Bariatric surgery versus conventional medical therapy for type 2 diabetes.
Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed. In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy). At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group). In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; ClinicalTrials.gov number, NCT00888836.).


Multisecond periodicities in basal ganglia firing rates correlate with theta bursts in transcortical and hippocampal EEG.
Multisecond oscillations in firing rate with periods in the range of 2-60 s (mean, 20-35 s) are present in 50-90% of spike trains from basal ganglia neurons recorded from locally anesthetized, immobilized rats. To determine whether these periodic oscillations are associated with similar periodicities in cortical activity, transcortical electroencephalographic (EEG) activity was recorded in conjunction with single- or dual-unit neuronal activity in the subthalamic nucleus (STN) or the globus pallidus (GP), and the data were analyzed with spectral and wavelet analyses. Multisecond oscillations in firing rates of 31% of the STN neurons and 46% of the GP neurons with periodicities significantly correlated with bursts of theta (4-7 Hz) activity in transcortical EEG. Further recordings of localized field potentials in the hippocampus and frontal or parietal cortices simultaneously with GP unit activity showed field potentials from the hippocampus, but not from the frontal or parietal cortices, exhibited bursts of theta rhythm that were correlated with GP firing rate oscillations. These results demonstrate a functional connectivity between basal ganglia neuronal activity and theta band activity in the hippocampus.


Subdural hematoma of the brainstem in a dog: magnetic resonance findings and treatment.
An 8-year-old, spayed female Dalmatian with a history of seizures was evaluated for cervical pain and bilateral scleral hemorrhages. Diagnostic evaluations revealed a mass displacing the ventral brainstem on magnetic resonance imaging (MRI). The mass was surgically removed and histologically confirmed to be a hematoma. The dog's neurological signs resolved completely after surgery. Although extradural, subdural, subarachnoid, and intraparenchymal hemorrhages have been reported in dogs and cats, this is the first known report of a subdural hematoma of the ventral brainstem in a dog. On the basis of the history and the appearance of the subdural hematoma on MRI, a traumatic event during the seizure episodes was considered the most likely cause of the subdural hematoma in this case.


miR145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer.
ALDH1(+)CD44(+) cells are putative tumor-initiating cells (TIC) in head and neck squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various cancers but the breadth of its mechanistic contributions and potential therapeutic applications are not completely known. Here, we report that ALDH1(+)CD44(+)-HNC cells express reduced levels of miR145. SPONGE-mediated inhibition of miR-145 (Spg-miR145) was sufficient to drive tumor-initiating characteristics in non-TICs/ALDH1(-)CD44-negative HNC cells. Mechanistic analyses identified SOX9 and ADAM17 as two novel miR145 targets relevant to this process. miR-145 expression repressed TICs in HNC in a manner associated with SOX9 interaction with the ADAM17 promoter, thereby activating ADAM17 expression. Notably, the SOX9/ADAM17 axis dominated the TIC-inducing activity of miR-145. Either miR-145 suppression or ADAM17 overexpression in non-TICs/ALDH1(-)CD44(-)-HNC cells increased expression and secretion of interleukin (IL)-6 and soluble-IL-6 receptor (sIL-6R). Conversely, conditioned medium from Spg-miR145-transfected non-TICs/ALDH1(-)CD44(-)-HNC cells was sufficient to confer tumor-initiating properties in non-TICs/ALDH1(-)CD44(-)-HNC and this effect could be abrogated by an IL-6-neutralizing antibody. We found that curcumin administration increased miR-145 promoter activity, thereby decreasing SOX9/ADAM17 expression and eliminating TICs in HNC cell populations. Delivery of lentivral-miR145 or orally administered curcumin blocked tumor progression in HNC-TICs in murine xenotransplant assays. Finally, immunohistochemical analyses of patient specimens confirmed that an miR-145(low)/SOX9(high)/ADAM17(high) phenotype correlated with poor survival. Collectively, our results show how miR-145 targets the SOX9/ADAM17 axis to regulate TIC properties in HNC, and how altering this pathway may partly explain the anticancer effects of curcumin. By inhibiting IL-6 and sIL-6R as downstream effector cytokines in this pathway, miR-145 seems to suppress a paracrine signaling pathway in the tumor microenvironment that is vital to maintain TICs in HNC.


Cardiovascular responses to handgrip isometric exercise in patients following cardiac transplantation.
The effects of cardiac denervation on the hemodynamic responses to isometric handgrip contraction were studied in patients 1--5 years after allograft cardiac transplantation. The objective of these studies was to determine the role of cardioacceleration and myocardial contractility on the increase in systemic arterial pressure during isometric exercise. Initially, noninvasive measurement of brachial artery pressure and heart rate during 60 seconds of isometric exercise at 50% of maximal voluntary contraction (50% MVC) were recorded in 23 cardiac transplant patients, 18 ischemic heart disease patients, and 15 healthy controls. While the increases in arterial pressure were not significantly different among the three groups and the heart rate response for the healthy controls and ischemic heart disease patients were similar, the transplant patient's heart rate remained essentially unchanged. In an attempt to determine the mechanisms for the increase in arterial pressure, despite any increase in heart rate in transplant patients, we recorded left ventricular volumes before and at the end of 50% MVC using fluoroscopy of tantalum midwall myocardial markers in seven cardiac transplant recipients and seven nontransplant cardiac surgery patients. The rise in arterial pressure during isometric exercise in both groups of patients resulted from a significant increase in peripheral vascular resistance but not in stroke volume or cardiac output. These data demonstrate that the rise in arterial pressure observed during isometric exercise can be achieved by increased peripheral vascular resistance alone in patients who lack the capacity to increase heart rate or stroke volume.


Occurrence and antimicrobial resistance of Salmonella strains from food of animal origin in southern Italy.
Six hundred fourteen strains of Salmonella enterica were isolated from 16,926 samples of food of animal origin collected in southern Italy from 2003 to 2012. The isolates were identified, serotyped, and challenged against 15 antibiotics according to the protocol defined at national level for veterinary isolates of Salmonella (EnterVet surveillance network). Salmonella serotypes Typhimurium, Hadar, Enteritidis, Derby, and 4,[5],12:i:- were those most frequently isolated. The widest resistances were recorded towards sulfonamides (69 % of the isolates), trimethoprim-sulfamethoxazole (52 % of the isolates), and tetracycline (51 % of the isolates). The rate of multidrug resistance of the isolates decreased significantly from the first 5 years of the study period (82.6 %) to the last 5 years (54.3 %).


Dissecting aneurysm of the petrous portion of the internal carotid artery. Case report and review of previous cases.
A "spontaneous" dissecting aneurysm of the petrous portion of the right internal cartoid artery in a 60 year old man was demonstrated angiographically. It showed a typical double lumen which is rarely demonstrated by angiography. It was probably of atherosclerotic origin. In addition, a survey of the positions and angiographic characteristics of the 29 traumatic and "spontaneous" dissecting aneurysms of the common and internal carotid arteries found in the literature is presented.


Chromosome changes connect immunodeficiency and cancer in ataxia-telangiectasia.
Ataxia-telangiectasia (AT) is a primary genetic immunodeficiency disease predisposing to cancer. Approximately 40% of patients with AT develop malignancy, usually of the lymphoid system. Increased chromosome breakage in AT leads to rearrangements such as translocations and inversions. The preferred chromosome breakpoints in AT involve genes in the immune system: the immunoglobulin (Ig) gene loci in chromosome bands 2p12, 14q32, and 22q11 and the T cell receptor (TCR) gene loci in chromosome bands 7p13, 7q35, and 14q11. Identical chromosome breakpoints are observed in chromosome rearrangements in normal T cells, Burkitt's lymphoma, and adult T cell leukemia. Molecular analysis of these chromosome rearrangements reveals recombination between an oncogene and Ig or between Ig and TCR. In AT, chromosome rearrangements connect the immune system to lymphoid cancer.


A Rorschach study of oral dependence in alcoholics and depressives.
Despite the strong association between alcoholism and orality in psychoanalytic theory, use of the Rorschach Inkblot Test to provide empirical support for such a link has yielded decidedly mixed results. However, Masling's Rorschach Oral-Dependency (ROD) scale has shown twice that people with alcoholism give more oral-dependent responses on the Rorschach than matched comparison groups (Bertrand & Masling, 1969; Weiss & Masling, 1970), which is supportive of classical analytic theory. In this study, we investigated alcohol groups, depression groups, and "normal" undergraduates with the ROD scale and found that the 2 clinical groups produced higher ROD scores than the undergraduates. In addition, recent studies by Duberstein and Talbot (1993) and Fowler, Hilsenroth, and Handler (1996) provide evidence for an object relations model of dependency that suggests that a balance between anaclitic dependence and complete independence, in which dependency needs are acknowledged but are not overwhelming, is most adaptive. This model of dependency was evaluated; it was found that a simple difference in group means provided a better fit with the data, although some evidence of an object relations model also was found. Finally, Rorschach and MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) levels of general defensiveness and primary process manifestations in Rorschach content were investigated to assess whether participants were responding defensively to the testing and whether there were any differences in the nature of oral-dependent responses between the clinical groups.


Analysis of Replicating Mitochondrial DNA by In Organello Labeling and Two-Dimensional Agarose Gel Electrophoresis.
Our understanding of the mechanisms of DNA replication in a broad range of organisms and viruses has benefited from the application of two-dimensional agarose gel electrophoresis (2D-AGE). The method resolves DNA molecules on the basis of size and shape and is technically straightforward. 2D-AGE sparked controversy in the field of mitochondria when it revealed replicating molecules with lengthy tracts of RNA, a phenomenon never before reported in nature. More recently, radioisotope labeling of the DNA in the mitochondria has been coupled with 2D-AGE. In its first application, this procedure helped to delineate the "bootlace mechanism of mitochondrial DNA replication," in which processed mitochondrial transcripts are hybridized to the lagging strand template at the replication fork as the leading DNA strand is synthesized. This chapter provides details of the method, how it has been applied to date and concludes with some potential future applications of the technique.


[Treatment of rheumatoid arthritis with the immunosuppresive agent, prorezid].
Prorezid treatment was applied to 30 patients with rheumatoid arthritis. It was applied per os with a daily dose of 300 mg to 12 subjects; to 18-intravenous drop infusion with 5 per cent serum glucose--daily dose 400 mg. Oral administration total dose-7-8 g; infusion-10-12 g. Drop infusion administration proved to be more effective and especially the combination of the preparation with salycilates, pirazolon derivatives, minimal doses of corticosteroids and antibiotics. Favourable effect on articular syndrome was obtained in 20 patients (66.6%) about 2-3 and sometimes 4-6 weeks after the onset of the treatment. First the articular pain was attenuated, latter on--the morning stiffness (3-4 week), the movements in the joints involved were improved, the edema decreased towards the 4-6th weeks. A complete normalization of the laboratory indices was observed in none of those patients. In 10 of the patients (33.3%) no clinical improvement was attained in the course of the treatment. In four of them--the improvement developed 4-6 months later, with a longer drug administration. Prorezid preparation is with a low toxicity, with manifestation of transitory side effects in single patients--diarrhoea, mild leukopenia. Alopecia was not observed. Those properties make the drug suitable for application in patients with rheumatoid arthritis whose treatment with the rest applied drugs failed to give results.


Race and gender disparities in rates of cardiac revascularization: do they reflect appropriate use of procedures or problems in quality of care?
Numerous studies have documented substantial differences by race and gender in the use of coronary artery bypass graft surgery and percutaneous coronary angioplasty. However, few studies have examined whether these differences reflect problems in quality of care. We selected a random sample stratified by gender, race, and income of 5026 Medicare beneficiaries aged 65 to 75 who underwent inpatient coronary angiography during 1991 to 1992 in 1 of 5 states. We compared the frequency of 2 problems in quality by race and gender: underuse or the failure to receive a clinically indicated revascularization procedure and receipt of revascularization when it was not clinically indicated. We used 2 independent sets of criteria developed by the RAND Corporation and the American College of Cardiology/American Hospital Association (ACC/AHA). We also examined survival of the cohort through March 31, 1994. Revascularization procedures were clinically indicated more frequently among whites than blacks and among men than women. Failure to receive revascularization when it was indicated was more common among blacks than among whites (40% vs. 23-24%, depending on the criteria, both P<0.001) but similar among men and women (25% vs. 22-24%, P>0.05). Racial disparities remained similar after adjusting for patient and hospital characteristics. Among patients rated inappropriate, use of procedures was greater for whites than blacks using RAND criteria (10.5% vs. 5.8%, P<0.01) and greater for men than for women (14.2% vs. 5.3% by RAND criteria, P=0.001; 8.2% vs. 4.0%% by ACC/AHA criteria, P=0.04). After multivariate adjustment, the disparities for race and gender remained similar and were statistically significant using RAND criteria. Mortality rates tended to validate our appropriateness criteria for underuse. Racial differences in procedure use reflect higher rates of clinical appropriateness among whites, greater underuse among blacks, and more frequent revascularization when it was not clinically indicated among whites. Underuse is associated with higher mortality. In contrast, men had higher rates of clinical appropriateness and were more likely to receive revascularization when it was not clinically indicated. There was no evidence of greater underuse among women.


Intracellular sodium, membrane potential, and contractility of rat mesenteric small arteries.
We have investigated effects of altered extracellular sodium, intracellular sodium concentration, and membrane potential on the contractile responses of rat isolated mesenteric small arteries (internal diameter ca. 200 microns), when mounted as ring preparations on an isometric myograph. To avoid possible neural effects, all vessels were denervated in vitro using 6-hydroxydopamine. In unstimulated vessels, exposure to low-Na+ solutions (25 mM sodium, sucrose, or choline-substituted) did not cause any response nor did exposure to ouabain (1 mM) for 1 hour [when intracellular sodium concentration increased to 64 mmol/(liter-cell)]. However, a response was obtained if ouabain-exposed vessels were subjected to low-sodium solutions (ca. 15% of maximal response). The magnitude of the response was dependent on the ratio of intracellular to extracellular sodium and was not inhibitable by the calcium blockers, felodipine (1 nM) or D600 (10 microM). This response could therefore be explained in terms of Na-Ca exchange mechanism. The responses of activated vessels to ouabain and to low-sodium solutions were also investigated. The responses of vessels to submaximal doses of noradrenaline or potassium were potentiated acutely by ouabain (by 10-30% of the maximal response), even if the extracellular sodium was reduced to 25 mM. In all cases, the potentiation by ouabain was accompanied by a depolarization (3-12 mV). However, only in the case of noradrenaline-activated vessels with normal extracellular sodium was the potentiation accompanied by an increase in intracellular sodium [by ca. 7 mmol/(liter-cell)]. Moreover, the latter response was inhibited by felodipine and D600. The results suggest that Na-Ca exchange mechanisms may be present in these vessels but that they only play a role under extreme conditions; under normal conditions the effect of ouabain on activated vessels seems to be primarily due to its depolarizing effect, and not to its effect on intracellular sodium.


[ICO-35 monoclonal antibodies to the antigen of acute lymphoblastic leukemia].
ICO-35 monoclonal antibodies (Mabs) were produced following BALB/c mouse immunization with peripheral blood cells from a patient with lymphoid type of chronic myeloid leukemia in blast crisis (SML BC) ICO-35. Mabs detect antigen on CD10-positive cells from patients with acute lymphoblastic leukemia, CML BC, CD10-positive cells of Reh line and are not bound to other cells. Comparative studies of reactivity of ICO-35 and K 503 Mabs to CD10 antigen revealed their similarity. However, in contrast to K503 ICO-35 Mabs do not react with granulocytes.


Fas ligand expression in esophageal carcinomas and their lymph node metastases.
Although esophageal adenocarcinomas (EADCA) have been shown to have substantially reduced or absent Fas expression, the status of Fas ligand (FasL) in these tumors, especially adenocarcinomas, is largely unknown. Using immunohistochemistry, the authors investigated FasL expression in sections of formalin fixed, paraffin embedded tissue from 13 EADCA. They also studied sections of 15 esophageal squamous cell carcinomas (ESCCA) and of lymph node metastases from 7 EADCA and 4 ESCCA. The percentage of FasL positive cells in each tumor was recorded. FasL expression in EADCA was compared with that in ESCCA and with lymph node status. Statistical analysis was performed using the Fisher exact test. No specific staining pattern was seen in adenocarcinomas. In ESCCA, FasL was often located in the cells at the periphery of tumor nests. All (100%) of EADCA showed FasL expression in greater than 25% of the cancer cells, and all were associated with lymph node metastasis. Fifty-three percent of ESCCA showed FasL expression in greater than 25% of the cancer cells and 33% had lymph node metastasis. Expression of FasL in greater than 25% of tumor cells was associated with a significantly higher incidence of lymph node metastasis (P=0.0001). All lymph node metastases from esophageal carcinomas showed FasL immunoreactivity in greater than 50% of the metastatic tumor cells. FasL expression in greater than 25% of cancer cells correlates with a high incidence of lymph node metastasis in esophageal carcinomas. All cancer metastases in lymph nodes express FasL in >50% of the cells. These findings indicate that FasL plays an important role in the immune evasion and metastasis of esophageal carcinomas.


Endoscopic carpal tunnel release. Chow technique.
The first cases using the set of instruments designed by James C. Y. Chow, MD, of Mount Vernon, Illinois, were performed in September of 1987 by the developer. His was the first written introduction of the technique of endoscopically assisted carpal tunnel release published by a US author. This technique has been practiced widely for 5 years. Serious complications can occur but may be avoidable.


Genetic diversity and population differentiation of chestnut blight fungus, Cryphonectria parasitica, in China as revealed by RAPD.
Seventeen Cryphonectria parasitica populations sampled from six regions in China were investigated using RAPD. Across all 169 isolates from the 17 populations evaluated, 52 of the 71 markers (73%) were polymorphic, total genetic diversity (h) was 0.1463, and Shannon's index was 0.2312. Diversity within populations accounted for 74% of total genetic diversity, and genetic differentiation among populations was 0.26 (G (ST) = 0.26). Gene flow was 1.4 among the populations; higher gene flow was found among populations within regions and among regions [N (m) (G (SR)) = 2.8 and N (m) (G (RT)) = 3.5]. The unweighted pair group mean analysis (UPGMA) dendrogram revealed two distinct clusters: the northern China group and the southern China group. The spatial autocorrelation analysis revealed that the variation at most loci was randomly distributed and lacked spatial structure, but several loci and closer distances were spatially structured. Human activity and habitat could also be important factors affecting genetic structure among C. parasitica populations in China. Genetic diversity was highest in Southwest China, descending in an orderly fashion to Northeast China. This pattern indicated that Southwest China might be the center of origin of C. parasitica in China. The present study provides useful information for understanding the origin and spread of chestnut blight fungus in China and valuable data for formulating relevant strategies for controlling the disease in China.


The use of polyclonal activators in the production of murine monoclonal and polyclonal antibodies.
We propose a new immunization method to stimulate a strong immune response against weak or diluted antigens. This technique is based on stimulation with polyclonal activators before exposure to the antigens. We also discuss the efficiency of various types of mitogen with particular regard to their capacity to produce monoclonal antibodies and serum antibodies. A specific immune response against soluble antigens is increased by pretreating mice with PPD. This preactivation permitted us to obtain monoclonal antibodies against weak antigens in a few days. No monoclonal antibodies were obtained by inoculating weak antigens or the activators by themselves.


HLA nomenclature and the IMGT/HLA sequence database.
Early in their study it was recognized that the genes encoding the HLA molecules were highly polymorphic and that there was a need for a systematic nomenclature. The result was the WHO Nomenclature Committee for Factors of the HLA System, which first met in 1968, and laid down the criteria for successive meetings. This committee meets regularly to discuss issues of nomenclature and has published 16 major reports documenting firstly the HLA antigens and more recently the genes and alleles. The standardization of HLA antigenic specificities has been controlled by the exchange of typing reagents and cells in the International Histocompatibility Workshops. Since 1989 when a large number of HLA allele sequences were first analysed and named, the job of curating and maintaining a database of sequences has been of prime importance. In 1998 the IMGT/HLA database became the official repository for HLA sequences. In addition to the nucleotide and protein sequences the database contains information of the cell from which the sequence was obtained. The database which provides tools for sequence analysis and the submission of new data, is updated quarterly and now contains over 1500 HLA allele sequences.


Molecular cloning and characterization of the gene encoding rat submandibular gland apomucin, Mucsmg.
Mucin glycoproteins are a major constituent of salivary secretions and play a primary role in the protection of the oral cavity. Rat submandibular glands (RSMG) synthesize and secrete a low molecular weight (114 kDa) mucin glycoprotein. We have isolated, partially sequenced, and characterized the gene which encodes the RSMG apomucin. The gene is encoded by three exons of 106 nt, 69 nt, and 991 nt, separated by introns of 921 nt and 12.5 kb. CAAT and TATA elements are present, at -68 and -26, respectively, in the 5' flanking sequence of the RSMG apomucin gene. The tandem repeat domain present in exon III consists of ten tandem repeats of 39 nt encoding the consensus sequence PTTDSTTPAPTTK. Sequence comparison and organization of the nucleic acid sequence encoding the tandem repeats of two alleles for this gene suggests that the apomucin gene has undergone recombinational events during its evolution. No significant sequence similarity was found with other mucin genes, or with other known salivary gland-specific genes. The gene was localized to rat chromosome 14 using somatic cell hybrids that segregate rat chromosomes. Since this, to our knowledge, represents the first RSMG mucin gene cloned, we have designated this gene Mucsmg.


Snore sound recognition: On wavelets and classifiers from deep nets to kernels.
In this paper, we present a comprehensive comparison of wavelet features for the classification of snore sounds. Wavelet features have proven to be efficient in our previous work; however, the benefits of wavelet transform energy (WTE) and wavelet packet transform energy (WPTE) features were not clearly established. In this study, we firstly present our updated snore sounds database, expanded from 24 patients (collected by one medical centre) to 40 patients (collected by three medical centres). We then study the effects of varying frame sizes and overlaps for extraction of the wavelet low-level descriptors, the effect of which have yet to be fully established. We also compare the performance of the WTE and WPTE features when fed into multiple classifiers, namely, Support Vector Machines (SVM), K-Nearest Neighbours, Linear Discriminant Analysis, Random Forests, Extreme Learning Machines, Kernel Extreme Learning Machines, Multilayer Perceptron, and Deep Neural Networks. Key results presented indicate that, when fed into a SVM, WTE outperforms WPTE (one-tailed z-test, p<;0.002). Further, WPTE can achieve a significant improvement when trained by a k-nearest neighbours classifier (one-tailed z-test, p <; 0.001).


Phylogeny of haemosporidian blood parasites revealed by a multi-gene approach.
The apicomplexan order Haemosporida is a clade of unicellular blood parasites that infect a variety of reptilian, avian and mammalian hosts. Among them are the agents of human malaria, parasites of the genus Plasmodium, which pose a major threat to human health. Illuminating the evolutionary history of Haemosporida may help us in understanding their enormous biological diversity, as well as tracing the multiple host switches and associated acquisitions of novel life-history traits. However, the deep-level phylogenetic relationships among major haemosporidian clades have remained enigmatic because the datasets employed in phylogenetic analyses were severely limited in either gene coverage or taxon sampling. Using a PCR-based approach that employs a novel set of primers, we sequenced fragments of 21 nuclear genes from seven haemosporidian parasites of the genera Leucocytozoon, Haemoproteus, Parahaemoproteus, Polychromophilus and Plasmodium. After addition of genomic data from 25 apicomplexan species, the unreduced alignment comprised 20,580 bp from 32 species. Phylogenetic analyses were performed based on nucleotide, codon and amino acid data employing Bayesian inference, maximum likelihood and maximum parsimony. All analyses resulted in highly congruent topologies. We found consistent support for a basal position of Leucocytozoon within Haemosporida. In contrast to all previous studies, we recovered a sister group relationship between the genera Polychromophilus and Plasmodium. Within Plasmodium, the sauropsid and mammal-infecting lineages were recovered as sister clades. Support for these relationships was high in nearly all trees, revealing a novel phylogeny of Haemosporida, which is robust to the choice of the outgroup and the method of tree inference.


[Arterial blood pressure and arterial stiffness in adolescents are related to gestational age].
Recent studies show that low birth weight (LBW) infants are at risk of increased arterial blood pressure (BP) in adulthood. Previous work from our centre and others suggests that arterial stiffness (AS) is increased in such patients. However, the respective roles of preterm birth and of intrauterine growth restriction (IUGR) are unclear. To characterize AS and BP in adolescents who were: born at term with an appropriate birth weight for gestational age (GA) (group 1, n=41); born preterm with an appropriate birth weight for GA (group 2, n=25); born at term and small for GA (group 3, n=24). Systemic BP was measured with an automated oscillometric device. AS was assessed by measuring pulse wave velocity (PWV) between carotid and radial arteries. 90 adolescents were studied at a mean (SD) age of 13.9 (1.2) years. Subjects from group 2 were born with a 33.6 (1.5) GA. Systolic BP, mean BP, and PWV were significantly increased in group 2 subjects in comparison to both group 1 (123 +/- 11 vs. 117 +/- 11 mmHg, p = 0.04; 88 +/- 7 vs. 83 +/- 7 mmHg, p = 0.03; 7.7 +/- 1.0 vs. 7.0 +/- 0.9 m/s, p = 0.02 respectively) and to group 3 (114 +/- 15 mmHg, p = 0.03: 79 +/- 8 mmHg, p = 0.001; 6.8 +/- 0.9 m/s, p = 0.005 respectively) subjects. Systolic BP, mean BP, and PWV were similar in group 1 and group 3 subjects. BP and AS are increased during adolescence in subjects born with a LBW due to preterm birth, while they are not altered in subjects when LBW is related to IUGR. It may be speculated that such changes predispose to long term hypertension and that preterm birth is involved in the early programming of arterial diseases in adulthood.


Identification and function of A1 adenosine receptors in normal and cystic fibrosis human airway epithelial cells.
A role for adenosine in the regulation of ion transport in pulmonary epithelial cells has recently been proposed. Although evidence exists documenting the presence and function of adenosine A2 receptors in airway epithelia, the presence of adenosine A1 receptors remains controversial. The present study used reverse transcriptase-polymerase chain reaction (PCR) and whole cell patch-clamp analysis to investigate A1 receptor presence and function in normal and cystic fibrosis (CF) human airway epithelial cells. Oligonucleotide primers complementary to the human brain A1 receptor sequence generated a PCR product of the predicted size (311 bp) in normal tracheal (9HTEo-) and CF submucosal (2CFSMEo-) airway cell lines and in primary cultures of CF nasal polyp epithelial cells. An oligonucleotide probe internal to the PCR primers hybridized with the 311-bp cDNAs by Southern blot analysis. cDNA sequencing demonstrated that the normal and CF airway cell PCR products are 100% identical to the corresponding sequence of the human brain adenosine A1 receptor. Northern blot analysis of 9HTEo-and 2CFSMEo- poly(A)+ RNA revealed the presence of two bands of approximately 3.0 and approximately 5.5 kb corresponding to the A1 receptor. Whole cell patch-clamp analyses demonstrated that 8-cyclopentyl-1,3-dipropylxanthine, a specific A1 receptor antagonist, increases adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- conductance in 9HTEo-airway cells and allows cAMP to increase Cl- conductance in 2CFSMEo- CF airway cells and CF nasal polyp epithelial cells in primary culture. These results provide evidence for the presence and function of A1 receptors in normal and CF airway epithelial cells and provide support for a role of adenosine A1 receptors in modulating airway epithelial cell Cl- transport.


Interval cancers in the Antwerp European randomised study of screening for prostate cancer study, using a 6 year screening interval.
The European randomised study of screening for prostate cancer (ERSPC) was initiated to evaluate the effect of Prostate Specific Antigen (PSA) screening on prostate cancer mortality. Variations in screening modalities between participating centres, such as the interval between screening rounds are likely to affect the outcome of screening. The study describes the number and characteristics of interval cancers in men in the screening arm of the Antwerp ERSPC aged 55-65 years at the time of randomisation and participating in the screening rounds they were invited for. The interval between the first screening rounds was 6 years on average. Interval cancers were defined as cancers diagnosed during the screening interval but not detected by screening. Cases with a positive screening test were considered as interval cancers if diagnosis through biopsy occurred more than 1 year after screening. Interval cancer cases were identified through linkage with cancer registries. Aggressive interval cancer was defined as cancer with at least one of the following characteristics: stage M1 or N1, Gleason score higher than 7 or World Health Organisation (WHO) score of 3. The 10 year cumulative incidence of interval cancers was 3.0% (n=50) and the cumulative incidence of aggressive interval cancers was 0.5% (n=8). During the first screening interval 36 interval cancers were detected. Of these 20 (55.6%) were detected more than 4 years after the initial screening and 5 (13.9%) were considered aggressive. All aggressive interval cancers emerged more than 4 years after initial screening. The occurrence of interval cancers in this study was higher than in the ERSPC centres that used a shorter screening interval. Aggressive interval cancers only started to emerge 4 years after initial screening.


Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients.
Parturients with heavy vaginal colonization of group B streptococci were selected randomly to receive either penicillin or no antibiotic. A simple and fast latex agglutination test, applied in 8977 consecutive parturients, detected 412 women with heavy colonization with group B streptococcus, 199 of whom were eligible for the study. The offspring of penicillin-treated women had a lower incidence of early-onset group B streptococcal disease (1.1%; 95% confidence interval 0-3.4%) than the controls (9.0%; 95% confidence interval 3.6--14.4%) (P less than .01). Among the offspring of streptolatex-negative parturients, the incidence of streptococcal disease was very low (0.07%). Thus, antibiotic prophylaxis of latex agglutination test-positive parturients would reduce the total incidence of group B streptococcal disease in the newborn by 25-80%.


Decreased expression of aortic KIR6.1 and SUR2B in hypertension does not correlate with changes in the functional role of K(ATP) channels.
ATP-dependent potassium (K(ATP)) channels are the target of multiple vasoactive factors and drugs. Changes in the functional role of ATP-dependent (K(ATP)) potassium channels in hypertension are controversial. The aim of the present study was to analyze the possible changes of ATP-sensitive potassium channels (K(ATP)) expression and function during hypertension. For this purpose, we used endothelium-denuded aorta segments from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) to analyze the 1) expression of K(ATP) subunits Kir6.1, Kir6.2 and SUR2B by immunohistochemistry and Western blot, 2) the K(ATP) currents recorded in the whole cell configuration of the patch-clamp technique and 3) the vasodilator response to the K(ATP) channel openers, pinacidil and cromakalim. Kir6.1 and SUR2B were expressed in the medial layer of the aorta from WKY rats and SHR rats, while Kir6.2 was not detected in aorta from either strain. Kir6.1 and SUR2B expression were decreased in hypertension. However, the vasodilator responses of pinacidil and cromakalim were similar in WKY rats and SHR rats. Moreover, pinacidil induced increase in K+ currents was also similar in WKY rats and SHR rats and also similarly inhibited by glybenclamide. Our data demonstrate for the first time direct evidence of decreased aortic Kir6.1/SUR2B subunit expression in hypertension, but preserved functional responses to K(ATP) channel openers.


The prevention of pregnancy-related venous thromboembolism.
Pregnancy-related venous thromboembolism (VTE) remains one of the leading causes of maternal mortality and morbidity in the developed world. There is a lack of high-level data surrounding the use of thromboprophylaxis in pregnancy. In the UK, following the publication of the first Royal College of Obstetricians and Gynaecologists (RCOG) guideline for VTE prophylaxis during pregnancy and the puerperium in 2004, a fall in maternal deaths secondary to VTE was observed during the subsequent triennium (2006-2008). For the first time since 1985, VTE was no longer the most common cause of maternal death. Low-molecular-weight-heparin (LMWH) is generally the agent of choice for thromboprophylaxis in this setting, and is considered safe and efficacious. The accurate risk stratification of women in order to allow the targeted provision of thromboprophylaxis is challenging. A number of international guidelines support risk assessment for pregnancy-related VTE and the provision of LMWH for those who are deemed at sufficiently high risk. This review describes the importance of VTE in pregnancy and the puerperium, the part played by different risk factors and the role of thromboprophylaxis in this group of patients.


Canine awake head-out plethysmography (HOP): characterization of external resistive loading and spontaneous laryngeal paralysis.
We applied a novel head-out plethysmographic (HOP) method to study awake canine responses to external resistive loading and natural laryngeal paralysis. Measurements of inspiratory and expiratory specific airway resistance (sRaw(insp), sRaw(exp)) were obtained before and after uni- and bidirectional loading (R(add) = 5 cmH(2)O/L/s) in large-breed dogs (n = 9). Mean sRaw(insp) after inspiratory, and sRaw(exp) after expiratory loading were 31.4 and 33.3 cmH(2)Os, respectively. Bidirectional loads induced a significantly greater rise in both sRaw(insp) and sRaw(exp) (55.1 and 61.3 cmH(2)Os) compared to unidirectional loading (P < 0.001). Yet, type of loading did not affect flow-volume indices. The mean R(aw) of dogs was 4.81 cmH(2)O/L/s. Expiratory loading resulted in a significant 8.8% increase in functional-residual-capacity (FRC), compared to FRC(baseline) (76.7 ml/kg). Dogs (n = 5) with laryngeal paralysis demonstrated a significant increase in sR(aw) and R(aw) compared to controls without changes in FRC. In conclusion, HOP precisely characterized sR(aw) in response to external resistive loading. Hence, we could accurately quantify airway obstruction in awake dogs with laryngeal paralysis.


Synthesis and antitumor activity of cyclopentadienyltitanium substituted polyoxotungstate [CoW11O39(CpTi)]7- (Cp=eta5-C5H5).
A novel polyoxotungstate [CoW(11)O(39)(CpTi)](7-) (Cp=eta(5)-C(5)H(5)) has been prepared. This complex exhibits the highest antitumor activity in vitro among the cyclopentadienyltitanium substituted polyoxometalates investigated and has a remarkable inhibitory action on three types of human cancer cells, SSMC-7721, HL-60 and HLC, in vivo.


Migrated Hickman catheters: a simple repositioning method using a stiff hydrophilic guidewire.
We present a simple guidewire insertion technique and a new way of prepping for the procedure for readvancement of partially retracted Hickman catheters with the aid of a stiff hydrophilic guidewire.


Lipid polymorphism.
The phase behavior of phospholipids may be monitored using 31P or 2H NMR techniques, which provide information concerning the motional properties of the lipid ensemble, which may then be correlated with structure. The lamellar/nonlamellar phase preferences of many lipids, either synthetic or naturally derived, may be controlled by factors such as variation in temperature, hydration, or of greater physiological relevance, pH, ionic strength, the presence of divalent cations such as calcium, or the presence of lipid soluble agents as anesthetics and alcohols. The ability of short-chain alcohols to stabilize a bilayer structure for egg PE may be rationalized in terms of the packing of lipids whose dynamic shapes are complementary, as illustrated in Figure 11. On the basis, short-chain alcohols would partition preferentially at the membrane/water interface and would thereby stabilize a lamellar structure. Larger-chain alcohols may partition deeper into the hydrophobic acyl chain region in order to minimize hydrocarbon/water contact and so may perturb the acyl chain packing, increasing the effective swept volume of the chains and so promoting hexagonal HII phase formation.


The dilemma of civil rights versus the right to treatment: questionable involuntary admissions to a mental hospital.
Admission to a close ward was analyzed at the Department of Psychiatry, University of Oulu using 888 patients and their 1861 assessment and treatment episodes. Of all referrals for involuntary assessment (n = 237, 12.7% of all episodes) a total of 44 (2.4%) used "questionable" juridical criteria: the final diagnosis was not psychosis. In the follow-up, the admission of the questionable patients was mainly considered a clinical necessity, and at least one third of them were diagnosed as being psychotic and 2 committed suicide. An elevated probability of belonging to the questionable group was seen among patients in their first treatment episode, with minimal professional education, female sex, short treatment time, or residence in a rural area. The result suggests that some inequality existed between women and men, less and more educated and residents of urban and rural areas. The results also reflect conflict between the ethics and clinical practice of involuntary commitment, and the phrasing of the law, especially its diagnostic limitation to psychotic states only.


[Scintigraphic study for the diagnosis of portosystemic shunts in dogs].
The technique of scintigraphy of the liver is presented by two case examples of dogs with portosystemic shunts. 99mtechnetium-pertechnetate was used as a marker. Comparison of velocity and height of the activity reaching liver and heart and lung allows a statement about the existence of a portosystemic shunt.


Infected total hip arthroplasty due to Actinomyces israelii after dental extraction. A case report.
Late infection of a total hip arthroplasty after dental extraction has been reported, but never with an organism that is found exclusively in mouth flora. Actinomyces israelii is an organism responsible for dental caries. A 61-year-old woman developed an infected total hip arthroplasty after dental work. She denies ever being instructed to take prophylactic antibiotics by her orthopedic surgeon, by her internist, or by her dentist. Considering the extensive morbidity and potential mortality of an infected hip prosthesis, it is essential that all physicians are aware of the indications for antibiotic prophylaxis following joint arthroplasty. Recommendations for antibiotic prophylaxis for dental manipulation are a loading dose of 2.0 g of penicillin V orally or 1.2 million U of aqueous procaine penicillin G with 1.0 gram of streptomycin given intramuscularly 30 minutes before dental work, followed by four doses of 0.5 g of penicillin V orally every six hours.


Automating phase singularity localization in mathematical models of cardiac tissue dynamics.
Electrical wave-fronts are responsible for contraction in heart tissue. Rotary wave-fronts break up into daughter waves and it is this break up that is believed to underlie ventricular fibrillation. Mathematical methods abound for simulation of fibrillation, and localizing the core of rotary wave-fronts (the phase singularities) is key to characterizing the state of fibrillation and effectiveness of defibrillation in these models. We present a formal method for automating this process in these various models. Automation will allow for side-by-side comparisons of suggested mechanisms of fibrillation, comparison of various models of these mechanisms and faster evaluation of defibrillation strategies making use of these models.


Synthesis of benzocyclobutenes by palladium-catalyzed C-H activation of methyl groups: method and mechanistic study.
An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C-H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc) 2 and P ( t )Bu 3 as catalyst, K 2CO 3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44-92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this "abnormal" regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(P ( t )Bu 3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C-H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain kappa (1)-coordination without extensive electronic reorganization.


'Keep the patient at the centre of everything you do'.
What is your job? I am nurse consultant for older people in acute care at NHS Fife in Scotland, where I lead on improving care, transitions and experience and service transformation. I am also national clinical lead for older people at Healthcare Improvement Scotland (HIS).


Validation of a new scale to assess olfactory dysfunction in patients with Parkinson's disease.
BAKCKGROUND: Olfactory dysfunction is present in up to 90% of Parkinson's disease (PD) patients. It is usually evaluated by means of objective standardized tests; however no self-administered scales have been developed for olfactory dysfunction bedside assessment. We present validation of a new scale to assess this symptom in PD patients. Seventy-five PD patients and 25 control subjects were evaluated using a Hyposmia Rating Scale developed in-house, combined with the extended Sniffin' Sticks test. Total score of the 6-item Hyposmia Rating Scale showed significant correlation with threshold, discrimination, identification and total Sniffin' Sticks test scores (r = 0.53; r = 0.60; r = 0.57; r = 0.65 respectively, p < 0.001 for all values). Area under the curve of the receiver operating curve for the ability of Hyposmia Rating Scale to discriminate patients with Sniffin' Sticks test total scores below or above the cut-off point was 80 ± 6% (p < 0.001). Considering Sniffin' Sticks test as the gold standard method for olfactory dysfunction detection, an affirmative response to a single screening question about smelling ability problems showed 35% sensitivity (95%CI = 23-47%) and 100% specificity. The best cut-off point for Hyposmia Rating Scale was 22.5 with a sensitivity of 70% (60-81%) and a specificity of 85% (65-100%). The Hyposmia Rating Scale here presented may offer a simple, cost-effective, time-saving and reliable approach to evaluate olfactory dysfunction in PD patients.


Timing of puberty and reserve capacity in adolescence as pathways to educational level in adulthood-a longitudinal study.
Family socioeconomic status (SES) is related to a child's educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence. To study whether family SES affects a child's adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence. Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n = 37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29-43 years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used. Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model. The results show that family SES affects the child's adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.


Detection of HHV-8 sequences and antigens in a MALT lymphoma associated with Sjögren's syndrome.
We describe the case of a bilateral parotid mucosa-associated lymphoid tissue (MALT) lymphoma associated with 2 years history of Sjögren's syndrome (SS), which was linked to human herpes virus 8 (HHV-8) infection. Using polymerase chain reaction (PCR) assay HHV-8 sequences were detectable in the lymphoma tissue of both sides. Serologic testing of the patient revealed HHV-8 antibodies in enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Immunohistologic staining with two antibodies against open reading frame (ORF) 26 and v-cyclin homologues of HHV-8 revealed positive staining of the salivary acinic cells whereas the lymphoma cells were negative. The potential influence of HHV-8 infection for MALT lymphoma development in this case and possible parallels to gastric MALT lymphoma are discussed.


Persistent negative symptoms in first episode patients with schizophrenia: results from the European First Episode Schizophrenia Trial.
Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.


Arm position and blood pressure: an audit.
Although arm position significantly alters blood pressure, this aspect of clinical behaviour has not been evaluated. Consequently, an audit of arm position preference involving 182 clinicians including physicians, general practitioners and nurses was performed. A marked variation in standing and sitting arm position preference, both between and within the three groups, was recorded, although approximately two-thirds of clinicians preferred the same arm position in the standing and sitting position. In particular, only 8 and 4% of clinicians chose the horizontal arm position in sitting and standing subjects, respectively. Choosing the dependent arm is a behaviour likely to lead to the overdiagnosis of hypertension and inappropriate treatment of hypertension because the dependent arm falsely elevates both systolic and diastolic blood pressure. These results should encourage national and international organizations to reaffirm the importance of the horizontal arm in the measurement of blood pressure.


Comparison of image quality between split-filter twin beam dual energy and single energy images in abdominal CT.
To compare the objective and subjective image quality between composed images from split-filter twin beam dual energy (TBDE) and single-energy computed tomography (SECT) in abdominal CT. In this prospective study, 103 patients were imaged using TBDE (n = 51) or SECT (n = 52). The CT number and noise were measured for the following six abdominal structures: liver, spleen, fat, muscle, aorta and portal vein. The normalised noise level for the liver was separately measured and compared. The consistency of the SNR and CT number was compared between the two groups. The subjective image quality was evaluated using six aspects in a blinded manner. Cohen's Kappa statistic was used to determine the level of agreement between the two radiologists. For the objective image quality comparison, the SNR of all structures was higher using TBDE compared to SECT (p < 0.05). The CT value for different structures were comparable between the two groups (p > 0.05). Among all patient sizes, the noise level for TBDE images was significantly lower (7-17% reduction) compared to the SECT images (p < 0.01). Furthermore, noise reduction's magnitude increases with body size. For image quality's subjective evaluation, TBDE images are superior for certain aspects. Cohen's Kappa values (0.7634-0.8460) suggest an adequate level of agreement between the two observers. TBDE scan mode can yield similar or even better objective and subjective image quality at the same level of radiation than conventional SECT. Quantitatively, TBDE images have a 7-17% reduction in noise, depending on the size of the scanned body regions.


Comparison of In-hospital Outcomes Between Transcatheter and Surgical Aortic Valve Replacement in Patients with Aortic Valve Stenosis: A Retrospective Cohort Study Using Administrative Data.
The number of surgeries for valvular heart disease performed in Japan has greatly increased over the past decade, and surgical aortic valve replacements (SAVR) constitute the vast majority of aortic valve replacement procedures. Although transcatheter aortic valve implantation (TAVI) was recently introduced, studies have yet to compare the clinical outcomes between TAVI and SAVR in the Japanese healthcare setting. This study aimed to compare in-hospital outcomes between TAVI and SAVR using a multicenter administrative database. Retrospective cohort study. Acute care hospitals in Japan. A total of 16,775 patients diagnosed with aortic valve stenosis. None. The main study outcome measure was in-hospital mortality. Based on multiple logistic regression analysis using inverse probability of treatment weighting, the odds ratio of in-hospital mortality for TAVI (relative to SAVR) was calculated to be 0.36 (95% confidence intervals: 0.13-0.98; p = 0.04). In patients aged 80 years or older, the odds ratio was even lower at 0.34 (95% confidence intervals: 0.15-0.73; p < 0.01). In addition, the incidences of reoperations, hemorrhagic complications, cardiac tamponade, and postoperative infections were significantly higher in the SAVR patients. This large-scale multicenter comparative analysis of TAVI and SAVR in Japan indicated that TAVI produced better clinical outcomes in patients with aortic valve stenosis. The improved outcomes were particularly notable in patients aged 80 years or older.


Variability in opioid prescribing in veterans affairs emergency departments and urgent cares.
The Veterans Health Administration (VHA) is the largest integrated health care system in the U.S., serving approximately 2.5 million Veterans in the Emergency Department/Urgent Care Centers (ED/UCC) each year. Variation in opioid prescribing by ED/UCC providers in the VHA is described. This is an observational study using administrative data from the VHA Pharmacy Benefits Management Services database to assess ED/UCC providers' opioid prescribing rates between October 1st, 2014 to June 30th, 2017 in 121 U.S. facilities. The opioid prescribing rate was defined as the number of opioid prescriptions written by the provider divided by the number of patients discharged from the ED/UCC by that provider, by quarter. A regression analysis was performed to estimate the association between time and prescribing rates by provider. Overall, the national trend in median prescribing rates decreased by 25.5% (p value = 0.00) from 9.1% ([range 1.5%-25.6%] to 6.4% [range 0.8%-21.8%]). The greatest rates of decline occurred between January 1st, 2016 to June 30th, 2017. The rate of provider opioid prescribing demonstrated wide variability between facilities (range: 0.5% to 39.1%). The prescribing rate for ED/UCC providers ranged from 0.2% to 100%. Between June 2016 and May 2017, 24 VHA ED/UCC providers were the highest opioid prescribers nationally in at least two of the four quarters (22%-70%), with rates two- to three-fold higher than their peers. ED/UCC providers in the VHA system nationally vary considerably in rates of opioid prescribing. A focused initiative tailored for ED/UCC providers is needed to decrease opioid prescribing variability.


Effect of semiquantitative culture results from complex host surgical wounds on dehiscence rates.
The primary aim of this study was to determine the effect of positive bacterial cultures at the time of closure on dehiscence rates. Pre- and post-débridement wound cultures from patients undergoing serial surgical débridement of infected wounds were compared with outcomes 30 days postoperatively. One-hundred patients were enrolled; 35 were excluded for incomplete culture data. Sixty-five patients were evaluated for species counts, including Coagulase negative Staphylococcus (CoNS), and semiquantitative culture data for each débridement. The post-débridement cultures on the date of closure had no growth in 42 patients (64.6%) of which 6 dehisced (14.3%), and 36 remained closed; with no statistically significant difference in dehiscence rates (p = 0.0664). Pre-débridement cultures from the 1st débridement of the 65 patients showed 8 patients had no growth, 29 grew 1 species, 19 grew 2 species, and 9 had 3-5 species. There was a reduction in the number of species and improvement of semiquantitative cultures with each subsequent débridement. The dehiscence rate for those who had 2 débridements (n = 42) was 21.4% at 30 day follow-up and 21.7% in those who had 3 débridements (n = 23). The number of débridements had no statistical significance on dehiscence rates. The presence of CoNS on the day of closure was a statistically significant risk for dehiscence within 30 days (p = 0.0091) postoperatively. This data demonstrates: (1) positive post-débridement cultures (scant/rare, growth in enrichment broth) at the time of closure did not affect overall dehiscence rates (p = 0.0664), (2) the number of species and semiquantitative culture results both improved with each subsequent débridement, (3) the number of surgical débridement did not influence postclosure dehiscence rates. (4) Positive cultures containing CoNS at the time of closure is a risk factor for dehiscence (p = 0.0091).


A method for geometric calibration of edge-on detectors in a CT-gantry.
Photon-counting edge-on detectors are currently being considered for use in clinical computed tomography (CT) systems. A method for geometric calibration of edge-on detectors mounted on a CT-gantry has been developed and evaluated. The method is complementary to the geometrical calibration methods developed for CT systems using flat-panel detectors and takes the extra dimension of the edge-on detectors (along the direction of the x-rays) into account. The method uses projection images of a simple phantom together with geometrical arguments to accurately estimate the orientation and relative position of the edge-on detectors. Both computer simulations and experimental measurements were used to verify the method. It is experimentally demonstrated that the method can determine the orientation of the detector with an accuracy of 0.08°. The method is also shown to be insensitive to errors in the modeled parameters used in the algorithm. The presented method can accurately determine the orientation and relative position of edge-on detectors mounted on a CT-gantry and can be used to evaluate the detector mounting and to produce an accurate forward model of the imaging system. Also, the method has potential to reduce the dimensionality of the geometric calibration of the full CT system since the direction of the x-rays with respect to the detector is measured.


Investigation on the distal screw of a trochanteric intramedullary implant (Fi-nail) using a simplified finite element model.
Numerous studies have been published concerning the characteristics and the behaviour of the intramedullary devices in the treatment of the intertrochanteric hip fractures. However, there is still room for further exploration and exploitation concerning the implant behaviour with respect to the parts of the implant assembly (nail, lag screw and distal screw). Towards this direction, the present paper aimed at revealing the effect of the position of the distal screw on the mechanical behaviour of the fixation device. For this purpose, a simplified model was developed and analysed with the finite element method. In total, five different locations for the distal screw were examined. In all cases, the bone was fixed at its distal end while the external load was applied at the tip of the lag screw towards the hip and in the form of orthonormal force components applied individually. The results of the FE analyses were illustrated in appropriately formed plots revealing the sensitivity of the behaviour of the implant with respect to the location of the distal screw. The main conclusion derived from the present investigation was that moving the distal screw apically decreases the stresses on the distal screw but increases the stresses on the lag screw. In turn, this indicates the existence of a location for the distal screw that compromises these two effects in an optimum way.


Antemortem chemical hypothyroxinemia.
Based on reports of hypothyroidism in intensive care unit patients, a preliminary study was instituted in which 40 patients coming to autopsy, with no history of thyroid disease, were studied to include gross and microscopic study of the thyroid gland and the performance of thyroid function tests on all serum specimens submitted within seven days of death. Initial studies show that with the exception of sudden cardiac death, all of the autopsy patients showed evidence of chemical hypothyroxinemia within three days preceding death without any histologic abnormalities of the thyroid gland. Thyroid function tests were subsequently studied of decedents and survivor controls matched for age, sex, disease, and stage of disease if applicable. The findings were similar.


Filling of extraction sockets with autogenous bone in cats.
To evaluate bone healing in the extraction socket of the feline mandibular canine tooth after grafting. Eighteen adult cats were submitted to unilateral extraction of mandibular canine tooth and divided into three groups. In group 1 (n=6), control, the extraction socket was left empty. In group 2 (n=6), the extraction socket was filled with autogenous cancellous bone from the iliac crest and in group 3 (n=6), with cortical bone chips from the iliac crest. Cats were euthanized at 6 weeks postoperative. Immediate postoperative radiographs in dorsoventral view showed a radiolucent area at the extraction wound. A decreased radiolucency was observed on the radiographs taken at 6 weeks postoperative. Histological examination showed formation of woven bone within the extraction socket. The percentage of newly formed bone within the extraction socket, measured by the histometry, showed no statistically significant difference among the values of the three groups (Kruskal-Wallis'test p>0.05) (group 1: 52.54 ± 15.46, group 2: 50.51 ± 5.01, group 3: 51.85 ± 9.52). The bone regeneration observed in the extraction sockets filled with autogenous cancellous bone or autogenous cortical bone chips was similar to that observed in the control sites, given an observation period of 6 weeks after extraction of the mandibular canine tooth.


[Primary malignant lymphoma in the dura and subdural space along the superior sagittal sinus. Case report].
A 56-year-old male with a 11-month history of late-onset epilepsy was hospitalized because of status epilepticus. The physical examination and laboratory data were normal. Neurological examination revealed weakness of the right leg. Coronal computed tomography showed a mass of slightly high density in the bilateral parietal convexity, with homogeneous enhancement by contrast medium. Magnetic resonance imaging disclosed an en-plaque epidural tumor in the parietal region along the superior sagittal sinus, which was normointense on T1- and T2-weighted images. Conventional and digital subtraction angiography showed an avascular mass between the superior sagittal sinus and the inner table of the skull at the parietal region. The mass was thought to be situated in the parietal epidural space. On surgery, however, the tumor was found to be located mainly in the dura and subdural space. The histological diagnosis was malignant lymphoma of the B cell type. Ga-scintigraphy, physical examination, and bone marrow and peripheral blood examinations disclosed no systemic abnormalities. Therefore, the tumor was interpreted as a primary intracranial malignant lymphoma. Reports of primary intracranial malignant lymphoma have been increasing, but most have been located in the cerebrum. The dural-subdural location in this case is evidently rare.


Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City: A PRESPOND Study.
The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore. Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation. Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89-0.98; p < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03-0.89; p = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21-48.8; p < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63-12.1; p < 0.01) were found to be associated with biologics initiation. Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.


Localized trabecular damage adjacent to interbody fusion devices.
An in vitro cadaveric study of interbody fusion devices (IFDs) with differing interface geometries. To quantify the trabecular damage and mechanical property degradation resulting from mechanical testing of bone-implant constructs and evaluate the dependence on the interface geometry. The success of an orthopedic implant depends, in part, on the interaction between the implant and the bone at its interface. IFDs must safely and effectively transfer load between the device and the neighboring vertebral cancellous bone on which the device is supported. Twenty-four vertebral pairs implanted with bilateral cylindrical or hexahedral IFDs were subjected to either 1% or 2.5% compressive strain. The change in structural stiffness and the presence of residual deformation caused by damage processes were measured. Histologic evidence of trabecular damage was quantified using polychromatic labeling and an image processing scheme. Statistical comparisons between groups within a strain level were made using the Mann-Whitney U test. RESULTS.: Permanent deformation and/or decreased structural stiffness was found in all specimens. The overall changes in mechanical stiffness properties were inconsistent with regard to the device interface geometry. Histologic damage was found in all specimens located in a region immediately adjacent to the implant. The distribution of the damage relative to the center of the device cross-section was significantly different for the 2 interface geometries. At the higher strain, damage and the mechanical effect of damage were greater for the cylindrical devices. Histologic damage was found in close proximity to the bone-implant interface and in all specimens, including those which did not demonstrate mechanical damage. Patterns of histologic damage corresponded directly to the bone-implant interface geometry. Gross structural measurements do not reliably detect changes caused by damage at the bone-implant interface.


Evidence based demonstration of the concept of 'field cancerization' by p53 expression in mirror image biopsies of patients with oral squamous cell carcinoma - an immunohistochemical study.
The main rationale for treatment failure and death of the patients with oral squamous cell carcinoma (OSCC) is loco-regional recurrence, development of second primary tumor (SPT) and metastasis, which could be well explained by concept of field cancerization. Identification of patients at high risk for development of SPT is an important part of research for cancer management. This study was designed keeping this aspect in mind and utilizing the increased expression of p53 as an indicator of existence of altered fields in mirror image biopsies of OSCC patients. Forty clinically diagnosed oral cancer patients were included in the study. Biopsy tissue samples from clinically diagnosed oral cancer patients (Group A) and the mirror image, clinically normal looking mucosa at corresponding contralateral anatomical site (Group B) were studied for histopathological evaluation and p53 immunoexpression. Tissue alterations were observed in Groups A and B. There was statistically significant (chi-square value - 126.6, p=0.0001) difference in grades of epithelial dysplasia and p53 immunoexpression in Group B. Spearman's Rank Correlation Coefficient shows non-significant positive correlation between epithelial dysplasia and p53 (r=0.28, p=0.05) in Group B. Evidence of presence of field cancerization, evaluated by histopathological alterations and enhanced p53 expression was observed in mirror image biopsies of OSCC patients. This could predict the altered state of oral mucosa secondary to carcinogen exposure. The realization of a genetically altered field as a cancer risk factor provides a new paradigm. It would be prudent to keep these patients under close observation and to advice them chemotherapeutic regimes.


Gaze palsy and exotropia in internuclear ophthalmoplegia.
Unilateral gaze palsy associated with internuclear ophthalmoplegia (INO), i.e., one-and-a-half syndrome, is well known. Exotropia can also be associated with INO, but it has been reported only rarely. We sought to determine the frequencies and courses of gaze palsy and exotropia in INO. Patients hospitalized with acute-onset INO during the period January 2009 through December 2013 were identified from our clinical registry. Associated gaze palsy and exotropia were evaluated in the identified patients. Twenty-five patients with unilateral INO and 7 patients with bilateral INO were included in this study. Of the 25 patients with unilateral INO, 4 (16.0.0%) had ipsilateral gaze palsy (one-and-a-half syndrome), 8 (32.0%) had exotropia (non-paralytic pontine exotropia), and 6 (24.0%) had both ipsilateral gaze palsy and exotropia (paralytic pontine exotropia). Six (85.7%) of the 7 patients with bilateral INO had exotropia. The gaze palsy persisted more than 1 week in 40.0% of patients, whereas the exotropia disappeared within 1 week in 92.9% of patients when the INO was unilateral. Exotropia is not uncommon in the acute stage of INO. However, it is often overlooked because of its short duration.


Extraneural metastases from medulloblastoma: long-term survival after sequentially scheduled chemotherapy and radiotherapy.
Extraneural relapse of medulloblastoma is an uncommon event which has typically been associated with a fatal outcome. We present a case of a 2 1/2-year-old male who developed extensive bone marrow and bone metastases 19 months after diagnosis and treatment of a medulloblastoma. This patient was successfully treated with a sequentially scheduled combination of vincristine, cyclophosphamide, and doxorubicin and remained free of disease for more than 5 years from the time of relapse.


A cost-utility analysis of dulaglutide versus insulin glargine as third-line therapy for Type 2 diabetes in Canada.
The prevalence of Type 2 diabetes in Canada is estimated to be 7.6% and rising. Given the substantial economic burden associated with Type 2 diabetes treatment, optimizing healthcare expenditure is extremely important. In the present analysis, we evaluated the cost-effectiveness of dulaglutide 1.5 mg, a once-weekly glucagon-like peptide 1 agonist as third-line therapy relative to insulin glargine from the perspective of a Canadian healthcare payer. A patient-level cost-utility model of Type 2 diabetes was developed to capture seven microvascular and macrovascular complications and severe and nonsevere hypoglycemia. Cohort characteristics and the relative efficacy of dulaglutide 1.5 mg and insulin glargine were derived from the AWARD-2 head-to-head trial, which was identified by systematic literature review. Cost data were derived from Canadian sources and expressed in 2016 Canadian dollars (CAD), and future cost and quality-adjusted life expectancy (QALE) estimates were discounted at 1.5% per annum. One-way and probabilistic sensitivity analyses were conducted. Based on the AWARD-2 trial, relative to insulin glargine, dulaglutide 1.5 mg was projected to increase QALE by 0.38 quality-adjusted life years and increase costs by CAD 19,773, resulting in an incremental cost-effectiveness ratio of CAD 52,580 per quality-adjusted life year gained. A computer simulation analysis showed that dulaglutide 1.5 mg would likely be cost-effective relative to insulin glargine in patients with Type 2 diabetes inadequately controlled on metformin and sulfonylurea in Canada.


Age-related differences in food intake, body weight, and survival of male F344 rats in 5 degrees C cold.
Male F344 rats, 3, 12 and 21 months old, were acclimated at 5 degrees C for 7 to 9 weeks. Controls were maintained at 23 degrees C. Food intakes and body weights were monitored weekly. All animals in these age groups survived. However, 25-month-old rats placed in 5 degrees C for 3 weeks had only a 46% survival. All age groups responded to 5 degrees C exposure by different but always significant increases in food intake. Peak food intake was 100% above basal in the 3- and 21-month-olds and 80% above the basal in the 12-month-olds. These increases were sufficient to maintain body weights in the 3- and 12-month-olds, but in the 3-month-olds growth was retarded. The 100% increase of food intake in the 21-month-olds was not adequate to maintain body weight. The 25-month-old rats also increased their food intake significantly in cold, but large weight loss incurred in both the survivors and the non-survivors. Food intake and energy efficiency were different at different ages and under different environmental conditions in male F344 rats.


Correlation between the expression of miR150 and FOXO4 and the local recurrence and metastasis of nasopharyngeal carcinoma after intensive radiotherapy.
To investigate the relationship between the expression of miR150 and FOXO4 in nasopharyngeal carcinoma (NPC) and the local recurrence and metastasis after intensive radiotherapy. 94 patients with NPC were selected in Hunan Provincial People's Hospital from May 2011 to May 2013. All patients received intensive radiotherapy. Thirty healthy controls were also included. The expression levels of miR150 and FOXO4 mRNA in blood lymphocytes were detected by RT-PCR. All patients with NPC were followed up for 36 months. Blood was drawn from patients to analyze the expression of miR150 and FOXO4. MiR150 inhibitor was used to treat NPC cells, and FOXO4 overexpression cell lines were established. Transwell invasion assay was performed to investigate the effects of miR150 expression inhibition and FOXO4 overexpression on cell invasion. Protein levels were detected by western blot. Compared with healthy controls, the levels of miR150 mRNA in NPC patients were significantly increased, while FOXO4 mRNA levels were significantly decreased (p<0.05). The levels of miR150 and FOXO4 were significantly correlated with distant metastasis and tumor recurrence (p<0.05). High expression level of miR150 or low expression level of FOXO4 significantly shortened the overall survival (OS) of patients (p<0.05). Cox's proportional hazards model showed that miR150 and FOXO4 were potential independent risk factors for NPC (p<0.05). The level of miR150 in patients with tumor recurrence was significantly higher than that in patients without tumor recurrence, while the level of FOXO4 in patients with tumor recurrence was lower than that patients without tumor recurrence (p<0.05). MiR150 expression inhibition or FOXO4 overexpression significantly reduced the invasion abilities of CNE1 and CNE2 cells and protein levels of matrix metalloproteinase2 (MMP2) and MMP9 (p<0.05). MiR150 and FOXO4 are closely related to the metastasis and recurrence of NPC, and are independent prognostic factors for NPC. MiR150 and FOXO4 are of clinical significance in predicting NPC prognosis.


Comparing local and remote motion aftereffects.
A new method, using phase-reversing sinusoidal gratings to cancel perceived motion, was developed to measure the motion aftereffect (MAE). This technique was used to show the existence of a remote MAE, i.e. an MAE in areas that were not directly stimulated during adaptation. In several experiments, this remote MAE was compared to the local MAE. The remote effect was generally weaker and of shorter duration. It showed no directional tuning within the investigated range, as compared to a tuning of +/- 60 deg of the local MAE. There was no adaptation effect to the component gratings of a plaid, indicating that the plaid was treated as a coherent pattern. The local MAE showed clear spatial frequency tuning, whereas the remote MAE varied little with spatial frequency difference, although there was a tendency towards frequencies lower than the adaptation frequency. The possibility is considered that both local and remote MAEs are generated in extrastriate areas.


External nasal nerve division: a treatment for post-traumatic neuralgia.
We present four patients complaining of neuralgic pains across the nasal bridge following trauma, who were successfully treated by division of the external nasal nerve. We believe it is a useful treatment in selected cases.


[Retroviruses and their importance in neurology].
Retroviruses comprise spumaviruses, lentiviruses and oncoviruses. After these taxonomic remarks neurologic-psychiatric-syndromes (multifocal leucencephalopathy, dementia-complex, vacuolar myelopathy and others) are described, that could be observed as manifestations of the "acquired immune deficiency syndrome". Some therapeutic measures are discussed, especially the administration of Zidovudine that shows good temporary results. Essentially Zidovudine works by misleading the Reserve Transkriptase by offering a "Fake-thymidine"--so misleading replication. Lastly the hypotheses concerning multiple sclerosis are put in relation to lentiviruses. Some animal variants of the viruses and their neurotropic features are described. This discovery has lead to those speculations--however, these speculations remain unsecure.


Anxiety, depression and informed consent in patients referred to a radiotherapy department.
Informing cancer patients is an ethical, legal and deontological aspect of patient management. Patients need clear instructions in order to be able to accept or refuse medical procedures. Many reports in the literature have shown differences among physicians in informing cancer patients. The aim of this study was to assess patients' understanding of diagnosis, planned radiotherapy and risk of early and late effects, their satisfaction with the discussion with the doctor and correlation with anxiety and depression after the disclosure of a cancer diagnosis. From April to July 2000 a physician with psychiatric training conducted interviews with patients after their consultation with the radiotherapist and asked them to fill in a questionnaire. Anxiety and depression were measured by means of a scoring system [HAD(A) and HAD(D)] such as the patient's satisfaction and the physician's belief in it. Eighty-two outpatients referred to our radiotherapy department were studied. We did not find any correlation between HAD(A) and HAD(D) scores and comprehension scores of disease, treatment schedule, side effects and patient satisfaction, or between any scores and presumed predictive variables such as diagnosis, gender, age, treatment aims, time from diagnosis, education, marital status, profession, life habits, and the role of the doctor obtaining the informed consent. We may conclude that informed consent does not seem to increase reactive anxiety or depression. Its quality is high in our department but must be improved.


Out of Physicians' Hands: TMA Challenges Unfair Quality Measures on Medication Adherence.
Only patients can pick up their own prescriptions, and only patients can propel that medication into their own bodies. Physicians can educate, emphasize, and admonish - but at the end of the day, they can't restrain and "pill" a squirming, uncooperative patient like a dog or cat. It's up to patients to do the right thing for themselves. Yet, some health plans' quality programs are putting that onus on physicians - through medication adherence metrics that determine whether physicians and accountable care organizations (ACOs) in value-based contracts receive bonus payments.


Functional roles of the tegument proteins of herpes simplex virus type 1.
Herpes virions consist of four morphologically distinct structures, a DNA core, capsid, tegument, and envelope. Tegument occupies the space between the nucleocapsid (capsid containing DNA core) and the envelope. A combination of genetic, biochemical and proteomic analysis of alphaherpes virions suggest the tegument contains in the order of 20 viral proteins. Historically the tegument has been described as amorphous but increasing evidence suggests there is an ordered addition of tegument during assembly. This review highlights the diverse roles, in addition to structural, that tegument plays during herpes viral replication using as an example herpes simplex virus type 1. Such diverse roles include: capsid transport during entry and egress; targeting of the capsid to the nucleus; regulation of transcription, translation and apoptosis; DNA replication; immune modulation; cytoskeletal assembly; nuclear egress of capsid; and viral assembly and final egress.


Sex steroids and neurogenesis.
The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives.


Inflammation and cerebral vasospasm after subarachnoid hemorrhage.
Morbidity and mortality of patients with aneurysmal subarachnoid hemorrhage (aSAH) is significantly related to the development of chronic cerebral vasospasm. Despite extensive clinical and experimental research, the pathophysiology of the events that result in delayed arterial spasm is not fully understood. A review of the published literature on cerebral vasospasm that included but was not limited to all PubMed citations from 1951 to the present was performed. The findings suggest that leukocyte-endothelial cell interactions play a significant role in the pathophysiology of cerebral vasospasm and explain the clinical variability and time course of the disease. Experimental therapeutic targeting of the inflammatory response when timed correctly can prevent vasospasm, and supplementation of endothelial relaxation by nitric oxide-related therapies and other approaches could result in reversal of the arterial narrowing and improved outcomes in patients with aSAH.


Psychosocial stress and chronic ethanol ingestion in male rats: effects on elevated plus maze behavior and ultrasonic vocalizations.
Psychosocial stress is known to enhance anxiety levels in rodents. The present study evaluated the effect of long-term ingestion of ethanol (EtOH) on anxiety levels of male Long Evans rats housed either singly or in triads (three/cage). Based on measures of offensive and defensive behaviors, triad-housed rats were designated as being dominant, subdominant or subordinate. The effect of chronic ingestion of a 6% EtOH solution was assessed on behaviors in the elevated plus maze (EPM) test, and on air-puffs elicited 22 kHz ultrasonic vocalizations (USV). EtOH naïve dominant rats showed less anxiogenic-like (open arms time) and displacement behavior (grooming), but more risk assessment behavior (stretch-attend postures) than their cage-mates or the single-housed rats. Intake of EtOH prior to the EPM test was lower in dominant and single-housed rats compared to subdominant and subordinate rats. Triad-housed rats, but not the single-housed rats, decreased their intake of EtOH after the EPM test. Overall, EtOH intake had an anxiolytic effect in all rats, but the effect was most prominent in single-housed rats. Furthermore, EtOH intake decreased air-puff induced USVs of triad-housed rats, but increased USVs of single-housed rats. These data indicate that housing condition and rank status influence the emotional state of male rats. Furthermore, the anxiolytic effect of voluntarily ingested EtOH was depended on these variables.


The neuropathological phenotype in transgenic mice expressing different prion protein constructs.
Neuropathologic examination of transgenic (Tg) mice which express different prion protein (PrP) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of PrPSc and whether PrP amyloid plaques form are the phenotypes of prion diseases. In Tg models of experimental scrapie, it was found that all of the parameters that define prion isolates ('strains') can be manipulated by changing the structure of PrP. In those studies, further evidence that PrPSc causes scrapie neuropathology and determines scrapie incubation time was obtained. In addition, the distribution of PrPSc in the brain was unique for each prion isolate. The implications of these findings are first, that prion isolates target different neuron populations for synthesis of nascent pathogenic PrPSc and, secondly, that prion isolate diversity is determined by neurons. In Tg mice which express mutated PrP mimicking human prion protein gene mutations linked to familial prion diseases, the neuropathological changes have been faithfully reproduced. A new age-related, neuromuscular disorder has also been identified in uninfected Tg mice which overexpress wild-type PrPc. All of the findings with different PrP constructs plus the absence of scrapie pathology in PrP null mice are the strongest argument that the prion protein is the main etiologic and pathogenic factor of prion disorders.


Adjuvant Treatments for Advanced Stage, Non-metastatic Upper Tract Urothelial Carcinoma: A Multicenter Study.
We assessed the efficacy of adjuvant treatments in patients with peripelvic/periureteral fat-infiltrating (pT3b), nonmetastatic upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. The multicenter data of 222 patients with pT3bN0-x disease treated with radical nephroureterectomy were analyzed. The effects of adjuvant radiation therapy and chemotherapy on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) were evaluated. Adjuvant radiation therapy and chemotherapy were given to 39 (17.6%) and 74 patients (33.3%), respectively. Seventeen patients (7.7%) received concomitant adjuvant radiation therapy and chemotherapy. The median follow-up duration was 34.4 months. After adjusting for age, sex, tumor location, multifocality, tumor grade, presence of lymphovascular invasion, surgical margin, execution of node dissection, and other types of concomitant adjuvant treatment (radiation therapy or chemotherapy) through propensity-scored matching, adjuvant radiation therapy significantly reduced the local recurrence (5-year LRFS, 83.9 vs 54.2%; P = .001), distant metastasis (5-year DMFS, 72.1 vs 48.1%; P = .032), and cancer-specific death (5-year CSS, 76.4% vs 55.5%; P = .038) in pT3b UTUC. However, in the same condition, adjuvant chemotherapy did not reduce the local recurrence (5-year LRFS, 69.0% vs 66.2%; P = .786), distant metastasis (5-year DMFS, 65.3% vs 61.1%; P = .436), and cancer-specific death (5-year CSS, 67.9% vs. 67.9%; P = .458) in pT3b UTUC. Our study suggests that adjuvant radiation therapy may be beneficial in patients with T3bN0-x UTUC; however, prospective clinical trials are needed to clarify this issue.


Adolescents, sex, and the media.
In the absence of effective sex education in the United States, the media have arguably become the leading sex educator for children and teenagers. Considerable research now exists that attests to the ability of the media to influence adolescents' attitudes and beliefs about sex and sexuality. In addition, new research has found a significant link between exposure to sexual content in the media and earlier onset of sexual intercourse. Although there is little research on the behavioral effects of "new" media, they are discussed as well. Suggestions for clinicians, parents, the federal government, and the entertainment industry are provided.


Utilization of preoperative urodynamic studies by Canadian gynaecologists.
(1) To determine the proportion of Canadian gynaecologists who have urodynamic studies (UDS) readily available; (2) to assess the preoperative UDS utilization patterns of Canadian gynaecologists in various clinical scenarios of stress urinary incontinence (SUI). A mail survey was sent to all 1266 obstetrician/gynaecologist members of the Society of Obstetricians and Gynaecologists of Canada (SOGC), as part of an international survey with the U.K., U.S.A., New Zealand, and Australia. Survey questions included geographic availability of UDS and specific types of urodynamics testing available. Utilization of urodynamics prior to anti-incontinence surgery was assessed in four clinical scenarios: (A) a history of uncomplicated primary stress urinary incontinence, (B) a history of mixed stress and urgency incontinence, (C) stress incontinence with a history of straining to void, and (D) recurrent stress incontinence. Of the 1266 surveys mailed, 230 (18%) were returned. Forty-four of the respondents did not manage incontinent women. Of the 186 respondents who did, 27% reported a special interest or additional postgraduate training in urogynaecology, and 73% were general gynaecologists. UDS were available in the same centre or city to 79% of respondents. For uncomplicated primary stress incontinence, 47% would always obtain preoperative UDS, 42% would not, and 11% would only if UDS were readily available. For the total group of respondents, in scenario A 47% would always obtain preoperative UDS, 42% would not, and 11% would only if UDS were readily available. Among general gynaecologists, in scenario A, if UDS were available in their city or centre of practice, 54% would always obtain preoperative UDS, as compared to 5% by general gynaecologists who did not have UDS available in their city or centre of practice. The data collected in this survey are compromised because of the low response rate. However, most (79%) of the respondents who manage women with urinary incontinence had access to urodynamics in the same centre or city. The utilization of urodynamics prior to surgical treatment of uncomplicated primary pure stress incontinence varies depending on the availability of such testing. An uncomplicated history of primary SUI and decreased availability of testing were two factors seen to have an effect of decreasing utilization of preoperative UDS. Hospital management did not always comply with SOGC guidelines for preoperative testing for SUI. Updating and dissemination of these guidelines is necessary to ensure "best" practice and highest quality of care for all women with SUI in Canada.


Carcinoma of the colon and rectum with liver involvement.
The records of 126 patients with adenocarcinoma of the colon and rectum who presented with liver involvement were reviewed. Prognosis was determined by the amount of metastases to the liver, which was usually extensive of ascites or a raised alkaline phosphatase level was present. The longest survival period was achieved with resection of the primary tumor along with hepatic lesions confined to a single lobe, especially those due to direct tumor infiltration. If liver deposits were found bilaterally, palliative resection of the primary lesion relieved intestinal symptoms. This may also prolong the survival time, because a fixed primary tumor appeared to diminish the outlook among patients with comparable liver disease. Palliative resection in the presence of ascites resulted in a high mortality, and the survival rate was no better than that after diversion procedures. We recommend resection without anastomosis for carcinoma of the rectosigmoid in patients with ascites and unresectable secondary lesions of the liver.