Biosynthesis of rat preprosomatostatin.
The biologically active forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28) arise by post-translational cleavage of prosomatostatin. Prosomatostatin in turn is derived from a larger precursor, preprosomatostatin. We have previously reported the structure of a complementary DNA molecule encoding rat preprosomatostatin. The nucleotide sequence of this cDNA indicated that SS-14 and SS-28 are located at the carboxy-terminus of a 116 amino acid precursor. At the amino-terminus of the precursor is a hydrophobic region characteristic of a leader or pre-sequence. Sequential Edman degradations of cell-free translation products synthesized in the presence of microsomal membranes indicate that preprosomatostatin is cleaved within the endoplasmic reticulum to form prosomatostatin, a precursor of 92 amino acids. To begin to elucidate the factors which regulate the expression of the rat somatostatin gene, we have determined the sequence of the gene isolated from recombinant bacteriophage libraries. The gene spans 1.2 kilobases in length and is interrupted within the coding sequence of prosomatostatin by a single intron of 630 bases. A variant of the Goldberg-Hogness promotor, TTTAAA, is located 31 bases upstream from the transcriptional start point. A repetitive sequence was identified in the 5' region of the gene within 650 bases of the promoter. The nucleotide sequence of this region reveals an alternating GT sequence 42 bases in length characteristic of DNA with Z-forming potential. Such sequences are thought to influence the expression of other eukaryotic genes.


Revascularization in left ventricular dysfunction: an update.
The purpose of this article is to provide an overview of revascularization in patients with coronary artery disease (CAD) and left ventricular dysfunction (LVD). Patients with significant CAD and LVD are a high-risk patient population. They make up a minority of the cases from the largest, prospective coronary revascularization trials. The Surgical Treatment for Ischemic Heart Failure (STICH) Trial and its substudies are the most important and well cited in this field. The 10-year data from STICH showed that surgical revascularization was associated with lower all-cause mortality compared with medical therapy. Several smaller studies have confirmed that surgical revascularization carries a significant risk of short-term mortality but overall improved long-term outcomes in patients with LVD. Data from multiple observational studies further confirm that coronary artery bypass graft (CABG) is superior to percutaneous coronary revascularization for long-term survival and freedom from repeat revascularization in patients with LVD. We suggest that patients with LVD undergoing CABG should be considered for multiarterial grafting and that some patients may benefit from an off-pump procedure. Surgical revascularization confers a long-term survival benefit in patients with significant CAD and LVD. Further studies will be needed to precisely determine the ideal candidate for surgical versus percutaneous revascularization.


Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: studies using medium to high doses in animal models.
Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for A1 and A2A receptors, which are colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses. Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses. Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas. Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses.


Analysis of mercury in hair of EPA region V population.
A scoping study, the National Human Exposure Assessment Survey (NHEXAS) was conducted in EPA Region V from July 1995 to May 1997. This probability-based population study provided an opportunity to examine the mercury levels in 182 participants who provided hair samples. A sensitive analytical procedure based on atomic fluorescence spectrometry was developed and evaluated for the analysis of Hg in approximately 5 mg of human hair. The correlation coefficient (r), the precision, and bias were 0.9983, < or = 1.6%, and < or = 8%, respectively, for standard curves in the hair matrix. The method detection limit (MDL), recovery of Hg in a certified sample (NIES-13), precision (% RSD) for duplicate extract analysis, and precision for duplicate sample analysis averaged 12 ppb (range 4 to 22 ppb), 100 +/- 3% (N=27), 4.6 +/- 2.8 (N=18), and 12.5 +/- 7.4 (N=17), respectively, over the 7 to 8 months of sample analysis. The low MDL yielded 95% of the samples with measurable values, permitting the entire distribution of Hg levels to be characterized. Comparison of annualized Hg distribution in hair with and without background correction revealed a negligible bias on the distribution (1.47% at the 90th percentile). Also, a comparison of the unweighted and nonannualized weighted Hg levels throughout the percentile distribution indicated a small deviation in the upper tail (95th percentile) and is attributable to the small sample size (N=182). The mean, median, and maximum of the annualized Hg levels in hair were 287, 204, and 3505 ppb, respectively. The 75th percentiles were 335 and 368 ppb for the weighted annualized and unweighted distributions, respectively. The percent of individuals in three age categories (0-24, 25-49, and 50 years and older) who exceeded the 75th percentile showed a linear increase with age. Males (N=81) had 10% and 20% lower mean levels than females (N=101) for unweighted and annualized weighted Hg data, respectively. The application of this methodology for characterizing hair Hg levels in fish-eating populations is discussed.


Ornithine alpha-ketoglutarate and creatine effects on growth and plasma metabolites of nursery pigs.
Four experiments were conducted to determine the effect of dietary ornithine alpha-ketoglutarate (OKG) and creatine monohydrate on growth performance and plasma metabolites of nursery pigs. In each experiment, treatments were replicated with four to five pens of four to six pigs each. Each experiment lasted from 3 to 4 wk and Phase I (1.6% Lys) and Phase II (1.3 to 1.5% Lys) diets were fed for 9 to 16 d each. In Exp. 1, pigs (4.7 kg and 15 d of age) were fed diets containing 0, .10, or .75% OKG. Daily gain during a 13-d Phase I period and ADFI during Phase I and overall (29 d) were increased (P < .10) in pigs fed .75% OKG. Gain:feed ratio was not affected (P > .10) by diet. In Exp. 2, pigs (7.1 kg and 23 d of age) were fed 0 or .50% OKG during Phase I only. During Phase I, II, and overall, ADG and ADFI were not affected (P > .10) by OKG supplementation, but gain:feed was decreased during Phase I (P < .04), Phase II (P < .08), and overall (P < .04). Plasma urea N (PUN), glucose, and NEFA concentrations were not affected (P > .10) by OKG supplementation in this experiment. In Exp. 3, pigs (5.8 kg and 20 d of age) were fed diets containing 0, .10, or .50% creatine. Creatine tended to linearly decrease ADG (P = .11) and plasma albumin (P = .12) and PUN (P < .10) concentrations in Phase II (d 12 to 26). In Exp. 4, 850 mg of OKG or 750 mg of creatine was provided daily by oral capsule to pigs 4 d before weaning to 2 d after weaning. Pigs within a litter received either no capsule or capsules containing OKG or creatine. After weaning, pigs that received no capsule before weaning received no treatment, .50% creatine, or .50% OKG in the nursery diet. Pigs that received OKG before weaning received no treatment or .50% OKG, and pigs that received creatine before weaning received no treatment or .50% creatine in the nursery diet. Pigs weighed 3.9 kg 4 d before weaning and 4.9 kg at weaning at an average age of 20 d. The OKG provided by capsule decreased ADG (P < .02) and ADFI (P < .09) during Phase II. The OKG did not affect (P > .10) plasma NEFA, glucose, or urea N concentrations. Creatine added to the nursery diet increased (P < .02) ADFI and decreased (P < .10) gain:feed during Phase II and overall. Creatine in the nursery diet also increased (P < .01) PUN, but it did not affect plasma glucose or NEFA concentrations. Creatine and OKG have variable effects on growth performance and plasma metabolites of nursery pigs.


Hypospadias and halogenated organic pollutant levels in maternal mid-pregnancy serum samples.
Environmental contaminants that disrupt endocrine function may contribute to hypospadias etiology. To compare levels of selected halogenated organic pollutants in women delivering infants with and without hypospadias. This study examined levels of nine polybrominated flame retardants (PBDEs), 30 polychlorinated biphenyls (PCBs) and nine persistent pesticides in mid-pregnancy serum samples from 20 women who delivered infants with hypospadias and 28 women who delivered unaffected infants, in California. Analytes were measured using isotope dilution high-resolution mass spectrometry. Values below individual limits of detection (LOD) for each analyte were imputed based on a truncated multivariate normal distribution. Levels of 17 analytes for which at least 50% of cases and controls had values above the LOD were compared using t-tests and by generating odds ratios from logistic regression analyses. Means were greater for cases than controls for 11 of the 17 reported analytes (4 of 5 PBDEs, 7 of 9 PCBs, and 0 of 3 other persistent pesticides), but none of the differences were statistically significant. Eleven of the 17 odds ratios exceeded one (the same analytes that had greater means), but none of the confidence intervals excluded one. After adjustment for sample processing time and foreign-born Hispanic race-ethnicity, only four of the odds ratios exceeded one. Levels of the PBDEs and PCBs were not statistically significantly different, but the sample size was small. The current study adds to a relatively limited knowledge base regarding the potential association of specific contaminants with hypospadias or other birth defects.


Expression microarray identifies the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells.
While glucocorticoids and the liganded glucocorticoid receptor (GR) have a well-established role in the maintenance of differentiation and suppression of apoptosis in breast tissue, the involvement of unliganded GR in cellular processes is less clear. Our previous studies implicated unliganded GR as a positive regulator of the BRCA1 tumour suppressor gene in the absence of glucocorticoid hormone, which suggested it could play a similar role in the regulation of other genes. An shRNA vector directed against GR was used to create mouse mammary cell lines with depleted endogenous levels of this receptor in order to further characterize the role of GR in breast cells. An expression microarray screen for targets of unliganded GR was performed using our GR-depleted cell lines maintained in the absence of glucocorticoids. Candidate genes positively regulated by unliganded GR were identified, classified by Gene Ontology and Ingenuity Pathway Analysis, and validated using quantitative real-time reverse transcriptase PCR. Chromatin immunoprecipitation and dual luciferase expression assays were conducted to further investigate the mechanism through which unliganded GR regulates these genes. Expression microarray analysis revealed 260 targets negatively regulated and 343 targets positively regulated by unliganded GR. A number of the positively regulated targets were involved in pro-apoptotic networks, possibly opposing the activity of liganded GR targets. Validation and further analysis of five candidates from the microarray indicated that two of these, Hsd11b1 and Ch25h, were regulated by unliganded GR in a manner similar to Brca1 during glucocorticoid treatment. Furthermore, GR was shown to interact directly with and upregulate the Ch25h promoter in the absence, but not the presence, of hydrocortisone (HC), confirming our previously described model of gene regulation by unliganded GR. This work presents the first identification of targets of unliganded GR. We propose that the balance between targets of liganded and unliganded GR signaling is responsible for controlling differentiation and apoptosis, respectively, and suggest that gene regulation by unliganded GR may represent a mechanism for reducing the risk of breast tumourigenesis by the elimination of abnormal cells.


Zwitterion and Oligo(ethylene glycol) Synergy Minimizes Nonspecific Binding of Compact Quantum Dots.
Quantum dots (QDs) are a class of fluorescent nanocrystals in development as labels for molecular imaging in cells and tissues. Recently, coatings for quantum dots based on multidentate polymers have improved labeling performance in a range of bioanalytical applications, primarily due to reduced probe hydrodynamic size. Now, an ongoing challenge is to eliminate nonspecific binding between these small probes and cellular components that mask specifically labeled molecules. Here, we describe insights into controlling and minimizing intermolecular interactions governing nonspecific binding using multidentate polymers with tunable hydrophilic functional groups that are cationic, anionic, zwitterionic (ZW), or nonionic (oligoethylene glycol; OEG). By fixing surface-binding groups and polymer length, coated colloids have similar sizes but diverse physicochemical properties. We measure binding to globular proteins, fixed cells, and living cells and observe a substantial improvement in nonspecific binding resistance when surfaces are functionalized with a combination of ZW and OEG. The independent underlying effects of counterion adsorption and flexibility appear to synergistically resist adsorption when combined, particularly for fixed cells enriched in both charged and hydrophobic moieties. We further show that ZW-OEG QDs are stable under diverse conditions and can be self-assembled with antibodies to specifically label surface antigens on living cells and cytoplasmic proteins in fixed cells. This surface engineering strategy can be adopted across the diverse range of colloidal materials currently in use and in development for biomedical applications to optimize their molecular labeling specificity.


Discovery and structure-activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors.
Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identified by structure-based design, starting from a fragment generated de novo, the 3-aminopyrid-2-one motif. Functionalization of the 3-amino group enabled rapid enhancement of the inhibitory activity against Itk, while introduction of a substituted heteroaromatic ring in position 5 of the pyridone fragment was key to achieving optimal selectivity over related kinases. A careful analysis of the hydration patterns in the kinase active site was necessary to fully explain the observed selectivity profile. The best molecule prepared in this optimization campaign, 7v, inhibits Itk with a K(i) of 7 nM and has a good selectivity profile across kinases.


Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes.
Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD₅₀) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD₅₀ values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD₅₀ values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD₅₀ values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms.


Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways.
Spasticity arises from hyperexcitability of the neural stretch reflex arc secondary to injury of the corticospinal tract. In response to injury, the density of glutamatergic inputs from afferent 1A fibers to motor neurons increases dramatically and adaptive changes occur in the morphology of microglia cells in the spinal cord. Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS. Stimulation of cannabinoid (CB)1 receptors reduces the hyperglutamatergic drive from sensory afferents to spinal cord motor neurons and blocks the synaptic effects of activated microglia and pro-inflammatory mediators (e.g. TNF-α) on glutamatergic transmission. Enhancing corticospinal tract excitability through intermittent theta burst stimulation inhibits the stretch reflex and spasticity by promoting long-term potentiation, a form of synaptic plasticity that requires stimulation of CB1 receptors. Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation. Key Messages: Glutamatergic and GABAergic pathways are involved in the regulation of muscle tone. CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways. THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits.


Both Bilateral Breast Volume Discrepancy and Asymmetric Anterior Chest Wall Shape Contribute to the Unsightly Breast Contour in Female Right Thoracic Idiopathic Scoliosis.
A retrospective radiographic study. To evaluate the asymmetry of breast volume (BV) and shape in female adolescent idiopathic scoliosis (AIS) patients and to define their relationship with deformed components of the anterior chest wall and curved spine. The higher incidence of asymmetric breast development in AIS was described by prior studies. However, the interplay between scoliosis curve magnitude and severity of breast asymmetry (BA) are unknown. A total of 73 surgically treated female right thoracic AIS patients classified as Lenke type I were enrolled in this study, with the average Cobb angle being 52.08±11.68 degrees. The Image J software was utilized to calculate BV. Both concave and convex radiographic parameters of breast shape were measured including the extraversion angle (EA), the coverage angle (CA), the axial breast height, the vertical breast height (VBH), and the nipple-to-sternum distance. The inclination angles of the concave and convex anterior chest wall were also assessed. BA was calculated according to the formula as follows: BA=(concave-convex)×BV/[(concave+convex)×BV]/2. The measurements of spinal deformity parameters included the Cobb angle, the RAsag angle, and the RAml angle. Paired t test was performed to analyze the asymmetry of breast shape, and Pearson correlation analysis was utilized to define the correlation between the breast shape, spinal deformity, and the inclination of anterior chest wall. The concave BV, EA, axial breast height, and vertical breast height were significantly larger than those of the convex side (P<0.05), whereas the concave CA and the inclination angle of the anterior chest wall were significantly smaller than those of the convex side (P<0.05). No difference was detected between the concave and the convex nipple-to-sternum distance (P>0.05). The averaged BA was 11.4%, with the ratio of asymmetry beyond 10% being 52.1%. No statistically significant relationships between BA and Cobb angle, RAsag angle, RAml angle were detected (P>0.05). The inclination angle of the anterior chest wall demonstrated significant correlation with EA (P<0.001) and CA (P<0.001), respectively. The incidence of BA in AIS is notable, with the concave breast being larger, more extroversive, and more concentrated than the convex breast. The discrepancy between concave and convex anterior chest wall inclination bound to scoliosis could have a major influence on breast orientation and profile, suggesting a synergistic role of anterior chest wall deformity and bilateral BV discrepancy in the formation of BA.


Isolation and characterization of the novel popeye gene family expressed in skeletal muscle and heart.
We identified a novel gene family in vertebrates which is preferentially expressed in developing and adult striated muscle. Three genes of the Popeye (POP) family were detected in human and mouse and two in chicken. Chromosomal mapping indicates that Pop1 and Pop3 genes are clustered on mouse chromosome 10, whereas Pop2 maps to mouse chromosome 16. We found evidence that POP1 and POP3 in chicken may also be linked and multiple transcript isoforms are generated from this locus. The POP genes encode proteins with three potential transmembrane domains that are conserved in all family members. Individual POP genes exhibit specific expression patterns during development and postnatally. Chicken POP3 and mouse Pop1 are first preferentially expressed in atrium and later also in the subepicardial compact layer of the ventricles. Chicken POP1 and mouse Pop2 are expressed in the entire heart except the outflow tract. All three Pop genes are expressed in heart and skeletal muscle of the adult mouse and lower in lung. Pop1 and Pop2 expression is upregulated in uterus of pregnant mice. Like the mouse genes, human POP genes are predominantly expressed in skeletal and cardiac muscle. The strong conservation of POP genes during evolution and their preferential expression in heart and skeletal muscle suggest that these novel proteins may have an important function in these tissues in vertebrates.


Development of a syngenic murine B16 cell line-derived melanoma susceptible to destruction by neuroattenuated HSV-1.
HSV-1 ICP34.5 mutants can slow progression of preformed tumors in rodent models. However, the current models available for study are limited due to the lack of a syngenic, low-immunogenic tumor model susceptible to HSV-1. Thus we have developed a new model to determine the role of the immune response in viral-mediated tumor destruction. The human herpesvirus entry (Hve) receptors (HveA, HveB, and HveC) and a control plasmid were transfected into B78H1 murine melanoma cells. Transfection of HveA and HveC conferred sensitivity to HSV-1 to these cells. A10 (HveA), C10 (HveC), and control cells were able to form tumors reproducibly in vivo. The transfection of the receptors into B78H1 cells did not induce a detectable in vivo immunogenicity to the tumors. Finally, A10 and C10 tumor-bearing mice treated with HSV-1 1716 had significant prolongation of survival compared to mock-treated mice. These data suggest that A10 and C10 will be useful as in vivo models for studying the role of the immune response in viral-mediated tumor destruction.


Inverse Modulation of Aurora Kinase A and Topoisomerase IIα in Normal and Tumor Breast Cells upon Knockdown of Mitochondrial ASncmtRNA.
Breast cancer is currently the most diagnosed form of cancer and the leading cause of death by cancer among females worldwide. We described the family of long non-coding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA) members. Knockdown of ASncmtRNAs using antisense oligonucleotides (ASOs) induces proliferative arrest and apoptotic death of tumor cells, but not normal cells, from various tissue origins. In order to study the mechanisms underlying this selectivity, in this study we performed RNAseq in MDA-MB-231 breast cancer cells transfected with ASncmtRNA-specific ASO or control-ASO, or left untransfected. Bioinformatic analysis yielded several differentially expressed cell-cycle-related genes, from which we selected Aurora kinase A (AURKA) and topoisomerase IIα (TOP2A) for RT-qPCR and western blot validation in MDA-MB-231 and MCF7 breast cancer cells, as well as normal breast epithelial cells (HMEC). We observed no clear differences regarding mRNA levels but both proteins were downregulated in tumor cells and upregulated in normal cells. Since these proteins play a role in genomic integrity, this inverse effect of ASncmtRNA knockdown could account for tumor cell downfall whilst protecting normal cells, suggesting this approach could be used for genomic protection under cancer treatment regimens or other scenarios.


Treatment of metastatic disease of the tibia.
Metastatic lesions to bone outnumber primary bone malignancies. Osseous metastases to the tibia tend to be less common than osseous metastases to other long bones. This study examined the treatment options for a population of patients with metastatic disease to the tibia, with surgical intervention being the cornerstone of treatment for the osseous lesion. A multicenter study had 592 patients with metastatic disease to the bone, with 26 lesions occurring in the tibia (4.4%) during a 13-year period. No patient had concurrent metastases distal to the elbow. After confirmation of metastatic disease, treatment consisted of surgical intervention in all patients, including plate osteosynthesis, intramedullary rodding and cementation, endoprosthetic replacement, and in most patients, postoperative radiation therapy. In 96% of patients, the reconstruction outlasted their life expectancy. All patients were satisfied with their reconstruction. Four complications were encountered in the postoperative period, all requiring additional surgery. Aggressive treatment of osseous metastasis is justified in patients with metastatic disease despite a limited life expectancy. Intervention by an orthopaedic oncologist may result in fewer reconstructive failures. Surgical intervention contributes to an improved quality of life and limb function, ease of nursing care, and may help in maintaining patient independence.


Visual depictions of female genitalia differ depending on source.
Very little research has attempted to describe normal human variation in female genitalia, and no studies have compared the visual images that women might use in constructing their ideas of average and acceptable genital morphology to see if there are any systematic differences. The objective of the present work was to determine if visual depictions of the vulva differed according to their source so as to alert medical professionals and their patients to how these depictions might capture variation and thus influence perceptions of 'normality'. A comparative analysis was conducted by measuring (a) published visual materials from human anatomy textbooks in a university library, (b) feminist publications (print and online) depicting vulval morphology and (c) online pornography, focusing on the most visited and freely accessible sites in the UK. Post hoc tests showed that labial protuberance was significantly less (p<0.001, equivalent to approximately 7 mm) in images from online pornography compared to feminist publications. All five measures taken of vulval features were significantly correlated (p<0.001) in the online pornography sample, indicating a less varied range of differences in organ proportions than the other sources where not all measures were correlated. Women and health professionals should be aware that specific sources of imagery may depict different types of genital morphology and may not accurately reflect true variation in the population, and consultations for genital surgeries should include discussion about the actual and perceived range of variation in female genital morphology.


Novel Abundant Oceanic Viruses of Uncultured Marine Group II Euryarchaeota.
Marine group II Euryarchaeota (MG-II) are among the most abundant microbes in oceanic surface waters [1-4]. So far, however, representatives of MG-II have not been cultivated, and no viruses infecting these organisms have been described. Here, we present complete genomes for three distinct groups of viruses assembled from metagenomic sequence datasets highly enriched for MG-II. These novel viruses, which we denote magroviruses, possess double-stranded DNA genomes of 65 to 100 kilobases in size that encode a structural module characteristic of head-tailed viruses and, unusually for archaeal and bacterial viruses, a nearly complete replication apparatus of apparent archaeal origin. The newly identified magroviruses are widespread and abundant and therefore are likely to be major ecological agents.


A health economic analysis of the use of rhBMP-2 in Gustilo-Anderson grade III open tibial fractures for the UK, Germany, and France.
The purpose of this study was to determine the cost savings from a societal perspective for recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III A and B open tibial fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Health care system costs (direct health care costs) and costs for productivity losses (indirect health care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma "BESTT study". Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/2008 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. For a 1 year perspective, overall treatment costs per patient after the initial surgery of the control vs. the rhBMP-2 group were 44,757 euros vs. 36,847 euros for the UK, 50,197 euros vs. 40,927 euros for Germany and 48,766 euros vs. 39,474 euros for France in favour of rhBMP-2 with overall savings overall savings per case of rhBMP-2 treatment of 7911 euros for the UK, 9270 euros for Germany, and 9291 euros for France which was mainly due to reduced productivity losses by significant faster fracture healing in the rhBMP-2 group (p=0.01). These savings largely offset the upfront price of rhBMP-2 of 2266 euros (1790 pounds) in the UK, euros 2970 in Germany, and 2950 euros in France. Total net savings can be estimated to be 9.6 million euros for the UK, 14.5 million euros for Germany, and 11.4 million euros for France. The results depend on the methodology used particularly for calculation of productivity losses and return-to-work time which was assumed to correspond with fracture healing time. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibial fractures, at a national level there are net cost savings from a societal perspective for all three countries.


[Determination of the free radical processes in condensates of exhaled air in children with recurrent bronchitis].
Free-radical processes were assessed in exhaled air condensates of healthy children and of those suffering from recurrent bronchitis during remission and at the onset of exacerbation. 3 percent hydrogen peroxide-induced chemiluminescence technique was employed with the results recorded by chemiluminometer, manufactured in this country. The data evidence an increase of the total induced chemiluminescence in the patients during exacerbation vs. that in healthy children; such measurements may become a valuable test in the diagnosis of chronic and recurrent pulmonary disease in children.


Transforaminal lumbar interbody fusion with a tantalum cage: lumbar lordosis redistribution and sacral slope restoration with a modified posterior technique.
Transforaminal lumbar interbody fusion (TLIF), a commonly used procedure in spine surgery, has the advantage of a lower incidence of nerve lesions compared to the posterior lumbar interbody fusion (PLIF) technique. The intersomatic arthrodesis has always been carried out with a single tantalum cage normally used for PLIF. Tantalum is a metal that is particularly used in orthopedic surgery. It has a modulus of elasticity similar to marrow and leads to high primary stability of the implant. Our study was a retrospective monocentric observational study evaluating clinical and radiological outcomes of tantalum cages in a modified TLIF technique with posterior instrumentation and autologous and/or homologous posterolateral bone grafting. The aim of the study was to evaluate clinical outcomes and the increase in or redistribution of lumbar lordosis. The intersomatic arthrodesis was always carried out with a single tantalum cage normally used for PLIF to reduce the neurological risk. We retrospectively studied 105 patients who were treated with a modified unilateral TLIF approach by two surgeons between 2013 and 2018. We evaluated the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for back pain, global lumbar lordosis, lordosis of L4-sacrum, segmental lordosis of functional motion units that underwent arthrodesis, pelvic tilt, pelvic incidence, and the sacral slope in 77 patients. All patients were suffering from grade III or IV Pfirrmann, instability, or foraminal post-laminectomy stenosis and/or grade I-II degenerative spondylolisthesis or low-grade isthmic spondylolisthesis. They had no significant sagittal imbalance, with a sagittal vertical axis (SVA) of < 5 mm. The average follow-up duration was 30 months. We achieved excellent clinical results, with only four cases of failure (5.2%). Moreover, we noticed a statistically significant redistribution of lumbar lordosis, with an average percentage increase in L4-S1 lordosis equal to 19.9% (P < 0.001), an average increase in the L4-S1/Lumbar lordosis (LL) ratio from 0.53 to 0.63 (P < 0.001), and a mean percentage increase in sacral slope equal to 7.6% (P < 0.001). Thanks to the properties of tantalum, our modified single-portal TLIF technique is a valid surgical solution to obtain a solid arthrodesis and restore the correct lumbar lordosis distribution while reducing neurological complications and the number of failures. 4 Trial registration statement: retrospective observational study, no trial registration.


Action of internal pronase on the f-channel kinetics in the rabbit SA node.
1. The hyperpolarization-activated If current was recorded in inside-out macropatches from sino-atrial (SA) node myocytes during exposure of their intracellular side to pronase, in an attempt to verify if cytoplasmic f-channel domains are involved in both voltage- and cAMP-dependent gating. 2. Superfusion with pronase caused a quick, dramatic acceleration of channel opening upon hyperpolarization and slowing, rapidly progressing into full blockade, of channel closing upon depolarization; these changes persisted after wash off of pronase and were irreversible, indicating proteolytic cleavage of channel regions which contribute to gating. 3. If recorded from patches normally responding to cAMP became totally insensitive to cAMP following pronase treatment, indicating partial or total removal of channel regions involved in the cAMP-dependent activation. 4. The fully activated I-V relationship was not modified by pronase, indicating that internal proteolysis did not affect the f-channel conductance. 5. The changes in If kinetics induced by pronase were due to a large depolarizing shift of the f-channel open probability curve (56.5 +/- 1.1 mV, n = 7). 6. These results are consistent with the hypothesis that cytoplasmic f-channel regions are implicated in dual voltage- and cAMP-dependent gating; also, since pronase does not abolish hyperpolarization-activated opening, an intrinsic voltage-dependent gating mechanism must exist which is inaccessible to proteolytic cleavage. A model scheme able to account for these data thus includes an intrinsic gating mechanism operating at depolarized voltages, and a blocking mechanism coupled to cAMP binding to the channel.


Systemic mastocytosis: progressive evolution of an occult disease into fatal mast cell leukemia: unique findings on an unusual hematological neoplasm.
Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors' knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL.


Appearance-Based Gaze Estimation for ASD Diagnosis.
Biomarkers, such as magnetic resonance imaging (MRI) and electroencephalogram have been used to help diagnose autism spectrum disorder (ASD). However, the diagnosis needs the assist of specialized medical equipment in the hospital or laboratory. To diagnose ASD in a more effective and convenient way, in this article, we propose an appearance-based gaze estimation algorithm-AttentionGazeNet, to accurately estimate the subject's 3-D gaze from a raw video. The experimental results show its competitive performance on the MPIIGaze dataset and the improvement of 14.7% for static head pose and 46.7% for moving head pose on the EYEDIAP dataset compared with the state-of-the-art gaze estimation algorithms. After projecting the obtained gaze vector onto the screen coordinate, we apply accumulated histogram to taking into account both spatial and temporal information of estimated gaze-point and head-pose sequences. Finally, classification is conducted on our self-collected autistic children video dataset (ACVD), which contains 405 videos from 135 different ASD children, 135 typically developing (TD) children in a primary school, and 135 TD children in a kindergarten. The classification results on ACVD shows the effectiveness and efficiency of our proposed method, with the accuracy 94.8%, the sensitivity 91.1% and the specificity 96.7% for ASD.


The isolation and characterization of the Escherichia coli DNA adenine methylase (dam) gene.
The E. coli dam (DNA adenine methylase) enzyme is known to methylate the sequence GATC. A general method for cloning sequence-specific DNA methylase genes was used to isolate the dam gene on a 1.14 kb fragment, inserted in the plasmid vector pBR322. Subsequent restriction mapping and subcloning experiments established a set of approximate boundaries of the gene. The nucleotide sequence of the dam gene was determined, and analysis of that sequence revealed a unique open reading frame which corresponded in length to that necessary to code for a protein the size of dam. Amino acid composition derived from this sequence corresponds closely to the amino acid composition of the purified dam protein. Enzymatic and DNA:DNA hybridization methods were used to investigate the possible presence of dam genes in a variety of prokaryotic organisms.


Role of Oxide/Metal Bilayer Electrodes in Solution Processed Organic Field Effect Transistors.
High performance, air stable and solution-processed small molecule 2,7-dioctyl[1]benzothieno[3,2-b]benzothiophene (C8-BTBT) based organic field-effect transistors (OFETs) with various electrode configurations were studied in detail. The contact resistance of OFET devices with Ag, Au, WO3/Ag, MoO3/Ag, WO3/Au, and MoO3/Au were compared. Reduced contact resistance and consequently improved performance were observed in OFET devices with oxide interlayers compared to the devices with bare metal electrodes. The best oxide/metal combination was determined. The possible mechanisms for enhanced electrical properties were explained by favorable morphological and electronic structure of organic/metal oxide/metal interfaces.


Yolk embolism associated with trauma in vitellogenic sea turtles in Florida (USA): a review of 11 cases.
Case information and postmortem examination findings are presented for 11 adult female sea turtles in reproductive form that died in Florida, USA. All had abundant, large vitellogenic follicles, and most were either gravid or had recently nested. Species included six loggerheads (Caretta caretta) and five green turtles (Chelonia mydas). Identified proximate causes of death included falls or entrapment by obstructions on nesting beaches, burial under collapsed dunes, and other traumatic injuries of different causes. Evidence of yolk embolization was found in 10 cases and suspected in an 11th turtle. Ten turtles also had various amounts of free intracoelomic yolk. Although the effects of yolk embolization are uncertain at this time, precedence of pathologic importance in other species suggests that embolism may complicate traumatic injuries, including seemingly minor events.


Forearm DXA Increases the Rate of Patients With Asymptomatic Primary Hyperparathyroidism Meeting Surgical Criteria.
A reduction in bone mineral density (BMD) is common in primary hyperparathyroidism (PHPT), above all at cortical sites. Guidelines for the management of asymptomatic PHPT (aPHPT) recommend a BMD evaluation at the lumbar spine, hip, and forearm. Surgery is recommended for patients with a T-score less than or equal to -2.5 at any of these sites. However, a BMD evaluation at the forearm is not routinely performed. To evaluate the impact of measuring forearm BMD in the clinical management of aPHPT. We retrospectively reviewed a prospective database of 172 patients with aPHPT, selecting the 116 patients in whom a dual x-ray absorptiometry (DXA) scan had been performed at all 3 sites. Seventy-four out of 116 patients had a densitometric diagnosis of osteoporosis (OP) at any site, and the forearm was the only site involved in 13/74 (group A, 17.6% of osteoporotic patients and 11.2% of the whole aPHPT cohort). Patients belonging to group A were significantly older than the other aPHPT patients, whereas no difference was found in biochemical measurements. Six out of 13 patients belonging to group A (5.2% of the whole aPHPT cohort) fulfilled surgical criteria based only on a forearm T-score. DXA at 3 sites revealed OP at the forearm, but not at the other sites, in 11.2% of aPHPT patients. Half of these cases met surgical criteria based on this one factor alone. These patients did not show any clinical (except age) or biochemical differences from the other patients. The implementation of forearm DXA increases the rate of patients with aPHPT meeting surgical criteria.


Streptococcal nucleases. I. Further studies on the A, B, and C enzymes.
Streptococcal DNAse C is more resistant to heat inactivation than the A or B enzyme. DNAses A and C are indifferent to the bacterial ribonucleic acid inhibitor whereas the B enzyme is markedly inhibited. Prolonged digestion with relatively large amounts of DNAse B results in chemical and biological destruction of the inhibitor. Ribonuclease as well as deoxyribonuclease activity is associated with the B enzyme. Both activities require divalent cations and both are inhibited by bacterial ribonucleic acid. The ratios of the two activities are constant in various preparations and after partial heat inactivation. Mutual inhibition of the two activities can be demonstrated in mixed substrate systems. The evidence presented is consistent with the view that the B enzyme is a single nuclease which can attack both deoxyribonucleic and ribonucleic acids.


Referral patterns of hip pain in patients undergoing total hip replacement.
This study was undertaken to determine the most common referral patterns of hip pain in patients scheduled to undergo primary and revision total hip replacement. The exact location of pain from the hip was recorded prospectively for 323 patients (358 hips) who had primary total hip replacement and for 94 patients who had revision of a loose total hip. Seventy-three percent of patients with primary hip disease had pain in the groin, and 27% had groin pain that referred to the knee. Eighty-nine percent of 57 patients who had femoral component loosening had thigh or knee pain, and all of the 34 patients who had a loose acetabular component with a well-fixed femoral implant had pain in the hip region without distal radiation of pain. These results indicate that in patients who have a painful total hip, thigh pain is highly suggestive of femoral component loosening and pain located around the hip region that does not radiate distally is associated with isolated acetabular component loosening.


Characterization of Staufen 1 ribonucleoprotein complexes.
In Drosophila oocytes and neuroblasts, the double-stranded RNA binding protein Staufen assembles into ribonucleoprotein particles, which mediate cytoplasmic mRNA trafficking and translation. Two different mammalian orthologues also appear to reside in distinct RNA-containing particles. To date, relatively little is known about the molecular composition of Staufen-containing ribonucleoprotein complexes. Here, we have used a novel one-step affinity purification protocol to identify components of Staufen 1-containing particles. Whereas the nucleocytoplasmic RNA-binding protein nucleolin is linked to Staufen in an RNA-dependent manner, the association of protein phosphatase 1, the microtubule-dependent motor protein kinesin and several components of the large and small ribosomal subunits with Staufen ribonucleoprotein complexes is RNA-independent. Notably, all these components do not co-purify with a second RNA-binding protein, hnRNPK (heterogeneous ribonucleoprotein K), demonstrating the high specificity of the purification protocol. Furthermore, pull-down and immunoprecipitation experiments suggest a direct interaction between Staufen 1 and the ribosomal protein P0 in vitro as well as in cells. In cell fractionation and sucrose gradient assays, Staufen co-fractionates with intact ribosomes and polysomes, but not with the isolated 40 S ribosomal subunit. Taken together, these findings imply that, in the cytoplasm of mammalian cells, an association with the ribosomal P-stalk protein P0 recruits Staufen 1 into ribosome-containing ribonucleoprotein particles, which also contain kinesin, protein phosphatase 1 and nucleolin.


Clarithromycin is inactive against Mycobacterium tuberculosis.
When 10% oleic acid-albumin-dextrose-catalase-enriched Mueller-Hinton agar medium was employed, the MICs of clarithromycin (CLARI) at which 50 and 90% of 12 strains of Mycobacterium tuberculosis were inhibited were 64 and > 128 micrograms/ml, respectively, which are significantly greater than the achievable peak CLARI concentrations in serum and in lung tissue in humans. In two different mouse experiments, 4 to 6 weeks of treatment with CLARI at 200 mg/kg of body weight six times weekly produced neither bactericidal nor bacteriostatic effects against M. tuberculosis. Therefore, we conclude that CLARI as a single drug is inactive against M. tuberculosis.


Effects of Simulated Hearing Loss on Bilingual Children's Consonant Recognition in Noise.
This study investigated the possible impact of simulated hearing loss on speech perception in Spanish-English bilingual children. To avoid confound between individual differences in hearing-loss configuration and linguistic experience, threshold-elevating noise simulating a mild-to-moderate sloping hearing loss was used with normal-hearing listeners. The hypotheses were that: (1) bilingual children can perform similarly to English-speaking monolingual peers in quiet; (2) for both bilingual and monolingual children, noise and simulated hearing loss would have detrimental impacts consistent with their acoustic characteristics (i.e., consonants with high-frequency cues remain highly intelligible in speech-shaped noise, but suffer from simulated hearing loss more than other consonants); (3) differences in phonology and acquisition order between Spanish and English would have additional negative influence on bilingual children's recognition of some English consonants. Listeners were 11 English-dominant, Spanish-English bilingual children (6 to 12 years old) and 12 English-speaking, monolingual age peers. All had normal hearing and age-appropriate nonverbal intelligence and expressive English vocabulary. Listeners performed a listen-and-repeat speech perception task. Targets were 13 American English consonants embedded in vowel-consonant-vowel (VCV) syllables. VCVs were presented in quiet and in speech-shaped noise at signal-to-noise ratios (SNRs) of -5, 0, 5 dB (normal-hearing condition). For the simulated hearing-loss condition, threshold-elevating noise modeling a mild-to-moderate sloping sensorineural hearing loss profile was added to the normal-hearing stimuli for 0, 5 dB SNR, and quiet. Responses were scored for consonant correct. Individual listeners' performance was summarized for average across 13 consonants (overall) and for individual consonants. Groups were compared for the effects of background noise and simulated hearing loss. As predicted, group performed similarly in quiet. The simulated hearing loss had a considerable detrimental impact on both groups, even in the absence of speech-shaped noise. Contrary to our prediction, no group difference was observed at any SNR in either condition. However, although nonsignificant, the greater within-group variance for the bilingual children in the normal-hearing condition indicated a wider "normal" range than for the monolingual children. Interestingly, although it did not contribute to the group difference, bilingual children's overall consonant recognition in both conditions improved with age, whereas such a developmental trend for monolingual children was observed only in the simulated hearing-loss condition, suggesting possible effects of experience. As for the recognition of individual consonants, the influence of background noise or simulated hearing loss was similar between groups and was consistent with the prediction based on their acoustic characteristics. The results demonstrated that school-age, English-dominant, Spanish-English bilingual children can recognize English consonants in a background of speech-shaped noise with similar average accuracy as English-speaking monolingual age peers. The general impact of simulated hearing loss was also similar between bilingual and monolingual children. Thus, our hypothesis that bilingual children's English consonant recognition would suffer from background noise or simulated hearing loss more than the monolingual peers was rejected. However, the present results raise several issues that warrant further investigation, including the possible difference in the "normal" range for bilingual and monolingual children, influence of experience, impact of actual hearing loss on bilingual children, and stimulus quality.


Fiberoptic tracheal intubation through a laryngeal mask airway in a child with Treacher Collins syndrome.
Treacher Collins syndrome (TCS) is a rare inherited condition characterized by bilateral and symmetric abnormalities of structures within the first and second bronchial arches. The mechanism of inheritance is autosomal dominant with variable expressivity. Because of this variability in expression, some affected individuals exhibit virtually no overt clinical manifestations. However, most children with TCS present with the following classic facial features: down-sloping palpebral fissures, colobomata of the lower eyelid, scanty lower eyelashes, malar hypoplasia, and micro- or retrognathia. Cleft palate is present in up to 35% of patients and an additional 30-40% have congenital palatopharyngeal incompetence. Abnormalities of the ear are very common and vary from minor malformations to severe microtia and hearing loss. Hearing loss may be due to atresia of the auditory canals or ossicular malformation of the middle ear. Despite these many development abnormalities, TCS patients are usually of normal intelligence. We report the case of a 3 1/2-yr-old patient with TCS undergoing cleft palate repair and discuss fiberoptic intubation through a laryngeal mask airway using two endotracheal (ETT) tubes secured via an ETT connector.


Triton hyperlipemia in dogs. II. Atheroscieross, diffuse lipidosis, and deletion of fat stores produced by prolonged administration of the non-tonic surface-active agent.
Fourteen dogs, fed a regular diet and given 250 mg/kg of triton (a non-ionic surface-active agent) intravenously every 4th day, exhibited a progressively severe hyperlipemia. Serum triglycerides were the first to increase. Cholesterol, mostly in the free form, and phospholipids showed elevation only at a later stage and increased at almost identical rates. The plasma-free fatty acid concentration was from 2 to 3 times above normal. With establishment of sustained hyperlipemia, there was reduction, followed by total disappearance, of the high density D 1.063 to 1.21 lipoprotein. Most of the cholesterol and phospholipids (70 to 75 per cent of the total) were found in the D 1.006 to 1.063 lipoprotein class, the remainder in the D < 1.006 class. Triglycerides were almost evenly distributed between these two classes. The concentration of the serum lipoprotein proteins was within normal limits. All of the animals died within from 4 to 5 months after receiving the first injection of triton. Autopsy findings consistently showed: (a) numerous lipidladen macrophages in the liver, spleen, and lymph nodes; (b) significant depletion of all fat stores; (c) presence of lipids, either free or engulfed in macrophages (foam cells), in the subintima of the coronary arteries, aorta, and pulmonary arteries, indicating an early stage of atherosclerosis. Concurrent daily administration of heparin (5 mg per kilogram of body weight) did not substantially change the course of the disease. Withdrawal of triton from animals that had been receiving the detergent for from 3 to 4 months, elicited a slow return to normal of the lipid pattern. In two dogs killed when normolipemia was reestablished, all tissues were normal with the minor exception of a few hepatic macrophages still laden with sudanophilic material. It is postulated that the primary action of the injected triton was on the lipid moieties of plasma lipoproteins with formation of complexes, which, as foreign bodies, were preferentially taken up by the cells of the reticuloendothelial system. Depletion of fat stores was probably secondary to increased lipid mobilization, as an attempt by these tissues to supply energy to the parenchymal cells unable to utilize triton-bound lipids.


Pemphigus foliaceus in the horse: a retrospective study of 20 cases.
Twenty horses with pemphigus foliaceus were seen over a period of 15 years in a veterinary medical teaching hospital. Breeds seen were seven quarterhorses, five thoroughbreds, three cross-bred horses, two Arabians and one of each of the following: standardbred, Tennessee walker and warmblood. There was no breed, age or sex predisposition. Nine were mares, ten were geldings and one was a stallion. Ages ranged from 2.5 months to 25 years, with a mean of 8.6 years. Sixteen (80%) of the pemphigus foliaceus horses first exhibited signs between September and February. There was a statistically significant more common occurrence of pemphigus foliaceus during those months. Signs in the four other horses were first noted in March, May or June. Three of those horses were < 13 months of age. Oedema (14/20) and crusts (13/20) were the most common lesions. Pain was present in 9/20 horses, pruritus in 7/20 and pyrexia in 7/20. Follow-up was available for 13 horses. Five of these horses were euthanased. In three horses the reason for euthanasia was laminitis secondary to treatment. Four horses remained lesion-free after medication was discontinued. Two horses required maintenance medication and are doing well at the time of writing.


Mycobacterium kansasii disease in patients infected with human immunodeficiency virus.
We evaluated the presenting characteristics, response to therapy, and outcome for 46 patients infected with Mycobacterium kansasii and human immunodeficiency virus (HIV). M. kansasii infection occurred late in HIV disease (mean CD4 lymphocyte count, 52.4/mm3), when most patients had already developed AIDS; 91.3% of the patients had pulmonary involvement, and 21.7% had disseminated disease. Clinical and radiographic findings were consistent with pulmonary disease and had been present for approximately 4 weeks. Fourteen of the treated patients had disease that resolved or abated (mean survival +/- SE, 73.7 weeks +/- 14.6 weeks), and 13 had disease that persisted unchanged or worsened (mean survival +/- SE, 57.3 +/- 15.8 weeks). The outcome was poor for 17 patients who did not receive effective therapy (mean survival +/- SE, 14.1 +/- 5.3 weeks). M. kansasii infection presents late in the course of HIV disease, and the lung is the organ most frequently involved. Survival is clearly influenced by therapy, and even patients who respond poorly to therapy survive longer than those who are not treated.


[Stimulation increase in evoked acoustic otoemissions].
Evoked otoacoustic emissions (OEAE) are an excellent evaluation method of the hearing organ and are principally useful in newborn screening. During the performance of this technique, doubtful cases sometimes exist and they are customarily considered as failures of the test, increasing the group of children to be re-evaluated. The program IL088 has the possibility of increasing the stimulus intensity (gain). We applied this gain to all children with doubtful OEAE in attempts to give a pass or fail score. The record of OEAE was accomplished with the system IL088 v3.5. It was applied to 70 ears of healthy newborns, a gain of +15 dB initially and/or +21 dB (if a pass score was not obtained). Some normal ears were included in this group as controls. Of the explored ears, 23 had a normal OEAE, 17 presented a doubtful response and in 30 cases the answers were negative (fail). This study demonstrates that in doubtful cases, the usefulness of increasing the gain is very high permitting that these cases accomplish pass criteria (15/17). In the ears with a lack of response there is an increased response, but it usually does not reach a passing level (6/30). In children with normal response the pass rate does not vary. The increase in gain in ears with a doubtful response offers a high a rentability, reducing the the initial failure rate of OEAE without altering the real failure rate or affecting those that initially pass allowing a reduction in the number of second evaluations.


Reconstructing Ecological Niche Evolution When Niches Are Incompletely Characterized.
Evolutionary dynamics of abiotic ecological niches across phylogenetic history can shed light on large-scale biogeographic patterns, macroevolutionary rate shifts, and the relative ability of lineages to respond to global change. An unresolved question is how best to represent and reconstruct evolution of these complex traits at coarse spatial scales through time. Studies have approached this question by integrating phylogenetic comparative methods with niche estimates inferred from correlative and other models. However, methods for estimating niches often produce incomplete characterizations, as they are inferred from present-day distributions that may be limited in full expression of the fundamental ecological niche by biotic interactions, dispersal limitations, and the existing set of environmental conditions. Here, we test whether incomplete niche characterizations inherent in most estimates of species' niches bias phylogenetic reconstructions of niche evolution, using simulations of virtual species with known niches. Results establish that incompletely characterized niches inflate estimates of evolutionary change and lead to error in ancestral state reconstructions. Our analyses also provide a potential mechanism to explain the frequent observation that maximum thermal tolerances are more conserved than minimum thermal tolerances: populations and species experience more spatial variation in minimum temperature than in maximum temperature across their distributions and, consequently, may experience stronger diversifying selection for cold tolerance.


Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease.
Eosinophils are important effector cells in airway inflammation, as pleiotropy and heterogeneity can be linked to various pathophysiologies in asthma and chronic obstructive pulmonary disease (COPD). Sputum eosinophils can reflect the heterogeneity of airway inflammation, and owing to their traits, blood eosinophils can be a surrogate and potential biomarker for managing both conditions. Blood eosinophils are activated via the stimulation of type 2 cytokines, such as interleukin (IL)-5, IL-4/13, granulocyte-macrophage colony-stimulating factor, IL-33, and thymic stromal lymphopoietin. There is sufficient evidence to support the relationship between the blood eosinophil count and clinical outcomes, including pulmonary function decline, exacerbations, all-cause mortality, and treatment response to inhaled corticosteroids and biologics. Thus, there is growing interest in the use of blood eosinophils for the management of these diseases. Compiling recent evidence, we herein review the significance of measuring blood eosinophils in asthma and COPD.


Trends in cervical cancer in the Netherlands until 2007: has the bottom been reached?
We explored trends in incidence and mortality of cervical cancer by age, stage and morphology, and linked the observed trends to screening activities. Data was retrieved from the Netherlands Cancer Registry during 1989-2007 (incidence) and Statistics Netherlands during 1970-2007 (mortality). Trends were evaluated by calculating the estimated annual percentage change (EAPC). Joinpoint regression analysis was used to detect changes in trends. Cervical intraepithelial neoplasia (CIN) detection rates were calculated by data from "the nationwide network and registry of histo- and cytopathology" during 1990-2006. Total age-adjusted incidence rate (European standardized rate (ESR)) was 7.9 per 100,000 woman years in 2007. During 1989-1998, incidence rates decreased with an EAPC of -1.3% (95% confidence interval (CI) -2.2 to -0.3), during 1998-2001 with -6.7% (95% CI: -16.4 to 4.1), and increased during 2001-2007 with 2.3% (95% CI: 0.4 to 4.2). Total mortality ESR was 1.9 per 100,000 woman years in 2007. Mortality rates decreased during 1970-1994 annually with -4.1% (95% CI: -4.6% to -3.7%), and with -2.6% (95% CI: -3.8% to -1.5%) during 1994-2007. The observed trend in total incidence is similar to the trend in squamous cell carcinomas in age group 35-54 years, suggesting that the observed trends are likely to be associated to changes in the screening program. This is supported by the trend in CINIII detection rates. In conclusion, incidence and mortality overall decreased and leveled off. On top of that there was an extra decrease that was compensated by a following recent increase in incidence, probably resulting from reorganization of the Dutch screening program.


Utilization of low-molecular-weight organic compounds by the filterable fraction of a lotic microbiome.
Filterable microorganisms participate in dissolved organic carbon (DOC) cycling in freshwater systems, however their exact functional role remains unknown. We determined the taxonomic identity and community dynamics of prokaryotic microbiomes in the 0.22 µm-filtered fraction and unfiltered freshwater from the Conwy River (North Wales, UK) in microcosms and, using targeted metabolomics and 14C-labelling, examined their role in the utilization of amino acids, organic acids and sugars spiked at environmentally-relevant (nanomolar) concentrations. To identify changes in community structure, we used 16S rRNA amplicon and shotgun sequencing. Unlike the unfiltered water samples where the consumption of DOC was rapid, the filtered fraction showed a 3-day lag phase before the consumption started. Analysis of functional categories of clusters of orthologous groups of proteins (COGs) showed that COGs associated with energy production increased in number in both fractions with substrate addition. The filtered fraction utilized low-molecular-weight (LMW) DOC at much slower rates than the whole community. Addition of nanomolar concentrations of LMW DOC did not measurably influence the composition of the microbial community nor the rate of consumption across all substrate types in either fraction. We conclude that due to their low activity, filterable microorganisms play a minor role in LMW DOC processing within a short residence time of lotic freshwater systems.


[Azole. 45(1). Uber 2,4-Dinitrophenylhydrazone von Morpholinonitroimidazolderivaten].
The three title compounds, namely (Z)-1-(4,5-dinitroimidazol-1-yl)-3-morpholinopropan-2-one 2,4-dinitrophenylhydrazone, C(16)H(17)N(9)O(9), (IV), (Z)-3-morpholino-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4-dinitrophenylhydrazone, C(20)H(25)N(9)O(8), (Va), and (E)-3-morpholino-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4-dinitrophenylhydrazone tetrahydrofuran solvate, C(20)H(25)N(9)O(8).C(4)H(8)O, (Vb), have been prepared and their structures determined. In (IV), the C-4 nitro group is nearly perpendicular to the imidazole ring and the C-4-NO(2) bond length is comparable to the value for a normal single Csp(2)-NO(2) bond. In (IV), (Va) and (Vb), the C-5 nitro group deviates insignificantly from the imidazole plane and the C-5-NO(2) bond length is far shorter in all three compounds than C-4-NO(2) in (IV). In consequence, the C-4 nitro group in (IV) is easily replaced by morpholine, while the C-5 nitro group in (IV), (Va) and (Vb) shows an extraordinary stability on treatment with the amine. The E configuration in (Vb) is stabilized by a three-centre hydrogen bond.


Progress in understanding the factors regulating reversibility of long-term potentiation.
Over the past two decades there has been a progressive understanding of the properties and mechanisms underlying long-term potentiation (LTP) of synaptic efficacy, a putative mechanism for learning and memory storage in the brain. Although LTP is remarkable for its stability, recent work has provided evidence that various manipulations can disrupt LTP if applied shortly after its induction. This kind of reversal of synaptic strength from the potentiated state to pre-LTP levels is termed depotentiation. Depotentiation of LTP is effectively induced by low-frequency afferent stimulation (1-5 Hz), brief periods of hypoxia, application of adenosine receptor agonists and brief cooling shocks. The examples of depotentiation described to date are input specific, and not differently expressed during development. The mechanisms responsible for this phenomenon remain to be fully characterized, although some possibilities are dependent on NMDA receptor activation, the increases in intracellular Ca2+, and altered states of protein kinases or phosphatases. In this review, we summarize the recent data concerning putative depotentiation mechanisms and the implications of this phenomenon in the mechanisms of "forgetting", and discuss the prevention of saturation of the storage capacity of a neuronal network.


Casein kinase I transduces Wnt signals.
The Wnt signalling cascade is essential for the development of both invertebrates and vertebrates, and is altered during tumorigenesis. Although a general framework for Wnt signalling has been elucidated, not all of the components have been identified. Here we describe a serine kinase, casein kinase I (CKI), which was isolated by expression cloning in Xenopus embryos. CKI reproduces several properties of Wnt signals, including generation of complete dorsal axes, stabilization of beta-catenin and induction of genes that are direct targets of Wnt signals. Dominant-negative forms of CKI and a pharmacological blocker of CKI inhibited Wnt signals in Xenopus. Inhibiting CKI in Caenorhabditis elegans generated worms with a mom phenotype, indicative of a loss of Wnt signals. In addition, CKI bound to and increased the phosphorylation of dishevelled, a known component of the Wnt pathway. These data indicate that CKI may be a conserved component of the Wnt pathway.


CYP86B1 is required for very long chain omega-hydroxyacid and alpha, omega -dicarboxylic acid synthesis in root and seed suberin polyester.
Suberin composition of various plants including Arabidopsis (Arabidopsis thaliana) has shown the presence of very long chain fatty acid derivatives C20 in addition to the C16 and C18 series. Phylogenetic studies and plant genome mining have led to the identification of putative aliphatic hydroxylases belonging to the CYP86B subfamily of cytochrome P450 monooxygenases. In Arabidopsis, this subfamily is represented by CYP86B1 and CYP86B2, which share about 45% identity with CYP86A1, a fatty acid omega-hydroxylase implicated in root suberin monomer synthesis. Here, we show that CYP86B1 is located to the endoplasmic reticulum and is highly expressed in roots. Indeed, CYP86B1 promoter-driven beta-glucuronidase expression indicated strong reporter activities at known sites of suberin production such as the endodermis. These observations, together with the fact that proteins of the CYP86B type are widespread among plant species, suggested a role of CYP86B1 in suberin biogenesis. To investigate the involvement of CYP86B1 in suberin biogenesis, we characterized an allelic series of cyp86B1 mutants of which two strong alleles were knockouts and two weak ones were RNA interference-silenced lines. These root aliphatic plant hydroxylase lines had a root and a seed coat aliphatic polyester composition in which C22- and C24-hydroxyacids and alpha,omega-dicarboxylic acids were strongly reduced. However, these changes did not affect seed coat permeability and ion content in leaves. The presumed precursors, C22 and C24 fatty acids, accumulated in the suberin polyester. These results demonstrate that CYP86B1 is a very long chain fatty acid hydroxylase specifically involved in polyester monomer biosynthesis during the course of plant development.


[In vitro sensitivity of Histoplasma capsulatum var. capsulatum to amphotericin B, ketoconazole, itroconazole and fluconazole].
The minimum inhibitory concentration (MIC) was determined by a micromethod of dilution in RPMI-1640 broth in order to know the sensitivity to amphotericin B, itraconazole, ketoconazole and fluconazole of 29 strains of Histoplasma capsulatum var capsulatum isolated in Cuba. Histoplasmosis is one of the main systemic mycosis at the world level and its incidence has increased during the last years, associated mainly with HIV infection and to the appareance of new epidemic outbreaks in different regions. The results obtained allowed to conclude that high values of IMC against fluconazole were found with a geometric mean of 55.5 ug/mL. For amphotericin B, ketoconazole and itraconazole, all the strains were inhibited at low concentrations with geometric means of 0.26, 0.17 and 0.125 ug/mL, respectively. The development for the first time in Cuba of a method to determine the IMC of the main antifungal drugs against H. capsulatum var capsulatum will make possible to establish the sensitivity patterns and to detect the appearance of resistance, which will contribute to know this important mycosis better.


Respiratory failure.
The respiratory system has two principal purposes - to maintain adequate arterial Pao2, and to regulate arterial Paco2 and thereby maintain a stable acid-base state. Both are necessary to sustain normal tissue metabolism. Respiratory failure can be defined in two ways: •failure of oxygenation, resulting in Pao2 < 8.0 kPa•failure of ventilation, resulting in Paco2 > 6.7 kPa with accompanying acid-base changes.


Unexplored Antarctic meteorite collection sites revealed through machine learning.
Meteorites provide a unique view into the origin and evolution of the Solar System. Antarctica is the most productive region for recovering meteorites, where these extraterrestrial rocks concentrate at meteorite stranding zones. To date, meteorite-bearing blue ice areas are mostly identified by serendipity and through costly reconnaissance missions. Here, we identify meteorite-rich areas by combining state-of-the-art datasets in a machine learning algorithm and provide continent-wide estimates of the probability to find meteorites at any given location. The resulting set of ca. 600 meteorite stranding zones, with an estimated accuracy of over 80%, reveals the existence of unexplored zones, some of which are located close to research stations. Our analyses suggest that less than 15% of all meteorites at the surface of the Antarctic ice sheet have been recovered to date. The data-driven approach will greatly facilitate the quest to collect the remaining meteorites in a coordinated and cost-effective manner.


Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals.
Nanotechnology is an innovative approach that has potential applications in nutraceutical research. Phytochemicals have promising potential for maintaining and promoting health, as well as preventing and potentially treating some diseases. However, the generally low solubility, stability, bioavailability and target specificity, together with the side effects seen when used at high levels, have limited their application. Indeed, nanoparticles can increase solubility and stability of phytochemicals, enhance their absorption, protect them from premature degradation in the body and prolong their circulation time. Moreover, these nanoparticles exhibit high differential uptake efficiency in the target cells (or tissue) over normal cells (or tissue) through preventing them from prematurely interacting with the biological environment, enhanced permeation and retention effect in disease tissues and improving their cellular uptake, resulting in decreased toxicity, In this review, we outline the commonly used biocompatible and biodegradable nanoparticles including liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly(lactic-co-glycolic acid) nanoparticles. We then summarize studies that have used these nanoparticles as carriers for epigallocatechin gallate, quercetin, resveratrol and curcumin administration to enhance their aqueous solubility, stability, bioavailability, target specificity and bioactivities.


Viral haemorrhagic disease of rabbits in the People's Republic of China: epidemiology and virus characterisation.
Viral haemorrhagic disease (VHD) is a new and severe infectious disease of rabbits, with a high rate of morbidity and mortality. The disease occurs throughout the year, affecting only adult rabbits and not other domestic animals, fowls or laboratory rodents. The transmission is horizontal, by direct or indirect contact, and through all routes. There is no evidence of congenital infection or biological vectors. The causative agent, viral haemorrhagic disease virus (VHDV), is present in all tissues, excretions and secretions. It is an icosahedral and nonenveloped parvo-like virus. The genome, as determined by classical methods, high performance chromatography and in vitro synthesis of double-stranded DNA, is linear, single-stranded DNA. VHDV can agglutinate human erythrocytes at very high titres, irrespective of blood groups, and has a stable reaction to many physical and chemical factors. VHDV has been adapted to grow on rabbit kidney cell strain (DJRK) culture and to produce cytopathic effect (CPE). Inactivated cell culture can protect inoculated rabbits against virulent VHDV. The disease is now effectively controlled in the People's Republic of China, but has not yet been completely eradicated.


GABAergic neurons that contain neuropeptide Y selectively target cells with the neurokinin 1 receptor in laminae III and IV of the rat spinal cord.
Neuropeptide Y (NPY) is contained in a population of GABAergic interneurons in the spinal dorsal horn and, when administered intrathecally, can produce analgesia. We previously identified a strong monosynaptic link between substance P-containing primary afferents and cells in lamina III or IV with the neurokinin 1 (NK1) receptor. Because some of these cells belong to the spinothalamic tract, they are likely to have an important role in pain mechanisms. In this study, we used confocal microscopy to examine the input to lamina III/IV NK1 receptor-immunoreactive neurons from NPY-containing axons. All of the cells studied received a dense innervation from NPY-immunoreactive axons, and electron microscopy revealed that synapses were often present at points of contact. Most NPY-immunoreactive boutons were also GABAergic, which supports the suggestion that they are derived from local neurons. The association between NPY-containing axons and NK1 receptor-immunoreactive neurons was specific, because postsynaptic dorsal column neurons (which were located in laminae III-V but did not possess NK1 receptors) and lamina I neurons with the NK1 receptor received significantly fewer contacts from NPY-immunoreactive axons. In addition, the NK1 receptor-immunoreactive lamina III/IV cells received few contacts from nitric oxide synthase-containing axons (which belong to a different population of GABAergic dorsal horn neurons). The NPY-containing axons appeared to be targeted to the NK1 receptor-immunoreactive neurons themselves rather than to their associated substance P-immunoreactive inputs. The dense innervation of these cells by NPY-containing axons suggests that they may possess receptors for NPY and that activation of these receptors may contribute to NPY-mediated analgesia.


In vitro analysis of anti-HPA-1a dependent platelet phagocytosis and its inhibition using a new whole blood phagocytosis assay (WHOPPA).
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a serious bleeding condition mostly caused by the reaction between maternal anti-HPA-1a antibodies and fetal platelets. This reaction leads to Fc-dependent platelet phagocytosis. Although several serological methods have been developed to identify maternal antibodies, a reliable laboratory parameter as a prognostic tool for FNAIT severity is still lacking. In this study, we developed whole blood platelet phagocytosis assay (WHOPPA), a flow cytometry-based phagocytosis assay that uses a pH-sensitive fluorescent dye (pHrodo-SE) to analyze anti-HPA-1a-dependent platelet phagocytosis in whole blood. WHOPPA revealed a high phagocytosis rate for the anti-HPA-1a opsonized platelets by monocytes but not by neutrophils. Analysis of different monocyte populations showed that all monocyte subsets, including classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes, were able to engulf opsonized platelets. A unique monocyte subset, termed shifted monocytes (CD14+CD16-), showed the highest phagocytosis rate and was detected after platelet engulfment. FcγR inhibition tests revealed that except for FcγRIIa, FcγRI and FcγRIII on monocytes were responsible for the phagocytosis of anti-HPA-1a opsonized platelets. Analysis of anti-HPA-1a antibodies from FNAIT cases (n = 7) showed the phagocytosis of HPA-1aa but not of HPA-1bb platelets by monocytes. The phagocytosis rate was highly correlated with bound antibodies measured by flow cytometry (p < 0001; r = 0.9214) and MAIPA assay (p < 0.001; r = 0.7692). The phagocytosis rates were equal for type I and II anti-HPA-1a antibodies recognizing the plexin-semaphoring-integrin (PSI) domain and PSI/epidermal growth factor 1 domain of β3 integrin, respectively. By contrast, type III anti-HPA-1a antibodies reacting with αvβ3 integrin did not induce platelet phagocytosis. Furthermore, effector-silenced mAbs against HPA-1a inhibited the phagocytosis of anti-HPA-1a opsonized platelets. In conclusion, WHOPPA is a reliable in vitro platelet phagocytosis assay that mimics the phagocytosis of anti-HPA-1a opsonized platelets in whole blood. This assay allows to prove platelet phagocytosis ex vivo and evaluate the inhibitory capacity of different inhibitors as therapeutically strategies for the prevention of fetal thrombocytopenia in FNAIT in the future.


Missing value imputation for physical activity data measured by accelerometer.
An accelerometer, a wearable motion sensor on the hip or wrist, is becoming a popular tool in clinical and epidemiological studies for measuring the physical activity. Such data provide a series of activity counts at every minute or even more often and displays a person's activity pattern throughout a day. Unfortunately, the collected data can include irregular missing intervals because of noncompliance of participants and therefore make the statistical analysis more challenging. The purpose of this study is to develop a novel imputation method to handle the multivariate count data, motivated by the accelerometer data structure. We specify the predictive distribution of the missing data with a mixture of zero-inflated Poisson and Log-normal distribution, which is shown to be effective to deal with the minute-by-minute autocorrelation as well as under- and over-dispersion of count data. The imputation is performed at the minute level and follows the principles of multiple imputation using a fully conditional specification with the chained algorithm. To facilitate the practical use of this method, we provide an R package accelmissing. Our method is demonstrated using 2003-2004 National Health and Nutrition Examination Survey data.


Fluctuations around equilibrium laws in ergodic continuous-time random walks.
We study occupation time statistics in ergodic continuous-time random walks. Under thermal detailed balance conditions, the average occupation time is given by the Boltzmann-Gibbs canonical law. But close to the nonergodic phase, the finite-time fluctuations around this mean are large and nontrivial. They exhibit dual time scaling and distribution laws: the infinite density of large fluctuations complements the Lévy-stable density of bulk fluctuations. Neither of the two should be interpreted as a stand-alone limiting law, as each has its own deficiency: the infinite density has an infinite norm (despite particle conservation), while the stable distribution has an infinite variance (although occupation times are bounded). These unphysical divergences are remedied by consistent use and interpretation of both formulas. Interestingly, while the system's canonical equilibrium laws naturally determine the mean occupation time of the ergodic motion, they also control the infinite and Lévy-stable densities of fluctuations. The duality of stable and infinite densities is in fact ubiquitous for these dynamics, as it concerns the time averages of general physical observables.


Revision Proximal Interphalangeal Arthroplasty: An Outcome Analysis of 75 Consecutive Cases.
To examine the outcomes and complications associated with revision proximal interphalangeal (PIP) joint arthroplasty. An analysis of 75 consecutive revision PIP joint arthroplasties in 49 patients, performed between 1998 to 2012, was performed. The mean age at the time of surgery was 58 years. Thirty-two patients had a history of prior PIP joint trauma, and 18 patients had rheumatoid arthritis. There were 12 constrained (silicone) implants and 63 nonconstrained implants (34 pyrocarbon and 29 metal-plastic). Over the 14-year period, 19 (25%) fingers underwent a second revision surgery. Second revision surgeries were performed for infection, instability, flexion contracture, and heterotopic ossification. The 2-, 5-, and 10-year survival rates were 80%, 70%, and 70%, respectively, for patients requiring a second revision for PIP joint arthroplasty. Worse outcomes were seen with postoperative dislocations, pyrocarbon implants, and when bone grafting was required. Two operations were complicated by intraoperative fractures, but neither required stabilization. Sixteen patients undergoing revision surgery experienced a postoperative complication, including 2 infections, 1 postoperative fracture, 3 cases of heterotopic ossification, and 10 PIP joint dislocations. The volar approach and the use of a pyrocarbon implant was associated with increased rates of heterotopic ossification, whereas preoperative instability increased the rates of PIP joint dislocation following revision. At a mean of 5.3 years (range, 2-10 years) follow-up, 98% of patients had good pain relief but decreased PIP joint total arc of motion. Proximal interphalangeal joint arthroplasty in the revision setting represents a challenge for surgeons. Revision arthroplasty was associated with a 70% 5-year survival but with a high incidence of complications. Instability was associated with worse outcomes. In this series, silicone and metal-polyethylene implants had lower rates of implant failure and postoperative complications than ones made from pyrocarbon.


Immunoregulatory activities of human trophoblasts mediated by polyamine complexes.
In a previous publication we described the presence in human placenta (HP) of immunosuppressive factors inhibiting the lymphoproliferative responses to mitogen. The results of further study reported herein indicate that the substance involved is of a syncytiotrophoblastic origin, that it is thermostable to 100 degrees C for 1 hr, and of low molecular weight, i.e. 3,500. It was defined as a polyamine conjugate with nucleic acids. Trophoblast cell extracts lost their immunosuppressive ability after heating in cultures of human lymphocytes supplemented with 5% autologous serum. These effects were, however, preserved both in cultures assayed in 5% fetal calf serum and in those to which purified polyamine oxidase (PAO) was added to autologous serum. Trophoblast cell extract was found to contain polyamine oxidases. Placental PAO can be inhibited by quinacrine a typical inhibitor of flavoprotein enzymes but not by isoniazid, an inhibitor of pyridoxal enzymes; this would suggest that the enzymes in human placenta are of a tissular rather than seric origin. The implication of these observations is that immunosuppression is mediated by oxidative products issued from an interaction between polyamine and polyamine oxidase in the syncytiotrophoblast cytosol. This interaction may constitute the basis for a local immunological barrier and may be involved in the protection of the fetus against maternal immune rejection.


The complete genome of klassevirus - a novel picornavirus in pediatric stool.
Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30-50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease. A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity suggests a novel picornavirus genus which we have designated klassevirus. Blinded screening of 751 stool specimens from both symptomatic and asymptomatic individuals revealed a second positive case of klassevirus infection, which was subsequently found to be from the index case's 11-month old twin. We report the discovery of human klassevirus 1, a member of a novel picornavirus genus, in stool from two infants from Northern California. Further characterization and epidemiological studies will be required to establish whether klasseviruses are significant causes of human infection.


Impact of illiteracy on depression symptomatology in community-dwelling older adults.
In many countries, illiteracy rates among aged people are quite high. However, only few studies have specifically investigated the impact of illiteracy on depression. Data for 1,890 elderly individuals (aged ≥65 years) were obtained from a nationwide dementia epidemiological study conducted in South Korea. Based on their reading ability, the participants were divided into three groups: totally illiterate, partially illiterate, and literate. The Korean version of the Geriatric Depression Scale - Short Form (SGDS-K) was used to detect depression (cut-off score = 8). Multivariate logistic regression analyses were used to assess the association between illiteracy and depression. To explore clinical features of depression in illiterate people, we performed logistic regression to calculate odds ratios of positive responses (or negative responses to reverse-coded items) for each SGDS-K item using literate individuals as the reference group. Totally illiterate participants had 2.41 times the odds and partially illiterate individuals had 1.59 times the odds of being depressed compared with literate participants after controlling for other variables. Compared with literate individuals, illiterate elderly persons were at increased odds for responding negatively to the majority of SGDS-K items, including "having memory problems," "others are better off than me," and "feeling worthless" even after controlling for various demographic and clinical factors. Illiteracy in elderly individuals was associated with a higher rate and increased severity of depression. Illiteracy negatively affected depression symptomatology, especially factors associated with self-esteem. Therefore, clinicians should carefully monitor for the presence of depression in illiterate elderly adults.


Experience of low volume split-dose bowel preparation for computed tomography colonography.
We propose a new preparation method for the computed tomography colonography (CTC). This method consists of giving a small volume (400 ml) of cleansing solution on the day before the examination and the same volume of solution on the day of the examination [low volume split-dose (LVSD) method]. Using this method, we compared the volume of residual fluid in the colon, the CT value of the residual fluid, and the quality of stool tagging with those for patients undergoing the conventional bowel preparation method. Polyp detectability of the CTC using this method and the acceptability of the preparation were also investigated. The volume of residual fluid in the colon with this method was smaller than that with the conventional method. The CT value of the residual fluid with this method was higher than that with the conventional method. Visual assessment of the quality of stool tagging with this method gave similar results to those obtained using the conventional method. The sensitivities were 95% for 5-10 mm polyps and 100% for polyps larger than 10 mm. The PPVs were 91% for 5-10 mm polyps and 100% for polyps larger than 10 mm. These results appear to be as good as in previous reports. In the questionnaires, about 80% of the answers were favorable regarding the volume and the taste of laxative. We conclude that LVSD bowel preparation method for CTC maintains polyp detectability and is better tolerated.


Association of CHA2 DS2 -VASc Score with Stroke, Thromboembolism, and Death in Hip Fracture Patients.
Patients undergoing hip fracture surgery have a 10 times increased risk of stroke compared with the general population. We aimed to evaluate the association between the CHA2 DS2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke/TIA [transient ischemic attack]/systemic embolism (2 points), vascular disease, age 65-74 years, and female sex) score and the risk of stroke, thromboembolism, and all-cause mortality in patients with hip fracture with or without atrial fibrillation (AF). Nationwide prospective cohort study. Danish hospitals. Subjects were all incident hip fracture patients in Denmark age 65 years and older with surgical repair procedures between 2004 and 2016 (n = 78,096). Participants were identified using the Danish Multidisciplinary Hip Fracture Registry. We calculated incidence rates, cumulative incidences, and hazard ratios (HRs) with 95% confidence intervals (CIs) by CHA2 DS2 -VASc score, stratified on AF history. The cumulative incidence of ischemic stroke 1 year after hip fracture increased with ascending CHA2 DS2 -VASc score, and it was 1.9% for patients with a score of 1 and 8.6% for patients with a score above 5 in the AF group. Corresponding incidences in the non-AF group were 1.6% and 7.6%. Compared with a CHA2 DS2 -VASc score of 1, adjusted HRs were 5.53 (95% CI = 1.37-22.24) among AF patients and 4.91 (95% CI = 3.40-7.10) among non-AF patients with a score above 5. A dose-response-like association was observed for all cardiovascular outcomes. All-cause mortality risks and HRs were substantially higher for all CHA2 DS2 -VASc scores above 1 in both the AF group and the non-AF group. Among patients with hip fracture, a higher CHA2 DS2 -VASc score was associated with increased risk of stroke, thromboembolism, and death. This finding applied both to patients with and without AF. Patients with high CHA2 DS2 -VASc scores had almost similar absolute risks for cardiovascular outcomes, irrespective of AF. J Am Geriatr Soc 68:1698-1705, 2020.


Blind integrity verification of medical images.
This work presents the first method of digital blind forensics within the medical imaging field with the objective to detect whether an image has been modified by some processing (e.g. filtering, lossy compression and so on). It compares two image features: the Histogram statistics of Reorganized Block-based Discrete cosine transform coefficients (HRBD), originally proposed for steganalysis purposes, and the Histogram statistics of Reorganized Block-based Tchebichef moments (HRBT). Both features serve as input of a set of SVM classifiers built in order to discriminate tampered images from original ones as well as to identify the nature of the global modification one image may have undergone. Performance evaluation, conducted in application to different medical image modalities, shows that these image features can help, independently or jointly, to blindly distinguish image processing or modifications with a detection rate greater than 70%. They also underline the complementarity of these features.