Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers: Ac-Ala-βACHC-Ala-NHBn.
The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, ( SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and ( SSRS) Ac-Ala-βACHC-Ala-NHBn ( SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα -Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C═O/axial NH or equatorial NH/axial C═O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C═O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.


Diagnostic accuracy of a new instrument for detecting cognitive dysfunction in an emergent psychiatric population: the Brief Cognitive Screen.
In certain clinical contexts, the sensitivity of the Mini-Mental State Examination (MMSE) is limited. The authors developed a new cognitive screening instrument, the Brief Cognitive Screen (BCS), with the aim of improving diagnostic accuracy for cognitive dysfunction in the psychiatric emergency department (ED) in a quick and convenient format. The BCS, consisting of the Oral Trail Making Test (OTMT), animal fluency, the Clock Drawing Test (CDT), and the MMSE, was administered to 32 patients presenting with emergent psychiatric conditions. Comprehensive neuropsychological evaluation served as the criterion standard for determining cognitive dysfunction. Diagnostic accuracy of the MMSE was determined using the traditional clinical cutoff and receiver operating characteristic (ROC) curve analyses. Diagnostic accuracy of individual BCS components and BCS Summary Scores was determined by ROC analyses. At the traditional clinical cutoff, MMSE sensitivity (46.4%) and total diagnostic accuracy (53.1%) were inadequate. Under ROC analyses, the diagnostic accuracy of the full BCS Summary Score (area under the curve [AUC]=0.857) was comparable to the MMSE (AUC=0.828). However, a reduced BCS Summary Score consisting of OTMT Part B (OTMT-B), animal fluency, and the CDT yielded classification accuracy (AUC=0.946) that was superior to the MMSE. Preliminary findings suggest the BCS is an effective, convenient alternative cognitive screening instrument for use in emergent psychiatric populations.


[Atrioventricular septal defect characteristics in infants with and without Down's syndrome: a Lebanese study].
Analyze the demographic and clinical characteristics of complete atrioventricular septal defect (AVSD), its association with Down's syndrome, with other cardiac and extra-cardiac anomalies, and finally the impact of consanguineous marriages on the incidence of AVSD. The sample consisted of 2195 consecutive patients with congenital heart defect, entered in the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut, between Jan 1999 and Dec 2007. 120 patients with AVSD were analyzed. The gathered data included age, sex, type of AVSD, mother's age, 1st and 2nd degree cousins, and other associated cardiac or extra-cardiac anomalies. AVSD was diagnosed in 5.5% of all patients with congenital heart disease, with 81.7% (n = 98) being complete AVSD. Male sex was predominant (58%). More than half (57.5%) were also diagnosed with Down's syndrome. The mean maternal age was 30.4 years (+/- 4.7 years) and consanguinity found in 16.7% of the cases. Cardiac and extra-cardiac anomalies (all in the esophagus and intestine) were associated in 15% and 6.7% respectively. Complete AVSD was significantly associated with Down's syndrome: 94% of patients with Down's syndrome had a complete AVSD. Digestive anomalies were also significantly more frequent with Down's syndrome (10% versus 2%, p = 0.02). Other cardiac anomalies, however, were less frequent with Down's syndrome (33% versus 7.7%, p = 0.02). Down's syndrome is more frequently associated with isolated and complete AVSD. Other anomalies may complicate the management of these patients. The cause of this probable genetic anomaly is still debated.


Community health workers and professional nurses: defining the roles and understanding the relationships.
The use of community health workers (CHWs) has been advocated in both developed and developing countries for many years. This article reports the findings of a descriptive research study that explored the relationship between CHWs and nurses working in resource-poor settings in South Africa. The findings of the study highlight dimensions of complex interactions occurring between these two main providers of care at the district level. Understanding the primary interaction of CHWs with nurses offers further understanding of the broader role of CHWs within the district health system. It is evident that CHWs are ideally suited to play a pivotal role in supporting the public health services. However, their role and functions are not formalized and the effectiveness of programs is often not rigorously evaluated. This article discusses some of the issues related to this cadre of health worker and their role in public health care structures.


The human NMDA receptor GluN2AN615K variant influences channel blocker potency.
N-methyl-D-aspartate (NMDA) receptors are glutamate receptors with key roles in synaptic plasticity, due in part to their Mg2+ mediated voltage-dependence. A large number of genetic variants affecting NMDA receptor subunits have been found in people with a range of neurodevelopmental disorders, including GluN2AN615K (GRIN2AC1845A) in two unrelated individuals with severe epileptic encephalopathy. This missense variant substitutes a lysine in place of an asparagine known to be important for blockade by Mg2+ and other small molecule channel blockers. We therefore measured the impact of GluN2AN615K on a range of NMDA receptor channel blockers using two-electrode voltage clamp recordings made in Xenopus oocytes. We found that GluN2AN615K resulted in block by Mg2+ 1 mmol/L being greatly reduced (89% vs 8%), block by memantine 10 μmol/L (76% vs 27%) and amantadine 100 μmol/L (45% vs 17%) being substantially reduced, block by ketamine 10 μmol/L being modestly reduced (79% vs 73%) and block by dextromethorphan 10 μmol/L being enhanced (45% vs 55%). Coapplying Mg2+ with memantine or amantadine did not reduce the GluN2AN615K block seen with either small molecule. In addition, we measured single-channel conductance of GluN2AN615K-containing NMDA receptors in outside-out patches pulled from Xenopus oocytes, finding a 4-fold reduction in conductance (58 vs 15 pS). In conclusion, the GluN2AN615K variant is associated with substantial changes to important physiological and pharmacological properties of the NMDA receptor. Our findings are consistent with GluN2AN615K having a disease-causing role, and inform potential therapeutic strategies.


Observations on the biochemical effects of transfusion of citrate-phosphate-dextrose stored blood in man.
Preliminary data on the biochemical effects of the transfusion of three units of CPD blood in man is presented. Free (ionized) calcium was found to decrease approximately two minutes following initiation of the transfusion of CPD stored blood at a rate of 50 ml/min. Due to mixing problems, arterial and not venous specimens were found necessary to monitor accurately the severity of these decreases. Parathyroid hormone in the peripheral blood was found to increase two to four minutes after the initiation of transfusion. Decreases in blood pressure were observed during transfusion. The blood pressure recovered when the transfusion was stopped and did not decrease any further after restarting the transfusion, were found out not to increase or decrease consistently, and only modest changes in plasma potassium were observed.


Clinical significance of anti-neutrophil cytoplasm antibodies detected by a standardized indirect immunofluorescence assay.
We assessed the use of a standardized antineutrophil cytoplasm antibody (ANCA) test in diagnosing Wegener's granulomatosis (WG), microscopic polyarteritis (mPA) and systemic vasculitis (SV). All samples (n = 779) tested for ANCA at our laboratory were identified, and clinical information was obtained for 783/779 patients by questionnaire, and by visits where necessary. The combined prevalence of WG/mPA/SV was 123/738 (17%). The ANCA test was positive in 48/68 WG patients (71%; 38 cANCA, 10 pANCA), 22/43 mPA patients (51%; 12 cANCA, 10 pANCA) and 3/12 SV patients (25%). WG and mPA patients in remission had similar frequencies of positive ANCA to those with active disease. The sensitivity and specificity for WG (71% and 80%) and mPA (51% and 80%) were lower than previously reported. In this high-prevalence population, the overall (WG/mPA/SV) positive predictive value was only 40%, and the sensitivity 59%. Only 29% of positive tests were from patients with active disease. Overall, 78% of test results gave a 'true' prediction. On this basis, a diagnosis of necrotizing vasculitis (WG/mPA/SV) can be neither made nor refuted by ANCA test alone.


Never Events in Radiology and Strategies to Reduce Preventable Serious Adverse Events.
The term never event in medicine was originally coined by Kenneth W. Kizer, MD, MPH, former chief executive officer of the National Quality Forum, to describe particularly shocking medical errors that should never occur, such as wrong-site surgery or death associated with introduction of a metallic object into the MRI area. With time, the National Quality Forum's list of never events, or "serious reportable events," has been expanded to include adverse events that are unambiguous, serious, and usually preventable. In this article, the never event framework has been used to describe (a) the errors that may occur in an imaging department that are serious and usually preventable with a review of the causative factors and (b) strategies to eliminate and reduce the adverse effects of these avoidable errors. These errors are often rooted in communication breakdowns and can only be eliminated with a true shift to a culture of open reporting and patient safety. ©RSNA, 2018.


The effect of galvanic stimulation on spontaneous nystagmus.
The question of the point of impact of the electric current in the galvanic vestibular test is not solved. An important feature is that, after destruction of both the vestibular end organs, a galvanic nystagmus can still be provoked. The effect of a direct current on the spontaneous nystagmus following partial or total destruction of the vestibular end organs was investigated. The frequency of the spontaneous nystagmus diminishes when the electric stimulus causes an eye movement in the same direction as the fast phase of the nystagmus, the frequency increases when the polarity of the electric stimulation is reversed. Simultaneous application of torsion-swing and electric stimulation causes a summation of the separate effects. Our findings confirm the conculsions drawn by Ledoux (4, 5) from his findings in frogs.


Associations between malaria-related ideational factors and care-seeking behavior for fever among children under five in Mali, Nigeria, and Madagascar.
Malaria remains one of the leading causes of morbidity and mortality among children under five years old in many low- and middle-income countries. In this study, we examined how malaria-related ideational factors may influence care-seeking behavior among female caregivers of children under five with fever. Data came from population-based surveys conducted in 2014-2015 by U.S. Agency for International Development-funded surveys in Madagascar, Mali, and Nigeria. The outcome of interest was whether a child under five with fever within two weeks prior to the survey was brought to a formal health facility for care. Results show a wide variation in care-seeking practices for children under five with fever across countries. Seeking care for febrile children under five in the formal health sector is far from a norm in the study countries. Important ideational factors associated with care-seeking behavior included caregivers' perceived social norms regarding treatment of fever among children under five in Nigeria and Madagascar, and caregiver's knowledge of the cause of malaria in Mali. Findings indicate that messages aimed to increase malaria-related knowledge should be tailored to the specific country, and that interventions designed to influence social norms about care-seeking are likely to result in increased care-seeking behavior for fever in children under five.


Characteristics of DSM-III borderline MMPI profiles.
Examined the distinction between the MMPI mean profile (8-4-2) obtained for a sample of 27 psychiatric inpatients diagnosed as borderline on the basis of DSM-III criteria, and the actual frequency distribution of scale elevations and code-types within the sample. Results of this study support the findings of previous investigations of a peak on scale 8, but suggest that the heterogeneity of this population will probably preclude the specification of any two- or three-point code type which would be obtained by even a sizable minority of a given sample.


Oxidative decomposition of rhodamine B dye in the presence of VO2+ and/or Pt(IV) under visible light irradiation: N-deethylation, chromophore cleavage, and mineralization.
In order to make clear the roles of dissolved O2 in the photocatalytic decomposition of organic pollutants and to discriminate different degradation pathways (N-deethylation, chromophore cleavage, and mineralization) during the degradation of dye, the photodegradation of rhodamine B (RhB) has been investigated using vanadate and/or platinum species as electron acceptors in the presence or absence of O2 under visible light irradiation. It was found that with VO2+ as electron acceptor, RhB underwent efficient N-deethylation under visible light irradiation and O2 was found to slow down this process significantly. Little mineralization has been observed in the presence and absence of O2 in VO2+ systems. By contrast, Pt(IV) resulted in the cleavage of conjugated chromophore structure (bleaching) of RhB dye under the otherwise identical conditions. In this case, the presence of O2 did not affect the bleaching rate of the dye, but enhanced greatly the mineralization. Both cleavage of conjugated chromophore structure and N-deethylation occurred simultaneously upon the coaction of VO2+ and Pt(IV) under visible light irradiation. The mineralization yield of the combined system was evidently higher than the expected summation of separate ones. TOC, XPS, and ESR results indicate that in the VO2+ and Pt(IV) combined system VO2+ not only oxidized RhB leading to deethylation but also oxidized the reduced Pt(II) to regenerate Pt(IV) leading to the further cleavage of chromophore structure of RhB, which behaved quite different from the separate ones. A mechanism was also proposed to interpret the different pathways for the oxidative photodecomposition of RhB under visible irradiation.


Depressed mood and smoking experimentation among preteens.
The authors examined children's depressed mood, parental depressed mood, and parental smoking in relation to children's smoking susceptibility and experimentation over 20 months in a cohort of 418 preteens (ages 10-12 at baseline) and their parents. Depressed mood in preteens was strongly related to experimentation but not to susceptibility. In cross-sectional analyses parental depressed mood was related to children's experimentation, but in longitudinal analyses parental depressed mood at baseline did not differentiate children who experimented from those who did not. Although parental smoking was strongly related to experimentation, it was not related to susceptibility either cross-sectionally or longitudinally. Depressed mood among preteens and parents appeared to be more strongly related to children's smoking behaviors than to their intentions to smoke.


Incidence of psychiatric disorders after extended residence in Antarctica.
The incidence of psychiatric disorders and depressive symptoms was examined in a cohort of American men and women who spent an austral winter at two different research stations in Antarctica to determine whether extended residence of nonindigenous inhabitants in a polar region is associated with psychiatric morbidity. Debriefings interviews with 220 men and 93 women were conducted by 3 psychiatrists and 1 clinical psychologist at McMurdo Station and South Pole Station at the end of the austral winter between 1994 and 1997. Crewmembers were assigned a DSM-IV diagnosis if they satisfied diagnostic criteria. Debriefed crewmembers also completed the Structured Interview Guide for the Hamilton Depression Inventory-Seasonal Affective Disorders version (SIGH-SAD). Thirty-nine (12.5%) crewmembers presented with symptoms that met the criteria for one or more DSM-IV disorders. After weighting the prevalence to account for the low participation rate of civilian personnel, the incidence of DSM-IV disorders was 5.2%. Mood disorders were the most common diagnoses, accounting for 30.2% of all diagnoses, followed by adjustment disorders (27.9%), sleep-related disorders (20.9%), personality disorders (11.6%), and substance-related disorders (9.3%). Depressive symptoms as measured by the SAD-SIGH were significantly associated with female gender, military occupation, station, year of expedition, and DSM-IV diagnosis. Differences in the distribution of symptoms and diagnoses by demographic and expedition characteristics suggests that the social environment may be a more powerful determinant than the physical environment of psychiatric disorders in a polar region.


The modulation of reactive oxygen species production from human polymorphonuclear cells by curdlan derivatives as dectin-1 agonists/antagonists.
Reactive oxygen species (ROS) are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases including diabetes, neurodegenerative diseases, cancer and also influence central cellular processes such as proliferation, apoptosis, senescence etc. If in these pathological or degenerative conditions characterized by free radicals excess, reactive species are not eliminated, they can maintain destructive processes, already initiated at different cellular levels. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention. Toll-like receptors and C-type lectin receptor class V--Dectin-1, as members of Pattern Recognition Receptors play an essential role in innate immune response against bacteria and fungi respectively, contributing to pathogens recognition, phagocytosis, ROS production and induction of pro-inflammatory cytokines secretion. Using a high performance chemiluminometric method, we studied the action of six Curdlan derivatives on the ROS production and release by activated human polymorphonuclear cells (PMNs) isolated from the peripheral blood of healthy donors. Our results demonstrated that Curdlan derivatives containing sulfopropyl groups did not activate human PMNs to release ROS. These compounds blocked Dectin-1 and were able to inhibit co-operation between Dectin-1 and TLR-2. Curdlan derivatives containing palmithoyl, carboxi-methyl and sulfopropyl groups increased ROS release by human PMNs activated at TLR-2 level. Taking into account the fact that Dectin-1 can actively collaborate with TLR-2 to modulate the subsequent adaptive immune response, we can presume that Curdlan derivatives containing sulfopropyl group or palmithoyl/carboxi-methyl/sulfopropyl groups, as possible Dectin-1 antagonists/agonists, could influence TLR-2 signaling.


Nurses' knowledge of and attitudes towards sexuality and the relationship of these with nursing practice.
Issues concerning sex and sexuality are relevant to nursing practice. The objective of this study was to determine the relationship between knowledge of and attitude towards sexuality, and nursing practice. Nursing practice in this case was defined as the discussion of sexuality with the patient, with particular reference to taking a sexual history on admission to the ward. A multi-choice questionnaire with sections establishing demographic details and nursing practice, and including the Sex, Knowledge and Attitude Test (SKAT), was administered to 357 registered general nurses (RGNs). Results show a relationship between knowledge and attitude but no relationship between either of these and the nursing practice scale. However, a slight but significant correlation between receiving teaching about sexual history taking and questioning patients about sexuality on admission suggests that nursing practice and knowledge are weakly related. There is evidence that factors other than those within the scope of this study influence all three independent variables, and these are discussed. The implications of the study suggest the need for an improvement in nurse education regarding sexuality at all stages of training.


Carriage of intestinal protozoal cysts in homosexuals.
A total of 83 male homosexuals were studied to ascertain the carriage of intestinal protozoal cysts. The homosexual group had a significantly (p less than 0.0005) higher prevalence than a control group. One or more types of protozoa were found in 33 homosexuals. The carriage of intestinal protozoal cysts was associated with particular sexual practices and promiscuity, but not with symptomatic bowel disorders. The possible implications of the carriage of these cysts are discussed.


Optimal superluminal systems.
We demonstrate that significant effects in the "superluminal propagation" of light pulses cannot be observed without involving systems whose gain explodes outside the pulse spectrum. We explicitly determine the minimum norm of the gain to attain given superluminal effects and the transfer function of the corresponding optimal system. The gain norms, which would be required with the most efficient systems considered up to now (dispersive media, photonic barriers) to attain the same effects, are shown to exceed the minimum by several orders of magnitude. We finally estimate the largest superluminal advances which could be attained in a realistic experiment.


A web-based intervention to promote applications for rehabilitation: a study protocol for a randomized controlled trial.
The German welfare system follows the principle "rehabilitation rather than pension," but more than the half of all disability pensioners did not utilize medical rehabilitation before their early retirement. A major barrier is the application procedure. Lack of information about the opportunity to utilize rehabilitation services restricts the chance to improve work ability and to prevent health-related early retirement by rehabilitation programs. The establishment of new access paths to medical rehabilitation services was, therefore, identified as a major challenge for rehabilitation research in a recent expertise. Thus, a web-based information guide was developed to support the application for a medical rehabilitation program. For this study, the development of a web-based information guide was based on the health action process approach. Four modules were established. Three modules support forming an intention by strengthening risk perception (module 1), positive outcome expectancies (module 2) and self-efficacy (module 3). A fourth module aims at the realization of actual behavior by offering instructions on how to plan and to push the application process. The study on the effectiveness of the web-based information guide will be performed as a randomized controlled trial. Persons aged 40 to 59 years with prior sick leave benefits during the preceding year will be included. A sample of 16,000 persons will be randomly drawn from the registers of 3 pension insurance agencies. These persons will receive a questionnaire to determine baseline characteristics. Respondents of this first survey will be randomly allocated either to the intervention or the control group. Both study groups will then receive letters with general information about rehabilitation. The intervention group will additionally receive a link to the web-based information guide. After 1 year, a second survey will be conducted. Additionally, administrative data will be used to determine if participants apply for rehabilitation and finally start a rehabilitation program. The primary outcomes are the proportion of applied and utilized medical rehabilitation services. Secondary outcomes are cognitions on rehabilitation, self-rated work ability, health-related quality of life and perceived disability, as well as days with sick leave benefits and days of regular employment. The randomized controlled trial will provide highest ranked evidence to clarify whether theory-driven web-based information supports access to rehabilitation services for people with prior sickness benefits. German Clinical Trials Register (Identifier: DRKS00005658 , 16 January 2014).


Nucleotide Substitution Model Selection is not Necessary for Bayesian Inference of Phylogeny with Well Behaved Priors.
Model selection aims to choose the most adequate model for the statistical analysis at hand. The model must be complex enough to capture the complexity of the data but should be simple enough not to overfit. In phylogenetics, the most common model selection scenario concerns selecting an adequate substitution and partition model for sequence evolution to infer a phylogenetic tree. Previously, several studies showed that substitution model under-parameterization can bias phylogenetic studies. Here we explored the impact of substitution model over-parameterization in a Bayesian statistical framework. We performed simulations under the simplest substitution model, the Jukes-Cantor model, and compare posterior estimates of phylogenetic tree topologies and tree length under the true model to the most complex model, the GTR+Γ+I substitution model, including over-splitting the data into additional subsets (i.e., applying partitioned models). We explored four choices of prior distributions: the default substitution model priors of MrBayes, BEAST2 and RevBayes and a newly devised prior choice (Tame). Our results show that Bayesian inference of phylogeny is robust to substitution model over-parameterization and over-partitioning but only under our new prior settings. All three current default priors introduced biases for the estimated tree length. We conclude that substitution and partition model selection are superfluous steps in Bayesian phylogenetic inference pipelines if well behaved prior distributions are applied and more effort should focus on more complex and biologically realistic substitution models.


Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients.
Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was combined with perioperative alemtuzumab-mediated lymphocyte depletion and rapamycin. To assess the means by which the alemtuzumab, belatacept and rapamycin (ABR) regimen controls belatacept-resistant rejection, we studied 20 ABR-treated patients and characterized peripheral lymphocyte phenotype and functional responses to donor, third-party and viral antigens using flow cytometry, intracellular cytokine staining and carboxyfluorescein succinimidyl ester-based lymphocyte proliferation. Compared with conventional immunosuppression in 10 patients, lymphocyte depletion evoked substantial homeostatic lymphocyte activation balanced by regulatory T and B cell phenotypes. The reconstituted T cell repertoire was enriched for CD28(+) naïve cells, notably diminished in belatacept-resistant CD28(-) memory subsets and depleted of polyfunctional donor-specific T cells but able to respond to third-party and latent herpes viruses. B cell responses were similarly favorable, without alloantibody development and a reduction in memory subsets-changes not seen in conventionally treated patients. The ABR regimen uniquely altered the immune profile, producing a repertoire enriched for CD28(+) T cells, hyporesponsive to donor alloantigen and competent in its protective immune capabilities. The resulting repertoire was permissive for control of rejection with belatacept monotherapy.


Selective adsorption/desorption of nucleic acids on submicron-sized polymeric particles.
DNA can be removed or separated by the selective adsorption/desorption on positively charged submicronsized polymeric particles (SSPP). The selective adsorption of DNA, in the presence of protein, on positively charged SSPP was accomplished by increasing the concentration of potassium phosphate or sodium phosphate. The adsorption of DNA was not affected by the concentration of potassium phosphate or sodium phosphate up to 1.2M. On the other hand, the adsoprtion of a protein (bovine serum albumin) was completely impeded by 170mM potassium phosphate. DNA adsorbed on SSPP could be desorbed by increasing the concentration of NaCl or KCl, thus it can be recovered. DNA desorbed from SSPP when the concentration of NaCl or KC was higher than 0.6M. A complete desorption of DNA was achieved at the concentration of NaCl or KCl above 1.2M.


Psychometric evaluation of the cultural competence assessment instrument among healthcare providers.
The relevance of healthcare provider cultural competency to the achievement of goals for reduction in extant health disparities has been demonstrated; however, there are deficits with regard to cultural competency measurement. To examine the test-retest reliability of the cultural competence assessment instrument (CCA) among hospice providers, and to examine the reliability and validity of the CCA among healthcare providers in nonhospice settings. Test-retest reliability of the CCA was assessed using a sample of 51 hospice respondents who completed the CCA at two time points. The internal consistency reliability and construct validity of the CCA for healthcare providers in nonhospice settings were evaluated using a convenience sample of 405 healthcare providers. The CCA demonstrated adequate test-retest reliability (r = .85, p = .002) in hospice providers over 4 months. Among healthcare providers in nonhospice settings, the CCA had an internal consistency reliability of .89 overall (.91 and .75 for the two subscales). Construct validity was supported by principal axis factor analysis, which showed two factors with item loadings above .40, explaining 56% of the variance. Mean scores of the CCA were significantly higher for providers who reported previous diversity training compared to those who had not. Findings for the psychometric properties of the CCA supported its potential as an instrument for measuring provider cultural competence. Knowledge gained will be useful for developing future research studies and specific cultural competence intervention approaches for healthcare providers that may decrease health disparities.


Cyclooxygenase-2 expression in primary and metastatic Merkel cell carcinoma.
Cyclooxygenase-2 (COX-2) is involved in the development and progression of many tumors, and its inhibition has been shown to block tumor growth. This study examined COX-2 expression in primary and metastatic Merkel cell carcinoma (MCC). Formalin-fixed paraffin-embedded tissues from 26 primary MCCs and 7 lymph node metastases were stained immunohistochemically with a monoclonal antibody directed against COX-2, and the percentage and intensity of staining were analyzed semiquantitatively. Immunopositivity for COX-2 was found in 20 primary tumors (77%), and was diffuse in 16 of them (80%). Staining intensity was strong in 5 tumors (19%), moderate in 6 (23%), and weak in 9 (35%). Five metastases (71%) showed similar staining. Prominent mitotic activity was associated with more diffuse COX-2 immunopositivity. No association was found between COX-2 expression and outcome. This study confirms that most MCCs express COX-2 and shows that COX-2 expression is related to one parameter of aggressive behavior--a high mitotic rate--but not to any others. The possibility of treating MCC with COX-2 inhibitors should be considered.


[Intercentral relations in rat spinal cord with local depression of the inhibitory processes].
The changes in certain reflex responses of the rat spinal cord after local depression of inhibitory processes by tetanus toxin (the so-called phenomenon of "determinative dispatch station") were studied. It is shown that the tonic and rhythmic activity generated by this locus in the lumbar part of the spinal cord evokes generalized activity of all spinal motoneurons with similar time characteristics. The depression of its neurons by glycine removes this phenomenon. The excitation of "determinative dispatch station" neurons in cervical segments causes a pathologically enhanced scratch reflex in the ipsilateral hind limb. The enhancing of the scratch reflex is not connected with the depression of inhibitory processes of lumbar motoneurons. The formation of the "determinative dispatch station" in cervical segments produces both excitatory and inhibitory influences on monosynaptic reflexes of the lumbar flexor motoneurons. The role of local inhibitory processes depression in the functioning of the nervous system is discussed.


SO2 adsorption on silica supported iridium.
The interaction of SO2 with Ir/SiO2 was studied by simultaneous in situ diffuse reflectance infrared Fourier transform spectroscopy and mass spectrometry, exposing the sample to different SO2 concentrations ranging from 10 to 50 ppm in the temperature interval 200-400 °C. Evidences of adsorption of sulfur species in both absence and presence of oxygen are found. For a pre-reduced sample in the absence of oxygen, SO2 disproportionates such that the iridium surface is rapidly saturated with adsorbed S while minor amounts of formed SO3 may adsorb on SiO2. Adding oxygen to the feed leads to the oxidation of sulfide species that either (i) desorb as SO2 and/or SO3, (ii) remain at metal sites in the form of adsorbed SO2, or (iii) spillover to the oxide support and form sulfates (SO42-). Notably, significant formation of sulfates on silica is possible only in the presence of both SO2 and O2, suggesting that SO2 oxidation to SO3 is a necessary first step in the mechanism of formation of sulfates on silica. During the formation of sulfates, a concomitant removal/rearrangement of surface silanol groups is observed. Finally, the interaction of SO2 with Ir/SiO2 depends primarily on the temperature and type of gas components but only to a minor extent on the inlet SO2 concentration.


Combining computational and biochemical studies for a rationale on the anti-aromatase activity of natural polyphenols.
Aromatase, an enzyme of the cytochrome P450 family, is a very important pharmacological target, particularly for the treatment of breast cancer. The anti-aromatase activity of a set of natural polyphenolic compounds was evaluated in vitro. Strong aromatase inhibitors including flavones, flavanones, resveratrol, and oleuropein, with activities comparable to that of the reference anti-aromatase drug aminoglutethimide, were identified. Through the application of molecular modeling techniques based on grid-independent descriptors and molecular interaction fields, the major physicochemical features associated with inhibitory activity were disclosed, and a putative virtual active site of aromatase was proposed. Docking of the inhibitors into a 3D homology model structure of the enzyme defined a common binding mode for the small molecules under investigation. The good correlation between computational and biological results provides the first rationalization of the anti-aromatase activity of polyphenolic compounds. Moreover, the information generated in this approach should be further exploited for the design of new aromatase inhibitors.


Targeting Intrinsic and Extrinsic Vulnerabilities for the Treatment of Multiple Myeloma.
Multiple myeloma (MM) is a malignant plasma cell disorder, clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. Over the past decade, MM therapy is significantly improved by the introduction of novel therapeutics such as immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), monoclonal antibodies (daratumumab and elotuzumab), histone deacetylase (HDAC) inhibitors (Panobinostat). The clinical success of these agents has clearly identified vulnerabilities intrinsic to the MM cell, as well as targets that emanate from the tumor microenvironment. Despite these significant improvements, MM remains incurable due to the development of drug resistance. This perspective will discuss more recent strategies which take advantage of multiple targets within the proteome recycling pathway, chromatin remodeling, and disruption of nuclear export. In addition, we will review the development of strategies designed to block opportunistic survival signaling that occurs between the MM cell and the tumor microenvironment including strategies for inhibiting myeloma-induced immune suppression. It has become clear that MM tumors continue to evolve on therapy leading to drug resistance. It will be important to understand the emerging drug resistant mechanisms and additional vulnerabilities that occur due to the development of clinical resistance. J. Cell. Biochem. 118: 15-25, 2017. © 2016 Wiley Periodicals, Inc.


Aluminum tolerance of two wheat cultivars (Brevor and Atlas66) in relation to their rhizosphere pH and organic acids exuded from roots.
Phytotoxicity of aluminum (Al) has become a serious problem in inhibiting plant growth on acid soils. Under Al stress, the changes of rhizosphere pH, root elongation, absorption of Al by wheat roots, organic acids exuded from roots, and some main factors related to Al-tolerant mechanisms have been studied using hydroponics, fluorescence spectrophotometry, and high performance liquid chromatography (HPLC). Two wheat cultivars, Brevor and Atlas66, differing in Al tolerance are chosen in the study. Accordingly, the rhizosphere pH has a positive effect on Al tolerance. Atlas66 (Al-tolerant) has higher capability to maintain high rhizosphere pH than Brevor (Al-sensitive) does. High pH can reduce Al3+ activity and toxicity, and increase the efficiency of exuding organic acids from the roots. More inhibition of root elongation has been found in Brevor because of the exposure of roots to Al3+ solution at low pH. Brevor accumulate more Al in roots than Atlas66 even at higher pH. Al-induced exudation of malic and citric acids has been found in Atlas66 roots, while no Al-induced organic acids have been found in Brevor. These results indicate that the Al-induced secretion of organic acids from Atlas66 roots has a positive correlation with Al tolerance. Comprehensive treatment of Al3+ and H+ indicates that wheat is adversely influenced by excess Al3+, rather than low pH.


Biting indices, host-seeking activity and natural infection rates of anopheline species in Boa Vista, Roraima, Brazil from 1996 to 1998.
The epidemiology of the transmission of malaria parasites varies ecologically. To observe some entomological aspects of the malaria transmission in an urban environment, a longitudinal survey of anopheline fauna was performed in Boa Vista, Roraima, Brazil. A total of 7,263 anophelines was collected in human bait at 13 de Setembro and Caranã districts: Anopheles albitarsis sensu lato (82.8%), An. darlingi (10.3%), An. braziliensis (5.5%), An. peryassui (0.9%) and An. nuneztovari (0.5%). Nightly 12 h collections showed that An. albitarsis was actively biting throughout the night with peak activities at sunset and at midnight. An. darlingi bit during all night and did not demonstrate a defined biting peak. Highest biting indices, entomological inoculation rates and malaria cases were observed seasonally during the rainy season (April-November). Hourly collections showed host seek activity for all mosquitoes peaked during the first hour after sunset. An. darlingi showed the highest plasmodial malaria infection rate followed by An. albitarsis, An. braziliensis and An. nuneztovari (8.5%, 4.6%, 3% and 2.6%, respectively). An. albitarsis was the most frequently collected anopheline, presented the highest biting index and it was the second most frequently collected infected species infected with malaria parasites. An. albitarsis and An. darlingi respectively, are the primary vectors of malaria throughout Boa Vista.


Gastric Juice MicroRNAs as Potential Biomarkers for Screening Gastric Cancer: A Systematic Review.
To date, the combination of gastroscopy with biopsy remains the only test validated for screening gastric cancer (GC). Currently, analysis of circulating microRNAs (miRNAs or miRs) is providing interesting information on GC prognosis, but since these molecules are shared by several types of cancer, its clinical use could be questionable and difficult. MicroRNAs in gastric juice (GJ) could represent a cogent alternative to screening GC by biopsy. We investigated the pertinent literature dealing with GC GJ microRNAs through four popular search engines (PubMed, Science Direct, Scopus and Google Scholar). As of 2017, only four studies had been published and were all from Chinese experience. MiR-421, miR-129, miR-21, miR-106a and miR-133a were the five molecules studied in the GJ of the enrolled patients. The GJ miRNA test is reliable and reproducible. The discussed GJ miRNAs appear to be new potential biomarkers for the screening of GC.


Sox2 inhibits Wnt-β-catenin signaling and metastatic potency of cisplatin-resistant lung adenocarcinoma cells.
Lung cancer remains one of the most common cancer-associated mortalities worldwide, and platinum-based doublet chemotherapies are recommended as the first‑line treatment for advanced non‑small cell lung cancer (NSCLC). However, the frequent development of multidrug resistance, to cisplatin regimens in particular, is a major cause of chemotherapy failure in patients with aggressive NSCLC. Wnt/β‑catenin signaling and sex‑determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to epidermal growth factor receptor‑targeting therapy in lung cancer. The present study aimed to explore the effects of Wnt/β‑catenin and Sox2 signaling on the chemoresistance of cisplatin‑resistant lung cancer cells by assessing the effects of Sox2 on Wnt/β‑catenin signaling activity, cell migration, invasion and clonogenicity, and susceptibility to cisplatin in lung adenocarcinoma A549 cells and cisplatin-resistant A549/DDP cells. The results demonstrated that an enforced expression of Sox2 led to inhibition of Wnt/β-catenin signaling activity, potentially by upregulating glycogen synthase kinase 3 β in A549 and A549/DDP cells. An overexpression of Sox2 promoted cell migration and invasion, in addition to enhancing the clonogenic capacity in A549 cells. Notably, knockdown Sox2 using short hairpin RNA led to an enhanced susceptibility of A549 and A549/DDP cells to cisplatin, along with increased cell apoptosis. The present study thus suggests that Sox2 may be an important regulator in development of chemoresistance of lung cancer cells and may be a novel therapeutic target for treatment chemoresistant lung cancer.


[Disruption of spatial memory in mice exposed to agroclavine].
The results of the study of the mnemotropic activity of the ergot alkaloid agroclavine are presented. Effects of this substance administered in doses of 1, 10, 25, 50, and 200 micrograms/kg on learning and spatial memory were studied in a Morris water maze. Agroclavine had no effect on learning but sharply impaired the retention. This memory impairment persisted for 48 h after the agroclavine administration. Agroclavine treatment did not affect the ability of mice to learn and retain a new skill. Possible mechanisms of the agroclavine effect on memory are discussed.


Modest release of adipsin/factor D by liposuction when using the superwet or tumescent technique.
Human adipsin is recognized to be identical to factor D, which plays an important role in activation of the alternative complement pathway. Since adipsin/factor D is present in high amounts in adipose tissue, liposuction theoretically could result in an increased release of this serine protease into the bloodstream. In the present study, adipsin/factor D was measured in 22 patients undergoing syringe-assisted liposuction using the superwet or tumescent technique. Despite a relatively high mean aspirate volume (2648 ml), only a very modest increase in adipsin/factor D concentration was found during liposuction. All values before, during, and after liposuction were within the range found in healthy blood donors. Furthermore, there was no correlation between adipsin/factor D values and C3 activation products. We conclude that liposuction with the present techniques results in a very modest release of adipsin/factor D that is not associated with increased complement activation.


The Effects of Fatigue From Overnight Shifts on Radiology Search Patterns and Diagnostic Performance.
The aim of this study was to assess the effect of overnight shifts (ONS) on radiologist fatigue, visual search pattern, and diagnostic performance. This experimental study was approved by the institutional review board. Twelve radiologists (five faculty members and seven residents) each completed two sessions: one during a normal workday ("not fatigued") and another in the morning after an ONS ("fatigued"). Each radiologist completed the Swedish Occupational Fatigue Inventory. During each session, radiologists viewed 20 bone radiographs consisting of normal and abnormal findings. Viewing time, diagnostic confidence, and eye-tracking data were recorded. Swedish Occupational Fatigue Inventory results demonstrated worsening in all five variables (lack of energy, physical exertion, physical discomfort, lack of motivation, and sleepiness) after ONS (P < .01). Overall, participants demonstrated worse diagnostic performance in the fatigued versus not fatigued state (P < .05). Total viewing time per case was longer when fatigued (35.9 ± 25.8 seconds) than not fatigued (24.8 ± 16.3 seconds) (P < .0001). Total viewing time per case was longer for residents (P < .05). Mean total fixations generated during the search increased by 60% during fatigued sessions (P < .0001). Mean time to first fixate on the fracture increased by 34% during fatigued sessions (P < .0001) and was longer for residents (P < .01). Dwell times associated with true- and false-positive decisions increased, whereas those with false negatives decreased. After ONS, radiologists were more fatigued with worse diagnostic performance, a 45% increase in view time per case, a 60% increase in total gaze fixations, and a 34% increase in time to fixate on the fracture. The effects of fatigue were more pronounced in residents.


Characterization and rescue of telomeric abnormalities in ICF syndrome type I fibroblasts.
Mutations in the human DNA methyltransferase 3B (DNMT3B) gene lead to ICF (immunodeficiency, centromeric region instability, and facial anomalies) syndrome type I. We have previously described a telomere-related phenotype in cells from these patients, involving severe hypomethylation of subtelomeric regions, abnormally short telomeres and high levels of telomeric-repeat-containing RNA (TERRA). Here we demonstrate that ICF-patient fibroblasts carry abnormally short telomeres at a low population doubling (PD) and enter senescence prematurely. Accordingly, we attempted to rescue the senescence phenotype by ectopic expression of human telomerase, which led to elongated telomeres with hypomethylated subtelomeres. The senescence phenotype was overcome under these conditions, thus dissociating subtelomeric-DNA hypomethylation per se from the senescence phenotype. In addition, we examined whether the subtelomeric methylation could be restored by expression of a normal copy of full length DNMT3B1 in ICF fibroblasts. Ectopic expression of DNMT3B1 failed to rescue the abnormal hypomethylation at subtelomeres. However, partial rescue of subtelomeric-hypomethylation was achieved by co-expression of DNMT3B1 together with DNA methyltransferase 3-like (DNMT3L), encoding a protein that functions as a stimulator of DNMT3A and DNMT3B. DNMT3B1 and DNMT3L are predominantly expressed during early embryonic development, suggesting that de novo subtelomeric DNA methylation during crucial stages of human embryonic development may be necessary for setting and maintaining normal telomere length.


Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study.
Sapropterin, a synthetic form of tetrahydrobiopterin (BH4), has been reported to improve symptoms in children with autism spectrum disorder (ASD). However, as BH4 is involved in multiple metabolic pathway that have been found to be dysregulated in ASD, including redox, pterin, monoamine neurotransmitter, nitric oxide (NO) and immune metabolism, the metabolic pathway by which sapropterin exerts its therapeutic effect in ASD effect remains unclear. This study investigated which metabolic pathways were associated with symptomatic improvement during sapropterin treatment. Ten participants (ages 2-6 years old) with current social and/or language delays, ASD and a central BH4 concentration 30 nM l(-1) were treated with a daily morning 20 mg kg(-1) dose of sapropterin for 16 weeks in an open-label fashion. At baseline, 8 weeks and 16 weeks after starting the treatment, measures of language, social function and behavior and biomarkers of redox, pterin, monoamine neurotransmitter, NO and immune metabolism were obtained. Two participants discontinued the study, one from mild adverse effects and another due to noncompliance. Overall, improvements in subscales of the Preschool Language Scale (PLS), Vineland Adaptive Behavior Scale (VABS), Aberrant Behavior Checklist (ABC) and autism symptoms questionnaire (ASQ) were seen. Significant changes in biomarkers of pterin, redox and NO were found. Improvement on several subscales of the PLS, VABS, ABC and ASQ were moderated by baseline and changes in biomarkers of NO and pterin metabolism, particularly baseline NO metabolism. These data suggest that behavioral improvement associated with daily 20 mg kg(-1) sapropterin treatment may involve NO metabolism, particularly the status of pretreatment NO metabolism.


[Familial tumoral calcinosis in three patients in the same family].
Tumoral calcinosis is a rare condition characterized by large calcific soft tissue deposits occurring predominantly in a periarticular location. Familial tumoral calcinosis was detected in three members of a family, namely, the father and two offsprings. The father underwent many operations since age 10 for occurrences or recurrences of mass lesions in the right posterior elbow, both hips, left gluteal region, and perineal region. His 16-year-old son underwent his first operation at the age of 10 for a lesion in the posterior elbow, which recurred at the same site and required another operation two years later. He underwent subsequent surgeries for lesions that appeared in the right elbow and right dorsal foot. Finally, the 12-year-old daughter was treated with surgery for a lesion in the right dorsal foot. In all the patients, pathologic diagnoses of all surgical specimens were reported as tumoral calcinosis. All had normocalcemia, hyperphosphatemia, and D hypervitaminosis.


Divergent Network Patterns of Amyloid-β Deposition in Logopenic and Amnestic Alzheimer's Disease Presentations.
Despite divergent clinical features, language and amnestic presentations of Alzheimer's disease (AD) appear to show comparable regional amyloid-β (Aβ) burden. By using a statistical network approach, we aimed to identify complex network patterns of Aβ deposition and explore the effect of apolipoprotein E (APOE) ε4 allele on cortical Aβ burden across AD phenotypes. Sixteen amnestic AD participants and 18 cases with logopenic-variant of primary progressive aphasia (lv-PPA) with a high cortical Aβ burden were selected. A comprehensive clinical assessment, Aβ imaging, and APOE genotyping were performed in all cases. Statistical network analysis was undertaken based on the estimation of sparse partial correlations of Aβ burden between cortical regions. Global and regional network statistical parameters as well as the effect of APOEε4 genotype on cortical Aβ were explored. The two groups showed equivalent distribution of cortical amyloid burden and frequency of APOEε4 genotype. Statistical network analysis, however, demonstrated divergent connectivity properties. The lv-PPA group demonstrated higher mean network degree and shorter characteristic path length than the amnestic AD group. Amnestic AD cases showed connectivity hubs confined to the mesial temporal and prefrontal lobes bilaterally, whereas lv-PPA cases showed hubs scattered across the whole cortical mantle. An interaction effect on total Aβ burden between APOE genotype and AD presentations was also detected. The network analysis reveals interregional network differences not evident using a simple comparison of Aβ burden. This suggests that regional neurotoxic effects may explain the phenotypical differences in AD presentation and that these can be modulated by APOE genotype.


Severe pruritus and myoclonus following intrathecal morphine administration in a dog.
During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated. During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated.


Trends in levels of cholesterol in Japanese children from 1993 through 2001.
Cardiovascular risk factors in children raise the possibility of cardiovascular disease later in life. We attempted to determine the current trends in cardiovascular risk factors among Japanese children. We examined fifth-graders at all the elementary schools in Iwata city in Japan every year from 1993 through 2001. We examined 4,673 boys and 4,484 girls, aged 10-11 years. Height, body weight, body mass index, and serum total cholesterol concentrations were measured. Regression analysis was used to evaluate the trends. The independent variable was the calendar year of the examination. The dependent variables were the anthropometric values and the serum total cholesterol concentration in each individual. The relationships between the year and the prevalence of hyperlipidemia and the prevalence of obesity were also examined. Both the heights of the girls and the body weights of the both sexes were positively associated with the year. The body mass index in both girls and boys also showed positive relationships with the calendar year. In addition, there was an increase in the prevalence of obesity. Concerning the levels of cholesterol, positive regression coefficients were shown between the total cholesterol concentration and the year in both sexes. Furthermore, there was an increase in prevalence of hyperlipidemia. These results indicate that during the past decade among Japanese children involved in the study, both the body mass index and the serum total cholesterol concentrations increased.


Four-rooted mandibular second premolar.
The diverse morphology of the root canal system of the mandibular premolar is a challenge for the clinician to clean, shape and obturate. A case report of a mandibular second premolar with four fused roots which separated at different levels along the apical third of its root and underwent endodontic treatment is presented, along with a review of the literature.


Methods used to evaluate usability of mobile clinical decision support systems for healthcare emergencies: a systematic review and qualitative synthesis.
The aim of this study was to determine the methods and metrics used to evaluate the usability of mobile application Clinical Decision Support Systems (CDSSs) used in healthcare emergencies. Secondary aims were to describe the characteristics and usability of evaluated CDSSs. A systematic literature review was conducted using Pubmed/Medline, Embase, Scopus, and IEEE Xplore databases. Quantitative data were descriptively analyzed, and qualitative data were described and synthesized using inductive thematic analysis. Twenty-three studies were included in the analysis. The usability metrics most frequently evaluated were efficiency and usefulness, followed by user errors, satisfaction, learnability, effectiveness, and memorability. Methods used to assess usability included questionnaires in 20 (87%) studies, user trials in 17 (74%), interviews in 6 (26%), and heuristic evaluations in 3 (13%). Most CDSS inputs consisted of manual input (18, 78%) rather than automatic input (2, 9%). Most CDSS outputs comprised a recommendation (18, 78%), with a minority advising a specific treatment (6, 26%), or a score, risk level or likelihood of diagnosis (6, 26%). Interviews and heuristic evaluations identified more usability-related barriers and facilitators to adoption than did questionnaires and user testing studies. A wide range of metrics and methods are used to evaluate the usability of mobile CDSS in medical emergencies. Input of information into CDSS was predominantly manual, impeding usability. Studies employing both qualitative and quantitative methods to evaluate usability yielded more thorough results. When planning CDSS projects, developers should consider multiple methods to comprehensively evaluate usability.


Early morbidity and mortality of non-therapeutic operations for penetrating trauma.
A retrospective study was performed in order to evaluate early morbidity and mortality associated with non-therapeutic operations for penetrating trauma. Over a 3-year period, 1,062 operations were performed on 1,015 patients for penetrating injury: abdomen 860, chest 103, neck 40, and extremities 58. A total of 230 (21.7%) of these operations were non-therapeutic. The incidence of significant complications directly related to the anesthesia or operation in this group of patients was 8.2 per cent. One patient with an additional major thoracic injury died secondary to complications related to a non-therapeutic abdominal operation (0.4%). The average hospital stay for uncomplicated non-therapeutic operations was 5.1 days, and for patients with complications 11.9 days. We conclude that non-therapeutic operations for penetrating trauma are associated with significant morbidity and mortality that must be considered when designing management schemes for penetrating injury.


Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study.
We sought to identify factors related to short-term outcome of foot ulcers in patients with diabetes treated in a multidisciplinary system until healing was achieved. Consecutively presenting patients with diabetes and worst foot ulcer (Wagner grade 1-5, below ankle) (n = 2,511) were prospectively followed and treated according to a standardised protocol until healing was achieved or until death. The number of patients lost to dropout was 31. The characteristics of the remaining 2,480 patients were: 1,465 men, age 68 +/- 15 years (range 18-96), type 1 diabetes 18%, type 2 diabetes 82% and insulin-treated 62%. The healing rate without major amputation in surviving patients was 90.6% (n = 1,867). Sixty-five per cent (n = 1,617) were healed primarily, 9% (n = 250) after minor amputation and 8% after major amputation; 17% (n = 420) died unhealed. Out of 2,060 surviving patients, 1,007 were neuroischaemic (48.8%). In a multiple regression analysis, primary healing was related to co-morbidity, duration of diabetes, extent of peripheral vascular disease and type of ulcer. In neuropathic ulcers, deep foot infection, site of ulcer and co-morbidity were related to amputation. Amputation in neuroischaemic ulcers was related to co-morbidity, peripheral vascular disease and type of ulcer. Age, sex, duration of diabetes, neuropathy, deformity and duration of ulcer or site of ulcer did not have an evident influence on probability of amputation. Patients with diabetic foot ulcer suffer from multi-organ disease. Factors related to outcome are correspondingly complex.


Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway.
Viral hemorrhagic septicemia virus (VHSV) is one of the most deadly infectious fish pathogens, posing a serious threat to the aquaculture industry and freshwater ecosystems worldwide. Previous work showed that VHSV sub-genotype IVb suppresses host innate immune responses, but the exact mechanism by which VHSV IVb inhibits antiviral response remains incompletely characterized. As with other novirhabdoviruses, VHSV IVb contains a unique and highly variable nonvirion (NV) gene, which is implicated in viral replication, virus-induced apoptosis and regulating interferon (IFN) production. However, the molecular mechanisms underlying the role of IVb NV gene in regulating viral or cellular processes is poorly understood. Compared to the wild-type recombinant (rWT) VHSV, mutant VHSV lacking a functional IVb NV reduced IFN expression and compromised innate immune response of the host cells by inhibiting translation. VHSV IVb infection increased phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in host translation shutoff. However, VHSV IVb protein synthesis proceeds despite increasing phosphorylation of eIF2α. During VHSV IVb infection, eIF2α phosphorylation was mediated via PKR-like endoplasmic reticulum kinase (PERK) and was required for efficient viral protein synthesis, but shutoff of host translation and IFN signaling was independent of p-eIF2α. Similarly, IVb NV null VHSV infection induced less p-eIF2α, but exhibited decreased viral protein synthesis despite increased levels of viral mRNA. These findings show a role for IVb NV in VHSV pathogenesis by utilizing the PERK-eIF2α pathway for viral-mediated host shutoff and interferon signaling to regulate host cell response.


Novel imidazolium-embedded N,N-dimethylaminopropyl-functionalized silica-based stationary phase for hydrophilic interaction/reversed-phase mixed-mode chromatography.
A novel imidazolium-embedded N,N-dimethylaminopropyl-functionalized silica-based stationary phase (Sil-ImCl) was prepared and further used for hydrophilic interaction/reversed-phase mixed-mode chromatography. The Sil-ImCl stationary phase was respectively characterized by Fourier transform infrared spectrometry, thermogravimetric analysis, and element analysis. A variety of hydrophilic or hydrophobic compounds were used to evaluate the retention mechanisms of the developed stationary phase, and the effects of buffer salt concentration and pH of mobile phase on the retention of these compounds were also investigated. The developed stationary phase was successfully applied for separation of nucleosides and nucleic acid bases, water-soluble vitamins, phenols, and positional isomers. Moreover, simultaneous separation of polar and nonpolar compounds was also achieved with high resolution, outperforming the commercially available C8 column and amino column. Furthermore, the Sil-ImCl stationary phase has been successfully applied for separation of secondary metabolites of Hansfordia sinuosae. All these results demonstrate that the Sil-ImCl stationary phase might be promising for separation of complex polar and nonpolar compounds with high efficiency, especially in biological industry.


Thoracolumbar Vertebral Endplate Defect Morphology: A Descriptive Study of Human Cadaveric Spines Using Micro-Computed Tomography.
A descriptive, cross-sectional cadaver study. This study aimed to provide a thorough depiction of vertebral endplate defects classified based on their morphologic features and reported with respect to size, location, and prevalence in the human cadaveric spines of older adults. Back pain has been associated with vertebral endplate defects; however, findings have been inconsistent. This is partially due to miscommunication surrounding the classification of endplate defects observed using clinical imaging, and limited knowledge of the types of defects present on the endplate and their prevalence. A comprehensive study of vertebral endplates is needed to clarify types of structural defects, their character, and prevalence. Using micro-computed tomography, 3-dimensional reconstructed images were created of 409 endplates from 19 cadaveric spines (9 men and 10 women; aged 62-91; T6-S1). Endplate defects were categorized based on their morphology, size, and location to investigate distribution patterns. Seven types of endplate defects were identified: Schmorl nodes, corner fracture or limbus vertebra, other fractures, erosion, jagged surface, calcification, and depressions. Defects were identified on 63.6% of endplates. Multiple defects were present on 19.1% of endplates. Fracture and erosion were the most common defect types. Defects were more common on the endplate cranial to the intervertebral disc and in male specimens ( P = 0.01). Defects were larger in the lumbar spine and the "total area of endplate defect" was larger on the cranial than the caudal endplate in the thoracic spine ( P < 0.05). This is the first study of which we are aware that provides a thorough depiction of the morphology and distribution of endplate defects across the entire lower thoracic and lumbar spine (T6-S1) using micro-computed tomography. Results support the presence of several distinct endplate defect phenotypes with different prevalence rates and provide a reference when considering endplate defects in the elderly.


The Effect of Salivary Contamination on the Shear Bond Strength of Seventh- and Eighth-generation Adhesive Systems.
To compare the effect of salivary contamination on the shear bond strength (SBS) of seventh- and eighth-generation adhesives. Specimens were randomly divided into group I and group II, subdivided into three subgroups of 11 samples. Subgroup IA-seventh-generation uncontaminated (control); adhesive; air-dried; light cured. Subgroup IB-seventh-generation adhesive; saliva application, air-dried; light cured. Subgroup IC-seventh-generation adhesive; saliva application, air-dried, reapplication of adhesive, air-dried, light cured. Subgroup IIA- eighth-generation uncontaminated (control); adhesive, air-dried; light cured. Subgroup IIB- eighth-generation adhesive; saliva application, air-dried; light cured. Subgroup IIC-eighth-generation adhesive, saliva application, air-dried, reapplication of adhesive, air-dried; light cured. Following bonding procedure, composite resin restoration was done and subjected to SBS analysis. Mean SBS of eighth-generation adhesive was higher compared to seventh with and without saliva contamination. Reduction of SBS in seventh- and eighth-generation after saliva contamination was regained by reapplication of adhesive, which was less compared to the control [statistically significant (p < 0.05) for seventh and statistically not significant for eighth-generations]. The eighth-generation adhesives show better SBS with and without saliva contamination and reapplication of eighth-generation adhesives significantly improved the SBS close to the control. Single-step self-etch adhesives are the adhesives which are currently used for bonding composite restorations to dentin. The adhesive bond strength can be adversely affected by moisture contamination, especially by saliva, which can lead to failure of restoration. So, it is imperative to study a material which gives better bond strength and is less affected by salivary contamination and effect of decontamination to regain the bond strength. The study concluded that eighth-generation adhesives showed higher mean SBS with and without saliva contamination and reapplication of eighth-generation adhesives significantly improved the bond strength close to the control group. Mohan MC, Geetha P, Soman D, et al. The Effect of Salivary Contamination on the Shear Bond Strength of Seventh- and Eighth-generation Adhesive Systems. Int J Clin Pediatr Dent 2023;16(S-1):S63-S66.


Magnetically recyclable Bi/Fe-based hierarchical nanostructures via self-assembly for environmental decontamination.
Pristine bismuth ferrite usually possesses weak magnetic properties (e.g., saturation magnetization Ms < 3 emu g(-1)) for practical magnetic separation applications. Herein, a superparamagnetic bismuth ferrite with coral-like hierarchical morphology (BFO-M) was fabricated through methanol solvothermal treatment of the as-prepared Bi2Fe4O9 nanoclusters (P-BFO). The BFO-M shows a higher Ms of ∼31 emu g(-1) compared to that of P-BFO treated in water (BFO-A), in ethanol (BFO-E) and in ethylene glycol (BFO-G). Compared to single-crystalline Bi2Fe4O9 (PS) and Bi2Fe4O9 clusters (NSP), BFO-M shows an excellent organic pollutant removal rate by virtue of its high adsorption capacity and catalytic activity when methyl orange (MO) is used as the model organic pollutant. BFO-M also exhibits good visible light photo-Fenton oxidation rates for pharmaceuticals and pesticides. Even at a low catalyst loading of 0.12 g L(-1), the removal rate of organic pollutants (e.g., 5-fluorouracil, isoproturon) can be ∼99% in 100 min under visible light irradiation. Besides, BFO-M is also a good adsorbent for different kinds of heavy metal ions (Pb(ii), Cr(iii), Cu(ii), As(v), etc.). For example, its maximal adsorption capacity for Pb(ii) is 214.5 mg g(-1). The used BFO-M can be recovered via magnetic separation. The outstanding performances of BFO-M can be ascribed to its coral-like hierarchical morphology which consists of the self-assembly of 1D nanowires (∼6 nm in diameter) and 2D ultrathin nanoflakes (∼4.5 nm in thickness). A schematic illustration of its morphology formation is proposed.


Structure of frozen-hydrated triad junctions: a case study in motif searching inside tomograms.
We used tomographic reconstructions of frozen-hydrated triad junctions to determine the structure of the macromolecular complex associated with calcium release from the sarcoplasmic reticulum (SR), during excitation-contraction coupling. Using a rapid motif search algorithm with a reference motif of the ryanodine receptor (RyR) provided by single-particle cryo-electron microscopy, 49 receptors were located in five tomograms. Following co-alignment of the receptors and division into quadrants centered on the 4-fold symmetry axis, the receptors were classified using multivariate statistics. Global and class averages reveal that the SR membrane in the vicinity of the receptor is highly curved, creating an open vestibule with a gap of 4nm between the receptor pore and the calsequestrin layer in the SR lumen. The in-plane densities in the calsequestrin layer have paracrystalline order, consistent with the packing of calsequestrin dimers in the three-dimensional crystal structure. Faint densities ("tethers") extend to the calsequestrin layer from densities in the SR membrane located 15nm from the symmetry axis of the RyR. In a class average of RyRs with proximal transverse tubules (TT), a cytoplasmic density is observed near the receptor that could represent the most consistent location of tethers observed in tomograms between the SR and TT membranes.


Endogenous prostaglandin D(2) synthesis decreases vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells.
We examined the role of prostaglandin D(2) (PGD(2)) in the expression of vascular cell adhesion molecule-1 (VCAM)-1 following interleukin-1beta (IL-1) stimulation in human umbilical vein endothelial cells (HUVEC) transfected with lipocaline-type PGD(2) synthase (L-PGDS) genes. HUVEC were isolated from human umbilical vein and incubated with 20 U/ml IL-1 and various concentrations of authentic PGD(2). The isolated HUVEC were also transfected with L-PGDS genes by electroporation. The L-PGDS-transfected HUVEC were used to investigate the role of endogenous PGD(2) in IL-1-stimulated VCAM-1 biosynthesis. We also used an anti-PGD(2) antibody to examine whether an intracrine mechanism was involved in VCAM-1 production. PGD(2) and VCAM-1 levels were determined by radio- and cell surface enzyme-immunoassay, respectively. VCAM-1 mRNA was assessed by RT-PCR. IL-1-stimulated VCAM-1 expression by HUVEC was dose-dependently inhibited by authentic PGD(2). L-PGDS gene-transfected HUVEC produced more PGD(2) than HUVEC transfected with the reporter gene alone. IL-1 induced increases in VCAM-1 expression in HUVEC transfected with reporter genes alone. However, this effect was significantly attenuated in the case of IL-1 stimulation of HUVEC transfected with L-PGDS genes, and accompanied by an apparent suppression of VCAM-1 mRNA expression. Neutralization of extracellular PGD(2) by anti-PGD(2)-specific antibody influenced neither VCAM-1 mRNA expression nor VCAM-1 biosynthesis. In conclusion, HUVEC transfected with L-PGDS genes showed increased PGD(2) synthesis. This increase was associated with attenuation of both VCAM-1 expression and VCAM-1 mRNA expression. The results suggest that endogenous PGD(2) decreases VCAM-1 expression and VCAM-1 mRNA expression, probably through an intracrine mechanism.


Preoperative imaging study of the spinal cord vascularization: interest and limits in spine resection for primary tumors.
The necessicity to localize the anterior spinal arteries before anterior approach of the spine stays controversial by orthopaedic surgeons. On the other hand the surgical treatment of thoracoabdominal aneurisms routinely sacrifices many segmental arteries pairs without spinal arteries localization. This, associated with spinal cord protection, results to few neurological complication. However, during vertebrectomies, the roots ligation completely interrupts the spinal cord blood supply at this level. In our experience the spinal arteries localization was systematically done before ninety-eight spine resections. In five cases an anterior radiculomedullary artery was ligated (four anterior radiculomedullary and one great anterior radiculomedullary arteries) without neurological complication, in two cases of extended resection (more than four levels) a neurological complication occurred. No spinal artery was identified at the resection level and the neurological complications were resolutive and did not seem related to definitive vascular problem. These accomplishments lead to discuss the importance of spinal arteries localization and preservation in this surgery. The discovery of an anterior radiculomedullary artery is not a contraindication to en-bloc vertebrectomy at this level, nevertheless in the case of great anterior radiculomedullary artery (Adamkiewicz) the surgical indication must be seriously debated. In fact, this case and those where multilevel resections (more than three levels) are indicated seem the most dangerous situations and the use of the different means of spinal cord protection could be indicated to decrease neurological risk. So before spine resection the spinal arteries localization could improve patient information and give more deciding factors for planning treatment.


Emerging rodent-associated Bartonella: a threat for human health?
Species of the genus Bartonella are facultative intracellular alphaproteobacteria with zoonotic potential. Bartonella infections in humans range from mild with unspecific symptoms to life threatening, and can be transmitted via arthropod vectors or through direct contact with infected hosts, although the latter mode of transmission is rare. Among the small mammals that harbour Bartonella spp., rodents are the most speciose group and harbour the highest diversity of these parasites. Human-rodent interactions are not unlikely as many rodent species live in proximity to humans. However, a surprisingly low number of clinical cases of bartonellosis related to rodent-associated Bartonella spp. have thus far been recorded in humans. The main purpose of this review is to determine explanatory factors for this unexpected finding, by taking a closer look at published clinical cases of bartonellosis connected with rodent-associated Bartonella species, some of which have been newly described in recent years. Thus, another focus of this review are these recently proposed species. Worldwide, only 24 cases of bartonellosis caused by rodent-associated bartonellae have been reported in humans. Possible reasons for this low number of cases in comparison to the high prevalences of Bartonella in small mammal species are (i) a lack of awareness amongst physicians of Bartonella infections in humans in general, and especially those caused by rodent-associated bartonellae; and (ii) a frequent lack of the sophisticated equipment required for the confirmation of Bartonella infections in laboratories that undertake routine diagnostic testing. As regards recently described Bartonella spp., there are presently 14 rodent-associated Candidatus taxa. In contrast to species which have been taxonomically classified, there is no official process for the review of proposed Candidatus species and their names before they are published. This had led to the use of malformed names that are not based on the International Code of Nomenclature of Prokaryotes. Researchers are thus encouraged to propose Candidatus names to the International Committee on Systematics of Prokaryotes for approval before publishing them, and only to propose new species of Bartonella when the relevant datasets allow them to be clearly differentiated from known species and subspecies.


NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn's disease.
To assess whether the polymorphisms of NOD2/CARD15, autophagy-related 16-like 1 (ATG16L1), and interleukin-23 receptor (IL23R) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn's disease (CD). Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15; rs2241880 A/G of ATG16L1, and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymorphism analysis. The polymorphisms rs2241880 A/G of the ATG16L1, and rs11209026 (R381Q) of the IL23R gene in the children's cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without colonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to controls (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. Polymorphism 3020insC in NOD2/CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not early-onset disease.


[Comparative study of determining the sites of airway obstruction in obstructive sleep apnea hypopnea syndrome between real-time CT scans and laryngofiberscope technology].
To compare 256-layer spiral computed tomography (CT) scan in sleep and laryngofiberscope technology for locating obstructive sites of upper airway in patients with obstructive sleep apnea hypopnea syndrome, analyze their advantages and disadvantages and discuss the clinical application values. A total of 59 patients with OSAHS diagnosed by polysomnography underwent spiral CT scan in awake and drug-induced sleep states and laryngofiberscope examination in awake state to assess the sites of airway obstruction. Real-time CT scans were completed successfully in all patients. There were airway obstruction at isolated retropalatal region (real-time CT revealing n = 26, laryngofiberscope revealing n = 34), retropalatal and retroglottal regions simultaneously (real-time CT revealing n = 19, laryngofiberscope revealing n = 10), retropalatal and epiglottal regions simultaneously (real-time CT revealing n = 6, laryngofiberscope revealing n = 2), retropalatal and retroglottal and epiglottal regions simultaneously (real-time CT revealing n = 7, laryngofiberscope revealing n = 3) and no airway obstruction (real-time CT revealing n = 1, laryngofiberscope revealing n = 10). There was not solitary airway obstruction at retroglottal or epiglottal region. The results of real-time CT scans and laryngofiberscope examination were statistically significant different in all regions, and real-time CT scanning compared with laryngofiberscope found more obstructive sites of upper airway [retropalatal region: 98.3% (n = 58) vs 81.4% (n = 48), χ(2) = 5.82, P < 0.05; retroglottal regions: 44.1% (n = 26) vs 22.0% (n = 13), χ(2) = 9.60, P < 0.01; epiglottal regions: 22.0% (n = 13) vs 8.5% (n = 5), χ(2) = 4.90, P < 0.05]. Compared with laryngofiberscope examination,real-time dynamic CT scans in drug-induced sleep state could get more information about anatomy changes of upper airway, providing relatively objective morphological basis for diagnosis and treatment of patients with OSAHS.


MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility.
Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.


Opposing roles for heat and heat shock proteins in macrophage functions during inflammation: a function of cell activation state?
Macrophages function both under normothermia and during periods of body temperature elevation (fever). Whether macrophages sense and respond to thermal signals in a manner which regulates their function in a specific manner is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of mild heating on macrophage cytokine production, and summarize thermally sensitive molecular mechanisms, such as heat shock protein (HSP) expression, which have been identified. Mild, physiologically achievable, hyperthermia has been shown to have both pro- and anti-inflammatory effects on macrophage inflammatory cytokine production and overall it is not clear how hyperthermia or HSPs can exert opposing roles on macrophage function. We propose here that the stage of activation of macrophages predicts how they respond to mild heating and the specific manner in which HSPs function. Continuing research in this area is needed which will help us to better understand the immunological role of body temperature shifts. Such studies could provide a scientific basis for the use of heat in treatment of inflammatory diseases.


Synthesis of nanocrystalline bismuth and its application to the detection of trace metals.
Surface modified carbon strip electrode with Bi nanopowder was suggested for a simultaneous analysis of Zn, Cd, and Pb ions by a square wave anodic stripping voltammetry, and the influence of the modifying Bi mass and particle size on the trace metal response was investigated. The Bi nanopowders with various particle size distributions were synthesized by an optimization of the gas condensation condition, in which a refractory crucible was applied for the evaporation of volatile Bi, and then immobilized on the surface of a working electrode. The result of the stripping measurements shows that when the modifying mass and the particle size of the Bi powder were in the range of 2 to 5 microg/cm2 and less than 300 nm, respectively, a well-developed and reproducible stripping response was obtained. The proposed "mercury-free" carbon strip electrode, modified with Bi nanopowder, is conveniently usable and directly applicable to a trace metal analysis without a pre-deposition of Bi and complicated surface polishing steps.


Diagnostic value of multislice computerized tomography angiography for aortic dissection: A comparison with DSA.
The aim of the present study was to compare multislice computed tomography angiography (MSCTA) and digital subtraction angiography (DSA) in the diagnosis of aortic dissection. In total, 49 patients with aortic lesions received enhanced computed tomography scanning, and three-dimensional (3D) images were reconstructed by volume rendering (VR), maximum intensity projection (MIP), multiplanar reformation (MPR) and curved planar reconstruction (CPR). The display rate of the entry tear site, intimal flap, true and false lumen from each reconstruction method was calculated. For 30 patients with DeBakey type III aortic dissection, the entry tear site and size of the first intimal flap, aortic maximum diameter at the orifice of left subclavian artery (LSCA), distance between the first entry tear site and the orifice of LSCA, and maximum diameter of aortic true and false lumens were measured prior to implantation of endovascular covered stent-grafts. Data obtained by MSCTA and DSA were then compared. For the entry tear site, MPR, CPR and VR provided a display rate of 95.92, 95.92 and 18.37%, respectively, and the display rate of the intimal flap was 100% in the three methods. MIP did not directly display the entry tear site and intimal flap. For true and false lumens, MPR, CPR, and VR showed a display rate of 100%, while MIP only provided a display rate of 67.35%. When MSCTA was compared with DSA, there was a significant difference in the display of entry site number and position (P<0.05), whereas no significant difference was shown in the measurement of aortic maximum diameter at the orifice of LSCA and the maximum diameter of true and false lumens (P>0.05). In conclusion, among the 3D post-processing reconstruction methods of MSCTA used, MPR and CPR were optimal, followed by VR, and MIP. MSCTA may be the preferable imaging method to diagnose aortic dissection and evaluate treatment of endovascular-covered stent-grafting, preoperatively.


SketchMetaFace: A Learning-based Sketching Interface for High-fidelity 3D Character Face Modeling.
Modeling 3D avatars benefits various application scenarios such as AR/VR, gaming, and filming. Character faces contribute significant diversity and vividity as a vital component of avatars. However, building 3D character face models usually requires a heavy workload with commercial tools, even for experienced artists. Various existing sketch-based tools fail to support amateurs in modeling diverse facial shapes and rich geometric details. In this paper, we present SketchMetaFace - a sketching system targeting amateur users to model high-fidelity 3D faces in minutes. We carefully design both the user interface and the underlying algorithm. First, curvature-aware strokes are adopted to better support the controllability of carving facial details. Second, considering the key problem of mapping a 2D sketch map to a 3D model, we develop a novel learning-based method termed "Implicit and Depth Guided Mesh Modeling" (IDGMM). It fuses the advantages of mesh, implicit, and depth representations to achieve high-quality results with high efficiency. In addition, to further support usability, we present a coarse-to-fine 2D sketching interface design and a data-driven stroke suggestion tool. User studies demonstrate the superiority of our system over existing modeling tools in terms of the ease to use and visual quality of results. Experimental analyses also show that IDGMM reaches a better trade-off between accuracy and efficiency.


Annexin A2 and Ahnak control cortical NuMA-dynein localization and mitotic spindle orientation.
Proper mitotic spindle orientation depends on the correct anchorage of astral microtubules to the cortex. It relies on the remodeling of the cell cortex, a process not fully understood. Annexin A2 (Anx2; also known as ANXA2) is a protein known to be involved in cortical domain remodeling. Here, we report that in HeLa cell early mitosis, Anx2 recruits the scaffold protein Ahnak at the cell cortex facing spindle poles, and the distribution of both proteins is controlled by cell adhesion. Depletion of either protein or impaired cortical Ahnak localization result in delayed anaphase onset and unstable spindle anchoring, which leads to altered spindle orientation. We find that Ahnak is present in a complex with dynein-dynactin. Furthermore, Ahnak and Anx2 are required for correct dynein and NuMA (also known as NUMA1) cortical localization and dynamics. We propose that the Ahnak-Anx2 complex influences the cortical organization of the astral microtubule-anchoring complex, and thereby mitotic spindle positioning in human cells. This article has an associated First Person interview with the first author of the paper.


Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism.
The unresponsiveness of metastatic melanoma to conventional chemotherapeutic and biological agents is largely due to the development of resistance to apoptosis. Pyrimethamine belongs to the group of antifolate drugs, and in addition to antiprotozoan effects, it exerts a strong proapoptotic activity, which we recently characterized in human T lymphocytes. However, no data regarding pyrimethamine anticancer activity are available thus far. To this end, we examined the in vitro effects of pyrimethamine on apoptosis, cell cycle distribution, and cell proliferation of human metastatic melanoma cell lines. The in vivo antitumor potential of pyrimethamine was evaluated in a severe combined immunodeficiency (SCID) mouse xenotransplantation model. Our data indicate that pyrimethamine, when used at a clinically relevant concentration, induced apoptosis in metastatic melanoma cells via the activation of the cathepsin B and the caspase cascade (i.e., caspase-8 and caspase-9) and subsequent mitochondrial depolarization. This occurred independently from CD95/Fas engagement. Moreover, pyrimethamine induced a marked inhibition of cell growth and an S-phase cell cycle arrest. Results obtained in SCID mice, injected s.c. with metastatic melanoma cells and treated with pyrimethamine, indicated a significant inhibitory effect on tumor growth. In conclusion, our results suggest that pyrimethamine-induced apoptosis may be considered as a multifaceted process, in which different inducers or regulators of apoptosis are simultaneously implicated, thus permitting death defects of melanoma cells to be bypassed or overcome. On these bases, we hypothesize that pyrimethamine could represent an interesting candidate for the treatment of metastatic melanoma.


Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP.
Strengthening of synaptic connections by NMDA (N-methyl-d-aspartate) receptor-dependent long-term potentiation (LTP) shapes neural circuits and mediates learning and memory. During the induction of NMDA-receptor-dependent LTP, Ca2+ influx stimulates recruitment of synaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, thereby strengthening synapses. How Ca2+ induces the recruitment of AMPA receptors remains unclear. Here we show that, in the pyramidal neurons of the hippocampal CA1 region in mice, blocking postsynaptic expression of both synaptotagmin-1 (Syt1) and synaptotagmin-7 (Syt7), but not of either alone, abolished LTP. LTP was restored by expression of wild-type Syt7 but not of a Ca2+-binding-deficient mutant Syt7. Blocking postsynaptic expression of Syt1 and Syt7 did not impair basal synaptic transmission, reduce levels of synaptic or extrasynaptic AMPA receptors, or alter other AMPA receptor trafficking events. Moreover, expression of dominant-negative mutant Syt1 which inhibits Ca2+-dependent presynaptic vesicle exocytosis, also blocked Ca2+-dependent postsynaptic AMPA receptor exocytosis, thereby abolishing LTP. Our results suggest that postsynaptic Syt1 and Syt7 act as redundant Ca2+-sensors for Ca2+-dependent exocytosis of AMPA receptors during LTP, and thereby delineate a simple mechanism for the recruitment of AMPA receptors that mediates LTP.


Early Cholangitis after Portoenterostomy in Children with Biliary Atresia.
Biliary atresia (BA) is a cholangiodestructive disease of the biliary tree. The first line of treatment is a Kasai portoenterostomy (PE) following which patients may develop cholangitis. We studied the effect of early cholangitis on the outcome of PE, namely jaundice clearance and early native liver survival (NLS). We reviewed the data of all children who developed cholangitis after PE from our prospectively maintained database of children with BA. The standardized treatment of all children in the database is described. The frequency and nature of these episodes were characterized, and the outcome of PE and NLS 1 year after PE was calculated. Of 62 children who underwent PE in our institutions, 27 developed cholangitis. All episodes of cholangitis occurred within 14 months of PE. Of 25 children who cleared jaundice in the overall series, 19 had cholangitis. The incidence of cholangitis was significantly higher in children who cleared jaundice. Nine children who had cholangitis are alive with native livers for more than 1 year after PE. Twelve children had intractable cholangitis. Three of these children are alive with native liver 1 year after PE. In our series, cholangitis occurred in most children who cleared jaundice. Furthermore, the 1-year NLS of children who developed cholangitis was 33%.


Ruthenium(II) carbonyl complexes bearing CCC-pincer bis-(carbene) ligands: synthesis, structures and activities toward recycle transfer hydrogenation reactions.
A new series of ruthenium(II) carbonyl complexes with benzene-based CCC-pincer bis-(carbene) ligands, [((R)CCC(R))Ru(CO)2(X)](0/+) and [((R)CCC(R))Ru(CO)(NN)](+) ((R)CCC(R) = 2,6-bis-(1-alkylimidazolylidene)benzene, R = Me or (n)Bu; X = I, Br, CH3CN, or 6-(aminomethyl)pyridine (ampy); NN = 2·CH3CN, or chelating ampy or bipyridine), was synthesized and fully characterized. X-Ray structure determinations revealed that these eight complexes have pseudo-octahedral configurations around the ruthenium center with the pincer ligand occupying three meridional sites. These complexes prove to be efficient precatalysts demonstrating very good activity and reusability for the transfer hydrogenation of ketones.