A Platinum(II) Organometallic Building Block for the Design of Emissive Copper(I) and Silver(I) Coordination Polymers.
The tritopic organometallic ligand trans-MeSC6H4C≡CPt(PMe3)2(C≡N) (L1) was prepared from cis-PtCl2(PMe3)2 and p-ethynyl(methyl thioether)benzene. Its versatility was shown with the formation of [CuX(L1)]n coordination polymers (CPs) with CuX salts in MeCN (X = I (CP1), CN (CP2), SCN (CP3)). These CPs were characterized by X-ray crystallography, thermal gravimetric analysis (TGA), and IR and Raman spectroscopy. CP1 consists of a 1D head-to-tail chain formed by tricoordinated -C≡N-CuI(η2-C≡C)- linkages, whereas CP2 is built upon a central (CuCN)n zigzag chain bearing dangling L1s held by -C≡N-Cu bonds. Finally, CP3 exhibits 2D sheets secured by Cu-N≡C-/-(Me)S-Cu bondings and transversal Cu-S-C≡N-Cu bridges. Concurrently, the CPs formed with AgX (X = NO3- (CP4 and CP5), CF3CO2- (CP6) PF6- (CP7)) exhibits 2D sheets with guest molecules (anion, solvents) inside the tight pores or between layers. These new materials are emissive: L1 (λ0-0 ∼465 nm), CP1-CP7 (500 < λmax < 620 nm). Their photophysical properties (absorption and emission spectra, emission lifetimes (∼0.2 < τe < 120 μs), and quantum yields in the solid state at 77 and 298 K) were analyzed. The various natures of the emissive excited states were addressed by density functional theory (DFT) and time-dependent DFT (TDDFT) computations. For CP1, this state is a triplet halide or pseudohalide to ligand charge transfer 3XLCT (CT = charge transfer; X = I; L = L1) and for CP2, it is 3XLCT (X = CN; L = L1). However, for CP3, it is 3XLCT (X = SCN; L = L1). For CP4, the T1 state is described as a [MeSC6H4(η2-C≡C)-Ag(NO3)]2 → [Pt]/C≡CC6H4SMe CT.


Human lymphocytes obtained from decidual tissue express killer activatory receptors as well as killer inhibitory receptors: analysis using a single strand conformation polymorphism method.
The objective was to clarify whether lymphocytes in decidual tissue express only killer inhibitory receptors (KIRs) or both KIRs and killer activatory receptors (KARs). A polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis method, using cDNA as a template, was applied to detect as many natural killer receptors (NKRs) expressed on natural killer (NK) cells as possible and to distinguish between KIRs and KARs. Using this method, we analyzed NKRs on lymphocytes in decidual tissue and maternal peripheral blood mononuclear cells (PBMCs) (n = 10) from the same individuals. More than 20 SSCP bands were detected for NKRs on both the lymphocytes in decidual tissue and the maternal PBMCs. The SSCP band patterns were different for each individual. KARs mRNA was detected in lymphocytes in decidual tissue according to the SSCP analysis results. Lymphocytes in decidual tissue express not only KIRs but also KARs; this finding suggests their roles in placentation and the maintenance of pregnancy.


Diffusion with finite-helicity field tensor: A mechanism of generating heterogeneity.
Topological constraints on a dynamical system often manifest themselves as breaking of the Hamiltonian structure; well-known examples are nonholonomic constraints on Lagrangian mechanics. The statistical mechanics under such topological constraints is the subject of this study. Conventional arguments based on phase spaces, Jacobi identity, invariant measure, or the H theorem are no longer applicable since all these notions stem from the symplectic geometry underlying canonical Hamiltonian systems. Remembering that Hamiltonian systems are endowed with field tensors (canonical 2-forms) that have zero helicity, our mission is to extend the scope toward the class of systems governed by finite-helicity field tensors. Here, we introduce a class of field tensors that are characterized by Beltrami vectors. We prove an H theorem for this Beltrami class. The most general class of energy-conserving systems are non-Beltrami, for which we identify the "field charge" that prevents the entropy to maximize, resulting in creation of heterogeneous distributions. The essence of the theory can be delineated by classifying three-dimensional dynamics. We then generalize to arbitrary (finite) dimensions.


Current update on Anaphylaxis: Anaphylaxis management in recent guidelines.
Anaphylaxis is a potentially fatal hypersensitivity reaction but frequently underrecognized. Although its incidence rates vary according to geographical location, it seems clear that there has been a general increase in recent years, either because of greater recognition of this entity or because it is progressing proportionally to the presence of allergic diseases in the world. The development of anaphylaxis management guidelines adapted to local or regional needs seems of utmost importance. Furthermore, it is necessary to assess their implementation and their positive effect regarding diagnosing and treating anaphylaxis. In this review we explore the currently existing definitions of anaphylaxis and its epidemiology, the potential triggers of anaphylaxis and guideline recommendations in terms of diagnosis and management, proposing a novel anaphylaxis calculator and reviewing the current scoring methods for anaphylactic episodes.


High-pressure gas phase femtosecond laser ionization mass spectrometry.
We describe a novel ion source for analytical mass spectrometry based on femtosecond laser ionization at pressures at and above atmospheric and characterize its performance when coupled to a tandem quadrupole/time-of-flight mass spectrometer. We assess source saturation limits, ionization and sampling efficiencies, the effective ionization volume, and limits of detection. We demonstrate 100% efficient ionization for a set of organic compounds and show that the degree of ion fragmentation over a range of laser powers is favorable compared to electron impact ionization, especially in that a substantial parent ion signal is always observed. We show how collisional cooling plays a role in controlling fragmentation at high pressures and address how ion-molecule chemistry can be controlled or exploited. High-pressure femtosecond laser ionization will allow "universal" and efficient ionization, presenting a research direction that will broaden the options for gas phase analysis beyond the capabilities of electron impact ionization.


[Visual and quantitative assessment of the effectiveness of non-vascularized bone grafting in osteonecrosis of the femoral head via CT-based radiomics and clinical data].
To investigate the value of CT-based radiomics and clinical data in predicting the efficacy of non-vascularized bone grafting (NVBG) in hip preservation, and to construct a visual, quantifiable, and effective method for decision-making of hip preservation. Between June 2009 and June 2019, 153 patients (182 hips) with osteonecrosis of the femoral head (ONFH) who underwent NVBG for hip preservation were included, and the training and testing sets were divided in a 7∶3 ratio to define hip preservation success or failure according to the 3-year postoperative follow-up. The radiomic features of the region of interest in the CT images were extracted, and the radiomics-scores were calculated by the linear weighting and coefficients of the radiomic features after dimensionality reduction. The clinical predictors were screened using univariate and multivariate Cox regression analysis. The radiomics model, clinical model, and clinical-radiomics (C-R) model were constructed respectively. Their predictive performance for the efficacy of hip preservation was compared in the training and testing sets, with evaluation indexes including area under the curve, C-Index, sensitivity, specificity, and calibration curve, etc. The best model was visualised using nomogram, and its clinical utility was assessed by decision curves. At the 3-year postoperative follow-up, the cumulative survival rate of hip preservation was 70.33%. Continued exposure to risk factors postoperative and Japanese Investigation Committee (JIC) staging were clinical predictors of the efficacy of hip preservation, and 13 radiomic features derived from least absolute shrinkage and selection operator downscaling were used to calculate Rad-scores. The C-R model outperformed both the clinical and radiomics models in predicting the efficacy of hip preservation 1, 2, 3 years postoperative in both the training and testing sets ( P<0.05), with good agreement between the predicted and observed values. A nomogram constructed based on the C-R model showed that patients with lower Rad-scores, no further postoperative exposure to risk factors, and B or C1 types of JIC staging had a higher probability of femoral survival at 1, 2, 3 years postoperatively. The decision curve analysis showed that the C-R model had a higher total net benefit than both the clinical and radiomics models with a single predictor, and it could bring more net benefit to patients within a larger probability threshold. The prediction model and nomogram constructed by CT-based radiomics combined with clinical data is a visual, quantifiable, and effective method for decision-making of hip preservation, which can predict the efficacy of NVBG before surgery and has a high value of clinical application.


A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.
People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.


Effect of Tai Chi exercise with the same frequency and different exercise duration on the bone mineral density of older women.
This study compared the effect of Tai Chi with the same frequency and different session duration on the bone mineral density (BMD) of older women. Healthy older women aged 55-70 years were randomly divided into the short-time group (N.=17), long-time group (N.=18), and control group (N.=17). The BMD of L<inf>2-4</inf> and the proximal femur were measured at baseline and after 48 weeks of intervention. From 0 to 48 weeks, the respective BMD values of L<inf>2-4</inf> and the femoral neck in the short-time and long-time groups increased by 8.8% and 7.5% (P<0.01) and 8.8% and 12.7% (P<0.01), while the BMD of the greater trochanter in the control group decreased by 3.0% (P<0.05). After 48 weeks, the BMD of L<inf>2-4</inf> and the femoral neck was greater in the short-time and long-time groups than the control group (P<0.001). Tai Chi for 30 or 60 minutes five times weekly for 48 weeks improves the BMD of L<inf>2-4</inf> and the femoral neck in older women but does not affect the BMD of the greater trochanter and Ward's triangle. Increasing the exercise duration does not increase the effect of Tai Chi on BMD.


Prevalence of dental caries among children aged 5-15 years from 9 countries in the Eastern Mediterranean Region: a meta-analysis.
Dental caries affects all age groups, although children are affected to a greater extent. Several studies have assessed the prevalence of dental caries in the World Health Organization (WHO) Eastern Mediterranean Region. However, prevalence data for dental caries have not been pooled for all countries in the Region. To estimate by meta-analysis the pooled prevalence of dental caries among children aged 5-15 years in the Region. The study protocol was registered in PROSPERO with registration number CRD42016037157. Twenty-one studies (37 estimates) were identified through systematic search for articles published between 1 January 2005 and 5 July 2018. The required data from each article were extracted into the datasheet. A random-effects meta-analysis was performed for the overall age group and for age 5, 12 and 15 years individually. Data were available for only 9 of the 21 countries in the Region. Heterogeneity between studies was high (I²>98%). There was considerable variation among the countries for the prevalence of dental caries at different ages. The pooled prevalence for deciduous dentition in children aged 5 years was 65% (45-85%); 61% (50-72%) for permanent dentition in children aged 12 years; 70% (64-75%) for children aged 15 years; and 66% (59-73%) for children aged 6-15 years. The most common index used for oral examination to calculate caries experience was WHO Basic Oral Health Survey Criteria, 1997. Dental caries continues to be an oral health concern among children in 9 countries in the Region.


miR-30a-5p Inhibits Proliferation and Migration of Lung Squamous Cell Carcinoma Cells by Targeting FOXD1.
To investigate the mechanism of miR-30a-5p inhibiting proliferation and migration of lung squamous cell carcinoma (LSCC) cells by targeting FOXD1. Bioinformatics was used to analyze differentially expressed genes in the TCGA_LUSC database. qRT-PCR was used to detect the expression levels of miR-30a-5p and FOXD1 in human normal lung epithelial cell line and human LSCC cell lines. The protein expression of FOXD1 was detected by western blot. The cell viability and colony formation abilities were examined by CCK-8 and colony formation assays, respectively. Wound healing and Transwell assays were performed to examine the migration and invasion abilities of cells. The targeted binding sites of miR-30a-5p and FOXD1 were predicted by bioinformatics, and dual luciferase assay was used to verify the targeted binding relationship between miR-30a-5p and FOXD1. miR-30a-5p was downregulated in LSCC tissues and cells, while FOXD1 was highly expressed. Overexpression of miR-30a-5p or silencing FOXD1 inhibited cell viability, colony formation ability, migration, and invasion of LSCC cells. miR-30a-5p inhibited the proliferation and migration of LSCC cells by downregulating the expression of FOXD1. miR-30a-5p can downregulate the expression of FOXD1 and inhibit the proliferation and migration of LSCC.


Simultaneously Enhanced Reverse Intersystem Crossing and Radiative Decay in Thermally Activated Delayed Fluorophors with Multiple Through-space Charge Transfers.
Thermally activated delayed fluorescence (TADF) materials with through-space charge transfers (CT) have attracted particularly interest recently. However, the slow reverse intersystem crossing (RISC) and radiative decay always limit their electroluminescence performances. Herein, TADF molecules with ortho-linked multiple donors-acceptor (ortho-Dn -A) motif are developed to create near-degenerate excited states for the reinforcement of spin-orbit coupling. The incorporation of both through-bond and through-space CT enlarges oscillator strength. The optimal ortho-D3 -A compound exhibits a photoluminescence quantum yield of ca. 100 %, a high RISC rate of 2.57×106 s-1 and a high radiative decay rate of 1.00×107 s-1 simultaneously. With this compound as the sensitizer, a TADF-sensitized-fluorescent organic light-emitting diode shows a maximum external quantum efficiency of 31.6 % with an ultrapure green Commission Internationale de L'Eclairage y coordinate value of 0.69.


Collagen XII mediated cellular and extracellular mechanisms in development, regeneration, and disease.
Collagen XII, a fibril-associated collagen with interrupted triple helices (FACIT), influences fibrillogenesis in numerous tissues. In addition to this extracellular function, collagen XII also directly regulates cellular function. Collagen XII is widely expressed in connective tissues, particularly tendons, ligaments, and the periodontium and periosteum, where it is enriched in the pericellular regions. Mutations in the collagen XII gene cause myopathic Ehlers-Danlos syndrome (mEDS), an early-onset disease characterized by overlapping connective tissue abnormalities and muscle weakness. Patients with mEDS exhibit delayed motor development, muscle weakness, joint laxity, hypermobility, joint contractures, and abnormal wound healing. A mEDS mouse model was generated by deletion of the Col12a1 gene, resulting in skeletal and muscle abnormalities with disorganized tissue structures and altered mechanical properties. Extracellularly, collagen XII interacts with collagen I fibrils and regulates collagen fibril spacing and assembly during fibrillogenesis. Evidence for the binding of collagen XII to other EDS-related molecules (e.g., decorin and tenascin X) suggests that disruption of ECM molecular interactions is one of the causes of connective tissue pathology in mEDS. Collagen XII also has been shown to influence cell behavior, such as cell shape and cell-cell communication, by providing physical connection between adjacent cells during tissue development and regeneration. The focus of this review is on the functions of collagen XII in development, regeneration, and disease.


Cu-Releasing Bioactive Glass Coatings and Their in Vitro Properties.
Bioactive glasses are well-known materials suitable for bone-related applications thanks to their biocompatibility and osteoconductivity. In order to improve their in vivo performance, the modification of the glass composition by adding ions with specific biological functions is required. As copper (Cu) possesses antibacterial properties, in this study, 5 wt % of CuO has been added to the 45S5 bioactive glass composition. The investigation of the effect of the Cu-containing bioactive glass on cellular behavior has revealed that the presence of Cu induces an early differentiation of human mesenchymal stem cells through osteoblast phenotype, promotes the expression of anti-inflammatory interleukin, and reduces proinflammatory interleukin expression. With the aim to produce coatings with antibacterial properties, the Cu-containing bioactive glass was used as the target material for the pulsed laser deposition (PLD) of bioactive thin films. PLD experiments were carried out at different substrate temperatures to study the effect on the film's characteristics. All of the films are compact, crack-free, and characterized by a rough morphology and good wettability. The in vitro bioactivity was demonstrated by the apatite growth on the coating surface, after soaking in simulated body fluid, revealed by Raman spectroscopy and scanning electron microscopy-energy dispersive X-ray analyses. The antibacterial study proved that the material showed more effective activity against three Gram-negative bacteria ( Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica) rather than against Gram-positive bacteria ( Staphylococcus aureus).


Risk Factors and Outcomes for Preoperative Stiffness Requiring Intervention Before Anterior Cruciate Ligament Reconstruction.
To date, there is a scarcity of literature related to the incidence of prolonged stiffness after an anterior cruciate ligament (ACL) tear that requires manipulation under anesthesia/lysis of adhesions (MUA/LOA) in the preoperative period before ACL reconstruction (ACLR) and how preoperative stiffness influences outcomes after ACLR. Preoperative stiffness requiring MUA/LOA would increase the risk for postoperative stiffness, postoperative complications, and the need for subsequent procedures after ACLR. Cohort study; Level of evidence, 3. The PearlDiver Research Program was used to identify patients who sustained an ACL tear and underwent ACLR using their respective International Classification of Diseases, 9th or 10th Revision, and Current Procedure Terminology (CPT) codes. Within this group, patients with preoperative stiffness were identified using the CPT codes for MUA or LOA. Significant risk factors for preoperative stiffness were identified through univariate and multivariate logistic regression analyses. Outcomes after ACLR were analyzed between patients with and without preoperative stiffness using multivariate logistic regression, controlling for age, sex, and Elixhauser Comorbidity Index. Between 2008 and 2018, 187,071 patients who underwent ACLR were identified. Of these patients, 241 (0.13%) underwent MUA/LOA before ACLR. Patients with preoperative stiffness began preoperative physical therapy significantly later than patients without stiffness (P = .0478) and had a delay in time to ACLR (P = .0003). Univariate logistic regression demonstrated that female sex, older age, anxiety/depression, obesity, and anticoagulation use were significant risk factors for preoperative stiffness (P < .05 for all). After multivariate regression, anticoagulation use was the only independent risk factor deemed significant (odds ratio, 6.69 [95% CI, 4.01-10.51]; P < .001). Patients with preoperative stiffness were at an increased risk of experiencing postoperative stiffness, deep vein thrombosis, pulmonary embolism, surgical-site infection, and septic knee arthritis after ACLR (P < .05 for all). Although the risk of preoperative stiffness requiring an MUA/LOA before ACLR is low, the study findings indicated that patients with preoperative stiffness were at increased risk for postoperative complications compared with patients with no stiffness before ACLR.


Alternative dosing schedules for cetuximab: a role for biweekly administration?
The anti-epidermal growth factor receptor targeted monoclonal antibody (MoAb) cetuximab has established efficacy as a single agent and in combination with other modalities (chemotherapy, radiation therapy) in head and neck cancer and metastatic colorectal cancer. The agent is typically administered weekly; however, the development of a biweekly dosing regimen for cetuximab would provide treatment flexibility when combined with biweekly or longer chemotherapy regimens. The feasibility for biweekly dosing with cetuximab is supported by several factors. Biweekly dosing with MoAbs has been effective in multiple tumor types. Although cetuximab is currently administered on a weekly schedule, pharmacokinetic data demonstrate that cetuximab has a long terminal half-life, allowing administration of a biweekly schedule. Results from phase I studies show that a biweekly schedule of cetuximab is well tolerated, exhibits similar pharmacokinetics and pharmacodynamics to conventional weekly dosing, and does not seem to compromise efficacy. Additional studies are therefore warranted to further evaluate biweekly dosing for cetuximab in order to optimize treatment outcomes and convenience for patients.


Trans-scaphoid Trans-lunotriquetral Perilunate Dislocation in a Patient with a Carpal Coalition.
Congenital carpal coalitions are rare conditions that arise from a failure or an incomplete cavitation of a common cartilaginous precursor of the carpal bones between the fourth and eighth week of intrauterine life. The incidence of coalitions has been estimated to occur in about 0.1% of the population and up to 1.6% in people of African descent. This study reports a case of trans-scaphoid trans-lunotriquetral perilunate dislocation with a lunotriquetral coalition and successful management with closed reduction, percutaneous fixation, and a thumb spica cast.


Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa.
This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated. The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies. Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.


Implementation of the NICE guideline - recommendations from the British Fertility Society for national criteria for NHS funding of assisted conception.
Assisted conception providers in England were surveyed to establish the uptake of NICE guideline for infertility particularly in respect of assisted conception and the criteria used to accept patients for NHS funded treatment. Detailed information on selection criteria was obtained from a group of commissioning consortia at an advanced stage in their arrangements. While there was an overall increase in the number of NHS IVF cycles purchased in England, implementation is stalled at one fresh cycle in the vast majority of Primary Care Trusts (PCTs). There is little consensus about the criteria used for acceptance into an NHS programme. This is particularly so in respect of social criteria which are often arbitrary and used as a rationing tool. This information complements that provided by the survey of Primary Care Trusts performed in March 2005 by the All Party Parliamentary Group on Infertility (APPGI) in partnership with the National Infertility Awareness Campaign (NIAC) which together provide a basis for recommendations for NHS funding. The recommendations presented should be applied across England and Wales to ensure consistency, fairness and equity of access.


Influence of metal coordination on the mismatch tolerance of ligand-modified PNA duplexes.
Recent studies on metal incorporation in ligand-modified nucleic acids have focused on the effect of metal coordination on the stability of metal-containing duplexes or triplexes and on the metal binding selectivity but did not address the effect of the sequence of the nucleic acid in which the ligands are incorporated. We have introduced 8-hydroxyquinoline Q in 10-mer PNA strands with various sequences and have investigated the properties of the duplexes formed from these strands upon binding of Cu(2+). Variable-temperature UV-vis spectroscopy shows that, in the presence of Cu(2+), duplexes are formed even from ligand-modified Q-PNA strands that have a large number of mismatches. Spectrophotometric titrations demonstrate that at any temperature, one Cu(2+) ion binds a pair of Q-PNA strands that each contain one 8-hydroxyquinoline, but below the melting temperature, the PNA duplex exerts a supramolecular chelate effect, which prevents the transformation in the presence of excess Cu(2+) of the 1:2 Cu(2+):Q-PNA complexes into 1:1 complexes. EPR spectroscopy gives further support for the existence in the duplexes of [CuQ(2)] moieties that are similar to the corresponding square planar synthetic complex formed between Cu(2+) and 8-hydroxyquinoline. As PNA duplexes show a preferred handedness due to the chiral induction effect of a C-terminal l-lysine, which is transmitted through stacking interactions within the duplex, only if the metal-containing duplex has complementary strands, does it show a chiral excess measured by CD spectroscopy. The strong effect of the metal-ligand moiety is suggestive of an increased correlation length in PNA duplexes that contain such moieties. These results indicate that strong metal-ligand alternative base pairs significantly diminish the importance of Watson-Crick base pairing for the formation of a stable PNA duplex and lead to high mismatch tolerance, a principle that can be used in the construction of hybrid inorganic-nucleic acid nanostructures.


Split-Bolus Portal Venous Phase Dual-Energy CT Urography: Protocol Design, Image Quality, and Dose Reduction.
The purpose of this study is to evaluate the image quality of split-bolus portal venous phase urography and the potential reduction of radiation dose by using a second-generation dual-source dual-energy CT (DECT) scanner. DECT urography was performed in 84 patients. Unenhanced CT was performed 20 minutes after drinking 800 mL of water. The split-bolus protocol consisted of a sequence of injections, as follows: 200 mL of normal saline (2.0 mL/s), 50 mL of contrast medium (2.5 mL/s) at 0 second, 70 mL of contrast medium (2.5 mL/s) at 360 seconds, and a saline flush of 25 mL. The scan was started at 420 seconds. Virtual unenhanced images were reconstructed from contrast-enhanced images. The mean CT density and signal-to-noise ratio (SNR) of the renal parenchyma, vessels, upper urinary tract, normal reference tissues, and tumors were measured for image quantitative analysis. Image quality and opacification of the collecting systems were rated by two radiologists using 3- or 4-point scales. The SNR of all measured sites, except the renal pelvis, showed a statistically significant correlation (p < 0.001) between the true unenhanced and virtual unenhanced images. The overall sensitivity of stone detection was 87.5% (28/32) in virtual unenhanced images. Image quality of the renal parenchyma, arteries, and veins was excellent in 59.5%, 75.0%, and 97.6% of cases, respectively. Opacification of the intrarenal collecting systems, proximal, middle, and distal ureters, and bladder was complete in 92.9%, 83.9%, 78.6%, 77.4%, and 26.2% of patients, respectively. Omitting the unenhanced scan can reduce the mean radiation dose from 15.6 to 6.7 mSv. Portal venous phase split-bolus DECT urography provides sufficient image quality with potential to reduce radiation exposure.


Finite-size scaling in the steady state of the fully asymmetric exclusion process.
Finite-size scaling expressions for the current near the continuous phase transition and for the local density near the first-order transition are found in the steady state of the one-dimensional fully asymmetric simple-exclusion process with open boundaries and discrete-time dynamics. The corresponding finite-size scaling variables are identified as the ratio of the chain length to the localization length of the relevant domain wall.


Finite element analysis of cervical facetectomy.
Moment-rotation responses and disc anulus stresses of intact and facetectomized C4-C6 cervical spinal units were analyzed using detailed, three-dimensional, finite element models. To evaluate biomechanical effects of progressive unilateral and bilateral facet resections on cervical spine segmental mobility (external response) and disc anulus stress (internal response). Experimental studies have demonstrated that facetectomy significantly increases segmental mobility of the cervical spine. The biomechanical effects of facetectomy on the internal response, however, have not been investigated. Moment-rotation responses of C4 with respect to C6 and von Mises stress in the disc anulus were examined using finite element models of a 0% (intact), 25%, 50%, 75%, and 100% unilaterally and bilaterally facetectomized cervical spinal unit. The model simulations were conducted under the pure-moment loading of 1.8 Nm in flexion, extension, lateral bending, and axial torsion. The intact model also was validated experimentally under the same conditions. The moment-rotation responses of the intact unit were within the ranges of experimental data. Cervical rotations increased with the increased degree of facet resection. The greatest change occurred between 50% and 75% facet resections in bilateral facetectomy. Similar patterns were found for disc anulus stresses, but to a greater extent. The maximum increase in rotation (11%) and in anulus stress (30%) occurred in lateral bending. Torsion was the least affected loading mode. The effects of unilateral facetectomy were considerably less than those of 75% bilateral facetectomy. Facetectomy has a greater effect on anulus stress than on intervertebral joint stiffness. Significant increase in anulus stresses and segmental mobility may occur when bilateral facet resection exceeds 50%.


Reactive oxygen species and not lipoxygenase products are required for mouse B-lymphocyte activation and differentiation.
A potential role for lipoxygenase (LO) products and reactive oxygen species (ROS) in mouse B-lymphocyte activation and differentiation was investigated. Previously published investigations with the nonspecific 5-LO (EC 220.127.116.11) and 12-LO (EC 18.104.22.168) inhibitors such as nordihydroguaiaretic acid (NDGA) and 6,7-dihydroxycoumarin (Esculetin), are misleading in that they suggest lymphocyte LO activity is required for activation and differentiation of these cells. In initial support of this concept, we report that NDGA and Esculetin completely inhibited B-lymphocyte activation mediated by either membrane immunoglobulin (mIg), or the lipopolysaccharide (LPS) receptor. NDGA and Esculetin completely inhibited cell enlargement and proliferation, exhibiting half maximal inhibitory concentrations (IC50S) of approximately 1 x 10(-6) M. In contrast, the highly specific 5-LO inhibitors BAY X 1005, MK-886 and Wy 50,295 did not inhibit cell enlargement or proliferation. Moreover, 5,8,11-eicosatriynoic acid (ETI) which inhibits 5- and 12-LO, and 5, 8, 11, 14-eicosatetraynoic acid (ETYA) which inhibits all known LOs did not affect B-lymphocyte proliferation. Interestingly, NDGA and Esculetin are antioxidants, unlike BAY X 1005, MK-886, Wy 50,295, ETI and ETYA. Our hypothesis was that the antioxidant activities of NDGA and Esculetin were reponsible for inhibiting B-lymphocyte activation and proliferation and we speculated that ROS and not LO activity was required for both processes. Additional antioxidants such as butylated hydroxy toluene, o-phenanthroline, thiourea, and alpha-tocopherol (vitamin E), also inhibited B-lymphocyte proliferation induced by either the LPS or mIg receptors. These agents exhibited IC50S of 1 x 10(-8) M, 5 x 10(-10) M, 6 x 10(-3) M and 5 x 10(-5) M, respectively. When resting B-lymphocytes were treated with a source of ROS (1 x 10(-5) M H2O2), cells enlarged in a temperature-sensitive manner, which is similar to LPS-induced enlargement. Both NDGA and Esculetin completely inhibited H2O2-induced enlargement. These results further indicate that ROS are required for B-lymphocyte activation and proliferation. Similar results were obtained for B-lymphocyte differentiation. NDGA and Esculetin completely inhibited the development of plasma cells and displayed IC50S of 5 x 10(-6) M. Conversely, BAY X 1005, MK-886, Wy 50,295, ETI, and ETYA did not block the formation of plasma cells. Therefore, ROS are also crucial for differentiation into plasma cells. These experiments are the first to directly illustrate that intracellular ROS mediate B-lymphocyte activation, proliferation and differentiation and that LO products are not required for these processes.(ABSTRACT TRUNCATED AT 400 WORDS)


Regulation of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression in rat hepatocytes in primary culture.
We have performed a comparative study on tPA and PAI-1 mRNA expression in primary cultures of rat hepatocytes and elucidated the possible regulation of these factors by certain hormonal stimulation. The tPA mRNA increased 2- to 4-fold in the presence of cholera toxin (CT), dibutyryl cyclic AMP (dbcAMP), or 3-isobutyl-1-methyl xanthine (IBMX), but slightly decreased in the presence of dexamethasone. The tPA activity was also changed by these agents in a similar fashion. On the contrary, PAI-1 mRNA decreased with CT, dbcAMP, or IBMX, but increased transiently with dexamethasone. From results obtained with cycloheximide, ongoing protein synthesis was judged to be required for both PAI-1 induction with dexamethasone and PAI-1 suppression with IBMX, but not for the tPA induction with IBMX. Dexamethasone exerted opposite regulatory effects on the tPA mRNA expression depending on its concentration: at 10(-8) to 10(-6) M, it suppressed the expression; whereas at 10(-10) M, it elevated the expression.


Biosynthesis of Diverse Antimicrobial and Antiproliferative Acyloins in Anaerobic Bacteria.
Metabolic profiling and genome mining revealed that anaerobic bacteria have the potential to produce acyloin natural products. In addition to sattazolin A and B, three new sattazolin congeners and a novel acyloin named clostrocyloin were isolated from three strains of Clostridium beijerinckii, a bacterium used for industrial solvent production. Bioactivity profiling showed that the sattazolin derivatives possess antimicrobial activities against mycobacteria and pseudomonads with only low cytotoxicity. Clostrocyloin was found to be mainly active against fungi. The thiamine diphosphate (ThDP)-dependent sattazolin-producing synthase was identified in silico and characterized both in vivo and in in vitro enzyme assays. A related acyloin synthase from the clostrocyloin producer was shown to be responsible for the production of the acyloin core of clostrocyloin. The biotransformation experiments provided first insights into the substrate scope of the clostrocyloin synthase and revealed biosynthetic intermediates.


A single WAP domain-containing protein from Litopenaeus vannamei possesses antiproteinase activity against subtilisin and antimicrobial activity against AHPND-inducing Vibrio parahaemolyticus.
The single WAP domain-containing protein (SWD) is a type III crustin antimicrobial peptide whose function is to defense the host animal against the bacterial infection by means of antimicrobial and antiproteinase activities. A study of SWD from Litopenaeus vannamei (LvSWD) is reported herein about its activities and function against bacteria, particularly the AHPND-inducing Vibrio parahaemolyticus (VPAHPND) that causes acute hepatopancreatic necrosis disease (AHPND). The LvSWD is mainly synthesized in hemocytes and up-regulated in response to VPAHPND infection. Over-expressed mature recombinant LvSWD (rLvSWD) and its WAP domain (rLvSWD-WAP) are able to strongly inhibit subtilisin but not trypsin, chymotrypsin and elastase. The rLvSWD inhibits subtilisin with the inhibition constant (Ki) of 14.3 nM. However, only rLvSWD exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. Unlike the rLvSWD, the rLvSWD-WAP does not possess antimicrobial activity. Therefore, the killing effect of rLvSWD on VPAHPND and Bacillus megaterium was studied. The MIC of 30 μM against VPAHPND is bactericidal whereas the MIC against B. megaterium is not. With four times the MIC of rLvSWD, the VPAHPND-treated post larval shrimp are able to survive longer with 50% survival rate as long as 78 h as compared to 36 h of the infected shrimp without rLvSWD. The antimicrobial activity of LvSWD against the VPAHPND infection suggests its potential application for disease control in aquaculture.


Pattern of Failure with Locally Advanced Cervical Cancer– A Retrospective Audit and Analysis of Contributory Factors
Background: The majority of the global burden of cervical cancer is affecting developing countries. Despite improvement in treatment of patients presenting at a locally advanced stage, approximately 50% experience recurrence within the 1st two years. This study was conducted to analyse contributory factors for recurrence within 24 months. Methods: The present retrospective study was undertaken to analyse factors affecting recurrence, type of failure and the follow up pattern of patients who completed treatment with a minimum follow-up period of 6 months during the study period of 5 years. Results: Out of 323 patients included in the study, 112 (34.7%) presented with recurrence within the follow-up period. The stage and histology had a significant impact on disease free survival (DFS). Of those who were followed-up regularly, recurrence was observed in 28.7% with a DFS of 81.3 months, in contrast to the 48. 5% patients with a DFS of 45.0 months for whom follow-up was irregular. The failure pattern was mostly in the form of nodal recurrence (61%). On univariate analysis, treatment time, EBRT and ICBT gap and mean EQD2 point A were found to associated with a better outcome in terms of 2yr DFS. On Cox regression analysis, stage, histology, treatment gap (HR-0.48) and follow up pattern (HR-0.24) retained their effects on survival. Point A dose was higher in patients without recurrence (P value 0.000) unlike other assymmetric parameters. Conclusion: Apart from point A cumulative dose (mean EQD2), stage, histology and treatment gap were the factors that affected early local failure. An interesting result was that follow-up pattern had a significant impact on DFS period.


Nutritional Content Dynamics and Correlation of Bacterial Communities and Metabolites in Fermented Pickled Radishes Supplemented With Wheat Bran.
Wheat bran supplementation in cereal food processing improves the nutritional value and quality of the final products. However, whether wheat bran has the potential as a biofortifier to enhance nutritional and flavor of fermented vegetables remains unknown. The study aimed to evaluate the potential of wheat bran supplementation for nutrition and flavor fortification during radish fermentation, and to explore the role of microorganisms in nutritional and flavor development. Using high-throughput sequencing coupled with high-performance liquid chromatography and headspace solid-phase microextraction-gas chromatography-mass spectrometry, the microbial community profiles and nutritional and flavor changes of wheat bran-treated samples were analyzed and compared with control samples. Correlation analysis between bacteria taxa with metabolites were also performed. The results showed that wheat bran treatment increased the content of most free amino acids (FAAs), α-linolenate, thiamine, and riboflavin in the samples (p < 0.05). In addition, the increased consumption of reducing sugar and glutamate in the wheat bran-treated samples was due to the production of secondary metabolites such as lactic acid, ethanol, acetic acid, and GABA (p < 0.05). Moreover, compared with control samples, the flavor of the wheat bran-treated pickled radish was preferable. Wheat bran increased the amount of alcohol, ester, acid, and ketones compounds but reduced the number of sulfides, which increased the aroma but decreased the pungent flavor. Additionally, the correlation analysis suggested that Lactobacillus, the most dominant genus, was boosted by wheat bran and was positively associated with most of FAAs, GABA, and lactate, while negatively associated with most sulfides. Therefore, compared with the control, wheat bran treatment could improve the nutritional values and sensorial properties of radish pickles. New areas of research should explore the co-fermentation of other vegetables with wheat bran, and the potential of this processing technique to provide consumers with products of high nutritional quality.


Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes.
Male and female BALB/c mice were inoculated with various concentrations of coxsackievirus, group B, type 3 (CVB3), ranging from 10 to 10(7) plaque-forming units (PFU). Lower viral doses (greater than 10(2) PFU) induced severe myocarditis in male mice but caused little injury in females. With 10(7) PFU, females also developed severe disease. Females may be relatively resistant to CVB3-induced myocarditis because virus entry into the blood and heart is less effective. Males given 125I-CVB3 show approximately 2-4 and 20-fold more radioactivity in the peripheral blood and heart, respectively, than females. No differences were observed between the sexes in 125I-bovine serum albumin penetration. Sex steroid hormones influence viremia and virus localization; females given exogenous testosterone and progesterone demonstrate ten times more virus in their hearts than animals given estradiol. The hormones may act by increasing virus receptor expression on endothelial cells and myocytes.


Coronary stent insertion into a 20-year-old Blalock-Taussig Shunt.
A 21 year-old female with complex congenital heart disease presented with declining exercise tolerance, presyncope and increasing cyanosis despite regular venesection. Her double inlet left ventricle with rudimentary right ventricle, restrictive ventricular septal defect and pulmonary stenosis had been managed with a Classic Left Blalock-Taussig (B-T) Shunt aged 2 months and a Modified Right B-T Shunt at 4 years. Aortography revealed a patent but significantly narrowed Left B-T shunt with impaired blood flow and an aneurysmal pulmonary artery. Angioplasty and stenting of the shunt was undertaken and a 4.0 x 12mm coronary stent deployed. The patient's arterial oxygen saturation improved from 76% on pulse oximetry to 85% post procedure and she reported significantly improved exercise tolerance upon follow-up.


Generation of superoxide (O2-.) from alveolar macrophages exposed to asbestiform and nonfibrous particles.
Active oxygen species are implicated causally in tumor promotion by 12-O-tetradecanoylphorbol-13-acetate and in cell damage by asbestos, a putative tumor promoter of the respiratory tract. To determine the properties of asbestos important in generation of the oxygen free radical, superoxide (O2-.), hamster and rat alveolar macrophages were exposed in vitro to nontoxic concentrations of fibrous (crocidolite, erionite, Code 100 fiberglass, sepiolite) and nonfibrous (riebeckite, mordenite, glass) particulates. The amount of O2-. released by cells in response to dusts was determined by measuring the reduction of cytochrome c in the presence and absence of superoxide dismutase. Results showed that all fibrous (defined as a greater than 3:1 length:diameter ratio) dusts caused a significant increase in both release of O2-. from rat macrophages and enhancement of zymosan-triggered O2-. from hamster macrophages. Nonfibrous particles were less active than fibers at comparable concentrations. These results suggest that the geometry of particulates is of critical importance in the generation of O2-. from cells of the respiratory tract.


Annual activity density of groundbeetles (Coleoptera: Carabidae) of a Celtis ehrenbergiana (Rosales: Celtidaceae) forest of Buenos Aires province, Argentina.
The aim of this study was to describe the annual activity cycle, the sex ratio, and the relationship between the weather variables and activity density of the 16 most abundant carabid species of a typical southeastern region of Pampasia, Argentina. The study focused on the southernmost Celtis ehrenbergiana (Klotzsch) Liebmann ( = C. tala Guillies ex Planch) native forest of the region, from March 2008 to March 2009, a period during which there was a marked draught associated with the La Niña phenomenon. Forty-five pitfall traps were emptied once every 2 wk, and the occurrence of larvae, tenerals, and subtenerals was recorded. Photoperiod, temperature, and precipitations explained 35% of the total variation in the catch. Total carabid activity was high in early autumn and late spring. Eight species reached their maximum activity in spring, five in winter, two in summer, and one in autumn. Possible reproductive strategies, the influence of different variables involved in the life cycles of the species, and the sex ratio and their limitations are discussed.


Antibiotic choices by paediatric residents and recently graduated paediatricians for typical infectious disease problems in children.
To evaluate antibiotic choices and recommendations for duration of therapy made by paediatric residents (PRs) and recently graduated paediatricians (RGPs) in several typical infectious disease conditions. In autumn 2002, a two-page questionnaire was sent to 276 core PRs in Canadian residency programs and to a random selection of 276 RGPs from across Canada. The questionnaire described 10 scenarios: otitis media, pharyngitis, sinusitis, bronchopneumonia, lobar pneumonia, meningitis, pyelonephritis, osteomyelitis, cellulitis, and fever and neutropenia. The participants were asked primarily about initial antibiotic selection and duration of treatment for each scenario. There were 251 participants (overall response rate of 45%). The two most common antibiotic recommendations constituted 85% or more of the total for all scenarios except acute otitis media, sinusitis, cellulitis, and fever and neutropenia. There was a twofold or more difference in the range of recommended duration of treatment for all scenarios and a threefold or more difference for sinusitis, meningitis and osteomyelitis. PRs were more likely than RGPs to use broader spectrum cephalosporins for pneumococcal pneumonia (33% versus 15%, respectively; P=0.001) and to treat sinusitis for just five to 10 days (39% versus 22%, respectively; P=0.01). Also, 33% of all participants recommended amoxicillin/clavulanate or a cephalosporin rather than amoxicillin for sinusitis. PRs and RGPs made similar and reasonable recommendations, largely in line with published guidelines, for most of the infectious disease scenarios presented. For some conditions, a significant minority of respondents unnecessarily recommended broad-spectrum antibiotics. The most variable responses were for duration of treatment, reflecting the lack of certainty in the published evidence base for many conditions.


Osteopontin deficiency dampens the pro-atherogenic effect of uraemia.
Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.e. inflammation and phenotypic modulation of smooth muscle cells (SMCs). We explored the role of OPN on vascular pathology in uraemic mice. Uraemia was induced by 5/6 nephrectomy in E KO and in OPN and E double KO mice (E/OPN KO). In E KO mice, uraemia increased the relative surface plaque area in the aortic arch (from 28 ± 2% [n = 15], to 37 ± 3% [n = 20] of the aortic arch area, P < 0.05). A positive correlation was observed between plasma OPN and aortic atherosclerosis in uraemic E KO mice (r(2) = 0.48, P = 0.001). In contrast, aortic atherosclerosis was not increased by uraemia in E/OPN KO mice. OPN deficiency in haematopoietic cells (including macrophages) did not affect development of uraemic atherosclerosis, even though OPN-deficient foam cells had decreased inflammatory capacity. Gene expression analyses indicated that uraemia de-differentiates SMCs in the arterial wall. This effect was dampened in whole-body OPN-deficient mice. The data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.


Diversification of self-organized architectures in supramolecular dye assemblies.
Upon complexation with bismelamine receptors (BMn) featuring different alkyl linker lengths (number of methylene groups (n) = 5-12), a barbituric acid merocyanine dye (1) can be loaded into diverse self-organized superstructures through multiple hydrogen-bonding interactions. UV/vis, dynamic light scattering, and NMR studies in cyclohexane demonstrate that the diversification of the primarily formed hydrogen-bonded species in solution occurs by varying the linker length of BMn. Hierarchical organization of the hydrogen-bonded species is achieved by slow evaporation of the solvent (forming solvent-free films), and the resulting superstructures are evaluated by polarized optical microscopy, X-ray diffraction, SEM, and AFM techniques. The formation of columnar structures with and without two-dimensional ordering are revealed for shorter (n = 5-7) and longer (n = 11, 12) linker bis(melamines), respectively. On the contrary, in the cases of n = 8-10, the formation of lamellar structures is unveiled. Several assemblies (n = 5, 7, 11) indicate the formation of a liquid crystalline mesophase in POM and DSC analyses. Hierarchical organization is also achieved in solution by prolonged aging, affording phase-separated crystalline nanofibers (n = 5, 7) and soft nanofibrils agglomerating into wormlike objects (n = 8), gel-forming continuous globular networks (n = 10), and nanofibers (n = 11, 12). These superstructural and morphological diversifications are an outcome of the variation in the primarily formed hydrogen-bonded supramolecular architectures. Using this strategy, diverse self-assembled materials will be obtained from a single dye component.


A guide to the regulation of selective autophagy receptors.
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications - phosphorylation, ubiquitination, acetylation and oligomerisation - that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.


Quantum streamlines within the complex quantum Hamilton-Jacobi formalism.
Quantum streamlines are investigated in the framework of the quantum Hamilton-Jacobi formalism. The local structures of the quantum momentum function (QMF) and the Polya vector field near a stagnation point or a pole are analyzed. Streamlines near a stagnation point of the QMF may spiral into or away from it, or they may become circles centered on this point or straight lines. Additionally, streamlines near a pole display east-west and north-south opening hyperbolic structure. On the other hand, streamlines near a stagnation point of the Polya vector field for the QMF display general hyperbolic structure, and streamlines near a pole become circles enclosing the pole. Furthermore, the local structures of the QMF and the Polya vector field around a stagnation point are related to the first derivative of the QMF; however, the magnitude of the asymptotic structures for these two fields near a pole depends only on the order of the node in the wave function. Two nonstationary states constructed from the eigenstates of the harmonic oscillator are used to illustrate the local structures of these two fields and the dynamics of the streamlines near a stagnation point or a pole. This study presents the abundant dynamics of the streamlines in the complex space for one-dimensional time-dependent problems.


Hierarchical models of rigidity percolation.
We introduce models of generic rigidity percolation in two dimensions on hierarchical networks and solve them exactly by means of a renormalization transformation. We then study how the possibility for the network to self organize in order to avoid stressed bonds may change the phase diagram. In contrast to what happens on random graphs and in some recent numerical studies at zero temperature, we do not find a true intermediate phase separating the usual rigid and floppy ones.


Influence of Amitraz and Oxalic Acid on the Cuticle Proteolytic System of Apis mellifera L. Workers.
This work verifies that amitraz and oxalic acid treatment affect honeybee cuticle proteolytic enzymes (CPE). Three bee groups were monitored: oxalic acid treatment, amitraz treatment, control. Electrophoresis of hydrophilic and hydrophobic CPE was performed. Protease and protease inhibitor activities (in vitro) and antifungal/antibacterial efficiencies (in vivo), were analyzed. Amitraz and oxalic acid treatment reduced hydrophobic, but did not affect hydrophilic, protein concentrations and reduced both hydrophilic and hydrophobic body surface asparagine and serine protease activities in relation to most substrates and independently of pH. The activities of natural cuticle inhibitors of acidic, neutral, and alkaline proteases were suppressed as a result of the treatments, corresponding with reduced antifungal and antibacterial activity. Electrophoretic patterns of low-, medium-, and high-molecular-weight proteases and protease inhibitors were also affected by the treatments.


Genetic correlations of intramuscular fat content and fatty acid composition among muscles and with subcutaneous fat in Duroc pigs.
There is an increasing interest in including intramuscular fat (IMF) content and fatty acid composition, particularly oleic acid (C18:1) content, in the selection objectives of pig lines for quality pork markets. These traits are costly and can be measured in more than 1 location, so knowing their correlation structure across muscles and with subcutaneous fat (SF) is necessary for developing optimum sampling and recording schemes. We analyzed the genetic and phenotypic correlations of IMF content and composition among 3 of the most relevant muscles (LM, gluteus medius muscle [GM], and semimembranosus muscle [SM]) and with the fatty acid composition of SF. All genetic correlations were positive but variable. For IMF, the genetic correlation between GM and LM was 0.68, and for fatty acids, the genetic correlation ranged from 0.62 for C18:1 to 0.82 for total PUFA. Genetic correlations of GM and LM with SM were much lower: 0.13 to 0.19 for IMF and 0.10 to 0.54 for fatty acids. Correlations for fatty acid composition in SF with GM and LM were moderate to high (0.29-0.53 and 0.43-0.75, respectively) but were null with SM. The expected responses for IMF in the 3 muscles and for C18:1 in each muscle and in SF to selection on records taken from only a single muscle or SF were estimated. Selection for IMF and C18:1 in GM is expected to lead to positive responses in IMF and C18:1 in LM and vice versa, although this can entail genetic lags of 20 to 45% in the muscle not directly selected for. Selection for C18:1 in SF is more effective for C18:1 in LM than in GM and of very limited value for IMF. In conclusion, the genetic correlations of IMF content and fatty acid composition among muscles and with SF, although positive, are variable enough to influence the genetic evaluation scheme for IMF and fat quality. They also indicate that GM and LM can be used alternatively for selection purposes.


Evaluation of primary/preferred language data collection.
A literature review was conducted to identify peer-reviewed articles related to primary/preferred language and interpreter-use data collection practices in hospitals, clinics, and outpatient settings to assess its completeness and quality. In January 2011, Embase (Ovid), MEDLINE (Ovid), PubMed, and Web of Science databases were searched for eligible studies. Primary and secondary inclusion criteria were applied to selected eligible articles. This extensive literature search yielded 768 articles after duplicates were removed. After primary and secondary inclusion criteria were applied, 28 eligible articles remained for data abstraction. All 28 articles in this review reported collecting primary/preferred language data, but only 18% (5/28) collected information on interpreter use. This review revealed that there remains variability in the way that primary/preferred language and interpreter use data are collected; all studies used various methodologies for evaluating and abstracting these data. Likewise, the sources from which the data were abstracted differed.


Tree-based analysis of microarray data for classifying breast cancer.
DNA microarray data have provided us with the opportunity to assess the expression levels for thousands of genes simultaneously. One of the uses of this information is to classify cancer tumors. A noted challenge in using microarray information is analytical. Following the work of Zhang et al. (1), we further pursue the use of recursive partitioning in analyses of microarray data for cancer classification. Not only does the recursive partitioning technique create intuitive classification rules, but also it is most flexible as to the handling of a massive number of genes, missing expressions, and multi-class tissues. Using a published data set (2), we demonstrate that the recursive partitioning technique creates a more precise and simpler classification rule than other commonly used approaches. In particular, we introduce the concept of A-tree and propose a procedure to assess a large number of A-trees. One of the identified genes (ERBB2) is in the close region of BRCA1 (17q21.1) and has been shown by others to have altered expression levels in breast cancer. Nonetheless, our identified genes warrant further investigation as to whether they play a role in the etiology of breast cancer.


[intracellular signal transmission].
Information is received by cells at their exterior surface in forms of hormones, growth factors, neurotransmitters, antigens and other signalling molecules. Their information must be transduced through binding to membrane receptors, so as to elicit the appropriate biological response from the manifold repertoire of a cell. The machinery used by a cell to translate the signal from exterior membrane-interactive ligands to the inside of the cells and to generate second messengers is the topic of this essay.


Average volume-assured pressure support for patients with obstructive sleep apnea with failed CPAP titration.
Obstructive sleep apnea (OSA) is a common disease, often treated using continuous positive airway pressure (CPAP) therapy. In many cases, patients fail a CPAP titration study due to inadequate control of the apnea-hypopnea index (AHI, events/hour) or due to treatment-emergent central sleep apnea (TE-CSA). We report our experience using a mode of non-invasive ventilation for alternative treatment of these patients. We reviewed records of adults who had OSA with AHI≥15 diagnosed on polysomnography (PSG) with failed CPAP titration and in whom titrations with average volume-assured pressure support (AVAPS) with auto-titrating expiratory positive airway pressure were performed. Forty-five patients, age 57.9±13.1 y, 26 males, body mass index (BMI) 40.2±8.7kg/m2. Reasons for CPAP titration failure included: TE-CSA (25, 55.6%) and inadequate control of AHI at maximum CPAP of 20cm H2O (20, 44.4%). Changes noted from baseline PSG to AVAPS titration: AHI: 65.3±29.3 decreased to 22.3±16.1 (p<0.001). Median time SpO2 ≤88%: 63.7 to 6.9min (p<0.001). In 16 patients the AHI was reduced to <15 and in 16 additional patients the AHI was reduced to <30. Improvement in AHI was not related to gender, age, or opioid use, but was correlated with BMI: ∆AHI=12.2 - (1.4 * BMI); p=0.05. AVAPS resulted in improved sleep architecture: median N3 sleep increased: 1.4% to 19.6% total sleep time (TST) (p<0.001), and median R sleep increased: 6.4% to 13.6% TST (p<0.01). For patients with OSA for whom CPAP titration failed, titration with AVAPS may be an effective treatment.


Effects of anti-estrogens on early pregnancy in guinea pigs.
To compare effects of various anti-estrogens on early pregnancy. Fifty regularly cycling guinea pigs were divided into five groups (five animals/group), of which three groups received 3 mg/kg body weight Nafoxidine, Centchroman, or Tamoxifen, respectively, on the 1st, 2nd, or 3rd day of pregnancy. The rest of the animals were kept as controls, and received either saline or propylene glycol. Autopsies were done on the 8th day of pregnancy in all the groups. Presence or absence of implantation sites was observed by using a stereomicroscope. Plasma levels of 17 beta-estradiol and progesterone and their receptors, as well as enzyme levels in the uterine tissue, were estimated. During normal early pregnancy there was an increase in the concentration of peripheral plasma levels of steroid hormones with respect to enzyme and steroid hormone receptor levels in the uterus. Administration of anti-estrogens showed a decreased trend in all the variables studied, especially in the tamoxifen-treated animals. The results of the study suggest that anti-estrogens, if administered during early pregnancy, can prevent the process of ovum implantation in this species.


Updates on upper eyelid blepharoplasty.
The human face is composed of small functional and cosmetic units, of which the eyes and periocular region constitute the main point of focus in routine face-to-face interactions. This dynamic region plays a pivotal role in the expression of mood, emotion, and character, thus making it the most relevant component of the facial esthetic and functional unit. Any change in the periocular unit leads to facial imbalance and functional disharmony, leading both the young and the elderly to seek consultation, thus making blepharoplasty the surgical procedure of choice for both cosmetic and functional amelioration. The applied anatomy, indications of upper eyelid blepharoplasty, preoperative workup, surgical procedure, postoperative care, and complications would be discussed in detail in this review article.


GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia.
Non-syndromic microcytic congenital sideroblastic anemia (cSA) is predominantly caused by defective genes encoding for either ALAS2, the first enzyme of heme biosynthesis pathway or SLC25A38, the mitochondrial importer of glycine, an ALAS2 substrate. Herein we explored a new case of cSA with two mutations in GLRX5, a gene for which only two patients have been reported so far. The patient was a young female with biallelic compound heterozygous mutations in GLRX5 (p.Cys67Tyr and p.Met128Lys). Three-D structure analysis confirmed the involvement of Cys67 in the coordination of the [2Fe2S] cluster and suggested a potential role of Met128 in partner interactions. The protein-level of ferrochelatase, the terminal-enzyme of heme process, was increased both in patient-derived lymphoblastoid and CD34+ cells, however, its activity was drastically decreased. The activity of ALAS2 was found altered and possibly related to a defect in the biogenesis of its co-substrate, the succinyl-CoA. Thus, the patient exhibits both a very low ferrochelatase activity without any accumulation of porphyrins precursors in contrast to what is reported in erythropoietic protoporphyria with solely impaired ferrochelatase activity. A significant oxidative stress was evidenced by decreased reduced glutathione and aconitase activity, and increased MnSOD protein expression. This oxidative stress depleted and damaged mtDNA, decreased complex I and IV activities and depleted ATP content. Collectively, our study demonstrates the key role of GLRX5 in modulating ALAS2 and ferrochelatase activities and in maintaining mitochondrial function.


Perspectives on local environmental security, exemplified by a rural South African village.
This paper analyzes the human-nature interaction in a village in rural South Africa. It discusses preconditions, perceptions, and consequences of natural resource use, and places these findings into a regional and historical context. Applying an interdisciplinary perspective, the study uses interviews, questionnaires, remote sensing, and participatory mapping to analyze land cover changes and local perceptions of the environment. The study area is located in a former homeland (Transkei), a setting where well-recorded conflicts in the human-nature sphere have previously been triggered by population pressure, apartheid policies, and other historical, political, and social reasons. A small-scale and subjective conceptualization of environmental security is used as an approach to analyze local livelihood strategies in a selected village. The results indicate that the environment is not the highest priority in local survival strategies. Instead, formal and informal jobs and governmental grants are the most important security strategies. There are thus no major conflicts resulting from the interaction between the local population and the natural resources in this specific area. Explanations to this pattern can partly be found in historical contexts, which include apartheid policies, re-localizations, and a system of migrant labor. The study also suggests that general truths about a region such as Transkei might be misleading in specific localities. For relevant and successful environmental management and development planning however, it is crucial that decision-makers be able to get a clear picture of local situations and adjust their plans accordingly.


Recruiting, interviewing, and hiring pharmacy personnel.
A practical approach to recruiting, interviewing, and hiring pharmacy personnel is presented. Recruiting applicants should be an ongoing function, and personnel departments can serve as an important resource. A good pool of applicants can be developed by contacts, referrals, and advertising and through schools of pharmacy and placement services. Federal and state regulations regarding equal employment opportunity and affirmative action are discussed. The first step of the interview process involves comparing the applications with a current job description. A strategy for conducting the interview should be developed before the meeting takes place. Some examples of basic questions and questions that can be used to explore the applicant's work experience, background, and motivational level are presented. Suggestions are made for documenting interviews. Details on making the hiring decision on the basis of the interview are discussed, and the process of actually offering the position is covered. Hiring new employees is a major commitment that demands careful consideration. Each step in the process of recruiting, interviewing, and hiring must be performed diligently to avoid problems later on.


15 years of experience with renal replacement therapy in patients starting therapy before age 20.
This study retrospectively evaluates the survival on renal replacement therapy among patients starting dialysis before their twentieth birthday. The cohort included all patients starting therapy from 1972 through August, 1987 at the University of Mississippi or Kidney Care, Inc. Fifty-five patients, median age 17 years, range 5-19 years, underwent 335 patient years of therapy. Nineteen initially received CAPD; 12 home hemodialysis, 2 were transplanted prior to dialysis, and the remaining 22 patients were entered into dialysis in a free standing facility. Thirty-one patients received a cadaveric transplant and four patients received a living related transplant. The median transplant survival was 1360 days. There were 10 patients on renal replacement therapy over 10 years and a survival plot projected a 70% survival at 10 years. Nine patients died. Three percent of the time on renal replacement therapy was spent hospitalized. Although the hospitalization rate is significant, the pediatric patient may be expected to have a long survival on renal replacement therapy.


Image stitching using an electrowetting-based liquid prism with a fabrication method.
In this paper, we propose a new method for image stitching using an electrowetting-based liquid prism. Several images were obtained by adjusting the voltages applied to four sidewalls of the liquid prism, and a panoramic image was achieved through an image stitching algorithm. The relationship between the tilting angle of the liquid prism and the normal vector of the liquid-liquid interface was presented. Novel fabrication method has been proposed to improve the performance of the liquid prism, including the addition of a new structure to prevent oil isolation, plastic chamber material, plastic laser cutting, and oil selection. The fabricated liquid prism has a size of 5 × 5 × 8 mm, a maximum beam steering angle of ±10.5 °, a response time of 19.1 ms, and a resolution of 14.25 lp/mm. The required number of images according to the overlapping area was presented through the simulation, and the image stitching using two or three images was demonstrated.


Insect Sex Determination Manipulated by Their Endosymbionts: Incidences, Mechanisms and Implications.
The sex-determining systems of arthropods are surprisingly diverse. Some species have male or female heterogametic sex chromosomes while other species do not have sex chromosomes. Most species are diploids but some species, including wasps, ants, thrips and mites, are haplodiploids (n in males; 2n in females). Many of the sexual aberrations, such as sexual mosaics, sex-specific lethality and conversion of sexuality, can be explained by developmental defects including double fertilization of a binucleate egg, loss of a sex chromosome or perturbation of sex-determining gene expression, which occur accidentally or are induced by certain environmental conditions. However, recent studies have revealed that such sexual aberrations can be caused by various groups of vertically-transmitted endosymbiotic microbes such as bacteria of the genera Wolbachia, Rickettsia, Arsenophonus, Spiroplasma and Cardinium, as well as microsporidian protists. In this review, we first summarize the accumulated data on endosymbiont-induced sexual aberrations, and then discuss how such endosymbionts affect the developmental system of their hosts and what kinds of ecological and evolutionary effects these endosymbionts have on their host populations.


Variability of performance status assessment between patients with hematologic malignancies and their physicians.
This study was conducted to determine the incidence of inter-observer variability in Eastern Cooperative Oncology Group (ECOG) performance status (PS) rating between patients with leukemia and lymphoma and their physicians. ECOG PS was assessed at diagnosis by patients and their physicians and stratified by disease subtype, gender, age, disease stage and education. Association between patient- and physician-rated PS and overall survival (OS) was stratified by subtype and prognostic risk score. Overall, 65% of patients and physicians rated PS the same. Age, disease stage and disease subtype were significant predictors of PS disagreement. PS was a significant predictor of OS irrespective of assessment by patients or physicians across all subtypes except those with Hodgkin lymphoma. These findings suggest the need for physicians to better communicate with patients when determining PS, as PS is a strong predictor of survival and is critical in treatment decisions, including determining fitness for cancer treatment.


Analysis of human cellular retinol-binding protein II promoter during enterocyte differentiation.
Cellular retinol binding protein II (CRBP II) is a vitamin A-binding protein that is expressed specifically in small intestinal villus absorptive cells. Previous studies have shown that retinoic acid upregulates endogenous human CRBP II gene expression in differentiated Caco-2 cells. To better characterize the regulation of human CRBP II expression, we analyzed the ability of receptor-selective agonists to enhance transcription from the 5'-upstream flanking region of the human CRBP II gene. Stable transfection experiments showed that the proximal 2.8-kb region of the human CRBP II gene is sufficient for retinoic acid inducibility in differentiated Caco-2 cells. However, direct sequence analysis and transient transfection experiments indicate that, unlike the rat CRBP II promoter, the human CRBP II promoter is not a direct retinoid X receptor target. The results indicate that the retinoic acid responsiveness of the human CRBP II promoter is mediated by an indirect mechanism and that this mechanism is associated with enterocyte differentiation.


[Prenatal sex determination via GBN saliva test. A comparison with the results of prenatal chromosomal analysis].
In 114 pregnant women the results of the GBN saliva test were compared with the results of sex determination by prenatal chromosomal analysis. GBN test results predicting boys corresponded in 40,7% of the cases with male karyotypes, whereas test results predicting girls corresponded in 56,5% with female karyotypes. Mean age of the women tested was 35,9 +/- 3,6 years. The test results in women aged 35 or younger did not show a better correlation with the chromosomal sexing than in older women (46,5% and 48,4%). Saliva tests performed in the 16th to 20th week of gestation corresponded to the same extent with the chromosomal sex of the fetuses as those performed in the 21st to 32nd week of gestation (48,5% and 46,2%). The mode of ascertainment of the pregnant women and other factors possibly influencing the results are discussed. It is concluded that the GBN saliva test is not suitable for prenatal sex prediction in women of the age group investigated.


Association between serum bilirubin and estimated glomerular filtration rate among elderly persons.
Chronic kidney disease (CKD) is a major public health problem. However, few studies have examined the significance of serum bilirubin as a risk factor for the development of CKD in the general Japanese population. The subjects comprised 413 men (mean age: 79±9 years; (range, 60-100 years) and 637 women (mean age: 81±8 years; range, 60-106 years) who visited the medical department of Seiyo Municipal Nomura Hospital. We examined the relationship between increased serum bilirubin and renal function that was evaluated by estimated glomerular filtration rate (eGFR) using CKD-EPI equations modified by a Japanese coefficient. Stepwise multiple regression analysis with eGFR as the objective variable, and adjusted risk factors as the explanatory variables, showed that serum bilirubin (β = 0.11, P<0.001) was significantly and independently associated with eGFR, in addition to gender, age, prevalence of antihypertensive medication, triglycerides, prevalence of antidiabetic medication, and serum uric acid. Compared with stages 1+2 (eGFR ≥60.0 ml/min/1.73 m2), mean multivariate-adjusted odds ratio {95% (confidence interval (CI)} for hypobilirubinemia (first quartile, <0.52 mg/dL) was 3.52 (range: 1.88-6.59). Next, to control potential confounding factors, data were further stratified by gender, age, medication (antihypertensive, antidyslipidemic, and antidiabetic agents), and prevalence of cardiovascular disease. The standardized coefficient for eGFR was significant in both groups, and there was no interaction between the groups. Our data demonstrated an independent positive association between serum bilirubin and eGFR in both genders. Low serum bilirubin level would be useful as a potential risk factor for renal function.


Epiphenomenon or Prognostically Relevant Interventional Target? A Novel Proportionality Framework for Severe Tricuspid Regurgitation.
Background Tricuspid regurgitation (TR) frequently develops in patients with long-standing pulmonary hypertension, and both pathologies are associated with increased morbidity and mortality. This study aimed to improve prognostic assessment in patients with severe TR undergoing transcatheter tricuspid valve intervention (TTVI) by relating the extent of TR to pulmonary artery pressures. Methods and Results In this multicenter study, we included 533 patients undergoing TTVI for moderate-to-severe or severe TR. The proportionality framework was based on the ratio of tricuspid valve effective regurgitant orifice area to mean pulmonary artery pressure. An optimal threshold for tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio was derived on 353 patients with regard to 2-year all-cause mortality and externally validated on 180 patients. Patients with a tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio ≤1.25 mm2/mm Hg (defining proportionate TR) featured significantly lower 2-year survival rates after TTVI than patients with disproportionate TR (56.6% versus 69.6%; P=0.005). In contrast with patients with disproportionate TR (n=398), patients with proportionate TR (n=135) showed more pronounced mPAP levels (37.9±9.06 mm Hg versus 27.9±8.17 mm Hg; P<2.2×10-16) and more severely impaired right ventricular function (tricuspid annular plane systolic excursion: 16.0±4.11 versus 17.0±4.64 mm; P=0.012). Moreover, tricuspid valve effective regurgitant orifice area was smaller in patients with proportionate TR when compared with disproportionate TR (0.350±0.105 cm2 versus 0.770±0.432 cm2; P<2.2×10-16). Importantly, proportionate TR remained a significant predictor for 2-year mortality after adjusting for demographic and clinical variables (hazard ratio, 1.7; P=0.006). Conclusions The proposed proportionality framework promises to improve future risk stratification and clinical decision-making by identifying patients who benefit the most from TTVI (disproportionate TR). As a next step, randomized controlled studies with a conservative treatment arm are needed to quantify the net benefit of TTVI in patients with proportionate TR.


Influencing governance of a public-private partnership in plant genomics: The societal interface group as a new instrument for public involvement.
The Centre for BioSystems Genomics (CBSG) is a Dutch public-private partnership in plant genomics active in potato and tomato research and exploitation. Its Societal Interface Group (SIG) has been developed to inform its communication strategy and governance practice. This new instrument identifies and discusses early signals from society by bringing together people from different societal backgrounds with members of CBSG management. This interactive learning process facilitates the inclusion of public concerns and needs in scientific developments in the field of plant genomics, and simultaneously enables genomics scientists to search for more societal aims, meanings, and starting points for their research agenda. Analysis of the SIG sessions revealed that the input of public expertise is not threatening or irrational, but provides the opportunity to harness the creative potential of future users highly relevant for the development of societal practices in which plant genomics plays a role.


Neutralizing monoclonal antibodies against Russian strain of the West Nile virus.
We have developed a panel of 16 hybridomas secreting neutralizing monoclonal antibodies (Nt- MAbs) to Russian isolate (LEIV-Vlg99-27889-human) of the West Nile virus (WNV). Most of the Nt-Mabs were either IgG1 or IgG3 subtypes. Nine of the 16 neutralizing MAbs detected WNV protein E in Western blot. According to their Nt-activities, Western blot results and cross-reactivity, the MAbs were divided into four groups. Monoclonal antibodies from group I were able to neutralize WNV strains Vlg99-27889, Vlg00-27924, Hp-94, A-1640, A-72, Tur-2914, and Eg101. The Nt-activity of MAbs from groups II-IV towards these WNV strains was variable. Recombinant fragments E(1-180), E(1-321), and E(260-466) of protein E were used for preliminary mapping of domains recognized by Nt-MAbs. Only five Nt-MAbs were able to react with the recombinant polypeptides. The MAbs 9E2, 7G9, 11G3, and 7E6 from group Ia recognized Nt-epitope(s) between amino acids 321 and 466 of protein E and Nt-MAb 4F11 (group III) reacted with residues 1-180. This demonstrates that two discrete regions of protein E are involved in neutralization of WNV. Our data on immunochemical, biological activities of Nt-MAbs and mapping of Nt-epitopes using recombinant polypeptides suggest at least 13 different Nt-epitopes for WNV.


Rapid detection and enumeration of Naegleria fowleri in surface waters by solid-phase cytometry.
A new method for the rapid and accurate detection of pathogenic Naegleria fowleri amoebae in surface environmental water was developed. The method is based on an immunofluorescent assay combined with detection by solid-phase cytometry. In this study we developed and compared two protocols using different reporter systems conjugated to antibodies. The monoclonal antibody Ac5D12 was conjugated with biotin and horseradish peroxidase, and the presence of cells was revealed with streptavidin conjugated to both R-phycoerythrin and cyanine Cy5 (RPE-Cy5) and tyramide-fluorescein isothiocyanate, respectively. The RPE-Cy5 protocol was the most efficient protocol and allowed the detection of both trophozoite and cyst forms in water. The direct counts obtained by this new method were not significantly different from those obtained by the traditional culture approach, and results were provided within 3 h. The sensitivity of the quantitative method is 200 cells per liter. The limit is due only to the filtration capacity of the membrane used.


Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.
Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups. The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months. Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively. Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.


When kidneys get old: an essay on nephro-geriatrics.
Aging is a nearly universal phenomenon in biology only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by steady loss of nephrons and a corresponding decrease in glomerular filtration rate (GFR) beginning about age 30 years. The mechanisms responsible for this observation is are elusive. However, defining chronic kidney disease based on arbitrary, fixed thresholds of GFR in the later phases of life can be problematical as it may over-diagnosis CKD in the elderly. A modest, persisting reduction of GFR (around 45-59 ml/min/1.73m2) without abnormal proteinuria does not seem to confer much of an adverse effect on mortality and remaining life expectancy in older adults and the development of end-stage renal disease in such subjects is very uncommon. Old kidneys should not be equated with "diseased" kidneys.


Fractional factorial design to investigate the influence of heavy metals and anions on acid neutralization behavior of cement-based products.
A major concern of cement-based solidification/stabilization of hazardous wastes is the interaction of waste contaminants on cement properties. Literature contains many examples of studies on the interference of individual contaminants on cement properties. Conversely, little information is available on how the interactions between contaminants affectthe properties of cement/waste systems. This paper provides a discussion on the interference mechanisms exerted by seven contaminants, five heavy metals and two anions, on cement hydration. The seven contaminants were selected on the basis of the typical composition of municipal solid waste incineration (MSWI) fly ash. Spiking experiments using pure compounds were performed according to a 2IV(7-3) fractional factorial design to simulate addition of MSWI fly ash to ordinary Portland cement. The acid neutralization behavior of the laboratory cement-contaminant mixtures was studied to detect the presence of solid phases responsible for the buffering capacity of the solid matrix. The results from the experimental work showed that Zn, Cl-, and SO4(2-) were the major factors influencing, occasionally in combination with other contaminants, strength and acid neutralization capacity of the cementitious products. The release of Cd, Cr, Cu, and Pb in the eluates as a function of pH also suggested possible chemical immobilization mechanisms of such metals within the hardened matrix.


A National Survey of EMR Usability: Comparisons between medical and nursing professions in the hospital and primary care sectors in Australia and Finland.
Electronic Medical Record Systems (EMRs) are now part of nursing and medical professionals daily work in the acute and primary care sectors in Australia. Usability is an important factor in their successful adoption and impacts upon clinical workflow, safety and quality, communication, and collaboration. This study replicates a significant body of work conducted by Finnish researchers applying a usability focused survey to understand medical and nursing professionals' experiences in the Australian context. As we implement EMRs across health systems, their usability and design to support clinicians to effectively deliver and document care, is essential. We conducted an observational study using a cross sectional survey, the National Usability-Focused HIS Scale (NuHISS) developed and validated by Finnish researchers. For this study 13 usability statements collected clinician impressions of EMRs related to technical quality, ease of use, benefits, and collaboration. We report the responses from medical and nursing professionals working in clinical practice settings in Australia, including primary care and hospital sectors in 2020. Nursing and medical professionals have different experiences with EMR usability. This depends on the sector they work in and the usability feature measured. In our sample, technical quality features were more positively experienced by doctors in the primary care sector than nurses as well as ease of obtaining patient information and prevention of errors. In the hospital sector nurses experiences with EMRs were more positive with respect to support for routine task completion, learnability, ease of obtaining patient information and entry of patient data. The NuHISS is a suitable tool for measuring the usability experiences of Australian clinicians and the EMRs utilised. Differences in usability experiences were noted between professional groups and sectors. A focus on the usability perspectives of clinicians when enhancing or developing EMR solutions is advocated.


A huge pleomorphic adenoma of the submandibular salivary gland.
The most common tumour of salivary gland is pleomorphic adenoma (PA). They are benign, painless, can grow into big tumours but usually do not affect nerves or lymph nodes. PA most commonly occurs in the parotid gland but it may involve submandibular, lingual and minor salivary glands also. They can attain giant proportions and weigh several kilograms. We report a giant PA arising in the submandibular gland and treated by complete surgical excision without any complication. A female patient presented with a tumour in the submandibular region and front of neck with a history of more than 18 years. The weight of the resected mass was 4.35 kg. Patient's fear of surgery and lack of awareness were the main reasons for her long-standing swelling. Such giant PAs of the submandibular gland are very rare in medical literature.


Complete distal femoral metaphyseal fractures: a harbinger of child abuse before walking age.
Next only to burns and bruises, fractures are the second most common sign of the physical form of child abuse. Although there is not a pathognomonic fracture pattern associated with child abuse, distal femur "corner" fractures are often considered a clue to diagnosis, particularly in children younger than 1 year old. We contend that complete metaphyseal fractures of the distal femur are a potential harbinger of child abuse in children before walking age. This was a retrospective study performed at 2 level 1 pediatric trauma centers. Query of a trauma database in a 10-year period yielded 29 children that sustained complete metaphyseal fractures of the distal femur. Medical charts and radiographs were reviewed. Data collection included age, sex, side, mechanism of injury, associated injuries, child protective services evaluation, and primary pediatrician notes. Of the 29 fractures, 20 occurred in children 1 year old or younger (before walking age) and formed the final studied group. The average age for the 14 boys and 6 girls was 6 months 10 days (range, 5 days to 1 year). Ten cases (50%) were confirmed to be a result of child abuse, and another 5 cases (25%) were highly suspicious for abuse. In all, 15 of the 20 children (75%) with complete distal femoral metaphyseal fractures were potentially victims of child abuse. Based on our results, we recommend that when evaluating children before walking age with a complete distal femur metaphyseal fracture, further inquiry for possible etiology of child abuse should be performed. Level IV--case series, diagnostic.


A translocation-defective telomerase with low levels of activity and processivity stabilizes short telomeres and confers immortalization.
Short, repetitive, G-rich telomeric sequences are synthesized by telomerase, a ribonucleoprotein consisting of telomerase reverse transcriptase (TERT) and an integrally associated RNA. Human TERT (hTERT) can repetitively reverse transcribe its RNA template, acting processively to add multiple telomeric repeats onto the same substrate. We investigated whether certain threshold levels of telomerase activity and processivity are required to maintain telomere function and immortalize human cells with limited lifespan. We assessed hTERT variants with mutations in motifs implicated in processivity and interaction with DNA, namely the insertion in fingers domain (V791Y), and the E primer grip motif (W930F). hTERT-W930F and hTERT-V791Y reconstitute reduced levels of DNA synthesis and processivity compared with wild-type telomerase. Of interest, hTERT-W930F is more defective in translocation than hTERT-V791Y. Nonetheless, hTERT-W930F, but not hTERT-V791Y, immortalizes limited-lifespan human cells. Both hTERT-W930F- and hTERT-V791Y-expressing cells harbor short telomeres, measured as signal free ends (SFEs), yet SFEs persist only in hTERT-V791Y cells, which undergo apoptosis, likely as a consequence of a defect in recruitment of hTERT-V791Y to telomeres. Our study is the first to demonstrate that low levels of DNA synthesis--on the order of 20% of wild-type telomerase levels--and extension of as few as three telomeric repeats are sufficient to maintain functional telomeres and immortalize limited-lifespan human cells.


Adverse events of cryopreserved hematopoietic stem cell infusions in adults: a single-center observational study.
Autologous hematopoietic stem cell (HSC) transplantation has been used for almost three decades for the management of malignant hematologic diseases and some solid tumors. Dimethyl sulfoxide (DMSO) is used as a cryoprotective agent for hematopoietic progenitor cells (HPCs) collected by apheresis (HPC-A). We evaluated the factors contributing to the occurrence of adverse events (AEs) of cryopreserved HPC-A infusion. Between January 2009 and June 2014, a total of 1269 (1191 patients) consecutive HPC-A infusions were given to adult patients undergoing autologous HSC transplantation at Barnes-Jewish Hospital. Only infusions on the first day of transplant were included in the analysis. AEs were reported in 480 (37.8%) infusions. The most common AEs were facial flushing in 189 (39.4%) infusions, nausea and/or vomiting in 183 (38.1%) infusions, hypoxia requiring oxygen in 139 (29%) infusions, and chest tightness in 80 (16.7%) infusions. Multivariate analysis using logistic regression showed that female sex (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.26; p < 0.0001), diagnosis other than multiple myeloma (OR, 1.44; 95% CI, 1.12-1.84; p = 0.004), larger volume of infusion per body weight (OR, 1.66; 95% CI, 1.29-2.15; p < 0.0001), and number of granulocytes infused per body weight (OR, 1.30; 95% CI, 1.01-1.67; p = 0.042) were significant predictors of occurrence of AEs during infusion. AEs due to HPC-A infusion occurred in more than one-third of patients. Interventions need to be instituted to reduce AEs and thus improve the safety of HPC-A infusion. Many of these toxicities can be attributed to DMSO, and this is reflected in the volume of infusion. It might be warranted to consider implementing DMSO-reducing protocols before infusion.