DNA Gyrase and Topoisomerase IV Mutations and their effect on Quinolones Resistant Proteus mirabilis among UTIs Patients.
This study aimed to highlight the importance of mutations within Proteus mirabilis genome that are related to fluoroquinolone resistance. This is a cross sectional study performed in different teaching hospitals in Khartoum State from June 2016 to May 2017. A total of (120) P mirabilis isolates from patients with symptoms of UTIs attending different hospitals in Khartoum State were examined. First, modified Kurby Bauer method was performed for phenotypical detection of resistant isolates. Then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing were applied for detection of mutations in GyrA, GyrB, ParC and ParE genes of isolates. P. mirabilis showed 30% resistance to ciprofloxacin. All samples revealed mutation at (serine 83) of GyrA and (serine 84) of ParC by Hinf1 restriction endonuclease digestion. Sequencing was performed for 12 samples. For each gene, two resistant and one susceptible strains were randomly selected. The mutations associated with ciprofloxacin resistant P. mirabilis were as follows; (1/3) GyrA (Ser 83 to Ile) and (2/3) ParC (Ser 81 to Ile). Also it revealed silent mutations at codons of GyrB 474 leucine (3/3), 585 valine (2/3), 612 histidine (1/3) and 639 asparagine (1/3) and ParE 469 isoleucine (2/3), 531 aspartic (2/3) and 533 glycine (1/3). Ciprofloxacin resistance in P. mirabilis could be monitored through detection of mutations within DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE).


De novo assembly of the zucchini genome reveals a whole-genome duplication associated with the origin of the Cucurbita genus.
The Cucurbita genus (squashes, pumpkins and gourds) includes important domesticated species such as C. pepo, C. maxima and C. moschata. In this study, we present a high-quality draft of the zucchini (C. pepo) genome. The assembly has a size of 263 Mb, a scaffold N50 of 1.8 Mb and 34 240 gene models. It includes 92% of the conserved BUSCO core gene set, and it is estimated to cover 93.0% of the genome. The genome is organized in 20 pseudomolecules that represent 81.4% of the assembly, and it is integrated with a genetic map of 7718 SNPs. Despite the small genome size, three independent lines of evidence support that the C. pepo genome is the result of a whole-genome duplication: the topology of the gene family phylogenies, the karyotype organization and the distribution of 4DTv distances. Additionally, 40 transcriptomes of 12 species of the genus were assembled and analysed together with all the other published genomes of the Cucurbitaceae family. The duplication was detected in all the Cucurbita species analysed, including C. maxima and C. moschata, but not in the more distant cucurbits belonging to the Cucumis and Citrullus genera, and it is likely to have occurred 30 ± 4 Mya in the ancestral species that gave rise to the genus.


Mapping of the RNA-binding domain of the cucumber mosaic virus movement protein.
A series of in-frame deletion mutants was used to identify a domain within the 3a protein of cucumber mosaic virus (CMV) that is required for RNA-binding activity. Deletions in the 3a gene were generated by PCR and restriction digestion, and the resulting mutated 3a sequences were cloned either in pT7-7 or in pGEX-5X3 expression vectors. The mutated 3a proteins or fusions with glutathione S-transferase (GST) were expressed in E. coli, purified, and their nucleic acid-binding activities analysed by photochemical UV cross-linking assays using digoxigenin-UTP-labelled RNA probes. Comparative analyses of seven mutated 3a proteins obtained from inclusion bodies and eight GST fusion proteins revealed that there is an RNA-binding domain located between amino acids 174 and 233. This RNA-binding domain is able to bind single-stranded RNA out of the context of the complete 3a movement protein and is highly conserved within both subgroups of CMV.


Upconversion-based lidar measurements of atmospheric CO2.
For the first time an upconversion based detection scheme is demonstrated for lidar measurements of atmospheric CO2-concentrations, with a hard target at a range of 3 km and atmospheric backscatter from a range of ~450 m. The pulsed signals at 1572 nm are upconverted to 635 nm, and detected by a photomultiplier tube, to test how the upconversion technology performs in a long range detection system. The upconversion approach is compared to an existing direct detection scheme using a near-IR detector with respect to signal-to-noise ratio and quantum efficiency. It is for the first time analyzed how the field-of-view of a receiver system, for long range detection, depends critically on the parameters for the nonlinear up-conversion process, and how to optimize these parameters in future systems.


Visual and anatomic outcomes with or without surgery in persistent fetal vasculature.
To determine visual and anatomic outcomes for patients with persistent fetal vasculature (PFV) observed or treated with surgery. Retrospective interventional consecutive case series. A total of 165 eyes of 150 patients diagnosed with PFV between January 1, 1983, and December 31, 2006, at the Bascom Palmer Eye Institute. Patients with media opacity, progressive glaucoma, or retinal detachment who were deemed to have visual potential underwent lensectomy, 3-port vitrectomy, or both, through a limbal or pars plicata/plana approach. Vision, postsurgical retinal attachment, lens status, need for eye removal, and rate of complications. Of the 81 eyes that underwent surgical repair, 70 had at least 6 months of follow-up (median 47 months) and 49 (70.0%) had form vision, defined as finger counting, fix-and-follow, or better. Twenty (95.2%) of 21 eyes without form vision had a significant posterior component of PFV (P < 0.001). Forty eyes had limbal incisions, and 30 eyes had pars plicata incisions. The choice of surgical approach did not have a statistically significant effect on final visual acuity or rate of complications (P=0.43). Postoperative events occurred in 28 eyes (40.0%). Retinal attachment was achieved in 54 eyes (77.1%), and 61 eyes (87.1%) were left aphakic. Eighty-four eyes were not offered surgery, of which 78 eyes (92.9%) had a posterior component of PFV. The median age at diagnosis was greater compared with the surgical group (197 vs. 67.5 days, P=0.00545). Fifty-eight eyes (69.0%) lacked form vision, and 39 eyes (46.4%) had no light perception. Posterior manifestations of PFV, bilaterality, and microphthalmia were associated with poorer visual outcomes (P < 0.001, 0.041, and 0.002, respectively). The majority of patients receiving surgical intervention for PFV achieved form vision. Posterior disease, microphthalmia, glaucoma, and amblyopia limited visual acuity outcomes even after aggressive intervention. The choice of limbal versus pars plicata approach produced similar visual and anatomic outcomes without a significant difference in rate of complications. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Study of epitopes of cholera enterotoxin-related enterotoxins by checkerboard immunoblotting.
Checkerboard immunoblotting, a versatile new technique for examining multiple antigen and antibody interactions simultaneously, was applied in studies of epitopes in the cholera enterotoxin (CT)-related heat-labile enterotoxin (LT) family. The purified antigens used included the following: the B-subunit proteins from two CTs (CT-B-1 and CT-B-2), from classical and El Tor biotype strains of Vibrio cholerae, respectively; human LT-B-1 (H-LT-B-1) and porcine LT-B (P-LT-B) derived from LTs produced by Escherichia coli strains of human (H) and porcine (P) origins, respectively; and genetically engineered chimeric P-LT-Bs with amino acid substitutions from H-LT-B-1. The antigens were used in native, partially denatured, and CNBr-fragmented forms. The antisera included a variety of mouse monoclonal antibodies against these proteins as well as polyclonal hyperimmune sera and sera from adult American volunteer vaccinees or convalescents from induced cholera. Rabbit antisera against synthetic peptides of the CT-B-1 subunit were also used. In some instances, the effect of GM1 ganglioside on antibody binding was evaluated. The reactivity of the monoclonal antibodies was directed primarily against conformational epitopes: some were specific for homologous antigen; some were promiscuously reactive; and some recognized particular related proteins. Individual amino acids (most notably amino acid 46) exerted a dominant effect on epitope formation--in some instances, in a complementary fashion. Epitope expression was also affected by distant amino acid residues (polar effects). Some reactions were blocked by GM1 treatment of the immobilized antigen, indicating that the epitope was involved in or affected by GM1 binding. Polyclonal antibody responses varied within and among animal species. Human serum antitoxic responses were higher in convalescents from induced cholera than in recipients of a genetically engineered live vaccine, and the convalescent sera (from El Tor biotype cholera patients) generally preferred CT-B-2 to CT-B-1. The results demonstrate the potential significance of the differences among these immunologically related enterotoxins and may help provide direction to further vaccine development.


Deep infection in tumor endoprosthesis around the knee: a multi-institutional study by the Japanese musculoskeletal oncology group.
The incidence of endoprosthesis failure has been well studied, but few studies have described the clinical characteristics of deep infection in tumor prostheses. This study aimed to analyze the characteristics of deep infection in tumor endoprostheses around the knee. We analyzed clinical data of 57 patients with deep infections involving tumor endoprostheses around the knee enrolled from the Japanese Musculoskeletal Oncology Group. Profile of clinical presentation including time between surgery and infection, initial symptoms/blood tests and microbial cultures was evaluated. In addition pre-, intra-, and postoperative clinical factors influencing clinical presentation and treatment outcomes of infections were analyzed. Mean interval between the initial operation and diagnosis was 13 months, and mean time required for infection control was 12 months. The most common pathogen was Staphylococcus. Infection control rates were significantly higher when prostheses were removed rather than salvaged. Ten-year prosthesis survival and limb salvage rates were 41.6% and 75.6%, respectively. Analysis of underlying clinical factors suggested that soft-tissue condition significantly influenced the duration of the infection control period and likelihood of limb salvage. Infection control is a prolonged process. Deep infection frequently results in amputation or prosthesis loss. Intensive analysis of clinical characteristics may aid infection control.


Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin.
Luteolin is 3',4',5,7-tetrahydroxyflavone found in celery, green pepper, and perilla leaf that inhibits tumorigenesis in animal models. We examined luteolin-mediated regulation of cell cycle progression and apoptosis in the HT-29 human colon cancer cell line. Luteolin decreased DNA synthesis and viable HT-29 cell numbers in a concentration-dependent manner. It inhibited cyclin-dependent kinase (CDK)4 and CDK2 activity, resulting in G1 arrest with a concomitant decrease of phosphorylation of retinoblastoma protein. Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P < 0.05) observed in cells treated with 40 micromol/l luteolin. Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment, although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspases 3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells. We demonstrate that luteolin promotes both cell cycle arrest and apoptosis in the HT-29 colon cancer cell line, providing insight about the mechanisms underlying its antitumorigenic activities.


Method of determination of light-scatterer distribution in edge-lit backlight units using an analytical approach.
We present a method to find the optimum distribution of scatterers in an edge-lit lightguide plate (LGP) for rendering a uniform distribution of the outcoupled light. We propose a simple mathematical model describing the light propagation in a waveguide with a distribution of scattering elements located on the lower surface of the waveguide. We have found a differential equation giving the distribution of scattering elements leading to a uniform irradiance along the LGP, and we propose a method to determine the value of the outcoupling coefficient of an individual scattering element from the irradiance (or radiance) measurements. We have verified the validity of this model by performing ray tracing simulations on an LGP with the scattering elements distributed according to the solution of the proposed differential equation, and we have found a quantitative agreement between the analytical results and the simulated ones. Also this model has been used to directly calculate the output power of a given embossed LGP.


Risperidone in combination with other drugs: Experimental research in individuals with autism spectrum disorder.
Many individuals with autism spectrum disorder simultaneously receive 2 or more drugs intended to improve their behavior, but few studies have evaluated the effects of such polypharmacy. This article summarizes those studies that have systematically examined the effects of risperidone, an antipsychotic drug that is approved by the U.S. Food and Drug Administration to treat "irritability" in children and adolescents with autism spectrum disorder, in combination with another drug with respect to experimental design, assessment techniques, drug co-administered, reported effects, and participant characteristics. The drug combinations that have been evaluated do not parallel those commonly co-administered to individuals with autism spectrum disorder in the United States, and there is no compelling empirical evidence to support the practice of prescribing risperidone in combination with another drug in an attempt to benefit individuals with autism spectrum disorder. (PsycINFO Database Record


Coronary vasospasm and acute myocardial infarction induced by a topical capsaicin patch.
Capsaicin is the active component of chili peppers, which has been shown to possess several beneficial effects. Currently, the best-known medical use of capsaicin is as a topical painkiller. Drug-induced myocardial infarction is not a common phenomenon and the underlying mechanism has been related with coronary spasm in the majority of cases. We present a 29-year-old man who experienced coronary vasospasm and acute myocardial infarction (AMI) which were possibly induced by the use of a topical capsaicin patch to relieve lumbago. He presented with chest pain of one hour onset. The electrocardiogram showed ST-segment elevation in the leads II, III, and aVF, consistent with inferior wall AMI. Echocardiography confirmed inferior hypokinesia. Urgent coronary angiography showed normal right and left coronary arteries. Since he had no cardiac risk factors for coronary artery disease, nor a history of recent emotional or physical stress, or ingestion of any illicit substance, the vasospasm and subsequent AMI was attributed to the use of the capsaicin patch for six days. Upon institution of appropriate treatment and removal of the patch, no new anginal attacks or ischemic episodes were seen within a follow-up of one month. This is the first case report of AMI induced by the use of a topical capsaicin patch.


Outcome following cardiopulmonary resuscitation in severe pediatric near-drowning.
Between April 1979 and September 1984, 66 children were admitted to the intensive care unit (ICU) at Childrens Hospital of Los Angeles after a severe near-drowning episode. Each patient required full cardiopulmonary resuscitation and had an initial Glasgow coma score (GCS) of 3 in a referring emergency room. Patients were reclassified according to results of a neurologic examination (GCS) on arrival in the ICU. The overall results showed 16 patients (24%) with apparently intact survival, 17 patients (26%) with vegetative survival, and 33 deaths (50%). No patient who arrived at the ICU with a GCS of 3 (flaccid) survived neurologically intact. Out of 37 such patients arriving in flaccid coma, 26 patients died and 11 patients suffered severe brain damage. The majority of patients with GCS of less than 6 underwent intracranial pressure (ICP) monitoring and aggressive therapy directed to control ICP. Despite adequate control of ICP and maintenance of cerebral perfusion pressure, 12 monitored patients survived in a vegetative neurologic state. The results justify aggressive emergency room resuscitation of severe pediatric near-drowning victims but suggest that cerebral resuscitative measures must be subjected to critical prospective evaluation.


Amyotrophic lateral sclerosis with IgM antibody against gangliosides GM2 and GD2.
We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.


Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem.
Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.


Rotating soliton solutions in nonlocal nonlinear media.
We discuss generic properties of rotating nonlinear wave solutions, the so called azimuthons, in nonlocal media. Variational methods allow us to derive approximative values for the rotating frequency, which is shown to depend crucially on the nonlocal response function. Further on, we link families of azimuthons to internal modes of classical non-rotating stationary solutions, namely vortex and multipole solitons. This offers an exhaustive method to identify azimuthons in a given nonlocal medium.


Measurement of the Nuclear Modification Factor and Prompt Charged Particle Production in p-Pb and pp Collisions at sqrt[s_{NN}]=5 TeV.
The production of prompt charged particles in proton-lead collisions and in proton-proton collisions at the nucleon-nucleon center-of-mass energy sqrt[s_{NN}]=5 TeV is studied at LHCb as a function of pseudorapidity (η) and transverse momentum (p_{T}) with respect to the proton beam direction. The nuclear modification factor for charged particles is determined as a function of η between -4.8<η<-2.5 (backward region) and 2.0<η<4.8 (forward region), and p_{T} between 0.2<p_{T}<8.0 GeV/c. The results show a suppression of charged particle production in proton-lead collisions relative to proton-proton collisions in the forward region and an enhancement in the backward region for p_{T} larger than 1.5 GeV/c. This measurement constrains nuclear PDFs and saturation models at previously unexplored values of the parton momentum fraction down to 10^{-6}.


Temporal Changes in Ebola Transmission in Sierra Leone and Implications for Control Requirements: a Real-time Modelling Study.
Between August and November 2014, the incidence of Ebola virus disease (EVD) rose dramatically in several districts of Sierra Leone. As a result, the number of cases exceeded the capacity of Ebola holding and treatment centres. During December, additional beds were introduced, and incidence declined in many areas. We aimed to measure patterns of transmission in different regions, and evaluate whether bed capacity is now sufficient to meet future demand. We used a mathematical model of EVD infection to estimate how the extent of transmission in the nine worst affected districts of Sierra Leone changed between 10th August 2014 and 18th January 2015. Using the model, we forecast the number of cases that could occur until the end of March 2015, and compared bed requirements with expected future capacity. We found that the reproduction number, R, defined as the average number of secondary cases generated by a typical infectious individual, declined between August and December in all districts. We estimated that R was near the crucial control threshold value of 1 in December. We further estimated that bed capacity has lagged behind demand between August and December for most districts, but as a consequence of the decline in transmission, control measures caught up with the epidemic in early 2015. EVD incidence has exhibited substantial temporal and geographical variation in Sierra Leone, but our results suggest that the epidemic may have now peaked in Sierra Leone, and that current bed capacity appears to be sufficient to keep the epidemic under-control in most districts.


Representation plurality and fusion for 3-D face recognition.
In this paper, we present an extensive study of 3-D face recognition algorithms and examine the benefits of various score-, rank-, and decision-level fusion rules. We investigate face recognizers from two perspectives: the data representation techniques used and the feature extraction algorithms that match best each representation type. We also consider novel applications of various feature extraction techniques such as discrete Fourier transform, discrete cosine transform, nonnegative matrix factorization, and principal curvature directions to the shape modality. We discuss and compare various classifier combination methods such as fixed rules voting- and rank-based fusion schemes. We also present a dynamic confidence estimation algorithm to boost fusion performance. In identification experiments performed on FRGC v1.0 and FRGC v2.0 face databases, we tried to find the answers to the following questions: 1) the relative importance of the face representation technique vis-à-vis the types of features extracted; 2) the impact of the gallery size; 3) the conditions, under which subspace methods are preferable, and the compression factor; 4) the most advantageous fusion level and fusion methods; 5) the role confidence votes in improving fusion and the style of selecting experts in the fusion; and 6) the consistency of the conclusions across different databases.


Cephalic phase insulin release in normal weight males: verification and reliability.
The existence and reliability of cephalic phase insulin release (CPIR) were tested in 20 normal weight males. Each subject was challenged three times with the same food stimulus over a 5-day period. Four baseline blood samples were taken at 5-min intervals before food ingestion and then every 2 min for 16 min postingestion. Significant increases in plasma insulin were found at 4 min postingestion on each trial day. CPIR was found to be highly reproducible between trials (r = 0.83; P less than 0.001). Fifty percent of the subjects exhibited a significant increase of plasma insulin above their own baseline mean on the first trial, whereas 75 and 72% exhibited increases on trials 2 and 3, respectively. Only two subjects (10%) did not demonstrate a response on any trial. A significant decline in plasma glucose was observed at 4 min postingestion on trials 2 and 3. No significant changes in plasma glucagon were found during any trial day. This study confirms a reliable CPIR in normal weight males.


Endogenous brain fluctuations and diagnostic imaging.
Much of the rising health care costs in aging populations can be attributed to congenital disease and psychiatric and neurologic disorders. Early detection of changes related to these diseases can promote the development of new therapeutic strategies and effective treatments. Changes in tissue, such as damage resulting from continued functional abnormality, often exhibit a time-delay before detection is possible. Methods for detecting functional alterations in endogenous brain fluctuations allow for an early diagnosis before tissue damage occurs, enabling early treatment and a more likely positive outcome. A literature review and comprehensive overview of the current state of knowledge about endogenous brain fluctuations is presented here. Recent findings of the association between various pathological conditions and endogenous fluctuations are discussed. A particular emphasis is placed on research showing the relationship between clinical measures and pathological findings to the dynamics of endogenous fluctuations of the brain. Recent discoveries of methods for detecting abnormal functional connectivity are discussed and future research directions explored.


A case of Klinefelter's syndrome associated with unilateral renal aplasia.
We describe a 22-year-old patient with Klinefelter's syndrome associated with unilateral renal aplasia. Unilateral absence of kidney was detected in our ongoing screening for renal abnormalities by renal ultrasound in male hypogonadism. The present abnormality may be a co-existing entity or previously unrecognized abnormality associated with Klinefelter's syndrome since there is not reported systematic screening for urinary tract abnormalities in patients with Klinefelter's syndrome in the literature.


A growing field: The regulation of axonal regeneration by Wnt signaling.
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.


Risk factors associated with hospital emergency visits among asthmatic schoolboys in Saudi Arabia.
This cross-sectional study was carried out to determine the prevalence of a positive history of hospital emergency visits (HHEV) among asthmatic Saudi schoolboys. Data were collected using self-administered questionnaires to parents. The prevalence rate for positive HHEV among questionnaire-diagnosed asthmatic boys (QDAs) was 65.0%. Factors associated with positive HHEV among QDAs were determined. Modifying the preventable factors associated with the total number of hospital emergency room visits is expected to decrease the severity and the disability of this disease.


Transcription factor CecR (YbiH) regulates a set of genes affecting the sensitivity of Escherichia coli against cefoperazone and chloramphenicol.
Genomic SELEX (systematic evolution of ligands by exponential enrichment) screening was performed for identification of the binding site of YbiH, an as yet uncharacterized TetR-family transcription factor, on the Escherichia coli genome. YbiH was found to be a unique single-target regulator that binds in vitro within the intergenic spacer located between the divergently transcribed ybiH-ybhGFSR and rhlE operons. YbhG is an inner membrane protein and YbhFSR forms a membrane-associated ATP-binding cassette (ABC) transporter while RhlE is a ribosome-associated RNA helicase. Gel shift assay and DNase footprinting analyses indicated one clear binding site of YbiH, including a complete palindromic sequence of AATTAGTT-AACTAATT. An in vivo reporter assay indicated repression of the ybiH operon and activation of the rhlE operon by YbiH. After phenotype microarray screening, YbiH was indicated to confer resistance to chloramphenicol and cefazoline (a first-generation cephalosporin). A systematic survey of the participation of each of the predicted YbiH-regulated genes in the antibiotic sensitivity indicated involvement of the YbhFSR ABC-type transporter in the sensitivity to cefoperazone (a third-generation cephalosporin) and of the membrane protein YbhG in the control of sensitivity to chloramphenicol. Taken together with the growth test in the presence of these two antibiotics and in vitro transcription assay, it was concluded that the hitherto uncharacterized YbiH regulates transcription of both the bidirectional transcription units, the ybiH-ybhGFSR operon and the rhlE gene, which altogether are involved in the control of sensitivity to cefoperazone and chloramphenicol. We thus propose to rename YbiH as CecR (regulator of cefoperazone and chloramphenicol sensitivity).


Expression of seasonality in Merinos d'Arles ewes of different genotypes at the MT1 melatonin receptor gene.
Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d'Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype -/- at a MnlI restriction site (allele - for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/- and -/-, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and -/-) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study.


Ileorectal anastomosis--familial adenomatous polyposis.
Familial adenomatous polyposis is a generalized growth disorder. The predominant cause of death is, however, colorectal cancer in the untreated patient. Prophylactic colectomy, whether it be proctocolectomy and ileostomy, colectomy with ileorectal anastomosis, or colectomy with an ileoanal pouch procedure, will dramatically reduce the mortality from large bowel cancer. It is important, however, to realize that because of the generalized nature of this condition and the possibility of developing extracolonic malignancy, the surgical approach chosen should not be considered one that will necessarily cure the disease. Colectomy with ileorectal anastomosis still leaves the potential for rectal cancer. However, death from rectal cancer is distinctly uncommon. The risk of death following ileorectal anastomosis from rectal cancer is actually less than the risk of dying from cancer of the duodenum or from desmoid tumors. Both of these lesions are unpredictable in patients with familial adenomatous polyposis, and usually occur following the patient's prophylactic colectomy. With this low incidence of death from rectal cancer following ileorectal anastomosis it would seem to be debatable whether the complexities of the ileoanal pouch procedure together with its longer recovery and higher complication rate are justified in the routine management of young people with an early diagnosis of familial adenomatous polyposis.


[Neuroleptic malignant syndrome].
The neuroleptic malignant syndrome (NMS) is presumably caused by neuroleptic blockade of dopamine receptors, mainly in the basal ganglia and hypothalamus. Symptoms include hyperthermia, muscular rigidity, and elevated serum creatine phosphokinase level, also autonomic dysfunction and, facultatively, impairment of consciousness. Clinical features, differential diagnosis and pathogenesis are discussed, as well as therapy with standard drugs as well as intravenous lisuride.


A scoping review of racial/ethnic disparities in sleep.
Despite remarkable achievements in ensuring health equity, racial/ethnic disparities in sleep still persist and are emerging as a major area of concern. Accumulating evidence has not yet been well characterized from a broad perspective. We conducted a scoping review of studies on sleep disparities by race/ethnicity to summarize characteristics of existing studies and identify evidence gaps. We searched PubMed, CINAHL, PsycINFO, and Web of Science databases for studies of racial/ethnic disparities in sleep. Studies that met inclusion criteria were retrieved and organized in a data charting form by study design, sleep measuring methods, sleep features, and racial/ethnic comparisons. One hundred sixteen studies were included in this review. Most studies focused on disparities between Whites and Blacks. Disproportionately fewer studies examined disparities for Hispanic, Asian, and other racial/ethnic groups. Self-reported sleep was most frequently used. Sleep duration, overall sleep quality, and sleep disordered breathing were frequently studied, whereas other features including sleep efficiency, latency, continuity, and architecture were understudied, particularly in racial minority groups in the US. Current study findings on racial/ethnic disparities in most of sleep features is mixed and inconclusive. This review identified significant evidence gaps in racial/ethnic disparities research on sleep. Our results suggest a need for more studies examining diverse sleep features using standardized and robust measuring methods for more valid comparisons of sleep health in diverse race/ethnicity groups.


Analysis of neurotransmitters in rat placenta exposed to flame retardants using IR-MALDESI mass spectrometry imaging.
Chemical exposures can adversely impact fetal development. For many compounds, including common flame retardants, the mechanisms by which this occurs remain unclear, but emerging evidence suggests that disruption at the level of the placenta may play a role. Understanding how the placenta might be vulnerable to chemical exposures is challenging due to its complex structure. The primary objective of this study was to develop a method for detecting placental neurotransmitters and related metabolites without chemical derivatization so changes in the abundance and spatial distribution of neurotransmitters in rat placenta following chemical exposure could be determined using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging. Without chemical derivatization, 49 neurotransmitters and their related metabolites were putatively identified in untreated rat placenta sections using mass measurement accuracy and spectral accuracy. A few neurotransmitters were less abundant in placentas that were exposed to various flame retardants and were further investigated by KEGG metabolic pathway analysis. Many of these downregulated neurotransmitters shared the same enzyme responsible for metabolism, aromaticl-amino acid decarboxylase, suggesting a mechanistic role. These data constitute a new approach that could help identify novel mechanisms of toxicity in complex tissues. Graphical abstract.


Chemical antagonism between photodynamic agents and chemotherapeutics: mechanism and avoidance.
We report a photochemical reaction-induced antagonism between the photodynamic agent (PS) and anti-cancer drugs during combined therapy. The annihilation of singlet oxygen and alkene-containing drugs into inactive drug hydroperoxides is responsible for the antagonism, and results in decreased efficacy against several cancer cell lines. Experimental and simulation results reveal that the annihilation abates with increasing distance between the PS and drugs via confining the PS and drugs into separated vehicles. As a result, antagonism can be switched to synergism in treating both drug sensitive and resistant cancer cells.


Comparative Evaluation of the Depth of Cure and Degree of Conversion of Two Bulk Fill Flowable Composites.
Since the development of resin based composites, several improvements have been made to improve their physical and chemical properties. In an attempt to fasten and simplify the restoration process, a new class of resin based composite materials, called the bulk fill resin based composites have been introduced, which has been claimed to achieve a depth of cure of 4 mm without affecting the properties of the material. To comparatively evaluate the depth of cure of two different bulk fill flowable composite resins by ISO 4049 method and to evaluate the degree of conversion of the same composite resins with Fourier Transform Infrared (FTIR) spectroscopy method. Composite resin specimens (n=10) per group were prepared with bulk fill flowable composites, Surefil SDR flow (Dentsply Caulk, Milford, DE, USA) designated as Group A and Filtek bulk fill (3M ESPE, St.Paul, MN, USA) designated as Group B. Depth of cure was determined according to "ISO 4049; Depth of Cure" method, and FTIR spectroscopy method was used to estimate the degree of conversion of both the bulk fill flowable composites. The degree of conversion of monomer to polymer was estimated individually in coronal half (Group A1 and B1) and pulpal half (Group A2 and Group B2) by dividing each specimens into two halves. The data were analysed using Student's unpaired t-test at 5% level of significance. The mean depth of cure of Group A was 3.89 mm (±0.103) and for Group B was 3.54 mm (±0.129). The degree of conversion percentage for Group A1=78.51 (±47.8), Group A2= 31.9 (±22.4), Group B1=39.8 (±5.2), Group B2=37.4 (±6.4). Statistical analysis revealed significant difference in the depth of cure between the two bulk fill flowable composites with Group A higher than Group B. The degree of conversion of the coronal half of Group A1 was significantly higher when compared to Group B1. Surefil SDR bulk fill resin has better depth of cure and degree of conversion compared to Filtek bulk fill composites.


Does protracted antiviral therapy impact on HCV-related liver cirrhosis progression?
To study the outcomes of patients with compensated hepatitis C virus-related cirrhosis. Twenty-four grade A5 and 11 grade A6 of Child-Pugh classification cirrhotic patients with active virus replication, treated for a mean period of 31.3 +/- 5.1 mo with moderate doses of interferon-alpha and ribavirin, were compared to a cohort of 36 patients with similar characteristics, without antiviral treatment. Salivary caffeine concentration, a liver test of microsomal function, was determined at the starting and thrice in course of therapy after a mean period of 11 +/- 1.6 mo, meanwhile the resistive index of splenic artery at ultra sound Doppler, an indirect index of portal hypertension, was only measured at the beginning and the end of study. Eight out of the 24 A5- (33.3%) and 5 out of the 11 A6- (45.45%) treated-cirrhotic patients showed a significant improvement in the total overnight salivary caffeine assessment. A reduction up to 20% of the resistive index of splenic artery was obtained in 3 out of the 8 A5- (37.5%) and in 2 out of the 5 A6- (40%) cirrhotic patients with an improved liver function, which showed a clear tendency to decrease at the end of therapy. The hepatitis C virus clearance was achieved in 3 out of the 24 (12.5%) A5- and 1 out of the 11 (0.091%) A6-patients after a median period of 8.5 mo combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but 3 patients (8.3%) had a worsening of the Child-Pugh score (P = 0.001). A prolonged antiviral therapy with moderate dosages of interferon-alpha and ribavirin shows a trend to stable liver function or to ameliorate the residual liver function, the entity of portal hypertension and the compensation status at acceptable costs.


Blood-pool imaging using technetium-99m-labeled liposomes.
This study evaluated two 99mTc-liposome formulations as potential blood-pool agents in comparison with standard 99mTc-red cells and 99mTc-human serum albumin (HSA). Liposomes with no surface modification or coated with polyethylene glycol (PEG) were labeled with 99mTc using the lipophilic chelator, HMPAO. Autologous red cells were labeled with 99mTc using in vitro or in vivo techniques. Technetium-99m-HSA was supplied commercially. Rabbits were injected intravenously with 99mTc-liposomes, 99mTc-red cells or 99mTc-HSA. Static images were acquired and blood samples collected. Technetium-99m-liposome images showed prominent blood-pool activity compared to lung and liver activities, which were similar to those acquired for 99mTc-red cells, but better than 99mTc-HSA. Heart-to-lung ratios were not significantly different between 99mTc-liposome formulations or for either formulation compared to 99mTc-red cells. The ratios were higher, however, than for 99mTc-HSA. Heart-to-liver ratios were higher for PEG 99mTc-liposomes than they were for neutral 99mTc-liposomes and 99mTc-HSA, but were not significantly different than 99mTc-red cells. Bladder activities for both 99mTc-liposome formulations were 3-6 times lower than for the other agents. PEG 99mTc-liposomes remained in circulation 1.6 times longer than any of the other agents. Technetium-99m-liposomes, independent of surface modification, had excellent circulation persistence and in vivo stability when compared to 99mTc-red cells and 99mTc-HSA. PEG 99mTc-liposomes performed better than neutral 99mTc-liposomes due to lower liver background activity. Advantages of PEG 99mTc-liposomes compared to 99mTc-red cells include: (a) only one venipuncture, (b) little exposure to patient's blood, (c) excellent in vitro and in vivo stability and (d) lack of drug interference.


Effects of testosterone and estrogen replacement on memory function.
Testosterone insufficiency has been associated with psychosexual problems, reduced psychological well-being, and negative metabolic consequences, whereas less is known about the effects on cognition. The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women. In a randomized, double-blind, placebo-controlled design, women with surgically induced menopause (n = 50; mean [SD] age, 54.0 [2.9] y) received estradiol valerate in combination with testosterone undecanoate or placebo. The women were assessed with a self-report questionnaire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline, at the time of crossover, and after completion of treatment. Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks. Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline. This was not observed in the women in the estrogen + testosterone treatment. Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment. However, there was no significant treatment effect between the two groups. Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo, while other memory functions were unaffected.


Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study.
Although accumulating evidence suggests that Helicobacter pylori plays a role in gastric carcinogenesis, the magnitude of the risk remains uncertain. We aimed to estimate the magnitude of the risk of gastric cancer associated with H. pylori infection by a large case-control study nested within a prospective cohort. Possible effect modification by CagA status, and serum pepsinogen status, as a marker of atrophic gastritis, was also considered to see its effect on developing gastric cancer. Subjects (n = 123,576) were followed up from 1990 to 2004; 511 gastric cancer cases matched to 511 controls were used in the analysis. Plasma immunoglobulin G antibody to H. pylori, CagA, and pepsinogen I and II were measured. The adjusted odds ratio (95% confidence interval) of gastric cancer associated with H. pylori infection was 5.1 (3.2-8.0). Assuming all CagA-positive subjects are true H. pylori positives doubled this risk. Atrophic gastritis was also associated with an elevated risk of gastric cancer and the risk increased further with pepsinogen levels. Subjects with pepsinogen levels indicative of severe atrophic gastritis may need careful examination regularly regardless of H. pylori infection. Those who have other pepsinogen levels but who are H. pylori seropositive are likely to benefit from H. pylori eradication therapy. Considering both the cost and the potential for misclassification that may occur using multiple serologic tests, caution is needed in interpreting or extrapolating these findings into a screening strategy.


The role of cardiac troponin I as a prognosticator in critically ill medical patients: a prospective observational cohort study.
Myocardial injury is frequently unrecognized in intensive care unit (ICU) patients. Cardiac troponin I (cTnI), a surrogate of myocardial injury, has been shown to correlate with outcome in selected groups of patients. We wanted to determine if cTnI level measured upon admission is an independent predictor of mortality in a heterogeneous group of critically ill medical patients. We conducted a prospective observational cohort study; 128 consecutive patients admitted to a medical ICU at a tertiary university hospital were enrolled. cTnI levels were measured within 6 h of admission and were considered positive (>0.7 ng/ml) or negative. A variety of clinical and laboratory variables were recorded. Both cTnI positive and negative groups were similar in terms of age, sex and pre-admission co-morbidity. In a univariate analysis, positive cTnI was associated with increased mortality (OR 7.0, 95% CI 2.44-20.5, p < 0.001), higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores and a higher rate of multi-organ failure and sepsis. This association between cTnI and mortality was more pronounced among elderly patients (>65 years of age). Multivariate analysis controlling for APACHE II score revealed that elevated cTnI levels are not independently associated with 28-day mortality. In critically ill medical patients, elevated cTnI level measured upon admission is associated with increased mortality rate. cTnI does not independently contribute to the prediction of 28-day mortality beyond that provided by APACHE II.


Experimental Candida albicans infection in conventional mice and germfree rats.
Swiss-Webster white mice were intravenously infected with various doses of Candida albicans, and the viable units in their spleens, livers, lungs, and kidneys were determined at various intervals after challenge. The results showed that C. albicans multiplied to a greater extent in the kidneys of mice than in their spleens, lungs, or livers. The infection in mice was chronic; increasing numbers of C. albicans were observed in their kidneys until about 17 to 24 days postchallenge. Clearance of C. albicans from infected kidneys was not symmetrical, since the number of viable C. albicans in one kidney did not coincide with the viable counts observed in the opposite kidney of that same animal. Male and female mice did not differ in their overall susceptibility (50% lethal dose test) or in the number of viable C. albicans in the kidneys at various time intervals after infection. C. albicans also multiplied in the kidneys of germfree rats; however, the peak of the C. albicans infection in their kidneys occurred earlier than in those of conventional mice.


Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to Ets binding sites.
The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction.


Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene.
Uridine phosphorylase (UPase) plays an important role in the activation of 5-fluorouracil and in the regulation of tissue and plasma concentration of uridine, a potential biochemical modulator of 5-fluorouracil therapy. UPase expression is affected by the c-H-ras oncogene and various cytokines through unknown mechanisms. To understand its expression and regulation, we cloned the murine UPase gene, defined its genomic organization, determined its 5'- and 3'-end flanking sequences, and evaluated the promoter activity. The UPase gene contains nine exons and eight introns, spanning a total of approximately 18.0 kb. Its promoter lacks canonical TATA and CCAAT boxes, although a CAATAAAAA TATA-like box is seen from -41 to -49. Furthermore, IFN regulatory factor 1, c/v-Myb, and p53 binding sites are present in the promoter region, indicating that UPase expression may be directly regulated by cytokines and oncogene products. The 1.2-kb flanking fragment showed promoter activity driving the expression of the luciferase gene in various mammalian cells. A TGGGG repeat sequence is seen in the 3'-end flanking region. This element is considered to be a potential recombination consensus hot spot that may contribute to the encoding of different UPase isoforms present in different tissues, both normal and neoplastic.


Stepwise enzymatic oligoribonucleotide synthesis including modified nucleotides.
A method has been developed for the routine synthesis of 2'(3')-o-monoacyl ribonucleoside 5'-diphosphates for stepwise synthesis of oligoribonucleotides with Escherichia coli polynucleotide phosphorylase. The use of triethyl orthoisovalerate allows the facile preparation of 2'(3')-o-isovaleryl-UDP, -CDP, -ADP, -GDP, -IDP, -EPLISON-APD, eplison-CDP, and N6-isopentenyl-ADP. The synthesis of N6-isopentenyl-ADP from ADP by N1-alkylation and the Dimroth rearrangement to N6 is reported. The effects of several factors including the nature of the divalent cation, pH, SALT CONCENTRATION, AND TIME ON THE EFFICIENCY OF THE POLYNUCLEOTIDE PHPSPHORYLASE CATALYZED SINGLE ADDITIONS OF THE 2'(3')-O-ISOVALERYL RIBONUCLEOSIDE 5'-DIPHOSPHATES TO AN OLIGORIBONUCLEOTIDE PRIMER ARE REPORTED. The syntheses of many tetranucleoside triphosphates and two pentanucleoside tetraphosphates in yields of 20-75 per cent are reported. The 2'(3')-o-isovaleryl derivatives of IDP, eplison-ADP, eplison-CDP, and N6-isopentenyl-ADP were all accepted by polynucleotide phosphorylase as substrates for the monoaddition reaction. The extension of the method to include the syntheses of oligoribonucleotides containing modified nucleosides offers a means of studying the role s of these modification by the use of relatively simple model compounds.


Ecological implications of condensed tannin structure: A case study.
Condensed tannins were isolated from bitterbnish (Purshia tridentata) and blackbrush (Coleogyne ramosissima). Structural analyses showed that both tannins were procyanidins of similar polymer length. The overall stereochemistries at C-3 and C-4, however, differed between the two tannins. These changes in stereochemistry resulted in blackbrush tannins being less preferred than bitterbrush tannins when offered to snowshoe hares (Lepus americanus). It is unlikely that differences in protein-precipitating abilities are the cause for the preference of the bitterbrush over the blackbrush tannins. Instead, we hypothesize that condensed tannins may be depolymerized and absorbed following ingestion. Differences in tannin structure can lead to different depolymerized products and rates of depolymerization, both of which may affect herbivore preferences.


Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study.
Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%. Benefit of the study is a possible limitation of unnecessary use of antibiotics. The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality. This trial is registered in the U.S. National Institutes of Health's register, located at http://www.clinicaltrials.gov. (NCT00854932).


Achieving cholesterol target in a managed care organization (ACTION) trial.
To objectively compare the results of a collaborative approach using pharmacists with the results of usual care for achieving a low-density lipoprotein cholesterol (LDL) goal of 100 mg/dl or less in outpatients with documented coronary heart disease (CHD) who are not at goal, and to document the effect on LDL after removal of such a collaborative model from the study population. Prospective, multiclinic, controlled study. Four clinics of a 19-clinic staff model health maintenance organization in Minneapolis and St. Paul, Minnesota. Two clinics treated the intervention patients, two the controls; one clinic for each group was suburban, and one for each was urban. Four hundred eighty-one patients aged 18 years or older with CHD and whose LDL levels were not at goal. Clinical pharmacists implemented the physician-approved care plan for each intervention patient; activities included managing lipid-lowering drug therapy and educating patients on cardiovascular risk reduction. Primary outcomes were changes in LDL level and the proportion of patients achieving goal LDL in the intervention versus the usual care (control) group. Secondary outcomes were the sustainability of the impact observed up to 18 months after discontinuation of the intervention. Mean+/-SD baseline LDL levels were 131+/-28 and 131+/-26 mg/dl (p=NS) for the intervention and control groups, respectively. After a mean of 6.5 months follow-up, 107 (72%) patients in the intervention group and 61 (18%) patients in the control group had attained their LDL goal (p<0.001). Mean LDL levels were reduced by 35.6 mg/dl (27.5%) and 6.7 mg/dl (4.6%) in the intervention and control groups, respectively (p<0.001). When the active program was discontinued, results of the 18-month follow-up indicated that 85 (65%) intervention patients remained at goal compared with 96 (42%) controls (p<0.001). This trial provides quantitative evidence to support the effectiveness of the collaborative approach as an intervention to optimize management of patients with CHD whose LDL levels are not at goal; this approach is specifically called for in the executive summary of the National Cholesterol Education Program Adult Treatment Panel III. Furthermore, this study documents both the magnitude and sustainability of the impact collaborative care models can have in managed care environments.


Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.
The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration. Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control. We studied the effects of octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the induction of STZ diabetes. Two days after induction of diabetes, kidney IGF-I was increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g tissue (P < 0.001) in diabetic animals. The diabetes-associated increase in renal IGF-I 48 h after STZ injection was totally prevented by octreotide (IGF = 780 +/- 57 ng/g tissue). However, 7 days after the induction of diabetes, kidney IGF-I was similar to that of control and was not affected by octreotide. No difference in serum IGF-I was observed between controls and diabetic rats after 2 days of diabetes; however, octreotide treatment resulted in a significant decrease of serum IGF-I after 2 days when compared with control rats (P < 0.05). Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group. Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls. Octreotide treatment prevented the diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days after the induction of diabetes, renal IGFBP-1 mRNA and protein were similarly increased in both octreotide-treated or untreated diabetic rats. Renal IGFBP-3 gene expression and protein and IGFPB-5 mRNA remained unchanged after 2 and 7 days of diabetes when treated or untreated with octreotide. We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.


The energetic of (CH2F2)2 investigated by TDL IR spectroscopy and DFT computations: From collision induced relaxation of ro-vibrational transitions to non-covalent interactions.
Difluoromethane (CH2F2) is an atmospheric pollutant presenting strong absorptions within the 8-12 μm atmospheric window, hence it can contribute to global warming. Its dimer, (CH2F2)2, is bound through weak hydrogen bonds (wHBs). Theoretically, wHBs are of paramount importance in biological systems, though their modeling at density functional theory (DFT) level requires dispersion correlations to be accounted for. In this work, the binding energy (3.1 ± 0.5 kcal mol(-1)) of (CH2F2)2 is experimentally derived from the foreign broadening coefficients of the monomer compound, collisionally perturbed by a range of damping gases. Measurements are carried out on CH2F2 ro-vibrational transitions by means of tunable diode laser spectroscopy. Six stationary points on the potential energy surface (PES) of the dimer are investigated at DFT level by using some of the last generation density functionals (DFs). The Minnesota M06 suite of functionals as well as range separated DFs and DFs augmented by the non-local (NL) van der Waals (vdW) dispersion corrections are considered. DFT results are compared to reference values at the estimated complete basis set (CBS) limit of CCSD(T) theory (coupled cluster with singles and doubles augmented by a perturbational estimate of connected triples) and to the experimental binding energy. The M06-2X, M06-HF, VV10, BLYP-NL, and B3LYP-NL DFs reproduce CCSD(T)/CBS binding energies with a mean absolute deviation <0.4 kcal mol(-1) and about the same deviation from the experimental value. The present results are of twofold relevance: (i) they show that binding energy of homodimers can be conveniently obtained from the monomer's foreign broadening coefficients and that the correct simulation of hydrogen bonds involved in (CH2F2)2 needs non-covalent interactions to be included into DFT; (ii) O2- and N2-pressure broadening parameters represent fundamental data for exploiting the efficacy of remote sensing measurements employed to retrieve temperature and concentration profiles of our atmosphere.


Application of contingent physical restraint to suppress stereotyped body rocking of profoundly mentally retarded persons.
The effectiveness of contingent restraint in reducing stereotyped body rocking of profoundly retarded subjects was investigated to determine (a) whether restraint reduced stereotyped body rocking and (b) the degree to which the effectiveness of restraint depended upon where in the behavioral sequence it was administered. Results showed that restraint, in comparison to no restraint, reduced the amount of body rocking. Also, restraint was judged to be generally more effective if it were applied when the subject was bent over in the middle of the response sequence rather than administered while the subject was sitting upright at the end of the response sequence. The results were interpreted in terms of response chaining and postural feedback. Implications for the utilization of physical restraint as a behavioral intervention were discussed.


Duplex sonography in the evaluation of carotid artery disease.
High-resolution duplex sonography was compared with biplane magnified carotid angiography in a prospective evaluation of 161 carotid arteries in 86 patients. The duplex scanner combined real-time B-mode imaging (7.5 MHz) with simultaneous range-gated pulsed Doppler frequency analysis (3 MHz). The degree of stenosis was usually determined by the true and residual lumen of the carotid artery at the atherosclerotic plaque on the transverse image. The Doppler frequency signals were automatically converted to velocity data by a minicomputer. The accuracy of the duplex system in detecting and assessing stenoses graded in 20% increments is demonstrated according to specificity, sensitivity, and positive and negative predictive value by both cumulative and subgroup analyses. A 93.7% sensitivity was shown for minimal (0-20%) stenosis and 100% sensitivity for severe (greater than 60%) stenosis. An apparent limitation of duplex sonography is the differentiation of a high-grade stenosis from occlusion (sensitivity, 82.6%; positive predictive value, 90.4%).


[Treatment of tension type headache: paracetamol and NSAIDs work: a systematic review].
Tension-type headache (TTH), also known as tension headache or muscle contraction headache is the most commonly experienced type of headache. Our aim was to evaluate the effectiveness of interventions in patients with TTH. We performed a systematic review according to the guidelines of the Cochrane Collaboration. Randomised trials reporting conservative treatments in patients with TTH with headache as outcome were included. In the analysis studies were grouped according to type of intervention: acute pain medication, preventive medication, physiotherapy interventions, behavioural interventions and interventions in children. A total of 152 trials were included in this review with 17.523 patients, of which 37 studies (24.3%) were considered to be of high quality. Nine studies could not be included in one of the five subgroups. ACUTE MEDICATION: (41 trials). The pooled analyses showed that NSAIDs and acetaminophen are more effective than placebo. No significant differences could be found between different types of NSAIDs, but ibuprofen showed fewer short-term side effects when compared to other NSAIDs. There was a significant difference in favour of NSAIDs when compared to acetaminophen. PREVENTIVE MEDICATION: (44 trials). Overall, the use of antidepressants does not show to be more effective than placebo, and no significant differences between different types of antidepressants were found. Furthermore there is limited evidence concerning the negative effects of propranolol on depression in TTH patients, when compared to placebo or biofeedback. There is conflicting evidence about the effectiveness of benzodiazepines and vasodilator agents compared to placebo. There is no evidence concerning the effectiveness of muscle relaxants compared to placebo. BEHAVIOURAL THERAPY: (44 trials). Eight studies compared relaxation treatment with a waiting list or attention placebo control, and 11 studies compared EMG biofeedback with placebo and in both interventions we found inconsistent results. Most trials lack adequate power to show statistical significant differences, but frequently recovery/improvement rates did not reach clinical relevance. PHYSIOTHERAPEUTIC INTERVENTIONS: (12 trials). A wide variety of interventions were evaluated, such as spinal manipulations, exercise and physical applications. Overall the studies showed inconsistent results. (11 trials). Eight studies evaluated the effectiveness of relaxation training. We found conflicting evidence for relaxation therapy compared with no treatment or other treatments. The evidence in this review suggests that NSAIDs and acetaminophen are both effective for short-term pain relief in patients with TTH. No specific type of NSAID was clearly more effective than others, but ibuprofen showed fewer side effects. There is insufficient evidence to either support or refute the effectiveness of preventive medication, physiotherapy, (spinal) manipulation, EMG biofeedback or cognitive behavioural treatment in patients with TTH.


Detection of Optic Disc Abnormalities in Color Fundus Photographs Using Deep Learning.
To date, deep learning-based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies. Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation. During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98-0.99), sensitivity 94% (95 CI: 91%-97%), and specificity 96% (95 CI: 93%-99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%. In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future.


[BB creatine kinase isoenzyme activity in the blood serum of patients with senile dementia, Alzheimer's disease and schizophrenia].
Total creatine kinase (CPK) activity and the activity of brain-type creatine kinase (CPK BB) was determined in the blood serum of schizophrenic patients, senile dementia and Alzheimer disease patients and mentally sane individuals by means of bioluminescence assay. The increased activity of total CPK in the serum of schizophrenics and a 2-fold increase of CPK BB activity in the serum of patients with these mental diseases was demonstrated. The findings suggest the presence of destructive processes not only in demented brains but also in the schizophrenic brains.


The role of endogenous dopamine in the hypermotility response to intra-accumbens AMPA.
The present study was designed to investigate the role of dopamine in the locomotor stimulant response produced by the bilateral administration of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) into the nucleus accumbens. The hypermotility produced by lower doses of AMPA (up to 0.25 microgram) was inhibited by either SCH23390 or sulpiride, a D1 and D2 receptor antagonist, respectively. The locomotor response to a higher dose of AMPA (0.5 microgram) was greater than the maximum response to intra-accumbal injection of amphetamine and was significantly inhibited only when both the D1 and D2 antagonists were administered together. Alpha-Methyl-p-tyrosine inhibited the locomotor response to AMPA (0.5 microgram), and this inhibition was reversed by the co-injection of AMPA with either SKF38393, a D1 agonist, or quinpirole, a D2 agonist, at doses which were ineffective in the absence of AMPA. AMPA when infused into the nucleus accumbens produced an increase in extracellular dopamine, suggesting that AMPA can enhance dopamine efflux. The injection of AMPA into the nucleus accumbens significantly increased the DOPAC/dopamine ratio, which is different from the decrease in ratio reported for amphetamine. These data suggest that the stimulation of locomotor activity by intra-accumbal AMPA may be the result of an enhancement in dopamine efflux as well as a change in the response to dopaminergic receptor activation.


A Quality Improvement Project to Support Post-Intensive Care Unit Patients with COVID-19: Structured Telephone Support.
More than 50% of intensive care unit (ICU) survivors suffer from long-lasting physical, psychosocial, and cognitive health impairments, also called "post-intensive care syndrome" (PICS). Intensive care admission during the COVID-19 pandemic was especially uncertain and stressful, both for patients and for their family. An additional risk of developing symptoms of PICS was feared in the absence of structural aftercare for the patient and family shortly after discharge from the hospital. The purpose of this quality improvement study was to identify PICS symptoms and to support post-intensive care patients and families in the transition from the hospital to the home. Therefore, we offered post-ICU patients and families structured telephone support (STS). This was a quality improvement study during the 2019 COVID-19 pandemic. A project team developed and implemented a tool to structure telephone calls to identify and order symptoms according to the PICS framework and to give individual support based on this information. We supported post-ICU patients diagnosed with COVID-19 pneumonia and their family caregivers within four weeks after hospital discharge. The reported findings were both quantitative and qualitative. Forty-six post-ICU patients received structured telephone support and reported symptoms in at least one of the three domains of the PICS framework. More than half of the patients experienced a loss of strength or condition and fatigue. Cognitive and psychological impairments were reported less frequently. Family caregivers reported fewer impairments concerning fatigue and sleeping problems and expressed a need for a continuity of care. Based on the obtained information, the ICU nurse practitioners were able to check if individual care plans were optimal and clear and, if indicated, initiated disciplines to optimize further follow-up. The implementation of the STS tool gave insight in the impairments of post-ICU patients. Surprisingly, family caregivers expressed fewer impairments. Giving support early after hospital discharge in a structured way may contribute to providing guidance in the individual care plans and treatment of the early symptoms of PICS (-F).


Interaction of staphylococcal enterotoxin B with cell cultures I. Effect of serum and testing procedures.
The cytopathic effect of staphylococcal enterotoxin B upon mammalian cell cultures is expressed fully only if the cultures are grown in human serum-supplemented media. Little cytotoxicity is seen if the cells are grown in horse serum-supplemented media and none is seen if the cells are grown in calf serum-supplemented media. The cytotoxicity of the toxin is reversible at any stage of intoxication. Cytotoxicity is rarely seen before 5 hr and is most often not evident before 8 hr. Cytoxicity is not lethal.


Morale in the English mental health workforce: questionnaire survey.
High-quality evidence on morale in the mental health workforce is lacking. To describe staff well-being and satisfaction in a multicentre UK National Health Service (NHS) sample and explore associated factors. A questionnaire-based survey (n = 2258) was conducted in 100 wards and 36 community teams in England. Measures included a set of frequently used indicators of staff morale, and measures of perceived job characteristics based on Karasek's demand-control-support model. Staff well-being and job satisfaction were fairly good on most indicators, but emotional exhaustion was high among acute general ward and community mental health team (CMHT) staff and among social workers. Most morale indicators were moderately but significantly intercorrelated. Principal components analysis yielded two components, one appearing to reflect emotional strain, the other positive engagement with work. In multilevel regression analyses factors associated with greater emotional strain included working in a CMHT or psychiatric intensive care unit (PICU), high job demands, low autonomy, limited support from managers and colleagues, age under 45 years and junior grade. Greater positive engagement was associated with high job demands, autonomy and support from managers and colleagues, Black or Asian ethnic group, being a psychiatrist or service manager and shorter length of service. Potential foci for interventions to increase morale include CMHTs, PICUs and general acute wards. The explanatory value of the demand-support-control model was confirmed, but job characteristics did not fully explain differences in morale indicators across service types and professions.


Fluoroquinolone-dependent DNA supercoiling by Vaccinia topoisomerase I.
Vaccinia topoisomerase I is a site-specific DNA strand transferase that acts through a DNA-(3'-phosphotyrosyl)-enzyme intermediate, resulting in relaxation of supercoiled DNA. Although Vaccinia topoisomerase I is not an essential enzyme, its role in early transcription makes it a potential antiviral target. We describe the interaction of Vaccinia topoisomerase I with fluoroquinolone antibiotics otherwise known to target DNA gyrase and topoisomerase IV in bacterial cells. The fluoroquinolone enrofloxacin inhibits DNA relaxation by Vaccinia topoisomerase I at concentrations similar to those required for inhibition by the coumarin drugs coumermycin and novobiocin. When Vaccinia topoisomerase I is presented with relaxed DNA in the presence of enrofloxacin, it executes the reverse reaction, supercoiling the DNA. Further characterization indicates that enrofloxacin does not interfere with the initial strand scission by Vaccinia topoisomerase I. The structurally related fluoroquinolones moxifloxacin and lomefloxacin have no effect on the topoisomerase at the concentrations at which enrofloxacin mediates DNA supercoiling. The mechanism with which Vaccinia topoisomerase I supercoils relaxed DNA, an energetically unfavorable, yet ATP-independent process, must entail protein-DNA contacts downstream of the cleavage site, as opposed to the free rotation mechanism proposed for DNA relaxation; as proposed for fluoroquinolone-mediated inhibition of gyrase, the drug may target a preformed topoisomerase I-DNA complex to induce conformational changes in the enzyme that permit such contacts.


Energy efficient and fast reversal of a fixed skyrmion two-terminal memory with spin current assisted by voltage controlled magnetic anisotropy.
Recent work (P-H Jang et al 2015 Appl. Phys. Lett. 107 202401, J. Sampaio et al 2016 Appl. Phys. Lett. 108 112403) suggests that ferromagnetic reversal with spin transfer torque (STT) requires more current in a system in the presence of Dzyaloshinskii-Moriya interaction (DMI) than switching a typical ferromagnet of the same dimensions and perpendicular magnetic anisotropy (PMA). However, DMI promotes the stabilization of skyrmions and we report that when perpendicular anisotropy is modulated (reduced) for both the skyrmion and ferromagnet, it takes a much smaller current to reverse the fixed skyrmion than to reverse the ferromagnet in the same amount of time, or the skyrmion reverses much faster than the ferromagnet at similar levels of current. We show with rigorous micromagnetic simulations that skyrmion switching proceeds along a different path at very low PMA, which results in a significant reduction in the spin current or time required for reversal. This can offer potential for memory applications where a relatively simple modification of the standard STT-RAM (to include a heavy metal adjacent to the soft magnetic layer and with appropriate design of the tunnel barrier) can lead to an energy efficient and fast magnetic memory device based on the reversal of fixed skyrmions.


Cytokine Regulation and Fast Inflammation Resolution in Early Rheumatoid Arthritis by Cerium-Modified Gold Nanoclusters.
Rheumatoid arthritis (RA) is an incurable chronic disorder that may induce autoinflammation and serious pain in the joints. Early diagnosis and treatment are important for RA prognosis. However, there is a lack of effective and objective diagnostic approaches. Levels of several immunity cytokines were found to change for patients with early RA, including IL-6, TNF-α, and IL-17 in serum. We assumed a combined change of these cytokines could predict early RA, and a total of 37 outpatients were found. After these patients with early symptoms had been followed for more than one year, 32 clinical cases of RA were diagnosed. The accuracy rate of the current method is >86%. We assumed the symptom relief could be achieved by regulating these cytokines and serum lipid-associated indicators. Thereafter, (R)-dihydrolipoic acid (R-DHLA)-stabilized gold nanoclusters (AuNCs) without (R-DHLA-AuNCs) and with cerium modification (R-DHLA-AuNCs-Ce) were employed for treatment of the RA rat model in vitro and in vivo. R-DHLA-AuNCs-Ce exhibited extraordinary reactive oxygen species-scavenging and anti-inflammation effects by regulating macrophage polarization, which was found to be more effective than methotrexate. The inflammation response of the joint microenvironment was also reduced with an exciting efficiency. By complex analysis of the pro-inflammatory cytokines and activity period indicators in vivo and in vitro, we concluded that macrophage-mediated inflammation exacerbated autoimmunity, which fully relieved the symptoms after administration of R-DHLA-AuNCs-Ce to RA rats.


Hypervirulent Group A Streptococcus of Genotype emm3 Invades the Vascular System in Pulmonary Infection of Mice.
Natural mutations of the two-component regulatory system CovRS are frequently associated with invasive group A Streptococcus (GAS) isolates and lead to the enhancement of virulence gene expression, innate immune evasion, systemic dissemination, and virulence. How CovRS mutations enhance systemic dissemination is not well understood. A hypervirulent GAS isolate of the emm3 genotype, MGAS315, was characterized using a mouse model of pulmonary infection to understand systemic dissemination. This strain has a G1370T mutation in the sensor kinase covS gene of CovRS. Intratracheal inoculation of MGAS315 led to the lung infection that displayed extensive Gram staining at the alveolar ducts, alveoli, and peribronchovascular and perivascular interstitium. The correction of the covS mutation did not alter the infection at the alveolar ducts and alveoli but prevented GAS invasion of the peribronchovascular and perivascular interstitium. Furthermore, the covS mutation allowed MGAS315 to disrupt and degrade the smooth muscle and endothelial layers of the blood vessels, directly contributing to systemic dissemination. It is concluded that hypervirulent emm3 GAS covS mutants can invade the perivascular interstitium and directly attack the vascular system for systemic dissemination.


The experiences of speech pathology referral and communicative participation in adults with cerebellar ataxia.
Purpose: The purpose of this study was to identify potential barriers to speech pathology referral in ataxia, as well as potential factors influencing satisfaction with speech pathology and communicative participation.Method: An online survey study included questions about participant demographics, referral and access to speech pathology, satisfaction with speech pathology, and communicative participation via the Communicative Participation Item Bank (CPIB).Results: We analysed 118 eligible responses from individuals with ataxia. Results from Bayesian regression models indicated that the overall referral rate to speech pathology was 64% for the respondents with a speech impairment, predicted by lower income, less education, and greater self-perceived speech severity. Additionally, sex, self-perceived speech severity, and length of speech impairment predicted more restricted communicative participation. For the respondents who were referred for speech pathology, overall satisfaction with speech pathology was neutral to high but most individuals reported little to no improvement in their speech.Conclusion: Referral rate to speech pathology was low given that dysarthria and dysphagia are highly likely to occur in ataxia. Considerations should be made for perceived speech severity, sex, and length of speech impairment in evaluating communicative participation. Lastly, there is a vital need for evidence-based treatment for ataxic dysarthria.


Pattern of neurological disorder presenting at a paediatric neurology clinic in Nigeria.
Neurological diseases account for more than 20% of the world's disease burden with majority of affected people living in Africa. However there is a paucity of literature on neurological disease in Africa. A retrospective review of 114 children with neurological problem seen at a paediatric neurological clinic in a 2-year. Delayed developmental milestone, convulsion and inability to walk were the 3 most common reasons for referral to our Paediatric neurology clinic. Cerebral palsy (55.3%), Seizure disorder (26.3%) and postmeningitic complications (6.2%) were the common neurological disorder seen at our neurology clinic. The Paediatric outpatient department (POPD) of our hospital was the main source of referral for most cases (83.2%) and 71.1% of all patients resides within Zaria metropolis. The default rate from follow-up was higher among children with cerebral palsy compared to children with seizure disorder (58.7% vs. 13.3%, P < 0.001). Lack of adequate facilities for proper rehabilitation of children with cerebral palsy could have been the main reason for the high default rate from follow-up.


Development of a Tongue Immobilization Device Using a 3D Printer for Intensity Modulated Radiation Therapy of Nasopharyngeal Cancer Patients.
This study aimed to reduce radiation doses to the tongue, a patient-specific semi-customized tongue immobilization device (SCTID) was developed using a 3D printer for helical tomotherapy (HT) of nasopharyngeal cancer (NPCa). Dosimetric characteristics and setup stability of the SCTID were compared with those of a standard mouthpiece (SMP). For displacement and robust immobilization of the tongue, the SCTID consists of four parts: upper and lower tooth stoppers, tongue guider, tongue-tip position guide bar, and connectors. With the SCTID and SMP, two sets of planning computed tomography and HT plans were obtained for 10 NPCa patients. Dosimetric and geometric characteristics were compared. Position reproducibility of the tongue with SCTID was evaluated by comparing with planned dose and adaptive accumulated dose of the tongue and base of the tongue based on daily setup mega-voltage computed tomography. Using the SCTID, the tongue was effectively displaced from the planning target volume compared to the SMP. The median mucosa of the tongue (M-tongue) dose was significantly reduced (20.7 Gy vs. 27.8 Gy). The volumes of the M-tongue receiving a dose of 15 Gy, 30 Gy, and 45 Gy and the volumes of the mucosa of oral cavity and oropharynx (M-OC/OP) receiving a dose of 45 Gy and 60 Gy were significantly lower than using the SMP. No significant differences was observed between the planned dose and the accumulated adaptive dose in any dosimetric characteristics of the tongue and base of tongue. SCTID can not only reduce the dose to the M-tongue and M-OC/OP dramatically, when compared to SMP, but also provide excellent reproducibility and easy visual verification.


Reproductive technologies as population control: how pronatalist policies harm reproductive health in South Korea.
Through the examination of pronatalist policies introduced in South Korea within the last decade, the aim of this commentary is to assess how such policies could harm women's reproductive health if they are practiced only for the purpose of population control. South Korea is a country with one of the lowest fertility rates in the world, and to increase population growth, since 2005, the Korean government has heavily regulated and promoted the use of reproductive technologies, including abortion technologies and assisted reproductive technologies (ARTs). This represents a dramatic shift from South Korea's historically antinatalist position: from the 1960s to the 1980s, abortion was widely practiced and encouraged by the government to reduce population growth, and the use of ARTs went unsupported by the government. However, when the total fertility rate reached 1.08 in 2005, the government strictly prohibited abortion and started promoting the use of ARTs to increase the nation's birthrate. Although under the current pronatalist policies, the Korean government has provided unprecedented incentives to couples seeking to have children, such as expanded maternal/paternal leave and childcare benefits, ironically, reproductive health indicators, such as maternal mortality and infant mortality, have not improved and, in some cases, have even worsened because the pronatalist policies fail to consider women's reproductive health and rights issues.


Performance evaluation of a laboratory developed PCR test for quantitation of HIV-2 viral RNA.
Management of Human Immunodeficiency Virus Type 2 (HIV-2) infections present unique challenges due to low viral titers, slow disease progression, and poor response to standard antiviral therapies. The need for a nucleic acid assay to detect and quantify HIV-2 virus has led to the development of a number of molecular-based assays for detection and/or quantification of HIV-2 viral RNA in plasma in order to provide laboratory evidence of HIV-2 infection and viral loads for use in treatment decisions. As HIV-2 is less pathogenic and transmissible than HIV-1 and has resistance to several of the antiretroviral drugs, delay of treatment is common. Cross sero-reactivity between HIV-1 and HIV-2 makes it difficult to distinguish between the two viruses based upon serological tests. As such we developed a quantitative reverse transcription PCR (qRT-PCR) assay targeting the 5' long terminal repeat of HIV-2 for detection and quantification of HIV-2 viral RNA in plasma to identify HIV-2 infection and for use in viral load monitoring. Serial dilutions of cultured HIV-2 virus demonstrated a wide dynamic range (10 to 100,000 copies/ml) with excellent reproducibility (standard deviation from 0.12-0.19), linearity (R2 = 0.9994), and a lower limit of detection at 79 copies/ml (NIH-Z). The assay is highly specific for HIV-2 Groups A and B and exhibits no cross reactivity to HIV-1, HBV or HCV. Precision of the assay was demonstrated for the High (Mean = 6.41; SD = 0.12) and Medium (Mean = 4.46; SD = 0.13) HIV-2 positive controls. Replicate testing of clinical specimens showed good reproducibility above 1,000 copies/ml, with higher variability under 1,000 copies/ml. Analysis of 220 plasma samples from HIV-2 infected West African individuals demonstrated significantly lower viral loads than those observed in HIV-1 infections, consistent with results of previous studies. Slightly more than seven percent of clinical samples (7.3%) demonstrated viral loads above 100,000 copies/ml, while 37.3% of samples were undetectable. The high sensitivity, specificity, precision, and linearity of the WRAIR qRT-PCR assay makes it well suited for detection and monitoring of HIV-2 RNA levels in plasma of infected individuals.


Effect of relative humidity on survival of Candida albicans and other yeasts.
Individual blastospores of Candida albicans were deposited on the surface of 50-mm membranes (Millipore Corp.) and placed within sealed glass chambers at various relative humidities (RH). After 48 hr, virtually all cells maintained at 100 and 10% RH had survived, but 84% of the cells maintained at 60% RH failed to develop into colonies when transferred to Sabouraud medium. No morphological abnormalities could be observed in cells surviving low RH values, but their initial rate of multiplication after transfer to Sabouraud medium was greatly reduced, compared to that demonstrated by cells maintained at 100% RH. At 60% RH, the exposure time required to kill 50% of the blastospores was 2 to 3.5 days. The inimical effect of 60% RH was confirmed in a total of 21 isolates of C. albicans. No deleterious effect was noted when 12 other species of yeasts were subjected to 10, 60, and 100% RH. The single isolate of Candida brumptii and 1 out of the 20 isolates of Cryptococcus neoformans tested also failed to grow after blastospores had been exposed to 60% RH for 4 days.