Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.
The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity as part of the inpatient workup if time allows, and the potential use of hemodialysis, prohemostatic agents, and reversal agents when available.


Asymptomatic atopy is associated with increased indoleamine 2,3-dioxygenase activity and interleukin-10 production during seasonal allergen exposure.
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan (TRP)-catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen-presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high-affinity receptor for IgE, FcepsilonRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin-10 (IL-10), a cytokine known for its down-regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells. This study was devised to understand the role of systemic IDO and IL-10 in the prevention of clinical apparent allergy. The concentration of TRP and the break-down product kynurenine were measured by high-performance liquid chromatography in- and off-season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non-atopic (NA) individuals (n=12) served as control. The concentration of plasma IL-10 was determined in parallel from these donors by ELISA in- and off-season. In clinically unresponsive but aeroallergen-sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL-10 levels were found during allergen exposure but not off-season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals. Enhanced systemic IDO activity as well as increased systemic levels of IL-10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.


Polymer-nanoparticle complexes: from dilute solution to solid state.
We report on the formation and the structural properties of "supermicellar" aggregates made from mineral nanoparticles and polyelectrolyte-neutral block copolymers in aqueous solutions. The mineral particles put under scrutiny are ultrafine and positively charged yttrium hydroxyacetate nanoparticles. Combining light, neutron, and X-ray scattering experiments, we have characterized the sizes and the aggregation numbers of the organic-inorganic complexes. We have found that the hybrid aggregates have typical sizes in the range of 100 nm and exhibit a remarkable colloidal stability with respect to ionic strength and concentration variations. Solid films with thicknesses up to several hundreds of micrometers were cast from solutions, resulting in a bulk polymer matrix in which nanoparticle clusters are dispersed and immobilized. It was found in addition that the structure of the complexes remains practically unchanged during film casting.


Scaling skin disorders.
Scaling skin disorders have similar features. Careful inspection to determine the characteristics of the primary lesion, along with distribution patterns and performance of routine diagnostic tests, usually lead to a correct diagnosis. Potassium hydroxide examination should be performed on most scaling skin disorders. If a microscope is not readily available, skin scrapings should be sent to a microbiology laboratory, or a microscope should be purchased and training obtained. A binocular microscope is preferable to view fungal hyphae. KOH examination requires supervised experience to become proficient.


Preparing Nurses for Genetic Medicine: Integration of a Brief Education Session in an Undergraduate Nursing Curriculum.
Few studies have focused on the genetic competencies of undergraduate nursing students. The aims of this study include measuring undergraduate nursing students' knowledge, perceived comfort, and attitude toward genetics, and gauging the effectiveness of a brief genetics education session. Undergraduate nursing students (N = 32) were recruited to participate in a survey. A subset (n = 6) then participated in a 1-hour review of basic genetic concepts and activities, with applications to clinical scenarios. Both groups repeated the survey and their results were compared. Students attending the education session had higher knowledge scores than the control group and reported higher levels of comfort with genetics-related tasks. No differences in student attitudes exist. This pilot study suggests that a brief but focused education session can increase the level of genetics knowledge and comfort in undergraduate nursing students. [J Nurs Educ. 2017;56(3):170-173.].


Assessment of somatosensory changes in Chinese temporomandibular disorders arthralgia patients by quantitative sensory testing.
Somatosensory changes in Chinese temporomandibular disorders (TMD) arthralgia patients have not been fully studied by the latest technologies. This study aims at assessing somatosensory changes in Chinese TMD arthralgia patients quantitatively. Standardised quantitative sensory testing (QST) was performed on the pain sites and contralateral sites of 40 patients diagnosed with TMD arthralgia according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) before and after medication; similar measures were taken in 40 age- and gender-matched healthy controls. Differences within and between groups were assessed through Z-scores, two-way ANOVA and loss/gain coding system. The pain sites of patients presented increased sensitivity to thermal stimuli and mechanical pain stimuli together with decreased sensitivity to mechanical tactile stimuli before medication (P < .001). Before treatment, 100% of patients had somatosensory abnormalities at the pain sites; the most frequent abnormalities were somatosensory gain to cold nociceptive, pinprick and pressure stimuli, and the most frequent loss/gain score was L0G3 (no somatosensory loss with a gain of thermal and mechanical somatosensory function; 70.0%). After treatment, although the clinical symptoms and signs of 40 patients disappeared, 80.0% of the patients' pain sites still showed multiple phenotype abnormalities. The most frequent loss/gain score was L0G2 (no somatosensory loss with a gain of mechanical somatosensory function; 35.0%). Multiple phenotypes of facial somatosensory abnormalities were detected in Chinese TMD arthralgia patients before and after treatment, despite the disappearance of clinical signs and symptoms. Individual variations indicate a possible need for subgroup classification, individualised management and mechanism-based treatment.


Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia.
Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations.


Drosophila centrosomin protein is required for male meiosis and assembly of the flagellar axoneme.
Centrosomes and microtubules play crucial roles during cell division and differentiation. Spermatogenesis is a useful system for studying centrosomal function since it involves both mitosis and meiosis, and also transformation of the centriole into the sperm basal body. Centrosomin is a protein localized to the mitotic centrosomes in Drosophila melanogaster. We have found a novel isoform of centrosomin expressed during spermatogenesis. Additionally, an anticentrosomin antibody labels both the mitotic and meiotic centrosomes as well as the basal body. Mutational analysis shows that centrosomin is required for spindle organization during meiosis and for organization of the sperm axoneme. These results suggest that centrosomin is a necessary component of the meiotic centrosomes and the spermatid basal body.


Estimation of stroke severity with National Institutes of Health Stroke Scale grading and retinal features: A cross-sectional study.
To estimate National Institutes of Health Stroke Scale (NIHSS) grading of stroke patients with retinal characteristics.A cross-sectional study was conducted in Shenzhen Traditional Chinese Medicine Hospital. Baseline information and retinal photos were collected within 2 weeks of admission. An NIHSS score was measured for each patient by trained doctors. Patients were classified into 0 to 4 score group and 5 to 42 score group for analysis. Three multivariate logistic models, with traditional clinical characteristics alone, with retinal characteristics alone, and with both, were built.For clinical characteristics, hypertension duration is statistically significantly associated with higher NIHSS score (P = .014). Elevated total homocysteine levels had an OR of 0.456 (P = .029). For retinal characteristics, the fractal dimension of the arteriolar network had an OR of 0.245 (P < .001) for the left eyes, and an OR of 0.417 (P = .009) for right eyes. The bifurcation coefficient of the arteriole of the left eyes had an OR of 2.931 (95% CI 1.573-5.46, P = .001), the nipping of the right eyes had an OR of 0.092 (P = .003) showed statistical significance in the model.The area under receiver-operating characteristic curve increased from 0.673, based on the model with clinical characteristics alone, to 0.896 for the model with retinal characteristics alone and increased to 0.931 for the model with both clinical and retinal characteristics combined.Retinal characteristics provided more information than clinical characteristics in estimating NIHSS grading and can provide us with an objective method for stroke severity estimation.


Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.


The prognostic value of blood glucose in patients with acute stroke.
We prospectively studied levels of blood glucose and glycohemoglobin, and their correlations with types, severity, and prognosis of stroke in 37 patients with brain infarction (BI) and 35 patients with brain hemorrhage (BH). We found that in the BH group, patients with an elevated glucose level due to stress, diabetes, or both, had a lower consciousness level on admission, larger hematoma size, higher incidence of rupture into the ventricles, and a worse 1-month outcome than patients with a normal glucose level (p less than 0.05). In patients with BI, however, no significant difference was found as related to levels of glucose, though a difference in 6-month mortality between stress hyperglycemic and normoglycemic patients (p less than 0.05) was found. We conclude that an elevated glucose level is associated with a worse clinical condition, larger hematoma size, higher incidence of rupture into the ventricles, and worse outcome in patients with BH. However, it seems to be the severity of the stroke, not the hyperglycemia, that causes the poor outcome. Hyperglycemia may be an epiphenomenon of stroke severity.


A multicentre survey of antimicrobial resistance in gram-negative isolates from Belgian intensive care units in 1994-1995. Belgian Multicenter ICU Study Group.
The aim of this prospective study was to evaluate the distribution and antibiotic susceptibility of aerobic Gram-negative bacilli isolated from patients in intensive care units in 18 Belgian hospitals during 1994 and 1995. A standardised method (i.e. the E-test) was used in each center to determine the minimum inhibitory concentrations of 12 major antibiotics against 1435 consecutive, non duplicate, Gram-negative isolates (close to 100 strains per hospital) during a period of 6 months. The isolates were mainly isolated from the lower respiratory tract (57.4%), urinary tract (17.7%), pus (7.9%) or blood specimens (7.8%) and were mainly P.aeruginosa (20.3%), E.coli (19.9%) and Enterobacter spp. (12.6%). Overall inducible Enterobacteriaceae (IE) accounted for 29.8% of all isolates, and E.aerogenes was the most frequently isolated species in this group (27.6%). The overall susceptibility rate (all species confounded) was about 70% to piperacillin, ticarcillin-clavulanic acid and ceftriaxone, 78% to piperacillin-tazobactam; 87% both to ceftazidime and to ciprofloxacin; and 90% to imipenem. Widespread resistance was observed in several IE species to third generation cephalosporins, broad-spectrum penicillins and to ciprofloxacin. By contrast, imipenem and the aminoglycosides still retained excellent activity against most multiresistant species. Although there were wide differences between hospitals in the frequencies of resistance to most antibiotics, these were not related to the types (general vs. university) of hospitals or to the number of beds. Some variations were however observed in the distribution of bacterial species: the prevalence of inducible Enterobacteriaceae was significantly higher in university than in general hospitals and in hospitals located in Brussels and in Wallonia than in the Flanders. Overall few trends in resistance rates were observed in comparison to a similar survey performed in 1991.


Effect of non-nicotinic moist snuff replacement and lobeline on withdrawal symptoms during 48-h smokeless tobacco deprivation.
The present study investigated the effects of two herbal components (BACCOFF and DIPSTOP) of a commercially available smokeless tobacco treatment program for reducing subjective withdrawal symptoms during deprivation. One component, BACCOFF, is a non-nicotinic chew. The second component, DIPSTOP, is a liquid containing the alkaloid lobeline, which to some extent mimics peripheral nicotinic effects. All participants (N = 22 males) were placed in four conditions: BACCOFF + DIPSTOP, BACCOFF + placebo control, DIPSTOP, and placebo control only. The conditions involved 48 h of deprivation, and subjects were exposed to one condition per week for 4 weeks. Withdrawal measures were taken at baseline, 24 h, and 48 h of deprivation. Individuals were randomly assigned, and conditions were counterbalanced. Results showed that BACCOFF, as compared with DIPSTOP, significantly reduced withdrawal symptoms but not craving. These data suggest that behavioral/sensory substitutes' influence on withdrawal might be routed through the product's ability to approximate the preferred moist snuff.


Comparison of Educational and Academic Quality of Laparoscopic Distal Pancreatectomy Videos on WebSurg® and YouTube® Platforms.
The aim of this study was to compare the educational and academic quality of laparoscopic distal pancreatectomy (LDP) videos on YouTube® and WebSurg® platforms. YouTube and WebSurg platforms were searched with the keyword "laparoscopic distal pancreatectomy". According to the exclusion criteria, 12 videos were found on WebSurg. To ensure a 1:1 ratio, the first 12 videos that met the criteria on YouTube were also analyzed. Journal of American Medical Association (JAMA) benchmark criteria were used to evaluate the reliability of the videos. The non-educational quality of the videos was calculated using the Global Quality Score (GQS), the educational and academic quality of videos was calculated using Laparoscopic Distal Pancreatectomy-specific score (LDP-SS) and Laparoscopic Surgery Video Educational Guidelines scoring system (LAP-VEGaS). The mean JAMA score was 1.58 on YouTube and 2.83 on WebSurg (P < .001). The median GQS was 2 on YouTube and 5 on WebSurg (P < .001). The median LAP-VEGaS score was 8 on YouTube and 14.5 on WebSurg (P < .001). The median LDP-SS score was 6 on YouTube and 9.5 on WebSurg (P = .001). According to the LAP-VEGaS, eleven (91.7%) of the WebSurg videos had a high score of 11 or more (P = .04). According to Spearman correlation analysis, there was a statistically significant positive correlation between LDP-SS and JAMA, GQS and LAP-VEGaS (r: .589, P = .002; r: .648, P = .001; r: .848, P < .001 respectively). The WebSurg is superior to the YouTube in terms of educational and academic value, quality, accuracy, reliability and usability in scientific meetings for LDP videos.


Investigation of the lipids of saprophytic mycobacteria in the U.S.S.R.
Three trends in the investigations of the specific lipids of rhodococci and related microorganisms are reflected: isolation and structural determination of new complex lipids, elucidation of the role of specific lipids in the cells and application of lipid composition for diagnostic studies of rhodococci and related organisms. Two groups of peptidolipids, differing in chromatographic mobility and peptide chain structure, have been found in the cells of Rhodococcus erythropolis. The compounds within each group differ in acyl moieties. Three peptidolipids of the polar group include glucose, so they are peptidoglycolipids. Glycolipids are represented by trehalose derivates. Trehalose dimycolate (cord factor) is dominant. Data concerning the role of lipids in typical features of rhodococci as the lipophilic cell wall, the ability to up-take a hydrophobic substrate and the resistance to influences from outside are given. Examples of application of mycolic acid composition in taxonomy of rhodococci and morphologically similar bacteria are given.


Radiation therapy palliation in malignancy-associated ureteral obstruction.
Between 1981 and 1985, 20 patients with malignancy-associated ureteral obstruction (MAUO) were given external beam irradiation with a palliative intent. In the majority of cases, MAUO was due to carcinoma of the cervix or prostate gland. Complete symptomatic relief occurred in 91% and measurable (neoplasm or its manifestation) improvement was seen in 23% of the evaluable patients. Significant alleviation of ureteral blockage was noted in about a third of cases. The overall median period of survival was 7.5 months.


Preoperative matching studies in the diagnosis of parathyroid adenoma for primary hyperparathyroidism: Can we avoid intraoperative PTH monitoring?
We aim to determine the utility of intraoperative parathyroid hormone (IOPTH) monitoring in patients with matching preoperative ultrasound and mibi SPECT for primary hyperparathyroidism for a single adenoma. All patients who underwent minimally invasive parathyroidectomy (MIP) for pseudohypoparathyroidism (PHP) for a single parathyroid adenoma, were included. An Ultrasound and mibi SPECT were performed in all patients. We defined matching studies when both coincided in the localization of the adenoma. IOPTH was performed in all patients and analyzed in three occasions: a baseline measurement at the anesthetic induction, immediately before, and 15 min after gland excision. Success was defined during the third measurement as a drop of IOPTH of at least 50% compared to the previous maximum value after gland excision. Demographics, intraoperative, postoperative variables and the utility of IOPTH monitoring were analyzed. A total of 218 MIP were performed. The average age was 60.1 years and 85% were female. Preoperative ultrasound and mibi SPECT coincided 100%. When the adenoma was localized, 15 min after its excision, IOPTH did not decrease in 9 patients (4.2%. OR 1.9%-7.69%); all of them underwent a bilateral neck exploration. The added-value of IOPTH accuracy for disease cure was 3.6%. There was a 99% of cure rate. The mean surgical time was 66.4 min and the waiting time for the third IOPTH result was 31 min. Performing IOPTH monitoring made the surgery about twice more expensive. Preoperative matching ultrasound and mibi SPECT for parathyroid adenoma localization in PHP, could avoid IOPTH monitoring in minimally invasive parathyroidectomies.


Pore-forming and haemolytic properties of the Gardnerella vaginalis cytolysin.
The pleomorphic bacterium Gardnerella vaginalis releases in the culture broth a haemolytic exotoxin (Gvh) which is probably a virulence determinant of this unique bacterium, implicated in gynaecological and urological disorders. This 59 kDa cytolysin was purified to homogeneity in just one chromatographic step directly from the culture supernatant, a final specific activity up to 1.9 x 10(6) HU mg-1 being obtained. The toxin-induced lesion on human erythrocytes results from the formation of a pore whose radius is approximately 2.4 nm. The damage is inhibited by osmotic protectants and shows a sigmoidal dose-response profile suggesting an aggregation process of haemolysin molecules on the target membrane to create the functional lesion. The extent and the kinetics of haemolysis are strongly dependent on temperature and an activation energy of 64.0 kJ mol-1 has been derived. Lipid membranes can be very efficient inhibitors of Gvh-haemolysis, being able to bind the toxin quite avidly. The inhibitory effect requires the presence of cholesterol and it is stronger when cholesterol is mixed with negatively charged phospholipids rather than with zwitterionic phospholipids, suggesting that a negative surface potential increases the affinity of the toxin for the lipid bilayer. The functional properties of Gvh have been compared with those of Clostridium perfringens thetatoxin (PFO) and Escherichia coli haemolysin (HlyA), which are representative of widespread haemolysins produced by Gram-positive and Gram-negative bacteria, respectively. The toxin shares several features with the family of the so-called 'sulphydryl-activated' cytolysins produced by Gram-positive bacteria, although Gvh does not truly belong to this family, being deactivated by beta-mercaptoethanol and being antigenically distinct from them. We report here for the first time the detection in the vaginal fluid of infected women of a specific IgA response against the toxin.


Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector.
Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death. FA is manifested clinically by progressive pancytopenia, variable physical anomalies, and predisposition to malignancy. Four complementation groups have been identified, termed A, B, C, and D. The gene for the FA complementation group C, FACC, has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA(C) cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells, suggesting that FA might be an ideal candidate for gene therapy. We demonstrated efficient transduction, expression, and phenotypic correction in lymphoblastoid cell lines derived from FA (C) patients using a recombinant adeno-associated virus (rAAV) vector containing the FACC gene. Molecular characterization of the transduced FACC gene showed an intact unrearranged proviral genome with expression sufficient to normalize cell growth, cell cycle kinetics and chromosomal breakage in the presence of MMC. These observations were extended by testing rAAV transduction in hematopoietic progenitor cells. Peripheral blood CD34+ cells isolated from a FA (C) patient and transduced with rAAV/FACC virus yielded 5-10-fold more progenitor colonies than mock-infected cells, consistent with genetic "rescue" of corrected cells. This is the first demonstration of rAAV gene correction in primary human hematopoietic progenitor cells and has important implications for gene therapy of hematopoietic disorders, specifically FA.


Phase I/II study with GM-CSF in patients with myelodysplastic syndromes.
The availability of rh GM-CSF has allowed the in vivo treatment of patients with cytopenia. Therefore a phase I/II trial was initiated to study the effect of rh GM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy. rh GM-CSF has been tested in 10 patients in doses from 15 micrograms/m2 to 150 micrograms/m2 given intravenously over 8 hours for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose dependent increase in leukocyte count was observed in 9 out of 10 patients. No change in reticulocyte numbers was seen and only one patient experienced an increase in platelet count. Toxicity mainly consisted of mild local phlebitis at the site of infusion and sternal pain after bolus injection. An increase in blast cell counts in some patients necessitated the start of low dose Ara-C therapy.


Tulobuterol patch alleviates allergic asthmic inflammation by blockade of Syk and NF-κB activation in mice.
Tulobuterol patch, one of strongest bronchodilators, was recently shown to improve bronchial hyperresponsiveness and significantly decrease the sputum eosinophil counts by combining with nonspecific anti-inflammatory drugs on patients with asthma. However, there is limited study on the anti-inflammatory activities of tulobuterol patch and its potential machenism. The tulobuterol patch significantly ameliorated inflammatory cell infiltration in the lung tissue, reduced the number of total leukocytes and its differential count, markedly reduced the production of IL-1β, TNF-α, IL-6, CCL-11 and IL-4 in bronchial alveolar lavage fluid, as well as a reduction in IL-4/IFN-γ ratio. Tulobuterol patch exhibited the best effect on allergic inflammation compared with formoterol and salbutamol. Furthermore, tulobuterol patch treatment significantly suppressed the expression and activation of Syk and its downdream signaling NF-κB and p-NF-κB. The present studies revealed that tulobuterol patch effectively ameliorated airway inflammatory responses in allergic asthma, and its mechanisms, at least partially, via down-regulating Syk/NF-κB pathway. An ovalbumin induced allergic asthma mouse model were used, and the effects of tulobuterol patch on allergic airway inflammation were evaluated. Also, its anti-airway inflammatory potential was compared with two other β2-agonists, salbutamol and formoterol. Its possible anti-inflammatory mechanisms were identified by using western blotting and immunohistochemistry.


Complementary and alternative drug therapy in arthritis.
Utilization of complementary and alternative medicine (CAM) is universal phenomenon. They are used commonly in chronic diseases like arthritis. To understand the pattern of utilization we undertook this study focussing mainly on the systems, where drug is administered orally. One hundred and fourteen patients suffering from rheumatoid arthritis (RA), satisfying American College of Rheumatology (ACR) criteria were interviewed for the modalities of therapy and drugs used. We analysed prescriptions of both conventional and CAM practitioners. Direct questionnaires regarding CAM were avoided. Fourty three percent (46/114) had used CAM drugs and 50% of them had used more than two modalities. Ayurveda followed by homeopathy were the two common CAM utilized by the patients. Majority believed conventional medicine has no cure for RA and adverse reactions were rare in CAM. These factors predominantly influenced their decision to use CAM. Family income, urban and rural living did not influence usage of CAM. The use of CAM increased as the duration of disease increased. Majority of the patients utilize CAM drugs, for treatment of arthritis. Their knowledge is essential to avoid drug interactions, recognise their reactions and also appreciate their risks and benefits. A scientific scrutiny to these practices and absolving them if beneficial is needed.


Oxidative Stress-Derived Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: A Concise Review.
Chronic obstructive pulmonary disease (COPD) is a progressive and disabling disorder marked by airflow limitation and extensive destruction of lung parenchyma. Cigarette smoke is the major risk factor for COPD development and has been associated with increased oxidant burden on multiple cell types in the lungs. Elevated levels of reactive oxygen species (ROS) may significantly affect expression of biological molecules, signaling pathways, and function of antioxidant defenses. Although inflammatory cells, such as neutrophils and macrophages, contribute to the release of large quantities of ROS, mitochondrial dysfunction plays a critical role in ROS production due to oxidative phosphorylation. Although mitochondria are dynamic organelles, excess oxidative stress is able to alter mitochondrial function, morphology, and RNA and protein content. Indeed, mitochondria may change their shape by undergoing fusion (regulated by mitofusin 1, mitofusin 2, and optic atrophy 1 proteins) and fission (regulated by dynamin-related protein 1), which are essential processes to maintain a healthy and functional mitochondrial network. Cigarette smoke can induce mitochondrial hyperfusion, thus reducing mitochondrial quality control and cellular stress resistance. Furthermore, diminished levels of enzymes involved in the mitophagy process, such as Parkin (a ubiquitin ligase E3) and the PTEN-induced putative kinase 1 (PINK1), are commonly observed in COPD and correlate directly with faulty removal of dysfunctional mitochondria and consequent cell senescence in this disorder. In this review, we highlight the main mechanisms for the regulation of mitochondrial quality and how they are affected by oxidative stress during COPD development and progression.


Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy.
Hypothyroidism is relatively common, occurring in approximately 5% of the general US population aged ≥12 years. Levothyroxine (LT4) monotherapy is the standard of care. Approximately, 5%-10% of patients who normalise thyroid-stimulating hormone levels with LT4 monotherapy may have persistent symptoms that patients and clinicians may attribute to hypothyroidism. A long-standing debate in the literature is whether addition of levotriiodothyronine (LT3) to LT4 will ameliorate lingering symptoms. Here, we explore the evidence for and against LT4/LT3 combination therapy as the optimal approach to treat euthyroid patients with persistent complaints. Recent literature indexed on PubMed was searched in March 2017 using the terms "hypothyroid" or "hypothyroidism" and "triiodothyronine combination" or "T3 combination." Relevant non-review articles published in English during the past 10 years were included and supplemented with articles already known to the authors. Current clinical evidence is not sufficiently strong to support LT4/LT3 combination therapy in patients with hypothyroidism. Polymorphisms in deiodinase genes that encode the enzymes that convert T4 to T3 in the periphery may provide potential mechanisms underlying unsatisfactory treatment results with LT4 monotherapy. However, results of studies on the effect of LT4/LT3 therapy on clinical symptoms and thyroid-responsive genes have thus far not been conclusive. Persistent symptoms in patients who are biochemically euthyroid with LT4 monotherapy may be caused by several other conditions unrelated to thyroid function, and their cause should be aggressively investigated by the clinician.


Cost-effectiveness of combination therapy of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone for previously untreated diffuse large B-cell lymphoma in Japan.
The POLARIX trial showed that Pola + R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) prolongs progression-free survival (PFS) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), the conventional standard of care, with a similar safety profile. However, Pola + R-CHP has not been evaluated from the viewpoint of health economics in Japan. This study evaluates the cost-effectiveness of Pola + R-CHP for previously untreated DLBCL from a Japanese public healthcare payer's perspective. A partitioned survival analysis model was constructed to estimate lifetime costs and effectiveness of Pola + R-CHP and R-CHOP in previously untreated DLBCL who had an International Prognostic Index score (IPI) score of ≥2. A parametric survival model was applied to data analyzed in the POLARIX trial to estimate the lifetime overall survival (OS) and PFS for each treatment. The parameters required for the model were based on the results of a literature search and expert opinion. The incremental cost-effectiveness ratio (ICER) of Pola + R-CHP vs. R-CHOP was JPY2,710,238 per quality-adjusted life year (QALY), less than the ICER of JPY7.5 million per QALY that is considered to be cost-effective based on the threshold of the Japanese cost-effectiveness evaluation system. One-way sensitivity analysis showed that the parameters influencing the results of the analysis were median PFS and the total cost per regimen of salvage chemotherapy, patient weight, and patient age. Probabilistic sensitivity analysis showed that the probability of Pola + R-CHP having superior cost-effectiveness was 99.2% when the reference value was JPY7.5 million. The results of scenario analysis suggested that prolongation of PFS was an important factor in the evaluation of cost-effectiveness in previously untreated DLBCL with or without prolongation of OS. This study suggests that Pola + R-CHP is a cost-effective treatment for previously untreated DLBCL in Japan under the public health insurance system.


On the failure load and mechanism of polycrystalline graphene by nanoindentation.
Nanoindentation has been recently used to measure the mechanical properties of polycrystalline graphene. However, the measured failure loads are found to be scattered widely and vary from lab to lab. We perform molecular dynamics simulations of nanoindentation on polycrystalline graphene at different sites including grain center, grain boundary (GB), GB triple junction, and holes. Depending on the relative position between the indenter tip and defects, significant scattering in failure load is observed. This scattering is found to arise from a combination of the non-uniform stress state, varied and weakened strengths of different defects, and the relative location between the indenter tip and the defects in polycrystalline graphene. Consequently, the failure behavior of polycrystalline graphene by nanoindentation is critically dependent on the indentation site, and is thus distinct from uniaxial tensile loading. Our work highlights the importance of the interaction between the indentation tip and defects, and the need to explicitly consider the defect characteristics at and near the indentation site in polycrystalline graphene during nanoindentation.


Changes in physical activity and body composition in postmenopausal women over time.
Higher physical activity (PA) has been associated with greater attenuation of body fat gain and preservation of lean mass across the lifespan. These analyses aimed to determine relationships of change in PA to changes in fat and lean body mass in a longitudinal prospective study of postmenopausal women. Among 11,491 women enrolled at three Women's Health Initiative clinical centers who were selected to undergo dual-energy x-ray absorptiometry, 8352 had baseline body composition measurements, with at least one repeated measure at years 1, 3, and 6. PA data were obtained by self-report at baseline and 3 and 6 yr of follow-up. Time-varying PA effect on change in lean and fat mass during the 6-yr study period for age groups (50-59 yr, 60-69 yr, and 70-79 yr) was estimated using mixed effects linear regression. Baseline PA and body composition differed significantly among the three age groups. The association of change in fat mass from baseline and time-varying PA differed across the three age groups (P = 0.0006). In women age 50-59 yr, gain in fat mass from baseline was attenuated with higher levels of PA. Women age 70-79 yr lost fat mass at all PA levels. In contrast, change in lean mass from baseline and time-varying PA did not differ by age group (P = 0.1935). The association between PA and change in fat mass varies by age group, with younger, but not older, women benefiting from higher levels of aerobic PA. Higher levels of aerobic activity are not associated with changes in lean mass, which tends to decrease in older women regardless of activity level. Greater attention to resistance training exercises may be needed to prevent lean mass loss as women age.


The Effect of Focus and Phrase Position on East Norwegian Lexical Tonal Accents.
Two experiments examined the acoustic correlates of the disyllabic tonal accent contrast in the Trøndersk dialect of Norwegian, and how narrow focus and phrasal position shape the contrast. Production results showed that both tonal accents have a high-low (HL) pitch contour, with different timing. In narrow focus, the pitch contrast was enlarged through asymmetrical F0 changes. When at the right edge of an accent phrase (AP), the accents were shown to have a higher L, lower AP H% tone, shorter stressed vowel, and longer final vowel. The alignment changes reflected tonal crowding while segmental modifications were due to the phrase-final lengthening in AP-final position. This work contributes to the literature on prosodic typology as well as on the implementation of prosodic focus and sentence intonation in languages with lexical pitch contrasts.


Punishing Atrocity Crimes in Transitional Contexts: Advancing Discussions on Adequacy of Alternative Criminal Sanctions Using the Case of Colombia.
Criminal trials and proportional prison sentences are generally seen as the most suitable way to deal with perpetrators of atrocity crimes. Notwithstanding, traditionally conceived criminal penalties, such as imprisonment, may discourage active responsibility-taking by offenders, disaffect victims by not meeting their needs and impede meaningful engagement between perpetrators and survivors. Arguably, alternative criminal sanctions may be appropriate punishment even for atrocity crimes when tried in transitional societies. Using the case of Colombia, this article analyses the justifications of punishment for atrocities in transitional contexts and discusses the adequacy of alternative criminal sanctions as penalties for atrocity crimes. It concludes that under certain conditions, alternative sanctions can be a viable punishment option that may promote active responsibility-taking and contribute to repairing harm, reintegrating offenders into the community and (re)constructing relationships while serving expressive rationales.


Microfluidic Imaging Flow Cytometry by Asymmetric-detection Time-stretch Optical Microscopy (ATOM).
Scaling the number of measurable parameters, which allows for multidimensional data analysis and thus higher-confidence statistical results, has been the main trend in the advanced development of flow cytometry. Notably, adding high-resolution imaging capabilities allows for the complex morphological analysis of cellular/sub-cellular structures. This is not possible with standard flow cytometers. However, it is valuable for advancing our knowledge of cellular functions and can benefit life science research, clinical diagnostics, and environmental monitoring. Incorporating imaging capabilities into flow cytometry compromises the assay throughput, primarily due to the limitations on speed and sensitivity in the camera technologies. To overcome this speed or throughput challenge facing imaging flow cytometry while preserving the image quality, asymmetric-detection time-stretch optical microscopy (ATOM) has been demonstrated to enable high-contrast, single-cell imaging with sub-cellular resolution, at an imaging throughput as high as 100,000 cells/s. Based on the imaging concept of conventional time-stretch imaging, which relies on all-optical image encoding and retrieval through the use of ultrafast broadband laser pulses, ATOM further advances imaging performance by enhancing the image contrast of unlabeled/unstained cells. This is achieved by accessing the phase-gradient information of the cells, which is spectrally encoded into single-shot broadband pulses. Hence, ATOM is particularly advantageous in high-throughput measurements of single-cell morphology and texture - information indicative of cell types, states, and even functions. Ultimately, this could become a powerful imaging flow cytometry platform for the biophysical phenotyping of cells, complementing the current state-of-the-art biochemical-marker-based cellular assay. This work describes a protocol to establish the key modules of an ATOM system (from optical frontend to data processing and visualization backend), as well as the workflow of imaging flow cytometry based on ATOM, using human cells and micro-algae as the examples.


Effective management of microbial contamination in cultured skin substitutes after grafting to athymic mice.
Cultured skin substitutes have become therapeutic alternatives for treatment of acute and chronic skin wounds, but all models of these substitutes are avascular and susceptible to microbial destruction during vascularization. To develop a practical management protocol for increased survival of skin substitutes, experimental wounds were contaminated with Pseudomonas aeruginosa and treated with a formulation of noncytotoxic antimicrobial agents (polymyxin B, neomycin, ciprofloxacin, mupirocin, amphotericin B) in a nutrient medium (vehicle). Cultured skin substitutes consisting of human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan sponges were grafted to 2 x 2 cm full-thickness wounds on athymic mice that were contaminated with the strain SBI-N of P. aeruginosa at 1 x 10(4), 1 x 10(5), and 1 x 10(6) organisms/wound. Experimental wounds were irrigated with 1 ml/day topical antimicrobial solution for 10 days, and controls received vehicle only. Two, three, and four weeks after grafting, wounds were traced and swabbed for microbial culture and areas were measured with planimetry. At 4 weeks, biopsy samples were scored histochemically for immunoreactivity to HLA antigens. Data analysis by chi-square, analysis of variance, and Tukey's test shows that treatment of contaminated wounds with noncytotoxic topical antimicrobials is associated with an increased area of healed wounds, positive detection of HLA antigens, and negative cultures for P. aeruginosa. These results show that microbial contamination of cultured skin substitutes on full-thickness wounds may be managed effectively during graft vascularization. However, this formulation of antimicrobial agents is not currently approved for human use and is investigational only. Effective management of microbial contamination suggests that clinical efficacy of avascular tissue analogs may be increased by local application of noncytotoxic antimicrobial agents.


Highly Sensitive and Quality Self-Testable Electrochemiluminescence Assay of DNA Methyltransferase Activity Using Multifunctional Sandwich-Assembled Carbon Nitride Nanosheets.
DNA methylation catalyzed by methylase plays a key role in many biological activities. However, developing a highly sensitive, simple, and reliable way for evaluation of DNA methyltransferase (MTase) activity is still a challenge. Here, we report a sandwich-assembled electrochemiluminescence (ECL) biosensor using multifunctional carbon nitride nanosheets (CNNS) to evaluate the Dam MTase activity. The CNNS could not only be used as an excellent substrate to conjugate a large amount of hairpin probe DNA to improve the sensitivity but also be utilized as an internal reliability checker and an analyte reporter in the bottom and top layers of the biosensor, respectively. Such a unique sandwich configuration of CNNS well coupled the advantages of ECL luminophor that were generally assembled in the bottom or top layer in a conventional manner. As a result, the biosensor exhibited an ultralow detection limit down to 0.043 U/mL and a linear range between 0.05 and 80 U/mL, superior to the MTase activity assay in most previous reports. We highlighted the great potential of emerging CNNS luminophor in developing highly sensitive and smart quality self-testable ECL sensing systems using a sandwiched configuration for early disease diagnosis, treatment, and management.


Co-stimulation with LFA-1 triggers apoptosis in gamma delta T cells on T cell receptor engagement.
Stimulation of T cells through the T cell receptor (TcR) initiate activation pathways, and paradoxically can also result in activation-induced cell death. Many factors influence a stimulated cell's decision to manifest one or the other. Here we show that co-stimulation with LFA-1 plays a key role in the choice between the two fates, differentiating between alpha beta and gamma delta T cells. Peripheral gamma delta. T cells but not alpha beta T cells undergo apoptosis upon co-cross-linking of TcR and LFA-1 in MRL lpr/lpr mice as well as +/+ mice. Our results suggest that apoptosis of gamma delta T cells is inducible by combined stimuli independent of the Fas-mediated pathway.


A suggested method of preparation of the large bowel for investigation and surgery.
A safe, effective method of large-bowel preparation is outlined, the emphasis being on a standardized technique for the average patient. The rationale for the use of the technique is briefly described, and there is a further section on the preparation of the bowel in a patient with a colostomy. The importance of a residue-free fluid diet and adequate saline purgation is stressed.


Stress Intensity and Exhaustion Among Infant and Toddler Teachers: Descriptive Analysis and Associations with Sources of Stress and Coping Strategy Use.
This study described infant/toddler teachers' (N = 106) perceptions of stress intensity and exhaustion (emotional, physical, mental) intensity. We examined the associations between stress and exhaustion and teachers' reports of stress sources and coping strategy use. Using ecological momentary assessment (EMA), teachers from Early Head Start (EHS), EHS childcare-partnerships, or independent childcare programs (midwestern U.S.) completed twice-weekly reports of: stress and exhaustion intensity; stress sources (workload, children's behaviors, personal life); and, coping strategies (support from colleagues, distraction, mindfulness techniques, reframing). Stress and exhaustion reports were similar to studies of preschool teachers. Workload and personal life stressors were associated with stress and all exhaustion types. Teachers used fewer than two different coping strategies/per reporting day. Only reframing was negatively associated with stress and emotional exhaustion. Teachers reported greater stress at end-of-week than beginning-of-week. Older teachers reported greater stress and emotional exhaustion. Although one-third of teachers reported ≥4 ACEs, early adversity was not associated with stress or exhaustion. We discuss the results relative to the sparse literature on infant/toddler teachers' well-being and suggest areas for professional development supports while underscoring the need for EHS federal policy makers and program administrators to consider how to reduce/streamline workload.


Non-invasive prediction of preterm birth in women with cervical insufficiency or an asymptomatic short cervix (≤25 mm) by measurement of biomarkers in the cervicovaginal fluid.
To determine whether various proteins in the cervicovaginal fluid (CVF) known to be involved in immune regulation, alone or in combination with clinical risk factors, can predict spontaneous preterm delivery (SPTD) in women with cervical insufficiency or a short cervix (≤25 mm). This retrospective cohort study included 62 asymptomatic women with cervical insufficiency (n = 27) or an asymptomatic short cervix (n = 35) at 18-27 weeks. CVF swab samples were taken for assays of vitamin D binding protein (VDBP), interleukin (IL)-8, matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and Dickkopf-related protein 3 (DKK3) before cervical examination, and maternal blood was collected for the determination of the C-reactive protein (CRP) level. The primary outcome measurement was SPTD at <32 weeks of gestation. Logistic regression analysis and receiver operating characteristic curves were used for the statistical analyses. The rate of SPTD at <32 weeks was 40.3% (25/62). The CVF levels of VDBP, TIMP-1, and DKK3, but not IL-8 and MMP-9, were significantly higher in the women who had SPTD at <32 weeks than in those who did not deliver spontaneously at <32 weeks. The women who had SPTD at <32 weeks had a significantly more advanced cervical dilatation at presentation and a higher level of serum CRP. Using the stepwise regression analysis, a prediction model was developed by combining various proteins in the CVF and clinical factors, resulting in the inclusion of cervical dilatation, CVF VDBP, and use of corticosteroids (area under curve, 0.909). In women with cervical insufficiency or a short cervix, VDBP, TIMP-1, and DKK3 in the CVF may be useful as non-invasive predictors of SPTD at <32 weeks. A combination of these markers and clinical factors appears to improve the predictability of SPTD compared with the markers alone.


Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.
Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose that isorhamnetin may contribute to blockade of the host-destructive processes mediated by IL-6 and could be a highly efficient modulator of the host response in the treatment of inflammatory periodontal disease. Further research in animal models of periodontitis is required to better evaluate, the potential of isorhamnetin as a novel agent for treating periodontal disease.


Photonic jet breakthrough for direct laser microetching using nanosecond near-infrared laser.
Nanosecond near-IR lasers are commonly used for industrial laser processing. In this paper, we demonstrate that a 70 μm diameter beam generated from a 5 W, 28 ns, near-IR (1064 nm) Nd:YAG laser can etch a silicon wafer with a lateral feature size as small as 1.3 μm. Surprisingly with this laser, microetching can also be achieved on glass, despite the low absorption of this material at this wavelength. This breakthrough is carried out in ambient air by using glass microspheres with diameters between 4 and 40 μm that generate a concentrated beam at their vicinity, a phenomenon referred to as a photonic jet. The roles of parameters such as laser fluence, pulse number, microsphere diameter, and distance between the microsphere and the sample are discussed. A good correlation has been observed between the computed photonic jet intensity distribution and the etched marks' geometry.


Cationic and anionic fragmentation of dichloromethane following inner-shell (Cl 1s) photoexcitation.
The cationic and anionic fragmentation of dichloromethane (CH2Cl2) molecule have been investigated in the energy range of the Cl K shell by using synchrotron radiation, ion yield spectroscopy, and electron-ion coincidence spectroscopy. Total and partial ion-yield and mass spectra have been recorded as a function of the photon energy. We were able to identify several singly and multiply charged cationic fragments and the following anionic species: H-; C-; Cl-. The present results provide the first experimental report of negative ion formation from a molecule excited at the Cl 1s edge. In addition, our electron-ion coincidence data provide strong evidence of the preservation of molecular alignment for the photodissociation of CH2Cl2 after deep core-electron resonant excitation.


Rhizoctonia wilt suppression of brinjal (Solanum melongena L) and plant growth activity by Bacillus BS2.
An antibiotic-producing and hydrogen-cyanide-producing rhizobacteria strain Bacillus BS2 showed a wide range of antifungal activity against many Fusarium sp. and brinjal wilt disease pathogen Rhizoctonia solani. Seed bacterization with the strain BS2 promoted seed germination and plant growth in leguminous plants Phaseolus vulgaris and non-leguminous plants Solanum melongena L, Brassica oleracea var. capitata, B. oleraceae var. gongylodes and Lycopersicon esculentum Mill in terms of relative growth rate, shoot height, root length, total biomass production and total chlorophyll content of leaves. Yield of bacterized plants were increased by 10 to 49% compared to uninoculated control plants. Brinjal sapling raised through seed bacterization by the strain BS2 showed a significantly reduced wilt syndrome of brinjal caused by Rhizoctonia solani. Control of wilt disease by the bacterium was clue to the production of antibiotic-like substances, whereas plant growth-promotion was due to the activity of hydrogen cyanide. Root colonization study confirmed that the introduced bacteria colonized the roots and occupied 23-25% of total aerobic bacteria, which was confirmed using dual antibiotic (nalidixic acid and streptomycin sulphate) resistant mutant strain. The results obtained through this investigation suggested the potentiality of the strain BS2 to be used as a plant growth promoter and suppressor of wilt pathogen.


Pharmacokinetic drug interactions with nevirapine.
Treatment of HIV infection is a multi-drug issue. Not only are there drugs for the treatment of HIV but also concomitant drugs for opportunistic infections, complications arising from the anti-retroviral therapy and other conditions related to a chronic disease. To have any understanding of drug-drug interactions in HIV treatment we need to appreciate the importance of key pharmacological areas including: 1) how each drug in a regimen is eliminated; 2) the potential for a drug to either induce or inhibit metabolic enzymes and/or transporters; 3) the therapeutic index of each drug. It is impossible to memorise all the possible drug-drug interactions in HIV, therefore understanding how drugs are metabolised/eliminated and the potential for a particular drug to modify the pharmacokinetics of another has predictive value even when substantive data are unavailable. NNRTIs interact with cytochrome P450 (CYP450) enzymes both as substrates and inducers. Because of the inductive effects caution must be exercised when using with protease inhibitors (either boosted or un-boosted with ritonavir). In this situation therapeutic drug monitoring may play a role in optimising response. There needs to be care when using many drugs with NNRTIs e.g. methadone, oral contraceptives, rifampicin, and there are some definite contraindications. By understanding pharmacological principles, it is possible to optimise use of multi-drug regimens.


[The determination of phenols in water: gas chromatographic identification by means of the electron affinity (author's transl)].
The electron affinities for 98 phenolic compounds have been determined using an electron capture detector (ECD) and a flame ionisation detector (FID). The signals of the two detectors were registered simultanously on a two channel recorder by splitting the gas stream at the column outlet for the ECD and the FID (1:1). The peak areas were corrected for equal concentration and instrument parameters and the relation peak area (ECD)/peak area (FID) was used as a measure of electron affinity. The values thus measured are given in a table. Among the phenolics found in water there are several groups with high or very high electron affinity, e.g. dichlorophenols, trichlorophenols, tetra- and pentachlorophenol; the values of these compounds are about 10(2), 10(3), 10(4), and 3 times 10(4) times higher, respectively, than that of phenol itself and its alkyl derivatives. For the mono- and dinitrophenols the corresponding figures are between 10(2) (o-nitrophenol) and 5 times 10(3) (dinitrophenols). A comparatively high value was measured for salicylic aldehyde: about 2.5 times 10(2) compared with phenol. The application of these values in the identification of some peaks in the gas chromatogram of a river water extract is demonstrated.


Synthesis of disubstituted tetrahydrocarbazoles with potential antidepressive activity.
A new series of disubstituted tetrahydrocarbazoles were synthesized. They are tested for antidepressive activity by the Porsolt's forced swimming test (one of the acute stress methods) and by the prevention of reserpine induced hypothermia and ptosis in mice. 3-Morpholino-1-[N-(6-methoxy-1,2,3,4- tetrahydrocarbozolyl)2-propanol, fumarate (XI) was demonstrated to be the most promising compound of this series. Besides, this series did not present the most common adverse effects of the conventional tricyclic-antidepressants (loss of locomotor coordination, ataxia and anticholinergic activity).


An Update on Host-Pathogen Interplay and Modulation of Immune Responses during Orientia tsutsugamushi Infection.
The obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions of O. tsutsugamushi, including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models.


Risk score to assess mortality risk in patients undergoing transvenous lead extraction.
The main aim of this study was to assess 1-year mortality and its predictors in a cohort of patients who underwent transvenous lead extraction (TLE) procedure. Retrospective analysis of clinical characteristics and 1-year follow-up of patients referred for a TLE procedure in a single, high-volume center between June 2006 and October 2014 was performed. The studied population included 130 patients (82 males; mean age 64 ± 15 years) implanted with pacemakers (74%), implantable cardioverter defibrillators (15%), or cardiac resynchronization therapy defibrillator (11%). Indications for the extraction included infective endocarditis (40.5%), pocket infection (18.5%), and lead fault or failure (41%). Total radiological success rate was 90% while clinical success rate was 93.5%. The cumulative 1-year mortality was 28%. Mortality was higher in a group of older patients (94.4% vs 68%, P = 0.001) and those with chronic kidney disease (33.3% vs 4.3 %, P = 0.0002) as well as in patients after removal of high voltage lead (88.9% vs 26.3%, P = 0.01). Higher mortality was also related to infection as an indication for TLE (37.2% vs 13.5%, P = 0.002). Following these findings a new risk score model named IKAR (I = infective indications; K = kidney dysfunction; A = age ≥ 56; R = removal of high voltage lead) was constructed. Patients with IKAR score ≥3 points were characterized by 79% mortality as compared to 16% in those with a score 1-2 points. One-year mortality of patients undergoing TLE procedure can be predicted by using IKAR risk score.


Study of low-molecular weight organic acids in maize roots under the stress of cadmium using capillary zone electrophoresis.
An indirect CE method was developed for the study of low-molecular weight organic acids (LMWOAs) in maize under the stress of cadmium. The influences of indirect reagents (phthalate, salicylic acid, and benzoic acid), coion concentration, and pH were studied. A buffer composed of 15 mmol/L benzoate and 0.2 mmol/L CTAB (pH 5.7) was used in the organic acid determination. The detection limit ranged between 0.5 and 6 micromol/L. The RSD (n = 14) of the method was found to be in the range of 0.11-0.49% for migration time and 1.25-4.72% for peak area. In the maize roots, obvious increases of LMWOAs were observed when the plants were under the stress of cadmium and/or organic acids. The recovery of standard organic acids added in real samples ranged from 85 to 116%.


Foot placement control and gait instability among people with stroke.
Gait instability is a common problem following stroke, as evidenced by increases in fall risk and fear of falling. However, the mechanism underlying gait instability is currently unclear. We recently found that young, healthy humans use a consistent gait stabilization strategy of actively controlling their mediolateral foot placement based on the concurrent mechanical state of the stance limb. In the present work, we tested whether people with stroke (n = 16) and age-matched controls (n = 19) used this neuromechanical strategy. Specifically, we used multiple linear regressions to test whether (1) swing phase gluteus medius (GM) activity was influenced by the simultaneous state of the stance limb and (2) mediolateral foot placement location was influenced by swing phase GM activity and the mechanical state of the swing limb at the start of the step. We found that both age-matched controls and people with stroke classified as having a low fall risk (Dynamic Gait Index [DGI] score >19) essentially used the stabilization strategy previously described in young controls. In contrast, this strategy was disrupted for people with stroke classified as higher fall risk (DGI </=19), particularly for steps taken with the paretic limb. These results suggest that a reduced ability to appropriately control foot placement may contribute to poststroke instability.


[Children obesity and its metabolic outcomes].
According to current statistics, there are, at an average child's general practice about seventy children registered with obesity, including fifty children indicated for long-term treatment of obesity due to medical indications, fifteen children are intended for targeted modifications in their diet, and in almost every practice there is a child with a pathognomonic obesity. Currently, we are exposed to food-borne pandemic coupled polygenic obesity, which is a chronic metabolic disease with societal consequences. Alimentary obesity mainly reflects an early onset of cardio-metabolic risk, but the clinical picture of complications of childhood obesity is broader and includes not only the risk of life-limitation, but also respiratory, gastrointestinal, neurological, orthopaedic and endocrine complications along with serious psychosocial problems. The effects caused by childhood obesity are reversible initially, and early identification and treatment is a major clinical challenge in preventing the development of serious metabolic, organ, psychological and societal complications.


Mucinous Adenocarcinoma of the Appendix: A Case Report.
Primary tumors of the appendix are unusual and most of them are carcinoids. Their main presentation is that of an acute appendicitis or as a palpable mass, mainly in the right lower quadrant. A 40 years old male patient presented in Dhaka Community Medical College Hospital, Dhaka, Bangladesh on 31st October 2013 with mucous adenocarcinoma of the appendix, which primarily presented as heaviness in right lower abdomen and atypical abdominal pain. Diagnosis of the disease was made after right hemicolectomy and histopathological analysis of the specimen. Mucin producing adenocarcinomas of the appendix are a category of rare cancers of the gastrointestinal tract. Although at present they are a well studied pathological entity, the crucial issue of their preoperative diagnosis remains unsolved.


[A study of the process by which a school-age child adapted to body image changes following open-heart surgery].
This case report attempts to explore the adaptive process of body image changes in school-age children suffering from congenital ventricular septal defect (VSD) following open-heart surgery. After establishing trust relationship, we applied atraumatic care, projective communication techniques, interviews, behavioral observation, storytelling and play in our interaction with that child. We found the child experienced "body image disturbance" after open-heart surgery and underwent a four stage adaptive process as follows: (1) Impact (questioning, perception of punishment for wrongdoing, loss, anger); (2) Retreat (denial, anxiety, withdrawal, escaping social contact, inferiority); (3) Acknowledgment (cognitive change, active participation, future-oriented concerns); and (4) Reconstruction (positive self-image, reconstructing body image). Nursing intervention provided the case with more opportunities for sensory feedback and positive reinforcement and also assisted the patient to adopt a positive view of the situation and then to reconstruct and realize the meaning of such surgery. We reinforced the social supporting system to promote self-confidence, self-esteem, and self-value. The child finally accepted the wounds resulting from the operation as a symbol of "bravery"; a breakthrough likely to help in the child's re-entrance to school and normalization of life. Study findings both enhanced pediatric nurse understanding of the adaptive process involved in body image change and provided knowledge essential to designing flexible-option nursing interventions tailored to meet the demands of different adaptation stages. Obviously, such a caring model designed to meet the differing needs of different body image changes has the potential to benefit of body image integration greatly and can provide the pediatric nursing framework in the future.


Ras protein expression as a marker for breast cancer.
Breast cancer, the most common neoplasm in women of all ages, is the leading cause of cancer-related mortality in women worldwide. Markers to help to predict the risk of progression and ultimately provide non-surgical treatment options would be of great benefit. At present, there are no available molecular markers to predict the risk of carcinoma in situ progression to invasive cancer; therefore, all women diagnosed with this type of malignancy must undergo surgery. Breast cancer is a heterogeneous complex disease, and different patients respond differently to different treatments. In breast cancer, analysis using immunohistochemical markers remains an essential component of routine pathological examinations, and plays an import role in the management of the disease by providing diagnostic and prognostic strategies. The aim of the present study was to identify a marker that can be used as a prognostic tool for breast cancer. For this purpose, we firstly used an established breast cancer model. MCF-10F, a spontaneously immortalized breast epithelial cell line was transformed by exposure to estrogen and radiation. MCF-10F cells were exposed to low doses of high linear energy transfer (LET) α particles (150 keV/μm) of radiation, and subsequently cultured in the presence of 17β-estradiol. Three cell lines were used: i) MCF-10F cells as a control; ii) Alpha5 cells, a malignant and tumorigenic cell line; and iii) Tumor2 cells derived from Alpha5 cells injected into nude mice. Secondly, we also used normal, benign and malignant breast specimens obtained from biopsies. The results revealed that the MCF-10F cells were negative for c-Ha-Ras protein expression; however, the Alpha5 and Tumor2 cell lines were positive for c-Ha-Ras protein expression. The malignant breast samples were also strongly positive for c-Ha-Ras expression. The findings of our study indicate that c-Ha-Ras protein expression may be used as a marker to predict the progression of breast cancer; this marker may also ultimately provide non-surgical treatment options for patients who are at a lower risk.


Comparison of Videofluoroscopic Swallowing Study and Radionuclide Salivagram for Aspiration Pneumonia in Children With Swallowing Difficulty.
To determine whether the use of both videofluoroscopic swallowing study (VFSS) and radionuclide salivagram was beneficial for detecting aspiration-induced pneumonia in children with swallowing difficulty. From 2001 to 2016, children who underwent both VFSS and salivagram consecutively for suspected aspiration or dysphagia were included in the study. Demographic data, findings of VFSS and salivagram, and medical records were reviewed. Aspiration pneumonia (AP) was present in 34 out of 110 children; 48 showed positive aspiration findings in VFSS and 33 showed positive aspiration findings in salivagram. Among the 62 children who were negative of aspiration in VFSS, 12 (19.4%) showed positive aspiration findings in salivagram. Four out of 12 children were diagnosed with AP. The aspiration findings in both VFSS and salivagram were significantly related to AP. However, the aspiration findings in the two tests were weakly consistent. Even if one test showed negative aspiration, it was helpful to additionally detect AP using another test, which showed positive aspiration finding. If aspiration findings were positive in only one of the two tests, the probability of AP was 38.5%, whereas if they were positive in both tests, the probability increased to 66.7%. If the aspiration findings were negative in both tests, AP did not occur with a probability of 90%. Salivagram is a valuable tool for monitoring of aspiration in children with swallowing difficulties. It could be helpful in assessment of children at a high risk of AP, even if the VFSS showed negative aspiration findings. Thus, testing for AP using both VFSS and salivagram is desirable.


Vascular aging and its relationship with lifestyles and other risk factors in the general Spanish population: Early Vascular Ageing Study.
To describe the prevalence of healthy vascular aging (HVA), normal vascular aging and early vascular aging (EVA) in a sample of Spanish population without cardiovascular disease. The relationship of vascular aging with lifestyle, cardiovascular risk factors, psychological and inflammatory risk factors is also analyzed. A total of 501 participants were recruited (49.70% men, aged 55.90 ± 14.24 years) by random sampling. Vascular aging was defined in three steps: Step 1: participants with vascular damage in carotid arteries or peripheral artery disease were classified as EVA. Step 2: with the percentiles of carotid-to-femoral pulse wave velocity (cfPWV) we used three criteria, first, the 10th and 90th cfPWV percentiles of the population studied by age and sex; second, the 10th and 90th percentiles of the European population reference values and third, the 25th and 75th cfPWV percentiles of the population studied by age and sex. Step 3: participants with hypertension or type 2 diabetes mellitus included in HVA were reclassified as normal vascular aging. Arterial stiffness was assessed with cfPWV using a Sphygmocor device. Physical activity was measured with an accelerometer. Psychological factors, lifestyle and other clinical information were obtained by standard questionnaire. The global prevalence of HVA was 8 and 14% (men 8 and 10%, women 9 and 18%), and 22 and 18% (men 26 and 23%, women 17 and 12%) for EVA, using criteria a and b, respectively. In the logistic regression analysis, vascular aging maintains positive associations with more sedentary time [odds ratio (OR) = 2.37 and 4.51], having triglycerides above 150 mg/dl (OR = 6.55 and 4.06), abdominal obesity (OR = 2.73 and 2.90), increased uric acid (OR = 4.63 and 2.98) and insulin resistance index homeostatic model assessment (OR = 4.05 and 6.78), and a negative association with less physical activity (OR = 0.29 and 0.28) using criteria a and b, respectively. One in 10 has HVA and one in five EVA. The prevalence of EVA is higher in men. Study results suggest that preventive strategies aimed at increasing physical activity, reducing sedentary time and decreasing obesity and insulin resistance improve vascular aging.


From The House with the Green Shutters to Our Lady of Perpetual Succour: the portrayal of alcohol in the modern Scottish novel.
In modern Scottish literature alcohol is a recurrent subject; this paper examines the different ways it is portrayed with particular emphasis on the novel. It has been seen as the resort of the weak-minded and the cause of personal degradation. It has been portrayed as a response to and a symptom of social disintegration. It has been depicted as leading to delirium and psychosis. On a positive note it has been hailed as a source of inspiration and as a means of celebration. It has helped some troubled characters find the road to redemption. Along the way we encounter various literary stereotypes of the drinker, while the pub forms the backdrop to much of the action.


Pharmacological approaches to targeting muscarinic acetylcholine receptors.
The presence of cholinergic system markers and muscarinic receptor subtypes in several tissues also of nonneuronal type has been largely demonstrated. Acetylcholine, synthesized in the nervous system, can locally contribute to modulate cell proliferation, survival and apoptosis. Considering that the cholinergic system functions are impaired in a number of disorders, the identification of new drugs regulating these functions appears of great clinical relevance. The possible involvement of muscarinic acetylcholine receptors in different pathologies has been proposed in recent years and is becoming an important area of study. However, the lack of selective muscarinic receptor ligands has for long time limited the therapeutic treatment based on muscarinic receptors as targets. To date, some muscarinic ligands such as xanomeline (patent, US5980933) or cevimeline (patents US4855290, US5571918) have been developed for the treatment of several pathologies (Alzheimer's and Sjogren's diseases). The present review will be focused on the potential effects produced by muscarinic receptor activation in different pathologies, including tumors. In fact, the potential use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that several muscarinic antagonists, already used in the treatment of genitourinary diseases (e.g. darifenacin, patent, US5096890, US6106864), have also been demonstrated to arrest the tumor growth in vivo. Moreover, the contribution of muscarinic receptors to analgesia is also reviewed. Finally, some of the most significant achievements in the field of bitopic/dualsteric ligands will be discussed and the molecules patented so far will be presented.


Preliminary characterization of angiogenic activity in media conditioned by cells from luteinized rat ovaries.
Angiogenic activity was detected in media conditioned by ovarian cells from superovulated, pseudopregnant (PMSG/human CG treated) immature Holtzman rats. Media conditioned by cells from luteinized rat ovaries stimulated the directed migration of rabbit endothelial cells or mouse Balb/c3T3 cells, but was not mitogenic to either cell type. That endotheliotropic activity was not associated with a steroid was indicated by the finding that chemoattractant activity was detected in fractions after reversed-phase C18 chromatography, which removes more than 95% of steroids present in the media, and that chemoattractant activity was precipitated by ammonium sulfate and by ethanol. Full chemoattractant activity was recovered after boiling (95 C for 30 min), lyophilization, dialysis, Sephadex G-25 desalting columns, and pH changes from 3-10. After Sephadex G-200 chromatography, chemoattractant activity emerged at elution volumes corresponding to 20,000-30,000 mol wt. Chemoattractant activity was not retained by Concanavalin A-Sepharose or gelatin-Sepharose, and was only partially retained by heparin-agarose. Chemoattractant activity was also partially retained on both cation and anion exchange columns. Our collective findings indicate the presence of a nonsteroidal, heat-stable, pronase-sensitive factor, nominal mol wt of 20,000-30,000, in media conditioned by cells from luteinized rat ovaries; this factor is chemoattractive but not mitogenic to endothelial cells. Ovarian-derived chemoattractant activity appears to be distinct from fibroblast growth factor because it lacked detectable mitogenic activity, and because fibroblast growth factor was not active in our cell migration bioassay. Because stimulation of endothelial cell migration is a key event during angiogenesis, demonstration of an ovarian endotheliotropic chemoattractant is consistent with our hypothesis that angiogenesis factors play a role in the paracrine regulation of ovarian function.


Cyclometalated Gold(III) Complexes Bearing DACH Ligands.
The synthesis of a novel class of cyclometalated gold(III) complexes supported by benzoylpyridine, benzylpyridine, and (1R,2R)-(+)-1,2-diaminocyclohexane (DACH) ligands, along with their crystal structures, is reported. These compounds provide a new scaffold to investigate biological properties of gold(III) complexes. The six complexes were prepared and characterized, following reactions of (C,N) cyclometalated gold(III) scaffolds, [Au(C^N)Cl2] with DACH, which yielded a new series of cyclometaled gold(III), 3-5, of the type [Au(C^NH)(DACH)2]+ and the nitrogen-substituted cyclometalated Au(III), 6-8, of the type [Au(C^N)(DACH)]2+. Antiproliferative activity of these complexes in a panel of cancer cells showed promising results with IC50 in the micromolar range and selectivity over normal epithelial cells, MRC5. Whereas 8 shows minimal interaction with superhelical DNA except at high gold concentrations of 500 μM, complex 5 does not show interaction even at 1000 μM. The complexes display significant uptake in OVCAR8 cancer cells within 200-1200 pmol/million cells with the exception of complex 4. Differential cellular uptake was observed for the complexes; for example, while 3 and 8 display significant uptake, 4 showed minimal uptake. The compounds proved to be stable under physiological conditions and were minimally affected by either glutathione or sodium ascorbate. Cell cycle studies reveal a G1 arrest induced by representative complexes. The results reveal that enhanced Au(III) stabilization promoted by combined cyclometalated and DACH ligands may offer ligand tuning insights for novel anticancer drug design.


[Expression of toll-like receptor mRNA in lung tissue in mice with hemorrhagic shock].
To investigate the influence and its significance of expression of Toll-like receptor mRNA in lung tissue of mice with hemorrhagic shock without resuscitation. Forty-five C57BL/6 mice were randomly divided into hemorrhagic shock group, lipopolysaccharide (LPS) group (positive control, 5 mg/kg LPS was injected into caudal vein), and sham-operation group (negative control), with 15 mice in each group. The hemorrhagic shock model was reproduced by heart puncture. The total RNA from lung tissue of mice in each group was extracted by Tripure reagent and the expression of Toll-like receptor 2 (TLR2) and TLR4 mRNA were measured by semi-quantitative reverse transcription-polymerase chain reaction. Hemorrhagic shock and LPS challenge increased lung neutrophil infiltration and erythrocyte diapedesis. The expression of TLR2 mRNA and TLR4 mRNA could be found in normal lung tissues, but they were increased at 0, 1, 2, 4, and 6 hours after hemorrhagic shock and LPS challenge. There was no change in the sham-operation group. The increased expression of TLR2 and TLR4 gene in lung tissue after hemorrhagic shock is closely correlated with the onset of acute lung injury. Though the innate immunity is enhanced, the animals are more susceptible to subsequent irritations. Over-expression of TLR2 and TLR4 may induce structural and functional damage to organs.


An Exact Formula for Calculating Inverse Radial Lens Distortions.
This article presents a new approach to calculating the inverse of radial distortions. The method presented here provides a model of reverse radial distortion, currently modeled by a polynomial expression, that proposes another polynomial expression where the new coefficients are a function of the original ones. After describing the state of the art, the proposed method is developed. It is based on a formal calculus involving a power series used to deduce a recursive formula for the new coefficients. We present several implementations of this method and describe the experiments conducted to assess the validity of the new approach. Such an approach, non-iterative, using another polynomial expression, able to be deduced from the first one, can actually be interesting in terms of performance, reuse of existing software, or bridging between different existing software tools that do not consider distortion from the same point of view.


Moral Injury in Veterans: Application of the Roy Adaptation Model to Improve Coping.
The objective of this article is to provide validation, application, and understanding of the concept of moral injury and build provider awareness to reduce veteran self-harm. Two focus groups were conducted: one to identify characteristics of moral injury and the other to refine the concepts and generate clinical approaches that address maladaptive coping strategies. The focus group sessions verified moral injury's existence, and focus group consensus centered on loss of role identity and shattering of the veteran's core integrity. The veteran's inability to self-reflect is identified as a significant contributor to the maladaptive thought process, creating internal triggers based on violations of deeply held beliefs. A Supplemental Digital Content video abstract is available at http://links.lww.com/ANS/A33.


Primary care physicians' perceptions of the effect of insurance status on clinical decision making.
Americans who do not have health insurance receive fewer health services and have poorer health status than those who have insurance. To better understand this disparity, in this study we characterize primary care physician's perceptions of what effect, if any, patients' insurance status has on their clinical decision making during office visits. Twenty-five physician members of CAPRICORN, a primary care practice-based research network in metropolitan Washington, DC, completed a brief paper-card survey instrument immediately after each patient encounter during 2 half-day office sessions. Participants saw patients in their usual manner and were given no additional information about their patients or their insurance. Eighty-eight percent of participating physicians reported making at least 1 change in clinical management as a result of a patient's insurance status. They reported altering their management during 99 of 409 patient encounters (24.2%). There was a significant difference in the percentage of visits that involved a change in management for privately insured, publicly insured, and uninsured patients (18.7%, 29.5%, and 43.5% respectively, P = .01). Physicians reported discussing insurance issues with patients during 62.6% of visits during which they made a change in management based on insurance status. Physicians incorporate their patients' insurance status into their clinical decision making and acknowledge they frequently alter their clinical management as a result. Additional research is needed to understand the effect of these changes on patient health and to assist both physicians and patients in enhancing the quality of care delivered within the constraints of the current insurance system.


Approaching an organic semimetal: Electron pockets at the Fermi level for a p-benzoquinonemonoimine zwitterion.
There is compelling evidence of electron pockets, at the Fermi level, in the band structure for an organic zwitterion molecule of the p-benzoquinonemonoimine type. The electronic structure of the zwitterion molecular film has a definite, although small, density of states evident at the Fermi level as well as a nonzero inner potential and thus is very different from a true insulator. In spite of a small Brillouin zone, significant band width is observed in the intermolecular band dispersion. The results demonstrate that Bloch's theorem applies to the wave vector dependence of the electronic band structure formed from the molecular orbitals of adjacent molecules in a molecular thin film of a p-benzoquinonemonoimine type zwitterion.


Prolonged QT dispersion in inflammatory bowel disease.
To investigate the frequency and factors of prolonged QT dispersion that may lead to severe ventricular arrhythmias in patients with inflammatory bowel disease (IBD). This study included 63 ulcerative colitis (UC) and 41 Crohn's disease (CD) patients. Forty-seven healthy patients were included as the control group. Heart rate was calculated using electrocardiography, corrected QT dispersion (QTcd) and the Bazett's formula. Homeostasis model assessment (HOMA) was used to determine insulin resistance (IR). HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR. Prolonged QTcd was found in 12.2% of UC patients, and in 14.5% of CD patients compared with the control group (P < 0.05). A significant difference was found between the insulin values (CD: 10.95 ± 6.10 vs 6.44 ± 3.28, P < 0.05; UC: 10.88 ± 7.19 vs 7.20 ± 4.54, P < 0.05) and HOMA (CD: 2.56 ± 1.43 vs 1.42 ± 0.75, P < 0.05; UC: 2.94 ± 1.88 vs 1.90 ± 1.09, P < 0.05) in UC and CD patients with and without prolonged QTcd. Disease behavior types were determined in CD patients with prolonged QTcd. Increased systolic arterial pressure (125 ± 13.81 vs 114.09 ± 8.73, P < 0.01) and age (48.67 ± 13.93 vs 39.57 ± 11.58, P < 0.05) in UC patients were significantly associated with prolonged QTcd. Our data show that IBD patients have prolonged QTcd in relation to controls. The routine follow-up of IBD patients should include determination of HOMA, insulin values and electrocardiogram examination.


Reliability of history of acetaminophen ingestion in intentional drug overdose patients.
The objective of this study was to determine the reliability of denial of acetaminophen ingestion in intentional drug overdose patients. All intentional drug overdose patients admitted to an emergency department who were able to provide a history were included. A detailed history was obtained on names, timing and number of medications ingested, and serum acetaminophen was assayed. Multidrug ingestion was defined as the reporting of ≥2 medications. Patients were considered 'reliable' if they reported acetaminophen ingestion and had detectable acetaminophen levels or the other way around. Validity parameters of acetaminophen history were assessed by sensitivity, specificity and positive and negative predictive values. A total of 154 patients were included. History was significantly more reliable in patients who denied ingestion of acetaminophen (n = 107) compared with patients who reported it (n = 47; 95.3% vs 65.9%, respectively; p < 0.0001, 95% CI of the difference 17.5%-41.2%). No suicidal patient who denied both acetaminophen and multidrug ingestions had a detectable acetaminophen level (negative predictive value 1, 95% CI 0.93-1.0). It is suggested that denial of both acetaminophen and multidrug ingestions by intentional drug overdose patients after a thorough history taking can be considered reliable for acetaminophen history. In facilities with limited resources, these patients may not require routine acetaminophen screening.


Magnetic resonance imaging (1.5 tesla) in patients with intractable focal seizures.
Magnetic resonance (MR) (1.5 tesla) studies were performed in ten patients with temporal lobe epilepsy and two with temporofrontal epilepsy. Two patients with temporal lobe epilepsy and one with temporofrontal epilepsy exhibited areas of increased signal intensity on T2-weighted images in the mesiobasal portion of the temporal lobe shown by electroencephalography to be the epileptogenic focus; no analogous abnormalities had been found in these patients on computed tomographic scans. Pathologic studies have not revealed a specific ultrastructural correlate for the MR findings in this group of patients. We found MR to be a useful, noninvasive diagnostic adjunct in the presurgical assessment of some patients with temporal lobe epilepsy. Where abnormalities were found, they corresponded with the epileptogenic focus as defined by electroencephalography.


Canine pancytopoenia in a Mediterranean region: a retrospective study of 119 cases (2005 to 2013).
To further clarify the causes of pancytopoenia and to investigate whether underlying cause or severity were associated with survival in an area endemic for vector-borne pathogens. Retrospective review of medical records of 119 dogs with and 238 dogs without pancytopoenia. Mixed-breed dogs and dogs younger than one year had higher odds of being pancytopoenic. The most common diagnoses included monocytic ehrlichiosis (n=42), leishmaniasis (n=28) and parvoviral enteritis (n=19). The mean white blood cell counts were lower in dogs with ehrlichiosis and parvoviral enteritis compared to dogs with leishmaniasis, while platelet counts were lower in ehrlichiosis compared to leishmaniasis or parvoviral enteritis. Total protein concentrations were lower in dogs with parvoviral enteritis compared to ehrlichiosis and leishmaniasis. Higher haematocrit, platelet and white cell counts were associated with better odds of survival. Infectious diseases appear to be the leading causes of canine pancytopoenia in endemic areas; severe leukopoenia (ehrlichiosis, parvoviral enteritis), thrombocytopoenia (ehrlichiosis) and hypoproteinaemia (parvoviral enteritis), represented potentially useful disease-specific diagnostic determinants. The severity of pancytopoenia significantly affects the clinical outcome.


Instrumentation in hysteroscopy.
The use of diagnostic and operative hysteroscopy has evolved rapidly over the past decade to become an integral part of gynecologic care. The hysteroscopies and ancillary equipment are readily available commercially, and the techniques can be mastered, as is true of any surgical technique, with an appropriate amount of supervised practice. With a good basic understanding of the types of equipment available and their appropriate uses, the maximum utility of the hysteroscopic technique can be fully realized in an environment of safety.


Efficient secretion and processing of heterologous proteins in Saccharomyces cerevisiae is mediated solely by the pre-segment of alpha-factor precursor.
A novel processing site was identified in fusions of the alpha-factor precursor of Saccharomyces cerevisiae following its 19 amino-terminal residues (pre-segment). Fusions of the pre-segment to heterologous proteins, including aminoglycoside phosphotransferase (APH) and human granulocyte-macrophage colony stimulating factor (hGM-CSF), were as efficiently secreted and processed as corresponding pre-pro fusions. Pre- and pre-pro fusions to hGM-CSF were identically N- and O-glycosylated. While pre-pro fusions to interleukin-1 beta were not cleaved, pre-fusions were correctly processed during secretion. The high secretion efficiency of pre-fusions suggests that the pro-segment of the alpha-factor precursor is not required for efficient secretion and processing of protein fusions.


Non-specific, on-probe cleanup methods for MALDI-MS samples.
High concentrations of contaminants such as salts and surfactants are often present in biological samples to solubilize or stabilize analytes such as proteins. Unfortunately, the presence of those contaminants often precludes direct analysis by MALDI-MS. Selective adsorption of analytes directly on modified MALDI probes, followed by rinsing to remove contaminants, overcomes this problem. This review focuses on various modifications of MALDI probes to allow the adsorption of proteins and DNA, even in a large excess of salt or surfactant. Interfaces deposited on the MALDI probes to adsorb analytes include films of commercial polymers, thin layers of matrix crystals, self-assembled monolayers, and ultrathin polymer films. Hydrophobic and ionic interactions both effect analyte adsorption on those interfaces, and patterned interfaces allow the concentration and purification of analyte molecules.