Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients.
Prescribing medication is an important aspect of almost all in-hospital treatment regimes. Besides their obviously beneficial effects, medicines can also cause adverse drug events (ADE), which increase morbidity, mortality and health care costs. Partially, these ADEs arise from medication errors, e.g. at the prescribing stage. ADEs caused by medication errors are preventable ADEs. Until now, medication ordering was primarily a paper-based process and consequently, it was error prone. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) is considered to enhance patient safety. Limited information is available on the balance between the health gains and the costs that need to be invested in order to achieve these positive effects. Aim of this study was to study the balance between the effects and costs of CPOE/CDSS compared to the traditional paper-based medication ordering. The economic evaluation was performed alongside a clinical study (interrupted time series design) on the effectiveness of CPOE/CDSS, including a cost minimization and a cost-effectiveness analysis. Data collection took place between 2005 and 2008. Analyses were performed from a hospital perspective. The study was performed in a general teaching hospital and a University Medical Centre on general internal medicine, gastroenterology and geriatric wards. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) was compared to a traditional paper based system. All costs of both medication ordering systems are based on resources used and time invested. Prices were expressed in Euros (price level 2009). Effectiveness outcomes were medication errors and preventable adverse drug events. During the paper-based prescribing period 592 patients were included, and during the CPOE/CDSS period 603. Total costs of the paper-based system and CPOE/CDSS amounted to €12.37 and €14.91 per patient/day respectively. The Incremental Cost-Effectiveness Ratio (ICER) for medication errors was 3.54 and for preventable adverse drug events 322.70, indicating the extra amount (€) that has to be invested in order to prevent one medication error or one pADE. CPOE with basic CDSS contributes to a decreased risk of preventable harm. Overall, the extra costs of CPOE/CDSS needed to prevent one ME or one pADE seem to be acceptable.


Plant-growth promotion by halotolerant black yeast Hortaea sp. strain PMGTC8 associated with salt crystals from solar saltern of Goa, India.
Plant-growth-promoting microbes are sustainable alternative to improve the soil fertility and plant-growth facilitating the nutrients uptake in normal and stressed environmental conditions. Among these, halotolerant and halophilic microorganisms with plant- growth-promoting ability are better candidates that could be exploited as bioinoculants in salinity affected agriculture soils. Considering this, the current study aimed to isolate, characterize and determine the plant-growth-promoting potential of the culturable halotolerant black yeast associated with salt crystals from the solar saltern of Goa, India. The results revealed 1.3 × 104 CFU/g of viable number of colonies on 25% NaCl Tryptone Yeast Extract (NTYE) agar after 30-45 days incubation. Among ten morphologically distinct isolates, a black pigmented strain PMGTC8 was characterized as yeast-like and appeared two celled with average size of 4.30 ± 0.14 µm under scanning electron micrograph. Based on phylogenetic analysis using internal transcribed spacer (ITS) marker, the isolate showed maximum similarity to genus Hortaea. Interestingly, Hortaea sp. strain PMGTC8 (OR527117) exhibited plant-growth-promoting characteristics and caused significantly (p < 0.01) higher germination rate (93.33%), vigor index (964.22), shoot (3.95 cm) and root length (6.38 cm), and fresh weight (0.039 g) of Oryza sativa var. Korgut. This halotolerant black yeast may play a role in nutrition of the plants growing in saline soils. Conclusively, the current findings report for the first time the plant-growth-promoting potential of Hortaea sp. strain PMGTC8 associated with salt crystals of solar saltern, Goa, India for its possible use as bio-fertilizers in saline agriculture soils.


Development of a method using image analysis for the measurement of cellulose-binding domains adsorbed onto cellulose fibers.
The surface concentration of CBD-FITC conjugates, adsorbed on cellulose fibers, was determined by image analysis. The program consists of two scripts, the first dedicated to the elaboration of the calibration curve. The emission of fluorescent light, detected by image analysis, is correlated with the concentration of CBD solutions. This calibration is then used (second script) to determine the concentration of CBDs adsorbed on cellulosic fibers. This method allows the direct estimation of the surface concentration of adsorbed CBDs, which usually is not accurately calculated from depletion studies, since the surface area is hardly known. By observing different spots in the surface of the fibers, site-specific information is obtained. It was verified that the physically heterogeneous fibers exhibit different amounts of adsorbed CBDs.


Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance.
Benzalkonium chlorides (BACs) are chemicals with widespread applications due to their broad-spectrum antimicrobial properties against bacteria, fungi, and viruses. This review provides an overview of the market for BACs, as well as regulatory measures and available data on safety, toxicity, and environmental contamination. We focus on the effect of frequent exposure of microbial communities to BACs and the potential for cross-resistant phenotypes to emerge. Toward this goal, we review BAC concentrations in consumer products, their correlation with the emergence of tolerance in microbial populations, and the associated risk potential. Our analysis suggests that the ubiquitous and frequent use of BACs in commercial products can generate selective environments that favor microbial phenotypes potentially cross-resistant to a variety of compounds. An analysis of benefits versus risks should be the guidepost for regulatory actions regarding compounds such as BACs.


TRAIL resistance in human neuroblastoma SK-N-AS cells is dependent on protein kinase C and involves inhibition of caspase-3 proteolytic processing.
Neuroblastoma is the most common solid extracranial cancer form in childhood with an etiology that is mostly unknown. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising future anticancer drug candidate, highly malignant neuroblastoma has been reported to acquire TRAIL resistance by mechanisms that are poorly understood. Here, we show by western blot analysis, and live cell imaging using anchored FRET sensors, that the resistance to TRAIL-induced apoptosis in human neuroblastoma SK-N-AS cells depends on an incomplete processing of procaspase-3, generating an immature and catalytically inactive 21 kDa fragment. We have previously shown that the naturally occurring compound curcumin can sensitize SK-N-AS cells to TRAIL. In the present study, we show that curcumin also has a similar effect on human neuroblastoma SHEP1 cells. Furthermore, we show that curcumin and TRAIL co-treatment induces complete maturation and activation of caspase-3 in both cell lines. The mechanisms behind this effect seem to be dependent on protein kinase C (PKC), since inhibition of PKC using bisindolylmaleimide XI, could also sensitize these cells to TRAIL through a similar effect on caspase-3 activation. Moreover, TRAIL co-treatment with bisindolylmaleimide XI or curcumin resulted in down-regulation of X-linked inhibitor of apoptosis protein. In conclusion, our study shows that PKC can be involved in TRAIL resistance in human neuroblastoma cells by preventing caspase-3 maturation.


Computational measurement of tumor immune microenvironment in gastric adenocarcinomas.
The use of four groups of tumor immune microenvironments (TME) based on PD-L1 and tumor-infiltrating T lymphocytes (TIL) is a reliable biomarker for anti-PD-1/PD-L1 inhibitor therapy. We classified the TME in 241 gastric cancers which were subdivided according to 40 EBV+, 76 microsatellite instability-high (MSI-H), and 125 EBV-/microsatellite-stable (MSS) subtypes by quantitative image analysis (QIA) and correlated the results with mRNA expression levels. The mean PD-L1 ratio and CD8 ratio in EBV+, MSI-H, and EBV-/MSS GCs were significantly different (P < 0.006). The PD-L1 ratio and CD8 ratio obtained by QIA correlated well with the RNA levels of PD-L1 (r = 0.63) and CD8 (r = 0.67), respectively. The TME were type I (PD-L1H/CD8H) in 45, type II (PD-L1L/CD8L) in 106, type III (PD-L1H/CD8L) in 8, and type IV (PD-L1L/CD8H) in 82 cases. The type I TME was significantly associated with high TIL (P = 3.0E-11) and EBV+ status (P = 8.55E-08). In conclusion, QIA results correlated well with the mRNA expression levels and classified TME of gastric cancers.


Generation and hypermnesia.
The multifactor account of the generation effect makes detailed predictions about the effects of generation on item-specific and relational encoding, predictions confirmed in four experiments using a multiple-test methodology. In pure-list designs with unrelated study items, generation produced more interest item gains (indexing greater item-specific processing) and more interest item losses (indexing less relational processing) relative to the read condition. In a mixed-list design, generation produced more gains but did not affect losses. With categorically-related study items, generation produced more gains but fewer losses (indicating enhanced relational encoding). Generation consistently produced hypermnesia whereas reading did so only for related study items. Also, a significant generation effect emerged on later tests under conditions (between-subjects design, unrelated study items) which typically yield no generation effect.


Molecular and cellular changes associated with the evolution of novel jaw muscles in parrots.
Vertebrates have achieved great evolutionary success due in large part to the anatomical diversification of their jaw complex, which allows them to inhabit almost every ecological niche. While many studies have focused on mechanisms that pattern the jaw skeleton, much remains to be understood about the origins of novelty and diversity in the closely associated musculature. To address this issue, we focused on parrots, which have acquired two anatomically unique jaw muscles: the ethmomandibular and the pseudomasseter. In parrot embryos, we observe distinct and highly derived expression patterns for Scx, Bmp4, Tgfβ2 and Six2 in neural crest-derived mesenchyme destined to form jaw muscle connective tissues. Furthermore, immunohistochemical analysis reveals that cell proliferation is more active in the cells within the jaw muscle than in surrounding connective tissue cells. This biased and differentially regulated mode of cell proliferation in cranial musculoskeletal tissues may allow these unusual jaw muscles to extend towards their new attachment sites. We conclude that the alteration of neural crest-derived connective tissue distribution during development may underlie the spatial changes in jaw musculoskeletal architecture found only in parrots. Thus, parrots provide valuable insights into molecular and cellular mechanisms that may generate evolutionary novelties with functionally adaptive significance.


The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.
Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.


Divergent development of autonomic and peripheral somatic neuropathies in NIDDM.
There is no information on the mutual occurrence and the development of autonomic and peripheral somatic neuropathies based on long-term follow-up of patients with non-insulin-dependent diabetes mellitus (NIDDM). We investigated the relation between the changes in autonomic function values and electrodiagnostic values, and the relation between the occurrence of autonomic neuropathy and peripheral somatic polyneuropathy in a group of patients with newly diagnosed NIDDM (n = 133, aged 45-65 years) at baseline and 5 and 10 years later. Parasympathetic autonomic neuropathy was diagnosed on the basis of heart rate variability during deep-breathing and sympathetic autonomic neuropathy on the basis of fall in systolic blood pressure while changing from supine to standing. Polyneuropathy was diagnosed on the basis of both clinical criteria and electrodiagnostic studies (nerve conduction velocity and response-amplitude values). In 10 years 36 patients died, mainly from cardiovascular causes. Altogether 78 patients completed the study. At 10 years, parasympathetic autonomic neuropathy was diagnosed in 61.3% of those with polyneuropathy and 66.7% of those without. Likewise, the frequency of sympathetic autonomic neuropathy was similar in those with polyneuropathy (21.9%) and those without (26.5%). The respective figures for combined (both parasympathetic and sympathetic) autonomic neuropathy were 10.0% and 18.8%. The worsening of parasympathetic and sympathetic autonomic function values was not related to the worsening in electrodiagnostic results with time. In conclusion, the development of autonomic and peripheral somatic neuropathies was divergent in patients with NIDDM suggesting different pathophysiological processes for these neuropathies.


Quantitative proteomics reveals subset-specific viral recognition in dendritic cells.
Dendritic cell (DC) populations consist of multiple subsets that are essential orchestrators of the immune system. Technological limitations have so far prevented systems-wide accurate proteome comparison of rare cell populations in vivo. Here, we used high-resolution mass spectrometry-based proteomics, combined with label-free quantitation algorithms, to determine the proteome of mouse splenic conventional and plasmacytoid DC subsets to a depth of 5,780 and 6,664 proteins, respectively. We found mutually exclusive expression of pattern recognition pathways not previously known to be different among conventional DC subsets. Our experiments assigned key viral recognition functions to be exclusively expressed in CD4(+) and double-negative DCs. The CD8alpha(+) DCs largely lack the receptors required to sense certain viruses in the cytoplasm. By avoiding activation via cytoplasmic receptors, including retinoic acid-inducible gene I, CD8alpha(+) DCs likely gain a window of opportunity to process and present viral antigens before activation-induced shutdown of antigen presentation pathways occurs.


Immunological characterization of a human homolog of the 65-kilodalton mycobacterial antigen.
A human mitochondrial protein, designated P1 (63 kilodaltons [kDa], shows extensive sequence homology (47% identical residues and an additional approximately 20% conserved changes) to the 65-kDa mycobacterial antigen. To understand the relationship of these proteins, the cross-reactivity of several monoclonal antibodies directed against the 65-kDa Mycobacterium leprae antigen towards human, Chinese hamster, chicken, and bacterial cells has been examined. A number of antibodies (Y1-2, ML 30-A2, and F47-9-1) were found to cross-react with a 63-kDa antigen in vertebrate cell extracts and stained mitochondria in immunofluorescence studies. Some of these antibodies also reacted with a P1-beta-galactosidase fusion protein in recombinant Escherichia coli cells, expressing part of the human P1 protein. These results provide strong evidence that P1 is the mammalian homolog of the 65-kDa antigen. The human P1 protein also shows significant similarity (P less than 0.001) to a number of other bacterial and viral proteins including the pol polyprotein of human immunodeficiency viruses and the penicillin-binding protein of Neisseria gonorrhoeae. The observed similarity between human P1 protein and the major antigenic proteins of pathogenic organisms (e.g., 60- to 65-kDa mycobacterial antigen) suggests its possible involvement in autoimmune diseases (e.g., rheumatoid arthritis) by antigenic mimicry.


Modelling rubella in Europe.
The prevention of congenital rubella syndrome (CRS), as a complication of rubella infection during pregnancy, is the main aim of rubella vaccination programmes. However, as vaccination of infants leads to an increase in the average age at which those who were not immunized become infected, certain rubella vaccination programmes can lead to an increase in the incidence of CRS. In this paper we use a mathematical model of the transmission dynamics of rubella virus to investigate the likely impact of different vaccination policies in Europe. The model was able to capture pre- and post-vaccination patterns of infection and prevalence of serological markers under a wide variety of scenarios, suggesting that the model structure and parameter estimates were appropriate. Analytical and numerical results suggest that endemic circulation of rubella is unlikely in Finland, the United Kingdom, The Netherlands, and perhaps Denmark, provided vaccine coverage is uniform across geographical and social groups. In Italy and Germany vaccine coverage in infancy has not been sufficient to interrupt rubella transmission, and continued epidemics of CRS seem probable. It seems unlikely that the immunization programmes in these countries are doing more harm than good, but this may be partly as a result of selective immunization of schoolgirls. Indeed, in both these countries, selective vaccination of schoolgirls with inadequate vaccination histories is likely to be an important mechanism by which CRS incidence is suppressed (unlike the other countries, which have had sufficiently high infant coverage rates to withdraw this option). Reducing inequalities in the uptake of rubella vaccine may bring greater health benefits than increasing the mean level of coverage.


Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates.
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has traditionally circulated in Africa and Asia, causing human febrile illness accompanied by severe, chronic joint pain. In Africa, epidemic emergence of CHIKV involves the transition from an enzootic, sylvatic cycle involving arboreal mosquito vectors and nonhuman primates, into an urban cycle where peridomestic mosquitoes transmit among humans. In Asia, however, CHIKV appears to circulate only in the endemic, urban cycle. Recently, CHIKV emerged into the Indian Ocean and the Indian subcontinent to cause major epidemics. To examine patterns of CHIKV evolution and the origins of these outbreaks, as well as to examine whether evolutionary rates that vary between enzootic and epidemic transmission, we sequenced the genomes of 40 CHIKV strains and performed a phylogenetic analysis representing the most comprehensive study of its kind to date. We inferred that extant CHIKV strains evolved from an ancestor that existed within the last 500 years and that some geographic overlap exists between two main enzootic lineages previously thought to be geographically separated within Africa. We estimated that CHIKV was introduced from Africa into Asia 70 to 90 years ago. The recent Indian Ocean and Indian subcontinent epidemics appear to have emerged independently from the mainland of East Africa. This finding underscores the importance of surveillance to rapidly detect and control African outbreaks before exportation can occur. Significantly higher rates of nucleotide substitution appear to occur during urban than during enzootic transmission. These results suggest fundamental differences in transmission modes and/or dynamics in these two transmission cycles.


Transmission electron microscopy.
Transmission electron microscopy has long been an important analytical tool in the field of microbiology. This unit describes preparation techniques for examining particulate samples as well as samples presenting more complex ultrastructural considerations that require analysis in thin sections. Negative staining is a useful technique for routine examination of particulate samples in suspension ranging from bacteria to purified macromolecules. In order to investigate the relationships between microbes and the environments with which they interface, fixed samples can be prepared for imaging in sections of 60- to 90-nm thickness. Due to the many steps in sample preparation for ultrastructural analysis of thin-sectioned samples, the major steps in the process are divided into fixation and initial processing of samples for thin sectioning, the embedment of samples into a plastic resin for sectioning, ultramicrotomy, and staining of samples. Procedures for immunolocalization of antigens in negatively stained and thin-sectioned preparations are also considered.


USP22 deficiency leads to myeloid leukemia upon oncogenic Kras activation through a PU.1-dependent mechanism.
Ras mutations are commonly observed in juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML). JMML and CMML transform into acute myeloid leukemia (AML) in about 10% and 50% of patients, respectively. However, how additional events cooperate with Ras to promote this transformation are largely unknown. We show that absence of the ubiquitin-specific peptidase 22 (USP22), a component of the Spt-Ada-GCN5-acetyltransferase chromatin-remodeling complex that is linked to cancer progression, unexpectedly promotes AML transformation in mice expressing oncogenic KrasG12D/+ USP22 deficiency in KrasG12D/+ mice resulted in shorter survival compared with control mice. This was due to a block in myeloid cell differentiation leading to the generation of AML. This effect was cell autonomous because mice transplanted with USP22-deficient KrasG12D/+ cells developed an aggressive disease and died rapidly. The transcriptome profile of USP22-deficient KrasG12D/+ progenitors resembled leukemic stem cells and was highly correlated with genes associated with poor prognosis in AML. We show that USP22 functions as a PU.1 deubiquitylase by positively regulating its protein stability and promoting the expression of PU.1 target genes. Reconstitution of PU.1 overexpression in USP22-deficient KrasG12D/+ progenitors rescued their differentiation. Our findings uncovered an unexpected role for USP22 in Ras-induced leukemogenesis and provide further insights into the function of USP22 in carcinogenesis.


[Recommendations for treatment of acne vulgaris].
Acne vulgaris is by far the most prevalent of adolescent skin disease, involving 60-80% of the teenage population. By androgen-stimulation the production of sebum is increased and by hyperkeratinisation the canal of the pilosebaceous follicle will be closed, thereby causing formation of comedones. These will get infected with Propionibacterium acnes. The treatment of acne vulgaris therefore consists in 4 steps: sebosuppression (with Benzoylperoxid), keratolysis (with Vitamin A-acid and Azelainacid), bakteriostasis and stopping inflammation (with antibiotics). A mild cure of the affected skin is necessary too.


Significance of integrin alpha2/beta1 in peritoneal dissemination of a human gastric cancer xenograft model.
In the present study, the role of integrin alpha2/beta1 in peritoneal dissemination of gastric cancer was investigated using an in vivo xenograft model for the highly metastatic MKN-45-P gastric cancer cells. Metastatic ability of MKN-45-P cells was significantly associated with the simultaneous expression of integrin alpha2 and alpha3 subunits. In an in vitro adhesion assay, neutralizing antibody for integrin alpha2 or beta1 subunit inhibited the adhesion of MKN-45-P cells to collagen type I and type IV. Moreover, the injection of anti-beta1 monoclonal antibody reduced the number of cancer cells on the peritoneum in nude mice that had been inoculated with MKN-45-P cells. These results suggest that integrin alpha2/beta1 represents a candidate target molecule available for the prevention of gastric cancer peritoneal dissemination.


Morphogenesis of a protein: folding pathways and the energy landscape.
Current knowledge on the reaction whereby a protein acquires its native three-dimensional structure was obtained by and large through characterization of the folding mechanism of simple systems. Given the multiplicity of amino acid sequences and unique folds, it is not so easy, however, to draw general rules by comparing folding pathways of different proteins. In fact, quantitative comparison may be jeopardized not only because of the vast repertoire of sequences but also in view of a multiplicity of structures of the native and denatured states. We have tackled the problem of the relationships between the sequence information and the folding pathway of a protein, using a combination of kinetics, protein engineering and computational methods, applied to relatively simple systems. Our strategy has been to investigate the folding mechanism determinants using two complementary approaches, i.e. (i) the study of members of the same family characterized by a common fold, but substantial differences in amino acid sequence, or (ii) heteromorphic pairs characterized by largely identical sequences but with different folds. We discuss some recent data on protein-folding mechanisms by presenting experiments on different members of the PDZ domain family and their circularly permuted variants. Characterization of the energetics and structures of intermediates and TSs (transition states), obtained by Φ-value analysis and restrained MD (molecular dynamics) simulations, provides a glimpse of the malleability of the dynamic states and of the role of the topology of the native states and of the denatured states in dictating folding and misfolding pathways.


Novel NGS pipeline for virus discovery from a wide spectrum of hosts and sample types.
The study of the microbiome data holds great potential for elucidating the biological and metabolic functioning of living organisms and their role in the environment. Metagenomic analyses have shown that humans, along with for example, domestic animals, wildlife and arthropods, are colonized by an immense community of viruses. The current Coronavirus pandemic (COVID-19) heightens the need to rapidly detect previously unknown viruses in an unbiased way. The increasing availability of metagenomic data in this era of next-generation sequencing (NGS), along with increasingly affordable sequencing technologies, highlight the need for reliable and comprehensive methods to manage such data. In this article, we present a novel bioinformatics pipeline called LAZYPIPE for identifying both previously known and novel viruses in host associated or environmental samples and give examples of virus discovery based on it. LAZYPIPE is a Unix-based pipeline for automated assembling and taxonomic profiling of NGS libraries implemented as a collection of C++, Perl, and R scripts.


Kinetics of early cholera infection in the removable intestinal tie-adult rabbit diarrhea model.
The colonization of the small intestine of adult rabbits challenged with 5 X 10(7) cells of Vibrio cholerae strain Ogawa 395 has been examined in the removable intestinal tie-adult rabbit diarrhea (RITARD) model. During the first 6 h of infection, numbers of both free and adherent vibrios increased at a rate representing a generation time of about 71 min. Detectable fluid output in response to infection began at about 4 to 5 h postchallenge, and overt diarrhea was observed as early as 11 h. By 8 h after challenge, adherent V. cholerae reached a saturation concentration on the intestinal epithelium of approximately 5 X 10(8) cells per g of intestine, whereas numbers of free cells continued to increase at an exponential rate for at least 12 to 14 h. The concentration of adherent cells remained relatively constant at the saturation level during this period. This saturation level was similar in all parts of the small intestine. The concentration of adherent organisms increased significantly in moribund animals, suggesting that factors responsible for the earlier saturation equilibrium began changing as animals neared death.


Exchange protein directly activated by cyclic AMP increases melanoma cell migration by a Ca2+-dependent mechanism.
Melanoma has a poor prognosis due to its strong metastatic ability. Although Ca(2+) plays a major role in cell migration, little is known about the role of Ca(2+) in melanoma cell migration. We recently found that the exchange protein directly activated by cyclic AMP (Epac) increases melanoma cell migration via a heparan sulfate-related mechanism. In addition to this mechanism, we also found that Epac regulates melanoma cell migration by a Ca(2+)-dependent mechanism. An Epac agonist increased Ca(2+) in several different melanoma cell lines but not in melanocytes. Ablation of Epac1 with short hairpin RNA inhibited the Epac agonist-induced Ca(2+) elevation, suggesting the critical role of Epac1 in Ca(2+) homeostasis in melanoma cells. Epac-induced Ca(2+) elevation was negated by the inhibition of phospholipase C (PLC) and inositol triphosphate (IP(3)) receptor. Furthermore, Epac-induced cell migration was reduced by the inhibition of PLC or IP(3) receptor. These data suggest that Epac activates Ca(2+) release from the endoplasmic reticulum via the PLC/IP(3) receptor pathway, and this Ca(2+) elevation is involved in Epac-induced cell migration. Actin assembly was increased by Epac-induced Ca(2+), suggesting the involvement of actin in Epac-induced cell migration. In human melanoma specimens, mRNA expression of Epac1 was higher in metastatic melanoma than in primary melanoma, suggesting a role for Epac1 in melanoma metastasis. In conclusion, our findings reveal that Epac is a potential target for the suppression of melanoma cell migration, and, thus, the development of metastasis.


Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice.
The gynecological disease endometriosis is characterized by the deposition and proliferation of endometrial cells outside the uterus and clinically is linked to low body mass index (BMI). Gene expression in the liver of these women has not been reported. We hypothesized that endometriosis may impact hepatic gene expression, promoting a low BMI. To determine the effect of endometriosis on liver gene expression, we induced endometriosis in female mice by suturing donor mouse endometrium into the peritoneal cavity and measuring the weight of these mice. Dual-energy X-ray absorptiometry (DEXA) scanning of these mice showed lower body weight and lower total body fat than controls. Microarray analysis identified 26 genes differentially regulated in the livers of mice with endometriosis. Six of 26 genes were involved in metabolism. Four of six genes were upregulated and were related to weight loss, whereas two genes were downregulated and linked to obesity. Expression levels of Cyp2r1, Fabp4, Mrc1, and Rock2 were increased, whereas Igfbp1 and Mmd2 expression levels were decreased. Lep and Pparg, key metabolic genes in the pathways of the six genes identified from the microarray, were also upregulated. This dysregulation was specific to metabolic pathways. Here we demonstrate that endometriosis causes reduced body weight and body fat and disrupts expression of liver genes. We suggest that altered metabolism mediated by the liver contributes to the clinically observed low BMI that is characteristic of women with endometriosis. These findings reveal the systemic and multiorgan nature of endometriosis.


Learning Curve for the Direct Superior Approach to Total Hip Arthroplasty.
Surgical learning curves are a representation of the number of cases required for a surgeon to reach a stable rate of outcomes and complications. In this study, the authors present the learning curve for the direct superior (DS) approach to total hip arthroplasty, which is a muscle-sparing modification to the mini-posterior technique. This was a retrospective analysis of the first 40 primary DS cases done by a single surgeon. These cases were divided into 2 groups of 20 and compared for intra- and postoperative complications, acetabular component positioning, and Harris Hip Score at 90 days after surgery. As a control, the first 20 primary mini-posterior cases were analyzed as the baseline performance of the surgeon and the DS approach. There was no statistically significant difference between the first and second sets of DS patients regarding Harris Hip Score, intraoperative complications, dislocations, estimated blood loss, length of hospital stay, and components positioned within the Lewinnek safe zone. The only statistically significant difference between the first and second sets of DS cases was a decrease in operating time (P<.001). This suggests that the learning curve is less than 20 patients. The results also indicate that the first 20 DS cases ambulated farther (P=.007) and had a shorter length of stay (P=.007), outperforming the mini-posterior approach. This study suggests that the DS learning curve is short for surgeons trained in the posterior approach. The data could be especially pertinent as 90-day results and safety are becoming increasingly important in evaluating performance for bundled-payment models. [Orthopedics. 2020;43(4):e237-e243.].


Assessment of Fecal Microflora Changes in Pigs Supplemented with Herbal Residue and Prebiotic.
Antibiotic usage in animals as a growth promoter is considered as public health issue due to its negative impact on consumer health and environment. The present study aimed to evaluate effectiveness of herbal residue (ginger, Zingiber officinale, dried rhizome powder) and prebiotic (inulin) as an alternative to antibiotics by comparing fecal microflora composition using terminal restriction fragment length polymorphism. The grower pigs were offered feed containing antibiotic (tetracycline), ginger and inulin separately and un-supplemented group served as control. The study revealed significant changes in the microbial abundance based on operational taxonomic units (OTUs) among the groups. Presumptive identification of organisms was established based on the fragment length of OTUs generated with three restriction enzymes (MspI, Sau3AI and BsuRI). The abundance of OTUs representing Bacteroides intestinalis, Eubacterium oxidoreducens, Selonomonas sp., Methylobacterium sp. and Denitrobacter sp. was found significantly greater in inulin supplemented pigs. Similarly, the abundance of OTUs representing Bacteroides intestinalis, Selonomonas sp., and Phascolarcobacterium faecium was found significantly greater in ginger supplemented pigs. In contrast, the abundance of OTUs representing pathogenic microorganisms Atopostipes suicloacalis and Bartonella quintana str. Toulouse was significantly reduced in ginger and inulin supplemented pigs. The OTUs were found to be clustered under two major phylotypes; ginger-inulin and control-tetracycline. Additionally, the abundance of OTUs was similar in ginger and inulin supplemented pigs. The results suggest the potential of ginger and prebioticsto replace antibiotics in the diet of grower pig.


Management of gallbladder cancer in India.
Gallbladder cancer is a highly aggressive disease with variable prevalence across the globe. Particularly the Indo-Gangetic belt in Northern India has an incidence as high as 21/100,000. Majority of cases are detected either incidentally on pathological evaluation of cholecystectomy specimens or present with advanced disease. Radical surgery remains the mainstay of cure but only a small subset of patients is operable at presentation, and even with curative surgery recurrence rates remain high. Much debate surrounds the management of gallbladder cancer, with continuously evolving standards regarding the extent of hepatic resection and lymphadenectomy, curative resection in patients presenting with jaundice, routine excision of bile duct, and the role of neoadjuvant chemoradiotherapy. In this review we present a synopsis of currently available evidence and emerging approaches in the management of gallbladder cancer in India.


Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles.
Thrombosis, the formation of a clot within a blood vessel, underlies a number of life-threatening cardiovascular disorders such as heart attack, ischemic stroke, pulmonary embolism, and deep vein thrombosis. These conditions affect the lives of millions of people worldwide and result in significant morbidity and mortality. It is thus crucial to develop novel methodologies to enhance the detection and treatment of these disorders. Thrombolysis, or the dissolution of blood clots, relies upon the administration of exogenous plasminogen activators (PAs) that lyse fibrin. Yet, there are several drawbacks to the use of current PAs, including significant risks of uncontrolled bleeding and suboptimal efficacy and pharmacokinetics. Nanomaterials are well positioned to address these priority issues in thrombolysis, via the alteration of PA pharmacokinetics and biodistribution. Additionally, due to the multifunctional nature of nanoparticles, these thrombolytics may be targeted to the site of occlusion, effectively concentrating the drug where it is most needed. Herein, we describe the methodology associated with the synthesis of a novel thrombus-targeted fibrinolytic nanoagent. At each step of the synthesis, we analyze the nanomaterials, including their physical properties and their ability to bind to thrombosis targets of interest. The effect of the conjugation of tPA to the nanoparticle surface on the amidolytic and fibrinolytic activities of nanoagents is also investigated. Lastly, the in vivo binding of the targeted thrombolytic to intravascular thrombi is examined.


CONTROL OF ANTICOAGULANT THERAPY: POSTAL COMPARISON BETWEEN FIVE CENTRES.
Laboratory techniques used in the control of oral anticoagulant therapy were compared at five centres. The methods studied were: (a) prothrombin-proconvertin (;P and P') technique with the centres using their own reagents. This resulted in major discrepancies between the centres. (b) P and P technique with all the centres using centrally supplied reagents. The discrepancies noted under (a) disappeared when (b) was employed. (c) Thrombotest: the centres used the same batch of reagent and the specimens were transmitted in glass or polystyrene containers. The centres obtained closely comparable results, whether transportation was in glass or polystyrene. (d) Onestage ;prothrombin' time with all the centres using the same reagents. When the results were read from a dilution curve there were discrepancies between the centres. For comparability of results between centres using anticoagulant therapy, centrally supplied P and P reagents or Thrombotest should be used. Since only the latter was commercially available as a centrally standardized reagent at the initiation of this trial, it emerged as the method of practical choice at the time.


Delays in fibrinolysis as primary reperfusion therapy for acute ST-segment elevation myocardial infarction.
In contemporary practice, the degree to which fibrinolytic therapy is administered in a timely fashion for ST-segment elevation myocardial infarction (STEMI) and its association with outcomes is not well-known. Our objective was to assess the performance of fibrinolytic therapy within the recommended 30-minute time frame for patients with STEMI. Patient characteristics associated with the timeliness of fibrinolytic therapy were evaluated. We also examined the association of timely fibrinolysis with key patient outcomes, including inpatient mortality, stroke, and cardiogenic shock. Logistic generalized estimating equations were used to account for baseline clinical factors and within-hospital clustering. Between January 2007 and June 2008, 3,219 STEMI patients in 178 hospitals received primary fibrinolytic therapy. Median door-to-needle (DTN) time was 34.0 minutes (interquartile range 22.0-54.0 minutes). However, only 44.5% met the American College of Cardiology/American College of Cardiology guideline DTN time of < or =30 minutes. Patient characteristics associated with longer fibrinolysis times included female gender (+17.8% longer vs men, 95% CI 11.9-24.1) and age > or =75 (+12.0% longer vs age <55, 95% CI 1.8-23.2). Timely (vs delayed) fibrinolysis was associated with a decreased risk of a composite outcome of death, shock, or stroke (6.2% vs 8.8%, adjusted odds ratio 0.74, 95% CI 0.56-0.98). Timely fibrinolytic therapy was associated with lower risk of a composite outcome of shock, death, or stroke, yet DTN times of < or =30 minutes were achieved in less than half of the patients studied. Thus, efforts to optimize regional systems of STEMI care should focus on shortening reperfusion times for patients who receive fibrinolysis, as well as those who receive primary percutaneous coronary intervention.


Mycobacterium infection directly observed in a surgical outpatient centre.
This study aims to check the presence and the role of the Mycobacterium tuberculosis infection, in an Ambulatory and Day Surgery Out-Patient Centre. Two periods of activity in this Centre are evaluated corresponding separately to the years 1989-1993 and 1994-1998 and the total number of patients, coming for examination, ambulatory or day surgery, hospitalization, postoperative follow-up, is considered, in order to identify the number of cases and the clinical signs of this disease. All cases were examined by the same team and the checks were completed, in the selected cases in which it was advisable, with radiological, bacteriological, bioptical, radiometrical exams and with the Elisa test (after informed consent). In the first period 1989-1993, 21,220 patients were examined and no case of tubercular infection was observed. In 1994-1998, 24,347 patients were examined and 4 cases of tubercular infection detected, which represent 0.016% of the patients attending the service. The clinical cases are as follows. Case 1: right sub-mammary lump, diameter 7 x 5 cm, smooth, oval, firm. Case 2: right breast swelling, diameter 5 cm, not sore, with deep attachments. The mammography and ultrasound scan indicate: the opacity is compatible with mali moris breast lesion. Case 3: coloured, immigrant, who presents back swelling, diameter 8 cm, with fluctuation. CT of the chest indicates opacity near left latissimus dorsi muscle, diameter 10 cm, without bronchopleural connections. Case 4: bleeding neoplastic ulcer of the wrist. At physical exam a right subclavear amphoric breath sound is noticed, corresponding at chest X-ray to an opacity including cavitation. In the 4 cases no lymph node in the regional effusion areas is detected. In the 4 cases surgical therapy is integrated with antituberculous chemotherapy till 6 months after operation. Mycobacterium tuberculosis infection has been increasing in the second group of years considered, as it is observed in European industrialized countries and North America. This increase corresponds to 0.016% in 24,374 patients examined in the period 1994-98. This infection must not be connected with the classic sites and traditional primary and post-primary symptons, but must be considered and identified in a surgical hospital out-patient centre, in unusual sites, sometimes masquerading as a false positive carcinoma, in patients with predisposition, because of old age, race, immunodepression (also if HIV negatives), resistance to treatment, previous tuberculous infection. In the cases identified deep diagnostic definition, the surgical treatment and a prolonged antituberculous chemotherapy are necessary.


Comparison of Relative Loudness Judgment in Children using Listening Devices with Typically Developing Children.
Introduction Loudness perception is considered important for the perception of emotions, relative distance and stress patterns. However, certain digital hearing devices worn by those with hearing impairment may affect their loudness perception. This could happen in devices that have compression circuits to make loud sounds soft and soft sounds loud. These devices could hamper children from gaining knowledge about loudness of acoustical signals. Objective To compare relative loudness judgment of children using listening devices with age-matched typically developing children. Methods The relative loudness judgment of sounds created by day-to-day objects were evaluated on 60 children (20 normal-hearing, 20 hearing aid users, & 20 cochlear implant users), utilizing a standard group comparison design. Using a two-alternate forced-choice technique, the children were required to select picturized sound sources that were louder. Results The majority of the participants obtained good scores and poorer scores were mainly obtained by children using cochlear implants. The cochlear implant users obtained significantly lower scores than the normal-hearing participants. However, the scores were not significantly different between the normal-hearing children and the hearing aid users as well as between the two groups with hearing impairment. Conclusion Thus, despite loudness being altered by listening devices, children using non-linear hearing aids or cochlear implants are able to develop relative loudness judgment for acoustic stimuli. However, loudness growth for electrical stimuli needs to be studied.


Oscillatory sensory selection mechanisms during intersensory attention to rhythmic auditory and visual inputs: a human electrocorticographic investigation.
Oscillatory entrainment mechanisms are invoked during attentional processing of rhythmically occurring stimuli, whereby their phase alignment regulates the excitability state of neurons coding for anticipated inputs. These mechanisms have been examined in the delta band (1-3 Hz), where entrainment frequency matches the stimulation rate. Here, we investigated entrainment for subdelta rhythmic stimulation, recording from intracranial electrodes over human auditory cortex during an intersensory audiovisual task. Audiovisual stimuli were presented at 0.67 Hz while participants detected targets within one sensory stream and ignored the other. It was found that entrainment operated at twice the stimulation rate (1.33 Hz), and this was reflected by higher amplitude values in the FFT spectrum, cyclic modulation of alpha-amplitude, and phase-amplitude coupling between delta phase and alpha power. In addition, we found that alpha-amplitude was relatively increased in auditory cortex coincident with to-be-ignored auditory stimuli during attention to vision. Thus, the data suggest that entrainment mechanisms operate within a delimited passband such that for subdelta task rhythms, oscillatory harmonics are invoked. The phase of these delta-entrained oscillations modulates alpha-band power. This may in turn increase or decrease responsiveness to relevant and irrelevant stimuli, respectively.


Anxiety in preoperative anesthetic procedures.
Preoperative anxiety is a common and poorly evaluated condition in patients who will undergo an anesthetic and surgical intervention. The objective of this study was to determine the prevalence of anxiety in a group of patients undergoing elective surgery, as assessed by the Amsterdam Anxiety Preoperative and Information (AAPI) scale. We studied 135 patients scheduled for elective surgery applying the AAPI scale 24 h before the surgical procedure to evaluate the presence of anxiety and patient characteristics. A descriptive analysis with mean +/- standard deviation for categorical variables was done. For intragroup differences, chi(2) test was used. Pearson correlation for the association between anxiety and postoperative complications was carried out. A value of p =0.05 was considered significant. One hundred six patients were surgically treated, 88% were female (average age 44 +/- 12 years). Some degree of preoperative anxiety was present in 72 patients (76%; p = 0.001) with a grade point average on the AAPI scale equal to 17 +/- 7 points, of which 95 (70%, OR = 5.08; p = 0.002) were females. Results of this study suggest the presence of high levels of preoperative anxiety in patients scheduled for elective surgery. The origin of the anxiety appears to be related to many factors that can be evaluated in pre-anesthetic consultation. Further study is needed to prevent the presence of this disorder.


Broad vs. narrow traits: a scoping review of measuring personality traits in teacher selection using the situational judgment test.
Situational Judgment Tests (SJTs) have gained popularity and are commonly used as a measurement technique in a variety of professions, particularly those that include hiring, promoting, and professional development. In various educational sectors around the world, SJTs are being utilized as a measure by which to choose individuals who possess the requisite non-academic attributes for the profession. The objective of this review is to identify and analyze the traits that are measured in teacher selection using SJTs, in terms of both broad and narrow traits. This review uses a scoping review approach comprising five stages which are: identifying the research question, identifying relevant studies, selecting the studies, charting the data and reporting the results. Seven empirical research studies on teacher selection using SJTs were identified in which broad and narrow traits are used differently in selection. In the studies, a broad trait-conscientiousness-and seven narrow traits-organization and planning; empathy and communication; adaptability and resilience; mindset; emotional regulation; professional ethics; and enthusiasm and motivation-were recognized. Analysis revealed, in line with other prior studies, that the traits discovered tended to be used as the foundation for teacher selection criteria. The use of broad and narrow traits as the basis for teacher selection criteria has implications for the selection of the "best" teacher candidates because both broad and narrow traits generally do not accurately measure the precise characteristics needed. Future studies should focus on measuring more precise characteristics without overlap between the targeted characteristics, in light of the conclusions from this review.


Quantitative assessment of second language learners' fluency: comparisons between read and spontaneous speech.
This paper describes two experiments aimed at exploring the relationship between objective properties of speech and perceived fluency in read and spontaneous speech. The aim is to determine whether such quantitative measures can be used to develop objective fluency tests. Fragments of read speech (Experiment 1) of 60 non-native speakers of Dutch and of spontaneous speech (Experiment 2) of another group of 57 non-native speakers of Dutch were scored for fluency by human raters and were analyzed by means of a continuous speech recognizer to calculate a number of objective measures of speech quality known to be related to perceived fluency. The results show that the objective measures investigated in this study can be employed to predict fluency ratings, but the predictive power of such measures is stronger for read speech than for spontaneous speech. Moreover, the adequacy of the variables to be employed appears to be dependent on the specific type of speech material investigated and the specific task performed by the speaker.


Site-directed mutagenesis of HgcA and HgcB reveals amino acid residues important for mercury methylation.
Methylmercury is a potent neurotoxin that is produced by anaerobic microorganisms from inorganic mercury by a recently discovered pathway. A two-gene cluster, consisting of hgcA and hgcB, encodes two of the proteins essential for this activity. hgcA encodes a corrinoid protein with a strictly conserved cysteine proposed to be the ligand for cobalt in the corrinoid cofactor, whereas hgcB encodes a ferredoxin-like protein thought to be an electron donor to HgcA. Deletion of either gene eliminates mercury methylation by the methylator Desulfovibrio desulfuricans ND132. Here, site-directed mutants of HgcA and HgcB were constructed to determine amino acid residues essential for mercury methylation. Mutations of the strictly conserved residue Cys93 in HgcA, the proposed ligand for the corrinoid cobalt, to Ala or Thr completely abolished the methylation capacity, but a His substitution produced measurable methylmercury. Mutations of conserved amino acids near Cys93 had various impacts on the methylation capacity but showed that the structure of the putative "cap helix" region harboring Cys93 is crucial for methylation function. In the ferredoxin-like protein HgcB, only one of two conserved cysteines found at the C terminus was necessary for methylation, but either cysteine sufficed. An additional, strictly conserved cysteine, Cys73, was also determined to be essential for methylation. This study supports the previously predicted importance of Cys93 in HgcA for methylation of mercury and reveals additional residues in HgcA and HgcB that facilitate the production of this neurotoxin.


Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate.
Phthalate esters have been used extensively as plasticizers of synthetic polymers. Recent studies have revealed that these esters induce atrophy of the testis, although its pathogenesis remains unknown. The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and immunohistochemical analysis revealed that oral administration of DEHP increased the generation of reactive oxygen species, with concomitant decrease in the concentration of glutathione and ascorbic acid in the testis, and selectively induced apoptosis of spermatocytes, thereby causing atrophy of this organ. Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP. Furthermore, MEHP selectively induced the release of cytochrome c from mitochondria of the testis. These results indicate that oxidative stress elicited by MEHP principally injured mitochondrial function and induced the release of cytochrome c, thereby inducing apoptosis of spermatocytes and causing atrophy of the testis.


An Immersive Computer-Mediated Caregiver-Child Interaction System for Young Children With Autism Spectrum Disorder.
Autism Spectrum Disorder (ASD) affects 1 in 54 children in the United States. A core social communication skill negatively impacted by ASD is joint attention (JA), which influences the development of language, cognitive, and social skills from infancy onward. Although several technology-based JA studies have shown potential, they primarily focus on response to joint attention (RJA). The other important component of JA, the initiation of joint attention (IJA), has received less attention from a technology-based intervention perspective. In this work, we present an immersive Computer-mediated Caregiver-Child Interaction (C3I) system to help children with ASD practice IJA skills. C3I is a novel computerized intervention system that integrates a caregiver in the teaching loop, thereby preserving the advantages of both human and computer-administered intervention. A feasibility study with 6 dyads (caregiver-child with ASD) was conducted. A near significant increase with medium effect size on IJA performance was observed. Meanwhile, physiology-based stress analysis showed that C3I did not increase stress of the caregivers over the course of the study. To the best of our knowledge, this is the first autonomous system designed for teaching IJA skills to children with ASD incorporating caregivers within the loop to enhance the potential for generalization in real-world.


The multifaceted effects of agmatine on functional recovery after spinal cord injury through Modulations of BMP-2/4/7 expressions in neurons and glial cells.
Presently, few treatments for spinal cord injury (SCI) are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm), a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm(2) weight for 1 min at thoracic vertebra (Th) 9 segment. Mice that received an intraperitoneal (i.p.) injection of Agm (100 mg/kg/day) within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs) are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST) demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following SCI.


The effect of organizational conditions (role conflict, role ambiguity, opportunities for professional development, and social support) on job satisfaction and intention to leave among social workers in mental health care.
This study examined the relationships between the organizational conditions of social workers practicing in mental health agencies and their job satisfaction and intention to leave. A sample of 259 social workers, practicing in sixteen mental health agencies in New York State completed a questionnaire that included several measures: role conflict, role ambiguity, social support, extent of opportunities for professional development, type of work activities, job satisfaction and intention to leave. Results showed that the organizational conditions are strong predictors for job satisfaction and intention to leave. The author suggests that it is possible to find an appropriate balance between the professional expectations of social workers and the business-driven aspect of the mental health care environment.


Perilymph fistula: a cause of auditory, vestibular, neurological and psychiatric disorder.
It is suggested that damage by mild trauma, viruses or bone disease to the otic capsule or to the membranes between the cochlea and the middle ear is common, and involved in many syndromes of obscure etiology. The clinical perilymph fistula (PF) syndrome can consist of any combination of the following: tinnitus, deafness, phonophobia, vertigo, ataxia, otalgia, facial palsy, headache, diplopia, blackouts, psychological distress. The following testable hypotheses are proposed: otitis media is due to perilymph in the middle ear, with secondary changes resulting from infection or inflammation: otosclerosis results from a slow leak in the presence of enzymes promoting bone growth: Meniere's syndrome follows reduced perilymph support for the endolymphatic system: Bell's palsy results from a perilymph provoked oedema in the bony facial nerve canal: PFs may be responsible for progressive rubella deafness, and for some cases of migraine, epilepsy, anxiety neurosis and hysteria: psychiatric sequelae of the PF syndrome predominate in the post-concussional syndrome and infantile autism: organisms can pass from the throat into the spinal fluid, causing meningitis or encephalitis. The tinnitus and vertigo are caused by random labyrinthine fluid movements, the headache and diplopia by reduced spinal fluid pressure.


Melatonin confers heavy metal-induced tolerance by alleviating oxidative stress and reducing the heavy metal accumulation in Exophiala pisciphila, a dark septate endophyte (DSE).
Melatonin (MT), ubiquitous in almost all organisms, functions as a free radical scavenger. Despite several reports on its role as an antioxidant in animals, plants, and some microorganisms, extensive studies in filamentous fungi are limited. Based upon the role of melatonin as an antioxidant, we investigated its role in heavy metal-induced stress tolerance in Exophiala pisciphila, a dark septate endophyte (DSE), by studying the underlying mechanisms in alleviating oxidative stress and reducing heavy metal accumulation. A significant decrease in malondialdehyde (MDA) and oxygen free radical (OFR) in E. pisciphila was recorded under Cd, Zn, and Pb stresses as compared to the control. Pretreatment of E. pisciphila with 200.0 μM exogenous melatonin significantly increased the activity of superoxide dismutase (SOD) under Zn and Pb stresses. Pretreatment with 200.0 μM melatonin also lowered Cd, Zn, and Pb concentrations significantly. Melatonin production was enhanced by Cd, Cu, and Zn after 2 d, and melatonin biosynthetic enzyme genes, E. pisciphila tryptophan decarboxylase (EpTDC1) and serotonin N-acetyltransferase (EpSNAT1), were transcriptionally upregulated. The overexpression of EpTDC1 and N-acetylserotonin O-methyltransferase (EpASMT1) in Escherichia coli and Arabidopsis thaliana enhanced its heavy metal-induced stress tolerance. The overexpression of EpTDC1 and EpASMT1 reduced the Cd accumulation in the whole A. thaliana plants, especially in the roots. Melatonin conferred heavy metal-induced stress tolerance by alleviating oxidative stress, activating antioxidant enzyme SOD, and reducing heavy metal accumulation in E. pisciphila. Melatonin biosynthetic enzyme genes of E. pisciphila also played key roles in limiting excessive heavy metal accumulation in A. thaliana. These findings can be extended to understand the role of melatonin in other DSEs associated with economically important plants and help develop new strategies in sustainable agriculture practice where plants can grow in soils contaminated with heavy metals.


Atypical antipsychotics produce within-session decrements on self-stimulation of the rat medial prefrontal cortex.
It has been described that "typical" antipsychotic drugs (APDs) induce characteristic within-session response decrements in operant behaviors, including intracranial self-stimulation (ICSS). In contrast, recent reports have shown that in food operant behavior, clozapine and a number of "atypical" APDs do not give rise to within-session effects. However, to elucidate whether or not this is a common property of atypical APDs, their effects on other operant models need to be studied. To address this question we investigated the temporal pattern of ICSS responding, after systemic administration of five atypical APDs and the typical antipsychotic, haloperidol. Rats were trained to lever press for electrical stimulation at the medial prefrontal cortex (mPFC), and response rates were recorded during each 3-min period of the 15-min session. Significant within-session response decrements on mPFC ICSS were observed with haloperidol, risperidone, sertindole and olanzapine but not with clozapine or ziprasidone. The magnitude of within-session decline produced by the APDs tested was positively correlated with their affinity for dopamine D2 receptors. The results show for the first time that atypical APDs are capable to induce within-session decrements on ICSS behavior, and suggest that this particular temporal pattern of responding is not exclusively characteristic of typical APDs. The results are also consistent with the hypothesis that the ability of APDs to induce greater within-session effects may be related, in part, to potent D2 antagonism.


Evolution in action: climate change, biodiversity dynamics and emerging infectious disease.
Climatological variation and ecological perturbation have been pervasive drivers of faunal assembly, structure and diversification for parasites and pathogens through recurrent events of geographical and host colonization at varying spatial and temporal scales of Earth history. Episodic shifts in climate and environmental settings, in conjunction with ecological mechanisms and host switching, are often critical determinants of parasite diversification, a view counter to more than a century of coevolutionary thinking about the nature of complex host-parasite assemblages. Parasites are resource specialists with restricted host ranges, yet shifts onto relatively unrelated hosts are common during phylogenetic diversification of parasite lineages and directly observable in real time. The emerging Stockholm Paradigm resolves this paradox: Ecological Fitting (EF)--phenotypic flexibility and phylogenetic conservatism in traits related to resource use, most notably host preference--provides many opportunities for rapid host switching in changing environments, without the evolution of novel host-utilization capabilities. Host shifts via EF fuel the expansion phase of the Oscillation Hypothesis of host range and speciation and, more generally, the generation of novel combinations of interacting species within the Geographic Mosaic Theory of Coevolution. In synergy, an environmental dynamic of Taxon Pulses establishes an episodic context for host and geographical colonization.


Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling.
New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.


T cells reactive to keratinocyte antigens are generated during induction of contact hypersensitivity in mice. A model for autoeczematization in humans?
The role of keratinocytes (KC) in contact hypersensitivity (CH) has been examined more with respect to cytokine secretion and tolerance induction and less as a source of antigenic proteins to which chemical haptens can conjugate. To determine whether KC-derived proteins can serve as antigenic carriers for haptens such as dinitrofluorobenzene (DNFB). We examined the capacity of draining lymph node cells from BALB/c mice sensitized to DNFB to proliferate in response to hapten or to hapten-conjugated protein extracts derived from a KC line (DNP-Pam KC extract). Using limiting dilution microculture of these lymph node cells, we established DNP-specific T cell clones as well as DNP-Pam KC extract-reactive T cell clones. We also examined the proliferative responses of the DNP-Pam KC extract-reactive clones and of lymph node cells from mice sensitized to different haptens. Lymph node cells from DNFB-sensitized mice proliferated well to hapten or to DNP-Pam KC extract. Six la(d)-restricted, alphabeta TCR-bearing, CD4+ clones were established: 4 proliferated specifically to soluble hapten (DNBS), whereas 2 proliferated in response to DNP-Pam KC extract. Surprisingly, the DNP-Pam KC extract-reactive clones proliferated as well to Pam KC extract without hapten. Lymph node cells from hapten-sensitized mice not only proliferated specifically in response to the hapten to which they were sensitized, but also proliferated to Pam KC extract without hapten. T cell clones generated during the induction of (CH) in mice include those reactive to hapten as well as those reactive to KC antigens independent of hapten. Analogous mechanisms in humans might account for autoreactive events such as id reactions associated with CH and angry back syndrome during patch testing.


Immediate coronary artery bypass surgery after platelet inhibition with eptifibatide: results from PURSUIT. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrelin Therapy.
The platelet GP IIb/IIIa inhibitor eptifibatide improves outcomes in patients with acute coronary syndromes. Patients requiring emergent coronary artery bypass grafting, however, may be at increased risk for bleeding if exposed to eptifibatide. Data from the PURSUIT trial were reviewed to assess this risk in patients undergoing coronary surgery immediately after exposure to eptifibatide. In PURSUIT, 10,948 patients who presented with non-ST segment elevation acute coronary syndromes were prospectively randomized to receive eptifibatide (180 microg/kg bolus plus 2 microg/kg/min infusion) or placebo. A total of 78 patients underwent immediate coronary artery bypass surgery within 2 hours of cessation of study drug (placebo, n = 46; eptifibatide, n = 32). Clinical outcome, bleeding, and transfusion requirements within this subset were examined. Major bleeding was not different between groups, occurring in 64% of patients receiving placebo and 63% of patients receiving eptifibatide. The incidence of blood transfusion was similar as well (57% vs 59%). Postoperative thrombocytopenia occurred less often after eptifibatide exposure. Perioperative myocardial infarction was significantly reduced in patients who received eptifibatide (46% vs 22%, p < 0.05). There was no difference in perioperative stroke (2.2% vs 6.3%) or mortality (6.3% vs 6.5%). Patients may safely undergo coronary artery bypass surgery within 2 hours of discontinuation of eptifibatide. Eptifibatide infusion in the immediate preoperative period had no adverse clinical effects, but did significantly decrease the incidence of perioperative myocardial infarction. Additionally, platelet counts after surgery were higher in the group of patients who received eptifibatide, perhaps indicative of a platelet-sparing effect during cardiopulmonary bypass.


[Oscillating potentials of the retina and superior colliculi and correlations with neuronal activity].
The oscillatory potentials of retina and superior colliculus induced with photostimuli were studied in unanesthetized rabbits. Increasing intensity of light flashes induces a better correlation of the responses in these structures. A common genesis of the oscillatory processes and neuronal activity was revealed. The peculiarities of formation of the short-latency responses in the superior colliculus and the specificity of generation of the responses of photostimuli of extreme brightness, are discussed.


Microfluidics in structural biology: smaller, faster em leader better.
Microfluidic technologies promise unprecedented savings in cost and time through the integration of complex chemical and biological assays on a microfabricated chip. Recent advances are making elements of this vision a reality, facilitating the first large-scale integration of microfluidic plumbing with biological assays. The power of miniaturization lies not only in achieving an economy of scale, but also in exploiting the unusual physics of fluid flow and mass transport on small length scales to realize precise and efficient assays that are not accessible with macroscopic tools. Diverse applications ranging from time-resolved studies of protein folding to highly efficient protein crystal growth suggest that microfluidics may become an indispensable tool in biology.


[Frequency and character of violations of cardiac rhythm according to data of intraday monitoring among healthy military servicemen of young age].
For investigation of character and frequency of detection of violations of rhythm and conductivity there was effectuated monitoring of ECG using Holter monitor. In investigation were included 238 military servicemen of young age (23-35 years old), situated in similar conditions of life, chosen according to practical health. Normative indexes of daily variation of arrhythmia were determined using method of non-parametric analyze of qualitative data. On the base of this method, acceptable for using in elaboration of normative values of physiological indexes, the norm could be called isolated cases of ectopic complexes of 5 ventricular and of 24 supraventricular extrasystoles (SVE) for a day. Ventricular extrasystoles (VE) are monotypic, SVE could be polytypic, also could be singular paired complexes. Also could be combination of VE and SVE. Other, more complicated violations of rhythm could be referred either to pathological evidence or to premorbid conditions. Violations of conductivity should be absent in norm.


Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia.
Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216-806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501-732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.


Nasalance scores in noncleft individuals: why not zero?
To determine whether oral or nasal acoustic energy is primarily responsible for nonzero nasalance scores observed during the production of nonnasal sentences by individuals with normal speech. Sixty adults with normal speech were asked to read the Zoo passage and produce three sustained vowels, (/i/, /a/ and /u/), with and without nares occlusion. There was a significant decrease in nasalance scores between the unoccluded and occluded conditions for all four stimulus pairs. The mean decrease across conditions ranged from 8 (/u/) to 25 (/i/). In the unoccluded condition, the nasalance score was significantly greater for /i/ than for the other stimuli. The findings suggest that the majority of acoustic energy detected by the nasometer's nasal microphone during the production of nonnasal utterances is the result of sound transmission through the nose. The data obtained during this investigation, coupled with information available from other studies, suggest that this may be due to transpalatal transmission. If correct, such a conclusion would have clinical implications for patients with palatal clefts, since residual structural abnormalities and scar tissue in a repaired cleft palate may increase, dampen, or in some way alter transpalatal acoustic transmission. Thus, surgical normalization of velopharyngeal port control may not be sufficient to eliminate hypernasality in all patients.


Enterotoxicity and cytotoxicity of Vibrio parahaemolyticus thermostable direct hemolysin in in vitro systems.
Vibrio parahaemolyticus is a marine bacterium known to be a common cause of seafood gastroenteritis worldwide. The thermostable direct hemolysin (TDH) has been proposed to be a major virulence factor of V. parahaemolyticus. TDH causes intestinal fluid secretion as well as cytotoxicity in a variety of cell types. In this study, we investigated the interplay between the hemolysin's enterotoxic and cytotoxic effects by using both human and rat cell monolayers. As revealed by microspectrofluorimetry, the toxin causes a dose-dependent increase in intracellular free calcium in both Caco-2 and IEC-6 cells. This effect was reversible only when low toxin concentrations were tested. The TDH-activated ion influx pathway is not selective for calcium but admits ions such sodium and manganese as well. Furthermore, in the same range of concentration, the hemolysin triggers a calcium-dependent chloride secretion. At high concentrations, TDH induces a dose-dependent but calcium-independent cell death as assessed by functional, biochemical, and morphological assays.


CLIC4 and Schnurri-2: a dynamic duo in TGF-beta signaling with broader implications in cellular homeostasis and disease.
CLIC4 is a highly conserved, multifunctional member of the chloride intracellular channel family of proteins. The protein is largely cytoplasmic but translocates to the nucleus upon a variety of stimuli including TGF-beta, TNF-alpha and etoposide. Nuclear resident CLIC4 causes growth arrest, terminal differentiation and apoptosis. Recently, it was discovered that TGF-beta causes CLIC4 to associate with Schnurri-2 and together they translocate to the nucleus and dissociate thereafter. The nuclear function of CLIC4 was further illuminated by the discovery that CLIC4 enhances TGF-beta signaling by associating with phospho-Smad2 and 3 and preventing their dephosphorylation. Enhanced TGF-beta dependent gene expression and growth inhibition are downstream consequences of this activity of CLIC4. In this article, we speculate on other consequences of the CLIC4 relation to TGF-beta signaling and the potential for CLIC4 to participate in other cellular functions related to normal homeostasis and disease.


Ocular metastasis of pulmonary oat cell carcinoma.
Decreased vision may be the initial symptom of metastatic disease. A case of metastasis to the choroid from the lung is presented together with a discussion of metastatic disease to the eye. Differential diagnosis of metastatic lesions and malignant melanoma is explored. Epidemiology, clinical features, prognosis and treatment options are discussed.


Physiological and behavioral changes in honey bees (Apis mellifera) induced by Nosema ceranae infection.
Persistent exposure to mite pests, poor nutrition, pesticides, and pathogens threaten honey bee survival. In healthy colonies, the interaction of the yolk precursor protein, vitellogenin (Vg), and endocrine factor, juvenile hormone (JH), functions as a pacemaker driving the sequence of behaviors that workers perform throughout their lives. Young bees perform nursing duties within the hive and have high Vg and low JH; as older bees transition to foraging, this trend reverses. Pathogens and parasites can alter this regulatory network. For example, infection with the microsporidian, Nosema apis, has been shown to advance behavioral maturation in workers. We investigated the effects of infection with a recent honey bee pathogen on physiological factors underlying the division of labor in workers. Bees infected with N. ceranae were nearly twice as likely to engage in precocious foraging and lived 9 days less, on average, compared to controls. We also show that Vg transcript was low, while JH titer spiked, in infected nurse-aged bees in cages. This pattern of expression is atypical and the reverse of what would be expected for healthy, non-infected bees. Disruption of the basic underpinnings of temporal polyethism due to infection may be a contributing factor to recent high colony mortality, as workers may lose flexibility in their response to colony demands.


Isolation of type A influenza and Newcastle disease viruses from migratory waterfowl in the Mississippi flyway.
Twenty-seven chicken red blood cell agglutinating agents were isolated from 187 tracheal swabbings of apparently healthy migratory mallard ducks (Anas platyrhynchos) in the Mississippi flyway. Twenty-four of the isolants were type A influenza virus; 3 lentogenic Newcastle disease viruses were isolated. Isolations were not made from either 65 giant Canada geese (Branta canadensis) or 60 Franklins' gulls (Larus pipixcan).


Differences in plasma and tissue aluminum concentrations due to different aluminum-containing drugs in patients with renal insufficiency and with normal renal function.
The gastrointestinal absorption of aluminum from orally administered aluminum-containing drugs is well documented. Retention of the absorbed aluminum leads to elevated levels of this metal in the tissue of patients with renal failure. We studied two groups of dialysis patients who had received equal amounts of the different aluminum-containing phosphate-binders Aludrox and Antiphosphat. It has recently been shown that Antiphosphat releases only a few aluminum ions in an environment of low pH. Consistent with this finding, we found the aluminum levels to be significantly higher in the plasma, bone, and hair of patients who had received Aludrox as phosphate binder. Subjects with normal renal function excreted most of the ingested and absorbed aluminum. No data are available concerning the tissue load of the element in these subjects. We studied two groups of patients with normal renal function who had received antacid drugs prior to neurosurgery on a brain tumor. The first group of patients were treated with an aluminum-rich antacid (Maalox 70); the other group received an aluminum-poor drug (magaldrate) for 10 days prior to the operation. Analysis of the brain-tissue removed revealed twofold higher aluminum levels in the patients who had received Maalox 70. These results indicate that administration of aluminum-containing drugs leads to a tissue load of aluminum in patients with an impaired renal function as well as in those with a normal function. The extent of the aluminum load depends on the aluminum content and the liberation rate of the drug.


Impact of Diabetes Mellitus on Radial and Ulnar Arterial Vasoreactivity after Radial Artery Cannulation: A Randomized Controlled trial.
Endothelial dysfunction associated with diabetes mellitus (DM) may influence arterial vasoreactivity after arterial stimulus, such as cannulation, and cause changes in diameter and blood flow. Despite the frequent use of arterial cannulation during anesthesia and critical care, little information is available regarding vasoreactivity of the radial and ulnar arteries and its influence on underlying DM. Forty non-DM and 40 DM patients, who required arterial cannulation during general anesthesia, were enrolled. Using duplex Doppler ultrasonography, we measured the patients' arterial diameter, peak systolic velocity, end-diastolic velocity, resistance index, and mean volume flow of both arteries at five different time points. After radial artery cannulation, ulnar arterial diameter and blood flow did not significantly increase in DM group, as they did in non-DM group. Ulnar arterial resistance index significantly increased in both groups, but the degree of decrease in DM group was significantly less than non-DM. Ulnar artery's ability to increase blood flow for compensating the sudden reduction of radial arterial flow in DM patients was significantly less than that in non-DM patients under general anesthesia. Such attenuated vasoreactivity of ulnar artery to compensate the reduced radial arterial flow may have to be considered in radial arterial cannulation for DM patients.


Enhanced lattice distortion, yield strength, critical resolved shear stress, and improving mechanical properties of transition-metals doped CrCoNi medium entropy alloy.
The effect of transition-metals (TM) addition on the mechanical properties of CrCoNi medium entropy alloys (MEAs) was investigated. Molecular dynamics (MD) simulations were carried out to evaluate the atomic distortion and yield strength and critical resolved shear stress (CRSS) quantitively. The MD simulation results indicate that the lattice distortion and yield strength agree with the other experimental results. The addition of 4 atomic% of transition metals enhances the lattice distortion and yield strength of the CrCoNi alloy by ∼30% and retains high ductility and strengthening ability. Also, the elastic moduli, anisotropy factor, Pugh's ratio, and the hardness were investigated. Furthermore, we performed MD simulations to obtain the CRSS and the root-mean-square-atomic-displacement (RMSAD) of equiatomic and near-equiatomic CrCoNi MEAs. We demonstrated that an approximately linear relationship exists between the RMSAD and the CRSS for these alloying systems. A more realistic embedded atom method (EAM) potential also verified the universality. These simulation results will be useful in the future development and research of CrCoNi-based quaternary alloys with improved mechanical properties.


Tuberous sclerosis with striking renal involvement in a family.
We describe five cases of tuberous sclerosis in members of one family, all having renal involvement but with differences in age of onset and mode of presentation. Clinical, laboratory, and pathologic features helpful in diagnosing this condition and in distinguishing it from polycystic kidney disease and renal neoplasms are stressed. Tuberous sclerosis should always be considered in differential diagnosis of patients with multiple cystic renal lesions, particularly when age of onset of symptoms ranges from infancy to adult life in different members of one family. Absence both of specific glomerular or tubular lesions in ultrastructure and of major abnormalities in renal tubular function supports the existing concept that replacement of nephrons by hamartomatous lesions is the cause of progressive renal failure.


Safety and usefulness of insular depth electrodes implanted via an oblique approach in patients with epilepsy.
This study investigates the feasibility, safety, and usefulness of depth electrodes stereotactically implanted within the insular cortex. Thirty patients with suspected insular involvement during epileptic seizure underwent presurgical stereotactic electroencephalographic recordings using 10 to 16 depth electrodes per patient. Among these, one or two electrodes were implanted via an oblique approach to widely sample the insular cortex. Thirty-five insular electrodes were implanted in the 30 patients without morbidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insular cortex. Stereotactic electroencephalographic recordings of seizures allowed the differentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15 patients with secondary insular involvement; and Group 3, five patients with an initial insular involvement. In temporal epilepsy (n = 17), the insula was never involved at the seizure onset but was frequently involved during the seizures (11 out of 17). In frontotemporal or frontal epilepsy, the insula was involved at the onset of seizure in five out of 13 patients. All patients in Groups 1 and 2 underwent surgery, with a seizure-free outcome in 76.2% of patients. In Group 3, only two of the five patients underwent surgery, with a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in Group 1 compared with Group 2 in this small series: results were good in 83.3% (Engel I) versus 72.7%. Insula can be safely explored with oblique electrodes. In temporal lobe epilepsy, insular involvement does not significantly modify the short-term postoperative outcome. Future larger studies are necessary to clarify the long-term prognostic value of insular spread.


Wastewater-based epidemiology combined with local prescription analysis as a tool for temporalmonitoring of drugs trends - A UK perspective.
This paper reports the application of wastewater-based epidemiology (WBE) for the monitoring of one city in the UK in years 2014-2018 as a means of 1) exploring relative temporal changes of illicit drug usage trends across 5 sampling weeks in 5 years, (2) assessing policy impact in reducing drug consumption, focussing particularly on mephedrone, which was classified as a class B drug in the UK in 2010, and the effects of subsequent regulation such as the novel psychoactive substances (NPS) bill of 2016, (3) investigating temporal changes in consumption of prescription pharmaceuticals vs illicit drug usage, and (4) comparing consumption of prescription drugs with WBE to enable more accurate verification of prescription drugs with abuse potential. Mephedrone was quantified only for the first two years of the study, 2014-2015, and remained undetected for the next three years of the study. This shows that given enough time changes in drug policy can have an effect on drug consumption. However, after the introduction of the 2016 NPS bill, between the third and fourth study years, there was an observable increase in the consumption of "classic" drugs of abuse such as cocaine, MDMA and ketamine suggesting a shift away from novel psychoactives. The unique prescription dataset allowed for a more accurate calculation of heroin consumption using morphine by examining other sources morphine. Additionally, for compounds with controlled prescription like methadone, trends in consumption estimated by wastewater and trends in prescription correlated. Wastewater-based epidemiology is a powerful tool for examining whole populations and determining the efficacy and direction of government actions on health, as it can, alongside prescription and wider monitoring data, provide a clear insight into what is being consumed by a population and what action is needed to meet required goals.


Real-time motion segmentation of sparse feature points at any speed.
We present a real-time incremental approach to motion segmentation operating on sparse feature points. In contrast to previous work, the algorithm allows for a variable number of image frames to affect the segmentation process, thus enabling an arbitrary number of objects traveling at different relative speeds to be detected. Feature points are detected and tracked throughout an image sequence, and the features are grouped using a spatially constrained expectation-maximization (EM) algorithm that models the interactions between neighboring features using the Markov assumption. The primary parameter used by the algorithm is the amount of evidence that must accumulate before features are grouped. A statistical goodness-of-fit test monitors the change in the motion parameters of a group over time in order to automatically update the reference frame. Experimental results on a number of challenging image sequences demonstrate the effectiveness and computational efficiency of the technique.


Cloning, expression, and molecular characterization of a small pea gene family regulated by low levels of ultraviolet B radiation and other stresses.
A pea (Pisum sativum) DNA fragment (termed MB3) was isolated by differential display of cDNAs obtained from total leaf RNA of ultraviolet B (UV-B) radiation-treated plants. Longer cDNAs were cloned by rapid amplification of cDNA ends in the 3' to 5' direction. Three different, but very similar, cDNAs were cloned, sadA, sadB, and sadC, the major difference between them being a 36-bp deletion in the coding region of sadB. Southern blotting confirmed the occurrence of at least three genes in the pea genome. Database comparisons of the SAD protein sequences revealed high identity (46%) and similarity (77%) with a putative tomato (Lycopersicon esculentum) short-chain alcohol dehydrogenase. Very low levels of UV-B radiation (the biologically effective radiation normalized to 300 nm = 0.08 W m(-2)) was shown to up-regulate expression, a dose considerably lower than that needed to induce expression of the well-known UV-B defensive chalcone synthase and phenylalanine ammonia lyase genes. RNase protection assay revealed that primarily sadA and sadC mRNA accumulation was enhanced by UV-B. In addition to UV-B irradiation, ozone fumigation, wounding, aluminum stress, and salt stress induced increased transcript levels of the sad genes in pea.


Heart rate as marker of sympathetic activity.
To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. We studied 243 subjects aged 50.0+/-12.1 years (mean +/- SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1+/-13.0 and 78.2+/-13.0 versus 69.2+/-11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7+/-202 and 400.3+/-217 versus 230.4+/-126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1+/-14.7 and 55.3+/-14.3 versus 27.8+/-11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2+/-10.0 versus 27.8+/-11.0 bursts/min, P < 0.001). These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.