of the middle cerebral artery (MCAO). EA (80-100 Hz, 1-3 mA) was applied to bilateral "Neiguan" (PC 6) and "Zusanli" (ST 36) for 30 min, once daily for 1 d, 3 d, 7 d, and 14 d, respectively. The animals' neurological defect was assessed using Zea-Longa scoring. The expression of Slit 2 and Robo 1 proteins in the cerebral cortex on the ischemic side was assayed using immunohistochemistry and Western blotting, respectively. In comparison with the control group, the neurological score was significantly higher in the model group (P < 0.05), and reduced considerably on day 7 and 14 after MCAO in the EA group compared with the model group (P < 0.05). Immunohistochemical results showed that in comparison with the control group, the immunoactivity levels of cerebral Slit 2 and Robo 1 were remarkably upregulated on day 1, 3 and 7 after MCAO in the model group (P < 0.05, P < 0.01), and backed to the control levels on day 14 (P > 0.05). While compared with the model group, the immunoactivity levels of cerebral Slit 2 and Robo 1 were further obviously upregulated on day 1, 3, 7 and 14 after cerebral ischemia in the EA group (P < 0.05, P < 0.01). The results of Western blotting about the expression levels of cerebral Slit 2 and Robo 1 proteins were nearly the same to those of immunohistochemical outcomes in the 4 subgroups apart from that the expression levels of both Slit 2 and Robo 1 proteins were still obviously higher on day 14 after MCAO in the model group (P < 0.01). EA intervention can significantly improve cerebral ischemia rats' neurological function and obviously upregulate the expression of cerebral Slit 2 and Robo 1 proteins, which may be one of the mechanisms of EA therapy for relieving cerebral infarction in clinic.


Stearoyl-CoA Desaturase-1 Enzyme Inhibition by Grape Skin Extracts Affects Membrane Fluidity in Human Colon Cancer Cell Lines.
The polyphenolic compounds present in grape extracts have chemopreventive and anticancer properties. Here, we studied the ability of two grape skin extracts (GSEs), Autumn Royal and Egnatia, to influence the cell motility and membrane fluidity regulated by the enzyme Stearoyl-CoA desaturase-1 (SCD1) which increases with the cancer aggressiveness. Caco2 and SW480 human colon cancer cell lines were treated with increasing concentrations of GSEs to evaluate cell proliferation and motility. SCD1 levels were evaluated in both treated cell lines, by membrane lipidomic analysis conducted by gas chromatography. The expression levels of SCD1 and other factors involved in the reorganization of the cytoskeleton and focal adhesions were assessed by Real-time PCR, Western Blotting, and Immunofluorescence staining. High-performance liquid chromatography (HPLC) analyses were performed to determine the phenolic composition in the GSEs, finding them more expressed in Autumn Royal than in Egnatia. Both treatments reduced the levels of SCD1, phospho-Rac1/Cdc42/Rac1/Cdc42 ratio, Cofilin, Vimentin, and phospho-Paxillin especially in Caco2 compared to SW480, showing a different behavior of the two cell lines to these natural compounds. Our findings show that GSEs block the cell migration and membrane fluidity through a new mechanism of action involving structural cellular components.


[Fall and fracture risk].
Falls and fall-related fractures are a major problem among older adults. These injuries often cause continuous pain, functional impairments, and mortality. While the majority of falls do not result in fractures, most fractures are due to falls. Especially, almost all hip fractures (95%) result from falls. And so, it is very important to analyze falls and risk factors for falls. A history of falls is the major independent predictor of future fall risk. To date, several strategies have been provided to control risk factors for fall. To prevent falls and fall-induced injuries and fractures, multicomponent exercise, home hazard assessment and modification and use of hip protectors have proven efficient.


Multiomic Approaches to Uncover the Complexities of Dystrophin-Associated Cardiomyopathy.
Despite major progress in treating skeletal muscle disease associated with dystrophinopathies, cardiomyopathy is emerging as a major cause of death in people carrying dystrophin gene mutations that remain without a targeted cure even with new treatment directions and advances in modelling abilities. The reasons for the stunted progress in ameliorating dystrophin-associated cardiomyopathy (DAC) can be explained by the difficulties in detecting pathophysiological mechanisms which can also be efficiently targeted within the heart in the widest patient population. New perspectives are clearly required to effectively address the unanswered questions concerning the identification of authentic and effectual readouts of DAC occurrence and severity. A potential way forward to achieve further therapy breakthroughs lies in combining multiomic analysis with advanced preclinical precision models. This review presents the fundamental discoveries made using relevant models of DAC and how omics approaches have been incorporated to date.


Dietary n-3 polyunsaturated fatty acids enhance hormone ablation therapy in androgen-dependent prostate cancer.
Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content.


[Role of Mitochondria in Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease].
Inflammatory bowel disease (IBD) is widespread in industrial countries with every 20th citizen being affected. Dysregulation of the epithelial barrier function is considered to play a key role in IBD. Permeability of the intestinal epithelium depends mostly on its self-renewal potential and the condition of intercellular junctions. Mitochondria are involved in regulating various intracellular processes in addition to their energy function. Recent data implicate mitochondria in intestinal epithelial barrier regulation and IBD. Mitochondrial dysfunction is possibly one of the factors that underlie the structural abnormalities of tight junctions and the cytoskeleton in intestinal epithelial cells and decrease the self-renewal capacity of the epithelium. The barrier function of the intestinal epithelium is consequently distorted, and IBD develops. The mechanisms of these processes are still unclear and require further research.


Simultaneous multichannel carrier-suppressed return-to-zero to non-return-to-zero format conversion using a fiber Bragg grating.
A novel multichannel carrier-suppressed return-to-zero (CSRZ) to non-return-to-zero (NRZ) format conversion scheme based on a single custom-designed fiber Bragg grating (FBG) with comb spectra is proposed. The spectral response of each channel is designed according to the algebraic difference between the CSRZ and NRZ spectra outlines. The tailored group delays are introduced to minimize the maximum refractive index modulation. Numerical results show that four-channel 200-GHz-spaced CSRZ signals at 40 Gbits/s can be converted into NRZ signals with high Q-factor and wide-range robustness. It is shown that our proposed FBG is robust to deviations of bandwidth and central wavelength detuning. Another important merit of this scheme is that the pattern effects are efficiently reduced owing to the well-designed spectra response.


Higher contact-force values associated with better mid-term outcome of paroxysmal atrial fibrillation ablation using the SmartTouch™ catheter.
Real-time measurement of contact force (CF) during catheter ablation of atrial fibrillation (AF) has been recently suggested to potentially impact procedural outcome. However, the role of CF intensity on mid-term results using the SmartTouch™ catheter has not been investigated so far. Pulmonary vein isolation (PVI) using the SmartTouch™ catheter was performed in 100 eligible patients (age 62 ± 8; 79% men) undergoing a first procedure of paroxysmal AF catheter ablation. Continuous CF monitoring during catheter ablation allowed calculation of mean CF per patient. Patients were dichotomized into high CF (≥22 g, upper quartile) and low CF (<22 g, remaining) and enroled in a standardized follow-up programme (after a 3-month blanking period), free from antiarrhythmic therapy, with regular evaluations including 24 h Holter recordings at 1, 3, 6, 9, 12, 18, and 24 months. Atrial fibrillation relapse was defined as any symptomatic or asymptomatic atrial arrhythmia lasting >30 s. The average CF among all procedures was 19.6 ± 3.7 g. Though complete PVI was eventually achieved in all cases in both groups, success using an exclusively anatomical approach was higher in the high CF group (92.0 vs. 72.0%; P = 0.04). During a mean follow-up of 19 ± 5 months, a lower incidence of AF relapse was observed in higher CF patients (4.0 vs. 20.0%; log rank P = 0.04). Pericardial tamponade occurred in one patient in the higher CF group. No thromboembolism or procedure-associated deaths were observed. Higher values of CF overall during antral PVI appear to be associated with a higher likelihood of sinus rhythm maintenance without significantly increasing the complication rate.


[Acute abdominal symptomatology and minor Salmonella infections].
The author points out how salmonellosis called "minor" during childhood may simulate an "acute abdomen" creating differential diagnostical surgical problems. On a casuisty of 1450 pediatrics cases, he has noted this circumstance ten times (1,45%) and six of these subjects have had to be urgently operated of appendicitis at the moment of their admission to the hospital. Only one of them presented a phlegmonens appendix. Instead, as complication of this sickness, during its lapse, two cases of intestinal occlusion have occurred, in two children, one of which showed numerous ulcers of typhou type of the small intestine. He concludes that frequent coprocoltures in all clinical cases of pediatric abdominal pathology are important.


Special considerations in wound bed preparation 2011: an update©.
This article builds and expands upon the concept of wound bed preparation introduced by Sibbald et al in 2000 as a holistic approach to wound diagnosis and treatment of the cause and patient-centered concerns such as pain management, optimizing the components of local wound care: Debridement, Infection and persistent Inflammation, along with Moisture balance before Edge effect for healable but stalled chronic wounds.


Radicals in ionic liquids.
Stable radicals and recombination of photogenerated lophyl radicals are investigated in ionic liquids. The 2,2,6,6-tetramethylpiperidine-1-yloxyl derivatives contain various substituents at the 4-position to the nitroxyl group, including hydrogen-bond-forming or ionic substituents that undergo additional interactions with the individual ions of the ionic liquids. Some of these spin probes contain similar ions to ionic liquids to avoid counter-ion exchange with the ionic liquid. Depending on the ionic liquid anion, the Stokes-Einstein theory or the Spernol-Gierer-Wirtz theory can be applied to describe the temperature dependence of the average rotational correlation time of the spin probe in the ionic liquids. Furthermore, the spin probes give information about the micropolarity of the ionic liquids. In this context the substituent at the 4-position to the nitroxyl group plays a significant role. Covalent bonding of a spin probe to the imidazolium ion results in bulky spin probes that are strongly immobilized in the ionic liquid. Furthermore, lophyl radical recombination in the dark, which is chosen to understand the dynamics of bimolecular reactions in ionic liquids, shows a slow process at longer timescale and a rise time at a shorter timescale. Although various reactions may contribute to the slower process during lophyl radical recombination, it follows a second-order kinetics that does not clearly show solvent viscosity dependence. However, the rise time, which may be attributed to radical pair formation, increases with increasing solvent viscosity.


Continuous light affects mineralization and delays osteoid incorporation in vertebral bone of Atlantic salmon (Salmo salar L.).
In order to study the effects of photoperiod on fish bone, Atlantic salmon (Salmo salar L.) were exposed to two light regimes (natural and continuous light) from January until June. During the experimental period, several parameters related to the inorganic (minerals) and organic (osteoid) phases were measured. Changes in the organic phase were related to mechanical strength (yield-load) and the expression of the genes sonic hedgehog (shh) and collagen type I alpha 2 (col I). Co-variation between yield-load and the expression of both shh and col I were detected in both groups. It was also shown that fish on the continuous light regime had delayed activation of osteoid incorporation. Mineralization properties were measured with stiffness, mineral incorporation per day and expression of alkaline phosphatase (alp) and matrix Gla protein (mgp). Stiffness, mineral incorporation and gene expression followed the same trend in both light groups in late spring, whereas an increase in the expression of mgp and alp was detected in April, followed by significantly higher stiffness at last sampling in both light groups. These results indicate that constant light affects mineralization and delays osteoid incorporation in Atlantic salmon during the spring. However, in this experiment light treatment did not promote the development of vertebral deformities. Our results also suggest that shh can be used as a marker of osteoblast proliferation and col I a marker of osteoid incorporation, and that both alp and mgp expression could be associated with a rapid increase in mineralization in Atlantic salmon vertebrae.


Development of a questionnaire to assess student behavioral confidence to undertake interprofessional education activities.
Measurement of the impact of interprofessional education (IPE) is the golden chalice educationalists chase. We undertook the development of a scale to measure IPE Academic Behavioral Confidence (IPE-ABC) in allied health, nursing, and social work pre-registration students. This work formed part of the evaluation of a large IPE framework embedded across two Scottish universities. General ABC has been shown to influence student perceptions of study experiences and it is thus reasonable to postulate that ABC could influence student perceptions of IPE. This research developed a questionnaire to ascertain health and social care students' confidence to engage in IPE, utilizing a mixed method approach. Fifteen different professional groups of pre-registration students (n = 565) participated in the assessment of the 38 item questionnaire. Exploratory factor analysis identified three factors: 1/interprofessional teamwork, 2/behaviors underpinning collaboration, and 3/interprofessional communication collectively accounting for 38.2% of the variance. Internal consistency of the overall scale (Cronbach's α = .93) was very good with subscales demonstrating very good internal consistency, 1 (α = .89), or respectable consistency 2 (α = .78) and 3 (α = .79). We conclude the IPE-ABC questionnaire could be utilized to enhance and assess the success of IPE related activities.


Plant fructans in stress environments: emerging concepts and future prospects.
Plants are sessile and sensitive organisms known to possess various regulatory mechanisms for defending themselves under stress environments. Fructans are fructose-based polymers synthesized from sucrose by fructosyltransferases (FTs). They have been increasingly recognized as protective agents against abiotic stresses. Using model membranes, numerous in vitro studies have demonstrated that fructans can stabilize membranes by direct H-bonding to the phosphate and choline groups of membrane lipids, resulting in a reduced water outflow from the dry membranes. Inulin-type fructans are flexible random-coiled structures that can adopt many conformations, allowing them to insert deeply within the membranes. The devitrification temperature (T(g)) can be adjusted by their varying molecular weights. In addition, above T(g) their low crystallization rates ensure prolonged membrane protection. Supporting, in vivo studies with transgenic plants expressing FTs showed fructan accumulation and an associated improvement in freezing and/or chilling tolerance. The water-soluble nature of fructans may allow their rapid adaptation as cryoprotectants in order to give optimal membrane protection. One of the emerging concepts for delivering vacuolar fructans to the extracellular space for protecting the plasma membrane is vesicle-mediated, tonoplast-derived exocytosis. It should, however, be noted that natural stress tolerance is a very complex process that cannot be explained by the action of a single molecule or mechanism.


[Maternal obesity and reproductive risk].
The prevalence of obesity in school children and pregnant women, a known risk factor of the reproductive cycle, has increased significantly over the last few years. To analyze the association between maternal obesity and the outcome of pregnancy and newborn health. To quantify the attributable population risk of obesity in relation to negative events of pregnancy. A prospective study in 883 pregnant women of 6 public health centers in Santiago. Weight, height, arm circumference, skinfold thicknesses, body mass index (BMI) and fat mass were determined in each trimester. Maternal socio demographic history, smoking habits, incidence of diseases during pregnancy, labor and newborn characteristics were analyzed. Logistic regressions of multiple factors were used to determine nutritional and non-nutritional variables associated to negative events, to determine the population attributable risk of each variable that the model retained. Controlling the effect of other variables, a BMI > or = 30 or initial body fat mass > or = 35% determined a greater risk for assisted labor with an odds ratio (OR) of 1.9 (95% confidence interval (CI) 1.3-2.9), gestational diabetes with an OR of 6.4 (95% CI 2.1-19.6), hypertension with an OR of 7.8 (95% CI 3.0-20.4), late fetal mortality with an OR of 3.4 (95% CI 1.2-10.0), p < 0.001. The risk was mostly associated with the initial maternal nutritional status and in a lesser degree, with the weight gained during pregnancy. Maternal obesity is an important risk factor during pregnancy. The prenatal control obesity could reduce approximately 10% of the cesarean sections and late fetal deaths and half of the hypertension and gestational diabetes cases.


[Social representations of patients and relatives regarding Type 1 Neurofibromatosis].
Type 1 Neurofibromatosis (NF1) is a disease with diverse manifestations. Few studies have addressed the psychological aspects associated with it from the perspective of those who have NF1 or their relatives. In this study 46 subjects were interviewed, 28 people with NF1 (Group P) and 18 relatives (Group F) seeking to identify the understanding of the day-to-day reality experienced by these two groups and possible distinctions between them, based on the social representations of each group. Data analysis was conducted using Classic Content Analysis. The respondents' answers were organized into categories and subcategories based on their meanings. The results revealed that the quantitative distribution of the categories had similar frequencies for both groups. However, important qualitative differences were observed in terms of the meanings of the answers. Difficulty in obtaining information about NF1 along with few references about social support networks by people with the disease or their family members contributed to the identification of a veil of social invisibility around NF1. These aspects highlight the need for greater investment in research and intervention related to NF1 in order to expand the social coping conditions for those afflicted with the disease.


Observation on the ice crystal formation process of large yellow croaker (Pseudosciaena crocea) and the effect of multiple cryoprotectants pre-soaking treatments on frozen quality.
By observing the formation behavior of ice crystals, the quality of food products under different freezing conditions can be intuitively judged. In this paper, large yellow croaker was taken as the research object, and a novel cryomicroscopic system was developed to directly observe the structure of ice crystals during the freezing process. The cryoprotective effects of 4% sucrose +4% sorbitol (SU + SO), 4% xylo-oligosaccharide (XO), 4% xylo-oligosaccharide + 0.3% tetrasodium pyrophosphate (XO + TSPP) and 0.2% antifreeze protein (AFP) at different freezing temperatures were investigated. And the evaluation indicators, such as cell deformation degree, equivalent diameters, roundness, elongation and fractal dimension were introduced to quantify the damage of ice crystals to muscle tissues and fibers. The results indicate that reducing the freezing temperature and adding cryoprotectants can improve the quality of large yellow croaker. AFP has the best cryoprotective effect, with a reduction in cell deformation degree of 54.78% and 67.83% compared to the Control group at -5 °C and -20 °C, respectively. SU + SO and XO have the equivalent antifreeze effect, which is slightly inferior to XO + TSPP. In addition, physical parameters of large yellow croaker samples were measured to verify the influence of ice crystal structure on product quality. Therefore, direct observation of the ice crystal formation process and evaluation of ice crystal structure can accurately reflect the quality of frozen products, which is of great significance for the development of refrigeration and preservation technology.


Participants' perceptions of a lifestyle approach to promoting physical activity: targeting deprived communities in Kingston-upon-Hull.
The health benefits of an active lifestyle have been extensively documented and generally accepted. In the UK, declining physical activity levels are a major contributing factor to a number of public health concerns such as obesity and coronary heart disease. Clearly, there is an urgent need to support people in developing sustainable active lifestyles. In 2003, a new lifestyle-based physical activity service called Active Lifestyles (AL) was set up in Kingston-upon-Hull to help local residents to become more active and develop healthier lifestyles. The service targeted the most deprived communities in the city. The aim of the study was to explore participants' perceptions of the operation and effectiveness of the AL service. Five focus groups were conducted in community centres and offices in the health promotion service in Kingston-upon-Hull. Sixteen white adult males (n = 5) and females (n = 11) participated in the study. Ages ranged from 15-73 years (mean age = 53 years). Data were analysed using a content analysis technique based on the 'framework' approach. Three broad themes emerged from the focus groups; the referral process; operational aspects of the AL service; and perceived benefits of the service. Overall, participants were extremely positive about the AL service. Many reported increased activity levels, modified eating habits, and enhanced awareness and education regarding healthier living. Most participants reported that local awareness of the AL service was low and greater promotion was required so more people could benefit. The success of the service was highly dependent upon the qualities and approach of the AL advisor. The service appears to have filled a gap in service provision since it offered support to the most sedentary, older, unfit and overweight individuals, many of whom live in the most deprived parts of Kingston-upon-Hull. Traditional exercise referral schemes that focus solely on facility-based exercise should be broadened to encompass everyday lifestyle activity, where referral to a gym or exercise facility is just one of a number of physical activity options.


Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial.
Heart failure disproportionately affects Black patients. Whether differences among race influence outcomes in advanced heart failure with use of a fully magnetically levitated continuous-flow left ventricular assist device remains uncertain. We included 515 IDE (Investigational Device Exemption) clinical trial patients and 500 Continued Access Protocol patients implanted with the HeartMate 3 left ventricular assist device in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3). Outcomes were compared between Black and White left ventricular assist device recipients for the primary end point of survival free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years, overall survival, adverse events, 6-minute walk distance, and quality of life scores. Of 1015 HeartMate 3 patients, 675 were self-identified as White and 285 as Black individuals. The Black patient cohort was younger, more obese and with a history of hypertension, and more nonischemic cause of heart failure, relative to the White patient group. Black and White patients did not experience a difference in the primary end point (81.1% versus 77.9%; hazard ratio, 1.08 [95% CI, 0.76-1.54], P=0.6568). Black patients were at higher risk of adverse events (calculated as events per 100 patient-years), including bleeding (75.4 versus 63.5; P<0.0001), stroke (9.5 versus 7.2; P=0.0183), and hypertension (10.1 versus 3.2; P<0.0001). The 6-minute walk distance was not different at baseline and 6 months between the groups, however, the absolute change from baseline was greater for White patients (median: +183.0 [interquartile range, 42.0-335.3] versus +163.8 [interquartile range, 42.3-315.0] meters, P=0.01). The absolute quality of life measurement (EuroQoL group, 5-dimension, 5-level instrument visual analog scale) at baseline and 6 months was better in the Black patient group, but relative improvement from baseline to 6 months was greater in White patients (median: +20.0 [interquartile range, 5.0-40.0] versus +25.0 [interquartile range, 10.0-45.0]; P=0.0298). Although the survival free of disabling stroke or reoperation to replace/remove a malfunctioning device at 2 years with the HM 3 left ventricular assist device did not differ by race, Black HeartMate 3 patients experienced a higher morbidity burden and smaller gains in functional capacity and quality of life when compared with White patients. These findings require efforts designed to better understand and overcome these gaps through systematic identification and tackling of putative factors. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02224755 and NCT02892955.


Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties in Bryansk Oblast, Russia: a population-based case-control study.
A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources.


Effects of xylazine on the urethral pressure profile of healthy dogs.
Thirteen healthy male dogs and 11 healthy female dogs were subjected to urodynamic assessment, using a simultaneous urethral pressure profile and urethral sphincter electromyogram (EMG). The study was done on the dogs in the nonsedated state and after xylazine sedation. Results showed a significant decrease in maximal urethral closure pressures in dogs of both sexes after they were given xylazine (from 79.79 cm of H2O to 23.00 cm of H2O in female dogs, and from 99.77 cm of H2O to 41.77 cm of H2O in male dogs). There was a significant reduction in EMG activities in dogs of both sexes after they were given xylazine. There was also little variability in measurements made on the same dog on consecutive days. Simultaneous intravesicular pressure and urethral pressure monitoring indicated that the effect of bladder distention on the urethral pressure profile was minimal and that there were no spontaneous detrusor contractions. This study indicates that xylazine produced a significant artifact in the simultaneous urethral pressure profile/EMG.


Lysozyme encapsulation into nanostructured CaCO3 microparticles using a supercritical CO2 process and comparison with the normal route.
The aim of the present work was to assess the merits of supercritical CO2 (SC-CO2) as a process for protein encapsulation into calcium carbonate microparticles. Lysozyme, chosen as a model protein, was entrapped during CaCO3 precipitation in two different media: water (normal route) and SC-CO2. The particles were characterized and compared in terms of size, zeta potential, morphology by SEM, crystal polymorph and lysozyme encapsulation. Fluorescent and confocal images suggested the encapsulation and core-shell distribution of lysozyme into CaCO3 obtained by the SC-CO2 process. A high encapsulation efficiency was reached by a supercritical CO2 process (50%) as confirmed by the increased zeta potential value, lysozyme quantification by HPLC and a specific bioassay (M. lysodeikticus). Conversely, lysozyme was scarcely entrapped by the normal route (2%). Thus, supercritical CO2 appears to be an effective process for protein encapsulation within nanostructured CaCO3 particles. Moreover, this process may be used for encapsulation of a wide range of macromolecules and bioactive substances.


Genetics and community health nursing.
Genetic discoveries affect the practice of community health nurses. These nurses identify groups at risk for genetic diseases and participate in newborn screening, carrier detection testing, and presymptomatic genetic testing programs. Community health nurses also provide direct nursing care to individuals with genetic disorders. Protecting clients from harmful use of genetic information, planning and implementing genetic screening programs, and identifying genetic resources are essential components of the community health nurse's role.


[Determination of glycyrrhizic acid binding sites by a phage display method].
Phages that expose peptides specifically interacting with glycyrrhizic acid (GA) were selected from a phage peptide library by affinity selection and ELISA. Amino acid sequence analysis of the selected peptides and human proteins with the SIM program revealed homology to tyrosine protein kinases, serine/threonine protein kinases, tyrosine phosphatases, and some receptors. Analysis of the peptide and virus protein sequences with the BLAST program showed that GA has affinity for various surface proteins of several human viruses such as HIV-1, hepatitis C virus, and herpesviruses.


Operation characteristics of soil blasting vibration test device under vibration load.
To improve the accuracy of vibration velocity monitoring during blasting in soil layers, this paper provides a method and device for data correction by combining finite element software and actual engineering test data. Based on the length of the test pedestal exposed to the surface of the geotechnical body, the finite element structural model corresponding to each length of the test pedestal is established. Moreover, a predetermined external excitation load is applied outside the finite element model and the correction function of the vibration data is obtained by analysis of the stress and vibration data. The device solves the problem of low accuracy of vibration velocity measurement in soil and establishes a correction method for measurement data. The results show the following: (1) With the propagation of blasting seismic waves, the maximum stress values of the test device appear in the footwall position, the middle of the extension rod, and the bottom position in that order. (2) At the end of the test, there is an obvious phenomenon of speed amplification at the top of the test device. (3) As the length of the test device exposed to the ground increases, the particle peak vibration velocity (PPV) of the test device varies exponentially with the PPV of the ground and the range of variation of the vibration velocity in the X-direction is the largest.


Fez function is required to maintain the size of the animal plate in the sea urchin embryo.
Partitioning ectoderm precisely into neurogenic and non-neurogenic regions is an essential step for neurogenesis of almost all bilaterian embryos. Although it is widely accepted that antagonism between BMP and its inhibitors primarily sets up the border between these two types of ectoderm, it is unclear how such extracellular, diffusible molecules create a sharp and precise border at the single-cell level. Here, we show that Fez, a zinc finger protein, functions as an intracellular factor attenuating BMP signaling specifically within the neurogenic region at the anterior end of sea urchin embryos, termed the animal plate. When Fez function is blocked, the size of this neurogenic ectoderm becomes smaller than normal. However, this reduction is rescued in Fez morphants simply by blocking BMP2/4 translation, indicating that Fez maintains the size of the animal plate by attenuating BMP2/4 function. Consistent with this, the gradient of BMP activity along the aboral side of the animal plate, as measured by pSmad1/5/8 levels, drops significantly in cells expressing Fez and this steep decline requires Fez function. Our data reveal that this neurogenic ectoderm produces an intrinsic system that attenuates BMP signaling to ensure the establishment of a stable, well-defined neural territory, the animal plate.


Plant pharming of a full-sized, tumour-targeting antibody using different expression strategies.
The aims of this work were to obtain a human antibody against the tumour-associated antigen tenascin-C (TNC) and to compare the yield and quality of plant-produced antibody in either stable transgenics or using a transient expression system. To this end, the characterization of a full-sized human immunoglobulin G (IgG) [monoclonal antibody H10 (mAb H10)], derived from a selected single-chain variable fragment (scFv) and produced in plants, is presented. The human mAb gene was engineered for plant expression, and Nicotiana tabacum transgenic lines expressing both heavy (HC) and light (LC) chain were obtained and evaluated for antibody expression levels, in vivo assembly and functionality. Affinity-purified H10 from transgenics (yield, 0.6-1.1 mg/kg fresh weight) revealed that more than 90% of HC was specifically degraded, leading to the formation of functional antigen-binding fragments (Fab). Consequently, H10 was transiently expressed in Nicotiana benthamiana plants through an Agrobacterium-mediated gene-transfer system. Moreover, the use of the p19 silencing suppressor gene from artichoke mottled crinkle virus raised antibody expression levels by an order of magnitude (yields of purified H10, 50-100 mg/kg fresh weight). Approximately 75% of purified protein consisted of full-sized antibody functionally binding to TNC (K(D) = 14 nm), and immunohistochemical analysis on tumour tissues revealed specific accumulation around tumour blood vessels. The data indicate that the purification yields of mAb H10, using a transient expression system boosted by the p19 silencing suppressor, are exceptionally high when compared with the results reported previously, providing a technique for the over-expression of anticancer mAbs by a rapid, cost-effective, molecular farming approach.


Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study.
Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown. In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA. There were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p = 0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high grade IDC was similar, and although EGFR alterations were exclusively found in high grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS. In conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high grade DCIS showed more copy number changes than low/intermediate grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high grade DCIS specific genes may be potential targets for treatment and/or predict progression.


Cohort differences in Big Five personality factors over a period of 25 years.
The notion of personality traits implies a certain degree of stability in the life span of an individual. But what about generational effects? Are there generational changes in the distribution or structure of personality traits? This article examines cohort changes on the Big Five personality factors Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience, among first-year psychology students in The Netherlands, ages 18 to 25 years, between 1982 and 2007. Because measurement invariance of a personality test is essential for a sound interpretation of cohort differences in personality, we first assessed measurement invariance with respect to cohort for males and females separately on the Big Five personality factors, as measured by the Dutch instrument Five Personality Factors Test. Results identified 11 (females) and 2 (males) biased items with respect to cohort, out of a total of 70 items. Analyzing the unbiased items, results indicated small linear increases over time in Extraversion, Agreeableness, and Conscientiousness and small linear decreases over time in Neuroticism. No clear patterns were found on the Openness to Experience factor. Secondary analyses on students from 1971 to 2007 of females and males of different ages together revealed linear trends comparable to those in the main analyses among young adults between 1982 onward. The results imply that the broad sociocultural context may affect personality factors.


The Mediating Role of Illness Cognitions in the Relationship Between Caregiving Demands and Caregivers' Psychological Adjustment.
The present study investigated whether illness cognitions mediated the relationship between caregiving demands and positive and negative indicators of adjustment in partners of patients with chronic pain. The sample of this cross-sectional study consisted of 151 partners (mean age=61.4 y, SD=13.6 y, 57% male) of patients with chronic pain (eg, back pain). The study was conducted in the Pain Centre of the University Medical Centre Groningen, The Netherlands, during November 2014 to June 2015. Participants completed questionnaires that assessed caregiving demands, illness cognitions, perceived burden, distress, positive affect, and life satisfaction. The results showed that among illness cognitions, acceptance of the illness mediated the association between caregiving demands and burden (b=0.16, 95% confidence interval [CI]: 0.05-0.28) and positive affect (b=-0.21, CI: -0.41 to -0.06). Helplessness mediated the association between caregiving demands and burden (b=0.46, CI: 0.26-0.69) and distress (b=0.35, CI: 0.19-0.53). Perceived benefits did not mediate any of these associations. The findings indicate that partners who experience more demands tend to appraise the consequences of the patients' pain condition more negatively, which in turn is associated with their emotional adjustment. The results suggest that illness cognitions play an important role in the psychological adjustment of partners. Enhancing acceptance of the illness and reducing feelings of helplessness could form the basis of interventions aiming at promoting psychological adjustment in partners, especially when it is difficult to reduce the demands.


Destabilizing missense mutations in the tumour suppressor protein p53 enhance its ubiquitination in vitro and in vivo.
p53 ubiquitination catalysed by MDM2 (murine double minute clone 2 oncoprotein) provides a biochemical assay to dissect stages in E3-ubiquitin-ligase-catalysed ubiquitination of a conformationally flexible protein. A mutant form of p53 (p53(F270A)) containing a mutation in the second MDM2-docking site in the DNA-binding domain of p53 (F270A) is susceptible to modification of long-lived and high-molecular-mass covalent adducts in vivo. Mutant F270A is hyperubiquitinated in cells as defined by immunoprecipitation and immunoblotting with an anti-ubiquitin antibody. Transfection of His-tagged ubiquitin along with p53(R175H) or p53(F270A) also results in selective hyperubiquitination in cells under conditions where wild-type p53 is refractory to covalent modification. The extent of mutant p53(R175H) or p53(F270A) unfolding in cells as defined by exposure of the DO-12 epitope correlates with the extent of hyperubiquitination, suggesting a link between substrate conformation and E3 ligase function. The p53(F270A:6KR) chimaeric mutant (where 6KR refers to the simultaneous mutation of lysine residues at positions 370, 372, 373, 381, 382 and 386 to arginine) maintains the high-molecular-mass covalent adducts and is modified in an MDM2-dependent manner. Using an in vitro ubiquitination system, mutant p53(F270A) and the p53(F270A:6KR) chimaeric mutant is also subject to hyperubiquitination outwith the C-terminal domain, indicating direct recognition of the mutant p53 conformation by (a) factor(s) in the cell-free ubiquitination system. These data identify an in vitro and in vivo assay with which to dissect how oligomeric protein conformational alterations are linked to substrate ubiquitination in cells. This has implications for understanding the recognition of misfolded proteins during aging and in human diseases such as cancer.


Design Patterns for Situated Visualization in Augmented Reality.
Situated visualization has become an increasingly popular research area in the visualization community, fueled by advancements in augmented reality (AR) technology and immersive analytics. Visualizing data in spatial proximity to their physical referents affords new design opportunities and considerations not present in traditional visualization, which researchers are now beginning to explore. However, the AR research community has an extensive history of designing graphics that are displayed in highly physical contexts. In this work, we leverage the richness of AR research and apply it to situated visualization. We derive design patterns which summarize common approaches of visualizing data in situ. The design patterns are based on a survey of 293 papers published in the AR and visualization communities, as well as our own expertise. We discuss design dimensions that help to describe both our patterns and previous work in the literature. This discussion is accompanied by several guidelines which explain how to apply the patterns given the constraints imposed by the real world. We conclude by discussing future research directions that will help establish a complete understanding of the design of situated visualization, including the role of interactivity, tasks, and workflows.


A study of dental anxiety in a Belfast population.
This study was undertaken to assess the levels and behavioural consequences of dental anxiety in a Belfast population. Fear is associated with poor attendance, leading to neglect and so Northern Ireland, with the highest caries rate in the United Kingdom, seemed a good place to examine dental anxiety and its relation to dental health status. A questionnaire was used to examine the prevalence and accompanying effects of dental anxiety. The results were statistically analysed.


Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases.
Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.


Fibrin films: overlooked hemostatic barriers against microbial infiltration.
The hemostatic response to vascular injury culminates in a fibrin clot network that forms an initial barrier to blood loss and also contributes to microbial host defense. Fibrinogen is cleaved by thrombin into fibrin monomers that spontaneously polymerize into protofibrils and form the extensive fiber networks characteristic of blood clots. In this issue of the JCI, Macrae and colleagues characterize an alternative fibrin structure in which fibrinogen and fibrin assemble into a continuous 2D film at the exterior face of the fibrin clot network. Fibrin films connect to the underlying fiber network through tethering fibers and provide a protective barrier to microbial infiltration. These findings shed new light on a previously overlooked mechanism of fibrin assembly at the clot surface and provide a link between hemostasis and innate immunity.


Socioeconomic drivers of mercury emissions in China from 1992 to 2007.
Mercury emissions in China have increased by 164% during 1992-2007. While major mercury producers were among energy combustion and nonferrous metal sectors, little is known for the socioeconomic factors driving the growth of emissions. In this paper we examine the underlying drivers and their contributions to the change of mercury emissions. Results show that changes in per capita GDP and GDP composition led to increased emissions which offset the reduction of emissions made possible by technology-induced decrease of mercury emissions intensity and changes in final demand mix. In particular, changes in final demand mix caused decreasing mercury emissions from 1992 to 2002 and increasing emissions from 2002 to 2007. Formation of fixed capital was the dominant driver behind the increase of mercury emissions, followed by the increasing urban population and net exports. This systems-based examination of socioeconomic drivers for China's mercury emission increase is critical for emission control by guiding policy-making and targets of technology development.


Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning.
LRRK2 (PARK8) is the most common genetic determinant of Parkinson's disease (PD), with dominant mutations in LRRK2 causing inherited PD and sequence variation at the LRRK2 locus associated with increased risk for sporadic PD. Although LRRK2 has been implicated in diverse cellular processes encompassing almost all cellular compartments, the precise functions of LRRK2 remain unclear. Here, we show that the Drosophila homolog of LRRK2 (Lrrk) localizes to the membranes of late endosomes and lysosomes, physically interacts with the crucial mediator of late endosomal transport Rab7 and negatively regulates rab7-dependent perinuclear localization of lysosomes. We also show that a mutant form of lrrk analogous to the pathogenic LRRK2(G2019S) allele behaves oppositely to wild-type lrrk in that it promotes rather than inhibits rab7-dependent perinuclear lysosome clustering, with these effects of mutant lrrk on lysosome position requiring both microtubules and dynein. These data suggest that LRRK2 normally functions in Rab7-dependent lysosomal positioning, and that this function is disrupted by the most common PD-causing LRRK2 mutation, linking endolysosomal dysfunction to the pathogenesis of LRRK2-mediated PD.


Early Postoperative Complications for Elderly Patients Undergoing Single-Level Decompression for Lumbar Disc Herniation, Ligamentous Hypertrophy, or Neuroforaminal Stenosis.
Lumbar decompression for disc herniation is frequently performed on elderly patients, and this trend will continue as the population ages. Clinical reports on the complications of lumbar discectomy show good results and cost effectiveness in young or middle-aged patients. To assess and compare the morbidity of single-level lumbar disc surgery for radicular pain in a cohort of patients greater than 80 yr of age to that of a middle-aged cohort. A total of 9451 patients who received a single-level lumbar decompression procedure for disc displacement without myelopathy were retrospectively selected from a multicenter validated surgical database from the American College of Surgeons National Surgical Quality Improvement Program. A cohort with 485 patients greater than 80 yr of age (80+) was compared with a middle-aged cohort with 8966 patients between 45 and 65 yr. Preoperative comorbidity and postoperative outcome variables observed included mortality, myocardial infarction, return to the operating room, sepsis, deep vein thrombosis, transfusions, cardiac arrest necessitating cardiopulmonary resuscitation, coma greater than 24 h, urinary tract infection, acute renal failure, use of ventilator greater than 24 h, pulmonary embolism, pneumonia, wound dehiscence, and postoperative infection. The preoperative comorbidities and characteristics were significantly different between the middle-aged and the 80+ cohorts, with the older cohort having many more preoperative comorbidities. There was statistically significantly greater postoperative morbidity among the 80+ cohort regarding pulmonary embolism (0.8% vs 0.2%, P = .037), intra/postoperative transfusion requirement (1.9% vs 0.7%, P = .01), urinary tract infection (1.2% vs 0.3%, P = .011), and 30-d mortality (0.4% vs 0.1%, P = .046). In this large sample of patients who received a single-level lumbar decompression procedure for disc displacement without myelopathy, elderly patients, particularly with American Society of Anesthesiologists class 3 and 4, had a statistically significant increase in morbidity and mortality, but the overall risk of complications remains low.


Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals.
We have previously shown that exposure to combustion-derived metals rapidly (within 20 min) activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), in the human bronchial epithelial cell line BEAS. To study the mechanisms responsible for metal-induced activation of ERK, we examined the effect of noncytotoxic exposures to As, Cu, V, or Zn on the kinases upstream of ERK in the epidermal growth factor (EGF) receptor signaling pathway. Western blotting using phospho-specific ERK1/2 antibody demonstrated the selective MEK1/2 inhibitor PD-98059 blocked metal-induced phosphorylation of ERK1/2. Meanwhile, Western blotting using a phospho-specific MEK1/2 antibody showed that these metals induce a rapid phosphorylation of MEK1/2. Kinase activity assays confirmed the activation of MEK1/2 by metal treatment. Immunoprecipitation studies demonstrated that As, Cu, V, or Zn induces EGF receptor phosphorylation. Furthermore, the EGF receptor-specific tyrosine kinase inhibitor (PD-153035) significantly blocked the phosphorylation of MEK1/2 initiated by metals. Interestingly, we observed low levels of Raf-1 activity that were not increased by metal exposure in these cells through kinase activity assay. Finally, transfection assays showed that MEK1/2 inhibition could inhibit trans-activation of Elk1, a transcription factor in the ERK pathway, in BEAS cells exposed to metals. Together, these data demonstrate that As, Cu, V, and Zn can activate the EGF receptor signaling pathway in BEAS cells and suggest that this mechanism may be involved in pulmonary responses to metal inhalation.


Multi-system progressive angiomatosis in a dog resembling blue rubber bleb nevus syndrome in humans.
A six-year-old, neutered, female golden retriever was presented with generalised, dark purple to black cutaneous nodules and gastrointestinal haemorrhage. Histopathologically, all cutaneous nodules were diagnosed as benign cavernous haemangiomas. Endoscopic analysis revealed similar nodules in the oesophagus, stomach and duodenum. At laparotomy, similar nodules were seen on the visceral peritoneal lining of abdominal organs. Metastatic haemangiosarcoma was ruled out based on histological features and lack of primary tumour in spleen, liver or heart ultrasonographically. Blood loss associated with gastrointestinal haemorrhage was managed with blood transfusion. To the authors' knowledge, this is the first canine case of multi-system progressive angiomatosis resembling blue rubber bleb nevus syndrome in humans.


Distribution of corticotropin-releasing factor neurons in the mouse brain: a study using corticotropin-releasing factor-modified yellow fluorescent protein knock-in mouse.
We examined the morphological features of corticotropin-releasing factor (CRF) neurons in a mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter. We previously generated the CRF-Venus knock-in mouse, in which Venus is inserted into the CRF gene locus by homologous recombination. In the present study, the neomycin phosphotransferase gene (Neo), driven by the pgk-1 promoter, was deleted from the CRF-Venus mouse genome, and a CRF-Venus∆Neo mouse was generated. Venus expression is much more prominent in the CRF-Venus∆Neo mouse when compared to the CRF-Venus mouse. In addition, most Venus-expressing neurons co-express CRF mRNA. Venus-expressing neurons constitute a discrete population of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) that project to the median eminence. Venus-expressing neurons were also found in brain regions outside the neuroendocrine PVH, including the olfactory bulb, the piriform cortex (Pir), the extended amygdala, the hippocampus, the neocortices, Barrington's nucleus, the midbrain/pontine dorsal tegmentum, the periaqueductal gray, and the inferior olivary nucleus (IO). Venus-expressing perikarya co-expressing CRF mRNA could be observed clearly even in regions where CRF-immunoreactive perikarya could hardly be identified. We demonstrated that the CRF neurons contain glutamate in the Pir and IO, while they contain gamma-aminobutyric acid in the neocortex, the bed nucleus of the stria terminalis, the hippocampus, and the amygdala. A population of CRF neurons was demonstrated to be cholinergic in the midbrain tegmentum. The CRF-Venus∆Neo mouse may be useful for studying the structural and functional properties of CRF neurons in the mouse brain.


Cartilage defect of lunate facet of distal radius after fracture treated with osteochondral autograft from knee.
We describe using an osteochondral autograft from the lateral femoral condyle of the knee to treat a symptomatic die-punch lesion of the lunate facet of the distal radius. An 18-year-old woman who sustained a distal radius fracture remained symptomatic after nonoperative treatment and diagnostic wrist arthroscopy with microfracture. We used a commercial harvesting system to transfer an osteochondral plug into a cartilage defect involving the lunate facet of the distal radius. At final follow-up, 34 months after surgery, the patient was assessed with a visual analog scale (VAS) and Disabilities of the Arm, Shoulder, and Hand (DASH) scores and with a comprehensive physical examination. Magnetic resonance arthrogram was used to assess articular cartilage status. VAS pain score improved from 7 before surgery to 0.5 after surgery. Postoperative DASH score was 0. The patient was asymptomatic and had satisfactory wrist motion without mechanical symptoms. Magnetic resonance arthrogram showed the transferred osteochondral autograft incorporated in excellent position.


Association of chronic lung disease with treatments and outcomes patients with acute myocardial infarction.
Although chronic lung disease (CLD) is common among patients with myocardial infarction (MI), little is known about the influence of CLD on patient management and outcomes following MI. Using the National Cardiovascular Data Registry's ACTION Registry-GWTG, demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after acute MI were compared between patients with (n = 22,624) and without (n = 136,266) CLD. Multivariable adjustment was performed to determine the independent association of CLD with treatments and adverse events. CLD (17.0% of non-ST-elevation MI [NSTEMI] and 10.1% of ST-elevation MI [STEMI] patients) was associated with older age, female sex, and a greater burden of comorbidities. Among NSTEMI patients, those with CLD were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft compared to those without; in contrast, no differences were seen in invasive therapies for STEMI patients with or without CLD. Multivariable-adjusted risk of major bleeding was significantly increased in CLD patients with NSTEMI (13.0% vs 8.1%, OR(adj) = 1.27, 95% CI = 1.20-1.34, P < .001) and STEMI (16.0% vs 10.5%, OR(adj) = 1.19, 95% CI = 1.10-1.29, P < .001). In NSTEMI, CLD was associated with a higher risk of inhospital mortality (OR(adj) = 1.21, 95% CI = 1.11-1.33); in STEMI no association between CLD and mortality was seen (OR(adj) = 1.05, 95% CI = 0.95-1.17). CLD is common among patients with MI and is independently associated with an increased risk for major bleeding. In NSTEMI, CLD is also associated with receiving less revascularization and with increased in-hospital mortality. Special attention should be given to this high-risk subgroup for the prevention and management of complications after MI.


Pool-based exercise for amelioration of pain in adults with fibromyalgia syndrome: A systematic review and meta-analysis.
To evaluate the effects of pool-based exercises on pain symptomatology among adults with fibromyalgia syndrome. A systematic review and meta-analysis were carried out using PRISMA guidelines. Database search was conducted by two independent reviewers. For meta-analysis, the visual analogue scale (VAS) score for pain was used as the primary outcome and the Fibromyalgia Impact Questionnaire (FIQ) score was utilized as the secondary outcome. A total of 42 out of 292 potentially eligible studies were selected for being read in full by reviewers, 14 of which were included in meta-analysis, being 10 of them used in sensitivity analysis of either the primary or secondary outcome. Data pooled from 10 randomized controlled trials (n = 508) revealed that patients who underwent pool-based exercises exhibited a significantly lower mean in VAS score as compared to controls (SMD = -0.27, 95% CI: -0.45 to -0.09). Regarding FIQ scores, data from 10 randomized controlled trials were pooled (n = 578) and a lower mean score was also shown in the group that underwent a pool-based exercise program (SMD = -0.29, 95% CI: -0.49 to -0.09). Limitations of this study include the small sample size and moderate dropout rates in currently available clinical trials. Pool-based exercise may provide some additional benefit for pain relief in adults with fibromyalgia as compared to either land-based or no physical exercise. Collectively, these findings suggest that pool-based exercise deserves further attention as a potential adjuvant therapeutic option for adults with fibromyalgia. PROSPERO registration number: CRD42019136755.


Conjoint and extended neural networks for the computation of speech codes: the neural basis of selective impairment in reading words and pseudowords.
The computation of speech codes (i.e. phonology) is an important aspect of word reading. Understanding the neural systems and mech- anisms underlying phonological processes provides a foundation for the investigation of language in the brain. We used high-resolution three-dimensional positron emission tomography (PET) to investigate neural systems essential for phonological processes. The burden of neural activities on the computation of speech codes was maximized by three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter cases). Brain activation patterns associated with these tasks were compared with those of two baseline tasks involving visual feature detection. Results suggest strong left lateralized epicenters of neural activity in rhyming irrespective of gender. Word rhyming activated the same brain regions engaged in pseudoword rhyming, suggesting conjoint neural networks for phonological processing of words and pseudowords. However, pseudoword rhyming induced the largest change in cerebral blood flow and activated more voxels in the left posterior prefrontal regions and the left inferior occipital-temporal junction. In addition, pseudoword rhyming activated the left supramarginal gyrus, which was not apparent in word rhyming. These results suggest that rhyming pseudowords requires active participation of extended neural systems and networks not observed for rhyming words. The implications of the results on theories and models of visual word reading and on selective reading dysfunctions after brain lesions are discussed.