Clinical intervention research in nursing.
As a healthcare profession nursing has a duty to develop practices that contribute to the health and well being of patients. The aim of this paper is to discuss current issues in clinical research within nursing. The paper defines clinical interventions research as a theoretically based, integrated and sequential approach to clinical knowledge generation. The paper provides specific criteria for defining a clinical intervention together with an overview of the stages involved in clinical research from problem identification to implementing knowledge in practice. The paper also explored the extent to which nursing research was focussed on clinical issues, through a snapshot review of all the original research papers in Europe's three leading nursing research journals. In total of 517 different papers were included and classified in the review. Of these 88% (n=455) were classified as non-clinical intervention and 12% (n=62) as clinical intervention studies. The paper examined the intervention studies in detail examining: the underpinning theory; linkage to previous (pre-clinical) work; evidence of granularity; protocol clarity (generalisable and parsimonious); the phase of knowledge development; and evidence of safety (adverse event reporting). The paper discusses some of the shortcomings of interventions research in nursing and suggests a number of ideas to help address these problems, including: a consensus statement on interventions research in nursing; a register of nursing intervention studies; the need for nursing to develop clinical research areas in which to develop potential interventions (nursing laboratories); and a call for nursing researchers to publish more research in nursing specific journals.


Impact of varying levels of expertise on decisions of category typicality.
Experts on domains of basic level object categories possess extensive knowledge of features used to both individuate and categorize groups of similar members. Two studies were conducted to determine the impact of high knowledge on intermediate and advanced experts' typicality decisions for basic and subordinate level category exemplars, and to investigate whether the pattern of influence of factors (in particular, central tendency and subjective familiarity) remained fixed throughout the continuum of expertise. Example goodness increased as a function of the level of specificity of the category for which typicality was rated. Subjective familiarity was the principal determinant of typicality for individuals with high knowledge, whereas central tendency was related to typicality when knowledge was not particularly high. Advanced and intermediate experts produced similar ratings of typicality, indicating that individuals' decisions of typicality do not change markedly once intermediate levels of competency have been attained. The incorporation of knowledge effects into models of semantic memory, as well as interactions among knowledge, psychological factors, and environmental factors in determining typicality, are discussed.


Rapid confirmatory identification of Mycobacterium bovis using a dot blotting immunodetection technique.
A safe, cost effective and accurate immunodetection technique for the rapid identification of Mycobacterium bovis colonies is described. One hundred and thirteen M. bovis isolates were differentiated from other species of mycobacteria using a M. bovis specific monoclonal antibody, with nitrocellulose membrane as the solid support. The technique confirms M. bovis identification in only 4 h compared to 3 weeks for conventional antibiotic sensitivity tests.


Identifying sex in non-fertile individuals of the moss Drepanocladus turgescens (Bryophyta: Amblystegiaceae) using a novel molecular approach.
Sex identification before sexual maturity is notoriously difficult in plants with separate sexes, but is crucial to address many life history related issues. To study the performance of the two sexes in the rarely sexually reproducing dioecious moss Drepanocladus turgescens a molecular sex marker is needed. The female-targeting marker previously developed for D. trifarius and D. lycopodioides amplifies for a few D. turgescens males, which can thus not be distinguished from females. In a significant addition to the earlier developed method we sequenced the portion successfully amplified by the primers PT-3f and PT-3r for six females and three males. Differences between males and females were revealed at five sequence positions. Examination of a total of fourteen females and seven marker amplifying males confirm that females and such males differ consistently at these positions. The usefulness of a previous protocol for moss sex identification is thus extended to another dioecious moss by the addition of a step where a portion of the sex-correlated region is sequenced.


[Pneumobilia and MRCP: value of sagittal view].
Pneumobilia can lead to artifacts at MRCP obtained from thick coronal and coronal oblique slabs. Axial and sagittal images can both show gas bubbles in bile ducts but sagittal images depict more easily the presence of an air-fluid level.


Relative bioavailability of a 5 mg mosapride/10 mg rabeprazole fixed dose combination tablet versus separate single tablets in healthy volunteers: a single-dose randomized open-label crossover study.
To evaluate the relative bioavailability of a new formulation containing 5 mg mosapride and 10 mg rabeprazole (T) and compare it with the branded formulations of both drugs co-administered in separate tablets (R) to meet the regulatory requirements of bioequivalence in Argentina. A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of either T or R formulations was followed by a 7-day washout period. Blood samples for mosapride were collected before administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, and 24 h after administration. Samples for rabeprazole were taken baseline and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8 and 10 h after dosing. Mosapride and rabeprazole concentrations were determined using a validated LC-MS/MS method. Adverse events were monitored based on clinical parameters and volunteer reports. The geometric means (90% CI) C(max) for mosapride in T and R were 23.13 (20.05-39.45) and 23.09 (21.69-32.37) ng/mL, the AUC(0-)(t) were 70.80 (66.23-102.37) and 70.81 (66.35-93.26) ng h/mL and the AUC(0-∞) were 74.05 (69.29-106.11) and 74.98 (70.43-97.77) ng h/mL. For rabeprazole T and R the C(max) were 197.42 (186.12-239.91) and 195.50 (186.08-250.07) ng/mL, the AUC(0-)(t) were 294.90 (275.13-374.15) and 296.96 (280.11-387.89) ng h/mL and the AUC(0-∞) were 301.12 (280.78-380.82) and 304.07 (286.60-394.21), respectively. No differences were detected between the formulations. The T/R ratios (90% CI) for C(max), AUC(0-)(t) and AUC(0-∞) were 100.17% (82.35-121.84), 99.99% (87.58-114.16) and 98.77% (87.02-112.11) for mosapride, and 100.99% (85.14-119.77), 99.31% (84.74-116.38) and 99.03% (85.07-115.28) for rabeprazole. No subject complained of adverse events. In this single-dose study, the mosapride/rabeprazole tablets (test formulation) met the criterion for bioequivalence with the reference formulations. Study limitations include single-dose, open-label design, and a small sample of healthy volunteers.


Management of Congenital Lung Malformations.
Congenital lung malformations represent a spectrum of lesions, each with a distinct cause and tailored clinical approach. This article will focus on the following malformations: congenital pulmonary airway malformations, formally known as congenital cystic adenomatoid malformations, bronchopulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst. Each of these malformations will be defined and examined from an embryologic, pathophysiologic, and clinical management perspective unique to that specific lesion. A review of current recommendations in both medical and surgical management of these lesions will be discussed as well as widely accepted treatment algorithms.


[Hormone receptors in breast cancer. Thoughts on the use of their determination as a test of hormone dependence in a hospital routine (author's transl)].
The determination of hormone receptors in tumour tissues including, among others, breast tumours is becoming routine examination in a greatly increasing number of clinical departments. We draw the attention of clinicians to the criteria of the quality necessary in such quantitative measurements and the limits of such an examination if it is to prove useful in directing the therapy of those clinics that use it in the light of the experience we have gained in the last 4 years.


Miniaturized, microarray-based assays for chemical proteomic studies of protein function.
Systematic analysis of protein and enzyme function typically requires scale-up of protein expression and purification prior to assay development; this can often be limiting. Miniaturization of assays provides an alternative approach, but simple, generic methods are in short supply. Here we show how custom microarrays can be adapted to this purpose. We discuss the different routes to array fabrication and describe in detail one facile approach in which the purification and immobilization procedures are combined into a single step, significantly simplifying the array fabrication process. We illustrate this approach by reference to the creation of arrays of human protein kinases and of human cytochrome P450s. We discuss methods for both ligand-binding and turnover-based assays, as well as data analysis on such arrays.


Polydopamine-cloaked Fe-based metal organic frameworks enable synergistic multidimensional treatment of osteosarcoma.
One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy, and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d-arginine (d-Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O2 to hydrogen peroxide and gluconic acid, blocking the cells' energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe3+, which reacts with H2O2 to produce reactive oxygen species and thus stimulates the conversion of d-Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe3+ to enhance the T1-weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.


Validation in dogs of a rapid digital angiographic technique to measure relative coronary blood flow during routine cardiac catheterization.
Assessment of the functional significance of anatomically defined coronary stenoses has been hampered by the lack of clinically applicable techniques of measuring coronary blood flow or flow ratios. A digital angiographic technique is reported that allows rapid analysis of relative regional coronary blood flow during routine cardiac catheterization. This technique was validated in dogs by comparing digital flow ratio estimates with electromagnetic-flow (EMF) ratio measurements. Fourteen open-chest dogs had EMF probes placed on the proximal left anterior descending artery before selective coronary angiography. Electrocardiographically gated images were acquired directly by a digital radiographic system during both baseline blood flow and either contrast or papaverine-induced hyperemia. Dual-parameter functional images were generated using color and intensity coding to represent contrast arrival time and contrast density, respectively. For analysis, myocardial areas of interest were created over the distal perfusion bed of the left anterior descending coronary artery. Mean contrast density/appearance time (CD/AT) values were computer calculated as the mean density divided by the mean arrival time for each. Coronary flow reserve was determined as the ratio of the CD/AT value for a hyperemic image divided by the CD/AT value for the corresponding baseline image. CD/AT ratios correlated well (r = 0.92) with actual EMF ratios (CD/AT Ratio = 0.90 EMF Ratio +0.12, n = 48 ratios). Reproducibility was +/- 13%. Interobserver (r = 0.99) and intraobserver (r = 0.98) variability was excellent. Thus, rapid, accurate and reproducible estimates of relative regional coronary blood flow are possible using digital radiography.


Effects of in vivo beta-adrenoceptor down-regulation on cardiac responses to prenalterol and pirbuterol.
The effects of beta-adrenoceptor down-regulation on rat left atrial responses to the full agonist isoproterenol and the partial agonists prenalterol and pirbuterol were studied. Atria from rats implanted with a mini-osmotic-pump subcutaneously delivering isoproterenol at 400 micrograms X kg-1 X h-1 for 4 days were 12-16 times less sensitive to isoproterenol than normal atria. Scatchard analyses indicated that the implantation of these mini-osmotic-pumps produced a 50% decrease in the number of beta-adrenoceptors in the ventricles with no alteration in the binding constant of [3H]dihydroalprenolol. Receptor down-regulation produced a parallel shift to the right of concentration-response curves to isoproterenol, and a complete suppression of responses to both partial agonists. The affinities of the partial agonists for the receptors were not altered; in desensitized atria the partial agonists were functional beta-antagonists blocking the responses to isoproterenol. The data are modeled by equations from classical receptor theory which predict the depression of responses to partial agonists with receptor down-regulation. These results are discussed with respect to the utility of prenalterol and pirbuterol in congestive heart failure since possible tachyphylaxis to these drugs with chronic usage could limit their value.


Incisional hernia repair in rats: description of the sublay technique under videomagnification system.
To describe the technique of sublay correction of incisional hernia in Wistar rats under videomagnification system. Five male rats of the species Rattus norvegicus, of the Wistar lineage, with body weight between 250-350 g and 60 days old were used. Incisional hernia was inducted in all animals. After that, the incisional hernia was immediately corrected by the sublay method. There were no cases of recurrence of the incisional hernia after placement of the polypropylene mesh using the sublay technique. No postoperative complications were observed. The technique is suitable for execution in Wistar rats.


Subchronic toxicity study in mice fed Spirulina maxima.
The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue-green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w/w) for 13 weeks. The alga ingestion had no effect on behavior, food and water intake, growth or survival. Terminal values in hematology and clinical chemistry did not reveal differences between treated and control groups. However, male and female mice showed significant changes in serum cholesterol levels at 20 and 30% algal concentrations, but a toxic effect of S. maxima was excluded. Post-mortem examination revealed no differences in gross or microscopic findings. Our results show that S. maxima up to high feeding levels did not produce adverse effects in mice after subchronic treatment.


Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.
The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.


Assessing the dry impinger method for condensable particulate matter from ultra-low emission coal-fired power plant measurement.
The dry impinger method is commonly used for the determination of condensable particulate matter (CPM) emissions. The coil and chamber condenser is used to build different dry impinger methods for CPM sampling. The comparative analysis of coil and chamber condenser is performed in a laboratory experiment to evaluate the deviation caused by SO2. Results showed that the positive deviation caused by SO2 in the chamber condenser is lower than that in the coil condenser under the same sampling conditions, especially under high humidity flue gas. The CPM emission characteristics from Hanchuan coal-fired power plant (CFPP) determined by both dry impinger methods are also investigated as well. The CPM and its most water-soluble ions (e.g., F-, Cl-, NO3-, SO42-, Na+, Ca2+ and NH4+) measured by method #2 (chamber condenser) are higher than that of method #1 (coil condenser). In addition, the esters in the CPM also increased with the CPM concentrations. Based on above evidences, it can be inferred that the dry impinger method with chamber condenser, will be recommended as the appropriate method for measuring CPM emitted from stationary sources, especially under the high humidity flue gas conditions.


Some considerations in the design of new antineoplastic agents.
The design of many antineoplastic agents has been based on atom or group replacement in normal metabolites. New dimensions are being added to this approach by the synthesis of transition state, bisubstrate and "suicide" inhibitors. These provide greater potency and in some cases selectivity. Leads for differential sensitivity of viral infected cells are appearing (5'-amino-5-iodo-3',5'-dideoxy-uridine, AIU). Equally important has been the development of repository and precursor forms of active drugs along with structures having altered physical and metabolic properties. In the future combination therapy may include drugs whose intrinsic antitumor activity is relatively low but which in combination provide the means of potentiating the antitumor activity of other agents (THU, deoxycoformycin, pyrazofurin). Finally, the potential for developing macromolecular "drugs" such as therapeutic enzymes and peptide hormone analogs must be viewed as a whole new area for drug design.


Structure and mechanism of enzymes involved in biosynthesis and breakdown of the phosphonates fosfomycin, dehydrophos, and phosphinothricin.
Recent years have seen a rapid increase in the mechanistic and structural information on enzymes that are involved in the biosynthesis and breakdown of naturally occurring phosphonates. This review focuses on these recent developments with an emphasis on those enzymes that have been characterized crystallographically in the past five years, including proteins involved in the biosynthesis of phosphinothricin, fosfomycin, and dehydrophos and proteins involved in resistance mechanisms.


Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.
The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in retinas exposed to advanced glycation end-products.


Bioactive Cembranoids from the Coral Sarcophyton trocheliophorum of Ximao Island.
Eight new cembranoids (sarcophytembranoids A-H, 1-8) and 10 known terpenoids (9-18) were obtained from the soft coral Sarcophyton trocheliophorum of Ximao Island. Notably, 11, 15, and 16 were obtained from a natural source for the first time. The structures of the new isolates were elucidated by extensive spectroscopic analysis, optical rotatory dispersion, and X-ray diffraction experiments. Although the isolated compounds did not show significant activity against the tested tumor cell lines, compounds 3, 7, 8, and 10-15 exhibited anti-inflammatory activities at 10 μM, and compounds 17 and 18 showed moderate protein tyrosine phosphatase 1B inhibition activities with the minimum inhibitory concentrations of 22.19 and 11.26 μM, respectively.


Myocardial kinetics of radiolabeled perfusion agents: basis for perfusion imaging.
The myocardial deposition of radiolabeled perfusion agents permits the noninvasive assessment of regional coronary blood flow. The design of imaging protocols and the optimal interpretation of clinical perfusion studies are based on an understanding of the kinetics of blood-tissue exchange for these compounds. Thallium 201 and the technetium 99m-labeled compounds sestamibi, teboroxime, and tetrofosmin show differing myocardial extraction and retention. This review focuses on studies that used cell culture, isolated heart, and intact animal models that form the basis of our current understanding of the myocardial kinetics of these imaging agents.


N-mononitrosopiperazine in urine after occupational exposure to piperazine.
We have shown previously that intake of the drug piperazine can result in the endogenous formation of N-mononitrosopiperazine (NPZ; Bellander et al., 1985). The present investigation deals with the possibility of endogenous formation of NPZ due to occupational exposure to piperazine in a chemical plant.


Lipidomic Profiling of Argania spinosa L. (Skeels) Following Drought Stress.
Argan tree is frequently constrained by environmental stresses, especially drought. Lipids play crucial roles in stress adaptation, but lipidomic profiles in Argania spinosa under drought stress is largely unknown. The aim of this study was to identify lipid components potentially responsive to drought stress from leaves in the four argan ecotypes. For this, non-polar metabolite profiling was carried out using gas chromatography-mass spectrometry. We identified 228 components, the majority of which belonged to fatty acids and prenol lipids classes. The principal component analysis and partial least-squares discriminant analysis were applied to the lipidomics data to determine the component changes between all ecotypes. Based on the common components present in all ecotypes under contrast conditions, 21 metabolites belong fatty acids were identified with significant change. It was concluded that the majority of these components show up-accumulation in their content and involve in different pathways, especially in alpha-linolenic acid metabolism. The findings of this study provided new insights into the lipidomic study of argan leaves under drought stress and may be eventually contribute to overcoming drought; in addition, this could serve as a base for future studies on transcriptomic and proteomic to enhance the drought tolerance of forest trees.


Enhanced optical confinement and lasing characteristics of individual urchin-like ZnO microstructures prepared by oxidation of metallic Zn.
We prepared urchin-like micron-sized ZnO cavities with high optical quality by oxidizing metallic Zn and proposed the mechanism that resulted in the growth of the urchin-like microstructures. The photoluminescence spectra of the ZnO microstructures had a predominant excitonic emission at room temperature. The lasing properties of the urchin-like ZnO microstructures were investigated systematically through excitation power- and size-dependent photoluminescence measurements. The results showed that a low lasing threshold with high quality factors could be achieved because of the high reflectivity of the optical reflectors formed by the tapered nanowires. The unique optical characteristics may facilitate the development of high-efficiency random lasers.


Magnetoelastic sensors in combination with nanometer-scale honeycombed thin film ceramic TiO2 for remote query measurement of humidity.
Ribbonlike magnetoelastic sensors can be considered the magnetic analog of an acoustic bell; in response to an externally applied magnetic field impulse the sensors emit magnetic flux with a characteristic resonant frequency. The magnetic flux can be detected external to the test area using a pick-up coil, enabling query remote monitoring of the sensor. The characteristic resonant frequency of a magnetoelastic sensor changes in response to mass loads. [L.D. Landau and E. M. Lifshitz, Theory of Elasticity, 3rd ed. (Pergamon, New York, 1986). p. 100].Therefore, remote query chemical sensors can be fabricated by combining the magnetoelastic sensors with a mass changing, chemically responsive layer. In this work magnetoelastic sensors are coated with humidity-sensitive thin films of ceramic, nanodimensionally porous TiO2 to make remote query humidity sensors.


[Hypophosphatasia in an adult, with late clinical manifestations (author's transl)].
A case of hypophosphatasia with osteomalacia and subtrochanteric pseudo-fractures is described in a 53 years old woman. Bone biopsy showed an excess of osteoid. Alkaline phosphatase activities in sera were low. There was no excretion in the urine of abnormal quantities of phosphoetanolamine. But alkaline phosphatase activities were low in bone and intestine. Two sons were affected by biological hypophosphatasia without clinical features. These data support the diagnosis of minimal hypophosphatasia in an adult.


Reduction of plasma renin activity by centrally-administered angiotensin II in anesthetized cats.
Cerebroventricular administration of angiotensin II elevated arterial pressure and reduced plasma renin activity (PRA) in renal venous blood in anesthetized cats. Further, there was an increase in the concentration of urinary sodium, as well as the rate of Na+ excretion. Acute renal denervation significantly reduced the effects of central angiotensin II on the PRA and on the natriuresis. The data suggested involvement of a neurogenic component in these effects. Further, it appears that there may be a reciprocal relationship between CSF renin activity and PRA.


Delayed decline of gamma-globin expression in infant age associated with the presence of Ggamma-158 (C-->T) polymorphism.
Persistent production of fetal hemoglobin (HbF) in adult has ameliorative effects on hemoglobinopathies and great efforts are currently made to achieve an exhaustive understanding of the molecular mechanisms of the switching in globin gene expression. One of the factors reported to be associated with the expression of fetal globin genes is the Xmn I Ggamma-158 polymorphism, although it is still unclear if it is involved in this mechanism either by itself or in strong linkage disequilibrium with other loci. Here, we report a novel effect of the Xmn I Ggamma-158 site that was found associated with a significant delayed decline of HbF production in infant age. The prolonged decay trend was enhanced when the Ggamma-158 C-->T substitution was co-inherited with a beta-thalassemic trait. Our observations reinforce the hypothesis that this region plays an important role in the expression of the gamma-globin genes and give new insights on the intriguing and still poorly understood mechanisms of globin gene expression switching.


The relationship between aminoterminal propeptide of type III procollagen and heart rate variability parameters in heart failure patients: a potential serum marker to evaluate cardiac autonomic control and sudden cardiac death.
Cardiac extra-cellular matrix (ECM) fibrosis plays an important role in the pathophysiology of heart failure (HF). It may provide electrical heterogeneity and a substrate for arrhythmogenicity, which may cause sudden cardiac death (SCD). Twenty-one patients with manifestations of HF and a left ventricular ejection fraction (LVEF) ≤50% were enrolled. The median age was 62 years and median LVEF was 33%. Time- and frequency-domain analysis of heart rate variability (HRV) on 24 h ambulatory electrocardiography recording was assessed. Serum markers of ECM turnover including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. The serum PIIINP concentration was correlated significantly with standard deviation of all normal to normal R-R intervals (SDNN) (r=-0.722, p=<0.001), percentage of adjacent NN interval differences >50 ms (pNN50) (r=-0.528, p=0.014), percentage of adjacent NN interval differences >20 ms (pNN20) (r=-0.545, p=0.002), very low frequency (VLF) (r=-0.490, p=0.024), low frequency (LF) (r=-0.491, p=0.024), and high frequency (HF) (r=-0.513, p=0.018). PINP, MMP-2, -9, TIMP-1 were not correlated with time- and frequency-domain analysis of HRV. PIIINP was significantly correlated with time- and frequency-domain analysis of HRV in HF patients. PIIINP is a potential serological marker to evaluate cardiac autonomic control and risk of SCD in HF patients.


A Rapidly and Highly Self-Healing Poly(Sulfobetaine Methacrylate) Hydrogel with Stretching Properties, Adhesive Properties, and Biocompatibility.
This study focuses on the preparation of stretchable zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels. To address the weak mechanical properties of chemically crosslinked PSBMA hydrogels, a physical crosslinking method utilizing hydrophobic interactions to crosslink hydrogels to approach tough properties is developed. Here, sodium dodecyl sulfate (SDS)-based micelle is used as a physical crosslinker to prepare physically crosslinked PSBMA (PSBMAphy ) hydrogels, and ethylene glycol dimethylacrylate (EGDMA) is used to prepare a control group of chemically crosslinked PSBMA (PSBMAchem ) hydrogels. The mechanical properties of the two hydrogels are compared, and PSBMAphy hydrogels exhibit greater flexibility than the PSBMAchem hydrogels. When the PSBMAphy hydrogels are subjected to external forces, the micelles act as dynamic crosslinking sites, allowing the stress to disperse and prevent the hydrogel from breaking. In addition, the PSBMAphy hydrogels have nearly 100% self-healing properties within 2.5 min. The PSBMAphy hydrogels exhibit usable adhesive properties to porcine skin and subcutis. MTT and hemolysis tests show that the PSBMAphy hydrogels have excellent biocompatibility and hemocompatibility. This study proposes that the multifunctional PSBMAphy hydrogels with micelles will be potential to carry drugs for use in drug delivery systems in the future.


Comprehensive Mapping of Key Regulatory Networks that Drive Oncogene Expression.
Gene expression is controlled by the collective binding of transcription factors to cis-regulatory regions. Deciphering gene-centered regulatory networks is vital to understanding and controlling gene misexpression in human disease; however, systematic approaches to uncovering regulatory networks have been lacking. Here we present high-throughput interrogation of gene-centered activation networks (HIGAN), a pipeline that employs a suite of multifaceted genomic approaches to connect upstream signaling inputs, trans-acting TFs, and cis-regulatory elements. We apply HIGAN to understand the aberrant activation of the cytidine deaminase APOBEC3B, an intrinsic source of cancer hypermutation. We reveal that nuclear factor κB (NF-κB) and AP-1 pathways are the most salient trans-acting inputs, with minor roles for other inflammatory pathways. We identify a cis-regulatory architecture dominated by a major intronic enhancer that requires coordinated NF-κB and AP-1 activity with secondary inputs from distal regulatory regions. Our data demonstrate how integration of cis and trans genomic screening platforms provides a paradigm for building gene-centered regulatory networks.


Definitions, components and processes of data harmonisation in healthcare: a scoping review.
Data harmonisation (DH) has emerged amongst health managers, information technology specialists and researchers as an important intervention for routine health information systems (RHISs). It is important to understand what DH is, how it is defined and conceptualised, and how it can lead to better health management decision-making. This scoping review identifies a range of definitions for DH, its characteristics (in terms of key components and processes), and common explanations of the relationship between DH and health management decision-making. This scoping review identified relevant studies from 2000 onwards (date filter), written in English and published in PubMed, Web of Science and CINAHL. Two reviewers independently screened records for potential inclusion for the abstract and full-text screening stages. One reviewer did the data extraction, analysis and synthesis, with built-in reliability checks from the rest of the team. We developed a narrative synthesis of definitions and explanations of the relationship between DH and health management decision-making. We sampled 61 of 181 included to synthesis definitions and concepts of DH in detail. We identified six common terms for data harmonisation: record linkage, data linkage, data warehousing, data sharing, data interoperability and health information exchange. We also identified nine key components of data harmonisation: DH involves (a) a process of multiple steps; (b) integrating, harmonising and bringing together different databases (c) two or more databases; (d) electronic data; (e) pooling data using unique patient identifiers; and (f) different types of data; (g) data found within and across different departments and institutions at facility, district, regional and national levels; (h) different types of technical activities; (i) has a specific scope. The relationship between DH and health management decision-making is not well-described in the literature. Several studies mentioned health providers' concerns about data completeness, data quality, terminology and coding of data elements as barriers to data utilisation for clinical decision-making. To our knowledge, this scoping review was the first to synthesise definitions and concepts of DH and address the causal relationship between DH and health management decision-making. Future research is required to assess the effectiveness of data harmonisation on health management decision-making.


EMD 281014, a new selective serotonin 5-HT2A receptor antagonist.
The 5-HT2A receptor ligand 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) selectively binds to human (h) and rat 5-HT2A receptors (IC50 values 0.35 and 1 nM, respectively; vs. 1334 nM for h5-HT2C) and inhibited 5-HT-stimulated [35S]guanosine 5'-O-3-thiotriphosphate (GTPgammaS)-accumulation in h5-HT2A transfected Chinese hamster ovary cells (IC50 9.3 nM). EMD 28014 counteracted the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced decrease of [3H]ketanserin binding in rat frontal cortex (ID50 0.4 mg/kg p.o.) and R-(-)-1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI)-induced head-twitch behaviour in mice (ID50 0.01 mg/kg s.c., 0.06 mg/kg p.o.), demonstrating unique selectivity and efficacy.


Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism.
The Glu298Asp gene polymorphism in NOS3 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta-analysis. All eligible case-control studies were searched in PubMed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. A total of 5522 cases and 4877 controls in 20 case-control studies were included. Obvious heterogeneity among studies was detected, and no significant association was observed between the NOS3 Glu298Asp polymorphism and AD risk. After exclusion of three studies, the heterogeneity disappeared and still no association was observed. In the subgroup analysis by ethnicity, we did not find any significant association between this polymorphism and AD risk in both Asians and Caucasians. This meta-analysis suggested that the NOS3 Glu298Asp gene polymorphism is not a strong risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of NOS3 gene and AD risk, more studies with large groups of patients are required.


Recent research on aetiology, development and phenomenology of self-injurious behaviour in people with intellectual disabilities: a systematic review and implications for treatment.
Behavioural interventions conceptualise self-injurious behaviour (SIB) as developing from early repetitive behaviours through acquisition of homeostatic functions in regulating stimulation and subsequent shaping into SIB through socially mediated or automatic operant reinforcement. Despite high success rates, such interventions rarely completely eliminate SIB, and overall effectiveness has not increased since the 1960s. Research (excluding studies of single genetic syndromes) on the early development, functional properties and phenomenology of SIB in persons with intellectual disabilities (IDs) published from 1999 to 2010 inclusive is reviewed. Despite evidence to support the operant shaping hypothesis, in some cases tissue-damaging SIB, especially head-banging, emerges at a similar or younger age than stereotyped behaviours or 'proto-SIB', often associated with tantrums following frustrative non-reward and/or abrupt situational transitions. Many young children show undifferentiated patterns of responding in functional analyses of SIB, and SIB is associated with aggression and impulsivity as well as with repetitive behaviour. One dynamic in the development of SIB may be Pavlovian conditioning of aggression, originally elicited by aversive events or frustrative non-reward, to stimuli associated with such situations. Integration into operant technology of interventions based on Pavlovian principles such as graduated exposure (with or without counterconditioning) to aversive stimuli may enhance the effectiveness of behavioural interventions.


Spontaneous alignment of permanent successors after enucleation of odontogenic cysts associated with primary teeth.
Pulpotomy and pulpectomy occasionally lead to cyst formation in the primary dentition. They show specific clinical features of large size, rapid growth, buccal expansion and displacement of permanent teeth. Complete enucleation of the cyst with extraction of the associated primary teeth and preservation of the permanent teeth appeared to be the most suitable treatment option. Normal alignment of the permanent teeth occurred spontaneously even their initial positions were highly unfavourable.


Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence.
Emerging evidence indicates that the immune and metabolic interactions control several aspects of the aging process and associated chronic diseases. Among several sites of immune-metabolic interactions, thymic demise represents a particularly puzzling phenomenon because even in metabolically healthy middle-aged individuals the majority of thymic space is replaced with ectopic lipids. The new T cell specificities can only be generated in a functional thymus and, peripheral proliferation of pre-existing T cell clones provides limited immune-vigilance in the elderly. Therefore, it is hypothesized that the strategies that enhance thymic-lymphopoiesis may extend healthspan. Recent data suggest that byproducts of thymic fatty acids and lipids result in accumulation of 'lipotoxic DAMPs' (damage associated molecular patterns), which triggers the innate immune-sensing mechanism like inflammasome activation which links aging to thymic demise. The immune-metabolic interaction within the aging thymus produces a local pro-inflammatory state that directly compromises the thymic stromal microenvironment, thymic-lymphopoiesis and serves a precursor of systemic immune-dysregulation in the elderly. New evidence also suggests that ectopic thymic adipocytes may develop from specific intrathymic stromal cell precursors instead of a passive process that is simply a consequence of thymic lymphopenia. Thus the complex bidirectional interactions between metabolic and immune systems may link aging to health, T cell senescence, and associated diseases. This review discusses the immune-metabolic mechanisms during aging - with implications for developing future therapeutic strategies for living well beyond the expected.


Administration of rhHGF-activator via portal vein stimulates the regeneration of cirrhotic liver after partial hepatectomy in rats.
Cirrhotic liver has less ability to regenerate than normal liver, but it can produce the precursor of hepatocyte growth factor (proHGF) similarly to normal liver after resection. Studies were performed to examine whether the exogenous administration of recombinant human (rh) HGF-activator converts proHGF to biologically active (mature) HGF, inducing an enhancement of liver regeneration in cirrhosis. Rats with liver cirrhosis were treated by 45% partial hepatectomy, and rhHGF-activator or vehicle was injected via the portal vein 24 h after resection. Liver injury and its regeneration, the conversion of proHGF to mature HGF, and the activation of its signal through HGF receptor (c-Met) were analyzed. rhHGF-activator improved the recovery of liver function after resection in cirrhotic liver as compared with the control group. rhHGF-activator also enhanced the proliferating cell nuclear antigen labeling index and liver regeneration rate. rhHGF-activator converted the proHGF to mature HGF, showing the maximal effect at 10 min after injection, which was followed by tyrosine phosphorylation of insulin receptor substrate (IRS)-1, and the association of IRS-1 with c-Met and phosphatidylinositol 3-kinase. Results demonstrate that the administration of rhHGF-activator stimulates the recovery of liver function and regeneration after resection in cirrhotic liver through the activation of proHGF and its intracellular signal. It may be potentially useful treatment for patients with liver cirrhosis.


Nintedanib treatment delays prostate dorsolateral lobe cancer progression in the TRAMP model: contribution to the epithelial-stromal interaction balance.
Prostate cancer (PCa) progression mechanism has been linked to epithelial proliferation, tumor invasion ability, and growth factors. Nintedanib (BIBF 1120) has been reported as being FGF and VEGF pathway inhibitors, exhibiting antitumor activity. Thus, the objective herein was to characterize the early Nintedanib treatment effects on the structure and molecules involved in the basal membrane, the extracellular matrix (ECM) maintenance, in addition to the angiogenesis and mitogenic processes at different grades of prostatic tumor development in TRAMP mice. Therefore, 45 male TRAMP mice were divided into control groups: 8-week-old mice (TC8), 12-week-old mice (TC12), and 16-week-old mice (TC16); and treated groups with 10 mg/kg/day Nintedanib dose for 4 weeks. The treated groups were euthanized at 12 (TN12) and 16 (TN16) weeks of age. Samples from the dorsolateral lobe were collected and processed for light microscopy, immunohistochemistry, Western blotting, and microvessel density analysis. The results showed that early Nintedanib treatment led to an increase of healthy epithelium frequency and a reduction of LGPIN and a maximum vascularization density in the TN12 group. Also, treatment led to a well-differentiated adenocarcinoma decrease and an α and β dystroglycan and also laminin 1 increase in the TN16 group. IGFR1 decreased in the TN16 group. To conclude, early Nintedanib treatment led to a reduction in cancer severity, interfering in both ECM compounds and angiogenesis process to then contribute to a balance, not only in the prostatic epithelium and stroma, but also in the epithelial-stromal interaction during PCa progression.


Molecular Characteristics and Genetic Analysis of Extensively Drug-Resistant Isolates with different Tn3 Mobile Genetic Elements.
Extensively drug-resistant (XDR) bacteria are the main caues for causing clinical infectious diseases. Our aim was to distinguish the present molecular epidemiological situation of XDR Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli isolates recovered from local hospitals in Changzhou. Antibiotic susceptibility and phenotypic analysis, multilocus sequence typing and Pulsed Field Gel Electrophoresis were performed to trace these isolates. Resistant phenotype and gene analysis from 29 XDR strains demonstrated that they mainly included TEM, CTX-M-1/2, OXA-48, and KPC products. A. baumannii strains belonged to sequence type (ST) ST224, and carrying the blaCTX-M-2/TEM gene. The quinolone genes aac(6')-ib-cr and qnrB were carrying only in A. baumannii and E.coli. Three (2.3%) of these strains were found to contain the blaNDM-1 or blaNDM-5 gene. A new genotype of K. pneumoniae was found as ST2639. Epidemic characteristics of the XDR clones showed that antibiotic resistance genes distributed unevenly in different wards in Changzhou's local hospitals. With the sequencing of blaNDM carrying isolates, the plasmids often carrying a highly conservative Tn3-relavent mobile genetic element. The especially coupled insert sequence ISKox3 may be a distinctive resistance gene transfer loci. The genotypic diversity variation of XDRs suggested that tracking and isolating the sources of antibiotic resistance especially MBL-encoding genes such as blaNDM-will help manage the risk of infection by these XDRs.


A genotype distribution of human papillomaviruses detected by polymerase chain reaction and direct sequencing analysis in a large sample of common warts in Japan.
There have been no large-scale epidemiological studies of human papillomavirus (HPV) genotype distribution of common warts in Japan. A total of 213 patients with common warts (104 males and 109 females) in Japan were studied to detect HPV genotype distribution by polymerase chain reaction (PCR) and direct sequencing analysis. The results were as follows: 94 HPV-1a (44.1%), 35 HPV-4 (16.4%), 30 HPV-65 (14.1%), 13 HPV-27 (6.1%), 13 HPV-2a (6.1%), 9 HPV-57b (4.22%), 3 HPV-16 (1.41%), 2 HPV-6a (0.94%), 2 HPV-63 (0.94%), and 1 case for each of HPV-3, -5, -5b, -7, -10, -21, -29, -47, -56, -57, -62, and -92 (0.47%, respectively). Four cases (1.88%) were found in which two different HPV types were detected within the lesions: one case of HPV-1a with HPV-16, one case of HPV-1a with HPV-65, one case of HPV-6a with HPV-8, and one case of HPV-65 with HPV-16. There were seven cases of mucosal types (3.3%), that is, two HPV-6a, three HPV-16, one HPV-56, and one HPV-62, and three cases of epidermodysplasia verruciformis (EV)-related types (1.41%), that is, one HPV-5, one HPV-5b (both of which belonged to a high-risk group), and one HPV-47 (which belonged to a low-risk group). To date, this is the largest sequencing-based study of HPV for common warts in Japan. It is said that common warts are induced predominantly by HPV-2, -27, and -57 in European population. However, the present results showed that in Japan they were induced mostly by HPV-1, -4, and -65. This suggests that regional differences in HPV genotype distribution may exist between European and Japanese populations.


Micro-structural characterization of black crust and laser cleaning of building stones by micro-Raman and SEM techniques.
Research concerning the formation and removal of black crusts on various historical objects is approached from many different angles. The so-called "yellowing effect", observed after laser treatment for cleaning purposes, has also received a lot of attention. Evidence regarding this phenomenon differs considerably and the actual mechanisms are still speculated on by researchers. In an attempt to elucidate the processes involved in the yellowing effect associated with laser cleaning, a new analytical technique has been used to investigate the black crust, a region of the sample cleaned by laser irradiation at 1064 nm and another region of the same sample subjected to further laser irradiation at 355 nm, on a limestone sample from the cathedral of Seville in Spain. Micro-Raman spectrometry offers the advantage of spatial chemical characterization of the stone, based upon its molecular makeup and was performed on the bulk body of the stone. Raman and scanning electron microscopy/energy dispersive X-ray spectrometry (SEM/EDXS) results indicate that the surfaces cleaned by irradiation at 1064 nm and by double irradiation at 1064 and 355 nm differed in terms of their calcium sulphate, calcium oxalate and iron oxide content, and that this could contribute to the difference in colour observed.


The prevalence of drugs in carbon monoxide-related deaths: a retrospective study, 2000-2003.
The objective of this study was to review demographic characteristics and drugs detected in carbon monoxide (CO)-related deaths from cases received by the Office of the Cuyahoga County Coroner in Cleveland, Ohio, from 2000-2003. Postmortem reports were reviewed, and decedents for which CO was listed as the cause of death were included. The data were compiled into 3 groups according to the official coroner's verdict as to the manner of death: accident, suicide, and homicide. Included in this study were 122 cases: 84 (69%) accidental, 31 (25%) suicide, and 7 (6%) homicide. Accident decedents were typically white males, aged 40-59 years, residing in Cleveland. Suicide decedents were also middle-aged, white males but residing in the suburbs. Homicide decedents under the age of 6 were characteristically black (N=2), while decedents over the age of 39 were predominately white (N=3). Carboxyhemoglobin (COHb) levels in suicide cases were higher than concentrations measured in accidental deaths. The highest percentage of suicide decedents (36%) had a COHb level>70% saturation, accident decedents (36%) between 50% and 69% saturation, and homicide decedents (71%) below 50% saturation. Ethanol (N=34) was detected in 28% of deaths, and therapeutic and/or abused drugs (N=50) were detected in 41% of deaths. Illicit drugs were detected in 11% of cases (cocaine/metabolites; THC/metabolites), other drug positives were therapeutic medications. The most common drugs detected were antidepressants and antihistamines in suicides and pain medications and antihistamines in accidents.


Microcystin-leucine-arginine induced neurotoxicity by initiating mitochondrial fission in hippocampal neurons.
Microcystin-leucine-arginine (MC-LR) can cross the blood-brain barrier (BBB) and demonstrate potent acute hippocampal neurotoxicity. Chronic exposure to MC-LR has been confirmed to cause learning and memory deficits in mice, but the potential molecular mechanism of MC-LR-caused neurotoxicity is still unclear. In this research, we observed that MC-LR induced oxidative stress, mitochondrial fission and apoptosis in HT-22 hippocampal neurons. Moreover, further studies identified that MC-LR induced mitochondrial fragmentation via activating Dynamin-related protein 1 (Drp1) and Mitochondrial fission factor (Mff), contributing to apoptosis of hippocampal neuronal cells. The observed effects were associated with increased intracellular Ca2+ and reduced activity of protein phosphatases 2A (PP2A) as results of MC-LR exposure in hippocampal neuron cells. Ca2+ activates CaMK II and Akt to enhance phosphorylation of Drp1 at Ser616 residue. Inhibition of PP2A activity increased AMPK activity to mediate phosphorylation of Mff. Our data proved that MC-LR can cause mitochondrial fragmentation in hippocampal neurons, which provides novel perception to explore the underlying molecular mechanism associated with MC-LR-induced neurotoxicity and Alzheimer's disease-like changes.


Determinants of Obstetricians' Pattern of Care for Sickle Cell Disease in Pregnancy.
Pregnancy in sickle cell disease (SCD) is high risk. With improved comprehensive obstetric care, pregnant females with SCD can achieve successful pregnancy outcomes, especially in resource-poor settings. To determine the predictors of Obstetricians' pattern of care for SCD in pregnancy in Nigeria. Self-administered, pre-tested, pre-validated questionnaires containing 18 questions on demographic details of obstetricians, and their pattern of practice towards antenatal care for pregnant SCD patients were distributed to attendees of the 2018 conference of the Society of Obstetrics and Gynaecology of Nigeria (SOGON). Regression analysis was done to determine the possible predictors, and a significant level was <0.05. Almost all the respondents (98.4%) considered pregnancy in SCD as high risk, and 96.2% proposed for preconception care in a tertiary hospital. The majority, (62%) agreed that antenatal visits in the first and second trimesters should be more frequent. The majority (96.2%) reported they would routinely order urine tests among other investigations. Majority of respondents,74.9% and 98.4% knew that foetal medicine specialists and haematologists should be part of preconception care team, respectively. Respondents' practice centre and designation, significantly contributed to their "willingness to consult a haematologist" (P = 0.004)," and willingness to consult a foetal specialist" (P = 0.047), while practice centre and practice population significantly contributed to their response to "ideal centre for management of SCD pregnancy": (P = 0.049), (P = 0.024) respectively. Obstetricians' level of training, practice centre, and practice population of pregnant women with SCD are significant contributors to their pattern of care towards antenatal care for pregnancy in SCD.


Quantification of colony-forming units for M. tuberculosis complex using gyrB-based real-time PCR assay.
It is inappropriate to select insertion sequence (IS) 6110 as the amplification target for the quantitative analysis of Mycobacterium tuberculosis complex (MTC). To develop a novel Taqman real-time polymerase chain reaction (RT-PCR) for the quantitative analysis of MTC by amplifying a single-copy PCR target. Analytic sensitivity and specificity, repeatability and reproducibility, and standard curve were estimated by analysing 18 reference strains and 100 clinical isolates. Diagnostic sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) were evaluated by detecting 50 clinical specimens. Quantitative accuracies of commercial and in-house Taqman RT-PCR were also compared. Analytic sensitivity of this method was 30 colony-forming units/ml and analytic specificity was 100%. In comparison with commercial Taqman RT-PCR (reference), diagnostic sensitivity, diagnostic specificity, PPV and NPV of the novel Taqman RT-PCR were respectively 85.7%, 94.4%, 85.7% and 94.4%. There was no significant difference between the two methods (χ(2) = 0.25, P > 0.05) and there was strong agreement between them (κ = 0.802, P < 0.05). In-house Taqman RT-PCR was more accurate than commercial assay. The novel RT-PCR is sensitive and specific for the detection of MTC and it is also accurate for quantitative analysis of MTC.


CD147 mediates chemoresistance in breast cancer via ABCG2 by affecting its cellular localization and dimerization.
CD147 and ABCG2 both have been reported to mediate Multidrug resistance (MDR) in breast cancer. Recent study demonstrates that CD147 could form a complex with ABCG2 on the cell membrane in primary effusion lymphoma. However, whether these two molecules regulate each other in breast cancer and result in MDR is not clear. We established four MCF-7 cell lines transfected with CD147 and/or ABCG2 and found that CD147 could increase the expression and dimerization of ABCG2, affect its cellular localization and regulate its drug transporter function. The findings derived from cells were confirmed subsequently in clinic samples of chemotherapy-sensitive/resistant breast cancer.


Precision of a new tool to measure visceral adipose tissue (VAT) using dual-energy X-Ray absorptiometry (DXA).
A new tool to quantify visceral adipose tissue (VAT) over the android region of a total body dual-energy x-ray absorptiometry (DXA) scan has recently been reported. The measurement, CoreScan, is currently available on Lunar iDXA densitometers. The purpose of the study was to determine the precision of the CoreScan VAT measurement, which is critical for understanding the utility of this measure in longitudinal trials. VAT precision was characterized in both an anthropomorphic imaging phantom (measured on 10 Lunar iDXA systems) and a clinical population consisting of obese women (n = 32). The intrascanner precision for the VAT phantom across 9 quantities of VAT mass (0-1,800 g) ranged from 28.4 to 38.0 g. The interscanner precision ranged from 24.7 to 38.4 g. There was no statistical dependence on the quantity of VAT for either the inter- or intrascanner precision result (p = 0.670). Combining inter- and intrascanner precision yielded a total phantom precision estimate of 47.6 g for VAT mass, which corresponds to a 4.8% coefficient of variance (CV) for a 1 kg VAT mass. Our clinical population, who completed replicate total body scans with repositioning between scans, showed a precision of 56.8 g on an average VAT mass of 1110.4 g. This corresponds to a 5.1% CV. Hence, the in vivo precision result was similar to the phantom precision result. The study suggests that CoreScan has a relatively low precision error in both phantoms and obese women and therefore may be a useful addition to clinical trials where interventions are targeted towards changes in visceral adiposity.


Donor Derivative Incorporation: An Effective Strategy toward High Performance All-Small-Molecule Ternary Organic Solar Cells.
Thick-film all-small-molecule (ASM) organic solar cells (OSCs) are preferred for large-scale fabrication with printing techniques due to the distinct advantages of monodispersion, easy purification, and negligible batch-to-batch variation. However, ASM OSCs are typically constrained by the morphology aspect to achieve high efficiency and maintain thick film simultaneously. Specifically, synchronously manipulating crystallinity, domain size, and phase segregation to a suitable level are extremely challenging. Herein, a derivative of benzodithiophene terthiophene rhodanine (BTR) (a successful small molecule donor for thick-film OSCs), namely, BTR-OH, is synthesized with similar chemical structure and absorption but less crystallinity relative to BTR, and is employed as a third component to construct BTR:BTR-OH:PC71BM ternary devices. The power conversion efficiency (PCE) of 10.14% and fill factor (FF) of 74.2% are successfully obtained in ≈300 nm OSC, which outperforms BTR:PC71BM (9.05% and 69.6%) and BTR-OH:PC71BM (8.00% and 65.3%) counterparts, and stands among the top values for thick-film ASM OSCs. The performance enhancement results from the enhanced absorption, suppressed bimolecular/trap-assisted recombination, improved charge extraction, optimized domain size, and suitable crystallinity. These findings demonstrate that the donor derivative featuring similar chemical structure but different crystallinity provides a promising third component guideline for high-performance ternary ASM OSCs.


Antioxidant effect of caffeic Acid on oxytetracycline induced lipid peroxidation in albino rats.
Caffeic acid is a well-known phenolic compound widely present in plant kingdom. The aim of this study was to investigate the possible protective effect of caffeic acid (CA) against oxytetracycline (OXT) induced hepatotoxicity in male Albino Wistar rats. A total of 30 rats weighing 150-170 g were randomly divided into five groups of six rats in each group. Oral administration of OXT (200 mg/kg body weight/day) for 15 days produced hepatic damage as manifested by a significant increase in serum hepatic markers namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and increased plasma and hepatic lipid peroxidation indices (TBARS and hydroperoxide). The present finding shows that the levels of enzymatic antioxidants namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were significantly decreased in OXT intoxicated rats. Upon oral administration of caffeic acid (40 mg/kg body weight/day) there were decreased hepatic marker activities, bilirubin and lipid peroxidation and increased enzymatic antioxidants in OXT + Caffeic acid group compared to Normal + OXT group(P < 0.05). Our study suggests that caffeic acid has antioxidant property and hepatoprotective ability against OXT induced toxicity.


Spinal hernia tissue autofluorescence spectrum.
The laser intervertebral disc decompression may provide appropriate relief in properly selected patients with contained disc herniations. The present investigation aims to characterise intervertebral disc material by autofluorescence induced by laser light. Degeneration of the intervertebral disc is associated with progressive biochemical changes in disc material. Percutaneous laser disc decompression has become rather popular for the treatment of lumbar disc herniation, but there are problems in the selection of patients. For this purpose, recognition of the disc composition is necessary. We propose a new type of spectroscopic investigation. It is advantageous to the characterization of intervertebral disc material. Intervertebral disc specimens were removed during open surgery from different disc locations. Preoperative patients' MRI was evaluated using the Pfirrmann disc degeneration and Komori scale for migrating of herniated nucleus pulposus. Adjacent slices of stained disc sections were evaluated by histology/histochemistry and autofluorescence spectra. Comparison of the MRI, spectral, histological and histochemical data was performed. The MRI Komori scale correlated with the histology Boos degeneration index. In the histochemistry, collagens other than collagens I and II of the disc were distinguished with best positive correlation coefficient (0.829) and best negative one (-0.904) of proteoglycans of sequester to Boos index. A correlation of the IV Gaussian component of the hernia spectra with the Boos index was established. The Gaussian component correlation with different collagen types and proteoglycan was determined for the disc and sequester. "Autofluorescence-based diagnosis" refers to the evaluation of disc degeneration by histological and histochemical evaluation; it can provide additional data on the degeneration of an intervertebral disc.


An exploratory study of adolescents and emerging adults with spina bifida knowledge of their individual education program: Implications for health care transition planning.
The purpose of this study was to explore adolescents and emerging adults (AEA) with spina bifida (SB) understanding of their Individualized Education Program (IEP) and to identify factors related to their knowledge about their own IEP. Data were collected from January 2015 to July 2016 from 79 adolescents with SB. A ten-item questionnaire including demographics and questions specifically addressing IEPs was used. Qualitative analysis followed an iterative, emergent approach. Two experienced coders independently read and coded each of the three open-ended questions. It was determined that the responses of all three questions could feasibly be merged as the analysis of responses were similar. This was a predominately 70 (88.7%) Hispanic sample of AEA with SB who ranged in age from 12 to 20 years (M= 15.3 years) consisting of 41 males and 38 females. All reported they have/had an IEP. Four major themes and eleven subthemes emerged from the analysis. Major themes were: The Barometer of How I Am Doing, Creating the Right Match for Learning, Obtaining the Assistance I Need, and Future Goals and Planning. Findings of this study reveal the IEP knowledge gaps and lack of lifestyle self-management skills AEA with SB reported pertaining to IEPs.


Inhibiting caspase-3 activity blocks beta-catenin degradation after focal ischemia in rat.
Beta-catenin can be cleaved by caspase-3 or degraded by activated glycogen synthase kinase-3beta via phosphorylating beta-catenin. We tested the hypothesis that beta-catenin undergoes degradation after stroke, and its degradation is dependent on caspase activity. Stroke was generated by permanent middle cerebral artery occlusion and 1 h of transient bilateral common carotid artery occlusion in rats. Active caspase-3 was expressed in the ischemic cortex from 5 to 48 h after stroke, whereas beta-catenin markedly degraded at 24 and 48 h after stroke. The caspase 3-specific inhibitor, Z-DQMD-FMK, attenuated beta-catenin degradation, but it did not affect phosphorylation of both beta-catenin and glycogen synthase kinase-3beta. In conclusion, beta-catenin degraded after stroke, and its degradation was caspase-3 dependent.


Effects of Traditional Chinese Exercises on Frailty, Quality of Life, and Physical Function on Frail and Pre-Frail Older People: A Systematic Review and Meta-Analysis.
To explore the effects of traditional Chinese exercises (TCEs) on the frailty status, quality of life, and physical function of frail and pre-frail older adults. Eight databases were searched from inception to March 28, 2022. Methodological quality and heterogeneity were assessed. Mean difference (MD) or standardized MD (SMD) were pooled using random-effects or fixed-effects meta-analysis, depending on heterogeneity. A total of 12 articles were included. Results showed relieved frailty status of frail and pre-frail older adults (SMD = -1.46; 95% CI [-2.39, -0.53]; p < 0.01); quality of life improved (SMD = 0.91, 95% CI [0.19, 1.63]; p < 0.01); grip strength enhanced doing Badaunjin (MD = 2.51, 95% CI [1.09, 3.93]; p < 0.01), but no significant improvement with Taichi (MD = 0.10, 95% CI [-2.3,2.5]; p = 0.93); dynamic balance ability improved (MD = -2.57, 95% CI [-2.90, -2.25], p < 0.01); 4.5-m walking time shortened (MD = -0.95; 95% CI [-1.70, -0.20]; p < 0.001); gait speed improved (MD = 0.04; 95% CI [0.01, 0.07]; p = 0.003); lower body endurance increased (MD = 33.78; 95% CI [10.99, 56.68]; p = 0.004); Lower limb flexibility improved (SMD = -2.07; 95% CI [-2.94, -1.21]; p < 0.01). This study showed that TCEs may be helpful in alleviating frailty status and improving the quality of life and physical functions of frail and pre-frail older adults. Lastly, additional high-quality clinical trials are warranted despite the limited strong evidence.


Smart chest X-ray worklist prioritization using artificial intelligence: a clinical workflow simulation.
The aim is to evaluate whether smart worklist prioritization by artificial intelligence (AI) can optimize the radiology workflow and reduce report turnaround times (RTATs) for critical findings in chest radiographs (CXRs). Furthermore, we investigate a method to counteract the effect of false negative predictions by AI-resulting in an extremely and dangerously long RTAT, as CXRs are sorted to the end of the worklist. We developed a simulation framework that models the current workflow at a university hospital by incorporating hospital-specific CXR generation rates and reporting rates and pathology distribution. Using this, we simulated the standard worklist processing "first-in, first-out" (FIFO) and compared it with a worklist prioritization based on urgency. Examination prioritization was performed by the AI, classifying eight different pathological findings ranked in descending order of urgency: pneumothorax, pleural effusion, infiltrate, congestion, atelectasis, cardiomegaly, mass, and foreign object. Furthermore, we introduced an upper limit for the maximum waiting time, after which the highest urgency is assigned to the examination. The average RTAT for all critical findings was significantly reduced in all prioritization simulations compared to the FIFO simulation (e.g., pneumothorax: 35.6 min vs. 80.1 min; p < 0.0001), while the maximum RTAT for most findings increased at the same time (e.g., pneumothorax: 1293 min vs 890 min; p < 0.0001). Our "upper limit" substantially reduced the maximum RTAT in all classes (e.g., pneumothorax: 979 min vs. 1293 min/1178 min; p < 0.0001). Our simulations demonstrate that smart worklist prioritization by AI can reduce the average RTAT for critical findings in CXRs while maintaining a small maximum RTAT as FIFO. • Development of a realistic clinical workflow simulator based on empirical data from a hospital allowed precise assessment of smart worklist prioritization using artificial intelligence. • Employing a smart worklist prioritization without a threshold for maximum waiting time runs the risk of false negative predictions of the artificial intelligence greatly increasing the report turnaround time. • Use of a state-of-the-art convolution neural network can reduce the average report turnaround time almost to the upper limit of a perfect classification algorithm (e.g., pneumothorax: 35.6 min vs. 30.4 min).


Can Technology Improve the Quality of Colonoscopy?
In order for screening colonoscopy to be an effective tool in reducing colon cancer incidence, exams must be performed in a high-quality manner. Quality metrics have been presented by gastroenterology societies and now include higher adenoma detection rate targets than in the past. In many cases, the quality of colonoscopy can often be improved with simple low-cost interventions such as improved procedure technique, implementing split-dose bowel prep, and monitoring individuals' performances. Emerging technology has expanded our field of view and image quality during colonoscopy. We will critically review several technological advances in the context of quality metrics and discuss if technology can really improve the quality of colonoscopy.


Evaluation of Learning in Oncology of Undergraduate Nursing with the Use of Concept Mapping.
This study aims to identify whether the use of concept mapping (CM) strategy assists a student to extend and revise their expertise in oncology and analyze the abilities developed in a student in order to go through theoretical to practical knowledge. This study is descriptive and qualitative, with 20 undergraduate students of the Undergraduate Nursing Course of Paulista School of Nursing of Federal University of São Paulo, Brazil. The critical incident technique and content analysis were used. There were 12 categories represented by facilities, difficulties, and learning applicability in oncology provided by CM strategy during the surgical and clinical nursing discipline. The graphics resource, CMapTools®, and the clinical case data arranged in mapping for resolution generated an active search and exercise of self-learning in oncology. Despite the challenges of the use of CM as a teaching strategy-pedagogical, the results suggested an increase of autonomy and clinical reasoning in nursing practice.


Regulation of fetal fibronectin production in human chorion cells.
Our purpose was to evaluate the role of human chorion in production of fetal fibronectin and to assess the regulation of fetal fibronectin production by inflammatory products and cytokines. Human chorion cells were grown in culture, and at confluence cells were incubated with and without lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha, and acetylsalicylic acid. Fetal fibronectin production was measured in the supernatants by means of enzyme-linked immunosorbent assay. Production of fetal fibronectin was increased by lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor-alpha. Acetylsalicylic acid had no effect on fetal fibronectin biosynthesis. Fetal fibronectin production by human chorion cells in vitro is stimulated by inflammatory products and mediators, which are considered to be important in the initiation of some cases of preterm labor.


Estrogenic activity and cytotoxicity of six anticancer drugs detected in water systems.
The aim of the present study was to investigate the in vitro estrogenic and the cytotoxic activity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to the five classes of Anatomical Therapeutic Classification (ATC) detected in wastewater systems. The estrogenic activity was assessed by YES-assay on Saccharomyces cerevisiae-RMY326 and E-screen on MCF-7 cells. The cytotoxic activity was assessed by MTT Cell Proliferation Assay on the MCF-7 and the MDA-MB-231 cells. The results of estrogenic activity, detected by E-screen and expressed as EC50, showed a high potential of imatinib (10(-7) μM) followed by cisplatin and 5-fluorouracil. Capecitabine was poorly estrogenic while etoposide and doxorubicin EC50 values were not possible to determine. Cytotoxicity was found at concentrations far from those detected in effluents. The potential endocrine activity of the most active drugs could be associated with human and wildlife risk when considering their occurrence in the environment.


Excellent clinical and radiological outcome following locking compression plate fixation of displaced medial clavicle fractures.
Treatment of medial clavicle fractures is still controversially discussed in the community of upper extremity surgeons. An increasing number of symptomatic non-unions following conservative treatment of displaced fractures led to the development of various surgical approaches. Aim of this study was to evaluate the clinical and radiological outcome following operative treatment of displaced medial end clavicle fractures. Patients who presented with a displaced fracture of the medial clavicle between September 2012 and December 2019 were retrospectively enrolled in this study. All patients were operatively treated with open reduction and internal fixation (ORIF) using an anatomically precontoured locking compression plate (LCP) originally designed for the lateral clavicle (Synthes®, Umkirch, Germany). Functional outcome was recorded using the American Shoulder and Elbow Surgeons (ASES) Score, the Munich Shoulder Questionnaire (MSQ), Shoulder Pain and Disability Index (SPADI) and Constant Score. Overall 18 patients with a mean age of 54.5 ± 23.5 years suffering from a displaced fracture of the medial clavicle were identified. The mean follow-up was 40.9 ± 26.2 months. The mean ASES accounted for 88.3 ± 20.8 points, the mean MSQ was 83.1 ± 21.7 points, the mean SPADI was 85.6 ± 22.5 and a mean normative age- and sex-specific Constant Score of 77.5 ± 19.1 points resulted. No minor or major complications were observed. Radiologic fracture consolidation was achieved in all patients after a mean of 6.4 months. Surgical treatment of displaced medial clavicle fractures using an anatomically precontoured locking plate originally designed for the lateral clavicle led to very good to excellent clinical and functional results. No: DRKS00024813 , retrospectively registered 19.03.2021 ( www.drks.de ).


The development of health care-seeking behaviors in traditional-age undergraduate college students.
Traditional-age undergraduate college students are embarking into the world of autonomous decision making. These decisions encompass not only academics but also lifestyle and life-skills. One of the life-skill areas in which students have difficulty is seeking health care independently. The aim of this pilot study is to gather qualitative data to help illuminate the process of the development of health care-seeking behaviors in traditional-age undergraduate college students (18-23 years). A purposive focus group sample of eight traditional-age undergraduate college students was recruited from a private university in the northeastern United States. Five major themes emerged: needing help or care, expectations, decision making, healthcare accessibility, and future needs. Health care for these student participants is expected upon demand by them in this "age of convenience." The findings indicate these traditional-age undergraduate college students view themselves as independent but still rely on parental supervision of health care. Implications for providing primary health care for this generation may include marketing strategies to meet this perspective of "24-7" care based upon this limited focus group, but further expanded studies are needed for generalizations.


Modification of the drop dialysis technique for use with larger volume samples.
Desalting of nucleic acids by the drop dialysis method is limited by the fact that only small volume samples can be used due to the lack of sample containment on the membrane filters. A specially modified Styrafoam cup can be used as a membrane filter holder which serves to contain the sample, thus permitting dialysis of larger sample volumes.


Body contouring by combined abdominoplasty and medial vertical thigh reduction: experience of 14 cases.
The common perception of beauty in the human body has shown a dramatic change over the past few decades culminating in a preoccupation not only with body weight, but also with body image. Obesity is becoming prevalent in our society, and yet generalised redundancy of skin following massive weight reduction can also be an affliction. Localised fat deposits in one or more regions of the trunk, upper arms and thighs are common and are virtually impossible to correct by diet, weight loss or exercise. Excision of the excess pendulous skin and/or the localised fat deposits are able to reduce or even eliminate the physical problems associated with the condition and contribute significantly to patient self-esteem. These procedures are usually multiple and extensive. Combining and reducing the number of such procedures while obtaining optimal results would be most beneficial to both the surgeon and the patient. We report our experience of 14 patients who underwent body contouring operations using combined abdominoplasty and medial thigh reduction with analysis of the results and discussion of the requirements and the advantages of the technique.


The prognostic implications of DSM-IV abuse criteria in drinking adolescents.
The validity of the DSM-IV diagnostic criteria for alcohol abuse has been questioned, and additional issues have been raised regarding the performance of this label in adolescents. While future diagnostic manuals might alter the approach to abuse, it is worthwhile to evaluate the implications of the current definition that has been in place since 1994. Six hundred and sixteen 12-19-year-old subjects (mean 16.5 years) were offspring identified in the Collaborative Study on the Genetics of Alcoholism (COGA) protocol who had ever consumed a full drink and who were followed up 5 years later using age-appropriate semi-structured interviews. Following the guidelines for evaluating the utility of the diagnostic labels of Robins and Guze [Robins, E., Guze, S.B., 1970. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am. J. Psychiat. 126, 983-987], the subjects with alcohol abuse were compared with other groups regarding clinical validators and clinical course. At initial interview, the pattern of most alcohol use and problem variables were least severe for teenagers with no diagnosis, intermediate for those with abuse, and the highest for individuals with alcohol dependence. At follow-up, 50% of those with initial abuse maintained that diagnosis, 19% developed dependence, and 31% had no DSM-IV diagnosis. Baseline alcohol abuse predicted follow-up diagnosis even when evaluated along with initial demographic and substance use characteristics. These results support some assets for the DSM-IV alcohol abuse criteria in these adolescents, including indications of both cross-sectional and predictive validities. Additional studies will need to compare the current abuse label with other possible approaches.


Site-specific acetylation of the proteasome activator REGγ directs its heptameric structure and functions.
The proteasome activator REGγ has been reported to promote degradation of steroid receptor coactivator-3 and cyclin-dependent kinase inhibitors p21, p16, and p19 in a ubiquitin- and ATP-independent manner. A recent comparative analysis of REGγ expression in mouse and human tissues reveals a unique pattern of REGγ in specific cell types, suggesting undisclosed functions and biological importance of this molecule. Despite the emerging progress made in REGγ-related studies, how REGγ function is regulated remains to be explored. In this study, we report for the first time that REGγ can be acetylated mostly on its lysine 195 (Lys-195) residue by CREB binding protein (CBP), which can be reversed by sirtuin 1 (SIRT1) in mammalian cells. Site-directed mutagenesis abrogated acetylation at Lys-195 and significantly attenuated the capability of REGγ to degrade its target substrates, p21 and hepatitis C virus core protein. Mechanistically, acetylation at Lys-195 is important for the interactions between REGγ monomers and ultimately influences REGγ heptamerization. Biological analysis of cells containing REGγ-WT or REGγ-K195R mutant indicates an impact of acetylation on REGγ-mediated regulation of cell proliferation and cell cycle progression. These findings reveal a previously unknown mechanism in the regulation of REGγ assembly and activity, suggesting a potential venue for the intervention of the ubiquitin-independent REGγ proteasome activity.


Coronary microvascular dysfunction and cardiovascular disease: Pathogenesis, associations and treatment strategies.
Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the pathophysiological mechanism of CMD is still limited at present, which greatly restricts its clinical diagnosis and treatment. Studies have shown that CMD is closely related to a variety of cardiovascular diseases, can aggravate the occurrence and development of cardiovascular diseases, and is closely related to a poor prognosis in patients with cardiovascular diseases. Improving coronary microvascular remodelling and increasing myocardial perfusion might be promising strategies for the treatment of cardiovascular diseases. In this paper, the pathogenesis and functional assessment of CMD are reviewed first, along with the relationship of CMD with cardiovascular diseases. Then, the latest strategies for the treatment of CMD and cardiovascular diseases are summarized. Finally, urgent scientific problems in CMD and cardiovascular diseases are highlighted and future research directions are proposed to provide prospective insights for the prevention and treatment of CMD and cardiovascular diseases in the future.


Tunable Nanoscale Evolution and Topological Phase Transitions of a Polar Vortex Supercrystal.
Understanding the phase transitions and domain evolutions of mesoscale topological structures in ferroic materials is critical to realizing their potential applications in next-generation high-performance storage devices. Here, the behaviors of a mesoscale supercrystal are studied with 3D nanoscale periodicity and rotational topology phases in a PbTiO3 /SrTiO3 (PTO/STO) superlattice under thermal and electrical stimuli using a combination of phase-field simulations and X-ray diffraction experiments. A phase diagram of temperature versus polar state is constructed, showing the formation of the supercrystal from a mixed vortex and a-twin state and a temperature-dependent erasing process of a supercrystal returning to a classical a-twin structure. Under an in-plane electric field bias at room temperature, the vortex topology of the supercrystal irreversibly transforms to a new type of stripe-like supercrystal. Under an out-of-plane electric field, the vortices inside the supercrystal undergo a topological phase transition to polar skyrmions. These results demonstrate the potential for the on-demand manipulation of polar topology and transformations in supercrystals using electric fields. The findings provide a theoretical understanding that may be utilized to guide the design and control of mesoscale polar structures and to explore novel polar structures in other systems and their topological nature.


Psychotic disorder caused by a general medical condition, with delusions. Secondary "organic" delusional syndromes.
Many medical and neurologic disorders cause psychosis with delusions. The pathophysiology of this final common pathway may shed light on idiopathic psychotic disorders such as schizophrenia. By focusing on the "basal ganglia-thalamocortical" and "corticostriatal-thalamocortical" loops that connect limbically related cortical regions with the mesolimbic-mesostriatal dopamine system we can view the neural network that may produce delusional thinking when its restitutive function fails. Given its importance in the memory system of the medial temporal lobe, as the recipient of the emotional valencing from the amygdala, and as a key "loop" structure for cognitive functional integrity, the hippocampus may be a nodal area in the development of rational as opposed to delusional thinking.


Diagnosis of Theileria equi infections in horses in the Azores using cELISA and nested PCR.
Equine piroplasmosis is a tick-borne disease of equids that is often caused by the parasite Theileria equi. We applied competitive ELISA (cELISA) and nested PCR diagnostic methods to detect this parasite in horses by screening 162 samples from mainland Portugal where the parasite is endemic, and 143 from the Azores representing both native and imported horse populations. We found that 2.8% of the Azorean samples tested positive exclusively by cELISA, 1.4% tested positive only by nested PCR, and 9.1% tested positive using both tests. Samples from the native Terceira Pony population were negative for both tests. The parasite was more prevalent in samples from mainland Portugal when both test methods were considered (9.3% positive exclusively by cELISA, 1.9% positive exclusively by nested PCR, and 16.7% positive for both tests). To our knowledge, this is the first time that molecular techniques have been used to detect T. equi in the Azores and the first report of this parasite in the archipelago. Based on this study, it is clear that the import of horses into the Azores and the movement of horses between the islands must be controlled to reduce the risk of new infections, contributing to the protection of native horse populations such as the Terceira Pony population.


Mice with diverse microbial exposure histories as a model for preclinical vaccine testing.
Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic T cell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and T cell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.


The role of bacteria in the blockage of biliary stents.
Recurrent jaundice and cholangitis due to stent occlusion by biliary sludge is a major complication of endoscopic stenting for malignant obstructive jaundice. Scanning electron microscopy study of the blocked stents revealed the sludge to consist of a mixture of bacteria and amorphous material. In vitro study using scanning electron microscopy demonstrated the attachment of bacteria to a segment of stent perfused with infected bile containing live bacteria. Associated with the microcolonies of bacteria was a collection of amorphous material forming a dense concretion on the surface of the stent. This phenomenon was not observed in experiments using sterile bile or with infected bile sterilized by formalin treatment or autoclaving. It was concluded that live bacteria are necessary for the initiation of biliary sludge formation which leads to subsequent stent blockage.


Fifteen ceramic gingival samples: A proposed gingival shade guide.
(1) To put forward a set of valid pink ceramic samples for subjective gingival colour selection in the Caucasian population, and (2) to assess the quality of the shade matches provided by the selected pink samples. The ceramic gingival shade samples (n = 133) were obtained by mixing pairs of basic colours from a single system. In each mixture, the proportions of the colours were altered in 10% increments, following the numerical order used by the manufacturers of the three colour systems under study (Heraceram, Vita VM9 and IPS Style). The CIELAB colour coordinates were recorded using spectrophotometry in three zones of healthy anterior gingiva (n = 360). The sample was randomly divided into two subsamples, each of which contained 180 participants. Subsample 1 was used to select the ceramic gingival samples that provided the best shade matches, using the k-means clustering method. Subsample 2 was used to assess the chromatic validity of the selected gingival samples, according to the coverage error. To identify the ceramic gingival samples that best represented participants' gingival colour, the minimum colour differences (ΔEab∗, ΔE00) between the cluster centroids and the 133 gingival samples were calculated. Fifteen gingival samples were selected: 8 from the Heraceram system, 4 from the VM9 system, and 3 from the IPS Style system. Coverage errors for the 15 gingival samples fell below the gingival clinical acceptability thresholds in the three gingival zones examined. The 15 ceramic gingival colour samples provide satisfactory coverage of the gingival colour space, with coverage errors below the ΔE00 clinical acceptability threshold of 2.9 units. These pink colour samples have the potential to provide good gingival shade matches in subjective colour selection. Mixing basic ceramic colours is a viable method for generating a series of pink shades that can be used as a physical gingival shade guide. The resulting guide provides valid results (under the acceptability thresholds) for subjective selection gingival colour selection in clinical practice.


Real-World Effectiveness of Dupilumab for Patients with Severe Asthma: A Retrospective Study.
Treatment with dupilumab, an anti-interleukin (IL)-4 receptor α monoclonal antibody that blocks both the IL-4 and IL-13 pathways, has demonstrated efficacy for the treatment of severe asthma (SA) with type 2 inflammation. However, few studies have focused on the efficacy of this biologic for the treatment of SA in a real-world setting. From April 2019 to December 2021, 26 Japanese patients with SA received dupilumab at Jikei University Hospital. We retrospectively evaluated the number of moderate-to-severe exacerbations, pulmonary function, maintenance dose of corticosteroids, biomarkers, and adverse events. During a mean follow-up period of 12.6 months, 10 patients received dupilumab as the first biologic, and 16 switched to dupilumab from other biologics. Dupilumab treatment significantly reduced the number of annual exacerbations from 3.4 ± 4.1 to 1.6 ± 2.7 (/person-year, p < 0.01) at the last follow-up regardless of previous biologic use. The Asthma Control Test score significantly improved in all patients by six months after administration but tended to worsen by 24 months in patients with previous biologic use. On the other hand, blood eosinophil counts (BECs) transiently increased and peaked three to six months after administration. The peak timing can be affected by previous biologic use. Adverse events included wheezing immediately after injection, hypereosinophilia, mild conjunctivitis, and relapse of chronic eosinophilic pneumonia in the patient switched from benralizumab. Dupilumab treatment was useful for patients with SA in a real-world setting. However, the BEC should be monitored carefully, especially in patients who previously received anti-IL-5/IL-5 receptor antibody.


Describing and predicting psychological distress after colorectal cancer.
Psychological distress in cancer survivors can be detrimental to treatment adherence and self-care tasks and is associated with poor health behaviors and decreased overall quality of life. The prevalence, course, and predictors of psychological distress after the diagnosis of colorectal cancer are to date not well described. A prospective survey of 1822 colorectal cancer patients was undertaken assessing psychological distress and hypothesized predictors including optimism, cancer threat appraisal, social support, and physical activity at 6 and 12 months postdiagnosis. Logistic regression identified correlates of psychological distress at 12 months postdiagnosis. The prevalence of global psychological distress was low: 8.3% and 6.7% at 6 and 12 months postdiagnosis, respectively. When baseline measures of independent variables were included in a logistic regression model, distress at 6 months postdiagnosis (odds ratio [OR]=10.84), comorbidities (OR=1.64), optimism (OR=0.93), cancer threat appraisal (OR=0.92), and social support (OR=0.94) were significantly associated with distress at 12 months postdiagnosis. A second logistic regression model that included concurrent measures of cancer threat appraisal, social support, and physical activity found that distress at 6 months postdiagnosis (OR=12.49), comorbidities (OR=1.64), optimism (OR=0.94), and concurrent cancer threat appraisal (OR=0.85) were significantly associated with distress at 12 months postdiagnosis. Distress screening at regular intervals is needed to efficiently detect colorectal cancer patients who require in-depth psychological intervention. Threat appraisal is a modifiable variable that should be included in interventions for colorectal cancer survivors. Further research is needed to investigate the potential for physical activity to reduce distress after cancer.


Regulation of human T-cell leukemia virus type 1 (HTLV-1) budding by ubiquitin ligase Nedd4.
The Gag protein of human T-cell leukemia virus type 1 (HTLV-1) contains the conserved sequences PPxY and PTAP, which are putative viral motifs required for budding (L-domain motifs). We show here that the PPxY motif, but not the PTAP motif, is essential for HTLV-1 virion budding from the plasma membrane. In addition, we show that overexpression of Nedd4 enhances HTLV-1 budding and that Nedd4 interacts with Gag via its WW domain. The HECT domain of Nedd4 is also required for budding. These results indicate that Nedd4 or a Nedd4-related ubiquitin ligase plays a critical role in HTLV-1 budding.