Defining the limits of homology modeling in information-driven protein docking.
Information-driven docking is currently one of the most successful approaches to obtain structural models of protein interactions as demonstrated in the latest round of CAPRI. While various experimental and computational techniques can be used to retrieve information about the binding mode, the availability of three-dimensional structures of the interacting partners remains a limiting factor. Fortunately, the wealth of structural information gathered by large-scale initiatives allows for homology-based modeling of a significant fraction of the protein universe. Defining the limits of information-driven docking based on such homology models is therefore highly relevant. Here we show, using previous CAPRI targets, that out of a variety of measures, the global sequence identity between template and target is a simple but reliable predictor of the achievable quality of the docking models. This indicates that a well-defined overall fold is critical for the interaction. Furthermore, the quality of the data at our disposal to characterize the interaction plays a determinant role in the success of the docking. Given reliable interface information we can obtain acceptable predictions even at low global sequence identity. These results, which define the boundaries between trustworthy and unreliable predictions, should guide both experts and nonexperts in defining the limits of what is achievable by docking. This is highly relevant considering that the fraction of the interactome amenable for docking is only bound to grow as the number of experimentally solved structures increases.


Swallowing-induced atrial tachycardia in an adolescent with hypertrophic cardiomyopathy: a case report.
Swallowing-induced tachycardia is a rare phenomenon, with only 50 cases documented worldwide. We present a unique case of an adolescent with hypertrophic cardiomyopathy (HCM) who presented with palpitations and a near syncopal episode. The patient was found to have a swallowing-induced atrial tachycardia. He underwent radiofrequency isolation of the right superior pulmonary vein and ablation of the right anterior ganglionated plexus, which led to a resolution of his symptoms. This case highlights the possible association between HCM and autonomic instability as potential aetiological mechanism for the tachycardia.


Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications.
Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy.


Cost-effectiveness of ranibizumab versus aflibercept in the treatment of visual impairment due to diabetic macular edema: a UK healthcare perspective.
Ranibizumab and aflibercept are alternative anti-vascular endothelial growth factor agents approved for the treatment of visual impairment (VI) due to diabetic macular edema (DME). To estimate, from a UK healthcare perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN) and ranibizumab 0.5 mg treat and extend (T&E) compared with aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8) in the treatment of VI due to DME. A Markov model previously reviewed by the National Institute for Health and Care Excellence was used to simulate the long-term outcomes and costs of treating DME. Health states were defined by increments of ten letters in best-corrected visual acuity (BCVA), with a 3-month cycle length. Patients could gain (or lose) a maximum of two health states between cycles. A 3-year treatment time frame and a lifetime horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Patient baseline characteristics and the efficacy of ranibizumab PRN were derived using data from the RESTORE study. The relative efficacies of ranibizumab PRN, ranibizumab T&E, and aflibercept were assessed with a network meta-analysis. Different utilities were assigned based on BCVA and whether the treated eye was the better- or the worse-seeing eye. Sensitivity analyses tested the robustness of the model. Lifetime costs per patient of treating DME were £20,019 for ranibizumab PRN, £22,930 for ranibizumab T&E, and £25,859 for aflibercept 2q8. Ranibizumab was dominant over aflibercept, with an incremental gain of 0.05 quality-adjusted life-years (QALYs) and cost savings of £5,841 (PRN) and £2,930 (T&E) compared with aflibercept. Ranibizumab PRN and ranibizumab T&E had 79% and 67% probability, respectively, of being cost-effective relative to aflibercept at a willingness-to-pay threshold of £20,000/QALY. When assuming the higher end of PRN injection frequency (15.9 over 3 years), the cost savings associated with ranibizumab were £3,969. From a UK healthcare perspective, ranibizumab provides greater health gains with lower overall costs than aflibercept in patients with VI due to DME.


[Experimental use of a pulsed CO2 laser in bone and osteoplastic operations on the maxillofacial area].
Weak efficiency of laser incisors in bone surgery is primarily connected to a lack in the optimization of laser beam parameters in the above conditions. Experimental data are presented in which bone specimens were sectioned using a beam of a pulsed of continuous CO2 laser. Pulsed irradiation had some advantages over the continuous one in that the marginal necrotic zone of the incision was substantially reduced. The perspectives of the pulsed CO2 laser in maxillofacial surgery are outlined as related to bone and osteoplastic interventions.


Nano- and Micro-Porous Chitosan Membranes for Human Epidermal Stratification and Differentiation.
The creation of partial or complete human epidermis represents a critical aspect and the major challenge of skin tissue engineering. This work was aimed at investigating the effect of nano- and micro-structured CHT membranes on human keratinocyte stratification and differentiation. To this end, nanoporous and microporous membranes of chitosan (CHT) were prepared by phase inversion technique tailoring the operational parameters in order to obtain nano- and micro-structured flat membranes with specific surface properties. Microporous structures with different mean pore diameters were created by adding and dissolving, in the polymeric solution, polyethylene glycol (PEG Mw 10,000 Da) as porogen, with a different CHT/PEG ratio. The developed membranes were characterized and assessed for epidermal construction by culturing human keratinocytes on them for up to 21 days. The overall results demonstrated that the membrane surface properties strongly affect the stratification and terminal differentiation of human keratinocytes. In particular, human keratinocytes adhered on nanoporous CHT membranes, developing the structure of the corneum epidermal top layer, characterized by low thickness and low cell proliferation. On the microporous CHT membrane, keratinocytes formed an epidermal basal lamina, with high proliferating cells that stratified and differentiated over time, migrating along the z axis and forming a multilayered epidermis. This strategy represents an attractive tissue engineering approach for the creation of specific human epidermal strata for testing the effects and toxicity of drugs, cosmetics and pollutants.


Lens design for a white-light cosine-transform achromat.
We describe the lens design for a twin-imaging white-light interferometer in which the interference pattern at the exit-pupil plane is the cosine transform of the spatial-intensity distribution of the object. The achromatic condition in terms of optical power is derived. The analysis of the transform aberration shows that the even aberrations, e.g., spherical aberration and field curvature, do not degrade the cosine transform and need not be corrected. This significant simplification permits us to design systems with good performance and uncomplicated lens structures. We present a lens design with three elements and a length of 320 mm. The system is capable of resolving more than 10(6) pixels with an operating spectral bandwidth of 100 nm. The results of an experiment with an early four-element design are also presented.


Distribution of health care expenditures for HIV-infected patients.
Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy. Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates. Among the 635 patients, total annual expenditures for patients with CD4+ cell counts <50 cells/microL (36,533 dollars per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts > or =350 cells/microL (13,885 dollars per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at approximately 10,500 dollars per patient per year across CD4+ cell count strata. Outpatient expenditures were 1558 dollars per patient per year; however, the clinic and physician component of these expenditures represented only 359 dollars per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%-84% of annual expenses). Physician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States.


The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells.
N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m6A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m6A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth. METTL3 mRNA and protein are expressed more abundantly in acute myeloid leukemia (AML) cells than in healthy HSPCs or other types of tumor cells. Furthermore, METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT, which contributes to the differentiation-promoting effects of METTL3 depletion. Overall, these results provide a rationale for the therapeutic targeting of METTL3 in myeloid leukemia.


Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Antibodies in Rural Areas, South Korea.
We investigated 1,228 residents of 3 rural areas in South Korea and determined that 50 (4.1%) were positive for severe fever with thrombocytopenia syndrome virus antibodies. Fever and gastrointestinal symptoms in the previous 3 years and career duration were associated with virus seropositivity.


How Japanese nurses participate in decision making: Infants with congenital life-threatening conditions.
In Japan, owing to the progress in medical technology, more children with congenital life-threatening conditions survive than ever before. Nurses who care for these children may also influence decision making in difficult situations. We aimed to describe Japanese nurses' approach toward medical decision making when caring for families of infants with congenital life-threatening conditions. Frequently, these nurses must care for and support parents with ambivalent feelings. Qualitative descriptive study. Participants were recruited from neonatal intensive care unit and paediatric wards at a university hospital in Japan from June to July 2016. Data were collected using semi-structured interviews and qualitatively analysed. Japanese nurses described these situations as "decision making regarding the child's medical care" and "daily life at hospitals." The themes included support of parents and the choices made about their children, nurses giving or holding their opinions about care choices, or withholding their opinions during decision-making events. The narratives included 5 focus areas: the parents; the children, the family as a whole; relationship between families and health care providers; and the effect of the clinical environment on the children and families. When caring for children with life-threatening congenital conditions, nurses should develop supportive relationships with parents and contribute to the clinical decision-making process with empathy and based on the most current research data.


Parental education in the treatment of childhood atopic eczema.
To evaluate the role of health education in the treatment of childhood atopic eczema, an eczema school was arranged for the parents. Fifty consecutive patients (aged 4 months-6 years 2 months) with atopic eczema of varying severity were randomly assigned into two groups; one group receiving routine information given by the physician during the medical visit, and the other group also visiting a trained nurse to receive further information on eczema treatment and practical training in controlling atopic eczema. The therapeutic effect was better in the group which had received extra guidance. We suggest that systematic training in eczema treatment should be organized as an important part of eczema treatment.


A double Meckel's diverticulum as obscure gastrointestinal bleeding cause. Report of a case.
Meckel's diverticulum is the most common developmental anomaly of the gastrointestinal tract, affecting 1-4% of the general population. It is usually an incidental finding during laparotomy for other causes; occasional complications are bleeding, obstruction, diverticulitis and perforation. Up to 60% of Meckel's diverticula harbor heterotopic mucosa (mostly gastric or pancreatic), neoplastic degeneration occurs in 1-5% of cases. We report herein a case of obscure gastrointestinal bleeding in a 25-years-old man, due to a double Meckel's diverticulum, both located into jejunum and ileum, harboring ectopic gastric mucosa, diagnosed by a small bowel double contrast enema and managed laparoscopically with a tangential resection. To the best of our knowledge this is an unfrequent case of such a variant of Meckel's diverticulum with ectopic gastric mucosa diagnosed by double contrast enema.


Character Strength and Mental Health Problems among Children from Low-Income Families in South Korea.
This study was conducted to understand the association between character strength and mental health problems among children in early adolescence from low-income families in South Korea. This study used a cross-sectional and descriptive study design with 214 fifth- and sixth-grade elementary school children from low-income families enrolled in 20 community centers and receiving government financial assistance. A bivariate probit model was used to examine the association between character strength and mental health problems in the children. We found that character strength lowers the likelihood of developing hyperactivity-inattention and emotional symptoms among children from low-income families. Additionally, adverse life events were associated with increased mental health problems, whereas adverse life events were not significantly correlated with character strength in the current study. Specific interventions should be developed to cultivate character strength among children in early adolescence from low-income families who are at a high risk of mental health problems under cumulative adverse life events.


Cytosolic RNA recognition pathway activates 14-3-3 protein mediated signaling and caspase-dependent disruption of cytokeratin network in human keratinocytes.
The skin is the primary boundary between the body and the environment. In addition to its properties as a physical barrier, skin keratinocytes actively participate in many defense mechanisms. Viral double-stranded RNA (dsRNA) is the most important viral structure involved in activation of immune response. Intracellular detection of dsRNA by cytoplasmic receptors activates well-characterized antiviral response, as well as pro-inflammatory response and apoptosis of virus-infected cells. Here, we have used quantitative subcellular proteomics to characterize the signaling pathways activated by cytosolic dsRNA recognition pathway in human keratinocytes. Cytoplasmic and mitochondrial proteomes were analyzed using 2-DE in combination with MS, immunoblotting and confocal microscopy. We have identified 239 reproducibly differentially expressed proteins upon dsRNA stimulation. The identified proteins include several key proteins involved in cytoskeletal dynamics, cell signaling, cell death, and stress response. Our analysis provides novel information how the cytokeratin network is disrupted in a caspase-dependent manner upon dsRNA stimulation as well as Encephalomyocarditis virus or Vesicular stomatitis virus infection. We show that this caspase-dependent disruption of cytokeratin is activated by cytoplasmic RNA recognition pathway. In addition, we show that viral infection activates 14-3-3 protein mediated signaling pathways in human keratinocytes which suggest an important role of 14-3-3 proteins in antiviral innate immune response.


A new procedure for purifying histone pairs H2A + H2B and H3 + H4 from chromatin using hydroxylapatite.
A method to purify histone groups H2A+H2B and H3+H4 using dissociation with NaCl and hydroxylapatite chromatography is presented. The procedure is simple, involves mild solvents, and provides milligram quantities of histones of high purity. The histone pairs prepared by this method can regenerate chromatin-like characteristics when combined and reconstituted with DNA.


Adnexal Lesion Imaging: Past, Present, and Future.
Currently, imaging is part of the standard of care for patients with adnexal lesions prior to definitive management. Imaging can identify a physiologic finding or classic benign lesion that can be followed up conservatively. When one of these entities is not present, imaging is used to determine the probability of ovarian cancer prior to surgical consultation. Since the inclusion of imaging in the evaluation of adnexal lesions in the 1970s, the rate of surgery for benign lesions has decreased. More recently, data-driven Ovarian-Adnexal Reporting and Data System (O-RADS) scoring systems for US and MRI with standardized lexicons have been developed to allow for assignment of a cancer risk score, with the goal of further decreasing unnecessary interventions while expediting the care of patients with ovarian cancer. US is used as the initial modality for the assessment of adnexal lesions, while MRI is used when there is a clinical need for increased specificity and positive predictive value for the diagnosis of cancer. This article will review how the treatment of adnexal lesions has changed due to imaging over the decades; the current data supporting the use of US, CT, and MRI to determine the likelihood of cancer; and future directions of adnexal imaging for the early detection of ovarian cancer.


Human melanoma TrkC: its association with a purine-analog-sensitive kinase activity.
The various members of the Trk tyrosine kinase family and p75 neurotrophin receptor (p75(NTR)) have been identified as signaling receptors for the structurally related members of the neurotrophins (NT) family. We have previously reported that NT treatment of murine and human brain-metastatic melanoma cells affects their invasive capacities and increases the production of extracellular-matrix degradative enzymes. These cells express aberrant levels of functional p75(NTR) and TrkC, the putative high-affinity receptor for the neurotrophin NT-3. Here we demonstrate that, by using sensitive immune-complex kinase assays in human brain-metastatic (70W) melanoma cells, TrkC receptors associate with a kinase activity exhibiting a dose-dependent susceptibility to inhibition by the purine-analogs 6-thioguanine and 2-aminopurine. The activity of this purine-analog-sensitive kinase (PASK) was induced by NT-3 in a time-dependent fashion, phosphorylating exogenous myelin basic protein (MBP) but not denatured enolase. It is similar to the one reported to relate with p75(NTR) and TrkA receptors and stimulated by the prototypic NT, nerve growth factor. Thus, PASKs may represent unique signaling components common to NT receptors that could engage joint downstream signaling effectors in brain-metastatic melanoma.


How Korean and White Americans Evaluate and Use Online Advertising and Non-advertising Sources for Prescription Drug Information.
This study examined Korean Americans' evaluation and use of online advertising and non-advertising sources of prescription drug information and compared the findings to those of white Americans. A mail survey was conducted with a disproportionate stratified sample of 600 adults (300 general population and 300 Korean Americans) who have ever taken or are currently taking prescription drugs regularly and reside in a metropolitan area in the Midwestern United States. While both Korean and white Americans evaluated online non-advertising sources more positively than advertising sources, the 2 groups were similar in their evaluation of both online advertising and non-advertising sources. White Americans tended to use more online advertising sources than did Korean Americans, but both groups were equally likely to use non-advertising sources. Evaluation and use of online advertising and non-advertising sources by Korean and white Americans were associated with different predictors.


[The characterization of semirigid coaxial antennae for interstitial and endocavitary microwave hyperthermia].
The increased dissemination of interstitial hyperthermia techniques requires suitable action in quality assurance for the used applicators. This work presents physical-technical methods for complete characterisation of interstitial and endocavitary coaxial antennas used for microwave hyperthermia. After a short introduction about the antennas' physical principle 2 fundamental experiments for acquisition of specific absorption rate (SAR) are described: There are the thermometric method, especially the power pulse technique, using a static solid state phantom and the direct measurement of the amplitude square of emitted electric field using miniaturized E-field probes in a fluid phantom. Principal problems occurring during E-field measurements in the near field zone of insulated antennas in media (phantom fluid) are discussed in detail. Characteristic relative SAR profiles were found for each tested applicator design. The profiles were described using the following parameters: depths of SAR maximum, effective heating lengths and lengths of the dead end of the antennas relative to the 50%-iso-SAR-surface. Antenna designs for endocavitary and interstitial purposes were measured at variable insertion depths. The changing SAR-patterns were discussed regarding the found measurement data. Additionally measurements of parallel and inclined antenna arrays consisting of 4 interstitial applicators are described. The final discussion give future perspectives to forthcoming developments for interstitial and endocavitary microwave hyperthermia.


Selective Permeation through One-Atom-Thick Nanoporous Carbon Membranes: Theory Reveals Excellent Design Strategies!
Research on the permeation of various species through one-atom-thick nanoporous carbon membranes has gained an unprecedented importance in the past decade, thanks to the development of numerous theoretical design strategies for a plethora of applications ranging from gas separation, water desalination, isotope separation, and chiral separation, to DNA sequencing. Although some of the recent experiments have demonstrated successful performance of such carbon membranes in sieving, many of the suggested applications are yet to be realized in experiments. This review aims to draw the attention of the theoretical as well as the experimental researchers working on two-dimensional carbon materials toward the recent theoretical developments probing the permeation of various species such as atoms, ions, small molecules, and biopolymers like DNA through carbon frameworks like graphynes, graphdiyne, graphenylenes, and various forms of nanoporous graphene, including graphene crown ethers. The underlying guiding principles toward the design of carbon-based membranes for nanofiltration are established using estimates of the adsorption energies, barrier heights for permeation, rates of permeation, selectivities, permeances, etc. The crucial roles of tunneling, temperature effects, chemical functionalities, and dynamical aspects of the nanopores are also highlighted, paving the way to a comprehensive description of the theoretical design strategies for tailoring the applicability of novel nanoporous carbon membranes in sieving and related aspects.


Syringeability of morphine ARER, a novel, abuse-deterrent, extended-release morphine formulation.
Background: Extended-release (ER) morphine formulations are commonly manipulated for non-oral routes of administration, particularly via injection. Morphine ARER, an abuse-deterrent formulation of ER morphine, has both physical and chemical properties that deter abuse. Objectives: To assess the syringeability of morphine ARER using in vitro laboratory studies. Methods: Intact, cut, or crushed morphine ARER tablets were incubated in 1, 5, or 10 mL of room temperature or 90°C water for 1, 5, 10, or 30 min of agitation. Crushed ER morphine tablets were assessed in 10 mL room temperature water. The difficulty to draw the mixture into a syringe was assessed on a scale of 1 (very easy) to 10 (impossible). If the prepared mixture was syringeable, released morphine was measured analytically. Results: Crushed and cut morphine ARER tablets formed a viscous material when subjected to a liquid environment and were rated as "impossible to syringe" in ≤5 mL water and were slightly syringeable in 10 mL water. In contrast, all syringeability tests of crushed ER morphine were rated as "very easy to syringe". After 30 min in room temperature water, crushed ER morphine released 75% morphine whereas intact, cut, and crushed morphine ARER tablets released a maximum of 12%, 12%, and 5% of the total morphine content. Heating extractions resulted in increased morphine release. Conclusion: The difficulty to syringe morphine ARER when manipulated suggests that morphine ARER has abuse-deterrent properties that may deter intravenous abuse.


Polycythemia vera blood burst-forming units-erythroid are hypersensitive to interleukin-3.
Because polycythemia vera (PV) is a clonal hematopoietic stem cell disease with a trilineage hyperplasia, and interleukin-3 (IL-3) stimulates trilineage hematopoiesis, we have studied the response of highly purified PV blood burst-forming units-erythroid (BFU-E) to recombinant human IL-3 (rIL-3). Whereas the growth of normal blood BFU-E in vitro rapidly declined by 40 and 60% after 24 and 48 h of incubation without 50 U/ml of rIL-3, the growth of PV BFU-E declined by only 10 and 30% under the same conditions, demonstrating a reduced dependence on rIL-3. A reduced dependence of PV BFU-E on recombinant human erythropoietin (rEP) was also present. Dose-response experiments showed a 117-fold increase in PV BFU-E sensitivity to rIL-3, and a 6.5-fold increase in sensitivity to rEP, compared to normal BFU-E, whereas blood BFU-E from patients with secondary polycythemia responded like normal BFU-E. Endogenous erythroid colony (EEC) formation, which is independent of the addition of rEP, was reduced by 50% after erythroid colony-forming cells were generated from PV BFU-E in vitro without rIL-3 for 3 d, whereas rEP-stimulated erythroid colonies were unaffected. These studies demonstrate a striking hypersensitivity of PV blood BFU-E to rIL-3, which may be the major factor in the pathogenesis of increased erythropoiesis without increased EP concentrations.


Simultaneous Fluorescence Visualization of Endoplasmic Reticulum Superoxide Anion and Polarity in Myocardial Cells and Tissue.
Diabetic cardiomyopathy (DCM) is a critical complication of diabetes, the accurate pathogenesis of which remains elusive. It is widely accepted that endoplasmic reticulum (ER) stress and abnormal fluctuations of reactive oxygen species (ROS) are considered to be closely associated with progress of DCM. In addition, DCM-induced changes of myocardial tissue and ROS-derived oxidation of proteins will cause changes of the hydrophilic and hydrophobic domains and may further seriously alter the myocardial cell polarity. Thus, real-time detection of ROS and polarity in ER of live cells and in tissue will contribute to revealing the exact molecular mechanisms of DCM. In this article, we first present an ER-targetable fluorogenic probe termed ER-NAPC for sensitive and selective detection of superoxide anion (O2•-). ER-NAPC can precisely target ER and visualize the increase of O2•- level in a live H9c2 cardiomyocyte cell during ER stress. Meanwhile, by combining ER-NAPC with a polarity-sensitive probe, ER-P, we accomplish the simultaneous fluorescence visualization of O2•- and polarity in ER of live cells and diabetic myocardial tissue. The dual-color fluorescence imaging results indicate that the O2•- level and polarity will synergistically rise during ER stress in live cells and diabetic myocardial tissue. The proposed dual-color imaging strategy may offer a proven methodology for studying coordinated variation of different parameters during ER stress oriented disease.


Modelling of Flexible Adhesives in Simple Mechanical States with the Use of the Darijani-Naghdabadi Strain Tensors and Kirchhoff-de Saint-Venant Elastic Potential.
Practical aspects of modelling of flexible adhesives with the energy conjugate measures of stress and strain of the Darijani-Naghdabadi (D-N) family are discussed. A possibility of description of materials exhibiting non-linear physical characteristics with the use of non-linear geometric relationships and linear elastic constitutive law is considered. Nominal stress vs. stretch relations are specified in cases of simple tension and simple shear with the use of the Kirchhoff-de Saint-Venant elastic potential and D-N energy conjugate stress and strain measures. Obtained theoretical estimates were compared with experimental results of simple tension and simple shear tests performed on Sika PM polyurethane (Cracow, Sika Poland). The deformation rate was fixed in order to minimize the influence of viscosity. Values of parameters α,β in the definition of the D-N strain tensor were optimized in order to provide good agreement between model predictions and experimental results. Observed discrepancies indicate that the proposed approach is not appropriate for constitutive modelling of the PM polymer. The presented approach is proposed to be used as a simple design model providing practical formulas describing the behavior of materials of non-linear characteristics in chosen mechanical states. Admissible values of exponents α,β are discussed regarding its bijectivity in a limited range of variation of principal stretches.


Oral pentoxifylline in therapy-resistant idiopathic OAT syndrome.
After previous treatment failure using tamoxifen either alone or in combination with kallikrein, 25 patients with idiopathic oligoasthenoteratozoospermia (OAT syndrome) were subjected to 3 months of treatment with pentoxifylline at a dosage of 1200 mg/day. The only statistically significant (p < .008) improvement detected in the post-therapeutic spermiograms was an increase of normal forms. All other ejaculate parameters (density, motility, swelling test, penetration test) remained unchanged, and there was only one post-therapeutic pregnancy. It would appear the pentoxifylline after failure of established treatment modalities is not a therapy of choice in idiopathic OAT syndrome.


Design and Clinical Application Effect Analysis of a New Type of Oral Fluid Suction Device for Patients with Orotracheal Intubation.
Tracheal intubation is an important access to general anesthesia surgery or respiratory support in critically ill patients. Orotracheal intubation is the most common method of establishing artificial airways in clinical practice. Tracheal intubation and mechanically assisted breathing are among the important steps in the clinical rescue of critically ill patients. During tracheal intubation, it easily causes iatrogenic skin damage, unclear mouth, ulcer, and other oral mucosal complications due to the improper fixation method and excellent dental pads. Therefore, the purpose of this study was to design a novel oral suction device for patients with orotracheal intubation and explore its safety, convenience, and comfort in the clinical application of orotracheal intubation patients. From October 2016 to April 2017, a total of 232 patients with mechanical ventilation through orotracheal intubation in the Department of Surgery and Critical Care Medicine were selected by the convenience sampling method. According to the random number table method, 232 cases were divided into the experimental group and control group, with 116 cases in each group. The experimental group used a self-designed oral fluid suction device to fix the tracheal intubation; the control group used the traditional method, placing ordinary disposable tooth pads, and then using 3M tape to fix the tracheal intubation. The incidence of oral mucosa and lip pressure ulcers, patient comfort, and tracheal tube displacement were observed and compared between the two groups. The incidence of oral mucosa and lip pressure ulcers in the observation group using the self-designed oral fluid suction device to fix the tracheal intubation was significantly lower than that in the control group. At the same time, the comfort of the patients was significantly higher than that of the control group, the incidence of tracheal tube displacement was significantly lower than that of the control group, and the differences between the above indicators were statistically significant (P < 0.05). For patients with orotracheal intubation, using a new oral fluid suction device to fix the tracheal intubation can effectively prevent the displacement of the tracheal intubation, protect the oral mucosa and lips, and reduce the pain of the patient. At the same time, the oral fluid suction device designed in this study has low production cost, strong practicability, and is suitable for clinical promotion.


Systemic antibiotic treatment for meibomian gland dysfunction-A systematic review and meta-analysis.
To review the efficacy and safety of oral doxycycline antibiotics versus macrolides in the treatment of meibomian gland dysfunction (MGD). Systematic review and meta-analysis. We performed a systematic search of electronic databases for all peer-reviewed published studies which included clinical outcomes of oral antibiotic MGD treatment. Individual study data were extracted and evaluated in a weighted pooled analysis, including total sign and symptom scores, meibomian gland secretion score, tear break-up time (TBUT), fluorescein staining score and rate of complications. Two thousand nine hundred and thirty-three studies were found, of which 54 were eligible for the systematic review, and six prospective studies were ultimately included for analysis, reporting on 563 cases from three countries. Age of affected patients ranged between 12 and 90 years. Overall, both treatment methods induced improvement in MGD signs and symptoms. In pooled analysis, macrolides were significantly superior in the total signs score (pooled standardized mean difference (SMD) -0.51, 95% confidence interval (CI): -0.99 to -0.03), meibomian gland secretion score (pooled SMD -0.25, 95%CI: [-0.48, -0.03]), TBUT (SMD -0.31, 95%CI: [-0.50, -0.13]) and fluorescein staining score (SMD -1.01, 95%CI: [-1.72, -0.29]). Moreover, while no severe complications were reported for both treatments, the macrolide group exhibited significantly less adverse events (pooled odds ratio 0.24 with a 95% CI of 0.16 to 0.34). Both macrolides and tetracyclines are effective treatments for MGD. In this study, macrolides exhibited better efficacy and safety profile compared to tetracyclines.


Effect of treatment on established osteoporosis in young women with amenorrhoea.
Amenorrhoea in women of reproductive age causes loss of bone mineral. This study assessed the effect of treatment of amenorrhoea on bone mineral density. Serial measurements of bone mineral density were obtained in women receiving treatment for amenorrhoea. Eighty-five women aged 17-40 with a past or current history of amenorrhoea, from various causes, with median duration of 46.5 months (range 8 months-21 years). Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry. Initial vertebral bone mineral density was low, mean 0.85 (SD 0.10) g/cm2. After an interval of 19.6 (SD 7.5) months on treatment there was a highly significant increase to 0.89 (SD 0.10) g/cm2 (P < 0.0005). This was equivalent to a gain in bone mass of 2.1% per year (95% confidence interval 1.5-2.8%). Improvement was seen in all diagnostic groups (except polycystic ovary syndrome) and with all types of therapy. We observed no difference in the response of previously untreated patients compared with those already on treatment, nor any change in response with increasing duration of treatment. No new fractures were reported during the study. Bone mineral density in young women with amenorrhoea is improved by appropriate treatment, but recovery is not substantial. Hence early diagnosis and therapy is essential to prevent bone loss.


A two-sample Bayesian t-test for microarray data.
Determining whether a gene is differentially expressed in two different samples remains an important statistical problem. Prior work in this area has featured the use of t-tests with pooled estimates of the sample variance based on similarly expressed genes. These methods do not display consistent behavior across the entire range of pooling and can be biased when the prior hyperparameters are specified heuristically. A two-sample Bayesian t-test is proposed for use in determining whether a gene is differentially expressed in two different samples. The test method is an extension of earlier work that made use of point estimates for the variance. The method proposed here explicitly calculates in analytic form the marginal distribution for the difference in the mean expression of two samples, obviating the need for point estimates of the variance without recourse to posterior simulation. The prior distribution involves a single hyperparameter that can be calculated in a statistically rigorous manner, making clear the connection between the prior degrees of freedom and prior variance. The test is easy to understand and implement and application to both real and simulated data shows that the method has equal or greater power compared to the previous method and demonstrates consistent Type I error rates. The test is generally applicable outside the microarray field to any situation where prior information about the variance is available and is not limited to cases where estimates of the variance are based on many similar observations.


Imperfect assessment and limited information preclude optimal strategies in male-male fights in the orb-weaving spider Metellina mengei.
Agonistic behaviour between male orb-web spiders Metellina mengei competing for access to female webs was examined in field experiments to test the major predictions of game theory. Winners of fights were significantly larger than losers, particularly with respect to the length of the first pair of legs, which are sexually dimorphic in this species and used extensively in agonistic encounters. The size of the winning male had no influence on contest intensity or duration, and neither did relative size. However, fight intensity and duration were both positively correlated with the size of the losing male. Resident males won significantly more contests than intruders. Winning intruders were significantly larger than winning residents and it was these winning intruders that tended to produce the longer fights. Female weight and hence reproductive value had a marked influence on fight intensity and duration of fights won by the intruder but not those won by the resident. This indicates that only the resident obtains information about the female. These data are discussed with reference to the discrepancy with theory and a failure of some contestants to obtain information on resource value and relative contestant size necessary to optimize fight strategy.


Bioactivities and Mode of Actions of Dibutyl Phthalates and Nocardamine from Streptomyces sp. H11809.
Dibutyl phthalate (DBP) produced by Streptomyces sp. H11809 exerted inhibitory activity against human GSK-3β (Hs GSK-3β) and Plasmodiumfalciparum 3D7 (Pf 3D7) malaria parasites. The current study aimed to determine DBP's plausible mode of action against Hs GSK-3β and Pf 3D7. Molecular docking analysis indicated that DBP has a higher binding affinity to the substrate-binding site (pocket 2; -6.9 kcal/mol) than the ATP-binding site (pocket 1; -6.1 kcal/mol) of Hs GSK-3β. It was suggested that the esters of DBP play a pivotal role in the inhibition of Hs GSK-3β through the formation of hydrogen bonds with Arg96/Glu97 amino acid residues in pocket 2. Subsequently, an in vitro Hs GSK-3β enzymatic assay revealed that DBP inhibits the activity of Hs GSK-3β via mixed inhibition inhibitory mechanisms, with a moderate IC50 of 2.0 µM. Furthermore, the decrease in Km value with an increasing DBP concentration suggested that DBP favors binding on free Hs GSK-3β over its substrate-bound state. However, the antimalarial mode of action of DBP remains unknown since the generation of a Pf 3D7 DBP-resistant clone was not successful. Thus, the molecular target of DBP might be indispensable for Pf survival. We also identified nocardamine as another active compound from Streptomyces sp. H11809 chloroform extract. It showed potent antimalarial activity with an IC50 of 1.5 μM, which is ~10-fold more potent than DBP, but with no effect on Hs GSK-3β. The addition of ≥12.5 µM ferric ions into the Pf culture reduced nocardamine antimalarial activity by 90% under in vitro settings. Hence, the iron-chelating ability of nocardamine was shown to starve the parasites from their iron source, eventually inhibiting their growth.


The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease.
There is growing evidence that chronic obstructive pulmonary disease (COPD) is a risk factor for coronary heart disease. Simvastatin is a hypolipemic drug with proven efficacy in the prevention of cardiovascular diseases. Observational studies showed that statins may be useful in the reduction of mortality from COPD. Experimental studies on animals showed anti-inflammatory effects of statins on the lung tissue. The aim of this study was to evaluate the influence of simvastatin on inflammatory markers in patients with COPD. Fifty-six patients (aged 44-80 years) with stable COPD (a mean forced expiratory volume in 1 second [FEV1] 55%), were randomly assigned (1:1) to receive simvastatin 40 mg/day or to receive no statin treatment. Blood samples were collected before, 2 weeks, and 3 months after statin administration. The levels of fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha, interleukin 6 (IL-6), and matrix metalloproteinase-9 were measured. The groups did not differ significantly in terms of demographic data, clinical symptoms, pharmacological treatment, spirometry, and lipid profile at baseline. Among comorbidities only arterial hypertension was more frequent in the statin group (32.1% vs. 17.9%, P = 0.03). After 2 weeks as well as 3 months of simvastatin treatment, no significant reduction of any measured inflammatory markers was observed. There was a nonsignificant reduction of CRP and IL-6 in the subgroup with FEV1 >50% during simvastatin treatment. There was a decrease in total cholesterol (from 5.7 to 4.7 mmol/l, P = 0.0018) and low-density lipoprotein cholesterol (from 3.46 to 2.47 mmol/l, P = 0.000037) in the statin group. In COPD patients, a 3-month treatment with simvastatin does not reduce circulating inflammatory markers.


Measurement of glutamate carboxypeptidase II (NAALADase) enzyme activity by the hydrolysis of [³H]-N-acetylaspartylglutamate (NAAG).
The peptide N-Acetylaspartylglutamate (NAAG) is hydrolyzed by N-Acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II) into N-Acetylated aspartate (NAA) and glutamate. Hydrolysis can be measured as described in this unit by employing radiolabeled NAAG (NAA-[(3)H]glu) as the substrate. The occurrence of NAALADase activity in a wide range of tissues has implications for a variety of physiological purposes. The assay described here is useful for the analysis of NAALADase activity and its inhibition in brain synaptosomal preparations, tissue homogenates and tissue culture cell pellets.


Nursing role in well-child care: Systematic review of the literature.
To describe and compare well-child care (WCC) in Australia, the Netherlands, and the United Kingdom (UK), focusing on the role of nurses and their interactions with other primary care providers in order to derive relevant lessons for Canada's interprofessional primary care teams. Ovid MEDLINE, EMBASE, and CINAHL were searched broadly using the search terms well child care, nursing role, and delivery of care and other synonymous terms. In addition, Google Scholar was used to search for gray literature, and reference mining revealed a few other relevant articles. The original search identified 929 articles. The inclusion criteria were the following: relevant to WCC delivery; focuses on Canada, the Netherlands, the UK, Australia, or an international comparison; describes care of healthy term infants; describes care provided in the community; and describes the role of the nurse in WCC delivery. An abstract review followed by full-text review condensed the search to 25 selected articles. Selected articles varied in method and scope; thus, a narrative synthesis was generated using thematic analysis. In Australia, the Netherlands, and the UK, many WCC tasks are performed by trained public health nurses in a separate but parallel system to family medicine, with interaction between nurses and FPs varying greatly among countries. In general, nurses' roles in WCC remained in the preventive care and screening domains, including monitoring development, providing health education, and supporting parents. The 3 overarching themes that were identified were around professional development and education, integration of care and interprofessional collaboration, and the nurses' role in an evolving health system. International examples, given Canada's primary care reforms, suggest it is time to examine greater role sharing in WCC between nurses and FPs in interdisciplinary primary care teams.


Microchips for macropods: First use of a microchip-automated door by a bridled nailtail wallaby (Onychogalea fraenata).
Commercially available microchip-automated devices for companion animals also have potential application with captive wildlife. To explore this potential, a captive bridled nailtail wallaby was trained to use a SureFlap Microchip Pet Door. Throughout the 62 day study the wallaby's interactions with the door increased in frequency and intensity, culminating in the repeated use of the microchip-automated door. This was the first record of any captive macropod being trained to use a microchip-automated device and demonstrates proof-of-concept that captive macropods can successfully utilize commercially available microchip-automated devices. Further research is recommended to develop methodology and evaluation techniques for training captive macropods while also exploring intra- and inter-species variations in responses.


Exploring the Molecular Mechanism of Qing Guang An Granule in Treating Glaucoma Using Network Pharmacology and Molecular Docking.
Qing Guang An Granule (QGAG), a Chinese patent medicine, has been used clinically to treat glaucoma for more than 20 years. To explore the possible mechanism of treatment of QGAG in glaucoma by using network pharmacology and molecular docking in this study. Active compounds and targets of each herb in QGAG were retrieved via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Glaucoma-related targets were acquired from OMIM and DisGeNET database. Key targets of QGAG against glaucoma were acquired by overlapping the above targets via the Venn diagram. Using the DAVID, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the key targets were performed. The docking process was performed using the AutoDock 4.2.6 and AutoDock Vina 1.1.2. The 55 active compounds and 173 targets were obtained and constructed a compound-target network. The 20 key targets of QGAG in treating glaucoma were acquired, and these targets are involved in the apoptotic process, cellular response to hypoxia, negative regulation of cell growth, and ovarian follicle development. The main pathways are p53, HIF-1, PI3K-Akt, and neurotrophin signaling pathway. QGAG may exert a protective effect by acting on the optic nerve at a molecular and systemic level. This study can provide a certain basis for future researches on exploring the QGAG in treating glaucoma and provide new ideas for developing new drugs.


Antagonism of Rhizosphere Streptomyces yangpuensis CM253 against the Pathogenic Fungi Causing Corm Rot in Saffron (Crocus sativus L.).
Plant diseases lead to a significant decline in the output and quality of Chinese herbal medicines. Actinomycetes play a vital role in the rhizosphere ecosystem. This is especially true for Streptomyces, which have become a valuable biological control resource because of their advantages in producing various secondary metabolites with novel structures and remarkable biological activities. The purpose of this study was to isolate an effective antagonistic actinomycete against the pathogen of corm rot in saffron. An antagonistic actinomycete, CM253, was screened from the rhizosphere soil samples of Crocus sativus, by plate co-culture with four pathogenic fungi (Fusarium oxysporum, Fusarium solani, Penicillium citreosulfuratum, and Penicillium citrinum). CM253 inhibited the growth and development of F. oxysporum hyphae by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, by analyzing the degrading enzyme, the growth-promoting performance, and the whole genome of strain CM253, it was identified as Streptomyces yangpuensis, which produces NH3, protease, glucanase, cellulase, IAA, and ACC deaminase. In addition, 24 secondary metabolite synthesis gene clusters were predicted in antiSMASH. We identified genes encoding 2,3-butanediol; methionine; isoprene (metH, mmuM, ispEFH, gcpE, idi, and ilvABCDEH); biofilm formation; and colonization (upp, rfbBC, efp, aftA, pssA, pilD, fliA, and dhaM). Above all, S. yangpuensis CM253 showed the potential for future development as a biocontrol agent.


Influenza: incidence, symptoms and treatment.
Influenza is a common respiratory condition that has a history of developing into epidemics and pandemics. Individuals at risk of influenza and related complications include older people, young children and individuals with chronic renal, cardiac and respiratory diseases. Influenza can begin suddenly and is accompanied by fever, chills, aches, pains, headaches, fatigue, cough and generalized weakness that can last up to 14 days. Complications of influenza include secondary bacterial pneumonia, post-influenza encephalitis, changes in cardiac electrocardiogram and secondary bacterial infections, such as Staphylococcus aureus-induced myositis. The influenza vaccine is the main form of treatment. Suitably qualified nurse prescribers and nurses who supply and administer the vaccine under patient group directions should be sufficiently knowledgeable about the virus and how its transmission can be prevented in order to educate patients at risk of developing influenza about the role of the vaccine in the prevention of the disease.


Diterpenoids and C13 Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis.
Croton yanhuii (Family Euphorbiaceae) is an annual aromatic plant endemic to Yunnan Province, China, which yields an aromatic, spicy oil used as a flavoring and fragrance. The aim of the present study was to acquire secondary metabolites from the leaves and twigs of C. yanhuii and to evaluate their cytotoxic activity. Five new diterpenoids, croyanhuins A-E (1-5), and one new C13 nor-isoprenoid, croyanhuin F (6), were isolated from the leaves and twigs of C. yanhuii. Their structures and absolute configurations were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS) and confirmed by electronic circular dichroism (ECD) spectra or single-crystal X-ray diffraction analysis. Among the new terpenoids, compounds 1 and 3 inhibited cell proliferation and viability in a dose- and time-dependent manner, whereas both induced cleavage of either caspase-3 or PARP-1 in the SW480 cell line. Additionally, we observed that Z-YVAD-FMK and Z-VAD-FMK, two caspase inhibitors, inhibited the compound-dependent cell viability loss, suggesting that either of them can induce pyroptosis and caspase-dependent apoptosis. These biological assay results revealed that compounds 1 and 3 induce different kinds of programmed cell death in SW480 cells.


Reliability and validity of TIPS wireless ECG prototypes.
The aims of the present study are to examine the reliability and validity of the Heart Rate signal registered using two self-made wireless ECG systems, R-Tips and TipsShirt, and to compare them with another commercial ECG device typically used in psychophysiology studies. An ECG simulator was used to artificially generate signals corresponding to different cardiac frequencies. Results of the reliability study showed that the signal acquisition, signal processing and signal transmission were reliable and valid for R-Tips and TipsShirt. Consequently, these wireless ECG prototypes could be used for studies where the freedom of movements of the participants is fundamental without any loss of quality in the registered signals.


Competing with Crohn's disease: management issues in active patients.
Crohn's disease is a chronic inflammatory bowel disorder that has genetic and environmental risk factors. Although moderate physical activity seems to reduce the risk of developing Crohn's disease, some high-performance athletes live with the disease. Uncontrolled Crohn's disease predisposes patients to numerous nutrient deficiencies and associated health issues such as anemia and osteoporosis. Low-intensity exercise has been shown to decrease flare-ups in sedentary patients; however, high-intensity exercise may lead to increased symptoms. Physicians play a crucial role in coordinating a team approach among the athlete, parents, coach, and athletic trainers to provide the best possible management of diet, training schedule, and treatment.


Expression of the Fis protein is sustained in late-exponential- and stationary-phase cultures of Salmonella enterica serovar Typhimurium grown in the absence of aeration.
The classic expression pattern of the Fis global regulatory protein during batch culture consists of a high peak in the early logarithmic phase of growth, followed by a sharp decrease through mid-exponential growth phase until Fis is almost undetectable at the end of the exponential phase. We discovered that this pattern is contingent on the growth regime. In Salmonella enterica serovar Typhimurium cultures grown in non-aerated SPI1-inducing conditions, Fis can be detected readily in stationary phase. On the other hand, cultures grown with standard aeration showed the classic Fis expression pattern. Sustained Fis expression in non-aerated cultures was also detected in some Escherichia coli strains, but not in others. This novel pattern of Fis expression was independent of sequence differences in the fis promoter regions of Salmonella and E. coli. Instead, a clear negative correlation between the expression of the Fis protein and of the stress-and-stationary-phase sigma factor RpoS was observed in a variety of strains. An rpoS mutant displayed elevated levels of Fis and had a higher frequency of epithelial cell invasion under these growth conditions. We discuss a model whereby Fis and RpoS levels vary in response to environmental signals allowing the expression and repression of SPI1 invasion genes.


Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness.
Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.


[Comparison of the color difference between teeth underwent cold light whitening and two kinds of shade guides].
To investigate which shade guide, Vitapan Classical or Vita Bleachedguide 3DMaster, is better matched with the color of teeth in judging whitening effect, by comparing the color difference between shade tabs and corresponding teeth underwent cold light tooth whitening. A total of 60 patients underwent Beyond cold light tooth whitening from May 2014 to April 2016. The patients were divided into two experimental groups according to the shade guide used. Vitapan Classical shade guide was used to judge whitening effect in one group, and Vita Bleachedguide 3DMaster shade guide was used in another. Shade matching was carried out before and after whitening in both the two groups, and the results were recorded by digital photographs. Shade matching procedures were carried out by two doctors independently. If they chose the same tab, it would be seen as the shade matching result; While if they chose different tabs, another doctor would be invited to make a decision. Photographs were taken in preset conditions: intraoral photos of the full dentition in the front, and the proportion of shooting was 1:3; aperture was F22; shutter speed was 1/200; intensity of flash was M/8; ISO value was 200. The photographs were analyzed by Photoshop software. Chromatic values were measured, and color difference values were calculated. Measuring of chromatic values was carried out by three doctors independently, and all the photos were measured twice by each doctor. Six measure results of each photo were recorded, and the maximum and the minimum were excluded, then the mean was seen as the final result. The color difference values were compared by independent-sample t test. Besides, changes of shade tabs after whitening in the two groups were recorded. Color difference value was 5.06±1.71 in Vitapan Classical group, and 3.39±1.36 in Vita Bleachedguide 3D-Master group. There was statistically significant difference between the two groups (t=4.68,P<0.001). Change of shade tabs was 3.63±1.75 in Vitapan Classical group, and 2.23±1.01 in Vita Bleachedguide 3DMaster group. Vita Bleachedguide 3D-Master is better matched with the color of teeth, so it is preferred in judging the effect of cold light tooth whitening.


A density functional theory study on the deformation behaviors of Fe-Si-B metallic glasses.
Density functional theory has been employed to investigate the deformation behaviors of glassy Fe-Si-B model systems prepared by ab initio molecular dynamics. The atomistic deformation defects which are closely related to the local dilation volumes or excess volumes and unstable bonding have been systematically analyzed. It has been found that the icosahedral structures are relatively stable under shear deformation until fracture occurs. Plastic flow is indicated by interruption of percolating icosahedral structures, caused by unstable Fe-Si bonding of p-s hybridization in nature.


Modified Orbitozygomatic Craniotomy for a Previously Coiled Anterior Communicating Artery Aneurysm: 2-Dimensional Operative Video.
Clip occlusion of previously coiled aneurysms poses unique technical challenges. The coil mass can complicate aneurysm neck access and clip tine approximation. This patient had a previously ruptured anterior communicating artery (ACOM) aneurysm that had been treated with coil embolization. On follow-up evaluation, the patient was found to have a recurrence of the aneurysm, which prompted an orbitozygomatic craniotomy for clip occlusion. The approach provided a favorable view of the aneurysm neck with the coil mass protruding outside the aneurysm dome. Indocyanine green fluoroscopy was used to assist with ideal permanent clip placement along the aneurysm neck. The segment of coils present outside the aneurysm neck was removed to reduce mass effect on the optic chiasm. Postoperative imaging demonstrated aneurysm obliteration. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


How sequence alignment scores correspond to probability models.
Sequence alignment remains fundamental in bioinformatics. Pair-wise alignment is traditionally based on ad hoc scores for substitutions, insertions and deletions, but can also be based on probability models (pair hidden Markov models: PHMMs). PHMMs enable us to: fit the parameters to each kind of data, calculate the reliability of alignment parts and measure sequence similarity integrated over possible alignments. This study shows how multiple models correspond to one set of scores. Scores can be converted to probabilities by partition functions with a 'temperature' parameter: for any temperature, this corresponds to some PHMM. There is a special class of models with balanced length probability, i.e. no bias toward either longer or shorter alignments. The best way to score alignments and assess their significance depends on the aim: judging whether whole sequences are related versus finding related parts. This clarifies the statistical basis of sequence alignment. Supplementary data are available at Bioinformatics online.


Processing speed in the 1st year of life: a longitudinal study of preterm and full-term infants.
Processing speed was assessed at 5, 7, and 12 months in full-term and preterm infants (birth-weight < 1,750 g). Speed was gauged directly in a new task by presenting infants with a series of paired faces, one that remained the same across trials and one that changed; trials continued until infants showed a consistent novelty preference. At all ages, preterms required about 20% more trials and 30% more time than full-terms to reach criterion. Among preterms, slower processing was associated with greater medical risk (e.g., respiratory distress syndrome). Developmental trajectories for speed (and attention) were similar for both groups. Thus, the deficits in processing speed previously found for preterms in childhood are already present in the 1st year of life.


Chlorine dioxide inactivation of Cryptosporidium parvum oocysts and bacterial spore indicators.
Cryptosporidium parvum, which is resistant to chlorine concentrations typically used in water treatment, is recognized as a significant waterborne pathogen. Recent studies have demonstrated that chlorine dioxide is a more efficient disinfectant than free chlorine against Cryptosporidium oocysts. It is not known, however, if oocysts from different suppliers are equally sensitive to chlorine dioxide. This study used both a most-probable-number-cell culture infectivity assay and in vitro excystation to evaluate chlorine dioxide inactivation kinetics in laboratory water at pH 8 and 21 degrees C. The two viability methods produced significantly different results (P < 0.05). Products of disinfectant concentration and contact time (Ct values) of 1,000 mg. min/liter were needed to inactivate approximately 0.5 log(10) and 2.0 log(10) units (99% inactivation) of C. parvum as measured by in vitro excystation and cell infectivity, respectively, suggesting that excystation is not an adequate viability assay. Purified oocysts originating from three different suppliers were evaluated and showed marked differences with respect to their resistance to inactivation when using chlorine dioxide. Ct values of 75, 550, and 1,000 mg. min/liter were required to achieve approximately 2.0 log(10) units of inactivation with oocysts from different sources. Finally, the study compared the relationship between easily measured indicators, including Bacillus subtilis (aerobic) spores and Clostridium sporogenes (anaerobic) spores, and C. parvum oocysts. The bacterial spores were found to be more sensitive to chlorine dioxide than C. parvum oocysts and therefore could not be used as direct indicators of C. parvum inactivation for this disinfectant. In conclusion, it is suggested that future studies address issues such as oocyst purification protocols and the genetic diversity of C. parvum, since these factors might affect oocyst disinfection sensitivity.


Inhalation of Ultrafine Zinc Particles Impaired Cardiovascular Functions in Hypertension-Induced Heart Failure Rats With Preserved Ejection Fraction.
Although it is possible for inhalation of ultrafine particles to impair human health, its effect is not clear in patients with HFpEF. This study investigated cardiac and hemodynamic changes in hypertension-induced rats of HFpEF after inhaling ultrafine zinc particles for a while. Multiple experimental measurements were carried out in DSS rats fed with high salt (HS) and low salt (LS) diets as well as HS diet with the inhalation of ultrafine zinc particles (defined as HP). Cardiac strain and strain rate were quantified by the speckle tracking echocardiography. The pressure and flow waves were recorded in the carotid artery and abdominal aorta and analyzed by the models of Windkessel and Womersley types. HS and HP rats were found to show lower strains on endocardium and epicardium than LS rats. The inhalation of ultrafine zinc particles further reduced the strain in the longitudinal direction on the endocardium of rats with HFpEF, but had relatively small effects on the epicardium. The inhalation of ultrafine zinc particles resulted in the increase of systemic resistance and the decrease of total vascular compliance as well as the increased PWV and induced more severe vascular stiffening in rats with HFpEF. In summary, the inhalation of ultrafine zinc particles deteriorated local myocardial dysfunctions in the LV and the hemodynamic environment in peripheral arteries in rats of HFpEF. This study is of importance to understand the mechanisms of cardiovascular impairments owing to air pollution.


Concerns related to the accurate identification of anterior derangement syndrome in mechanical diagnosis and therapy for low back pain: A case report.
Background: In Mechanical Diagnosis and Therapy (MDT), patients with low back pain (LBP) are classified into subgroups to guide a management strategy. A common subgroup where symptoms improve with lumbar extension is labeled posterior derangement syndrome. A less common subgroup where symptoms improve with lumbar flexion is labeled anterior derangement syndrome. Case Presentation: The patient was a 23-year-old woman with intermittent LBP and discomfort over the left lower extremity was initially diagnosis with posterior derangement syndrome. At the initial and second consultations, postural correction and home exercises with lumbar extension were prescribed. However, at the third consultation, sustained lumbar extension revealed worsening of symptoms and function, which resulted in a revised diagnosis of anterior derangement syndrome. Complete recovery was achieved using exercises with lumbar flexion over 6 weeks. Outcomes: The patient wore the LUMOback in daily life, which is a wearable device measuring pelvic angle and acceleration, for 1 week before the initial MDT consultation and for 6 weeks until discharge. The posture scores (%) is the proportion of time in a week with neutral pelvic tilt. In this patient, the posture score decreased greater than a minimum detectable change of 11.7% when MDT classification changed to anterior derangement. Conclusions: This case report indicates the importance of sustained loading to identify the correct derangement syndrome, and follow-up sessions to confirm or reject the initial diagnosis by monitoring symptom and functional changes carefully. Habitual posture may be associated with reduction and aggravation of symptoms.


Laparoscopic radical prostatectomy: perioperative outcomes and morbidity of 559 consecutive cases in Siriraj Hospital, Thailand.
To evaluate perioperative outcomes and morbidity of laparoscopic radical prostatectomy in Siriraj Hospital during a 5-year experience. Five hundred fifty nine patients who underwent laparoscopic radical prostatectomy (LRP) by seven surgeons at Siriraj Hospital between September 2004 and September 2009 were included in the study. Data of perioperative results and postoperative parameters were retrospectively evaluated. Mean operative time was 257 minutes SD 75 (range 125 to 680 min). The mean operative time of the first 100 cases was significantly higher than of the last 100 cases (307 ml/min SD 95 versus 223 ml/min SD 56; p-value = 0.001). Mean estimated blood loss was 779 ml SD 607 (range 40 to 6,000 ml). Of 559 patients, 148 patients (26.5%) had blood transfusions. The blood transfusion rate in the first 100 cases was significantly higher than those of the last 100 cases (36.5% versus 15%; p-value = 0.016). The median duration of catheterization time was 8 days. The mean time of drain insertion was 4.2 days SD 1.8 (range 2 to 18 days) postoperatively. Hospital stay was 8.8 days SD 7.6 (range 3 to 149 days). Overall perioperative complications rate was 17.1%. Of these patients, 13.4% were minor complication (Clavien 1, 2) and 3.7% were major complication (Clavien 3, 4). There were no mortalities. Late complication rate was 2.1%, which most of them were stricture of anastomosis. Perioperative outcomes and morbidity of LRP in a 5-year period were acceptable. Laparoscopic radical prostatectomy is technically demanding with an initially longer operative time and higher blood transfusion rate. The learning curve of the surgical team is needed to achieve good results.


MIT-001 Restores Human Placenta-Derived Mesenchymal Stem Cells by Enhancing Mitochondrial Quiescence and Cytoskeletal Organization.
Inflammation is a major cause of several chronic diseases and is reported to be recovered by the immuno-modulation of mesenchymal stem cells (MSCs). While most studies have focussed on the anti-inflammatory roles of MSCs in stem cell therapy, the impaired features of MSCs, such as the loss of homeostasis by systemic aging or pathologic conditions, remain incompletely understood. In this study, we investigated whether the altered phenotypes of human placenta-derived MSCs (hPD-MSCs) exposed to inflammatory cytokines, including TNF-α and IFN-γ, could be protected by MIT-001, a small anti-inflammatory and anti-necrotic molecule. MIT-001 promoted the spindle-like shape and cytoskeletal organization extending across the long cell axis, whereas hPD-MSCs exposed to TNF-α/IFN-γ exhibited increased morphological heterogeneity with an abnormal cell shape and cytoskeletal disorganization. Importantly, MIT-001 improved mitochondrial distribution across the cytoplasm. MIT-001 significantly reduced basal respiration, ATP production, and cellular ROS levels and augmented the spare respiratory capacity compared to TNF-α/IFN-γ-exposed hPD-MSCs, indicating enhanced mitochondrial quiescence and homeostasis. In conclusion, while TNF-α/IFN-γ-exposed MSCs lost homeostasis and mitochondrial quiescence by becoming over-activated in response to inflammatory cytokines, MIT-001 was able to rescue mitochondrial features and cellular phenotypes. Therefore, MIT-001 has therapeutic potential for clinical applications to treat mitochondrion-related inflammatory diseases.


Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy.
Indices of post awakening cortisol secretion (PACS), include the rise in cortisol (cortisol awakening response: CAR) and overall cortisol concentrations (e.g., area under the curve with reference to ground: AUCg) in the first 30-45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min (between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting. Healthy females (N=49, 20.5±2.8 years) selected for differences in TWB collected saliva samples (S1-4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps). Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p<.005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median=8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.


Treatment strategies for childhood noninfectious chronic uveitis: an update.
Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, noninfectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, for example, juvenile idiopathic arthritis, a significant number of cases in children show no associated signs or symptoms and are labeled as idiopathic. We reviewed the available literature. Taking into account this evidence, an anti-inflammatory therapy based on an immunomodulatory approach seems a reasonable strategy for noninfectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive strategy is supported only at evidence level III. Our aim is to review the currently available medical strategies for the treatment of childhood sight-threatening chronic uveitis. Uveitis in children can be severe. Methotrexate is the drug of choice for recalcitrant cases, and biologic therapies can be useful in selected situations.


Design to Assist Better Youthhood for Adolescents with Lower-Limb Disability through Virtual Reality Sports.
Background: Youths with lower limb dysfunction display low levels of sports participation, which limits their growth and self-development, both physically and mentally. Recently, VR technology has proven its profound value in the psychological evaluation and treatment, rehabilitation, and immersive training of people in need. We have proposed, designed, and developed a VR rock-climbing game for youths with lower-limb dysfunction that allows them to engage in enjoyable and purposeful in-game tasks that simultaneously bring about intensive real-world exercise. Methods: Pilot studies were conducted on college students whose lower limbs were fixed to chairs. Heart rate monitoring, a flow questionnaire, interviews, and observation were conducted for each participant to evaluate the impact of the VR rock-climbing game. The collected data were trimmed on the basis of Cronbach's alpha and corrected item−total correlation (CITC) to guarantee the data's reliability. Results: The average value of each flow experience dimension was greater than 4 (0.76 < SD < 0.91). According to the flow-based analysis and the whole-process feeling distribution (WPFD), the evaluated study brought about the participants' happiness and a sense of mastery and achievement. Conclusions: By bringing about a deep and enjoyable immersion in VR, it remarkably promotes the participants' intention to participate in exercises.


A novel delta zero-thalassemia arising from a frameshift insertion, detected by direct sequencing of enzymatically amplified DNA.
We describe a novel mutation in the delta globin gene of a compound heterozygote for delta o thalassemia and a deletion type G gamma + (A gamma delta beta) zero thalassemia. The delta was amplified using the polymerase chain reaction (PCR), and the amplified material was used in a direct sequencing experiment. The nucleotide sequence of the mutant delta gene showed that the insertion of an extra nucleotide at the third position of codon 91 in the second exon, which gives rise to a premature stop codon at position 94, leads to the silencing of this gene. The presence of the mutation in the carriers of delta-thalassemia in this family was confirmed by dot blot hybridization. A possible model for the insertion of the extra nucleotide is discussed.


Structural evolution and magnetic properties of Co(II) coordination polymers varied from 1D to 3D constructed by 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene.
Seven Co(II) coordination polymers, [Co(btx)(3)(H(2)O)(2)](ClO(4))(2)·(btx)·2H(2)O (1), [Co(btx)(3)(H(2)O)(2)](BF(4))(2)·(btx)·2H(2)O (2), [Co(btx)(2)(H(2)O)(2)](NO(3))(2)·2H(2)O (3), [Co(btx)(2)Cl(2)] (4), [Co(btx)(BA)(2)(H(2)O)(2)]·2HBA (5), [Co(btx)(IPA)] (6) and [Co(3)(btx)(3)(BTA)(2)(H(2)O)(2)] (7) (btx = (1,4-bis(1,2,4-triazol-1-ylmethyl)benzene), HBA = benzoic acid, H(2)IPA = isophthalic acid, H(3)BTA = benzene-1,3,5-tricarboxylic acid), have been hydrothermally synthesized and characterized. 1 and 2 are isostructural and show a 1D Co-μ(2)-btx-Co chain structure, in which btx acts as both a bridging and terminal ligand. 3 is also a 1D chain structure but different from 1 and 2. The Co(II) ions are bridged by double μ(2)-btx to form Co(2)-btx(2) rings, which were further connected into 1D chains by sharing the Co(II) ions of the rings. 4 exists as a 2D grid with (4,4) topology structure. When aromatic acid was introduced to the synthetic system, three other coordination polymers 5-7 were obtained. In 5, the 1D chain is as that of 1, except that the terminal ligand was replaced by BA(-). 6 shows a two-fold parallel interpenetration framework featuring a 6-c uninodal net with (3(3),4(6),5(5),6) Schlafli topological symbol. 7 is an interesting 3D framework, which contains a 2-nodal net motif with the unprecedented (3(6),4(2),5(6),6)(3(9),4(9),5(3))(2) topology structure. The influence of the varieties of the structures and magnetic properties are studied and discussed in detail.


Insight into multi-site mechanisms of glycosyl transfer in (1-->4)beta-D-glycans provided by the cereal mixed-linkage (1-->3),(1-->4)beta-D-glucan synthase.
Synthases of cellulose, chitin, hyaluronan, and all other polymers containing (1-->4)beta-linked glucosyl, mannosyl and xylosyl units have overcome a substrate orientation problem in catalysis because the (1-->4)beta-linkage requires that each of these sugar units be inverted nearly 180 degrees with respect to its neighbors. We and others have proposed that this problem is solved by two modes of glycosyl transfer within a single catalytic subunit to generate disaccharide units, which, when linked processively, maintain the proper orientation without rotation or re-orientation of the synthetic machinery in 3-dimensional space. A variant of the strict (1-->4)beta-D-linkage structure is the mixed-linkage (1-->3),(1-->4)beta-D-glucan, a growth-specific cell wall polysaccharide found in grasses and cereals. beta-Glucan is composed primarily of cellotriosyl and cellotetraosyl units linked by single (1-->3)beta-D-linkages. In reactions in vitro at high substrate concentration, a polymer composed of almost entirely cellotriosyl and cellopentosyl units is made. These results support a model in which three modes of glycosyl transfer occur within the synthase complex instead of just two. The generation of odd numbered units demands that they are connected by (1-->3)beta-linkages and not (1-->4)beta-. In this short review of beta-glucan synthesis in maize, we show how such a model not only provides simple mechanisms of synthesis for all (1-->4)beta-D-glycans but also explains how the synthesis of callose, or strictly (1-->3)beta-D-glucans, occurs upon loss of the multiple modes of glycosyl transfer to a single one.


Native Seed Supply and the Restoration Species Pool.
Globally, annual expenditure on ecological restoration of degraded areas for habitat improvement and biodiversity conservation is approximately $18bn. Seed farming of native plant species is crucial to meet restoration goals, but may be stymied by the disconnection of academic research in seed science and the lack of effective policies that regulate native seed production/supply. To illustrate this problem, we identified 1,122 plant species important for European grasslands of conservation concern and found that only 32% have both fundamental seed germination data available and can be purchased as seed. The "restoration species pool," or set of species available in practice, acts as a significant biodiversity selection filter for species use in restoration projects. For improvement, we propose: (1) substantial expansion of research and development on native seed quality, viability, and production; (2) open-source knowledge transfer between sectors; and (3) creation of supportive policy intended to stimulate demand for biodiverse seed.


Referral Compliance Following a Diabetes Screening in a Dental Setting: A Scoping Review.
With type 2 diabetes prevalence increasing in Australia, and the condition associated with significant morbidity and mortality, screening for dysglycaemia in the dental setting has been proposed to identify asymptomatic individuals. Screening commences with a risk assessment, and individuals identified at elevated risk for having diabetes are then referred to their medical practitioner for confirmation of their glycemic status. Therefore, for screening to be effective, individuals need to adhere to their oral health professionals' (OHP) advice and attend their medical follow-ups. This review aims to investigate the literature on referral compliance following a risk assessment in the dental setting and identify barriers and facilitators to screened individuals' referral compliance. A scoping review of the literature was undertaken, selecting studies of diabetes screening in a dental setting that recorded compliance to referral to follow-up, and explored any barriers and facilitators to adherence. Fourteen studies were selected. The referral compliance varied from 25 % to 90%. Six studies reported barriers and facilitators to attending medical follow-ups. Barriers identified included accessibility, cost, knowledge of the condition, and OHP characteristics.


Application of monolithic columns in pharmaceutical analysis. Determination of indomethacin and its degradation products.
Comparison of HPLC methods using conventional particle-based and monolithic columns for determination of indomethacin and its two degradation products, viz. 5-methoxy-2-methylindoleacetic acid and 4-chlorobenzoic acid, was carried out. Ketoprofen was used as an internal standard for data evaluation throughout the study. Conventional separation was based on analytical column Zorbax SB-Phenyl (75x4.6 mm; 3.5 microm particles) used with a mobile phase composition of acetonitrile and phosphoric acid 0.2% (50:50, v/v) and isocratic flow at 0.6 mL/min. Three different lengths of Chromolith columns RP-18e (25x4.6 mm, 50x4.6 mm, and 100x3 mm) were tested with respect to the validation parameters peak asymmetry, resolution, height equivalent to a theoretical plate, repeatability, and after optimisation compared to values obtained using a conventional Zorbax column. The developed methods were used to determine all three compounds in a pharmaceutical formulation--Indobene gel. Chromatographic parameters were comparable to those of a conventional particle-based column. The analysis time was shortened as expected (retention times were lowered by a factor of two). Moreover, the repeatability of peak areas and retention times obtained with a 50 mm monolithic column was greatly improved (RSD values were lower than 0.40%).


Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors.
Waglerin-1 (Wtx-1) is a 22-amino acid peptide that is a competitive antagonist of the muscle nicotinic receptor (nAChR). We find that Wtx-1 binds 2100-fold more tightly to the alpha-epsilon than to the alpha-delta binding site interface of the mouse nAChR. Moreover, Wtx-1 binds 100-fold more tightly to the alpha-epsilon interface from mouse nAChR than that from rat or human sources. Site-directed mutagenesis of residues differing in the extracellular domains of rat and mouse epsilon subunits indicates that residues 59 and 115 mediate the species difference in Wtx-1 affinity. Mutation of residues 59 (Asp in mouse, Glu in rat epsilon) and 115 (Tyr in mouse, Ser in rat epsilon) converts Wtx-1 affinity for the alpha-epsilon interface of one species to that of the other species. Studies of different mutations at position 59 indicate both steric and electrostatic contributions to Wtx-1 affinity, whereas at position 115, both aromatic and polar groups contribute to affinity. The human nAChR also has lower affinity for Wtx-1 than mouse nAChR, but unlike rat nAChR, residues in both alpha and epsilon subunits mediate the affinity difference. In human nAChR, polar residues (Ser-187 and Thr-189) confer low affinity, whereas in mouse nAChR aromatic residues (Trp-187 and Phe-189) confer high affinity. The overall results show that non-conserved residues at the nAChR binding site, although not crucial for activation by ACh, govern the potency of neuromuscular toxins.


[Risk factors for development and recurrence of peptic ulcer disease].
Peptic ulcer disease (PUD) is one of the common gastrointestinal diseases, and its medical management has been developed so much that the incidence of its serious complications, such as bleeding and perforation, are declining significantly. Its prevalence in Korea is not definitely decreased, probably due to increasing proportion of elderly patients and their rising usage of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. This study was conducted to identify the risk factors for development and recurrence of peptic ulcer disease in Korea. From 2003 to 2008, upper gastrointestinal endoscopy and detailed personal questionnaires were performed for patients who visited Department of Gastroenterology at Seoul National University Bundang Hospital. In total, 475 PUD patients and 335 non-ulcer dyspepsia patients were included. The results of questionnaires and repeated upper gastrointestinal endoscopy at initial diagnosis time and follow-up periods were analyzed. Multivariable analysis showed that male, H. pylori infection, NSAIDs use and smoking were risk factors for the development of PUD. The use of proton pump inhibitors (PPIs) and H2 receptor antagonists has significantly reduced the risk of PUD in patients who had taken NSAIDs and/or aspirin. H. pylori infection was found as the only risk factor for the recurrence of PUD. For the old patients who are taking drugs, such as NSAIDs and aspirin, concomitant use of PPIs or H2 receptor antagonists should be considered to protect from the development of PUD. H. pylori eradication has been confirmed again to be essential for the treatment of PUD patients infected with H. pylori.


Updating meta-analytic research findings: Bayesian approaches versus the medical model.
The authors examine 3 methods of combining new studies into existing meta-analyses: (a) adding the new study or studies to the database and recalculating the meta-analysis (the medical model); (b) using the Bayesian procedure advocated by F. L. Schmidt and J. E. Hunter (1977) and F. L. Schmidt, J. E. Hunter, K. Pearlman, and G. S. Shane (1979) to update the meta-analysis; and (c) using the Bayesian methods advocated by these authors and M. T. Brannick (2001) and M. T. Brannick, S. M. Hall, and Y. Liu (2002) to estimate study-specific parameters. Method b was found to severely overweight new studies relative to the previous studies contained in the meta-analysis, and Method c was found to do the same while also requiring an assumption with a low prior probability of being correct, causing the method to violate Bayesian principles. The authors present an alternative Bayesian procedure that does not suffer from these drawbacks and yields meta-analytic results very similar to those obtained with the medical model. They recommend use of the medical model or this alternative Bayesian procedure.


Cell cycle and complement inhibitors may be specific for treatment of spinal cord injury in aged and young mice: Transcriptomic analyses.
Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury, but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database (accession number GSE93561) were used, including spinal cord samples from 3 young injured mice (2-3-months old, induced by Impactor at Th9 level) and 3 control mice (2-3-months old, no treatment), as well as 2 aged injured mice (15-18-months old, induced by Impactor at Th9 level) and 2 control mice (15-18-months old, no treatment). Differentially expressed genes (DEGs) in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method, with a threshold of adjusted P < 0.05 and |logFC(fold change)| > 1.5. Protein-protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix-receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle (upregulation of PLK1) and complement (upregulation of C3) activation, respectively. These findings were confirmed by functional analysis of genes in modules (common, 4; aged, 2; young, 1) screened from protein-protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.


Differences in Efficacy between Short- and Long-Course Antibiotic Agents for Joint Prosthesis Infection: A Systematic Review and Meta-Analysis.
Background: To evaluate systematically the failure rate of short versus long courses of antibiotic agents for prosthetic joint infections (PJIs). Methods: PubMed, Embase, and Cochrane Library databases were searched for controlled studies of short- and long-course antibiotic agents for joint prosthesis infections, all from the time of database creation to April 2022. Literature search, quality evaluation, and data extraction were performed independently by two researchers, and the primary outcome was the rate of surgical failure after antibiotic treatment. Stata 11.0 software was then applied for meta-analysis. Publication bias was assessed using Begg test. Heterogeneity was assessed using the I2 test, and fixed or random effects models were used accordingly. Meta-regression was used to determine the causes of heterogeneity. Results: A total of 14 articles involving 1,971 participants met the inclusion criteria, including 12 observational studies and two randomized controlled trials. Meta-analysis showed no difference between short and long courses of antibiotic agents (relative risk, 1.08; 95% confidence interval [CI], 0.89-1.32). The results of the subgroup analysis showed no differences between the failure rates of patients with PJI treated with short and long courses of antibiotic agents in studies with different study areas, different treatment modalities, and different locations of the artificial joints. Conclusions: Patients with PJIs may not require long-term or lifelong antibiotic agents after surgical treatment, and short-term (four to six weeks) antibiotic therapy is usually safe.