Factors affecting competence for transformation in Staphylococcus aureus.
A chemically defined medium has been developed for isolation of amino acid-requiring mutants of Staphylococcus aureus strain 8325, and for use as a selective medium in transformation assays. Variables affecting transformation of both plasmid and chromosomal markers have been studied. The optimal pH and temperature for transformation are 6.75 to 7.0 and 30 C, respectively. Ca ions are required for transformation, and only cells lysogenic for the phage phi11 can be transformed. Superinfection of competent cells with phi11 does not increase the transformation frequency. Maximal number of transformants is obtained after 20 min of contact between cells and deoxyribonucleic acid. The transformation frequencies for the plasmid marker erythromycin resistance (ero) and the chromosomal markers trp, thy, and cyt are of the same order of magnitude, whereas the frequency for the chromosomal marker tyr is approximately one order of magnitude lower.


The pressure-stabilized polymorph of indium triiodide.
A layered rhombohedral polymorph of indium(III) triiodide is synthesized at high pressure and temperature. The unit cell symmetry and approximate dimensions are determined by single crystal X-ray diffraction. Its R3̄ crystal structure, with a = 7.214 Å, and c = 20.47 Å, is refined by the Rietveld method on powder X-ray diffraction data. The crystal structure is based on InI6 octahedra sharing edges to form honeycomb lattice layers, though with considerable stacking defects. Different from ambient pressure InI3, which has a monoclinic molecular structure and a light-yellow color, high pressure InI3 is layered and has an orange color. The band gaps of both the monoclinic and rhombohedral variants of InI3 are estimated from diffuse reflectance measurements.


Web-based support for self-management strategies versus usual care for people with COPD in primary healthcare: a protocol for a randomised, 12-month, parallel-group pragmatic trial.
The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) may increase the level of physical activity (PA), improve health-related quality of life (HRQoL) and reduce healthcare use. Whether web-based support in addition to prompts (email and SMS) could be used to promote self-management strategies to facilitate behaviour change in people with COPD is not clear. This clinical trial aims to generate evidence on the effect of a web-based solution, the COPD Web, in a cohort of people with COPD in a primary healthcare context. The overall design is a pragmatic randomised controlled trial with preassessments and postassessments (3 and 12 months) and an implementation and user experience evaluation. People with a diagnosis of COPD, treated in primary healthcare will be eligible for the study. A total of 144 participants will be enrolled through advertisment or by healthcare professionals at included primary healthcare units and, after fulfilled baseline assessment, randomised to either control or intervention group. All participants will receive usual care, a pedometer and a leaflet about the importance of PA. Participants in the intervention will, in addition, get access to the COPD Web, an interactive self-managed website that aims to support people with COPD in self-management strategies. They will also continuously get support from prompts with a focus on behaviour change.The effect on participants' PA, dyspnoea, COPD-related symptoms, HRQoL and health economics will be assessed using accelerometer and questionnaires. To identify enablers and barriers for the use of web-based support to change behaviour, semistructured interviews will be conducted in a subgroup of participants at the 3 months follow-up. Ethical approval has been received from the Regional Ethical Review Board in Umeå, Sweden. Dnr 2018-274 and dnr 2019-05572. Findings will be presented at conferences, submitted for publication in peer-reviewed journals and presented to the involved healthcare professionals, participants and patient organisations. NCT03746873.


[Hopopleura edentula (Anoplura, Hoplopleuridae), a parasite of voles of the genus Clethrionomys].
The louse Hoplopleura edentula Fahrennolz occurs not only on the vole Clethrionomys glareolus Schreb. but also on the other members of the genus widely distributed in the USSR, C. rutilus Pall. and C. rufocanus Sund. The characters distinguishing H. edentula from the close species H. acanthopus (Burm.) described from Microtus arvalis Pall. are the differences in the shape of the dorsal lobe of the pleural plate of the third abdominal segment and in the size of the male copulative organ.


Modern management of the cleft lip and palate patient.
Although many hospital-based specialists will be involved in the management of cleft lip and palate patients, the GDP plays a key role in the preservation of the dentition with its supporting alveolar bone. Without this, the ideal treatment objectives of improved aesthetics, good speech, good function and positive self-image of the patient cannot be achieved.


Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review.
Dietary polyphenols constitute a large family of bioactive substances potential beneficial effect on metabolic syndrome (MetS). This review summarizes the results of clinical studies on patients with MetS involving the chronic supplementation of a polyphenol-rich diet, foods, extracts or with single phenolics on the features of MetS (obesity, dyslipidemia, blood pressure and glycaemia) and associated complications (oxidative stress and inflammation). Polyphenols were shown to be efficient, especially at higher doses, and there were no specific foods or extracts able to alleviate all the features of MetS. Green tea, however, significantly reduced body mass index and waist circumference and improved lipid metabolism. Cocoa supplementation reduced blood pressure and blood glucose. Soy isoflavones, citrus products, hesperidin and quercetin improved lipid metabolism, whereas cinnamon reduced blood glucose. In numerous clinical studies, antioxidative and anti-inflammatory effects were not significant after polyphenol supplementation in patients with MetS. However, some trials pointed towards an improvement of endothelial function in patients supplemented with cocoa, anthocyanin-rich berries, hesperidin or resveratrol. Therefore, diets rich in polyphenols, such as the Mediterranean diet, which promote the consumption of diverse polyphenol-rich products could be an effective nutritional strategy to improve the health of patients with MetS. © 2016 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.


Growth inhibition of murine melanoma and human colon carcinoma by recombinant human platelet factor 4.
Although it is well established that angiogenesis is essential to tumor development, no human protein with high specificity and efficacy for prevention of angiogenesis has been characterized. In a previous study, we demonstrated that recombinant platelet factor 4 (rPF 4) inhibited angiogenesis in the chicken chorioallantoic membrane. In the present study, we have extended that finding to the use of recombinant human platelet factor 4 (rHuPF 4) to inhibit solid tumor growth in the mouse. rHuPF 4 effectively suppressed the growth of the B16-F10 murine melanoma in syngeneic C57BL/6J hosts and prevented the growth of primary tumors of both B16-F10 murine melanoma and HCT 116 human colon carcinoma in semisyngeneic CByB6F1/J female athymic nude mice. These two transformed cell lines were completely insensitive to rHuPF 4 in vitro at levels (50 micrograms/mL) that extensively inhibit normal endothelial cell proliferation. The migration of human endothelial cells was also inhibited at these concentrations of rHuPF 4, suggesting a second mechanism by which rHuPF 4 may modulate capillary development. The observed antitumor effects of rHuPF 4 might be due to the inhibition of angiogenesis. This finding could have implications for the development of novel therapeutic approaches to angiogenic diseases. Alternative, and possibly concurrent, mechanisms of the rHuPF 4 antitumor effect include lymphokine-activated killer cell activation and the induction of other cytokines.


Computational drug repositioning of atorvastatin for ulcerative colitis.
Ulcerative colitis (UC) is a chronic inflammatory disorder with limited effective therapeutic options for long-term treatment and disease maintenance. We hypothesized that a multi-cohort analysis of independent cohorts representing real-world heterogeneity of UC would identify a robust transcriptomic signature to improve identification of FDA-approved drugs that can be repurposed to treat patients with UC. We performed a multi-cohort analysis of 272 colon biopsy transcriptome samples across 11 publicly available datasets to identify a robust UC disease gene signature. We compared the gene signature to in vitro transcriptomic profiles induced by 781 FDA-approved drugs to identify potential drug targets. We used a retrospective cohort study design modeled after a target trial to evaluate the protective effect of predicted drugs on colectomy risk in patients with UC from the Stanford Research Repository (STARR) database and Optum Clinformatics DataMart. Atorvastatin treatment had the highest inverse-correlation with the UC gene signature among non-oncolytic FDA-approved therapies. In both STARR (n = 827) and Optum (n = 7821), atorvastatin intake was significantly associated with a decreased risk of colectomy, a marker of treatment-refractory disease, compared to patients prescribed a comparator drug (STARR: HR = 0.47, P = .03; Optum: HR = 0.66, P = .03), irrespective of age and length of atorvastatin treatment. These findings suggest that atorvastatin may serve as a novel therapeutic option for ameliorating disease in patients with UC. Importantly, we provide a systematic framework for integrating publicly available heterogeneous molecular data with clinical data at a large scale to repurpose existing FDA-approved drugs for a wide range of human diseases.


Differential effects of D1 and D2 dopamine agonists on stereotyped locomotion in rats.
The study examines the effect of selective D1 dopamine stimulation with SKF38393 (1.25-10 mg/kg), on stereotyped locomotion induced by the D2 agonist, quinpirole (0.5 mg/kg). Quinpirole induces repeated travel along a few routes in a limited portion of the environment. Co-administration of low doses of SKF38393 (1.25-2.5 mg/kg) produces the following results: the rate of route perseveration is not affected; the area explored expands to encompass the entire periphery of the open field; and, spatial distribution of locomotion is transformed from routes that cross the center under quinpirole to travel only along the edge. Under higher doses of SKF38393, locomotion ceases. These findings suggest that D1 and D2 stimulation may control the spatial organization of locomotion in oppositional rather than synergistic manner.


Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification.
COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus belonging to the Coronaviridade family, a single-strand positive-sense RNA genome, has been spreading around the world and has been declared a pandemic by the World Health Organization. On 17 January 2022, there were more than 329 million cases, with more than 5.5 million deaths. Although COVID-19 has a low mortality rate, its high capacities for contamination, spread, and mutation worry the authorities, especially after the emergence of the Omicron variant, which has a high transmission capacity and can more easily contaminate even vaccinated people. Such outbreaks require elucidation of the taxonomic classification and origin of the virus (SARS-CoV-2) from the genomic sequence for strategic planning, containment, and treatment of the disease. Thus, this work proposes a high-accuracy technique to classify viruses and other organisms from a genome sequence using a deep learning convolutional neural network (CNN). Unlike the other literature, the proposed approach does not limit the length of the genome sequence. The results show that the novel proposal accurately distinguishes SARS-CoV-2 from the sequences of other viruses. The results were obtained from 1557 instances of SARS-CoV-2 from the National Center for Biotechnology Information (NCBI) and 14,684 different viruses from the Virus-Host DB. As a CNN has several changeable parameters, the tests were performed with forty-eight different architectures; the best of these had an accuracy of 91.94 ± 2.62% in classifying viruses into their realms correctly, in addition to 100% accuracy in classifying SARS-CoV-2 into its respective realm, Riboviria. For the subsequent classifications (family, genera, and subgenus), this accuracy increased, which shows that the proposed architecture may be viable in the classification of the virus that causes COVID-19.


An fMRI study of neural interaction in large-scale cortico-thalamic visual network.
To date there is still no proper neuroimaging methods suitable for noninvasively providing both detailed spatial and temporal information of neural interaction across large-scale brain networks. This limitation has impeded the advance of neuroscience research. In an attempt to overcome this challenge, Ogawa et al. applied a paired-stimulus paradigm, which is composed of a pair of stimuli separated by a variable inter-stimulus interval (ISI), to decode temporal information of neural interaction from amplitude modulation of the blood-oxygenation-level-dependent (BOLD) responses elicited by the neural interaction pursued [Ogawa, S., Lee, T.-M., Stepnoski, R., Chen, W., Zhu, X.H., Ugurbil, K., 2000. An approach to probe neural systems interaction by functional MRI at neural time scale down to milliseconds. Proc. Natl. Acad Sci. U S A 97, 11026-11031.]. Although application of this paradigm has been demonstrated in a few publications, most of them only focused on investigating cortico-cortical interaction. Considering the vital roles that cortico-thalamic networks play in brain communication and function, extending the applicability of this method to studying cortico-thalamic neural interaction should be significant. In this study, we applied the paired-visual-stimulus paradigm to simultaneously measure the BOLD amplitude modulations as a function of ISI in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) in the cat brain. The results reveal that both V1 and LGN BOLD responses were significantly suppressed when the visual system was within the refractory period at ISI<or=1 s and the suppression extent was gradually recovered when ISI became longer. Both BOLD and electrophysiological measurements show a facilitatory activity in V1 at ISI approximately 1.5 s, but not in LGN. Furthermore, there was additional and consistent reduction in the LGN BOLD response compared to V1 within the range of ISI below 4 s, which is likely controlled by inhibitory effects through the cortico-geniculate feedback. These findings together suggest that the dynamic fMRI approach applied in this study is sensitive to neuronal inhibitory and facilitatory interactions and it should be useful for noninvasively investigating large-scale cortico-thalamic neural networks.


Friction-lowering capabilities and human subject preferences for a hydrophilic surface coating on latex substrates: implications for increasing condom usage.
Personal lubricants can increase user satisfaction with male condoms by reducing friction and yielding a slippery sensation. However, lubricants pose disadvantages of dilution in physiologic fluids and sloughing away over repeated articulations. To address these drawbacks, a latex surface modification, which becomes lubricious in the presence of physiologic fluid, has been developed and evaluated. This study assesses (i) the frictional performance of the lubricious coating compared to non-coated latex and latex lubricated by personal lubricant, (ii) the level of agreement between human-perceived slipperiness and machine-measured friction, and (iii) human preference for a hypothetical male condom containing the lubricious coating. Friction coefficient of the lubricious coating was 53% lower than that of non-coated latex and approximately equal to that afforded by personal lubricant. A touch test and survey of a small population sample (N = 33) revealed a strong correlation (R 2 = 0.83) between human-perceived slipperiness and machine-measured friction. A majority of participants (73%) expressed a preference for a condom containing the lubricious coating, agreeing that an inherently slippery condom that remained slippery for a long duration would increase their condom usage. Such a coating shows potential to be an effective strategy for decreasing friction-associated pain, increasing user satisfaction and increasing condom usage.


Description of Gluconacetobacter sacchari sp. nov., a new species of acetic acid bacterium isolated from the leaf sheath of sugar cane and from the pink sugar-cane mealy bug.
A new species of the genus Gluconacetobacter, for which the name Gluconacetobacter sacchari sp. nov. is proposed, was isolated from the leaf sheath of sugar cane and from the pink sugar-cane mealy bug, Saccharicoccus sacchari, found on sugar cane growing in Queensland and northern New South Wales, Australia. The nearest phylogenetic relatives in the alpha-subclass of the Proteobacteria are Gluconacetobacter liquefaciens and Gluconacetobacter diazotrophicus, which have 98.8-99.3% and 97.9-98.5% 16S rDNA sequence similarity, respectively, to members of Gluconacetobacter sacchari. On the basis of the phylogenetic positioning of the strains, DNA reassociation studies, phenotypic tests and the presence of the Q10 ubiquinone, this new species was assigned to the genus Gluconacetobacter. No single phenotypic characteristic is unique to the species, but the species can be differentiated phenotypically from closely related members of the acetic acid bacteria by growth in the presence of 0.01% malachite green, growth on 30% glucose, an inability to fix nitrogen and an inability to grow with the L-amino acids asparagine, glycine, glutamine, threonine and tryptophan when D-mannitol was supplied as the sole carbon and energy source. The type strain of this species is strain SRI 1794T (= DSM 12717T).


Poststress measurements of left ventricular function with gated perfusion SPECT: comparison with resting measurements by using a same-day perfusion-function protocol.
To investigate the relationship between the development of ischemia during stress testing and the changes in left ventricular ejection fraction (LVEF) measurements obtained after stress and at rest with a same-day perfusion-function imaging protocol. One hundred twenty-six patients underwent a same-day rest-stress (61%) or stress-rest (39%) protocol and gated single photon emission computed tomography (SPECT). Perfusion analysis was performed with a 12-segment model. Defects were scored (0 = no defect, 1 = mild defect, 2 = moderate defect, and 3 = severe defect); differences between the summed stress and resting scores of greater than three indicated substantial ischemia. Resting and poststress LVEFs correlated significantly (r = 0.97, P <.001); however, patients with and patients without ischemia had significant differences in poststress versus resting LVEFs (-4.0 vs 1.0, respectively; P <.01). In patients with ischemia versus patients without ischemia, subgroup analysis stress-rest (-2.5 vs 1.0, P =.047) and rest-stress (-4.0 vs 1.0, P =.006) protocols yielded similar results. In patients with clinically important stress-induced perfusion abnormalities, the LVEF after stress was significantly lower than the LVEF at rest with same-day rest-stress and stress-rest imaging protocols. In the clinical setting, poststress LVEFs may be lower than true resting measurements, particularly in patients with moderate to severe stress-induced ischemia.


Analytical approximations of the firing rate of an adaptive exponential integrate-and-fire neuron in the presence of synaptic noise.
Computational models offer a unique tool for understanding the network-dynamical mechanisms which mediate between physiological and biophysical properties, and behavioral function. A traditional challenge in computational neuroscience is, however, that simple neuronal models which can be studied analytically fail to reproduce the diversity of electrophysiological behaviors seen in real neurons, while detailed neuronal models which do reproduce such diversity are intractable analytically and computationally expensive. A number of intermediate models have been proposed whose aim is to capture the diversity of firing behaviors and spike times of real neurons while entailing the simplest possible mathematical description. One such model is the exponential integrate-and-fire neuron with spike rate adaptation (aEIF) which consists of two differential equations for the membrane potential (V) and an adaptation current (w). Despite its simplicity, it can reproduce a wide variety of physiologically observed spiking patterns, can be fit to physiological recordings quantitatively, and, once done so, is able to predict spike times on traces not used for model fitting. Here we compute the steady-state firing rate of aEIF in the presence of Gaussian synaptic noise, using two approaches. The first approach is based on the 2-dimensional Fokker-Planck equation that describes the (V,w)-probability distribution, which is solved using an expansion in the ratio between the time constants of the two variables. The second is based on the firing rate of the EIF model, which is averaged over the distribution of the w variable. These analytically derived closed-form expressions were tested on simulations from a large variety of model cells quantitatively fitted to in vitro electrophysiological recordings from pyramidal cells and interneurons. Theoretical predictions closely agreed with the firing rate of the simulated cells fed with in-vivo-like synaptic noise.


Hip arthroplasty in patients with cirrhosis of the liver.
We retrospectively reviewed 45 hip arthroplasties which were performed over a period of 20 years in 38 patients with cirrhosis of the liver. There was a high perioperative 30-day complication rate (26.7%). Advanced cirrhosis was associated with a higher risk of complications (p = 0.004) as also was increased age, a high level of creatinine, a low level of albumin, a low platelet count, ascites, encephalopathy and an increased operative blood loss. The survival of the prosthesis at five years was 77.8% and infection was a major cause of failure. In view of the high rate of early complications and the limited longevity of the prosthesis, surgeons who perform hip arthroplasty on such patients should counsel them appropriately preoperatively.


Ecologically relevant spatial memory use modulates hippocampal neurogenesis.
The adult hippocampus in birds and mammals undergoes neurogenesis and the resulting new neurons appear to integrate structurally and functionally into the existing neural architecture. However, the factors underlying the regulation of new neuron production is still under scrutiny. In recent years, the concept that spatial memory affects adult hippocampal neurogenesis has gained acceptance, although results attempting to causally link memory use to neurogenesis remain inconclusive, possibly owing to confounds of motor activity, task difficulty or training for the task. Here, we show that ecologically relevant, spatial memory-based experiences of food caching and retrieving directly affect hippocampal neurogenesis in mountain chickadees (Poecile gambeli). We found that restricting memory experiences in captivity caused significantly lower rates of neurogenesis, as determined by doublecortin expression, compared with captive individuals provided with such experiences. However, neurogenesis rates in both groups of captive birds were still greatly lower than those in free-ranging conspecifics. These findings show that ecologically relevant spatial memory experiences can directly modulate neurogenesis, separate from other confounds that may also independently affect neurogenesis.


Presepsin Levels of Patients with Crimean-Congo Hemorrhagic Fever.
Levels of presepsin (a soluble cluster of differentiation subtype 14 [CD14]) are thought to increase in cases of bacterial infection. CD14 has also been found to play a role in the pathogenesis of various viral diseases. Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral infection. Our study focuses on presepsin levels as a biomarker for CCHF. Serum presepsin levels in a CCHF group (n = 59) and control group (n = 28) were compared. Patients with CCHF were classified according to severity grading score as having mild, moderate, or severe infection and were allocated to corresponding subgroups (groups 1, 2, and 3, respectively). Presepsin levels were measured in serum samples by using a commercial enzyme-linked immunosorbent assay kit. The mean presepsin levels in the CCHF group as a whole and the healthy group were found to be significantly different (1,499.46 ± 411.96 pg/ml and 430.68 ± 61.21 pg/ml, respectively). The mean presepsin levels of the CCHF subgroups (1, 2 and 3) and the healthy group were also found to be significantly different (1,204.53 ± 371.18, 1,464.21 ± 338.37, 2,007.36 ± 82.18, and 430.68 ± 61.21 pg/ml, respectively) (p < 0.05). We also found that as the severity of the disease increased, the presepsin level also increased. We postulate that the presepsin levels could be used as a supportive biomarker for diagnosis and follow-up of the disease.


A nonparametric two-dimensional display for classification.
A two-dimensional display whose coordinates are related to the distance to the kth-nearest neighbor of each class is presented. Applications of the display to minimum error, minimum cost, minimax, and Neyman-Pearson type classifier designs are given. The display is shown to present risk information in a manner that easily allows the specification of reject regions. Two methods of error estimation using the display, an error counting technique and a risk averaging method, are detailed. It is shown that the classifiers that result are generalizations of the standard k-NN majority vote classifier. As a result of the properties of the display, classifiers can be readily evaluated and modified. In addition, a condensing algorithm that preserves the nearest neighbor error count of any preclassified data set is described. The display is used to graphically illustrate the distance relationships that are central to the algorithm.


Adaptable, turn-on maturation (ATOM) fluorescent biosensors for multiplexed detection in cells.
A grand challenge in biosensor design is to develop a single-molecule, fluorescent protein-based platform that can be easily adapted to recognize targets of choice. Here, we created a family of adaptable, turn-on maturation (ATOM) biosensors consisting of a monobody (circularly permuted at one of two positions) or a nanobody (circularly permuted at one of three positions) inserted into a fluorescent protein at one of three surface loops. Multiplexed imaging of live human cells coexpressing cyan, yellow and red ATOM sensors detected biosensor targets that were specifically localized to various subcellular compartments. Fluorescence activation involved ligand-dependent chromophore maturation with turn-on ratios of up to 62-fold in cells and 100-fold in vitro. Endoplasmic reticulum- and mitochondria-localized ATOM sensors detected ligands that were targeted to those organelles. The ATOM design was validated with three monobodies and one nanobody inserted into distinct fluorescent proteins, suggesting that customized ATOM sensors can be generated quickly.


[An algorithm for psychotropics for the mentally handicapped: psychiatric diagnosis in three stages].
Psychiatric treatment of mentally handicapped patients is still in its infancy because these patients are diagnosed by means of inadequate DSM vignettes that were not developed for such a homogeneous group and that do not have the status of diagnoses based on aetiology and pathophysiology. To raise awareness that the psychiatrist dealing with this group of patients needs to have a thorough knowledge of the syndromes involved which can be accompanied by psychiatric and somatic comorbidity and also needs to have expertise in linked disciplines such as genetics, epileptology and pharmacology. On the basis of the international scientific literature an attempt was made to identify the rationale that underlies the current practice of treating challenging behaviour with a fairly random selection of psychotropics. A diagnostic algorithm was formulated which can help the psychiatrist to provide evidence-based specialised advice on treatment and which can also prevent the occurrence of harm or damage. The top-down orientation of current diagnostic procedures, which tries to link symptoms to an underlying pathology, should be counterbalanced by a bottom-up approach in which the aetiology is the starting point. If this principle is observed, a well-founded proposal about treatment can sometimes be put forward. In all other cases treatment at present is little more than symptomatic pharmacotherapy involving a few well-documented psychotropics.


The Bethesda System for Reporting Thyroid Cytopathology: Validating at Tribhuvan University Teaching Hospital.
Introduction Fine needle aspiration cytopathology (FNAC) is widely used for the stratification of thyroid nodules. Objective The objective of the present study is to validate FNAC reporting based on The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) at our institution and to calculate the risk of malignancy in each category. Methods This was a descriptive cross-sectional study conducted jointly at the Department of Ear, Nose and Throat and at the Department of Pathology for a period of 1.5 years (May 2018 to November 2018). All cases presenting with thyroid swelling in the outpatient department were investigated with ultrasonography (USG) of the neck, thyroid function test, and FNAC. All FNAC reporting was done according to TBSRTC. Results A total of 134 thyroidectomies were performed during the study period. The female to male ratio was 5.3:1. The age ranged from 11 to 74 years old. with a mean age of 51 years old. The FNAC has a specificity of 84.9%, a sensitivity of 89.4%, a positive predictive value of 86.4%, a negative predictive value of 88.2%, and an accuracy of 87.3% in detecting thyroid cancer. The implied risk of malignancy (ROM) in Bethesda II, III, IV, V and VI is 11.7%, 25%,40%,76.6% & 96%, respectively. Conclusion The four studied categories had a ROM comparable to other studies, except for the Bethesda III category. Further studies with larger sample sizes and with the use of USG guidance for the aspiration from the thyroid swelling may give better results by reducing the number of false negative and false positive cases.


Stereospecific opiate-binding sites occur in coated vesicles.
We prepared clathrin-coated vesicles from bovine forebrain utilizing sucrose or deuterium oxide-Ficoll density gradient centrifugation followed by permeation chromatography. Homogeneity was monitored by electron microscopy (EM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). EM revealed that the predominant (up to 98% of the total) organelles were coated vesicles and empty hexagonal baskets. Diameters of the coated vesicles ranged from 37 to 120 nm with a mean of 65.2 +/- 2.2. Upon SDS-PAGE of the coated vesicle fraction, the most prominent band appeared at 180,000 daltons. There were also three additional bands at 100,000, 50,000 and 35,000 daltons, giving the overall pattern characteristic of coated vesicles. Both 0.5 nM tritiated naltrexone and etorphine displayed specific binding to coated vesicles. Naltrexone binding in coated vesicles from gradient fractions was increased 2.5-fold over the original 100,000 X g pellet. An additional 4-fold enrichment in specific binding was observed after permeation chromatography which was concomitant with an increase in the volume density of coated vesicles in electron micrographs. Naltrexone binding was stereospecific and etorphine binding was inhibited by 100 mM NaCl (40%). Both naltrexone and etorphine binding were inhibited by 50 microM guanyl-5'-yl imidodiphosphate (40 to 50%). In summary, purified bovine brain-coated vesicles contained high affinity stereospecific opiate alkaloid-binding sites with characteristic opioid binding properties.


Determination of iron in solutions with the ferric-xylenol orange complex.
Formation of a colored complex between ferric iron and xylenol orange has been used in a variety of applications, but there is disagreement about the number of complexes that exist, their stoichiometry, pH dependence, solvent effects, and other parameters. In this study we investigated the use of the complex to measure micromolar concentrations of iron in aqueous and alcohol solutions. The results show that the optimum wavelength for the measurement is 560 nm, that only a 1:1 ferric:xylenol orange complex forms, and that its molar absorption coefficient is affected by the solvent, the source of the xylenol orange, and the pH. Under the recommended conditions, formation of the complex is completed in less than 5 min and it is stable in several solvents. Its molar absorption coefficient in 25 mM H(2)SO(4) is 20,100 or 14,500 M(-1) cm(-1), depending on the source of the dye. A recommended protocol for the use of the assay is given.


The carbonate-silicate cycle and CO2/climate feedbacks on tidally locked terrestrial planets.
Atmospheric gaseous constituents play an important role in determining the surface temperatures and habitability of a planet. Using a global climate model and a parameterization of the carbonate-silicate cycle, we explored the effect of the location of the substellar point on the atmospheric CO(2) concentration and temperatures of a tidally locked terrestrial planet, using the present Earth continental distribution as an example. We found that the substellar point's location relative to the continents is an important factor in determining weathering and the equilibrium atmospheric CO(2) level. Placing the substellar point over the Atlantic Ocean results in an atmospheric CO(2) concentration of 7 ppmv and a global mean surface air temperature of 247 K, making ∼30% of the planet's surface habitable, whereas placing it over the Pacific Ocean results in a CO(2) concentration of 60,311 ppmv and a global temperature of 282 K, making ∼55% of the surface habitable.


[Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].
To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.


Nuclear expression of β-catenin promotes RB stability and resistance to TNF-induced apoptosis in colon cancer cells.
Tumor necrosis factor (TNF)-α promotes tumor development under chronic inflammation. Because TNF also activates caspase-8, selective inhibition of TNF-induced extrinsic apoptosis would be required for inflammation-associated tumor growth. In a mouse model of inflammation-associated colon carcinogenesis, we found nuclear expression of β-catenin in tumors of wild-type, but not mutant, mice that were made resistant to TNF-induced apoptosis by a germline mutation blocking caspase cleavage of the retinoblastoma (RB) protein, despite similar frequencies of β-catenin exon-3 mutations in these two genetic backgrounds. TNF-induced apoptosis was also attenuated in human colon cancer cell lines with genetically activated β-catenin. However, we found that HCT116 cells, which contain an activated allele of β-catenin but do not express nuclear β-catenin, were sensitive to TNF-induced apoptosis. In HCT116 cells, TNF stimulated efficient RB cleavage that preceded chromatin condensation. In contrast, TNF did not induce RB cleavage in colon cancer cells expressing nuclear β-catenin and these cells could be sensitized to basal and/or TNF-induced apoptosis by the knockdown of β-catenin or RB. In the apoptosis-resistant colon cancer cells, knockdown of β-catenin led to a reduction in the RB protein without affecting RB mRNA. Furthermore, ectopic expression of the caspase-resistant, but not the wild-type, RB re-established resistance to TNF-induced caspase activation in colon cancer cells without β-catenin. Together, these results suggest that nuclear β-catenin-dependent RB stabilization suppresses TNF-induced apoptosis in caspase-8-positive colon cancer cells.


Evolution of molybdenum nitrogenase during the transition from anaerobic to aerobic metabolism.
Molybdenum nitrogenase (Nif), which catalyzes the reduction of dinitrogen to ammonium, has modulated the availability of fixed nitrogen in the biosphere since early in Earth's history. Phylogenetic evidence indicates that oxygen (O2)-sensitive Nif emerged in an anaerobic archaeon and later diversified into an aerobic bacterium. Aerobic bacteria that fix N2 have adapted a number of strategies to protect Nif from inactivation by O2, including spatial and temporal segregation of Nif from O2 and respiratory consumption of O2. Here we report the complement of Nif-encoding genes in 189 diazotrophic genomes. We show that the evolution of Nif during the transition from anaerobic to aerobic metabolism was accompanied by both gene recruitment and loss, resulting in a substantial increase in the number of nif genes. While the observed increase in the number of nif genes and their phylogenetic distribution are strongly correlated with adaptation to utilize O2 in metabolism, the increase is not correlated with any of the known O2 protection mechanisms. Rather, gene recruitment appears to have been in response to selective pressure to optimize Nif synthesis to meet fixed N demands associated with aerobic productivity and to more efficiently regulate Nif under oxic conditions that favor protein turnover. Consistent with this hypothesis, the transition of Nif from anoxic to oxic environments is associated with a shift from posttranslational regulation in anaerobes to transcriptional regulation in obligate aerobes and facultative anaerobes. Given that fixed nitrogen typically limits ecosystem productivity, our observations further underscore the dynamic interplay between the evolution of Earth's oxygen, nitrogen, and carbon biogeochemical cycles. Molybdenum nitrogenase (Nif), which catalyzes the reduction of dinitrogen to ammonium, has modulated the availability of fixed nitrogen in the biosphere since early in Earth's history. Nif emerged in an anaerobe and later diversified into aerobes. Here we show that the transition of Nif from anaerobic to aerobic metabolism was accompanied by both gene recruitment and gene loss, resulting in a substantial increase in the number of nif genes. While the observed increase in the number of nif genes is strongly correlated with adaptation to utilize O2 in metabolism, the increase is not correlated with any of the known O2 protective mechanisms. Rather, gene recruitment was likely a response to more efficiently regulate Nif under oxic conditions that favor protein turnover.


The golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma.
The significance of occult hypoperfusion (OH) in the development of respiratory complications (RC), multiple system organ failure (MSOF), and death, and the effect of rapid identification and correction of OH in the severely injured trauma patient was investigated. A pilot retrospective study and the analysis of a prospective protocol to correct OH were performed. Pilot study: all trauma patients admitted to our Level I trauma center between February and December of 1995, who survived greater than 48 hours, had an Injury Severity Score greater than or equal to 20, and intensive care unit stays greater than 48 hours were evaluated. Prospective study: patients admitted between January 1, 1996, and April 30, 1997, who survived greater than 24 hours, with Injury Severity Score greater than or equal to 20, and who were hemodynamically stable (systolic blood pressure greater than 100, pulse rate less than 120, and urine output greater than 1 mL/kg per hour) were included. Serum lactic acid (LA) levels were measured at arrival and at proscribed intervals. In the pilot study, initial LA levels were examined in relation to outcome and complications. In the prospective study, patients with two consecutive LA levels greater than 2.5 mmol/L underwent invasive monitoring and vigorous resuscitation to correct their lactic acidosis. Among the 31 patients studied in the pilot study, there were 4 deaths, 6 cases of MSOF, and 13 patients with RC. Lactic acidosis and poor cardiac performance, as evidenced by low cardiac index (CI) with normal filling pressures, were seen in all cases of MSOF and RC, as well as in all deaths. From these results, the prospective study was performed. Eighty-five intensive care unit patients met criteria for inclusion in the study. Six additional patients were excluded because of severe, untreatable intracranial hypertension at admission to the intensive care unit. Fifty-eight of these patients had OH in the first 24 hours. Forty-four patients corrected their OH within 24 hours with vigorous resuscitation. There were no deaths, three cases of MSOF, and 10 cases of RC in those patients who corrected OH within 24 hours. Persistent OH (>24 hours) was seen in 14 patients, despite resuscitative efforts, 43% of whom died. MSOF and RC were present in 36% and 50% of cases, respectively (p<0.05). Initial lactic acidosis is associated with lower cardiac performance and higher morbidity and mortality. Persistent OH is associated with higher rates of RC, MSOF, and death after severe trauma. Early identification and aggressive resuscitation aimed at correcting continued elevation in serum lactate improves survival and reduces complications in severely injured trauma patients.


Copper complexes of anionic nitrogen ligands in the amidation and imidation of aryl halides.
Copper(I) imidate and amidate complexes of chelating N,N-donor ligands, which are proposed intermediates in copper-catalyzed amidations of aryl halides, have been synthesized and characterized by X-ray diffraction and detailed solution-phase methods. In some cases, the complexes adopt neutral, three-coordinate trigonal planar structures in the solid state, but in other cases they adopt an ionic form consisting of an L 2Cu (+) cation and a CuX 2 (-) anion. A tetraalkylammonium salt of the CuX 2 (-) anion in which X = phthalimidate was also isolated. Conductivity measurements and (1)H NMR spectra of mixtures of two complexes all indicate that the complexes exist predominantly in the ionic form in DMSO and DMF solutions. One complex was sufficiently soluble for conductance measurements in less polar solvents and was shown to adopt some degree of the ionic form in THF and predominantly the neutral form in benzene. The complexes containing dative nitrogen ligands reacted with iodoarenes and bromoarenes to form products from C-N coupling, but the ammonium salt of [Cu(phth) 2] (-) did not. Similar selectivities for stoichiometric and catalytic reactions with two different iodoarenes and faster rates for the stoichiometric reactions implied that the isolated amidate and imidate complexes are intermediates in the reactions of amides and imides with haloarenes catalyzed by copper complexes containing dative N,N ligands. These amidates and imidates reacted much more slowly with chloroarenes, including chloroarenes that possess more favorable reduction potentials than some bromoarenes and that are known to undergo fast dissociation of chloride from the chloroarene radical anion. The reaction of o-(allyloxy)iodobenzene with [(phen) 2Cu][Cu(pyrr) 2] results in formation of the C-N coupled product in high yield and no detectable amount of the 3-methyl-2,3-dihydrobenzofuran or 3-methylene-2,3-dihydrobenzofuran products that would be expected from a reaction that generated free radicals. These data and computed reaction barriers argue against mechanisms in which the haloarene reacts with a two-coordinate anionic copper species and mechanisms that start with electron transfer to generate a free iodoarene radical anion. Instead, these data are more consistent with mechanisms involving cleavage of the carbon-halogen bond within the coordination sphere of the metal.


The Technology Horizon for Photocatalytic Water Treatment: Sunrise or Sunset?
Advanced oxidation processes via semiconductor photocatalysis for water treatment have been the subject of extensive research over the past three decades, producing many scientific reports focused on elucidating mechanisms and enhancing kinetics for the treatment of contaminants in water. Many of these reports imply that the ultimate goal of the research is to apply photocatalysis in municipal water treatment operations. However, this ignores immense technology transfer problems, perpetuating a widening gap between academic advocation and industrial application. In this Feature, we undertake a critical examination of the trajectory of photocatalytic water treatment research, assessing the viability of proposed applications and identifying those with the most promising future. Several strategies are proposed for scientists and engineers who aim to support research efforts to bring industrially relevant photocatalytic water treatment processes to fruition. Although the reassessed potential may not live up to initial academic hype, an unfavorable assessment in some areas does not preclude the transfer of photocatalysis for water treatment to other niche applications as the technology retains substantive and unique benefits.


Cervical spine involvement as initial manifestation of rheumatoid arthritis: a case report.
Rheumatoid arthritis' synovitis affects mostly small hand and feet joints, although it may compromise any joint with a synovial lining. Cervical involvement occurs usually in longstanding disease in over half of these patients. We report the case of a 35-year old male patient who was referred to our outpatient clinic for a 2-year severe and disabling inflammatory neck pain, with incomplete response to intramuscular non-steroidal anti-inflammatory drugs and unremarkable cervical imaging studies. He also mentioned self-limited episodes of symmetric polyarthralgia involving hands, wrists, elbows, knees and feet, which started after his cervical complaints. On laboratorial workup, positive rheumatoid factor and anti-citrullinated peptide antibody and negative HLA-B27 were found. Cervical spine magnetic resonance imaging revealed atlantoaxial subluxation and odontoid process inflammatory pannus and erosions. Rheumatoid arthritis with cervical spine involvement as initial manifestation of disease was the definite diagnosis. The patient was started on methotrexate and prednisone and he was referred to neurosurgery outpatient clinic for cervical spine fixation.


Purification of recombinant nucleocapsid protein of Newcastle disease virus from unclarified feedstock using expanded bed adsorption chromatography.
In the present work, a single-step purification of recombinant nucleocapsid protein (NP) of the Newcastle disease virus (NDV) directly from unclarified feedstock using an expanded bed adsorption chromatography (EBAC) was developed. Streamline 25 column (ID = 25 mm) was used as a contactor and Streamline chelating adsorbent immobilized with Ni2+ ion was used as affinity adsorbent. The dynamic binding capacity of Ni2+ -loaded Streamline chelating adsorbent for the NP protein in unclarified feedstock was found to be 2.94 mg ml(-1) adsorbent at a superficial velocity of 200 cm h(-1). The direct purification of NP protein from unclarified feedstock using expanded bed adsorption has resulted in a 31% adsorption and 9.6% recovery of NP protein. The purity of the NP protein recovered was about 70% and the volume of processing fluid was reduced by a factor of 10. The results of the present study show that the IMA-EBAC developed could be used to combine the clarification, concentration and initial purification steps into a single-step operation.


Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI.
During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T(2)*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7T and 17.2T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine). We showed that the brain/vessels contrast in T(2)*-weighted images at 17.2T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation.


Involvement of Mossy Cells in Sharp Wave-Ripple Activity In Vitro.
The role of mossy cells (MCs) of the hippocampal dentate area has long remained mysterious. Recent research has begun to unveil their significance in spatial computation of the hippocampus. Here, we used an in vitro model of sharp wave-ripple complexes (SWRs), which contribute to hippocampal memory formation, to investigate MC involvement in this fundamental population activity. We find that a significant fraction of MCs (∼47%) is recruited into the active neuronal network during SWRs in the CA3 area. Moreover, MCs receive pronounced, ripple-coherent, excitatory and inhibitory synaptic input. Finally, we find evidence for SWR-related synaptic activity in granule cells that is mediated by MCs. Given the widespread connectivity of MCs within and between hippocampi, our data suggest a role for MCs as a hub functionally coupling the CA3 and the DG during ripple-associated computations.


cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors.
Cells adhere to vitronectin substrates through a cell surface receptor that recognizes an Arg-Gly-Asp sequence in vitronectin. The receptor is a glycoprotein composed of a 150-kDa alpha and a 115-kDa beta subunit. The alpha subunit consists of two disulfide-bonded chains of 125 kDa and 25 kDa. cDNA clones were isolated for the alpha subunit of the vitronectin receptor from a phage lambda gt11 expression library made with RNA from a human fibroblast cell line, IMR-90. The identity of the clones that had been selected from the library based on immunological criteria was verified by comparison of DNA and protein sequences. NH2-terminal sequences were obtained for each of the alpha-subunit chains. The sequence of the 25-kDa chain of the alpha subunit was found in a cDNA clone, and the amino acid sequence deduced from the cDNA establishes the complete amino acid sequence of the 25-kDa chain. This chain contains a membrane-spanning domain as well as a putative intracytoplasmic region that is 32 amino acids long and consists mostly of polar amino acids. Comparison of the cDNA and protein sequences shows that the 25-kDa chain is generated by proteolytic cleavage of an alpha-subunit precursor, the partial sequence of which is contained in the cDNA clones. These clones contain 1910 base pairs of open reading frame and a 3' untranslated sequence. RNA blot hybridization detected one transcript of about 7 kilobases in RNA from fibroblastic and epithelial cells. Together, the cDNA clones cover 4442 bases of this RNA. The alpha-subunit sequence showed strong homology with the sequence of the alpha subunit of fibronectin receptor. Moreover, the NH2-terminal protein sequence of the 125-kDa chain was homologous with the NH2-terminal sequences of two other cell surface proteins, lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen 1 (Mac-1), which have been implicated as receptors for adhesion proteins of leukocytes. These results establish several of the structural features in the vitronectin receptor and suggest the existence of a superfamily of receptors for cell adhesion proteins.


Coalescence of bubbles and drops in an outer fluid.
When two liquid drops touch, a microscopic connecting liquid bridge forms and rapidly grows as the two drops merge into one. Whereas coalescence has been thoroughly studied when drops coalesce in vacuum or air, many important situations involve coalescence in a dense surrounding fluid, such as oil coalescence in brine. Here we study the merging of gas bubbles and liquid drops in an external fluid. Our data indicate that the flows occur over much larger length scales in the outer fluid than inside the drops themselves. Thus, we find that the asymptotic early regime is always dominated by the viscosity of the drops, independent of the external fluid. A phase diagram showing the crossovers into the different possible late-time dynamics identifies a dimensionless number that signifies when the external viscosity can be important.


Stochastic modeling for the expression of a gene regulated by competing transcription factors.
It is widely accepted that gene expression regulation is a stochastic event. The common approach for its computer simulation requires detailed information on the interactions of individual molecules, which is often not available for the analyses of biological experiments. As an alternative approach, we employed a more intuitive model to simulate the experimental result, the Markov-chain model, in which a gene is regulated by activators and repressors, which bind the same site in a mutually exclusive manner. Our stochastic simulation in the presence of both activators and repressors predicted a Hill-coefficient of the dose-response curve closer to the experimentally observed value than the calculated value based on the simple additive effects of activators alone and repressors alone. The simulation also reproduced the heterogeneity of gene expression levels among individual cells observed by Fluorescence Activated Cell Sorting analysis. Therefore, our approach may help to apply stochastic simulations to broader experimental data.


Bacteriological Quality of Street Foods and Antimicrobial Resistance of Isolates in Hawassa, Ethiopia.
Microbial contamination of ready-to-eat foods and beverages sold by street vendors and hawkers has become an important public health issue. In Ethiopia, health risks related to such kinds of foods are thought to be common. Thus, this study has tried to determine the bacteriological quality of ready- to- eat foods sold on streets. A cross-sectional study was conducted on street foods in Hawassa City from May to September 2014. A total of 72 samples from six food items such as local bread ('ambasha' and 'kita'), raw fish, chilli ('awaze'), avocado and cooked potato were collected. Bacterial isolation, colony count and antimicrobial susceptibility testing were made following standard microbiological techniques. About 31% of the food samples showed total colony counts ranging from 1.7×105 to 6.7×106 colony-forming unit per gram (CFU/g) which is beyond the acceptable limits set for microbiological quality of ready- to -eat foods. The mean coliform and Enterobacteriaceae counts in raw fish, 'kita' and 'ambasha' were also higher than the limits. E.coli was the most frequent isolate (29.6%) followed by Salmonella species (12.7% and S.aureus (9.9%). All isolates were 100% sensitive to ciprofloxacin. About 89% of Salmonella sp was resistant to chloramphenicol. Alarmingly, 14.3% of S.aureus was resistant to vancomycin. This study confirmed considerable rate of contamination in street vended foods in Hawassa City. The identified foodborne bacteria and antibiotic resistance isolates could pose a public health problem in that locality. Therefore, regular inspection, health education and training of vendors on food handling and safety practices are recommended.


Cutting edge: the human cytomegalovirus UL40 gene product contains a ligand for HLA-E and prevents NK cell-mediated lysis.
Human CMV has evolved multiple strategies to interfere with immune recognition of the host. A variety of mechanisms target Ag presentation by MHC class I molecules resulting in a reduced class I cell-surface expression. This down-regulation of class I molecules is expected to trigger NK cytotoxicity, which would have to be counteracted by the virus to establish long-term infection. Here we describe that the human CMV open reading frame UL40 encodes a canonical ligand for HLA-E, identical with the HLA-Cw03 signal sequence-derived peptide. Expression of UL40 in HLA-E-positive target cells conferred resistance to NK cell lysis via the CD94/NKG2A receptor. Generation of the UL40-derived HLA-E ligand was also observed in TAP-deficient cells. The presence of a functional TAP-independent HLA-E ligand in the UL40 signal sequence implicates this viral gene as an important negative regulator of NK activity.


[Characteristics of soil nematode community in Abies georgei var. smithii forest gaps in south-east Tibet, China].
In order to understand the characteristics of soil nematode community in the Abies georgei var. smithii forest gaps in southeast Tibet, an investigation was conducted to study the variations of soil nematode community at different depths of 0-30 cm soil layer in the gaps and non-gaps. The nematode individual density, diversity index, and trophic group index were taken to analyze the composition and structural characteristics of the soil nematode community. A total of 26801 soil nematodes belonging to 2 classes, 5 orders, and 64 genera were collected by shallow dish method. The nematode individual density was averagely 3552 ind x 100 g(-1) dry soil, and the individuals had a highly surface-gathering characteristics. In the gap soils, the dominant genera were Tylencholaimus and Filenchus, while the dominant trophic group was bacterivores. The soil organic matter was decomposed by both bacteria and fungi. The ecological index results showed that the nematodes diversity and richness were related to gap size. The characteristics of soil nematode community in the gaps were different from those in closed stand and forest open land, and this difference indicated the potential for using nematodes as the environmental indicator species.


Molecular characterization of a bean alpha-amylase inhibitor that inhibits the alpha-amylase of the mexican bean weevil Zabrotes subfasciatus.
Cultivated varieties of the common bean (Phaseolus vulgaris L.) contain an alpha-amylase inhibitor (alpha AI-1) that inhibits porcine pancreatic alpha-amylase (PPA; EC 126.96.36.199) and the amylases of certain seed weevils, but not that of the Mexican bean weevil, Zabrotes subfasciatus. A variant of alpha AI-1, called alpha AI-2, is found in certain arcelin-containing wild accessions of the common bean. The variant alpha AI-2 inhibits Z. subfasciatus alpha-amylase (ZSA), but not PPA. We purified alpha AI-2 and studied its interaction with ZSA. The formation of the alpha AI-2-ZSA complex is time-dependent and occurs maximally at pH 5.0 or below. When a previously isolated cDNA assumed to encode alpha AI-2 was expressed in transgenic tobacco seeds, the seeds contained inhibitory activity toward ZSA but not toward PPA, confirming that the cDNA encodes alpha AI-2. The inhibitors alpha AI-1 and alpha AI-2 share 78% sequence identity at the amino acid level and they differ in an important region that is part of the site where the enzyme binds the inhibitor. The swap of a tripeptide in this region was not sufficient to change the specificity of the two inhibitors towards their respective enzymes. The three-dimensional structure of the alpha AI-1/PPA complex has just been solved and we recently obtained the derived amino acid sequence of ZSA. This additional information allows us to discuss the results described here in the framework of the amino acid residues of both proteins involved in the formation of the enzyme-inhibitor complex and to pinpoint the amino acids responsible for the specificity of the interaction.


The Psychological Predictors of Acute and Chronic Pain in Women Following Breast Cancer Surgery: A Systematic Review.
Numerous psychological factors have been found to be associated with acute and chronic pain following breast cancer surgery. However, individual studies tend to be limited to a small number of predictors and many fail to employ prospective designs. This study aimed to identify a broader range of psychological predictors of acute and chronic pain following breast cancer surgery through a systematic review of relevant prospective studies. Web of Science, psychINFO, PubMed, and MEDLINE databases were searched to identify relevant prospective cohort studies. Studies were included if women were to undergo mastectomy or wide local excision, if psychological factors were assessed before surgery, and pain assessed after surgery. Twelve studies (representing 11 independent cohorts) met the inclusion criteria and described 10 psychological predictors. Anxiety and depression were the most frequently assessed psychological factors, and were measured in 9 of the 12 studies. Anxiety and psychological robustness emerged as significant predictors of acute pain. Distress was the strongest predictor of chronic pain. The relationship between depression and chronic postsurgical pain was, at best, mixed. This review has identified a range of psychological predictors of acute and chronic pain following breast cancer surgery; however, the evidence was conflicting and limited. Future studies should demonstrate adequate power and take account of known confounders.


Early cephalopod evolution clarified through Bayesian phylogenetic inference.
Despite the excellent fossil record of cephalopods, their early evolution is poorly understood. Different, partly incompatible phylogenetic hypotheses have been proposed in the past, which reflected individual author's opinions on the importance of certain characters but were not based on thorough cladistic analyses. At the same time, methods of phylogenetic inference have undergone substantial improvements. For fossil datasets, which typically only include morphological data, Bayesian inference and in particular the introduction of the fossilized birth-death model have opened new possibilities. Nevertheless, many tree topologies recovered from these new methods reflect large uncertainties, which have led to discussions on how to best summarize the information contained in the posterior set of trees. We present a large, newly compiled morphological character matrix of Cambrian and Ordovician cephalopods to conduct a comprehensive phylogenetic analysis and resolve existing controversies. Our results recover three major monophyletic groups, which correspond to the previously recognized Endoceratoidea, Multiceratoidea, and Orthoceratoidea, though comprising slightly different taxa. In addition, many Cambrian and Early Ordovician representatives of the Ellesmerocerida and Plectronocerida were recovered near the root. The Ellesmerocerida is para- and polyphyletic, with some of its members recovered among the Multiceratoidea and early Endoceratoidea. These relationships are robust against modifications of the dataset. While our trees initially seem to reflect large uncertainties, these are mainly a consequence of the way clade support is measured. We show that clade posterior probabilities and tree similarity metrics often underestimate congruence between trees, especially if wildcard taxa are involved. Our results provide important insights into the earliest evolution of cephalopods and clarify evolutionary pathways. We provide a classification scheme that is based on a robust phylogenetic analysis. Moreover, we provide some general insights on the application of Bayesian phylogenetic inference on morphological datasets. We support earlier findings that quartet similarity metrics should be preferred over the Robinson-Foulds distance when higher-level phylogenetic relationships are of interest and propose that using a posteriori pruned maximum clade credibility trees help in assessing support for phylogenetic relationships among a set of relevant taxa, because they provide clade support values that better reflect the phylogenetic signal.


The early management of the burn wound and observations on hypertrophic scarring. With special reference to the deep dermal level and hypertrophic scarring.
Much confusion about the management of the burn wound still exists in many a clinician's mind. This is an attempt to clarify the problem and create a better understanding of the importance of assessing the various depths of penetration of the thermal agent. The treatment varies from the use of minimal bland dressings left undisturbed to aggressive early tangential excision and skin grafting. This is discussed together with the rationale for this approach and some problems associated with it. A 'critical depth' of penetration at the deep dermal level, which spares the acini of the sweat glands, is suggested as the factor initiating later development of hypertrophic scarring. This can be prevented by early excision and skin grafting.


Kidney transplantation for end-stage renal disease secondary to familial Mediterranean fever.
Although kidney transplantation (KT) is widely used for treating renal amyloidosis secondary to familial Mediterranean fever (FMF), data concerning transplant outcome are limited and inconsistent. The aim of this study was to determine the long-term outcome of KT in patients with amyloidosis secondary to FMF. Kidney transplantation outcome in 24 patients with FMF was compared to that in 72 controls matched for age, gender of recipient, and type of the donor that underwent KT due to end-stage renal disease (ESRD) not caused by FMF. Mean follow-up time was 80.3 ± 55.1 months in the FMF group, vs. 86.5 ± 47.6 months in the control group. Death-censored graft survival at five and 10 yr in the FMF group was 95.8% and 78.4%, respectively, and was comparable to that in the control group. In the FMF group, five- and 10-yr patient survival (87.5 and 65.6%) was shorter than in the control group, but the difference was not statistically significant. The findings show that long-term outcome of KT in the patients with amyloidosis secondary to FMF was comparable to that in patients with ESRD not caused by FMF. Recurrence of amyloidosis in the allograft, gastrointestinal intolerance, and fatal infections remain as major complications during the post-transplant period.


In search of an auditory engram.
Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory.


Distributed deep learning across multisite datasets for generalized CT hemorrhage segmentation.
As deep neural networks achieve more success in the wide field of computer vision, greater emphasis is being placed on the generalizations of these models for production deployment. With sufficiently large training datasets, models can typically avoid overfitting their data; however, for medical imaging it is often difficult to obtain enough data from a single site. Sharing data between institutions is also frequently nonviable or prohibited due to security measures and research compliance constraints, enforced to guard protected health information (PHI) and patient anonymity. In this paper, we implement cyclic weight transfer with independent datasets from multiple geographically disparate sites without compromising PHI. We compare results between single-site learning (SSL) and multisite learning (MSL) models on testing data drawn from each of the training sites as well as two other institutions. The MSL model attains an average dice similarity coefficient (DSC) of 0.690 on the holdout institution datasets with a volume correlation of 0.914, respectively corresponding to a 7% and 5% statistically significant improvement over the average of both SSL models, which attained an average DSC of 0.646 and average correlation of 0.871. We show that a neural network can be efficiently trained on data from two physically remote sites without consolidating patient data to a single location. The resulting network improves model generalization and achieves higher average DSCs on external datasets than neural networks trained on data from a single source.


On genetically determined human serum cholinesterases.
The existence of genetically determined human serum cholinesterase variants (actlcholine acyl-hydrolase; EC 188.8.131.52) has been recognized by the use of a short acting muscle relaxant, suxamethonium. This polymorphism is now explained by at least four alleles belonging to an autosomal locus Ch1 or E1 depending on the nomenclature. These are: the usual gene, the dibucaine-resistant gene, the fluoride-resistant gene and the silent gene. At present, the modes of transmission for the silent genes is confusing and lack proper understanding. Another variant, not an allele of the first group, is recognized by gel electrophoresis, belong to a second locus Ch2 or E2. Evidence has been presented that many more rare serum cholinesterase variants may exist. Besides these genetic variants, normal serum cholinesterase is known to exist in multiple molecular forms. The present article attempts to discuss the polymorphism of human cholinesterase in relation to their chemical and genetic characteristics and their possible function.


Nature-driven approaches to non-natural terpene analogues.
Covering: up to 2019The reactions catalysed by terpene synthases belong to the most complex and fascinating cascade-type transformations in Nature. Although many accept only one natural terpene precursor and convert it with high selectivity into only one product, several of these remarkable biocatalysts were recently shown to have a surprising plasticity towards non-natural substrate analogues. For an easy access to the topic also for readers who are new to the field, this review will first briefly cover the principles of natural terpene biosynthesis. This is followed by a chapter that highlights purely chemical transformations mimicking terpene synthase catalysed reactions. Then, the main focus of this article will shed light on the recent advances of terpene synthase catalysed transformations of synthetic substrate analogues. As will be demonstrated, a simple conceptual approach extensively broadens the chemical space that can be reached with terpene synthases.


Phototherapeutic keratectomy for climatic droplet keratopathy, KKESH Excimer Laser Study Group. King Khaled Eye Specialist Hospital.
Phototherapeutic keratectomy (PTK) is an effective treatment for many superficial corneal disorders. The efficacy of PTK for the treatment of climatic droplet keratopathy (CDK) has not been reported. We report the results of excimer laser (Summit Technology, Inc, Waltham, Mass) PTK on 75 eyes (67 patients) with "smooth" climatic droplet keratopathy (55 eyes) and "irregular" climatic droplet keratopathy (20 eyes) in whom more than 6 months of follow up are available. PTK was successful in reducing corneal opacification in both smooth (98%) climatic droplet keratopathy and irregular (80%) climatic droplet keratopathy. Achievement of a clear or mildly hazy cornea following PTK was more likely to occur with smooth (80%) climatic droplet keratopathy than irregular (25%) climatic droplet keratopathy (P = 0.01). Eyes with smooth climatic droplet keratopathy were more likely to obtain more than one line of improved uncorrected (56% vs. 25%) or spectacle-corrected visual acuity (61.8% vs. 21.2%) than those with irregular climatic droplet keratopathy (P = 0.03 and 0.005, respectively). Delayed re-epithelialization (longer than 14 days) was more common in irregular CDK (21%) than in smooth CDK (9%), as was the incidence of secondary microbial keratitis (10.0% vs. 1.8%). PTK is effective in reducing superficial corneal opacification in CDK, although serious complications may occur, especially in advanced irregular CDK.


Fingolimod: an oral disease-modifying therapy for relapsing multiple sclerosis.
This paper presents a summary of the current knowledge of the mechanism of action of fingolimod (FTY720; Gilenya®; Novartis Pharma Stein AG, Stein, Switzerland) and the phase 2 and 3 studies that have been performed on the drug. This study will discuss specific safety issues that should be considered when initiating this therapy. Multiple sclerosis (MS), an inflammatory disease of the central nervous system, is considered to be a leading cause of neurologic disability in young adults, and predominantly affects young women. The past two decades have seen significant growth in therapeutic options for relapsing forms of MS, including FTY720. Fingolimod (FTY720) is a sphingosine-1-phosphate receptor modulator, and currently the approved dosage is 0.5 mg daily. Notable side effects include bradycardia in the first hours after administration and macular edema. There may be an increased risk of herpetic infections (varicella zoster virus and herpes simplex virus) associated with this medication. This oral therapy has been shown to be effective in double-blind, placebo-controlled studies, and in trials comparing it to weekly interferon beta-1a therapy. However, the long-term efficacy and safety of this oral medication in relapsing MS, including the effect on reduction of disability progression and cognitive decline, remains to be established.


Plasma dopa decarboxylase activity in treatment-resistant recent-onset psychosis patients.
Treatment resistance (TR) in psychosis is a major clinical problem. A biomarker predicting TR against conventional antipsychotic drugs would be relevant, potentially reducing unnecessary delay to adequate treatment with clozapine. Dopa decarboxylase (DDC) activity in the striatum, measured with positron emission tomography, is elevated in responders, but not in treatment-resistant patients. Plasma DDC activity could be a surrogate marker for DDC brain activity, and thus a potential biomarker that could be used in daily clinical practice. Therefore, we determined plasma DDC activity in 40 male patients with recent-onset psychosis, of whom the majority had started treatment, whereby 21 turned out to be treatment responders and 19 treatment resistant during follow up. We observed no significant group differences. Furthermore, symptom severity was not associated with plasma DCC activity. We did observe a trend level difference in the distribution of plasma DDC activity across categories of medication, with subsequent post hoc analysis showing lower DDC activity in risperidone-using patients. This may suggest that risperidone could influence plasma DDC activity. Based on these results, plasma DDC activity does not appear to be a promising biomarker for TR in recent-onset psychosis patients who are already receiving antipsychotic treatment.


[Suspicion of systemic diseases through nails abnormalities].
Nails are protective, thin, horny growth at the end of fingers and toes. Abnormalities of the fingernails and toenails can provide both subtle and obvious clues to common medical problems or severe systemic diseases. Inheritance, minor injuries, common habits, the use of cosmetics and a variety of infections account for many changes in the appearance of nails. Awareness of normal nail variants, abnormalities and their disease associations will be beneficial to detect systemic diseases.


Effects of intracanal mineral trioxide aggregate and calcium hydroxide during four weeks on pH changes in simulated root surface resorption defects: an in vitro study using matched pairs of human teeth.
Diffusion of hydroxyl ions from intracanal calcium hydroxide (CH) through dentin is used to arrest external inflammatory root resorption. However, long-term and short-term CH placement has been associated with an increased risk of root fracture. Intracanal mineral trioxide aggregate (MTA) might provide an alternative to CH as a source of hydroxyl ions. This in vitro study compared the effects of intracanal MTA and CH on hydroxyl ion diffusion through dentin by measuring pH changes over time in simulated root surface resorption defects prepared in matched pairs of teeth; the null hypothesis tested was that there is no difference. Root surface cavities were prepared 5 mm from the apex in extracted human permanent anterior teeth (21 matched pairs) and 7 additional teeth (controls). Root canals were instrumented to size 50/.04 and filled with either tooth-colored MTA (ProRoot) or CH (UltraCal XS); control teeth were filled with saline. The pH in root surface cavities was measured at 3 hours, 24 hours, 1 week, 2 weeks, 3 weeks, and 4 weeks. In controls, pH readings did not differ significantly during the 4 weeks (P > .05, repeated-measures analysis of variance [ANOVA]). For the experimental intragroup effects, significant pH changes occurred over time in the MTA group (P = .005, repeated-measures ANOVA) and the CH group (P < .0001). For the experimental intergroup effects, the overall mean pH was higher in the MTA group (8.66; standard error [SE], 0.07) compared with the CH group (8.46; SE, 0.07) (P = .014, paired t test). At 4 weeks pH was higher in the MTA group (8.30; SE, 0.16) compared with the CH group (7.90; SE, 0.11) (P = .011); at all other time points intergroup differences were insignificant. The null hypothesis was rejected. Intracanal MTA and CH groups differed in their overall effect on pH measured in simulated root surface resorption defects. At 4 weeks intracanal placement of MTA compared with CH resulted in a small but significantly higher pH.


The determination of treatment effect of chitosan oligosaccharide in lambs with experimentally cryptosporidiosis.
In this study, it was aimed to investigate the efficacy of chitosan oligosaccharide administrations in different doses of experimental infected lambs with Cryptosporidium parvum. 32 male lambs were used in the study and the lambs were divided into 4 groups with 8 lambs in each group. Groups 1, 2 and 3, twice a day, were administered chitosan oligosaccharide at a dose of 100, 500, and 1000 mg/kg for 7 days, respectively, with milk replacer. In group 4, lambs with cryptosporidiosis were subjected to normal feeding as control without drug administration. Clinical examinations of lambs were made before treatment (day 0) and on days 1, 3, 5 and 7 after treatment and 5 ml of blood was collected from vena jugularis for blood analysis of all lambs. Weight changes of lambs were recorded at 0, 7, 14, and 21 days. Stool specimens were collected pre-treatment (day 0) and on days 1, 3, 5, 7, 14 and 21 post-treatment to determine oocyst excretion of lambs with cryptosporidiosis. Lambs with a mean oocyte counts >10 after stool examination were included to the treatment. Changes in clinical hematology, blood gases and biochemical parameters were observed during the course of treatment, but these changes were limited. Weight loss was observed at 7th day according to 0th day the lambs with experimental cryptosporidiosis but gradually weight increase was observed at 14th and 21st days and these changes were similar in all groups. Oocyst excretion decreased in all groups during treatment. According to 0th day, there was a significant (p < 0.05) decrease in oocyte excretions in the third day in group 1 and 2, and in day 5 in the group 3 and 4. Significant changes (p < 0.05) were observed in oocyst excretions on the third and fifth days among the groups. As a result, in lambs with experimental cryptosporidiosis, chitosan oligosaccharide improved in clinical signs and stool character shorter than the positive control group and the administration of chitosan oligosaccharide at doses of 100, 500 and 1000 mg/kg for 7 days significantly reduced oocyst excretion but not enough to remove cryptosporidiosis completely.


Sterol metabolism during germination of conidia of Aspergillus fumigatus.
The sterol content of germinating conidia of the opportunistic pathogenic fungus Aspergillus fumigatus has been correlated with germination phase and sensitivity to polyene antibiotics. The sterol and sterol ester contents of walls did not change during germination. The sterol ester content of membranes and cell sap remained constant during germination, whereas the sterol content increased during the outgrowth of germ tubes. On the basis of differential extraction studies it was concluded that the loss of resistance to polyenes that occurred in the early stages of swelling of conidia during germination was not due to a movement of sterol or sterol ester out of the wall. Radioactive-labelling experiments demonstrated that, although the amounts of conidial wall sterol and sterol ester did not change during germination, they were metabolically active. Changes in the turnover rate of wall and membrane sterol and sterol ester during germination were investigated and their relationship to a possible mechanism for the change from resistance to sensitivity to polyene antibiotics is discussed.


Nonthermal effects of radiofrequency-field exposure on calcium dynamics in stem cell-derived neuronal cells: elucidation of calcium pathways.
Intracellular Ca(2+) spikes trigger cell proliferation, differentiation and cytoskeletal reorganization. In addition to Ca(2+) spiking that can be initiated by a ligand binding to its receptor, exposure to electromagnetic stimuli has also been shown to alter Ca(2+) dynamics. Using neuronal cells differentiated from a mouse embryonic stem cell line and a custom-built, frequency-tunable applicator, we examined in real time the altered Ca(2+) dynamics and observed increases in the cytosolic Ca(2+) in response to nonthermal radiofrequency (RF)-radiation exposure of cells from 700 to 1100 MHz. While about 60% of control cells (not exposed to RF radiation) were observed to exhibit about five spontaneous Ca(2+) spikes per cell in 60 min, exposure of cells to an 800 MHz, 0.5 W/kg RF radiation, for example, significantly increased the number of Ca(2+) spikes to 15.7+/-0.8 (P<0.05). The increase in the Ca(2+) spiking activities was dependent on the frequency but not on the SAR between 0.5 to 5 W/kg. Using pharmacological agents, it was found that both the N-type Ca(2+) channels and phospholipase C enzymes appear to be involved in mediating increased Ca(2+) spiking. Interestingly, microfilament disruption also prevented the Ca(2+) spikes. Regulation of Ca(2+) dynamics by external physical stimulation such as RF radiation may provide a noninvasive and useful tool for modulating the Ca(2+)-dependent cellular and molecular activities of cells seeded in a 3D environment for which only a few techniques are currently available to influence the cells.


[Heinrich Hoffmann's Der Struwwelpeter (1845/1859): a parody on the romantic cult of childhood].
This article analyzes the cultural dynamics of the construction and deconstruction of childhood images, by means of a case study of Heinrich Hoffmann's classic picture book, Der Struwwelpeter (1845/1859). Childhood images are the joint product of sciences (especially anthropology, pedagogy and developmental psychology) and arts (especially painting, photography and (children's) literature). These images are historically variable, because childhood is the permanent target of idealization and demystification. This article interprets Der Struwwelpeter as a demystication of Romantic idealizations of childhood as propounded by Romantic Naturphilosophie and, more specifically, the pedagogy of Friedrich Fröbel (1772-1852). In my view, this picture book satirizes the developmentalism and the pastoryl idyll which informed the Romantic image of childhood, through its verbal and visual components. As I argue at length, this satire directly bears upon leading scientific and political controversies of Hoffmann's time.


Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry.
The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of human immunodeficiency virus-type 1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins. In addition, US28 mediated infection by cell line-adapted HIV-1 for which CXCR4 was an entry cofactor.


Changes in Coagulation following Brain Injury.
Traumatic brain injury (TBI) is a worldwide public health concern due to increasing mortality, affecting around 10 million patients per year. A wide variety of clinical presentations are a function of the magnitude of injury and the anatomical perturbation of the brain parenchyma, supporting structures, and cerebral vasculature, with subsequent alteration of the blood-brain barrier. These disturbances correspond with the evolution of intracerebral hemorrhage and clinical outcomes. The associated hemostatic alterations associated with TBI are caused by the disruption of the delicate balance between bleeding and thrombosis formation, which can exacerbate initial injury. TBI-associated coagulopathy is a function of a cross-talk between coagulation and inflammation, with varying influences on the immunomodulation and regulation of coagulation that occur on platelets and the endothelium of injured TBI patients. In addition to the severity of initial injury, the following factors modulate the hemocoagulative response to TBI: time from the onset of injury to treatment, age, gender, catecholamine secretion, platelet dysfunction, endotheliopathy, premorbid anticoagulation, fibrinolysis, tissue factor, and activated protein C contribution. All these entities are intertwined and influence the pathologic evolution of TBI. These factors have implications for therapeutic options such as the choice of blood components for transfusion and hemostatic agents such as tranexamic acid. Monitoring hemostatic changes of TBI patients requires an understanding of these interactions between immunology and coagulation, which can be discerned by point-of-care viscoelastic testing with specific limitations. This review considers the implications of these interrelated influences on the evaluation of coagulopathy in TBI.


Assessment of children's own health status using visual analogue scale and descriptive system of the EQ-5D-Y: linkage between two systems.
The objective of the study is to derive a scoring system for the EQ-5D child-friendly version (EQ-5D-Y) from a population-based sample of children based on their own health state assessments on the descriptive system and the visual analogue scale (VAS). We used data from the 2008 and 2010 Raising Healthy Eating and Active Living Kids in Alberta surveys of grade five students aged primarily 10-11 years and their parents in the Canadian province of Alberta. We applied a random split sample approach. Two-thirds of the sample (modeling sample) was used for the estimation of the EQ-5D-Y VAS. The remaining one-third sample (validation sample) was used for the examination of the prediction accuracy of the estimation model. Multilevel linear regression was used to estimate EQ-5D-Y VAS score and produce EQ-5D-Y index values from the children's self-rated states described in the EQ-5D-Y and the accompanying VAS values. The mean EQ-5D-Y VAS-based index value was 0.891 (SD 0.133) in the modeling sample and 0.885 (SD 0.134) in the validation sample. The own VAS-based index generally showed logical consistency, with lower values for health states that were logically worse. There was no statistically significant difference between the observed and the predicted VAS values in this sample. This study elicited a value set for health states defined by the EQ-5D-Y that is based on respondents' own VAS ratings from a large representative sample of Canadian children. Future study is needed to validate this type of value set among different age groups of children.


Differing renal effects of activated and nonactivated isoelectric peaks of human prorenin in rats.
Isoelectric species of renin are physically heterogeneous. Recent evidence suggests that they may differ functionally, with some species producing natriuresis and diuresis, whereas others have no effect. A physiological function of secreted prorenin has not been documented in any species. The present study was designed to confirm and describe for the first time the renal effects of certain isoelectric species of prorenin. Anesthetized Sprague-Dawley rats were injected (0.1 ml) with trypsin-activated or nonactivated prorenin obtained from human ovarian follicular fluid. The dose chosen was calculated as sufficient to produce 2,300 ng angiotensin I.h-1.100 g rat body wt-1 in the presence of excess sheep substrate. Blood pressure, creatinine clearance, urine flow rate, and urine sodium, potassium, and osmolar excretion were measured. Activated prorenin from isoelectric peaks at isoelectric points (pI) 5.1, 5.2, 5.4, and 5.6 produced marked increases in urine volume (sixfold) and sodium excretion (7- to 10-fold) compared with the group receiving the vehicle (1% albumin in 0.9% saline). Activated prorenin from peaks at pI 4.9 and 5.8 produced no significant increase over the vehicle-only experiments. Captopril pretreatment (1 mg/kg iv) completely blocked the effects of peaks at pI 5.4 and 5.6. Interestingly, injection of nonactivated prorenin from peaks at pI 5.4 and 5.6 produced effects similar to the injection of activated prorenin from these peaks. Similarly, this effect was blocked by pretreatment with captopril. In summary, only certain isoelectric peaks of human prorenin whether activated, to active renin, or nonactivated produced a marked natriuresis and diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)


Liquid Biopsy in Alzheimer's Disease Patients Reveals Epigenetic Changes in the PRLHR Gene.
In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer's disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients' lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, we found higher methylation levels in AD patients in the promoter region of PRLHR, a gene involved in energy balance regulation. Our aim was to further characterize PRLHR's role in AD and to evaluate if the liquid biopsy technique would provide life access to this brain information in a non-invasive way. First, we extended the methylation mapping of PRLHR and validated previous methylome results via bisulfite cloning sequencing. Next, we observed a positive correlation between PRLHR methylation levels and AD-related neuropathological changes and a decreased expression of PRLHR in AD hippocampus. Then, we managed to replicate the hippocampal methylation differences in plasma cfDNA from an additional cohort of 35 AD patients and 35 controls. The isolation of cfDNA from the plasma of AD patients may constitute a source of potential epigenetic biomarkers to aid AD clinical management.


Dual-LED imaging for finger liveliness detection and its evaluation with replicas.
Unattended fingerprint identification systems need to reject input attempts by a replica. Previously, we proposed detecting the color changes of a finger during an input action as a signature of liveliness. To improve its reliability, a dual-LED imaging system is investigated. It employs two LEDs with peak emissions at 530 and 630 nm to cover the spectral ranges where live fingers show characteristic changes. Using nine types of replicas and the live fingers of 42 participants, we have recorded and analyzed 153 input trials. The two groups of data are successfully separated by some defined criteria.


[Monitoring time of interictal epileptiform discharges by long-term video EEG in patients with epilepsy].
Objective: To optimize the monitoring time of interictal epileptiform discharges (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG). Methods: The cumulative percentages of IED detected by VEEG in 346 epilepsy patients (349 times) with different purposes, different waking sleep states and different MRI findings were retrospectively analyzed. According to the purposes, there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124 times) for preoperative evaluation and 58 patients (60 times) for adjustment of medications. According to MRI results, there were responsible lesions in 98 patients (98 times) and no responsible lesions in 173 patients (174 times). Results: Among 346 patients (349 times), IED was detected within 24 h in 231 patients (times). The percentage of detection in patients with purpose of preoperative evaluation was higher than those with purpose of diagnosis and medication adjustment. The detection of LED was gradually increased in first 8 h with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time, particularly in the second stage of sleep. The cumulative percentage of IED in patients with abnormal MRI findings was higher in all periods. It reached 83.7% within 8 h, and then tended to be stable. Conclusion: The study shows that LED should be monitored by VEEG at least 8 hours and should include the second stage of sleep in patients with epilepsy. Patients with refractory epilepsy and with abnormal lesions on MRI should record IED more frequently.


Newly graduated nurses' stress, coping, professional identity and work locus of control: Results of a cross-sectional study in Shanghai, Hong Kong and Taipei.
The study aimed to explore and compare stress, coping, professional identity and work locus of control of new graduate nurses among Shanghai, Hong Kong and Taipei. The transition from a student to a staff nurse role is recognized as a stressful experience and can be a rough journey. Many newly graduated nurses find it challenging to cope with their new roles in their first few months. A cross-sectional research was used in the study. This study was completed in Shanghai, Hong Kong and Taipei with newly graduated nurses working in hospitals. A total of 591 graduate nurses who had worked within 1 year in hospitals were recruited using convenient sampling. Data were collected using a structured questionnaire, including demographics, the occupational stress scale, the Chinese trait coping style questionnaire, the nurse professional identity scale and the work locus of control scale (Chinese version). The newly graduated nurses in Shanghai had significantly lower (p < 0.05) work stress score (2.65 ± 0.67) compared with their counterparts in Hong Kong (2.99 ± 0.69) and Taipei (2.94 ± 0.60). Newly graduated nurses in Shanghai tended to choose positive coping to deal with stressful situations, whereas those in Hong Kong would be more likely to adopt negative attitudes (p < 0.05). The newly graduated nurses in Taipei had the lowest level of professional identity (3.25 ± 0.55, p < 0.05), and their work control tended to be external (46.13 ± 6.20). In contrast, those in Shanghai (52.75 ± 6.04) and Hong Kong (59.41 ± 7.29) tended to be controlled internally. The study findings revealed the differences among newly graduated nurses in Shanghai, Hong Kong and Taipei with their level of stress, coping, professional identity and work locus of control. Proper leadership, mentoring for newly graduated nurses, and emphasis on first aid nursing training, emotional management and management of stress in newly graduated nurse transition programmes were suggested. By comparing the results in the three regions, we recommend that nursing managers promote the right leadership style. In addition to coaching, nursing managers can assign additional mentors to newly graduated nurses to help them supplement their clinical knowledge and skills with psychological support. These mentors can come from senior nurses or nursing managers working on less demanding tasks. In addition to the existing post transfer training programmes, new graduate nurses should also focus on emergency nursing training, emotional management training and stress management training.


Nomenclature on proteases, proteinases, and peptidases.
INTRODUCTIONIn 1984, the International Union of Biochemistry and Molecular Biology (IUBMB) recommended the use of the term peptidase for the subset of peptide bond hydrolases (Subclass EC3.4.). The widely used term protease is synonymous with the term peptidase. Proteases comprise two groups of enzymes: endoproteases and exoproteases. This article summarizes the characteristics of the main types of proteases.