Bronchopulmonary lavage cytology in the dog: normal findings.
Fiberoptic bronchoscopy was used to obtain cytologic specimens from all lung lobes of 9 normal Beagle dogs. Three specimen collection techniques (bronchial lavage, bronchial brushing and bronchial pinch biopsy imprints) and two staining procedures (Wright-Giemsa and Papanicolaou) were used and evaluated. Bronchial lavage was the most satisfactory technique for collection of samples from the deep lung and bronchial brushings were preferred for potential bronchial tree mural lesions. Wright-Giemsa was the stain of choice because mast cells could not be identified and eosinophilic leukocytes could be identified only with difficulty in Papanicolaou stained specimens. Total and differential cell counts were determined on all bronchial lavages from all lung lobes in order to establish baseline reference values. Total nucleated cell counts ranged from 260-120/microliters. There were no significant differences among mean total nucleated cell counts for the different lung lobes. Mean total nucleated cell counts were between 420 and 630 cells/microliters. Approximately 95% of all nucleated cells in normal lavages were undifferentiated alveolar macrophages. Most of the other cells seen were neutrophils, eosinophils, possible globule leukocytes and mast cells. Ciliated and nonciliated epithelial cells comprised less than 1% of the total nucleated cell population.


[Treatment of spasticity in cerebral palsy with botulinum toxin].
A review of the pathophysiological and developmental basis, measurement scales and the usefulness of botulinum toxin A injections in selected muscles for the treatment of spasticity in children with cerebral palsy. Cerebral palsy is the most common cause of spasticity in children. The increase in muscle length is achieved through the addition of sarcomeres in series at the level of the muscle tendinous junction. The regulation of the number of sarcomeres seems to be determined by the lengthening of the muscle. The muscle contracture is a shortening of the length of a muscle as a result of a decrease in the number of sarcomeres. Spasticity and motor function assessment scales used in children with cerebral palsy: a) Modified Ashworth scale for the assessment of spasticity; b) modified Tardieu scale for the assessment of dynamic muscle length; c) muscle spasms frequency scale; d) modified Medical Research Council scale for muscle strength; e) hip adductor muscle tone scale; f) global pain scale with affective facial expression represented in a drawing; g) goniometric measurement of the joint range of movement; h) Palisano gross motor function measure; i) observational video gait analysis scale. Recommended guidelines for dosing the botulinum toxin A: 1. Total maximum dose administered per visit up to 15 U/kg or a total of 400 U; 2. Dose range of large muscles 3 to 6 U/kg per visit; 3. Dose range of small muscles 1 to 3 U/kg per visit; 4. Maximum dose per injection site: 50 U dividing the total planned unit dose/muscle into equal amounts/injection site; 5. Frequency: no more than one injection every 3 months, frequently once every 6 or more months. Botulinum toxin A injection is a well tolerated, safe and effective procedure in the treatment of children with spastic cerebral palsy.


Low-Cost Peptide Microarrays for Mapping Continuous Antibody Epitopes.
With the increasing need for understanding antibody specificity in antibody and vaccine research, pepscan assays provide a rapid method for mapping and profiling antibody responses to continuous epitopes. We have developed a relatively low-cost method to generate peptide microarray slides for studying antibody binding. Using a setup of an IntavisAG MultiPep RS peptide synthesizer, a Digilab MicroGrid II 600 microarray printer robot, and an InnoScan 1100 AL scanner, the method allows the interrogation of up to 1536 overlapping, alanine-scanning, and mutant peptides derived from the target antigens. Each peptide is tagged with a polyethylene glycol aminooxy terminus to improve peptide solubility, orientation, and conjugation efficiency to the slide surface.


The effects of oral acetylsalicylic acid on blood fluidity and infusion speed in the cancer patients with PICC.
This study aimed to examine the influence of oral acetylsalicylic acid on blood fluidity and infusion speed in the cancer patients with Peripherally Inserted Central Catheter (PICC). PICC is placed for prolonged chemotherapy of cancer patients. The fibrin sheaths, which consist of cellular substance and non-cellular substance, generate at the place of insertion and grow down all over the catheter. Finally they cover the vent of the catheter and lead to catheter dysfunctions such as the decrease of infusion speed. In addition, the high viscosity status of cancer patients could lead to acute embolization, which adds to the high risk of death. Randomized controlled trial. This research was carried out between April 2013 and January 2014 in the second hospital of Xiangya, Central South University in Changsha, China. Initially 96 cancer participants with PICC were chosen and randomly allocated to experimental and control group. The participants of the experimental group were conducted route PICC maintain technique and took acetylsalicylic acid 100 mg per day after dinner, while the control group received route PICC maintain technique only. The infusion speed and hemorheology indexes of the two groups were tested before our study and at the end of the 2nd and 4th months with several instruments. Repeated measures analysis of variance indicated that taking acetylsalicylic acid orally had significant main effect on high shear blood viscosity and red blood cell deformability index (P < 0.05), and it also had significant main effect as well as time effect on plasma viscosity (P < 0.05); and time had significant main effect as well as interaction effect with oral acetylsalicylic acid on low shear blood viscosity and red blood cell aggregation index (P < 0.05). Repeated measures ANOVA also showed that taking acetylsalicylic acid orally had significant main effect, time effect and interaction effect on infusion speed (P < 0.01). Oral acetylsalicylic acid could improve hemorheology condition and the infusion speed related to fibrin sheath in the cancer patients.


A retrospective audit of young adults who received permanent pacemakers at a teaching hospital in the Western Cape, South Africa.
While most pacemaker implantations occur in older individuals, younger patients also receive pacemakers. In these, degenerative conduction system disease is less likely to be the cause of atrioventricular block (AVB), with other diseases being more common. There is, however, a paucity of data on this group as well as on younger pacemaker recipients that have undergone pacemaker implantation for reasons other than AVB. The aim of this study was to perform an audit of young adult permanent pacemaker recipients. This was a retrospective record review, conducted in the Division of Cardiology at Tygerberg Hospital, Cape Town, South Africa. We included 169 adult patients between the ages of 18 and 60, who received permanent pacemakers between 2010 and 2020. A subgroup analysis of patients 55 years and younger was also performed. Third degree AVB was the most common indication for pacemaker implantation (n = 115; 68%), followed by high degree AVB (n = 23; 13.6%) and sick sinus syndrome (SSS; n = 14; 8.3%). A specific underlying cause for conduction system abnormalities was found in only 25.4% of patients (n = 43), with most of them being 55 years or younger (n = 32; 30.8% of patients ≤ 55 years). Specific causes that were identified included prosthetic valve implantation and/or valve repair (n = 14; 8.3%), myocardial infarction (n = 6; 3.6%), cardiac sarcoidosis (n = 5; 3.0%), coronary artery bypass grafting (n = 3; 1.8%), cardiomyopathy (n = 2; 1.2%), muscular dystrophy (n = 2; 1.2%), congenital heart disease (ventricular septal defect; atrioventricular septal defect; Tetralogy of Fallot; bicuspid aortic valve; n = 6; 3.6%), acute myocarditis (n = 1; 0.6%), atrial myxoma removal (n = 1; 0.6%), planned AV node ablation (n = 2; 1.2%), and following a previous stab in the chest (n = 1; 0.6%). Given that the mean age of our study population was high, the low number of identified underlying causes in the whole cohort (≤60 years) may reflect some AVB due to age related degeneration of the conductions system in the patients 56 to 60 years age, but also raises the possibility that these patients may be less likely to be extensively investigated for an underlying cause than those ≤55 years, where diseases such as sarcoidosis were more readily confirmed. As access to advanced diagnostic tools improves, the percentage of young pacemaker recipients with an underlying cause identified may increase.


Vascular Enlargement as a Predictor of Nodal Involvement in Bladder Cancer.
In bladder cancer (BC), the evaluation of lymph node (LN) involvement at preoperative imaging lacks specificity. Since neoangiogenesis is paired with lymphatic involvement, this study aims to evaluate the presence of perivesical venous ectasia as an indirect sign of LN involvement, together with other conventional CT findings. All the patients who underwent radical cystectomy (RC) for BC between January 2017 and December 2019 with available preoperative contrast-enhanced CT (CECT) within 1 month before surgery were included. Patients without available pathological reports (and pTNM stage) or who underwent neoadjuvant treatments and palliative RC were excluded. Two readers in blind assessed the nodal shape and hilum, the short axis, and the contrast enhancement of suspicious pelvic LNs, the Largest Venous Diameter (LVD) efferent to the lesion, and the extravesical tumor invasion. In total, 38 patients (33 males) were included: 17 pT2, 17 pT3, 4 pT4; pN+: 20/38. LN short axis > 5 mm, LN enhancement, and LVD > 3 mm were significantly correlated with N+ at pathology. LVD > 3 mm had a significantly higher sensitivity and specificity (≥90%, AUC = 0.949) and was an independent predictor (p = 0.0016).


'Head and heart'--neurological and psychological reactions to open heart surgery.
Neurological and psychological reactions to open-heart surgery are widely underestimated phenomena and occur in a much higher incidence than one might expect. When analyzed retrospectively, up to 3.8% of patients who underwent cardiac surgery at the Hamburg University Hospital exhibited these reactions, whereas 35%-50% presented with symptoms and signs of perioperative CNS dysfunctions in prospective studies at our department. About the same percentages are detected in prospective studies of the patients' perioperative psychopathology, stating that a great number of cardiac patients exceed the normal range of anxious, tense, and depressive moods in this setting. The consequences of these findings for the patients' quality of life and the impact for the perioperative management of patients undergoing open-heart surgery are discussed. The current prospective studies, preliminary results of which are presented here, are part of an international interdisciplinary study, initiated to bring more light into the complicated relations between ECC-assisted cardiac surgery, anaesthesiology, neurology and psychology.


Molecular dynamics simulation of cytochrome c3: studying the reduction processes using free energy calculations.
The tetraheme cytochrome c3 from Desulfovibrio vulgaris Hildenborough is studied using molecular dynamics simulation studies in explicit solvent. The high heme content of the protein, which has its core almost entirely made up of c-type heme, presents specific problems in the simulation. Instability in the structure is observed in long simulations above 1 ns, something that does not occur in a monoheme cytochrome, suggesting problems in heme parametrization. Given these stability problems, a partially restrained model, which avoids destruction of the structure, was created with the objective of performing free energy calculations of heme reduction, studies that require long simulations. With this model, the free energy of reduction of each individual heme was calculated. A correction in the long-range electrostatic interactions of charge groups belonging to the redox centers had to be made in order to make the system physically meaningful. Correlation is obtained between the calculated free energies and the experimental data for three of four hemes. However, the relative scale of the calculated energies is different from the scale of the experimental free energies. Reasons for this are discussed. In addition to the free energy calculations, this model allows the study of conformational changes upon reduction. Even if the precise details of the structural changes that take place in this system upon individual heme reduction are probably out of the reach of this study, it appears that these structural changes are small, similarly to what is observed for other redox proteins. This does not mean that their effect is minor, and one example is the conformational change observed in propionate D from heme I when heme II becomes reduced. A motion of this kind could be the basis of the experimentally observed cooperativity effects between heme reduction, namely positive cooperativity.


A semi-Markov multistate cure model for estimating intervention effects in stepped wedge design trials.
Multistate models are useful for studying exposures that affect transitions among a set of health states. However, they can be challenging to apply when exposures are time-varying. We develop a multistate model and a method of likelihood construction that allows application of the model to data in which interventions or other exposures can be time-varying and an individual may to be exposed to multiple intervention conditions while progressing through states. The model includes cure proportions, reflecting the possibility that some individuals will never leave certain states. We apply the approach to analyze patient vaccination data from a stepped wedge design trial evaluating two interventions to increase uptake of human papillomavirus vaccination. The states are defined as the number of vaccine doses the patient has received. We model state transitions as a semi-Markov process and include cure proportions to account for individuals who will never leave a given state (e.g. never receive their next dose). Multistate models typically quantify intervention effects as hazard ratios contrasting the intensities of transitions between states in intervention versus control conditions. For multistate processes, another clinically meaningful outcome is the change in the percentage of the study population that has achieved a specific state (e.g. completion of all required doses) by a specific point in time due to an intervention. We present a method for quantifying intervention effects in this manner. We apply the model to both simulated and real-world data and also explore some conditions under which such models may give biased results.


Monoclonal antibodies to Escherichia coli 50S ribosomes.
Hybridoma cell lines that produce monoclonal antibodies directed against 50S Ribosomal proteins have been isolated. Spleen cells (from BALB/c mice immunized with 50S ribosomal subunits extracted from Escherichia coli) were fused to mouse myeloma cell line SP2/O-Ag 14. The initial screening for antibody producing hybridomas was carried out by a double antibody sandwich method; hybridomas were subsequently cloned in soft agar. Antibodies were characterized by their specific binding to individual 50S ribsomal proteins separated on phosphocellulose columns and in two-dimensional polyacrylamide gels. The assignments were confirmed with purified single ribosomal proteins. Of four clones analyzed thus far, two are identical with specificity for r-protein L5. The other clones produce two different antibodies directed against r-protein L20. Each monoclonal antibody formed ribosome dimers visualizable in the electron microscope. Dimers could be reacted with a different second antibody to form chains containing 8 or more ribosomes, which may be useful for structural studies.


Risk Factors and Methods for Predicting Ovarian Hyperstimulation Syndrome (OHSS) in the in vitro Fertilization.
Ovarian hyperstimulation syndrome (OHSS) is the most severe and life-threatening complication of assisted reproductive technologies (ART). OHSS is based on an excessive ovarian response to ovarian stimulation; however, the pathogenesis has not been fully understood yet. The most serious complications of OHSS are thromboembolic complications and ovarian torsion. The current study describes the risk factors for the development of ovarian hyperstimulation syndrome and proposes a method for specific prediction of this syndrome. This study was designed to investigate 671 therapeutic cycles in the IVF program during 2009-2018. All patients were divided into two groups. Group one (n=56) included women who developed OHSS during the IVF procedure. Group two (n=615) consisted of women who did not have this complication during the IVF procedure. All the observation and examination outcomes were entered into a specially developed questionnaire, and then into a Microsoft Excel spreadsheet. The data were processed by variable statistics using Statistica 10.0. Analyzing of the recorded data revealed that the rate of OHSS was higher in the group of younger women, aged 30.76±3.67 years, in comparison with those aged 32.78±4.40 years in the group of patients without OHSS (p<0.05). The analysis of the initial phase of the reproductive system has confirmed that the group of patients with OHSS had a higher level of prolactin, 462.84±191.56 mIU/L in comparison with 363.43±187.84 mIU/L, which corresponded to the group of women without OHSS (p<0.05). In our results, 7.15±1.04% of cases with OHSS had obesity, while of the patients from the group without OHSS suffered from it (p<0.05). OHSS is the most severe iatrogenic complication of ART, therefore it is extremely important to consider its risk factors and take timely preventive measures. This study has established a high relationship between the studied risk factors and ovarian hyperstimulation syndrome and proposed a model for predicting this syndrome.


Reinforcing properties of lorazepam in normal volunteers.
These experiments were designed to test the positive reinforcing property of a benzodiazepine in normal volunteer subjects. A choice procedure was used to measure preference for lorazepam, a benzodiazepine with a relatively short plasma half-life, over placebo. In separate experiments, subjects were given a choice between three doses of lorazepam (0.5, 1.0 and 2.0 mg, p.o.) and placebo, and in a fourth experiment subjects were given a choice between lorazepam (1.0 mg) and a therapeutically equipotent dose of diazepam (5 mg). Subjective effects of the drugs were monitored using an experimental version of the Profile of Mood States and a shortened version of the Addiction Research Center Inventory. Subjects showed no preference for 0.5 mg lorazepam over placebo (49% drug choice) or for 1.0 mg lorazepam over diazepam (46% lorazepam choice). However, subjects preferred placebo to both 1.0 and 2.0 mg lorazepam (32% and 16% drug choice for 1.0 and 2.0 mg, respectively). Subjective effects were consistent with the drug's known sedative and anxiolytic properties. Relative to diazepam, lorazepam had a longer duration of effect than might be expected from its plasma half-life. Differences in the pharmacokinetic properties of the two drugs account for the results. The results showed that lorazepam is not an effective positive reinforcer in these subjects, suggesting that it also does not have high dependence potential in this population.


Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals.
There have been increasing efforts to relate drug efficacy and disease predisposition with genetic polymorphisms. We present statistical tests for association of haplotype frequencies with discrete and continuous traits in samples of unrelated individuals. Haplotype frequencies are estimated through the expectation-maximization algorithm, and each individual in the sample is expanded into all possible haplotype configurations with corresponding probabilities, conditional on their genotype. A regression-based approach is then used to relate inferred haplotype probabilities to the response. The relationship of this technique to commonly used approaches developed for case-control data is discussed. We confirm the proper size of the test under H(0) and find an increase in power under the alternative by comparing test results using inferred haplotypes with single-marker tests using simulated data. More importantly, analysis of real data comprised of a dense map of single nucleotide polymorphisms spaced along a 12-cM chromosomal region allows us to confirm the utility of the haplotype approach as well as the validity and usefulness of the proposed statistical technique. The method appears to be successful in relating data from multiple, correlated markers to response.


Growth of rat salivary glands after terbutaline or dobutamine.
Six days after commencement of a regimen of twice daily administration of 25, 50, or 75 mg/kg body wt doses of the beta 1 adrenergic agonist, dobutamine, or the beta 2 adrenergic agonist, terbutaline, submandibular and parotid glands of rats were enlarged in size. The beta 1 receptor was responsible for mediation of these changes with both agonists, since the effects of either agonist were prevented when a 10 mg/kg dose of the beta 1 antagonist, atenolol, was injected 20 min prior to the agonists but were not prevented when the beta 2 antagonist butoxamine, was given prior to each agonist. The increase in gland size caused by dobutamine was more marked than that induced by terbutaline; total amount of DNA of the parotid gland was also higher with dobutamine than with terbutaline. The response of the parotid gland to each dose of either agonist was greater than that of the submandibular gland, suggesting that the parotid gland has more beta receptors than does submandibular gland. The data also show that the increase in cell size precedes an increase in cell number. The increase in cell size depends on activation of fewer receptors than are required for the increase in DNA, since at the same dose of dobutamine, e.g., increase in cell size but not cell number was observed; moreover, the same dosage effected an increase in DNA of parotid but not submandibular gland. The data thus show that enlargement of both glands, as well as increase in size and number of their acinar cells, is dependent on activation of beta 1 adrenoceptors only.


ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs.
We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.


Decomposition of supplementary vitamin C in diets compounded for laboratory animals.
Processing may result in losses approaching 20% of the added vitamin C. The extent of these losses depends upon the process and is apparently related to temperature and moisture. Storage losses are also related to processing conditions, and no more than 50% of the vitamin C present in the diet immediately after 6 weeks. These results indicate that the current practice of including 1000 mg/kg of vitamin C in pelleted guinea-pig diets should be satisfactory, provided such diets are used within 6 weeks of manufacture and are stored during this period in conditions conducive to stability, that is dry, not exposed to direct sunlight and, preferably, with an even cool temperature.


Kernel-based learning framework for discovering the governing equations of stochastic jump-diffusion processes directly from data.
Discovering the underlying mathematical-physical equations of complex systems directly from observational data has been a challenging inversion problem. We propose a data-driven framework for identifying dynamical information in stochastic diffusion or stochastic jump-diffusion systems. The probability density function is utilized to relate the Kramers-Moyal expansion to the governing equations, and the kernel density estimation method, improved by the Fourier transform idea, is used to extract the Kramers-Moyal coefficients from the time series of the state variables of the system. These coefficients provide the data expression of the governing equations of the system. Then a data-driven sparse identification algorithm is used to reconstruct the underlying dynamic equations. The proposed framework does not rely on prior assumptions, and all results are obtained directly from the data. In addition, we demonstrate its validity and accuracy using illustrative one- and two-dimensional examples.


Intravascular large B-cell lymphoma in the United States (US): a population-based study using Surveillance, Epidemiology, and End Results program and National Cancer Database.
A population-based study of intravascular large B-cell lymphoma (IVLBCL) in the US was conducted to determine incidence, demographic and clinical characteristics, prognostic factors, and survival compared with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). In the years 2000-2013, the age-adjusted incidence rate of IVLBCL was 0.095 (case/1,000,000). The incidence of IVLBCL increased significantly from 2000 to 2013 (annual percentage change = 9.84, p = 0.002). We identified 344 patients with IVLBCL. The median age at diagnosis was 70 years. The median 1, 3, and 5-year OS rates for IVLBCL were 66.2, 51.8, and 46.3%, respectively. After propensity matching, the 5-year overall survival of IVLBCL was comparable to DLBCL NOS (46.4 versus 46.5%, p = 0.53). On multivariate analysis advanced age, advanced stage and having Medicaid or Medicare insurance predicted worse OS, whereas female gender and use of radiation therapy predicted better OS.


Response to ozone in two lettuce varieties on chlorophyll a fluorescence, photosynthetic pigments and lipid peroxidation.
The effect of different O3 concentrations on two lettuce (Lactuca sativa L.) varieties (Valladolid and Morella) was investigated through chlorophyll (Chl) a fluorescence parameters, photosynthetic pigments (Chl a, b and total carotenoid), lipid peroxidation and crop yield. Ozone fumigation caused: a decrease in maximum quantum yield of photosystem II (PSII) photochemistry (Fv/Fm) in mature leaves, a reduction in the non-cyclic electron flow (phiPSII) and a lower capacity to reoxidize the QA pool (qP). These reductions were significant in the Valladolid var. but not in the Morella var. A significant decrease in Chl a, b and in the total carotenoids was observed in the Valladolid var. but not in the Morella var. mainly under O3 fumigation conditions. We observed that the NPQ parameter did not increase in parallel to the qP reduction seen in the Valladolid var. O3 fumigation with respect to air charcoal filtered air conditions. This fact could be associated with a lower capacity for dissipation of non-radiative excess energy and it may be closely correlated with significant decreases in photosynthetic pigment concentration. A decrease in NPQ from air ozone-free to ozone fumigation in the Morella var. can be explained by the need to maintain the photochemical quenching under O3 stress. It may also be associated with a slight increase in photosynthetic pigments. The differences between the two varieties may indicate that the Valladolid var. is more susceptible to O3 damage.


Dietary lipid requirements of adult lobsters, Homarus americanus (M.E.).
The effects of several dietary lipids on adult American lobster (Homarus americanus) were assessed over a 10 month feeding period. Cod liver oil (CLO) resulted in greater precent weight gains, feed conversion, percent edible meat and higher serum protein and hemocyte counts than either corn oil (CO) or hydrogenated coconut oil (HCO). These differences were probably due to an essential fatty acid (EFA) requirement by the lobster for linolenic series omega3 or other fatty acids present in CLO. The linoleic or omega6 fatty acids of CO appeared to have some sparing effect on several of the EFA deficiency symptoms. It was found that 5% CLO was optimal for mean percent weight gain, molt incidence, feed conversion and hemocyte counts of lobsters. Further increases in dietary CLO to 10% and 15% resulted in no significant improvement of any of the condition indices used. There was a decrease in serum protein and calcium when lobsters were fed a non-saponifiable sterol deficient diet. The addition of 1% cholesterol to the diet raised the serum protein, but resulted in even a greater decrease in the serum calcium level.


Probabilistic computing with voltage-controlled dynamics in magnetic tunnel junctions.
Probabilistic (p-) computing is a physics-based approach to addressing computational problems which are difficult to solve by conventional von Neumann computers. A key requirement for p-computing is the realization of fast, compact, and energy-efficient probabilistic bits. Stochastic magnetic tunnel junctions (MTJs) with low energy barriers, where the relative dwell time in each state is controlled by current, have been proposed as a candidate to implement p-bits. This approach presents challenges due to the need for precise control of a small energy barrier across large numbers of MTJs, and due to the need for an analog control signal. Here we demonstrate an alternative p-bit design based on perpendicular MTJs that uses the voltage-controlled magnetic anisotropy (VCMA) effect to create the random state of a p-bit on demand. The MTJs are stable (i.e. have large energy barriers) in the absence of voltage, and VCMA-induced dynamics are used to generate random numbers in less than 10 ns/bit. We then show a compact method of implementing p-bits by using VC-MTJs without a bias current. As a demonstration of the feasibility of the proposed p-bits and high quality of the generated random numbers, we solve up to 40 bit integer factorization problems using experimental bit-streams generated by VC-MTJs. Our proposal can impact the development of p-computers, both by supporting a fully spintronic implementation of a p-bit, and alternatively, by enabling true random number generation at low cost for ultralow-power and compact p-computers implemented in complementary metal-oxide semiconductor chips.


An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.
Aim: The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagnetic field to alter biologic signaling within cells. Objective: To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). Methods: In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion. Safety was assessed by incidence of adverse events associated with the Voyager. Patients were followed until death. Results: A total of 75 patients were enrolled and treated for at least one day with the Voyager (safety population). Device-related adverse events were uncommon and generally did not result in interruption or withdrawal from treatment. There were no serious adverse events associated with Voyager. A total of 60 patients were treated for at least one month (clinical utility population). The median progression-free survival (PFS) was 17 weeks (4.3 months) in the Voyager only group (n = 24) and 21 weeks (5.3 months) in the Voyager + concurrent therapy group (n = 36). The median overall survival (OS) was 7 months in the Voyager only group and 9 months in the Voyager + concurrent therapy group. In patients treated with Voyager + concurrent therapy, the median OS for patients enrolled with their 1st or 2nd recurrence (n = 26) was 10 months, while in patients enrolled with their 3rd or 4th recurrence (n = 10) OS was 7 months. Conclusion: The data support the safety and feasibility of the Voyager for the treatment of rGBM. Further prospective study of the device is warranted. Trial Registration Number: NCT02296580 (ClinicalTrials.gov).


Persistent memory of diffusing particles.
The variance of the advection-diffusion processes with variable coefficients is exactly decomposed as a sum of dispersion terms and memory terms consisting of correlations between velocity and initial positions. For random initial conditions, the memory terms quantify the departure of the preasymptotic variance from the time-linear diffusive behavior. For deterministic initial conditions, the memory terms account for the memory of the initial positions of the diffusing particles. Numerical simulations based on a global random walk algorithm show that the influence of the initial distribution of the cloud of particles is felt over hundreds of dimensionless times. In case of diffusion in random velocity fields with finite correlation range the particles forget the initial positions in the long-time limit and the variance is self-averaging, with clear tendency toward normal diffusion.


Using social media to engage nurses in health policy development.
To explore nurses' views on future priorities for the profession and to examine social media as an engagement tool to aid policy discussion and development. Nurses are often not directly involved in policy creation and some feel it is a process they cannot easily influence. A descriptive mixed methods study of a Twitter chat hosted by the Chief Nursing Officer for Scotland was undertaken. Data were gathered using an analytics platform and NCapture software. The framework approach aided thematic analysis to draw out themes. Sixty-four people took part in the Twitter chat (#CNOScot) and posted 444 tweets. Nurses called for investment in technology, nursing research, education and mental health. Primary care and advanced practice roles to support older adults with complex health and social care needs were also seen as vital to develop further. Social media can help reach and engage nurses in policy discussion and ensure there is better continuity between policy and practice but some groups risk being excluded using this digital medium. Nursing leaders should consider social media as one of many engagement strategies to ensure nurses and other stakeholders participate in policy debate that informs health strategy development.


[Numerical simulation study of type B aortic dissection using patient-specific reverse engineering and fluid-structure interaction].
Objective: To construct computational fluid model of type B aortic dissection using patient-specific reverse engineering and fluid-structure interaction, and evaluate the application of computational fluid model on aortic remodeling of type B aortic dissection. Methods: Consecutive computed tomographic angiograph data was acquired from a patient with type B aortic dissection at initial diagnosis, 1 week and 6 years after endovascular repair of primary tear entry and 3 months after endovascular repair of distal tear erosion. Three-dimensional model of aortic dissection was reversely reconstructed by Mimics, and then the model was smoothened by Geomagic. Computational fluid dynamic numerical simulation was performed in ANSYS by the means of two-way fluid-structure interaction, and the relation between blood dynamic characteristic and thrombosed remodeling of type B aortic dissection was evaluated. Results: The computational fluid model of type B aortic dissection using patient-specific reverse engineering and fluid-structure interaction method was successfully constructed. Local peak of blood pressure on the convex surface of junction at aortic arch and descending aorta was found. The wall stress was much higher at the false lumen than that at the true lumen, and the peak of wall stress converged on the edge and tear entry of false lumen. After the exclusion of proximal tear entry, the blood streamline was decreased significantly and flowed reversely. Blood flow in the remaining false lumen was retrograded from the entry at left iliac artery and formed turbulence at the top of false lumen, which was benefit for dissection thrombus remodeling. The higher pressure at the false lumen was associated with the new formation of aortic aneurysm at the distal tear. Conclusion: The computational fluid model of aortic dissection based on patient-specific reverse engineering and fluid-structure interaction method can successfully reveal the relatively truly blood dynamic and wall pressure characteristic of type B aortic dissection.


Bone marrow-derived mesenchymal stromal cells promote colorectal cancer cell death under low-dose irradiation.
Radiotherapy remains one of the cornerstones to improve the outcome of colorectal cancer (CRC) patients. Radiotherapy of the CRC not only help to destroy cancer cells but also remodel the tumour microenvironment by enhancing tumour-specific tropism of bone marrow-derived mesenchymal stromal cell (BM-MSC) from the peripheral circulation. However, the role of local MSCs and recruited BM-MSC under radiation were not well defined. Indeed, the functions of BM-MSC without irradiation intervention remained controversial in tumour progression: BM-MSC was previously shown to modulate the immune function of major immune cells, resulting in an impaired immunological sensitivity and to induce an increased risk of tumour recurrence. In contrast, it could also secrete various cytokines and possess anticancer effect. Three co-cultivation modules, 3D culture modules, and cancer organoids were established. The induction of cytokines secretion in hBM-MSCs after irradiation was analysed by ELISA array and flow cytometry. AutoMac separator was used to separate hBM-MSC and CRC automatically. Cells from the co-cultured group and the control group were then irradiated by UV-C lamp and X-ray. Proliferation assay and viability assay were performed. In this study, we show that BM-MSCs can induce the EMT progression of CRC cells in vitro. When irradiated with low doses of ultraviolet radiation and X-rays, BM-MSCs show an anti-tumour effect by secreting certain cytokine (TNF-α, IFN-γ) that lead to the inhibition of proliferation and induction of apoptosis of CRC cells. This was further verified in a 3D culture model of a CRC cell in vitro. Furthermore, irradiation on the co-culture system induced the cleavage of caspase3, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase in cancer cells. The signal pathways above might contribute to the cancer cell death. Taken together, we show that BM-MSC can potentially promote the effect of radiotherapy in CRC.


[Endomyocardial fibrosis associated to Antiphospholipid syndrome. Case report and review].
A 29-year-old man with a history of seizures, was admitted due to an episode of unconsciousness recovered and hypertension with renal disfunction. The electrocardiogram mimicked a hypertrophic cardiomyopathy, but, by Doppler echocardiography, this was discarded because it suggested endomyocardial fibrosis which was confirmed by cardiac magnetic resonance imaging with late enhancement. Since the episode of unconsciousness, brain imaging studies were performed showing vascular sequelae and microangiopathic lesions. These vascular lesions asocciated with renal disfunction with proteinuria within nephrotic range, intensified the search for the etiology arriving to the diagnosis of antiphospholipid syndrome. The patient was discharged with antihypertensive therapy, acenocoumarol, antiepileptic and immunosuppressive drugs.


Barthel Index and Outcome of Open Bypass for Critical Limb Ischemia.
Daily activity should be an important factor to consider when deciding on a treatment strategy for critical limb ischemia (CLI), and we hypothesized that there was a close relationship between activities of daily living (ADL) and prognosis. The aim of this study was to investigate the association between ADL and outcomes of open bypass for CLI.Methods and Results:A total of 226 patients undergoing infrainguinal bypass for CLI between January 2005 and December 2015 were reviewed. They were divided into 2 groups based on Barthel index (BI) at admission (pre-BI; ≥60 and <60) and compared with respect to the incidence of early adverse events and 3-year overall survival and amputation-free survival. Adverse events were more frequently observed in patients with pre-BI <60. Patients with pre-BI <60 had worse long-term outcomes. On multivariable analysis, hypoalbuminemia, end-stage renal disease, and BI at discharge <60 were significant predictors of 3-year outcomes, whereas pre-BI <60 was not a significant predictor of either outcome. It is not BI at admission, but BI at discharge that determines long-term outcome.


Developmental expression profile of quaking, a candidate gene for schizophrenia, and its target genes in human prefrontal cortex and hippocampus shows regional specificity.
Decreased expression of oligodendrocyte/myelin-related (OMR) genes, including quaking (QKI), is a consistent finding in gene expression studies of post-mortem brain from subjects with schizophrenia, and these changes are most prominent in the hippocampus vs. the prefrontal cortex (PFC). Although expression of QKI and other OMR genes has been examined in rodents, little is known about their developmental trajectory in the human brain. Therefore, we examined expression of QKI and several putative mRNA targets of QKI in human PFC and hippocampus at different ages. The pattern of QKI expression in the PFC resembled that reported in rodents, with high QKI-5 in the fetal brain and an increase in QKI-6 and QKI-7 during the period of active myelination, although QKI-5 expression did not decrease substantially during postnatal development in the PFC in humans as it does in rodent brain. Most of the putative QKI target genes also showed linear increases in expression with increasing age in the PFC. In contrast, expression of these genes showed little evidence of developmental regulation in the hippocampus. Correlations between expression levels of the nuclear vs. cytoplasmic QKI isoforms, and putative splicing targets of the former, also differed between tissues. Thus, we speculate that a robust increase in OMR gene expression normally occurs with age in the PFC, but not in the hippocampus, which may explain why decreases in OMR gene expression in schizophrenia are more pronounced in the latter tissue. We also suggest that OMR transcripts might be processed by different splicing proteins in different tissues.


[Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes].
To observe the effects of tetrahydropalmatine, dehydrocorydaline, berberine and palmatine on anoxia and peroxidation injuries in cardiomyocytes, and study the marterial basis of the anti-ischemia effect on myocardium of Rhizoma Corydalis. Neonatal rat cardiomyocytes were cultured in vitro, and subjected to an anoxia-reoxia and the hydrogen peroxide injury models. The four compounds were added into the culture medium. The cell viability was measured by MTT method to determine the safe concentrations and the anti-hydrogen peroxide injury effects of the compounds. The LDH activity in culture mediums was measured with the enzyme reaction dynamics-monitoring method to value the anti-anoxia injury effects of the compounds. At most up to 500 mg x L(-1), tetrahydropalmatine showed no sinificant effect on the cell viability, while dehydrocorydaline, berberine and palmatine significantly decreased the cell viability, exceeding 6.3, 0.6 and 6.3 mg x L(-1), respectively (P < 0.05 or P < 0.01). Tetrahydropalmatine, dehydrocorydaline, berberine and palmatine significantly inhibited LDH leakage induced by anoxia-reoxia injury, at concentrations of 50-100, 1.25-5, 4 and 30 mg x L(-1), respectively (P < 0.05 or P < 0.01). None of the four compounds showed significant effect on the hydrogen peroxide injury. The anti-ischemia effect in myocardium of Rhizoma Corydalis is related to the direct protective effects on cardiomyocytes of its components, tetrahydropalmatine, dehydrocorydaline, berberine and palmatine, amomg which tetrahydropalmatine and dehydrocorydaline are the most important, the former with high safety and low efficacy, while the latter with low safety and high efficacy. And the direct protective effects on cardiomyocytes of these four components may be attained through mechanisms other than anti-peroxidation.


Arctium lappa L. root polysaccharides ameliorate CCl4-induced acute liver injury by suppressing oxidative stress, inflammation and apoptosis.
In this study, water-soluble polysaccharides purified from burdock root were used to intervene in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) of BRL3A hepatocytes and rats. Our results indicated that CCl4 significantly inhibited hepatocyte viability and upregulated the expression of reactive oxygen species (ROS), malondialdehyde (MDA), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and the pro-apoptotic protein Bax. However, Arctium lappa L. root polysaccharides (ALP) could effectively ameliorate liver function and histopathology, oxidative stress, and inflammatory markers. In addition, ALP reduced the expression of apoptotic markers and promoted the proliferation of damaged hepatocytes. In conclusion, ALP possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation and apoptosis in ALI.


Development of a competitive indirect enzyme-linked immunosorbent assay based on monoclonal antibodies for the detection of 2-dodecylcyclobutanone in irradiated beef.
A highly sensitive and specific competitive indirect enzyme-linked immunosorbent assay (ciELISA) based on monoclonal antibodies was developed for the detection of 2-dodecylcyclobutanone (2-DCB), a chemical marker for irradiated lipid-containing foods. 2-Oxocyclobutane undecanoic acid was used as an alternative to 2-DCB and conjugated to BSA and OVA via a conventional carbodiimide condensation reaction to prepare the immunogen and the coating antigen for 2-DCB. The monoclonal antibody against 2-DCB was obtained using the hybridoma technique, with a high specificity and low cross-reactivity for 2-tetradecylcyclobutanone (2-TCB; <8%) and other structurally related compounds (<0.1%). The ciELISA method was applicable at optimal experimental conditions of 0.001-100 μg/mL 2-DCB in a buffer solution, with an IC50 value of 0.25 μg/mL and a limit of detection (defined as the IC20) of approximately 0.004 μg/mL. The recovery efficiency of 2-DCB from ground beef patties ranged from 84.4 to 109.8%. The intra-assay and interassay coefficients of variation were <10.0 and <12.0%, respectively. The proposed method was validated by gas chromatography-mass spectrometry with high correlation. The same method was used to detect 2-DCB in ground beef patties irradiated at 0.5, 1.0, 3.0, 5.0, and 7.0 kGy; the 2-DCB concentration linearly increased with the radiation dose.


Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.
The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions.


Postoperative residual curarization with cisatracurium and rocuronium infusions.
Monitoring of neuromuscular blockade still often relies on clinical judgement. Moreover, there are substantial national differences in the use of agents to 'reverse' their effects. We investigated the recovery characteristics and incidence of postoperative residual curarization after cisatracurium and rocuronium infusions for long duration interventions without systematic antagonism. In 30 patients undergoing major surgery, we measured infusion dose requirements for rocuronium and cisatracurium during propofol anaesthesia. Infusions were discontinued at the beginning of surgical closure; spontaneous recovery of neuromuscular function was awaited in both groups. Neostigmine (50 microg kg(-1)) was administered only when a patient started to wake without a train-of-four ratio (TOF) of 0.9. In the cisatracurium and rocuronium groups, four (27%) and one (7%) patients, respectively, had a TOF ratio > or = 0.9 at the end of surgery. The TOF ratio in each group at that time was 51 +/- 32% for cisatracurium and 47 +/- 31% for rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of reversal was 63 +/- 7% for cisatracurium and 40 +/- 19% for rocuronium (P = 0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10 +/- 9 min for cisatracurium and 18 +/- 13 min for rocuronium (P = n.s.). Patients receiving a cisatracurium or rocuronium infusion have a high incidence of postoperative residual curarization when the block is not antagonized. When 'reversal' is not attempted, cisatracurium seems to be safer than rocuronium.


Performance monitoring in obsessive-compulsive disorder and social anxiety disorder.
Overactive performance monitoring, indexed by greater error-related brain activity, has been frequently observed in individuals with obsessive-compulsive disorder (OCD). Similar alterations have been found in individuals with major depressive and generalized anxiety disorders. The main objective was to extend these findings by investigating performance monitoring in individuals with social anxiety disorder (SAD) and to evaluate the specificity of performance-monitoring changes in OCD. Event-related potentials were used to examine error-related brain activity during a flanker task in 24 individuals with OCD, 24 individuals with SAD, and 24 healthy controls with no history of neurological or psychiatric disorders. Error-related negativity (ERN) and correct-related negativity served as electrophysiological indicators for performance monitoring. Enhanced ERN was expected for both clinical groups, but differential associations with clinical symptoms were explored. ERN amplitudes were larger in individuals with OCD and SAD than in healthy controls. Correlational analyses did not reveal significant associations between ERN and clinical symptomatology in OCD, but a significant correlation with depressive symptoms was found in the SAD group. These findings further strengthen the idea that overactive performance monitoring is independent of clinical symptoms in OCD. Furthermore, it may also represent a transdiagnostic vulnerability indicator, although the relationship with clinical symptoms observed in the SAD group needs additional evaluation.


Regulation of thalamic neurite outgrowth by the Eph ligand ephrin-A5: implications in the development of thalamocortical projections.
The cerebral cortex is parcellated into different functional domains that receive distinct inputs from other cortical and subcortical regions. The molecular mechanisms underlying the specificity of connections of cortical afferents remain unclear. We report here that the Eph family tyrosine kinase receptor EphA5 and the ligand ephrin-A5 may play a key role in the exclusion of the limbic thalamic afferents from the sensorimotor cortex by mediating repulsive interactions. In situ hybridization shows that the EphA5 transcript is expressed at high levels in both cortical and subcortical limbic regions, including the frontal cortex, the subiculum, and the medial thalamic nuclei. In contrast, ephrin-A5 is transcribed abundantly in the sensorimotor cortex. Consistent with the complementary expression, the ligand inhibited dramatically the growth of neurites from neurons isolated from the medial thalamus but was permissive for the growth of neurites from lateral thalamic neurons, which is primarily nonlimbic. Similarly, the growth of neurites from Eph-A5-expressing neurons isolated from the subiculum was inhibited by ephrin-A5. Our studies suggest that the Eph family ligand ephrin-A5 serves as a general inhibitor of axonal growth from limbic neurons, which may serve to prevent innervation of inappropriate primary sensorimotor regions, thus contributing to the generation of specificity of thalamic cortical afferents.


Pre-operative functional status as a predictor of morbidity and mortality after elective cervical spine surgery.
Patients seeking cervical spine surgery are thought to be increasing in age, comorbidities and functional debilitation. The changing demographics of this population may significantly impact the outcomes of their care, specifically with regards to complications. In this study, our goals were to determine the rates of functionally dependent patients undergoing elective cervical spine procedures and to assess the effect of functional dependence on 30-day morbidity and mortality using a large, validated national cohort. A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program data files from 2006 to 2013 was conducted to identify patients undergoing common cervical spine procedures. Multivariate logistic regression models were generated to analyse the independent association of functional dependence with 30-day outcomes of interest. Patients with lower functional status had significantly higher rates of medical comorbidities. Even after accounting for these comorbidities, type of procedure and pre-operative diagnosis, analyses demonstrated that functional dependence was independently associated with significantly increased odds of sepsis (odds ratio (OR) 5.04), pulmonary (OR 4.61), renal (OR 3.33) and cardiac complications (OR 4.35) as well as mortality (OR 11.08). Spine surgeons should be aware of the inherent risks of these procedures with the functionally dependent patient population when deciding on whether to perform cervical spine surgery, delivering pre-operative patient counselling, and providing peri-operative management and surveillance. Cite this article: Bone Joint J 2017;99-B:824-8.


Structural insights into the proton pumping by unusual proteorhodopsin from nonmarine bacteria.
Light-driven proton pumps are present in many organisms. Here, we present a high-resolution structure of a proteorhodopsin from a permafrost bacterium, Exiguobacterium sibiricum rhodopsin (ESR). Contrary to the proton pumps of known structure, ESR possesses three unique features. First, ESR's proton donor is a lysine side chain that is situated very close to the bulk solvent. Second, the α-helical structure in the middle of the helix F is replaced by 3(10)- and π-helix-like elements that are stabilized by the Trp-154 and Asn-224 side chains. This feature is characteristic for the proteorhodopsin family of proteins. Third, the proton release region is connected to the bulk solvent by a chain of water molecules already in the ground state. Despite these peculiarities, the positions of water molecule and amino acid side chains in the immediate Schiff base vicinity are very well conserved. These features make ESR a very unusual proton pump. The presented structure sheds light on the large family of proteorhodopsins, for which structural information was not available previously.


Ameloblastic fibro-odontoma: a case report.
Ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor consisting of both ectodermal and mesenchymal components. It occurs predominantly in children and adolescents, especially in the mandibular posterior region. Histopathologically, AFO exhibits the combination of ameloblastic fibroma-like tissue and complex odontoma. A case of AFO in a 1-year-old child was presented. It produced an expansile lesion over the upper right anterior region and showed typical histopathological features of AFO. She was treated by enucleation with no recurrence observed after a follow-up period of 1 year.


Efficacy of a Self-Hypnotic Relaxation App on Pain and Anxiety in a Randomized Clinical Trial: Results and Considerations on the Design of Active and Control Apps.
Despite an explosion of mobile app offerings for management of pain and anxiety, the evidence for effectiveness is scarce. Placebo-controlled trials are the most desirable but designing inactive placebo apps can be challenging. For a prospective randomized clinical trial with 72 patients in a craniofacial pain center, we created an app with self-hypnotic relaxation (SHR) for use with iOS and Android systems. A placebo background audio (BA) app was built with the same look and functionality. Both iOS and Android SHR apps alone and in comparison to the BA group significantly reduced pain and anxiety during the waiting-room time. The Android BA app significantly reduced anxiety but not pain. The iOS BA app affected neither pain nor anxiety, functioning as an ideal placebo. Usage analysis revealed that different default approaches of the iOS and Android devices accounted for the difference in results.


Whole Genome Analysis and Targeted Drug Discovery Using Computational Methods and High Throughput Screening Tools for Emerged Novel Coronavirus (2019-nCoV).
A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.


Regulation of signal transduction through protein cysteine oxidation.
The production of reactive oxygen species (ROS) accompanies many signaling events. Antioxidants and ROS scavenging enzymes in general have effects that indicate a critical role for ROS in downstream signaling, but a mechanistic understanding of the contribution of ROS as second messengers is incomplete. Here, the role of reactive oxygen species in cell signaling is discussed, emphasizing the ability of ROS to directly modify signaling proteins through thiol oxidation. Examples are provided of protein thiol modifications that control signal transduction effectors that include protein kinases, phosphatases, and transcription factors. Whereas the effects of cysteine oxidation on these proteins in experimental systems is clear, it has proven more difficult to demonstrate these modifications in response to physiologic stimuli. Improved detection methods for analysis of thiol modification will be essential to define these regulatory mechanisms. Bridging these two areas of research could reveal new regulatory mechanisms in signaling pathways, and identify new therapeutic targets.


Gene network analysis to determine the effect of hypoxia-associated genes on brain damages and tumorigenesis using an avian model.
Hypoxia refers to the condition of low oxygen pressure in the atmosphere and characterization of response to hypoxia as a biological complex puzzle, is challenging. Previously, we carried out a comparative genomic study by whole genome resequencing of highland and lowland Iranian native chickens to identify genomic variants associated with hypoxia conditions. Based on our previous findings, we used chicken as a model and the identified hypoxia-associated genes were converted to human's orthologs genes to construct the informative gene network. The main goal of this study was to visualize the features of diseases due to hypoxia-associated genes by gene network analysis. It was found that hypoxia-associated genes contained several gene networks of disorders such as Parkinson, Alzheimer, cardiomyopathy, drug toxicity, and cancers. We found that biological pathways are involved in mitochondrion dysfunctions including peroxynitrous acid production denoted in brain injuries. Lewy body and neuromelanin were reported as key symptoms in Parkinson disease. Furthermore, calmodulin, and amyloid precursor protein were detected as leader proteins in Alzheimer's diseases. Dexamethasone was reported as the candidate toxic drug under the hypoxia condition that implicates diabetes, osteoporosis, and neurotoxicity. Our results suggested DNA damages caused by the high doses of UV radiation in high-altitude conditions, were associated with breast cancer, ovarian cancer, and colorectal cancer. Our results showed that hypoxia-associated genes were enriched in several gene networks of disorders including Parkinson, Alzheimer, cardiomyopathy, drug toxicity, and different types of cancers. Furthermore, we suggested, UV radiation and low oxygen conditions in high-altitude regions may be responsible for the variety of human diseases.


Cortisol response and ovarian hormones in juvenile and cycling female Cebus monkeys: effect of stress and dexamethasone.
We examined cortisol profiles in relation to ovarian hormones and their response to a repeated composite stressor with and without dexamethasone suppression. To evaluate the day-to-day changes in circulating cortisol relative to ovarian hormones, we subjected five adult female Cebus apella monkeys daily to restraint, sedation, transport to a neighboring room for femoral venipuncture, and return to the cage throughout the menstrual cycle. The cortisol response to the repeated stressor for blood collection, its relationship with the ovarian function, and the effects of dexamethasone were evaluated in six juveniles (18-24 months old) and five adult females in the luteal phase. Blood was sampled at time 0; then the monkeys received the vehicle and their blood was sampled again at 1, 2, 4, and 24 hr. This experiment was repeated 3 weeks later, with dexamethasone (i.m. 2 mg/Kg) injected instead of vehicle. Plasma aliquots were assayed for cortisol, progesterone, and estradiol. The results revealed that from middle infancy and throughout adulthood, hypercortisolism is the norm in female Cebus monkeys. The high cortisol values remained unchanged across the cycle despite the cyclic changes in estradiol and progesterone levels. Juvenile monkeys exhibited a higher cortisol response to stress than adults, and both juvenile and adult monkeys exhibited the typical suppression by dexamethasone. A rapid suppression of progesterone co-occurred in parallel with cortisol after dexamethasone injection in juvenile monkeys, suggesting that most circulating progesterone originates in the adrenals. In contrast, adult females exhibited an overincrement of progesterone levels, in parallel with a rise in cortisol, in response to the stressor, and this effect was exacerbated by dexamethasone. The findings suggest that hypercortisolism is insufficient to disrupt ovarian development toward a normal cyclical function, and that ovarian steroids have no influence on day-to-day circulating cortisol levels. On the other hand, the overincrement of progesterone levels induced by stress and/or glucocorticoids during the early luteal phase is unlikely to interfere with the development of this phase and implantation in this monkey species.


Comparison of structural connectivity in Parkinson's disease with depressive symptoms versus non-depressed: a diffusion MRI connectometry study.
ABSTRACTObjective:Research on psychobiological markers of Parkinson's disease (PD) remains a hot topic. Non-motor symptoms such as depression and REM sleep behavior disorder (RBD) each attribute to a particular neurodegenerative cluster in PD, and might enlighten the way for early prediction/detection of PD. The neuropathology of mood disturbances remains unclear. In fact, a few studies have investigated depression using diffusion magnetic resonance imaging (diffusion MRI). Diffusion MRI of PD patients without comorbid RBD was used to assess whether microstructural abnormalities are detectable in the brain of 40 PD patients with depression compared to 19 patients without depression. Diffusion MRI connectometry was used to carry out group analysis between age- and gender-matched PD patients with and without depressive symptoms. Diffusion MRI connectometry is based on spin distribution function, which quantifies the density of diffusing water and is a sensitive and specific analytical method to psychological differences between groups. A significant difference (FDR = 0.016129) was observed in the left and right uncinate fasciculi, left and right inferior longitudinal fasciculi, left and right fornices, left inferior fronto-occipital fasciculus, right corticospinal tract, genu of corpus callosum, and middle cerebellar peduncle. These results suggest the prominent circuits involved in emotion recognition, particularly negative emotions, might be impaired in comorbid depressive symptoms in PD.


Dual light-emitting diode-based multichannel microscopy for whole-slide multiplane, multispectral and phase imaging.
We report the development of a multichannel microscopy for whole-slide multiplane, multispectral and phase imaging. We use trinocular heads to split the beam path into 6 independent channels and employ a camera array for parallel data acquisition, achieving a maximum data throughput of approximately 1 gigapixel per second. To perform single-frame rapid autofocusing, we place 2 near-infrared light-emitting diodes (LEDs) at the back focal plane of the condenser lens to illuminate the sample from 2 different incident angles. A hot mirror is used to direct the near-infrared light to an autofocusing camera. For multiplane whole-slide imaging (WSI), we acquire 6 different focal planes of a thick specimen simultaneously. For multispectral WSI, we relay the 6 independent image planes to the same focal position and simultaneously acquire information at 6 spectral bands. For whole-slide phase imaging, we acquire images at 3 focal positions simultaneously and use the transport-of-intensity equation to recover the phase information. We also provide an open-source design to further increase the number of channels from 6 to 15. The reported platform provides a simple solution for multiplexed fluorescence imaging and multimodal WSI. Acquiring an instant focal stack without z-scanning may also enable fast 3-dimensional dynamic tracking of various biological samples.


Approximate search for known gene clusters in new genomes using PQ-trees.
Gene clusters are groups of genes that are co-locally conserved across various genomes, not necessarily in the same order. Their discovery and analysis is valuable in tasks such as gene annotation and prediction of gene interactions, and in the study of genome organization and evolution. The discovery of conserved gene clusters in a given set of genomes is a well studied problem, but with the rapid sequencing of prokaryotic genomes a new problem is inspired. Namely, given an already known gene cluster that was discovered and studied in one genomic dataset, to identify all the instances of the gene cluster in a given new genomic sequence. Thus, we define a new problem in comparative genomics, denoted PQ-TREE SEARCH that takes as input a PQ-tree T representing the known gene orders of a gene cluster of interest, a gene-to-gene substitution scoring function h, integer arguments [Formula: see text] and [Formula: see text], and a new sequence of genes S. The objective is to identify in S approximate new instances of the gene cluster; These instances could vary from the known gene orders by genome rearrangements that are constrained by T, by gene substitutions that are governed by h, and by gene deletions and insertions that are bounded from above by [Formula: see text] and [Formula: see text], respectively. We prove that PQ-TREE SEARCH is NP-hard and propose a parameterized algorithm that solves the optimization variant of PQ-TREE SEARCH in [Formula: see text] time, where [Formula: see text] is the maximum degree of a node in T and [Formula: see text] is used to hide factors polynomial in the input size. The algorithm is implemented as a search tool, denoted PQFinder, and applied to search for instances of chromosomal gene clusters in plasmids, within a dataset of 1,487 prokaryotic genomes. We report on 29 chromosomal gene clusters that are rearranged in plasmids, where the rearrangements are guided by the corresponding PQ-trees. One of these results, coding for a heavy metal efflux pump, is further analysed to exemplify how PQFinder can be harnessed to reveal interesting new structural variants of known gene clusters.


[Effects of stimulation of SmI and electroacupuncture on nociceptive responses of the ventrobasal complex].
In order to confirm the idea that the cerebral cortex is involved in acupuncture analgesia through descending modulation, the effects of stimulation of SmI and electroacupuncture on nociceptive responses of VB neurons were investigated. The experiments were carried out on lightly anesthetized rats. Single unit activities of VB neurons were extracellularly recorded with glass microelectrodes. The results showed that both electrical stimulation of SmI (n = 11) and electroacupuncture at left. "Huantiao" (G30) point (n = 11) could inhibit the nociceptive responses of VB neurons and their effects were similar. These results suggested that SmI may play a role in acupuncture analgesia through corticofugal modulation on VB.


Induction of tolerogenic dendritic cells by vitamin D receptor agonists.
Dendritic cells induce and regulate T cell responses, and tolerogenic dendritic cells (DCs) can promote the development of regulatory T cells with suppressive activity. Thus, the possibility to manipulate DCs using different pharmacological or biological agents enables them to exert tolerogenic activities, could be exploited to better control a variety of chronic inflammatory conditions, from autoimmune diseases to allograft rejection. A variety of both biological and pharmacological agents can induce tolerogenic DCs, and several in vitro studies have demonstrated that human regulatory T cells can be induced by DCs manipulated to acquire and/or enhance tolerogenic properties, with in vivo data also accumulating. Within this context, we have explored the immunoregulatory activities of vitamin D receptor (VDR) agonists, secosteroid hormones able to induce tolerogenic DCs and regulatory T cells. Tolerogenic DCs induced by a short treatment with VDR agonists promote CD4(+) CD25(+) Foxp3(+) suppressor T cells that are able to mediate transplantation tolerance and to arrest the development of autoimmune diseases. VDR agonists not only favour the induction of CD4(+) CD25(+) regulatory T cells, but can also enhance their recruitment to inflammatory sites. VDR agonists have been proven effective and safe drugs in a variety of autoimmune disease and graft rejection models, highlighting their potential applicability to chronic inflammatory conditions sustained by autoreactive or alloreactive immune responses. In addition to the topical treatment of psoriasis, a Th1-mediated autoimmune disease of the skin where VDR agonists are the most used topical drugs; these agents might eventually find a broader application in the treatment of inflammatory conditions, where their modulatory effects on DCs enhancing T cells with regulatory functions could turn out to be quite beneficial.


Prognostic value of tissue Doppler-Derived E/e' on early morbid events after cardiac surgery.
The tissue Doppler-derived surrogate for left ventricular diastolic pressure, E/e', has been used to prognosticate outcome in a variety of cardiovascular conditions. In this study, we determined the relationship of intraoperative E/e' to the use of inotropic support, duration of mechanical ventilation (MV), length of intensive care unit stay (ICU-LOS), and total hospital stay (H-LOS) in patients requiring cardiac surgery. The records of 245 consecutive patients were retrospectively reviewed to obtain 205 patients who had intraoperative transesophageal echocardiography examinations prior to coronary artery bypass grafting and/or valvular surgery. Cox proportional hazards and logistic regression models were used to analyze the relation between intraoperative E/e' or LVEF and early postoperative morbidity (H-LOS, ICU-LOS, and MV) and the probability that a patient would require inotropic support. With adjustments for other predictors (female gender, hypertension, diabetes, history of myocardial infarction, emergency surgery, renal failure, procedure type, and length of aortic cross-clamp time), an elevated E/e' ratio (>or=8) was significantly associated with an increased ICU-LOS (49 versus 41 median h, P = 0.037) and need for inotropic support (P = 0.002) while baseline LVEF was associated with inotropic support alone (P < 0.0001). These data suggest that the tissue Doppler-derived index of left ventricular diastolic filling pressure may be a useful indicator for predicting early morbid events after cardiac surgery, and may even provide additional information from that of baseline LVEF. Further, patients with elevated preoperative E/e' may need more careful peri- and postoperative management than those patients with E/e' <8.


Catastrophic microangiopathy induced by high-titre factor VIII inhibitors after liver transplantation for haemophilia A with cirrhosis.
Liver transplantation may induce immune tolerance to factor VIII inhibitors but de novo development of inhibitors after transplantation may cause intractable haemorrhage. We report a patient with mild haemophilia A and high-titre FVIII inhibitors who received an orthotopic liver transplantation for complications of hepatitis C virus cirrhosis. Recombinant activated FVII was used in addition to routine haemostatic agents. Conventional immunosuppression was supplemented with antithymocyte globulin and cyclophosphamide. FVIII inhibitors disappeared from the circulation with liver transplantation but they were found to have bound to the graft endothelium, which became activated and induced catastrophic microangiopathy. A subsequent anamnestic response resulted in FVIII inhibitor titres of 1000 Bethesda Units. Uncontrollable haemorrhage persisted until the recipient's death. In patients with high-titre FVIII inhibitors resilient desensitization is required before liver transplantation.


Genetic characterisation of a cohort of children clinically labelled as GH or IGF1 insensitive: diagnostic value of serum IGF1 and height at presentation.
GH insensitivity (GHI) encompasses growth failure, low serum IGF1 and normal/elevated serum GH. By contrast, IGF1 insensitivity results in pre- and postnatal growth failure associated with relatively high IGF1 levels. From 2008 to 2013, 72 patients from 68 families (45M), mean age 7.1 years (0.4-17.0) with short stature (mean height SDS -3.9; range -9.4 to -1.5), were referred for sequencing. As a genetics referral centre, we have sequenced appropriate candidate genes (GHR, including its pseudoexon (6Ψ), STAT5B, IGFALS, IGF1, IGF1R, OBSL1, CUL7 and CCDC8) in subjects referred with suspected GHI (n=69) or IGF1 insensitivity (n=3). Mean serum IGF1 SDS was -2.7 (range -0.9 to -8.2) in GHI patients and 2.0, 3.7 and 4.4 in patients with suspected IGF1 insensitivity. Out of 69 GHI patients, 16 (23%) (19% families) had mutations in GH-IGF1 axis genes: homozygous GHR (n=13; 6 6Ψ, two novel IVS5ds+1 G to A) and homozygous IGFALS (n=3; one novel c.1291delT). In the GHI groups, two homozygous OBSL1 mutations were also identified (height SDS -4.9 and -5.7) and two patients had hypomethylation in imprinting control region 1 in 11p15 or mUPD7 consistent with Silver-Russell syndrome (SRS) (height SDS -3.7 and -4.3). A novel heterozygous IGF1R (c.112G>A) mutation was identified in one out of three (33%) IGF1-insensitive subjects. Genotyping contributed to the diagnosis of children with suspected GHI and IGF1 insensitivity, particularly in the GHI subjects with low serum IGF1 SDS (<-2.0) and height SDS (<-2.5). Diagnoses with similar phenotypes included SRS and 3-M syndrome. In 71% patients, no diagnosis was defined justifying further genetic investigation.


Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility.
Dietary excess triggers accumulation of pro-inflammatory microglia in the mediobasal hypothalamus (MBH), but the components of this microgliosis and its metabolic consequences remain uncertain. Here, we show that microglial inflammatory signaling determines the immunologic response of the MBH to dietary excess and regulates hypothalamic control of energy homeostasis in mice. Either pharmacologically depleting microglia or selectively restraining microglial NF-κB-dependent signaling sharply reduced microgliosis, an effect that includes prevention of MBH entry by bone-marrow-derived myeloid cells, and greatly limited diet-induced hyperphagia and weight gain. Conversely, forcing microglial activation through cell-specific deletion of the negative NF-κB regulator A20 induced spontaneous MBH microgliosis and cellular infiltration, reduced energy expenditure, and increased both food intake and weight gain even in absence of a dietary challenge. Thus, microglial inflammatory activation, stimulated by dietary excess, orchestrates a multicellular hypothalamic response that mediates obesity susceptibility, providing a mechanistic rationale for non-neuronal approaches to treat metabolic diseases.


The Relationship between Macular Pigment and Vessel Density in Patients with Type 1 Diabetes Mellitus.
Macular pigment density and microvascular density on optical coherence tomography angiography (OCTA) were measured in a cohort of type 1 diabetes mellitus (T1DM) patients with retinopathy in the attempt to shed light on the pathophysiology of this condition. Eighty-two consecutive eyes of 59 patients with diabetic retinopathy examined at the Eye Clinic of the University of Naples Federico II from November 2016 to April 2017 were enrolled in this prospective study. Eighty normal eyes of 40 age-matched subjects without diabetes mellitus, without a history of glaucoma or evidence of intraocular surgery, and without retinal pathologic features constituted the control group. All patients and controls underwent a complete ophthalmic examination, best corrected visual acuity evaluation according to the ETDRS visual logMAR scale, measurement of intraocular pressure, OCTA, and evaluation of macular pigment. There were no significant age differences between patients and controls. Both macular pigment measurements and vessel density measured by OCTA were significantly lower in patients than in controls. A moderate correlation was found between vessel density in all ETDRS sectors and macular pigment parameters. There was a reduction in macular pigment and in OCTA vessel density in T1DM patients with retinopathy, which may have prognostic value in determining disease progression.


A Multicentre Study of Thromboprophylaxis in Pregnancy.
Venous thromboembolism (VTE) is a leading cause of maternal mortality. The risk increases with increasing maternal age, mode of delivery and medical co-morbidities. Thromboprophylaxis with low molecular weight heparin (LMWH) has been shown to be both safe and efficacious. The aim of this study was to prospectively investigate the incidence of maternal risk factors in pregnant women admitted to hospital, to calculate their VTE risk status and to investigate if they were receiving appropriate thromboprophylaxis. All patients admitted to the participating hospitals on the day of investigation were assessed for risk of VTE on the basis of hospital chart review. Five Hundred and forty women were recruited from 16 hospitals. Almost 32% (31.7%) were receiving thromboprophylaxis with LMWH. Just under 80% of patients were on the correct thromboprophylaxis strategy as defined by the RCOG guideline but 49% were under-dosed. The odds of receiving appropriate thromboprophylaxis were significantly increased if the woman was >35 years 0or with parity>3.


Rho2 is a target of the farnesyltransferase Cpp1 and acts upstream of Pmk1 mitogen-activated protein kinase signaling in fission yeast.
We have previously demonstrated that knockout of the calcineurin gene or inhibition of calcineurin activity by immunosuppressants resulted in hypersensitivity to Cl- in fission yeast. We also demonstrated that knockout of the components of the Pmk1 mitogen-activated protein kinase (MAPK) pathway, such as Pmk1 or Pek1 complemented the hypersensitivity to Cl-. Using this interaction between calcineurin and Pmk1 MAPK, here we developed a genetic screen that aims to identify new regulators of the Pmk1 signaling and isolated vic (viable in the presence of immunosuppressant and chloride ion) mutants. One of the mutants, vic1-1, carried a missense mutation in the cpp1+ gene encoding a beta subunit of the protein farnesyltransferase, which caused an amino acid substitution of aspartate 155 of Cpp1 to asparagine (Cpp1(D155N)). Analysis of the mutant strain revealed that Rho2 is a novel target of Cpp1. Moreover, Cpp1 and Rho2 act upstream of Pck2-Pmk1 MAPK signaling pathway, thereby resulting in the vic phenotype upon their mutations. Interestingly, compared with other substrates of Cpp1, defects of Rho2 function were more phenotypically manifested by the Cpp1(D155N) mutation. Together, our results demonstrate that Cpp1 is a key component of the Pck2-Pmk1 signaling through the spatial control of the small GTPase Rho2.


A wavepacket study of the low-energy charge transfer process in the S(3+) + H reaction using time-resolved electronic densities.
A theoretical investigation of the low-energy charge transfer process induced by the S(3+) + H reaction collision is presented. High level ab initio MRCI/CASSCF quantum chemical methods have been used to evaluate the relevant potential energy curves and non-adiabatic couplings. Using the coupled potentials, the dynamics of the system in the few eV energy range has been investigated by means of time-dependent wavepacket propagations. The main channels involved in the process of charge transfer are identified and an approach to follow in real time the electronic density during the collision is introduced.


Treatment of periodontal disease using xanthan based chlorhexidine gel.
People of all ages are suffering from periodontal disease. It causes indirect damage in the oral cavity. It is of interest to evaluate the efficacy of xanthan-based chlorhexidine gel (Xan-CHX) in patients with mild-severe chronic periodontitis. Five patients with 60 sites were divided in two groups. Group A (treated with SRP) and group B (treated with Chlosite i.e., SRP + CHL). The recorded clinical parameters were Plaque index (PI), Gingival index (GI), Bleeding index (BI), and Clinical attachment Level (CAL) with sub gingival plaque subjected to microbial analysis. Significant reduction was observed in both groups. However, group B (treated with Chlosite i.e., SRP + CHL) showed statistically significant improvement on above mentioned parameters as compared to group A. Data suggest that in the treatment of periodontal disease (viz. PI, GI, BI and CAL) combination of SRP and Chlosite showed added benefits over only SRP.


[Conservative surgical treatment for keratocysts of basal cell naevomatosis. Some results (author's transl)].
Excision of keratocysts of basal cell nevomatosis using the principle of conservative surgical treatment of maxillary cysts is usually followed by good secondary bone reconstruction without recurrence. Certain precautions are however necessary, the most important being the resection of the parts of the gums adherent to the cyst wall (where perhaps the cyst developed and where recurrences are most likely to occur). Any tooth germ which may be attached to the cyst must also be removed. Postoperative follow-up must include supervision of the bone reconstruction and tooth germ which have not yet developed (even in the absence of an image of a cyst) until the end of adolescence. In adult age, however, there is very little risk of new keratocysts cysts developing.


Sleep duration and growth outcomes across the first two years of life in the GUSTO study.
Short sleep duration is thought to be a factor contributing to increased body mass index (BMI) in both school-age children and adults. Our aim was to determine whether sleep duration associates with growth outcomes during the first two years of life. Participants included 899 children enrolled in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Anthropometric data (weight and body length) and parental reports of sleep duration were collected at 3, 6, 9, 12, 18, and 24 months of age. A mixed-model analysis was used to evaluate the longitudinal association of BMI and body length with sleep duration. In subgroup analyses, effects of ethnicity (Chinese, Indian, and Malay) and short sleep at three months of age (≤12 h per day) were examined on subsequent growth measures. In the overall cohort, sleep duration was significantly associated with body length (β = 0.028, 95% confidence interval [CI] 0.002-0.053, p = 0.033), but not BMI, after adjustment for potential confounding factors. Only in Malay children, shorter sleep was associated with a higher BMI (β = -0.042, 95% CI -0.071 to -0.012, p = 0.005) and shorter body length (β = 0.079, 95% CI 0.030-0.128, p = 0.002). In addition, shorter sleep was associated with a higher BMI and shorter body length in children who slept ≤12 h per day at three months of age. The association between sleep duration and growth outcomes begins in infancy. The small but significant relationship between sleep and growth anthropometric measures in early life might be amplified in later childhood.


Predicting the Intention to Pursue Certified Professional Accountancy Qualification Among the Accounting Students.
The global progress empowers the development of new business and expansion of existing business. The availability of sufficient accounting professional are necessary to manage and document the business activities. However, youth are less inclined to purse accounting as profession to keep the progress of global and local economic development. The current study aimed to explore the formation of the intention to pursue Certified Professional Accountancy Qualification (CPAQ) with factor of capabilities, career opportunities, job security with respect to the extended theory of planned behavior (TPB), i.e., attitude, subjective norms and perceived behavioral control. The study adopted a cross-sectional design and collected quantitative data from a total of 339 accounting students from Malaysia using an online survey. The finding revealed that capabilities and career opportunities influenced the students' intention to pursue CPAQ. Meanwhile, perceived behavioral control had significantly affect the students' decision to pursue CPAQ, which is in line with the TPB. The study concentrated on the importance of these factors in influencing the students' intention and decision to pursue CPAQ. The study offered vital implications for accounting educators and educational institutions to promote the accounting profession as choice and students engage in pursuing CPAQ. The Malaysian government should encourage and support accounting students financially for pursuing CPAQ by providing job security and enhancing subjective norms that may enable these students to complete the required professional qualifications. The study's limitations and future research opportunities are documented at the end of this article.


Usefulness and Complications of Needle Knife Fistulotomy as a Rescue Procedure in Patients with Pancreaticobiliary Disease.
Needle knife fistulotomy (NKF) is a technique to facilitate pancreatic and biliary duct access during ERCP. The double-guidewire technique (DGT) is also used in cases of difficult cannulation, but it can increase the incidence of post-ERCP-pancreatitis (PEP). This study examined the success and complication rates of NKF after unsuccessful standard cannulation or DGT in patients with pancreaticobiliary disease. The data of 209 patients who received NKF as a rescue procedure between January 2009 and December 2016 were reviewed retrospectively. The cannulation success and complication rates were assessed. The overall cannulation success rate was 90.4%. The success rates of patients who received NKF after standard cannulation or DGT were similar (82.6% [142/172] and 73.0% [27/37], respectively, p=0.179). Furthermore, there was no significant difference in the incidence of procedure-related adverse events between the two groups (10.5% [18/172] and 16.2% [6/37], respectively, p=0.391). Endoscopic retrograde pancreatic drainage (ERPD) insertion decreased the incidence of PEP (0% [0/16] in ERPD and 14.6% [19/130] in non-ERPD, p=0.132) among patients who received PD cannulation. NKF is an effective and safe method that can be considered for rescue management after the initial failure of standard cannulation or DGT. NKF following standard cannulation can be preferred over NKF following DGT because of the higher success rate and the lower rate of pancreatitis, but the difference was not significant. PD stenting in patients at high risk of PEP can be considered to decrease pancreatitis.


Classification of leprosy into multibacillary and paucibacillary groups: an analysis.
Classification of leprosy patients into multibacillary and paucibacillary determines the duration of their treatment. Misclassification leads to increased risk of relapse due to insufficient treatment if a multibacillary patient is classified as paucibacillary. This also prolongs the time the patient is infective. Over the years, the criteria used for classification (for treatment purpose) of leprosy patients have changed significantly from bacterial index measuring approach through number of skin lesions. The reliability of both of these criteria has been questioned. Several studies have shown that the presence of antibodies to the Mycobacterium leprae-specific antigens correlates with the bacterial load of a leprosy patient. Further, there are reports where results of serology and bacteriological approaches have been found to agree substantially. Thus, serology seems to be a worthwhile convenient alternative tool for classification of leprosy into multibacillary or paucibacillary. Nevertheless, in view of the limitations of various classification criteria, follow-up studies are called for to understand the efficiency of various approaches in preventing relapse after treatment. The method ensuring the lowest rate of relapse could be adopted for future use in classifying these patients.


The bacterial virulence factors VopL and VopF nucleate actin from the pointed end.
VopL and VopF (VopL/F) are tandem WH2-domain actin assembly factors used by infectious Vibrio species to induce actin assembly in host cells. There is disagreement about the filament assembly mechanism of VopL/F, including whether they associate with the filament barbed or pointed end. Here, we used multicolor total internal reflection fluorescence microscopy to directly observe actin assembly with fluorescently labeled VopL/F. In actin monomer assembly reactions, VopL/F exclusively nucleate actin filament assemblies, remaining only briefly associated with the pointed end. VopL/F do not associate with the ends of preassembled filaments. In assembly reactions with saturating profilin, ∼85% of VopL/F molecules also promote nucleation from the pointed end, whereas a smaller fraction (<15%) associate for ∼25 s with the barbed end of preassembled filaments, inhibiting their elongation. We conclude that VopL/F function primarily as actin nucleation factors that remain briefly (∼100 s) associated with the pointed end.


Predicting experimental properties of integral membrane proteins by a naive Bayes approach.
Integral membrane proteins (iMPs) are challenging targets for structure determination because of the substantial experimental difficulties involved in their sample preparation. Accordingly, success rates of large-scale structural genomics consortia are much lower for this class of molecules compared to globular targets, underscoring the pressing need for predictive strategies to identify iMPs that are more likely to overcome laboratory bottlenecks. On the basis of the target status information available in the TargetDB repository, we describe the first large-scale analysis of experimental behavior of iMPs. Using information on recalcitrant and propagating iMP targets as negative and positive sets, respectively, we present naive Bayes classifiers capable of predicting, from sequence alone, those proteins that are more amenable to cloning, expression, and solubilization studies. Protein sequences are represented in the space of 72 features, including amino acid composition, occurrence of amino acid groups, ratios between residue groups, and hydrophobicity measures. Taking into account unequal representation of main taxonomic groups in the TargetDB, sequence database had a beneficial effect on the prediction results. The classifiers achieve accuracies of 70%, 63-70%, and 61% in predicting the amenability of iMPs for cloning, expression, and solubilization, respectively, thus making them useful tools in target selection for structure determination. Our assessment of prediction results clearly demonstrates that classifiers based on single features do not possess acceptable discriminative power and that the experimental behavior of iMPs is imprinted in their primary sequence through relationships between a restricted set of key properties. In most cases, sets of 10-20 protein features were found actually relevant, most notably, the content of isoleucine, valine, and positively-charged residues.


The potential of the coelomic fluid in sea cucumber as an antioxidant.
In a biological system the product of free-radical induced-lipid peroxidation are conjugated dienes (CDs), lipid peroxides and malondialdehyde (MDA). Its control depends on antioxidant activities. Antioxidant defend the body system by controlling the damage caused by the free radicals. This paper describes lipid peroxidation process and antioxidant activities present in three species of holothuroid obtained from the coastal waters of Terengganu, Malaysia. Among the three species studied, the coelomic fluid of Bohadschia mamorata vitiensis contained the highest level of protein (7.24 + 0.04)g/L. The coelomic fluid of Stichopus badionotus Selenka contained the highest level of superoxide dismutase (SOD) (9.46 + 0.99)X 105 IU/g protein, MDA (16.46 + 1.28)nmol/g protein and total antioxidant activities (AOA) (58.81 + 5.70) %. In Stichopus variegatus Semper the coelomic fluid only demonstrated the highest level of CDs (94.19 + 11.34) RU/g protein compared with the other two species. This preliminary study indicated that some form of antioxidant activities are present in the coelomic fluid of holothuroids.