A new double right border binary vector for producing marker-free transgenic plants.
Once a transgenic plant is developed, the selectable marker gene (SMG) becomes unnecessary in the plant. In fact, the continued presence of the SMG in the transgenic plant may cause unexpected pleiotropic effects as well as environmental or biosafety issues. Several methods for removal of SMGs that have been reported remain inaccessible due to protection by patents, while development of new ones is expensive and cost prohibitive. Here, we describe the development of a new vector for producing marker-free plants by simply adapting an ordinary binary vector to the double right border (DRB) vector design using conventional cloning procedures. We developed the DRB vector pMarkfree5.0 by placing the bar gene (representing genes of interest) between two copies of T-DNA right border sequences. The β-glucuronidase (gus) and nptII genes (representing the selectable marker gene) were cloned next followed by one copy of the left border sequence. When tested in a model species (tobacco), this vector system enabled the generation of 55.6% kanamycin-resistant plants by Agrobacterium-mediated transformation. The frequency of cotransformation of the nptII and bar transgenes using the vector was 66.7%. Using the leaf bleach and Basta assays, we confirmed that the nptII and bar transgenes were coexpressed and segregated independently in the transgenic plants. This enable separation of the transgenes in plants cotransformed using pMarkfree5.0. The results suggest that the DRB system developed here is a practical and effective approach for separation of gene(s) of interest from a SMG and production of SMG-free plants. Therefore this system could be instrumental in production of "clean" plants containing genes of agronomic importance.


Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins.
Sequences rich in glutamine (Q) and asparagine (N) residues often fail to fold at the monomer level. This, coupled to their unusual hydrogen-bonding abilities, provides the driving force to switch between disordered monomers and amyloids. Such transitions govern processes as diverse as human protein-folding diseases, bacterial biofilm assembly, and the inheritance of yeast prions (protein-based genetic elements). A systematic survey of prion-forming domains suggested that Q and N residues have distinct effects on amyloid formation. Here, we use cell biological, biochemical, and computational techniques to compare Q/N-rich protein variants, replacing Ns with Qs and Qs with Ns. We find that the two residues have strong and opposing effects: N richness promotes assembly of benign self-templating amyloids; Q richness promotes formation of toxic nonamyloid conformers. Molecular simulations focusing on intrinsic folding differences between Qs and Ns suggest that their different behaviors are due to the enhanced turn-forming propensity of Ns over Qs.


Association of acute psychosocial stress with oxidative stress: Evidence from serum analysis.
Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expected to have higher levels of OxSt. Because our previous study showed inconsistent changes in conventional molecular markers for stress responses in the neuroendocrine and immune systems, we analyzed the same serum samples using a separate reducing capacity assay that provides a more global measurement of OxSt. This assay uses the moderately strong oxidizing agent iridium (Ir) to probe a sample's reducing capacity. Specifically, we characterized OxSt by this Ir-reducing capacity assay (Ir-RCA) using two measurement modalities (optical and electrochemical) and we tuned this assay by imposing an input voltage sequence that generates multiple output metrics for data-driven analysis. We defined five OxSt metrics (one optical and four electrochemical metrics) and showed: (i) internal consistency among each metric in the measurements of all 40 samples (baseline and post TSST for N=20); (ii) all five metrics were consistent with expectations of higher levels of OxSt for the SCZ group (three individual metrics showed statistically significant differences); and (iii) all five metrics showed higher levels of OxSt Post-TSST (one metric showed statistically significant difference). Using multivariant analysis, we showed that combinations of OxSt metrics could discern statistically significant increases in OxSt for both the SCZ and HC groups 90 min after the imposed acute psychosocial stress.


A Right to Access to Emergency Health Care: The European Court of Human Rights Pushes the Envelope.
This article argues that the European Court of Human Rights (ECtHR) seems to have recently acknowledged that there is a right to access to emergency health care in the member states of the Council of Europe. The Chamber of the ECtHR found that a state's failure to design a regulatory framework that guarantees access to health care in emergency situations violates the substantial limb of Article 2 European Convention on Human Rights (ECHR) that protects the right to life. It is argued that the newly established requirements seem to be reasonable but that there seem to be no sufficient safeguards to ensure that the ECtHR does not substitute its own assessment for that of medical professionals.


The handover process and triage of ambulance-borne patients: the experiences of emergency nurses.
One of the most important tasks that a nurse faces in the emergency room, when receiving a patient, is handover and the triage function. The aim of the study was to explore the experiences of nurses receiving patients who were brought into hospital as emergencies by ambulance crews through an analysis of the handover and triage process. A qualitative descriptive interview study inspired by the phenomenological method was used with six emergency nurses. There are three elements to a handover: a verbal report, handing over documented accounts and the final symbolic handover when a patient is transferred from the ambulance stretcher onto the hospital stretcher. The study identified that the verbal communication between ambulance and emergency nurses was often very structured. The ideal handovers often involved patients with very distinct medical problems. The difficult handover or the 'non-ideal' one was characterized by a significantly more complicated care situation. The handover function was pivotal in ensuring that the patient received the correct care and that care was provided at the appropriate level. The most seriously afflicted patients arrived by ambulance; therefore, the interplay between pre-hospital and hospital personnel was vital in conveying this important information. To some extent, this functioned well, but this research has identified areas where this care can be improved.


Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.
There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.


Expanding HAART treatment to all currently eligible individuals under the 2008 IAS-USA Guidelines in British Columbia, Canada.
In 2008, the IAS-USA published the revised guidelines for the use of HAART in adults substantially increasing the number of individuals eligible for HAART. The epidemic in British Columbia (BC) is mainly among men who have sex with men and those with injection drug use. Here, we explored the potential impact of different HAART coverage scenarios, based on the new guidelines, on the HIV-related incidence, morbidity and mortality in BC, Canada. We built a mathematical transmission model to investigate different HAART coverage scenarios (50%, 60%, 75% and 100%) of those medically eligible to receive HAART under the 2008 IAS guidelines. All new scenarios were compared to the current coverage in BC under the 2006 IAS guidelines (i.e. baseline scenario). In BC, it is estimated that 25-30% of individuals are unaware of their status. Costs were drug-related and reported in Canadian dollars. HIV-related morbidity and mortality were estimated based on the disability-adjusted life years (DALY) methodology. Currently, there are 4379 individuals on HAART under the IAS 2006 guidelines and 6781 individuals who qualify for treatment based on the new guidelines. Within 5 years, increasing HAART coverage decreased yearly new infections by at least 44.8%. In the 50% scenario, in 5 years, DALY decreased by 53% corresponding to 4155 averted DALYs, and in 25 years it decreased by 66% corresponding to 5837 averted DALYs. The effect was even stronger if the 75% scenario was chosen instead. Compared to the 100% expansion scenario, we observed an excess in annual direct treatment expenditures at the end of 5 years of approximately 1 million dollars in the 75% scenario, and of approximately 2 million dollars in the 50% scenario. The individual and public health benefits of these new guidelines are immense. The results show that by increasing the number of individuals on HAART save lives, it is cost averting, and it positively impacts society by decreasing the number of new HIV infections. Thus, public health community should consider incremental gains when considering guidelines and policy.


LAMA tumor in the rat as an experimental model for pre-B-cell leukemia.
A late pre-B-cell leukemia model in the rat, the LAMA tumor, is described. A mouse monoclonal antibody (HIS30) was developed against LAMA cells. HIS30 reacts with a membrane antigen in tumor tissue, whereas its reactivity with normal tissues is limited to the zona glomerulosa of the adrenal cortex and to the adrenal medulla. HIS30 was used for both the immunohistological detection of tumor cells in tissue sections and the immunolocalization of tumor cells in vivo. To enable in vitro studies with the LAMA model, an in vitro growing cell line (LAMA-K1) was established from the LAMA tumor. LAMA-K1 is immunophenotypically similar to the original tumor. Two tumor transplantation models were characterized. In the first model LAMA was implanted s.c., and local tumor growth occurred at the injection site, which was then followed by lymphatogenic and subsequently hematogenic tumor spread. In the second model i.v. transplantation caused direct hematogenic tumor dissemination. In both models early dissemination was especially prominent to the bone marrow, spleen, and liver. Later in the disease most visceral organs became involved, and partial paralysis of the animal was observed in the end stage of the disease. In combination with HIS30, the LAMA pre-B-cell tumor offers a model for both the investigation of in vivo transplanted tumor cells and for the in vivo detection of tumor cells by HIS30 in LAMA tumor-bearing rats.


Deviant Peer Preferences: A Simplified Approach to Account for Peer Selection Effects.
The goal of this study is to present and validate a simple method for accounting for peer selection on offending based on a respondent's self-reported preferences for friends who engage in criminal behavior. Using primary panel data (n = 611), having a preference for peers who offend (the measure of peer selection) relates positively and significantly to offending behavior. The selection measure, which carries the advantage of being closely aligned to criminological theory, renders the peer offending/perso nal offending relationship nonsignificant. Our selection variables also out perform a more traditional means of capturing peer selection effects.


Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.
Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.


[Construction of Tet-on inducible CXCR1 eukaryotic expression plasmid and identification of the expression character in NIH3T3 cells].
To construct tetracycline (Tet)-controlled inducible vector CXCR1-pTREhyg, and then detect the expression character of CXCR1 under the regulation of Dox in NIH3T3 cells. A full length cDNA of human CXCR1 was cloned from sample of fibroblast like synovium (FLS) in rheumatoid arthritis (RA) patient by RT-PCR and then sub-cloned into the pTREhyg plasmid after sequence analysis. CXCR1-pTREhyg and pTet-on was co-transfected with Lipofect2000 to NIH3T3 cells, and the expression of IL-8RA was detected by Western blot after given different concentration of Dox. Western blot showed that CXCR1 could be induced by Dox in NIH3T3 cells, and the phosphorylated Erk-1/2 level was significantly increased after IL-8 stimulation. Tet inducible recombinant vector of CXCR1-pTREhyg was successfully constructed, and it could be expressed in NIH3T3 cells. The stimulation of IL-8 obviously changed the activity of Erk-1/2 in the transfected NIH3T3 cells. This work has laid foundations for further study on the relationship between CXCR1 and RA disease.


PEG-Coated Large Mesoporous Silicas as Smart Platform for Protein Delivery and Their Use in a Collagen-Based Formulation for 3D Printing.
Silica-based mesoporous systems have gained great interest in drug delivery applications due to their excellent biocompatibility and high loading capability. However, these materials face challenges in terms of pore-size limitations since they are characterized by nanopores ranging between 6-8 nm and thus unsuitable to host large molecular weight molecules such as proteins, enzymes and growth factors (GFs). In this work, for an application in the field of bone regeneration, large-pore mesoporous silicas (LPMSs) were developed to vehicle large biomolecules and release them under a pH stimulus. Considering bone remodeling, the proposed pH-triggered mechanism aims to mimic the release of GFs encased in the bone matrix due to bone resorption by osteoclasts (OCs) and the associated pH drop. To this aim, LPMSs were prepared by using 1,3,5-trimethyl benzene (TMB) as a swelling agent and the synthesis solution was hydrothermally treated and the influence of different process temperatures and durations on the resulting mesostructure was investigated. The synthesized particles exhibited a cage-like mesoporous structure with accessible pores of diameter up to 23 nm. LPMSs produced at 140 °C for 24 h showed the best compromise in terms of specific surface area, pores size and shape and hence, were selected for further experiments. Horseradish peroxidase (HRP) was used as model protein to evaluate the ability of the LPMSs to adsorb and release large biomolecules. After HRP-loading, LPMSs were coated with a pH-responsive polymer, poly(ethylene glycol) (PEG), allowing the release of the incorporated biomolecules in response to a pH decrease, in an attempt to mimic GFs release in bone under the acidic pH generated by the resorption activity of OCs. The reported results proved that PEG-coated carriers released HRP more quickly in an acidic environment, due to the protonation of PEG at low pH that catalyzes polymer hydrolysis reaction. Our findings indicate that LPMSs could be used as carriers to deliver large biomolecules and prove the effectiveness of PEG as pH-responsive coating. Finally, as proof of concept, a collagen-based suspension was obtained by incorporating PEG-coated LPMS carriers into a type I collagen matrix with the aim of designing a hybrid formulation for 3D-printing of bone scaffolds.


Studies on the mechanism of action of Riley virus. IV. The reticuloendothelial system and impaired plasma enzyme clearance in infected mice.
The plasma clearance of intravenously injected rabbit muscle LDH was studied. In normal mice the clearance followed a biphasic exponential curve comprising an initial fast and subsequent slow phase. Riley virus-infected mice showed only the slow phase of enzyme clearance. The change from fast to slow clearance rate in normal mice appeared to depend upon the level of plasma enzyme activity rather than on the amount of enzyme cleared. Treatment of mice with RES-blocking agents (cholesterol oleate and carbon) inhibited the fast clearance phase, whereas an RES-stimulating agent (stilbestrol) caused an accelerated rate of enzyme clearance. Riley virus infection was found to inhibit the clearance of phosphoglucose isomerase, but had no effect on the clearance of alanine transaminase. The activity of the former enzyme is raised in the plasma of infected mice, whereas the activity of the latter enzyme is unaltered.


[The development of anorexia nervosa in people with an autism spectrum disorder; a qualitative, retrospective study].
To improve treatment options for women with autism spectrum disorder (ASD) in combination with anorexia nervosa (an), it is necessary to better understand which risk factors are involved in the development of an in this target audience.
 AIM: To identify risk factors for the development of an in people with ASD.
 METHOD: Six women with ASD who are, or have been suffering from an, were interviewed about the development of their eating disorder. The data were analyzed using the thematic analysis method.
 RESULTS: Regarding these participants, the generally accepted risk factors for developing an also appear to play a role, where it is possible that people with ASD form a vulnerable group for these risk factors. Characteristics specific for ASD were found to also contribute to the development of an in these participants.
 CONCLUSION: For women with ASD it is important to be aware of a vulnerability to develop an. Extra support in areas where they experience difficulties is therefore necessary. The ASD specific characteristics can be aggravating or sustaining factors for an and should therefore be included in the treatment.


Creating a human-induced pluripotent stem cell-based NKX2.5 reporter gene assay for developmental toxicity testing.
To test large numbers of chemicals for developmental toxicity, rapid in vitro tests with standardized readouts for automated data acquisition are needed. However, the most widely used assay, the embryonic stem cell test, relies on the counting of beating embryoid bodies by visual inspection, which is laborious and time consuming. We previously developed the PluriBeat assay based on differentiation of human induced pluripotent stem cells (hiPSC) that we demonstrated to be predictive for known teratogens at relevant concentrations using the readout of beating cardiomyocytes. Here, we report the development of a novel assay, which we term the PluriLum assay, where we have introduced a luciferase reporter gene into the locus of NKX2.5 of our hiPSC line. This enabled us to measure luminescence intensities instead of counting beating cardiomyocytes, which is less labor intensive. We established two NKX2.5 reporter cell lines and validated their pluripotency and genetic stability. Moreover, we confirmed that the genetically engineered NKX2.5 reporter cell line differentiated into cardiomyocytes with the same efficiency as the original wild-type line. We then exposed the cells to valproic acid (25-300 μM) and thalidomide (0.1-36 µM) and compared the PluriBeat readout of the cardiomyocytes with the luminescence intensity of the PluriLum assay. The results showed that thalidomide decreased luminescence intensity significantly with a higher potency and efficacy compared to the beating readout. With this, we have developed a novel hiPSC-based assay with a standardized readout that may have the potential for higher throughput screening for developmental toxicity.


[The dynamic morbidity with ischemic heart disease in the Republic of Kazakhstan].
A study of statistic data on the prevalence of ischemic heart disease (IHD) in 1998-2002 in the Republic of Kazakhstan showed an uptrend. Therefore, there is a need in defining actual prevention measures to cut the number of primary IHD cases.


Contrast enhancement: a physiological effect of striatal dopamine?
Dopamine functions as an important neuromodulator in the dorsal striatum and ventral striatum/nucleus accumbens. Evidence is accumulating for the idea that striatal neurons compete with each other for control over the animal's motor resources, and that dopamine plays an important modulatory role that allows a particular subset of neurons, encoding a specific behavior, to predominate in this competition. One means by which dopamine could facilitate selection among competing neurons is to enhance the contrast between stronger and weaker excitations (or to increase the "signal to noise ratio" among neurons, where the firing of the most excited neurons is assumed to transmit signal and the firing of the least excited to transmit noise). Here, we review the electrophysiological evidence for this hypothesis and discuss potential cellular mechanisms by which dopamine-mediated contrast enhancement could occur.


Stress modulates instrumental learning performances in horses (Equus caballus) in interaction with temperament.
The present study investigates how the temperament of the animal affects the influence of acute stress on the acquisition and reacquisition processes of a learning task. After temperament was assessed, horses were subjected to a stressor before or after the acquisition session of an instrumental task. Eight days later, horses were subjected to a reacquisition session without any stressor. Stress before acquisition tended to enhance the number of successes at the beginning of the acquisition session. Eight days later, during the reacquisition session, contrary to non-stressed animals, horses stressed after acquisition, and, to a lesser extent, horses stressed before acquisition, did not improve their performance between acquisition and reacquisition sessions. Temperament influenced learning performances in stressed horses only. Particularly, locomotor activity improved performances whereas fearfulness impaired them under stressful conditions. Results suggest that direct exposure to a stressor tended to increase acquisition performances, whereas a state of stress induced by the memory of a stressor, because it has been previously associated with the learning context, impaired reacquisition performances. The negative effect of a state of stress on reacquisition performances appeared to be stronger when exposure to the stressor occurred after rather than before the acquisition session. Temperament had an impact on both acquisition and reacquisition processes, but under stressful conditions only. These results suggest that stress is necessary to reveal the influence of temperament on cognitive performances.


Induction of cell cycle arrest and apoptosis by BCG infection in cultured human bronchial airway epithelial cells.
Bronchial airway epithelial cells (BAEpC) are among the first cells to encounter M. tuberculosis following airborne infection. However, the response of BAEpC to M. tuberculosis infection has been little studied. This study investigates the response of a human BAEpC cell line (BEAS-2B) to infection with Mycobacterium bovis Bacille Calmette Guerin (BCG). Cultured human BEAS-2B cells were experimentally infected with BCG. Uninfected BEAS-2B cultures were included as controls. Following infection, BEAS-2B cells were evaluated by various methods at various time points up to 3 days. Cell proliferation was evaluated by cellular bioreduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Distribution of cells along the cell cycle was evaluated by FACS analysis of cellular DNA. Apoptotic cells were identified by cell death ELISA and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method. Eighty-four apoptosis-relevant genes were screened by PCR gene microarray. Translation of Fas, Fas ligand (Fas-L), and Fas-associated death domain (FADD) were evaluated quantitatively by real-time PCR. Expression of Fas and FADD proteins was evaluated by immunofluorescence and Western blot. Activity of caspase-3 and caspase-8 was evaluated by colorimetric assay of their enzymatic activity. BCG infection of BEAS-2B cells inhibits proliferation, induces cell cycle arrest at the G(0)/G(1) phase, causes apoptosis, modulates transcription of multiple apoptosis-relevant genes, promotes translation of Fas, Fas-L, and FADD, upregulates expression of Fas and FADD proteins, and increases activity of caspase-3 and caspase-8. Infection with BCG does not cause any significant change in the secretion of TGF-beta. The roles of Fas and FADD as mediators of BCG-induced apoptosis in BEAS-2B cells were tested by partial blockade of Fas and FADD expression with silencing RNA. Partial blockade of Fas or FADD expression results in a decreased apoptotic response to BCG infection. In conclusion, BCG induces cell cycle arrest and apoptosis in BEAS-2B cells. BCG induced apoptosis of BEAS-2B cells via the Fas death receptor pathway.


Gene expression genetics of the striatum of Diversity Outbred mice.
Brain transcriptional variation is a heritable trait that mediates complex behaviors, including addiction. Expression quantitative trait locus (eQTL) mapping reveals genomic regions harboring genetic variants that influence transcript abundance. In this study, we profiled transcript abundance in the striatum of 386 Diversity Outbred (J:DO) mice of both sexes using RNA-Seq. All mice were characterized using a behavioral battery of widely-used exploratory and risk-taking assays prior to transcriptional profiling. We performed eQTL mapping, incorporated the results into a browser-based eQTL viewer, and deposited co-expression network members in GeneWeaver. The eQTL viewer allows researchers to query specific genes to obtain allelic effect plots, analyze SNP associations, assess gene expression correlations, and apply mediation analysis to evaluate whether the regulatory variant is acting through the expression of another gene. GeneWeaver allows multi-species comparison of gene sets using statistical and combinatorial tools. This data resource allows users to find genetic variants that regulate differentially expressed transcripts and place them in the context of other studies of striatal gene expression and function in addiction-related behavior.


Enhancing nurse and physician collaboration in clinical decision making through high-fidelity interdisciplinary simulation training.
To determine whether interdisciplinary simulation team training can positively affect registered nurse and/or physician perceptions of collaboration in clinical decision making. Between March 1 and April 21, 2009, a convenience sample of volunteer nurses and physicians was recruited to undergo simulation training consisting of a team response to 3 clinical scenarios. Participants completed the Collaboration and Satisfaction About Care Decisions (CSACD) survey before training and at 2 weeks and 2 months after training. Differences in CSACD summary scores between the time points were assessed with paired t tests. Twenty-eight health care professionals (19 nurses, 9 physicians) underwent simulation training. Nurses were of similar age to physicians (27.3 vs 34.5 years; p = .82), were more likely to be women (95.0% vs 12.5%; p < .001), and were less likely to have undergone prior simulation training (0% vs 37.5%; p = .02). The pretest showed that physicians were more likely to perceive that open communication exists between nurses and physicians (p = .04) and that both medical and nursing concerns influence the decision-making process (p = .02). Pretest CSACD analysis revealed that most participants were dissatisfied with the decision-making process. The CSACD summary score showed significant improvement from baseline to 2 weeks (4.2 to 5.1; p < .002), a trend that persisted at 2 months (p < .002). Team training using high-fidelity simulation scenarios promoted collaboration between nurses and physicians and enhanced the patient care decision-making process.


Image-guided fine-needle aspiration cytology of ovarian tumors: An assessment of diagnostic efficacy.
Image-guided fine-needle aspiration cytology (FNAC) of ovarian lumps is being increasingly used for the successful diagnosis of ovarian tumors, although borderline cases may be difficult to diagnose by this method. To demonstrate the efficacy of image-guided FNAC in diagnosing ovarian tumors (benign and malignant) and to evaluate the usefulness of cytology as a mode of easy and rapid diagnosis of ovarian lumps. The study was conducted on 42 female patients. Clinical evaluation and relevant investigations were carried out. Diagnosis was established by FNAC performed under image guidance (ultrasonography/computed tomography). The cytological diagnosis was confirmed by histopathological examination. Cytological diagnosis was rendered on all the 42 ovarian lesions, with a correct diagnosis in 34 cases, resulting in a diagnostic accuracy of 80.9%. Most of the cases with discordant diagnoses were surface epithelial tumors of low malignant potential and required histopathological examination for a final diagnosis. Image-guided FNAC is an inexpensive, rapid and fairly accurate procedure for the diagnosis of ovarian lesions. It provides a safe alternative to the more expensive, time consuming and cumbersome surgical route to diagnosis.


Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer.
Phase I studies of [N-(2-hydroxypropyl)methacrylamide] (HPMA) copolymer-doxorubicin previously showed signs of activity coupled with 5-fold decreased anthracycline toxicity in chemotherapy-refractory patients. Here we report phase II studies using a similar material (FCE28068) in patients with breast (n=17), non-small cell lung (NSCLC, n=29) and colorectal (n=16) cancer. Up to 8 courses of PK1 (280 mg/m(2) doxorubicin-equivalent) were given i.v., together with 123I-labelled imaging analogue. Toxicities were tolerable, with grade 3 neutropenia more prominent in patients with breast cancer (4/17, 23.5% compared with 5/62, 8.1% overall). Of 14 evaluable patients with breast cancer 3 had partial responses (PR), all anthracycline-naïve patients. In 26 evaluable patients with NSCLC, 3 chemotherapy-naïve patients had PR. In contrast, none of the 16 evaluable patients with colorectal cancer responded. Imaging of 16 patients (5 with breast cancer, 6 NSCLC, 5 colorectal cancer) showed obvious tumour accumulation in 2 metastatic breast cancers, although unfortunately no images were obtained from patients who responded. These results show 6/62 PR with limited side effects, supporting the concept that polymer-bound therapeutics can have modified and improved anticancer activities and suggesting the approach should be explored further for breast cancer and NSCLC.


Intravitreal injection therapy in the treatment of noninfectious uveitis.
Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects.


Temperature dependence of nickel stabilization in inorganic oxide matrices.
Scanning electron microscopy, X-ray diffractometry, X-ray absorption spectroscopy, and other means are used to investigate the effect of thermal treatment temperature, 105-1100 degrees C, on the immobilization of nickel (Ni) by the inorganic oxides of latosol. Ni is more firmly immobilized by the latosol with increasing temperature. Spectral analyses indicate that a shoulder toward the edge-jump appears in the spectra of X-ray absorption near-edge structure for the samples heated at 900 and 1100 degrees C. Moreover, the intensity of the main peak at the edge increases with higher temperature; this information indicates the distortion of the divalent nickel [Ni(II)] environment in the samples heated at 900 and 1100 degrees C. Nevertheless, the distortion is absent from the samples heated at 105 and 500 degrees C. The fact of the distortion of the Ni(II) environment suggests the occurrence of a chemical reaction between the Ni compound and the inorganic matrices of the latosol soil during the heating process at 900 and 1100 degrees C. In addition, the extended X-ray absorption fine structure results correspond well to the X-ray absorption near-edge structure results; the former are supportive of the occurrence of a distorted Ni(II) environment in the samples heated at 900 and 1100 degrees C. The wet-chemistry results show that the samples heated at 900-1100 degrees C leach less Ni than the 105-500 degrees C samples do. The change of the Ni environment is related to the observation that less Ni is leached from the samples heated at 900-1100 degrees C. Furthermore, the pore closing phenomenon is observed only in the 1100 degrees C sample; this phenomenon corresponds with the fact that the 1100 degrees C sample leaches less Ni than the 900 degrees C sample does.


MultiVision: Designing Analytical Dashboards with Deep Learning Based Recommendation.
We contribute a deep-learning-based method that assists in designing analytical dashboards for analyzing a data table. Given a data table, data workers usually need to experience a tedious and time-consuming process to select meaningful combinations of data columns for creating charts. This process is further complicated by the needs of creating dashboards composed of multiple views that unveil different perspectives of data. Existing automated approaches for recommending multiple-view visualizations mainly build on manually crafted design rules, producing sub-optimal or irrelevant suggestions. To address this gap, we present a deep learning approach for selecting data columns and recommending multiple charts. More importantly, we integrate the deep learning models into a mixed-initiative system. Our model could make recommendations given optional user-input selections of data columns. The model, in turn, learns from provenance data of authoring logs in an offline manner. We compare our deep learning model with existing methods for visualization recommendation and conduct a user study to evaluate the usefulness of the system.


Roles of human beta-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells.
Human beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. In this study, the expression and inducibility of beta-defensins at the ocular surface were investigated in vitro and in vivo. Expression of human beta-defensins (hBD) was determined by RT-PCR and immunohistochemistry in tissues of the ocular surface and lacrimal apparatus. Cultured corneal and conjunctival epithelial cells were stimulated with proinflammatory cytokines and supernatants of different ocular pathogens. Real-time PCR and ELISA experiments were performed to study the effect on the inducibility of hBD2 and 3. Expression and inducibility of mouse beta-defensins-2, -3 and -4 (mBD2-4) were tested in a mouse ocular surface scratch model with and without treatment of supernatants of a clinical Staphylococcus aureus (SA) isolate by means of immunohistochemistry. Here we show that hBD1, -2, -3 and -4 are constitutively expressed in conjunctival epithelial cells and also partly in cornea. Healthy tissues of the ocular surface, lacrimal apparatus and human tears contain measurable amounts of hBD2 and -3, with highest concentrations in cornea and much lower concentrations in all other tissues, especially tears, suggesting intraepithelial storage of beta-defensins. Exposure of cultured human corneal and conjunctival epithelial cells to proinflammatory cytokines and supernatants of various bacteria revealed that IL-1beta is a very strong inductor of hBD2 and Staphylococcus aureus increases both hBD2 and hBD3 production in corneal and conjunctival epithelial cells. A murine corneal scratch model demonstrated that beta-defensins are only induced if microbial products within the tear film come into contact with a defective epithelium. Our finding suggests that the tear film per se contains so much antimicrobial substances that epithelial induction of beta-defensins occurs only as a result of ocular surface damage. These findings widen our knowledge of the distribution, amount and inducibility of beta-defensins at the ocular surface and lacrimal apparatus and show how beta-defensins are regulated specifically.


Reactions and Receptivity to Framing HIV Prevention Message Concepts About Pre-Exposure Prophylaxis for Black and Latino Men Who Have Sex with Men in Three Urban US Cities.
Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada®) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the PrEP efficacy data. Despite being concerned that other MSM would interpret the messages to mean that condom use was unnecessary while taking PrEP, participants themselves primarily understood PrEP as a supplement rather than a replacement for condoms. Based on their experience with taking antiretroviral medication, HIV-positive men considered condom use a more feasible form of HIV prevention than PrEP. Participants' responses suggest that more information about PrEP and the clinical trial would support the legitimacy of PrEP and the messages as a whole. These details may enhance believability in the concept of PrEP and reinforce confidence in the validity of the efficacy result.


[Clinical course and treatment of herpetic trigeminal ganglionic neuropathy].
45 patients were observed in the periods of both acute herpes zoster and postherpetic neuralgia (PHN). In most of the patients herpetic eruptions were located in the areas of innervation of the first branch of the trigeminal nerve. In acute period of the disease there were used aciclovir, helepin or alpisarinum, antiherpetic immunoglobulin, deoxyribonuclease, non-narcotic analgetics were used. Of 28 patients residual PHN was observed in 6 cases, delayed PHN (during 3 months)--in 2 patients. The PHN development was characteristic for elderly patients, delayed request for medical care, concomitant diseases, eruptions with hemorrhagic component and secondary pyodermia and considerable residual sensory deficit. In therapy of PHN the most effective drugs were amitriptylin, non-narcotic analgetics, anticonvulsants as well as acupuncture and electroacupuncture. Relief of a typical deafferentation of pain syndrome was achieved by means of ultrasonic destruction of the trigeminal nucleus (one case). Early therapy of acute herpes zoster does not prevent completely PHN development, but it decreased considerably probability of its forming as well as the severity of its course.


[Correlated study of visual evoked potentials-polyneuropathy in diabetic patients without retinopathy].
The functional study of visual pathways by means of pattern reversals VEPs (visual evoked potentials) was used as a noninvasive method in the study of diabetic patients, but the correlations between alterations in VEPs and the involvement of peripheral nervous system were not explored. Among 35 diabetic patients not suffering from retinopathy, we tested early deteriorations in visual pathways by means of pattern reversals VEPs and we considered similarities between these alterations, clinical metabolic parameters of the disease and clinical and paraclinical aspects of polyneuropathy (PNP). Four of these patients were insulin-dependent and 31 non-insulin-dependent, all with normal electroretinography and fluorangiography. Monitoring control of diabetes was performed by measuring hemoglobin HbA1. The control group was composed of 35 healthy subjects with normal neurologic and ophthalmologic examinations and normal visual acuity. In all subjects we tested four peripheral nerve conduction velocities (PNCV) (sensory and motor conduction of median nerve, motor conduction of peroneal nerve, anthidromic sensory conduction of sural nerve) diabetic patients were distributed in two groups according to the presence (group A, 15 patients) or absence (group B, 20 patients) of polyneuropathy. Pattern reversals PEVs were recorded after mono and binocular stimulation; screen was 25 x 18 cm with black and white check board pattern, check size 1.1 cm. Subject-to-stimulus distance was 1 m, corresponded to a visual angle of 38 degrees. Active electrode were located in Oz, O1 and O2, reference electrode in Fz.(ABSTRACT TRUNCATED AT 250 WORDS)


Healthcare workers' knowledge and attitudes towards COVID-19 in Saudi Arabia.
The world is facing a devastating challenge in the COVID-19 (coronavirus disease 19) outbreak. Healthcare workers (HCWs) provide the first line of defense against any disease outbreak. Thus, the present study is designed to assess HCWs' attitudes towards, knowledge of, and awareness of COVID-19. A cross-sectional observational study was conducted using an online survey on social media; the participants were 597 adults. The study was conducted from March to April 2020. The questionnaire was randomly administered on Arabic-language social media applications; the 26-item survey assessed knowledge levels, attitudes, and practices. The analysis includes 597 complete responses from HCWs; participants included physicians, nurses, medical students, and pharmacists. Most participants were females aged 18 to 25 years. Most participants agreed that the virus can spread via direct and indirect contact. Most participants indicated that they wash their hands; avoid touching their eyes, nose, or mouth; and avoid crowded places to protect themselves against infection. Most indicated that a bat was the original source of the virus. Most participating HCWs indicated that the symptoms of COVID-19 include fever, cough, and shortness of breath. Most of the participants also indicated that there is no specific treatment for patients infected with COVID-19. The findings of this work can support the design of effective measures to prevent and control COVID-19 infections during the pandemic. The results also highlight where improvement is needed to HCWs' knowledge of and attitudes towards COVID-19; the findings also highlight the best healthcare practices regarding this illness.


Gradient-Based Local Causal Structure Learning.
Finding the causal structure from a set of variables given observational data is a crucial task in many scientific areas. Most algorithms focus on discovering the global causal graph but few efforts have been made toward the local causal structure (LCS), which is of wide practical significance and easier to obtain. LCS learning faces the challenges of neighborhood determination and edge orientation. Available LCS algorithms build on conditional independence (CI) tests, they suffer the poor accuracy due to noises, various data generation mechanisms, and small-size samples of real-world applications, where CI tests do not work. In addition, they can only find the Markov equivalence class, leaving some edges undirected. In this article, we propose a GradieNt-based LCS learning approach (GraN-LCS) to determine neighbors and orient edges simultaneously in a gradient-descent way, and, thus, to explore LCS more accurately. GraN-LCS formulates the causal graph search as minimizing an acyclicity regularized score function, which can be optimized by efficient gradient-based solvers. GraN-LCS constructs a multilayer perceptron (MLP) to simultaneously fit all other variables with respect to a target variable and defines an acyclicity-constrained local recovery loss to promote the exploration of local graphs and to find out direct causes and effects of the target variable. To improve the efficacy, it applies preliminary neighborhood selection (PNS) to sketch the raw causal structure and further incorporates an l1 -norm-based feature selection on the first layer of MLP to reduce the scale of candidate variables and to pursue sparse weight matrix. GraN-LCS finally outputs LCS based on the sparse weighted adjacency matrix learned from MLPs. We conduct experiments on both synthetic and real-world datasets and verify its efficacy by comparing against state-of-the-art baselines. A detailed ablation study investigates the impact of key components of GraN-LCS and the results prove their contribution.


The COUP-TFs compose a family of functionally related transcription factors.
The chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily and function in transcriptional regulation of a wide variety of genes. The COUP-TFs purified from HeLa nuclear extract by COUP-affinity chromatography are composed of multiple M(r) forms. The Low M(r) COUP-TFs (43,000, 44,000, 46,000, and 47,000 M(r)) produce a relatively fast migrating complex (C1) with DNA in electrophoresis mobility shift assays, while the high M(r) forms (66,000, 68,000, 72,000, and 74,000 M(r)) produce a slower migrating (C2) complex. The high M(r) COUP-TFs were purified by gel filtration chromatography and independently formed the C2 DNA complex, probably acting as dimers. The high M(r) forms are indistinguishable from the low M(r) COUP-TFs in DNA binding and in enhancement of in vitro transcription from the ovalbumin promoter. The finding of multiple COUP-TF forms led us to clone a second low M(r) COUP-TF, "COUP-TF2." The COUP-TF2 sequence has very strong homology with COUP-TF1. The N-termini of COUP-TF1 and COUP-TF2 are least similar, but both contain glutamine-rich and proline-rich motifs, putative activation domains.


Intensity-modulated radiation therapy dose prescription and reporting: Sum and substance of the International Commission on Radiation Units and Measurements Report 83 for veterinary medicine.
Institutions' adherence to protocol, quality assurance, and radiation parameter reporting are key to adequately interpret and compare treatment outcomes in radiation oncology. In 2017, the editorial board for Veterinary Radiology & Ultrasound adapted author guidelines on "technical information for radiation therapy (RT)". These guidelines provide a framework to report the RT treatment process in manuscripts resulting from veterinary clinical trials. In spite of this framework, however, in implementing IMRT, we have identified different "interpretations" of the extended prescription and reporting recommendations of the International Commission on Radiation Units and Measurements (ICRU 83), even within our small team. In the following commentary review, we provide a short summary of various detailed aspects of the ICRU 83 recommended (IMRT) prescription and reporting, including (a) absorbed target dose specification and prescription, (b) homogeneity and conformity, and (c) reporting of absorbed dose in organs at risk. In particular, we want to share our thoughts on possible dangers of noncompliance in adhering to protocol, prescription, and reporting. As veterinary IMRT publications still sparsely adhere to the recommendations of the ICRU, we were motivated to summarize the recommendations to facilitate appropriate reporting for IMRT in future veterinary studies.


A 12-month, multicenter, parallel group comparison of dexamethasone intravitreal implant versus ranibizumab in branch retinal vein occlusion.
Dexamethasone intravitreal implant and intravitreal ranibizumab are indicated for the treatment of macular edema secondary to retinal vein occlusion. This non-inferiority study compared dexamethasone with ranibizumab in patients with branch retinal vein occlusion. In this randomized, 12-month head-to-head comparison, subjects with branch retinal vein occlusion were assigned to dexamethasone 0.7 mg at day 1 and month 5 with the option of retreatment at month 10 or 11, or ranibizumab 0.5 mg at day 1 and monthly through month 5 with subsequent as-needed injections at month 6-month 11. The primary efficacy outcome was the mean change from baseline in best-corrected visual acuity at month 12; secondary outcomes included average change in best-corrected visual acuity, proportion of eyes with ≥10- and ≥15-letter gain/loss, change in central retinal thickness, and change in Vision Functioning Questionnaire-25 score. In all, 307 of a planned 400 patients were enrolled in the study and received (mean) 2.5 dexamethasone injections (n = 154) and 8.0 ranibizumab injections (n = 153) over 12 months. The mean change from baseline in best-corrected visual acuity at month 12 was 7.4 letters for dexamethasone versus 17.4 letters for ranibizumab (least-squares mean difference (dexamethasone minus ranibizumab), -10.1 letters; 95% confidence interval, -12.9, -7.2; p = 0.0006). Dexamethasone and ranibizumab improved best-corrected visual acuity and anatomical outcomes; however, dexamethasone did not show non-inferiority to ranibizumab in this under-powered study. Dexamethasone was associated with an increased risk of intraocular pressure elevation and cataract progression, but a lower injection burden, compared to ranibizumab.


Influence of beliefs about cervical cancer etiology on Pap smear use among Latina immigrants.
To assess Latina immigrants' beliefs about the role of sexual activities in cervical cancer etiology and the impact of the beliefs on Papanicolaou (Pap) smear use. Previous research has found that Latinas, particularly immigrants, believe that cervical cancer is related to 'unwise' sexual activities; however, their beliefs about the nature of the relationship are unclear. We conducted semi-structured face-to-face interviews with a non-probability purposive sample of 20 Mexican immigrant women who resided in Orange County, California regarding their beliefs about risk factors for cervical cancer and Pap smear use. We used qualitative content analysis to identify major themes. Three investigators independently reviewed transcripts of the audio-taped interviews to identify themes and came to a consensus about them. The women had a mean age of 39 years and had resided in the USA for an average of 16.3 years. We identified several themes. The majority of respondents had limited knowledge about cervical cancer and no knowledge about human papillomavirus (HPV); believed that infections caused by physical trauma, certain sexual activities, and poor hygiene caused cervical cancer; believed that they only needed a Pap smear if they developed symptoms of a pelvic infection; and felt that women who engaged in 'unwise' sexual behaviors, in particular, should receive regular Pap smear exams. The results suggest that culturally related beliefs about the etiology of cervical cancer play a role in the decision to obtain Pap smears for Latina immigrants. The findings may help to explain why researchers have found Latino ethnicity to be an independent predictor of Pap smear use. They also suggest that programs designed to improve cervical cancer screening, particularly among Latina immigrants, should stress the nature of HPV transmission, its role in the etiology of cervical cancer, and the importance of Pap smear screening in the absence of symptoms.


Cannabis-induced basal-mid-left ventricular stress cardiomyopathy: A case report.
Cannabis, popularly known as marijuana, is a recreational drug derived from the plant Cannabis Sativa. It has been recognized as the most widely used mood-altering substance in the world and is falsely perceived as a safe substance by the public at large. This is mostly due to lack of awareness of its adverse effects as well as successful attempts for legalization of its use in many states. We present a unique case of a 56-year-old man who presented with neurological deficits concerning for stroke. Soon after presentation, he required endotracheal intubation for airway protection due to worsening mental status changes and pulmonary edema. Echocardiogram revealed severe hypokinesis of the basal and mid-left ventricular (LV) walls with hyperdynamic motion of the apex (reverse takotsubo). Coronary angiography revealed no obstructive disease. Urine toxicology screen was positive for Δ-9-tetrahydrocannabinol. The patient then stated to have used excess marijuana before the symptom onset, while denying any recent emotional stressors. The findings were consistent with stress cardiomyopathy (SC) triggered by marijuana use. Myocardial infarction, stroke, and peripheral arteriopathy have been increasingly reported in younger individuals using marijuana. SC appears to be another unique complication of marijuana use triggered through its effects on the autonomic nervous and endocannabinoid systems.


Frequency of specific osteopathic manipulative treatment modalities used by candidates while taking COMLEX-USA Level 2-PE.
As one of the key measures of clinical skills assessment, the Comprehensive Osteopathic Medical Licensing Examination-USA Level 2-Performance Evaluation (COMLEX-USA Level 2-PE) is used to rate candidates' performance of osteopathic manipulative treatment (OMT). To evaluate the frequency of specific OMT modalities used by COMLEX-USA Level 2-PE candidates and to report frequent use on the basis of clinical presentation. With enhanced scoring procedures in place, OMT physician-examiners identified and documented specific OMT techniques that were performed by candidates at the 28 colleges of osteopathic medicine and branch campuses that had eligible students at that time. A frequency analysis for OMT techniques, according to clinical content axis, was applied to all candidates (N=4757) for the 2010-2011 testing cycle. Students used a wide range of specific OMT techniques. Candidates performed 24,202 instances of specific OMT techniques, including 10,471 myofascial/soft tissue (43.3%), 3942 muscle energy (16.3%), 1676 sinus drainage (6.9%), 1476 inhibition (6.1%), 1221 fascial release (5.0%), 1171 rib raising (4.8%), 918 lymphatic (3.8%), and 866 counterstrain (3.6%). A few students (<0.01%) used high-velocity, low-amplitude (HVLA), a technique that is prohibited from use on the COMLEX-USA Level 2-PE because of the potential hazard of repeatedly treating a standardized patient with thrust technique to the same segment in a given day. Additional techniques included functional, facilitated positional release, balanced ligamentous tension, and visceral. Use of techniques also varied according to the clinical presentation of the standardized patient (ie, cardiovascular, respiratory, neuromusculoskeletal, gastrointestinal, or other) and chronicity (ie, acute or chronic). Findings contributed to a better understanding of the types of OMT techniques being used by candidates taking COMLEX-USA Level 2-PE. Frequency of use of specific OMT modalities varied according to clinical case presentation.


Experimental Tribulus terrestris poisoning in sheep: clinical, laboratory and pathological findings.
Eleven native sheep, 1-2 years old, of both sexes were randomly divided into two groups, 6 sheep being allocated to the experimental group and 5 serving as controls. The sheep in the experimental group were fed 80% Tribulus terrestris and 20% alfalfa hay and wheat straw, while the control sheep were given a mixture of 40% alfalfa hay and 60% wheat straw. Clinical signs of hepatogenous photosensitivity were observed from day 11, including reddening and crust formation on the muzzle, nose, ears and eyelids, depression, weight loss, icterus, conjunctivitis, and yellow discoloration of the urine. Laboratory findings on weekly samples indicated significant differences (p < 0.05) in white blood cell count, total plasma protein and fibrinogen, total and direct bilirubin, blood urea nitrogen and creatinine concentrations, and aspartate aminotransferase and alkaline phosphatase activities. There were no significant differences in the packed cell volume, in the neutrophil, lymphocyte or eosinophil counts, or in the serum calcium, phosphorus, potassium, sodium or chloride concentrations. At necropsy of the experimental animals, there were various degrees of generalized icterus and the livers were swollen and discolored by bile pigment. Histopathological examination revealed varying amounts of crystalloid material in the bile ducts and renal tubules, hepatocellular degeneration, biliary fibrosis and proliferation, renal tubular necrosis and focal necrosis of cardiac muscle.


[Enterosorption in the treatment of patients with chronic urticaria].
A synthetic carbon sorbent (SKNP-2) was included in the treatment of 197 patients with relapsing urticaria. Courses lasted 7, 14, 20 days. The clinical effect was favourable and its efficacy increased with prolongation of the therapy course time using the enterosorbent. Immunological parameters did not change in the course of treatment.


Pre-aggregation kinetics and intermediates of α-synuclein monitored by the ESIPT probe 7MFE.
The defining feature of the extensive family of amyloid diseases is the formation of networks of entangled elongated protein fibrils and amorphous aggregates exhibiting crossed β-sheet secondary structure. The time course of amyloid conversion has been studied extensively in vitro with the proteins involved in the neurodegenerative pathology of Parkinson's disease (α-synuclein), Alzheimer's disease (Tau) and Huntington's disease (Huntingtin). Although much is known about the thermodynamics and kinetics of the transition from a soluble, intrinsically disordered monomer to the fibrillar end state, the putative oligomeric intermediates, currently considered to be the major initiators of cellular toxicity, are as yet poorly defined. We have detected and characterized amyloid precursors by monitoring AS aggregation with ESIPT (excited state intramolecular protein transfer) probes, one of which, 7MFE [7-(3-maleimido-N-propanamide)-2-(4-diethyaminophenyl)-3-hydroxychromone], is introduced here and compared with a related compound, 6MFC, used previously. A series of 140 spectra for sparsely labeled AS was acquired during the course of aggregation, and resolved into the relative contributions (spectra, intensities) of discrete molecular species including the monomeric, fibrillar, and ensemble of intermediate forms. Based on these findings, a kinetic scheme was devised to simulate progress curves as a function of key parameters. An essential feature of the model, one not previously invoked in schemes of amyloid aggregation, is the catalysis of molecular fuzziness by discrete colloidal nanoparticles arising spontaneously via monomer condensation upon exposure of AS to ≥ 37 °C.


Fellow eye changes in optic neuritis correlate with the risk of multiple sclerosis.
Recent studies demonstrate early diffuse central nervous system (CNS) inflammation in patients with multiple sclerosis (MS). The clinically unaffected (fellow) eye of patients with unilateral optic neuritis (ON) may reflect the status of normal-appearing white matter in the CNS, which can be assessed electrophysiologically. To study the relationship between electrophysiological parameters in the fellow eye of ON patients, and risk of conversion to MS. Forty-eight consecutive patients with acute unilateral ON were examined 12 months after ON of which 14 had MS, 19 remained high risk (HR) for MS, and 15 had low risk (LR) for MS according to McDonald's criteria. Twenty-five age-matched controls were also tested. Amplitude and latency of multifocal visual evoked potential (mfVEP) in the fellow eyes of patients at 12 months were analyzed and compared with controls. Average mfVEP amplitude was 240 +/- 35, 232 +/- 36, 181 +/- 38, and 169 +/- 48 nV for controls, LR, HR, and MS groups respectively. Average mfVEP latency for controls, LR, HR, and MS patients was 139.7 +/- 5.5, 141.7 +/- 3.6, 145.9 +/- 8.9, and 152.0 +/- 9.9 ms respectively. The magnitude of latency prolongation and amplitude decline 12 months after the initial episode was proportional to the risk of MS. The prognostic significance of these changes as predictors of subsequent MS should be investigated longitudinally.


Postnatal growth of abandoned preterm babies.
Eighteen abandoned low birth weight infants matched for sex and gestational age with infants who had mothers were followed up till discharge or death. Anthropometric measurements were taken on recruitment and then weekly. Initially all infants were on breast milk. For the abandoned ones, milk was obtained from other mothers. Results show that the abandoned infants were on breast milk until they attained a mean weight of 1960gm. This coincided with a postnatal age of 6 weeks. For the rest of the period they were on artificial feed. Mean birth weight was 1403 +/- 302 and 1337 +/- 204 for cases and controls respectively while the mean gestation was 30 weeks. Anthropometric measurements were similar at the beginning of the study and both groups regained birth weight at 2 weeks. Thereafter the rate of weight gain of 16gm per day for the cases was significantly lower than that of 22gm per day for the controls. Similarly midarm circumference increases were much lower in the cases than in controls (0.2cm versus 0.4 per week). There were however no significant differences in length and head circumference increases. A significant number of cases (94.4%) had one or more episodes of serious infection and 38.9% died. None of the control infants died and only 10.5% had serious infection.


Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase.
Beta-lactamase confers resistance to penicillin-like antibiotics by hydrolyzing their beta-lactam bond. To combat these enzymes, inhibitors covalently cross-linking the hydrolytic Ser70 to Ser130 were introduced. In turn, mutant beta-lactamases have emerged with decreased susceptibility to these mechanism-based inhibitors. Substituting Ser130 with glycine in the inhibitor-resistant TEM (IRT) mutant TEM-76 (S130G) prevents the irreversible cross-linking step. Since the completely conserved Ser130 is thought to transfer a proton important for catalysis, its substitution might be hypothesized to result in a nonfunctional enzyme; this is clearly not the case. To investigate how TEM-76 remains active, its structure was determined by X-ray crystallography to 1.40 A resolution. A new water molecule (Wat1023) is observed in the active site, with two configurations located 1.1 and 1.3 A from the missing Ser130 Ogamma; this water molecule likely replaces the Ser130 side-chain hydroxyl in substrate hydrolysis. Intriguingly, this same water molecule is seen in the IRT TEM-32 (M69I/M182T), where Ser130 has moved significantly. TEM-76 shares other structural similarities with various IRTs; like TEM-30 (R244S) and TEM-84 (N276D), the water molecule activating clavulanate for cross-linking (Wat1614) is disordered (in TEM-30 it is actually absent). As expected, TEM-76 has decreased kinetic activity, likely due to the replacement of the Ser130 side-chain hydroxyl with a water molecule. In contrast to the recently determined structure of the S130G mutant in the related SHV-1 beta-lactamase, in TEM-76 the key hydrolytic water (Wat1561) is still present. The conservation of similar accommodations among IRT mutants suggests that resistance arises from common mechanisms, despite the disparate locations of the various substitutions.


[Metabolic and hemodynamic effects of pioglitazone in obese patients with type 2 diabetes].
The purpose of the study was to evaluate the effectiveness and safety of pioglitazon, a hypoglycemizing preparation belonging to the group of thiazolidinediones, in treatment of diabetes mellitus (DM) type 2. Twenty DM type 2 patients were included in the study. The use of pioglitazon during 12 weeks resulted in a significant decrease in glycated hemoglobin, fasting glycemia, and postprandial reduction in insulinemia and insulinoresistance index HOMA-IR, as well as an improvement of lipid blood spectrum and the lessening of visceral obesity. Besides, a positive effect on arterial pressure was noted. The study revealed no significant adverse effects; good tolerance to treatment was noted in 90% of the patients.


Adding Continuous Vital Sign Information to Static Clinical Data Improves the Prediction of Length of Stay After Intubation: A Data-Driven Machine Learning Approach.
Bedside monitors in the ICU routinely measure and collect patients' physiologic data in real time to continuously assess the health status of patients who are critically ill. With the advent of increased computational power and the ability to store and rapidly process big data sets in recent years, these physiologic data show promise in identifying specific outcomes and/or events during patients' ICU hospitalization. We introduced a methodology designed to automatically extract information from continuous-in-time vital sign data collected from bedside monitors to predict if a patient will experience a prolonged stay (length of stay) on mechanical ventilation, defined as >4 d, in a pediatric ICU. Continuous-in-time vital signs information and clinical history data were retrospectively collected for 284 ICU subjects from their first 24 h on mechanical ventilation from a medical-surgical pediatric ICU at Boston Children's Hospital. Multiple machine learning models were trained on multiple subsets of these subjects to predict the likelihood that each of these subjects would experience a long stay. We evaluated the predictive power of our models strictly on unseen hold-out validation sets of subjects. Our methodology achieved model performance of >83% (area under the curve) by using only vital sign information as input, and performances of 90% (area under the curve) by combining vital sign information with subjects' static clinical data readily available in electronic health records. We implemented this approach on 300 independently trained experiments with different choices of training and hold-out validation sets to ensure the consistency and robustness of our results in our study sample. The predictive power of our approach outperformed recent efforts that used deep learning to predict a similar task. Our proposed workflow may prove useful in the design of scalable approaches for real-time predictive systems in ICU environments, exploiting real-time vital sign information from bedside monitors. (ClinicalTrials.gov registration NCT02184208.).


Differences in low back pain behavior are reflected in the cerebral response to tactile stimulation of the lower back.
Two groups of patients with chronic low back pain (cLBP) were scanned with functional magnetic resonance imaging during stimulation of the lower back; those showing 4 or 5 positive Waddell signs (WS-H) and those showing 1 or none (WS-L) as an index of pain-related illness behavior. We hypothesized that patients showing good versus poor adjustment to cLBP mobilize cortical affective-cognitive functions differently in response to sensory stimulation and show increased reorganization of somatosensory cortex corresponding to the back. Some patients with cLBP go on to develop significant disability while the majority do not, and physical disease or psychosocial factors alone do not account for the difference. Neuroimaging studies have suggested abnormalities in cortical pain modulation systems can lead to variable pain and behavioral responses, which may account for these differences. METHODS.: Fifteen WS-L and 13 WS-H patients were scanned with functional magnetic resonance imaging while receiving intense tactile stimulation to the lower back. Questionnaire measures of psychosocial function were also collected. There were no significant differences in cLBP duration or lumbar stimulation tolerance threshold between the 2 groups. Significantly more activation was seen in the WS-L versus WS-H group in regions previously associated with normal affective-cognitive processing of sensory input including posterior cingulate and parietal cortices; the magnitude of this activation negatively correlated with catastrophizing scores. WS-H patients showed a modest medial shift in primary somatosensory cortex activation relative to the WS-L group. Successful adjustment to cLBP is associated with a patient's ability to effectively engage a sensory modulation system. In patients in whom such activation does not occur, subjective lack of control maypredispose to altered affective and behavioral responses with poor adjustment to pain. Pain experience may be furthermodified by reorganization of somatosensory cortex, contributing to maintenance of the chronic pain state.


Effects of stevioside on glucose transport activity in insulin-sensitive and insulin-resistant rat skeletal muscle.
Stevioside (SVS), a natural sweetener extracted from Stevia rebaudiana, has been used as an antihyperglycemic agent. However, little is known regarding its potential action on skeletal muscle, the major site of glucose disposal. Therefore, the purpose of the present study was to determine the effect of SVS treatment on skeletal muscle glucose transport activity in both insulin-sensitive lean (Fa/-) and insulin-resistant obese (fa/fa) Zucker rats. SVS was administered (500 mg/kg body weight by gavage) 2 hours before an oral glucose tolerance test (OGTT). Whereas the glucose incremental area under the curve (IAUC(glucose)) was not affected by SVS in lean Zucker rats, the insulin incremental area under the curve (IAUC(insulin)) and the glucose-insulin index (product of glucose and insulin IAUCs and inversely related to whole-body insulin sensitivity) were decreased (P<.05) by 42% and 45%, respectively. Interestingly, in the obese Zucker rat, SVS also reduced the IAUC(insulin) by 44%, and significantly decreased the IAUC(glucose) (30%) and the glucose-insulin index (57%). Muscle glucose transport was assessed following in vitro SVS treatment. In lean Zucker rats, basal glucose transport in type I soleus and type IIb epitrochlearis muscles was not altered by 0.01 to 0.1 mmol/L SVS. In contrast, 0.1 mmol/L SVS enhanced insulin-stimulated (2 mU/mL) glucose transport in both epitrochlearis (15%) and soleus (48%). At 0.5 mmol/L or higher, the SVS effect was reversed. Similarly, basal glucose transport in soleus and epitrochlearis muscles in obese Zucker rats was not changed by lower doses of SVS (0.01 to 0.1 mmol/L). However, these lower doses of SVS significantly increased insulin-stimulated glucose transport in both obese epitrochlearis and soleus (15% to 20%). In conclusion, acute oral SVS increased whole-body insulin sensitivity, and low concentrations of SVS (0.01 to 0.1 mmol/L) modestly improved in vitro insulin action on skeletal muscle glucose transport in both lean and obese Zucker rats. These results indicate that one potential site of action of SVS is the skeletal muscle glucose transport system.


Passive NaCl transport in the flounder urinary bladder: predominance of a cellular pathway.
The urinary bladder of the winter flounder is a high-resistance epithelium that can absorb Na and Cl in an electrically silent manner. This active absorption (mucosa-to-serosa) of NaCl is, apparently uniquely, inhibited by mucosal hydrochlorothiazide (HCTZ). These experiments evaluated the notion that virtually all of the cellular Na and Cl permeation could be inhibited by mucosal HCTZ. Mucosal Ba2+ reduced the transepithelial conductance from 0.74 +/- 0.08 to 0.60 +/- 0.06 mS/cm2. Mucosal HCTZ reduced the serosa-to-mucosa flux (backflux) of Na from 0.70 +/- 0.08 to 0.29 +/- 0.03 mueq.cm-2.h-1 and the backflux of Cl from 1.92 +/- 0.22 to 0.38 +/- 0.03 mueq.cm-2.h-1. The treatment with these two agents caused the sum of the partial ionic conductances for Na and Cl to approximate the measured transepithelial conductance. In response to the imposition of a transepithelial voltage, the HCTZ-insensitive Na and Cl backfluxes behaved largely as predicted by the laws of simple ionic diffusion, although there was still a detectable cellular backflux. As judged from dilution voltages and tracer fluxes, the diffusional (paracellular) pathway(s) is nonselective for Na and Cl. The HCTZ-sensitive cellular Na and Cl backfluxes are dependent on the presence of mucosal Na and Cl. Neither backflux is significantly inhibited by serosal application of commonly used inhibitors of Na or Cl transport. The results demonstrate that the majority of passive Na and Cl flux is via a cellular pathway. The translocation across the apical membrane probably involves the same NaCl cotransport process responsible for NaCl absorption.


iPSC modeling of rare pediatric disorders.
Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.


Mapping resting-state brain networks in conscious animals.
In the present study we mapped brain functional connectivity in the conscious rat at the "resting state" based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models.


Comparison of seeding methods for visualization of the corticospinal tracts using single tensor tractography.
To compare five different seeding methods to delineate hand, foot, and lip components of the corticospinal tract (CST) using single tensor tractography. We studied five healthy subjects and 10 brain tumor patients. For each subject, we used five different seeding methods, from (1) cerebral peduncle (CP), (2) posterior limb of the internal capsule (PLIC), (3) white matter subjacent to functional MRI activations (fMRI), (4) whole brain and then selecting the fibers that pass through both fMRI and CP (WBF-CP), and (5) whole brain and then selecting the fibers that pass through both fMRI and PLIC (WBF-PLIC). Two blinded neuroradiologists rated delineations as anatomically successful or unsuccessful tractography. The proportions of successful trials from different methods were compared by Fisher's exact test. To delineate hand motor tract, seeding through fMRI activation areas was more effective than through CP (p<0.01), but not significantly different from PLIC (p>0.1). WBF-CP delineated hand motor tracts in a larger proportion of trials than CP alone (p<0.05). Similarly, WBF-PLIC depicted hand motor tracts in a larger proportion of trials than PLIC alone (p<0.01). Foot motor tracts were delineated in all trials by either PLIC or whole brain seeding (WBF-CP and WBF-PLIC). Seeding from CP or fMRI activation resulted in foot motor tract visualization in 87% of the trials (95% confidence interval: 60-98%). The lip motor tracts were delineated only by WBF-PLIC and in 36% of trials (95% confidence interval: 11-69%). Whole brain seeding and then selecting the tracts that pass through two anatomically relevant ROIs can delineate more plausible hand and lip motor tracts than seeding from a single ROI. Foot motor tracts can be successfully delineated regardless of the seeding method used.


A Men's Workplace Health Intervention: Results of the POWERPLAY Program Pilot Study.
To explore physical activity and eating behaviors among men following the implementation of a gender-sensitive, workplace health promotion program. Using a pre-post within-subjects design, computer-assisted telephone interviewing (CATI) was used to collect health-related information along with physical activity and fruit/vegetable intake at baseline and after 6 months. At baseline, participants (N = 139) consumed 3.58 servings of fruit and vegetables/day and engaged in an average of 229.77 min/week moderate-vigorous physical activity (MVPA). At 6 months, daily fruit/vegetable intake did not increase, whereas MVPA increased by 112.3 min/week. The POWERPLAY program successfully increased weekly MVPA. Engaging men in health promotion can be a challenge; here, the workplace served as a valuable environment for achieving positive change.


Mathematical analysis of applied loads on skeletal muscles during manual therapy.
Because of the lack of accurate values for mechanically applied forces in osteopathic manipulative treatment, osteopathic physicians must apply mechanical forces intuitively. However, excessive loading and high velocity maneuvers carry risks for patients. To determine the loads required to produce compression, shear, extension, and twist on biceps muscle during manual therapy. A mathematical analysis valid for the in vivo state of biceps muscle was performed to determine the loads produced in a simple elastic biceps muscle model and a more realistic viscoelastic biceps muscle model. Loads of 7% lesser pressure were needed to produce 10% deformation of biceps muscle using the viscoelastic model, compared with the elastic model. In the viscoelastic model, there was stress relaxation of 18% of maximum pressure when muscle was deformed by 10% over 60 seconds and maintained in that state for 200 seconds. With quick maneuvers, the viscoelasticity effect was decreased. The biceps muscle is 15 times stiffer in the direction parallel to the muscle fibers than in the direction perpendicular to the fibers. The results of the present study may be used by osteopathic physicians to adjust their manual techniques to match viscoelastic properties of specific tissues. Because biceps muscle is viscoelastic, the results obtained with the viscoelastic model would be more useful than the results obtained with the elastic model for determining viscoelastic loads on this muscle.


Yin Yang 1 controls cerebellar astrocyte maturation.
Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain mature astrocytes in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.


Antitumor effect of positively charged resin in the hamster cheek pouch model.
Following the signal observation that contact with positively charged dextran resin (PCDR) inhibited the growth of cultured mammary (Hs578T and MDA-MB-231), pancreatic (H2T), and myeloma (RR-658) tumor cell lines, studies were developed in the hamster cheek pouch model using hamster H2T pancreatic tumor cells to determine if the antiproliferative effect of PCDR could inhibit tumorigenesis. In these studies, the control population represented groups injected with H2T cells alone or in combination with either neutral or negatively charged resin. When cells (5 x 10(2) to 1 x 10(5)) and PCDR were administered simultaneously, the tumor incidence (percent engraftment) and growth of tumors that already had been established were significantly reduced. When PCDR was injected into already established 1-35-mm2 H2T tumors (engraftment for 21 days = 96%), the resin suppressed the growth of the smallest tumors (< 10 mm2). In none of these trials was the somatic growth of the host hamsters affected. PCDR contact with H2T cells in vitro for 4 days or used to treat growing solid tumors for 72 days significantly reduced cellular ornithine decarboxylase activity. While the mechanism of PCDR action has not been established, the observations have implications for in vivo tumor therapeutic models.


External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle.
To investigate by electromyography (EMG), the presence of complex repetitive discharges (CRDs) and decelerating bursts (DBs) in the striated external urethral sphincter during the menstrual cycle in female volunteers with no urinary symptoms and complete bladder emptying. Healthy female volunteers aged 20-40 years, with regular menstrual cycles and no urinary symptoms were recruited. Volunteers completed a menstruation chart, urinary symptom questionnaires, pregnancy test, urine dipstick, urinary free flow and post-void ultrasound bladder scan. Exclusion criteria included current pregnancy, use of hormonal medication or contraception, body mass index of >35 kg/m(2) , incomplete voiding and a history of pelvic surgery. Eligible participants underwent an external urethral sphincter EMG, using a needle electrode in the early follicular phase and the mid-luteal phase of their menstrual cycles. Serum oestradiol and progesterone were measured at each EMG test. In all, 119 women enquired about the research and following screening, 18 were eligible to enter the study phase. Complete results were obtained in 15 women. In all, 30 EMG tests were undertaken in the 15 asymptomatic women. Sphincter EMG was positive for CRDs and DBs at one or both phases of the menstrual cycle in eight (53%) of the women. Three had CRDs and DBs in both early follicular and mid-luteal phases. Five had normal EMG activity in the early follicular phase and CRDs and DBs in the mid-luteal phase. No woman had abnormal EMG activity in the early follicular phase and normal activity in the luteal phase. There was no relationship between EMG activity and age, parity or serum levels of oestradiol and progesterone. CRDs and DB activity in the external striated urethral sphincter is present in a high proportion of asymptomatic young women. This abnormal EMG activity has been shown for the first time to change during the menstrual cycle in individual women. CRDs and DBs are more commonly found in the luteal phase of the menstrual cycle. The importance of CRDs and DBs in the aetiology of urinary retention in young women remains uncertain. The distribution and or quantity of abnormal EMG activity in the external urethral sphincter may be important. In a woman with urinary retention the finding of CRDs and DBs by needle EMG does not automatically establish Fowler's syndrome as the explanation for the bladder dysfunction. Urethral pressure profilometry may be helpful in establishing a diagnosis. Opiate use and psychological stress should be considered in young women with urinary retention.


Self-reported distress in patients with ovarian cancer: is it related to disease status?
Patients with epithelial ovarian cancer have a poor prognosis and often undergo intensive treatment. These patients are therefore at risk for experiencing distress and reduced quality of life. The aim of this study was to explore the self-reported distress severity, experienced problems, and quality of life in relation to their disease status. This cross-sectional study was conducted in 2011 at a University Medical Center. Women with ovarian cancer (n = 273), both during and after treatment, were asked by mail to fill in self-report questionnaires. Distress was measured using with the Distress Thermometer (DT), Hospital Anxiety and Depression Scale, and Impact of Event Scale. Problems and quality of life were assessed with the problem list of the DT, and European Organization for Research and Treatment of Cancer Quality of Life C-30 and OV28. The questionnaire data of 104 patients were analyzed. Screening with the DT revealed distress in 32% [mean (SD), 3.1 (2.6)]. Distress was found with the Hospital Anxiety and Depression Scale in 14% [8.6 (5.9)] and with the Impact of Event Scale in 18% of the patients [17.5 (15.5)]. No significant differences were found in distress severity and self-reported problems between patients with and without recurrence. In both groups, the problems fatigue, condition, and neuropathy were most reported. Patients with distress (DT ≥ 5) experienced significantly worse functioning, more problems, and lower quality of life than patients without distress (P < 0.01). This study showed that disease status in patients with ovarian cancer seems to have no influence on distress, quality of life, and the problems encountered. However, distressed patients experienced more problems, with physical and emotional functioning, and had lower quality of life. The problems fatigue, physical condition, and neuropathy are the most prevailing.


Fingolimod-Associated Intracerebral Lymphoproliferative Disorder.
Most epidemiological studies indicate that incidence of cancer in multiple sclerosis patients is lower than general population. However these studies were performed prior to the emergence of disease-modifying therapies (DMTs). The incidence of cancer may be influenced by newer generation DMTs which are immunomodulatory or immunosuppressant. We describe an atypical case of intracerebral plasmacytic lymphoproliferative disorder in a 47 years old patient on fingolimod. As worldwide usage of oral and infusion DMTs increases, heightened clinical suspicion and early recognition of these serious adverse events remain crucial.


The relationship among state laws, district policies, and elementary school-based measurement of children's body mass index.
School-based measurement of children's body mass index (BMI) is a useful tool for tracking childhood obesity rates, and may be an effective intervention strategy for reducing the increasing trends in obesity. This article examines the relationship between state law, district policy, and school-level BMI measurement practices. Data were collected during 3 school years (2006-2007, 2007-2008, 2008-2009) as part of an annual study on health policies and practices in a nationally representative sample of US public elementary schools. Data collected included school-level data via a mailed questionnaire, and district-level policies and state laws from publicly available sources. We examined whether state laws and district policies were linked to school-level BMI measurement, either directly, or via a mediation effect. Schools were most likely to measure student BMI if there was a state law in place (65.0% of schools) than where there was not a state law regarding BMI measurement (38.4% of schools; χ(2) = 120.91, p < .001). However, school-level BMI measurement did not differ by whether the district had a relevant policy or not (49.8% vs. 49.2%, ns). These effects held up in multivariate logistic regression models controlling for relevant school-level covariates (region, race/ethnicity, location, school size, and socioeconomic status). Schools in the south and those with a majority of White students were most likely to measure students' BMI. State laws are associated with school-level BMI measurement, and therefore may be a helpful tool in monitoring and addressing childhood obesity.


The long-run benefits of punishment.
Experiments have shown that punishment enhances socially beneficial cooperation but that the costs of punishment outweigh the gains from cooperation. This challenges evolutionary models of altruistic cooperation and punishment, which predict that punishment will be beneficial. We compared 10- and 50-period cooperation experiments. With the longer time horizon, punishment is unambiguously beneficial.


Fuzzy logic for plant-wide control of biological wastewater treatment process including greenhouse gas emissions.
The application of control strategies is increasingly used in wastewater treatment plants with the aim of improving effluent quality and reducing operating costs. Due to concerns about the progressive growth of greenhouse gas emissions (GHG), these are also currently being evaluated in wastewater treatment plants. The present article proposes a fuzzy controller for plant-wide control of the biological wastewater treatment process. Its design is based on 14 inputs and 6 outputs in order to reduce GHG emissions, nutrient concentration in the effluent and operational costs. The article explains and shows the effect of each one of the inputs and outputs of the fuzzy controller, as well as the relationship between them. Benchmark Simulation Model no 2 Gas is used for testing the proposed control strategy. The results of simulation results show that the fuzzy controller is able to reduce GHG emissions while improving, at the same time, the common criteria of effluent quality and operational costs.