Interactions of syndecan-1 and heparin with human collagens.
Glycosaminoglycan (GAG)-collagen interactions play important roles in cell adhesion and extracellular matrix assembly; however, the chemical bases for these interactions are not fully understood. We have used affinity co-electrophoresis (ACE) (Lee, M.K. and Lander, A.D., Proc. Natl. Acad. Sci, USA, 88, 2768-2772, 1991) to study the binding of the heparan sulphate proteoglycan syndecan-1 and heparin to human collagens. [35S]Syndecan-1 [from normal murine mammary gland (NMuMG) epithelial cells] and low-M(r) (approximately 6 kDa) [125I]heparin were subjected to electrophoresis through agarose gel lanes containing human collagens at various concentrations, and binding affinities were measured from shifts in migration of the labelled materials. Results demonstrate that the affinities of each collagen for syndecan-1 and low-M(r) heparin were similar, and followed the order: type V >> type IV approximately type III approximately type I > type VI >> type II, and ranged in Kd from approximately 10(-8) to approximately 3 x 10(-6) M. These data suggest that syndecan-1 and heparin may contain similar collagen-binding determinants. It was also found that the same heparin subpopulation was selectively bound with high affinity by each of the collagens. The published amino acid sequences of the six collagens were examined for what are thought to be heparin-binding consensus sequences (Cardin, A.D. and Weintraub, H.J.R., Arteriosclerosis, 9, 21-32, 1989). The presence of such sequences did not correlate with affinity for heparin or syndecan-1, and collagens I, II and III lacked such sequences entirely. The data suggest that collagens may use novel types of binding sites to interact with GAGs.


Atmospheric Chemistry of 2-Amino-2-methyl-1-propanol: A Theoretical and Experimental Study of the OH-Initiated Degradation under Simulated Atmospheric Conditions.
The OH-initiated degradation of 2-amino-2-methyl-1-propanol [CH3C(NH2)(CH3)CH2OH, AMP] was investigated in a large atmospheric simulation chamber, employing time-resolved online high-resolution proton-transfer reaction-time-of-flight mass spectrometry (PTR-ToF-MS) and chemical analysis of aerosol online PTR-ToF-MS (CHARON-PTR-ToF-MS) instrumentation, and by theoretical calculations based on M06-2X/aug-cc-pVTZ quantum chemistry results and master equation modeling of the pivotal reaction steps. The quantum chemistry calculations reproduce the experimental rate coefficient of the AMP + OH reaction, aligning k(T) = 5.2 × 10-12 × exp (505/T) cm3 molecule-1 s-1 to the experimental value kexp,300K = 2.8 × 10-11 cm3 molecule-1 s-1. The theoretical calculations predict that the AMP + OH reaction proceeds via hydrogen abstraction from the -CH3 groups (5-10%), -CH2- group, (>70%) and -NH2 group (5-20%), whereas hydrogen abstraction from the -OH group can be disregarded under atmospheric conditions. A detailed mechanism for atmospheric AMP degradation was obtained as part of the theoretical study. The photo-oxidation experiments show 2-amino-2-methylpropanal [CH3C(NH2)(CH3)CHO] as the major gas-phase product and propan-2-imine [(CH3)2C═NH], 2-iminopropanol [(CH3)(CH2OH)C═NH], acetamide [CH3C(O)NH2], formaldehyde (CH2O), and nitramine 2-methyl-2-(nitroamino)-1-propanol [AMPNO2, CH3C(CH3)(NHNO2)CH2OH] as minor primary products; there is no experimental evidence of nitrosamine formation. The branching in the initial H abstraction by OH radicals was derived in analyses of the temporal gas-phase product profiles to be BCH3/BCH2/BNH2 = 6:70:24. Secondary photo-oxidation products and products resulting from particle and surface processing of the primary gas-phase products were also observed and quantified. All the photo-oxidation experiments were accompanied by extensive particle formation that was initiated by the reaction of AMP with nitric acid and that mainly consisted of this salt. Minor amounts of the gas-phase photo-oxidation products, including AMPNO2, were detected in the particles by CHARON-PTR-ToF-MS and GC×GC-NCD. Volatility measurements of laboratory-generated AMP nitrate nanoparticles gave ΔvapH = 80 ± 16 kJ mol-1 and an estimated vapor pressure of (1.3 ± 0.3) × 10-5 Pa at 298 K. The atmospheric chemistry of AMP is evaluated and a validated chemistry model for implementation in dispersion models is presented.


[Hazards of electrosurgery].
Burn accidents due to the use of electrosurgical instruments (electrotomy, electrocoagulation) are uncommon but generally serious: explosion of inflammable anaesthetics or antiseptics, local tissue necrosis by an uncontrollable current or coagulation necrosis by a high current. An appropriate use of electrosurgical instruments based on the correct range of indications is the basis for the prevention of accidents.


A novel integrated multifunction micro-sensor for three-dimensional micro-force measurements.
An integrated multifunction micro-sensor for three-dimensional micro-force precision measurement under different pressure and temperature conditions is introduced in this paper. The integrated sensor consists of three kinds of sensors: a three-dimensional micro-force sensor, an absolute pressure sensor and a temperature sensor. The integrated multifunction micro-sensor is fabricated on silicon wafers by micromachining technology. Different doping doses of boron ion, placement and structure of resistors are tested for the force sensor, pressure sensor and temperature sensor to minimize the cross interference and optimize the properties. A glass optical fiber, with a ladder structure and sharp tip etched by buffer oxide etch solution, is glued on the micro-force sensor chip as the tactile probe. Experimental results show that the minimum force that can be detected by the force sensor is 300 nN; the lateral sensitivity of the force sensor is 0.4582 mV/μN; the probe length is linearly proportional to sensitivity of the micro-force sensor in lateral; the sensitivity of the pressure sensor is 0.11 mv/KPa; the sensitivity of the temperature sensor is 5.836 × 10(-3) KΩ/°C. Thus it is a cost-effective method to fabricate integrated multifunction micro-sensors with different measurement ranges that could be used in many fields.


The osteogenic potential of pseudoarthrosis tissue and bone from human scaphoid non-unions.
Scaphoid fractures have the highest prevalence of non-union in the human body, but little is known about the osteogenic potential of cells at the pseudoarthrosis. It was our goal to determine whether cells isolated from non-unions could be stimulated to differentiate into osteoblasts and produce bone in vitro. Fifteen human scaphoid non-unions were excised during surgery and bone from either side of the non-union and the fibrocartilagenous central regions were harvested. Osteoblastic populations were subcultured from these. The number of bone nodules (colonies of osteoblast cells that produced bone) from all three regions was similar to the number of nodules derived from iliac bone cultures from the same patients. Treatment of cells with rhBMP-2 resulted in a 3- to 10-fold increase in bone nodule formation in vitro from cells derived from the non-unions. These data demonstrate that cells at the pseudoarthrosis have osteogenic capability and can be stimulated by rhBMP-2, possibly increasing the ability to heal.


A decreased serum omentin-1 level may be an independent risk factor for peripheral arterial disease.
Recent evidence suggests that omentin-1, a visceral adipose-derived cytokine, may play a role in atherosclerosis The aim of this study was to evaluate whether serum omentin-1 levels are associated with peripheral artery disease (PAD) and its severity. The present study was cross-sectional and observational. We enrolled 123 patients with PAD and 50 age-matched subjects without PAD. The cardiovascular risk factors, ankle-brachial index (ABI), and serum omentin-1 levels were assessed in all participants Patients with PAD had significantly lower omentin-1 levels than those without PAD (206. ±48.4 vs. 345. ±80 ng/mL, respectively; 0.001). A correlation analysis revealed positive correlations between the omentin-1 level and the ABI ( 0.52, P=0.008). After adjusting for cardiovascular risk factors, a decreased omentin-1 level was found to be an independent predictor of both PAD and its severity as measured by ABI in multivariate logistic regression analysis. The current study suggests a strong association between decreased serum omentin-1 levels and PAD and its severity. Thus, omentin-1 may be a novel biomarker for PAD.


Effects of neuromuscular electrical stimulation on exercise capacity and quality of life in COPD patients: a systematic review and meta-analysis.
Neuromuscular electrical stimulation (NMES) has been shown to produce benefits in the muscle function of chronic obstructive pulmonary disease (COPD) patients. The definite effectiveness of NMES, applied in isolation or concurrently with conventional pulmonary rehabilitation (PR) or exercise training, remains unclear. This review was to determine the effects of NMES on exercise capacity, functional performance, symptoms, and health-related quality of life (HRQoL) in COPD patients. Electronic databases (PubMed, Embase, Web of Science, the Cochrane Library) were searched for relevant randomized controlled trials (RCTs). Two investigators independently screened the eligible studies up to February 2020 that used NMES as the intervention group. The outcome measures were 6-min walking distance (6MWD), peak rate of oxygen uptake (VO2 peak), St George's Respiratory Questionnaire (SGRQ), and symptoms of dyspnoea and fatigue. Data were extracted using a predefined table and papers were appraised using Downs and Black tool. We analyzed 13 RCTs with 447 COPD patients. In the analysis of 6MWD, pooled estimates showed a significant increase in the NMES group, compared with the control group (mean difference (MD) = 27.05, 95% confidence interval (CI): 8.46-45.63, P<0.001). There were also improvements in symptoms of dyspnea or leg fatigue, and reduction in London Chest Activity of Daily Living (LCADL) scores. No statistically significant difference was observed in VO2 peak, peak power, and SGRQ. NMES could improve exercise capacity and reduce perceived sensation of dyspnea during exercise in patients with COPD, but not to be recommended as an effective alternative training modality in the rehabilitation of stable COPD patients.


Glomerular lesions in experimental infections of Schistosoma mansoni in Cebus apella monkeys.
Three monkeys (Cebus apella) experimentally infected with Schistosoma mansoni studied for periods of 19, 14, and 11 months showed deposits containing gamma-globulin in subendothelial and subepithelial basal membranes and in basement membranes proper. The glomeruli showed mild reactivity characterized by local hypertrophy and hyperplasia of mesangial cells. Such findings were close to those observed by us in the kidney of hepatosplenic schistosomiasis patients without evidence of renal disease. The distribution of the deposits, both in human and experimental disease, are suggestive of preformed, non-glomerular antigen-antibody complexes that form in a zone of excess antigen and become trapped in the glomerular capillaries.The possibility exists, but has not yet been proved beyond doubt, that renal disease in schistosomiasis patients could be the end result of this pathogenetic mechanism.


Accuracy of MR angiography compared with radionuclide scanning in identifying the cause of pulmonary arterial hypertension.
MR imaging has proven accurate in identifying patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, we know of no attempt to distinguish patients with CTEPH from patients with other causes of pulmonary arterial hypertension (PAH). Primary pulmonary hypertension (PPH) is the disease most frequently confused with CTEPH. We examined patients with CTEPH or PPH and control subjects to identify MR imaging features that might distinguish CTEPH from PPH, to compare the accuracy of MR angiography (MRA) with that of radionuclide scanning, and to determine the cardiac and pulmonary vascular measurements in these groups. T1-weighted and two-dimensional multiplanar spoiled gradient-recalled scans were obtained in 30 patients with CTEPH who had undergone conventional pulmonary angiography, 10 patients with PPH, and 13 control subjects with no known vascular disease. Ventilation-perfusion scans were available in all patients with CTEPH and in six of the 10 patients with PPH. The MR scans were assessed independently by two radiologists who evaluated the appearance of segmental vessels and noted the presence of mosaic perfusion. Cardiac chambers and pulmonary vessels were measured on T1-weighted spin-echo scans. The two radiologists used MR angiograms to reliably distinguish between patients with CTEPH and those with PPH. The accuracy of MR angiograms matched that of ventilation-perfusion scans (92%). On T1-weighted scans, the two radiologists used cardiac and pulmonary vascular measurements to distinguish patients with PAH from control subjects but failed to distinguish between patients with CTEPH and those with PPH. MRA is useful in distinguishing patients with CTEPH from those with PPH. In this population, MRA had an accuracy that was identical to that of radionuclide scanning. Vascular and cardiac measurements made on MR scans reliably identified patients with PAH but did not distinguish between patients with CTEPH and those with PPH.


A case of alternating bundle branch block in combination with intra-Hisian block.
We describe a 66-year-old woman who had an alternating bundle branch block consisting of coexisting occurrence of right bundle branch block (RBBB) and left bundle branch block (LBBB) combined with Mobitz type II atrioventricular block (AVB). A prolonged PQ interval was associated with the RBBB pattern whereas it was not apparent in the LBBB pattern. Electrophysiologic study revealed that the LBBB pattern was combined with a double His bundle potential. On the other hand, the RBBB pattern was combined with a markedly prolonged HV interval with a low voltage monophasic His bundle potential, which we speculated was the former part of the split His bundle potential seen during the LBBB pattern. A combination of the longitudinal dissociation in the His bundle and the gap phenomenon at the intra-Hisian block portion may account for this observation.


Trauma injury in adult underweight patients: A cross-sectional study based on the trauma registry system of a level I trauma center.
The aim of this study was to investigate and compare the injury characteristics, severity, and outcome between underweight and normal-weight patients hospitalized for the treatment of all kinds of trauma injury.This study was based on a level I trauma center Taiwan.The detailed data of 640 underweight adult trauma patients with a body mass index (BMI) of <18.5 kg/m and 6497 normal-weight adult patients (25 > BMI ≥ 18.5 kg/m) were retrieved from the Trauma Registry System between January 1, 2009, and December 31, 2014. Pearson's chi-square test, Fisher's exact test, and independent Student's t-test were performed to compare the differences. Propensity score matching with logistic regression was used to evaluate the effect of underweight on mortality.Underweight patients presented a different bodily injury pattern and a significantly higher rate of admittance to the intensive care unit (ICU) than did normal-weight patients; however, no significant differences in the Glasgow Coma Scale (GCS) score, injury severity score (ISS), in-hospital mortality, and hospital length of stay were found between the two groups. However, further analysis of the patients stratified by two major injury mechanisms (motorcycle accident and fall injury) revealed that underweight patients had significantly lower GCS scores (13.8 ± 3.0 vs 14.5 ± 2.0, P = 0.020), but higher ISS (10.1 ± 6.9 vs 8.4 ± 5.9, P = 0.005), in-hospital mortality (odds ratio, 4.4; 95% confidence interval, 1.69-11.35; P = 0.006), and ICU admittance rate (24.1% vs 14.3%, P = 0.007) than normal-weight patients in the fall accident group, but not in the motorcycle accident group. However, after propensity score matching, logistic regression analysis of well-matched pairs of patients with either all trauma, motorcycle accident, or fall injury did not show a significant influence of underweight on mortality.Exploratory data analysis revealed that underweight patients presented a different bodily injury pattern from that of normal-weight patients, specifically a higher incidence of pneumothorax in those with penetrating injuries and of femoral fracture in those with struck on/against injuries; however, the injury severity and outcome of underweight patients varied depending on the injury mechanism.


Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery.
Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed. Several wild-type and genetically engineered vaccinia virus (VACV) strains have been tested in both preclinical and clinical trials with promising results. Greater understanding and advancements in molecular biology have enabled the generation of genetically engineered oncolytic viruses for safer and more efficacious treatment, including arming VACVs with cytokines and immunostimulatory molecules, anti-angiogenic agents, and enzyme prodrug therapy, in addition to combining VACVs with conventional external and systemic radiotherapy, chemotherapy, immunotherapy, and other virus strains. Furthermore, novel oncolytic vaccinia virus strains have been generated that express reporter genes for the tracking and imaging of viral therapy and monitoring of therapeutic response. Further study is needed to unlock VACVs' full potential as part of the future of cancer therapy.


Innate anti-viral immunity is associated with the protection elicited by the simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus monkeys.
The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status. Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production. Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain. Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.


Inelastic tunneling spectroscopy using scanning tunneling microscopy on trans-2-butene molecule: spectroscopy and mapping of vibrational feature.
Inelastic tunneling spectroscopy (IETS) measurement using scanning tunneling microscopy (STM) with a commercially available STM set up is presented. The STM-IETS spectrum measured on an isolated trans-2-butene molecule on the Pd(110) shows a clear vibrational feature in d2I/dV2 at the bias voltage of 360 mV and -363 mV, which corresponds to the nu(C-H) mode (d2I/dV2 approximately 10 nA/V2). In addition, we have obtained an image by mapping the vibrational feature of nu(C-H) in d2I/dV2. The image is obtained by scanning the tip on the surface with the feedback loop activated while the modulation voltage is superimposed on the sample voltage. With the method that is readily performable with conventional software, we have clearly differentiated the molecules of trans-2-butene and butadiene through the mapping of the vibrational feature, demonstrating its capability of chemical identification in atomic scale.


Anemia in patients with neoplastic diseases.
A specific and characteristic type of anemia is not a feature of all malignant disease. To the contrary, the nature of the anemia will depend upon the causative mechanism, of which blood loss and accelerated erythrocyte removal appear to be the most frequently seen and the most clearly defined. Recognition of anemia due to loss of blood is relatively simple if the subtlety of blood loss in the stool is borne in mind and persistent testing to demonstrate it is carried out. Indeed, anemia characterized by chronic loss of blood in men can only mean chronic gastrointestinal bleeding if certain rare hemoglobin abnormalities can be ruled out. Anemia due to accelerated erythrocyte removal may also be recognized by simple measures. After transfusions raise hemoglobin values to near normal levels, the disappearance of the transfused blood and the rapid return of the pretransfusion severity of anemia are good evidence of the presence of such a mechanism, if blood loss can be ruled out.Adequate management of the anemia of malignant disease depends upon a clear understanding of the various mechanisms involved. It is highly probable that attention to this feature will, in many instances, significantly prolong the productive life of persons with malignant disease.


Application of LogitBoost Classifier for Traceability Using SNP Chip Data.
Consumer attention to food safety has increased rapidly due to animal-related diseases; therefore, it is important to identify their places of origin (POO) for safety purposes. However, only a few studies have addressed this issue and focused on machine learning-based approaches. In the present study, classification analyses were performed using a customized SNP chip for POO prediction. To accomplish this, 4,122 pigs originating from 104 farms were genotyped using the SNP chip. Several factors were considered to establish the best prediction model based on these data. We also assessed the applicability of the suggested model using a kinship coefficient-filtering approach. Our results showed that the LogitBoost-based prediction model outperformed other classifiers in terms of classification performance under most conditions. Specifically, a greater level of accuracy was observed when a higher kinship-based cutoff was employed. These results demonstrated the applicability of a machine learning-based approach using SNP chip data for practical traceability.


[Depressive symptoms and the Idiopathic Parkinson's Syndrome (IPS): a review].
The prevalence of the Ideopathic Parkinson's Syndrome sums up to 2% and ranks second in the list of neurodegenerative diseases. Beside psychotic, cognitive and behavioural symptoms that go along with the IPS, the authors focus on epidemiology, pathogenesis as well as diagnosis and therapy of depressive symptoms seen in the context of IPS. Metaanalytic data on the prevalence of depressive symptoms sum up to 31%. As depression in IPS relies on a complex interaction of psychological and biological causes the clinical picture is difficult to assess because symptomatology differs from classical depression. Dopamine agonists as well as antidepressants present the mainstay in biological therapeutic interventions. A therapeutic algorithm based on theoretical considerations is presented.


Conical intersection control of heterocyclic photochemical bond scission.
The photochemistry of the heterocycle 5,6-dihydro-1-methyl-5,5-diphenylpyridin-2(1H)-one (compound 1 in the text) leads to two competitive reactions (the reactions are depicted in the Introduction to the article). These arise from fission of bond a, between the nitrogen (N-6) and C-1, and bond b, between C-4, with the two phenyl substituents, and C-5, adjacent to the nitrogen. Scission of bond a alone leads to a zwitterionic intermediate which can be trapped by nucleophiles, while cleavage of bonds a and b together affords two fragments--a ketene and an imine. The ketene could be intercepted with nucleophiles and the imine trimerized. Computation reveals little weakening of bonds a and b. But as stretching begins, conical intersections are encountered, leading to ground-state products.


Enhanced self-mixing interferometry based on volume Bragg gratings and laser diodes emitting at 405-nm wavelengths.
Self-mixing interferometry (SMI) represents a robust, self-aligned technique for metrology applications. Recently, it has been shown that the detection of the frequency-modulated (FM) signal enhances the conventional SMI signal based on the amplitude modulation. Here, an all-optical, simple and effective alternative approach to detect the FM self-mixing signal is presented. We demonstrate the enhanced self-mixing approach using a laser diode emitting at 405 nm and a volume Bragg grating (VBG) to map frequency to intensity modulations for further optical detection. Our approach overcomes the spectral range limitation of the edge filtering approach based on molecular absorption filters, since the VBGs can be fabricated at any spectral range.


Functionalized nanoparticles: Tailoring properties through surface energetics and coordination chemistry for advanced biomedical applications.
Significant advances in nanoparticle-related research have been made in the past decade, and amelioration of properties is considered of utmost importance for improving nanoparticle bioavailability, specificity, and catalytic performance. Nanoparticle properties can be tuned through in-synthesis and post-synthesis functionalization operations, with thermodynamic and kinetic parameters playing a crucial role. In spite of robust functionalization techniques based on surface chemistry, scalable technologies have not been explored well. The coordination enhancement via surface functionalization through organic/inorganic/biomolecules material has attracted much attention with morphology modification and shape tuning, which are indispensable aspects in the colloidal phase during biomedical applications. It is envisioned that surface amelioration influences the anchoring properties of nano interfaces for the immobilization of functional groups and biomolecules. In this work, various nanostructure and anchoring methodologies have been discussed, aiming to exploit their full potential in precision engineering applications. Simultaneous discussions on emerging characterization strategies for functionalized assemblies have been made to gain insights into functionalization chemistry. An overview of current advances and prospects of functionalized nanoparticles has been presented, with an emphasis on controllable attributes such as size, shape, morphology, functionality, surface features, Debye and Casimir interactions.


Biomimetic tumor microenvironment on a microfluidic platform.
Tumor microenvironment is a highly complex system consisting of non-cancerous cells, soluble factors, signaling molecules, extracellular matrix, and mechanical cues, which provides tumor cells with integrated biochemical and biophysical cues. It has been recognized as a significant regulator in cancer initiation, progression, metastasis, and drug resistance, which is becoming a crucial component of cancer biology. Modeling microenvironmental conditions of such complexity in vitro are particularly difficult and technically challenging. Significant advances in microfluidic technologies have offered an unprecedented opportunity to closely mimic the physiological microenvironment that is normally encountered by cancer cells in vivo. This review highlights the recent advances of microfluidic platform in recapitulating many aspects of tumor microenvironment from biochemical and biophysical regulations. The major events relevant in tumorigenesis, angiogenesis, and spread of cancer cells dependent on specific combinations of cell types and soluble factors present in microenvironmental niche are summarized. The questions and challenges that lie ahead if this field is expected to transform the future cancer research are addressed as well.


The Effect of Intravenous Ketamine in Suicidal Ideation of Emergency Department Patients.
Suicidal ideation is an emergent problem in the Emergency Department (ED) that often complicates patient disposition and discharge. It has been shown that ketamine possesses fast acting antidepressant and anti-suicidal effects. This study was conducted to examine the effects of a single intravenous bolus of ketamine on patients with suicidal ideations in ED. Forty-nine subjects with suicidal ideations with or without an unsuccessful suicide attempt, received 0.2 mg/kg of ketamine. Scale for suicidal ideation (SSI) and Montgomery-Abserg depression-rating scale (MADRS) were evaluated before and 40, 80 and 120 minutes after drug intervention. The results were compared using the paired t-test and patients were followed up 10 days after ED admission for remnant suicide ideation. SSI (df: 3, 46; F=80.7; p<0.001) and MADRS (df: 3, 46; F=87.2; p<0.001) scores significantly dropped after ketamine injection; the SSI score before and after 20, 40, and 80 minutes of ketamine injection were 23.0±6.7, 16.2±5.2, 14.3±4.3, and 13.6±4.0 respectively. The MADRS scores were 38.2±9.3, 25.6±7.1, 22.7±6.3, and 22.1±5.95 at the same time intervals. 25.5% of patients were hospitalized, 63.3% received medications and 12.2% discharged. 6.2% of patients had suicidal ideations ten days after ED disposition. It seems that Ketamine could not be a good choice for fast reduction of suicidal ideations in ED patients. Further studies are needed to determine the optimal dose of ketamine for different patients.


Addressing Chemophobia: Informational versus affect-based approaches.
This study investigated the effect of two communication strategies (informational and affect-based) in reducing chemophobia, the irrational fear of chemicals. In an online experiment, participants (N = 448) were randomly assigned to one of three groups ("control", "knowledge", or "affect" group). The following dependent variables were assessed: chemophobia, knowledge of basic toxicological principles, affect towards chemicals, benefit perception of the use of chemicals, and preference for natural substitutes in consumer products. The results showed that only the informational approach, which conveys knowledge of basic toxicological principles, significantly decreased chemophobia and the preference for natural substitutes in consumer products. The affect-based approach significantly increased positive affect towards chemicals and the benefit perception of their use, but did not decrease chemophobia. This suggested that the provision of relevant information about basic toxicological principles is a more effective strategy than merely addressing laypeople's affect towards chemicals to reduce chemophobia. Relevant knowledge could be taught in schools or disseminated by toxicologists and scientists who are trusted by the public.


Ligand binding and self-association cooperativity of β-lactoglobulin.
Unlike most small globular proteins, lipocalins lack a compact hydrophobic core. Instead, they present a large central cavity that functions as the primary binding site for hydrophobic molecules. Not surprisingly, these proteins typically exhibit complex structural dynamics in solution, which is intricately modified by intermolecular recognition events. Although many lipocalins are monomeric, an increasing number of them have been proven to form oligomers. The coupling effects between self-association and ligand binding in these proteins are largely unknown. To address this issue, we have calorimetrically characterized the recognition of dodecyl sulfate by bovine β-lactoglobulin, which forms weak homodimers at neutral pH. A thermodynamic analysis based on coupled-equilibria revealed that dimerization exerts disparate effects on the ligand-binding capacity of β-lactoglobulin. Protein dimerization decreases ligand affinity (or, reciprocally, ligand binding promotes dimer dissociation). The two subunits in the dimer exhibit a positive, entropically driven cooperativity. To investigate the structural determinants of the interaction, the crystal structure of β-lactoglobulin bound to dodecyl sulfate was solved at 1.64 Å resolution.


The response of human neutrophils to a chemotactic tripeptide (N-formyl-methionyl-leucyl-phenylalanine) studied by microcinematography.
A quantitative microcinematographic technique for the measurement of cellular motion in response to chemical influences is described. The data are analyzed by using a magnetic digitizer connected to a computer, permitting comparison of several characteristics of such motion. When human granulocytes are placed in a gradient of formyl-methionyl-leucyl-phenylalanine (fMLP) (concentration 10(-6)-10(-8) mol/L) against buffer, the motion of the cells is increased in velocity (chemokinesis) and is directed toward the chemoattractant, as measured by the orientation of the vector of motion. This directionality is confirmed by positive values for the McCutcheon index and analysis of directed linear displacement. Concentrations of fMLP below 10(-9) mol/L did not result in chemokinesis or chemotaxis, presumably due to insufficient stimulus. Concentrations of 10(-6) mol/L fMLP and greater resulted in marked stimulation of the cell surface but reduced directionality and velocity of motion compared with cells in a more optimal gradient. Motion of the unstimulated cells tended to be ortholinear , and this was not increased by the presence of a gradient of fMLP. Hence, as previously shown, the Random Walk analysis, which does not give weight to the direction of motion, is not useful in the analysis of the response of these cells to a chemotaxin in this system.


Pulmonary involvement in mixed connective tissue disease: comparison with other collagen vascular diseases using high resolution CT.
The purpose of this work was to compare the CT findings of lung involvement in patients with mixed connective tissue disease (MCTD) with those in patients with other CTDs: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM). CT scans of 35 patients with interstitial lung disease and associated MCTD were evaluated retrospectively. The CT assessment included determination of the findings and evaluation of whether the findings in MCTD were different from those in other CTDs. The frequency of ground-glass opacity in MCTD was significantly lower than in CTDs (p < 0.05). The frequency of honeycombing in MCTD was lower than in SSc (p < 0.05) and higher than in PM-DM (p < 0.005). Regarding the predominant CT patterns, the frequency of septal thickening in MCTD was significantly higher than in CTDs (p < 0.05). CT findings in MCTD were a combination of those in other CTDs.


Verbal intercourse and sexual communication: impediments to STD prevention.
This article explores the problems of risky sexual behavior by examining the ways people verbally negotiate sexual interaction regarding sexually transmitted diseases. Based on in-depth interviews with 124 adults (ages 21-63) who are infected with genital herpes, the article shows that knowledge about sexually transmitted diseases is not necessarily related to the action needed for their prevention. People are more afraid of being rejected by a partner than they are of contracting an STD (except, of course, AIDS). By examining difficulties people have with sexual health discourse and showing how these difficulties are related to both the problem of communicating politeness and the problem of representing the self and the sexual other, this article demonstrates that STD prevention programs overlook a very important emotional and communicative issue: the lack of a culturally sanctioned language with which to discuss sexual health with partners.


Magnetic properties of Fe(x)Pt(y)Au(100-x-y) nanoparticles.
Fe(x)Pt(y)Au(100-x-y) nanoparticles of size 3.5 nm were prepared by polyol reduction of platinum acetylacetonate and gold acetate and the thermal decomposition of iron pentacarbonyl. The as-synthesized nanoparticles with disordered fcc structure were then heat treated to transform to the L1(0) structure with high magnetocrystalline anisotropy. By tuning the stoichiometry of the Fe(x)Pt(y)Au(100-x-y) nanoparticles, the phase transition temperature was reduced by more than 200 degrees C. After the annealing 500 degrees C, for instance, the highest coercivity of 18 kOe was obtained from the Fe51Pt36Au13 nanoparticles which is substantially higher compared to 2 kOe for Fe51Pt49 nanoparticles annealed at the same temperature. In addition to the high coercivity, the saturation magnetization value obtained from Fe51Pt36Au13 nanoparticles was 47 emu/g which is similar to that for the Fe51Pt49 nanoparticles, indicating that there is no trade-off between the coercivity and the saturation magnetization upon Au doping.


On the core bacterial flora of Ixodes persulcatus (Taiga tick).
Ixodes persulcatus is a predominant hard tick species that transmits a wide range of human and animal pathogens. Since bacterial flora of the tick dwelling in the wild always vary according to their hosts and the environment, it is highly desirable that species-associated microbiomes are fully determined by using next-generation sequencing and based on comparative metagenomics. Here, we examine such metagenomic changes of I. persulcatus starting with samples collected from the wild ticks and followed by the reared animals under pathogen-free laboratory conditions over multiple generations. Based on high-coverage genomic sequences from three experimental groups-wild, reared for a single generation or R1, and reared for eight generations or R8 -we identify the core bacterial flora of I. persulcatus, which contains 70 species that belong to 69 genera of 8 phyla; such a core is from the R8 group, which is reduced from 4625 species belonging to 1153 genera of 29 phyla in the wild group. Our study provides a novel example of tick core bacterial flora acquired based on wild-to-reared comparison, which paves a way for future research on tick metagenomics and tick-borne disease pandemics.


Flow Boiling Enhancement Using Three-Dimensional Contact-Line Pinning on Hierarchical Superbiphilic Micro/Nanostructures.
Flow boiling is a promising method for the cooling of sensitive computational and industrial components, facilitating the transportation of large quantities of heat at near-constant temperature and in a small form factor. The prevention of vapor film formation is a fundamental challenge for the enhancement of boiling systems, and an impetus therefore exists for the discovery of new techniques to segregate nucleating bubbles during their formation. Herein, we utilize the strong capillary forces generated by nanostructures to pin the liquid/vapor interface in three dimensions and thereby control the coalescence and flow interactions of developing bubbles. We demonstrate this principle on both symmetrical and asymmetrical superbiphilic microstructures, showing enhancement of peak heat transfer coefficient by 81% and 113%, respectively, when compared to the best superhydrophilic and superhydrophobic analogues. Our approach shows a potential future direction for engineered boiling micro/nanostructures, wherein bubble dynamics are directly manipulated on bespoke, three-dimensional substrates.


Effects of claudin-1 downregulation on the physiological processes of gallbladder cancer SGC996 cells.
Gallbladder cancer has a high recurrence and mortality rate, with limited treatment options. Therefore, elucidating the underlying molecular mechanisms of this disease would be beneficial to achieve an earlier diagnosis and potentially identify novel treatment targets. Claudin-1 is a tight junction protein associated with the development and prognosis of several types of cancer, and our preliminary studies have demonstrated that claudin-1 expression is elevated in gallbladder cancer tissues. Therefore, the aim of the present study was to investigate the effects of downregulating claudin-1 on the physiological processes of gallbladder cancer cells. The gallbladder cancer SGC996 cell line was transfected with claudin-1-RNA interference lentivirus (LV-CLDN1-RNAi) to downregulate claudin-1 expression, and the downstream effects on cell proliferation, the cell cycle, apoptosis and cell invasion were investigated. Following transfection with LV-CLDN1-RNAi, the results of an MTT assay revealed that downregulating claudin-1 did not affect the proliferation of the SGC996 cells. However, flow cytometry analysis demonstrated that the number of cells arrested in the G1 phase increased significantly, whereas the amount of cells arrested in the S phase was significantly reduced. Annexin V-APC single-color staining demonstrated that downregulating claudin-1 expression increased the ratio of cell apoptosis, which was confirmed by the results of western blot analysis, in which levels of the pro-apoptotic B-cell lymphoma 2 (Bcl-2)-associated X protein and anti-apoptotic Bcl-2 protein were increased and decreased, respectively. Finally, a Transwell assay indicated that claudin-1 downregulation inhibited cell invasion. Overall, the results from the present study indicated that downregulating claudin-1 expression promoted the apoptosis of gallbladder cancer cells and inhibited cell invasion, indicating that claudin-1 may be involved in the recurrence and metastasis of gallbladder cancer. These insights provide theoretical and experimental foundations for considering claudin-1 as a novel target for the treatment of gallbladder cancer.


Knowledge, Attitude and Use of Evidence-Based Practice among nurses active on the Internet.
to determine the evidence-based practice (EBP) competence of Spanish and Latin-American nurses participating in professional forums on the Internet and estimate the influence of socio-demographic and professional factors on their competence, which was defined as knowledge of, attitude towards, and implementation of EBP. An online survey was administered to a convenience sample of nurses active in Internet forums, comprising validated Spanish versions of the Evidence-Based Practice Questionnaire (EBPQ) and Practice Environment Scale of the Nursing Work Index (PES-NWI) and socio-demographics and professional variables. 314 questionnaires were obtained (76.96%). The mean EBPQ score was 5.02 out of 7 (95%CI, 4.89-5.14). The variables associated with a higher competence in EBP were academic level, (p<03001), professional category (p=0.001), country of work (p<0.001), perception of practice environment (p=0,018) and research activities (p<0,036). These nurses showed a moderate level of EBP competence. They revealed a positive attitude towards EBP and achieved intermediate scores in both EBP-related skills and knowledge and their implementation. Higher academic levels and professional categories were associated with greater EBP competence. A practice environment perceived to be unfavorable has a negative influence on EBP implementation.


Lymphoplasmacytic lymphoma isolated to an extraocular muscle.
A 44-year-old woman presented with a 1-month history of right-sided tearing, redness, and chronic headache. Clinical examination was notable for 4-mm proptosis and decreased visual acuity OD. Orbital CT demonstrated isolated enlargement of the right lateral rectus. Surgical biopsy was undertaken after an unsuccessful trial of oral steroids. Histopathology and immunophenotyping demonstrated a lymphoplasmacytic lymphoma. External beam radiation induced regression of the lymphoma with decreased proptosis and improved visual acuity.


Evaluation of the facial artery on computed tomographic angiography using 64-slice multidetector computed tomography: implications for facial reconstruction in plastic surgery.
Preoperative knowledge of a patient's individual variations in facial artery anatomy would benefit plastic surgeons for reconstructive planning. The authors evaluated the feasibility of multislice computed tomographic angiography in vascular mapping of the facial artery. In total, 187 facial arteries in 94 patients without facial tumor or vascular disease were studied. Anatomical variations of the facial artery were classified into four types: type 1, a short course that terminates proximal to the superior labial artery; type 2, an intermediate course that terminates distal to the superior labial artery near the nasolabial fold; type 3, a classic course that extends to the lateral nasal ala beyond the nasolabial fold with an angular branch; and type 4, duplex with dominant lateral angular branch. Facial artery patterns were compared with dominant patterns of the facial-submental artery bifurcation. The extent of the inferior and superior labial artery was evaluated separately. Sixty-four facial artery branches (34 percent) were classified as type 1, 74 (40 percent) as type 2, and 45 (24 percent) as type 3. Type 4 was seen in only four branches (2 percent). The facial artery was dominant in the facial-submental artery bifurcation in 84 percent of type 3 facial arteries. Three-dimensional volume-rendered images allow detailed visualization of the facial artery and its branches and help preoperative mapping. Facial computed tomographic angiography allows detailed visualization of the facial artery and its branches and is a potential noninvasive imaging tool for preoperative vascular mapping for facial reconstructive operations.


Collagen I and thrombin activate MMP-2 by MMP-14-dependent and -independent pathways: implications for airway smooth muscle migration.
Increased proinflammatory mediators and ECM deposition are key features of the airways in asthma. Matrix metalloproteinases (MMPs) are produced by airway smooth muscle (ASM) cells and have multiple roles in inflammation and tissue remodeling. We hypothesized that components of the asthmatic airway would stimulate MMP production and activation by ASM and contribute to airway remodeling. We measured human ASM-derived MMP mRNA, protein, and activity by real-time RT-PCR, zymography, Western blotting, and MMP activity assay. Collagen I and thrombin caused a synergistic increase in MMP-2 protein and total MMP activity but paradoxically decreased MMP-2 mRNA. Additionally, collagen I activated MMP-2 in culture supernatants independent of the cell surface. Together, collagen I and thrombin strongly enhanced MMP-14 mRNA and protein but had no effect individually, suggesting increased MMP-14, the activating protease for MMP-2, may be partially responsible for MMP-2 activation. Furthermore, collagen I reduced tissue inhibitor of metalloproteinase-2 protein (TIMP-2). We examined the role of MMPs in functions of ASM related to airway remodeling and found migration and proliferation were MMP dependent, whereas adhesion and apoptosis were not. Ilomastat inhibited migration by 25%, which was also inhibited by TIMPs 1-4 and increased by the MMP-2 activator thrombin. These in vitro findings suggest that the environment within the airways of patients with asthma enhances MMP-2 and -14 protein and activity by a complex interaction of transcriptional and posttranscriptional mechanisms, which may contribute to ASM migration.


A case of hepatocellular carcinoma with marked hyperfibrinogenemia.
The present report concerns a case of hepatocellular carcinoma (HCC) with marked hyperfibrinogenemia. The plasma fibrinogen level reached as high as 1,704 mg/dl. Since treatment against HCC resulted in reduction of plasma fibrinogen and PIVKA-II, an HCC marker, the hyperfibrinogenemia appears to be related to HCC. Immunohistochemically, the HCC specimen from this patient reacted strongly with antiserum to human fibrinogen, suggesting that the elevated fibrinogen was due to synthesis of this protein by the carcinoma cells, not to decreased fibrinolytic activity.


Genes associated with thermosensitive genic male sterility in rice identified by comparative expression profiling.
Thermosensitive genic male sterile (TGMS) lines and photoperiod-sensitive genic male sterile (PGMS) lines have been successfully used in hybridization to improve rice yields. However, the molecular mechanisms underlying male sterility transitions in most PGMS/TGMS rice lines are unclear. In the recently developed TGMS-Co27 line, the male sterility is based on co-suppression of a UDP-glucose pyrophosphorylase gene (Ugp1), but further study is needed to fully elucidate the molecular mechanisms involved. Microarray-based transcriptome profiling of TGMS-Co27 and wild-type Hejiang 19 (H1493) plants grown at high and low temperatures revealed that 15462 probe sets representing 8303 genes were differentially expressed in the two lines, under the two conditions, or both. Environmental factors strongly affected global gene expression. Some genes important for pollen development were strongly repressed in TGMS-Co27 at high temperature. More significantly, series-cluster analysis of differentially expressed genes (DEGs) between TGMS-Co27 plants grown under the two conditions showed that low temperature induced the expression of a gene cluster. This cluster was found to be essential for sterility transition. It includes many meiosis stage-related genes that are probably important for thermosensitive male sterility in TGMS-Co27, inter alia: Arg/Ser-rich domain (RS)-containing zinc finger proteins, polypyrimidine tract-binding proteins (PTBs), DEAD/DEAH box RNA helicases, ZOS (C2H2 zinc finger proteins of Oryza sativa), at least one polyadenylate-binding protein and some other RNA recognition motif (RRM) domain-containing proteins involved in post-transcriptional processes, eukaryotic initiation factor 5B (eIF5B), ribosomal proteins (L37, L1p/L10e, L27 and L24), aminoacyl-tRNA synthetases (ARSs), eukaryotic elongation factor Tu (eEF-Tu) and a peptide chain release factor protein involved in translation. The differential expression of 12 DEGs that are important for pollen development, low temperature responses or TGMS was validated by quantitative RT-PCR (qRT-PCR). Temperature strongly affects global gene expression and may be the common regulator of fertility in PGMS/TGMS rice lines. The identified expression changes reflect perturbations in the transcriptomic regulation of pollen development networks in TGMS-Co27. Findings from this and previous studies indicate that sets of genes involved in post-transcriptional and translation processes are involved in thermosensitive male sterility transitions in TGMS-Co27.


Protein structure in context: the molecular landscape of angiogenesis.
A team of students, educators, and researchers has developed new materials to teach cell signaling within its cellular context. Two nontraditional modalities are employed: physical models, to explore the atomic details of several of the proteins in the angiogenesis signaling cascade, and illustrations of the proteins in their cellular environment, to give an intuitive understanding of the cellular context of the pathway. The experiences of the team underscore the use of these types of materials as an effective mode for fostering students' understanding of the molecular world and the scientific method used to define it.


cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori.
Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a large family of zincendopeptidases which play important roles in degradation of extracellular matrix (ECM) and various inflammatory diseases. Therefore, we examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors, such as vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori-infected patients upon the MMP-7 mRNA mucosal levels. We also determined the correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time polymerase chain reaction (PCR). The presences of cagA and vacA virulence factors was evaluated using PCR. MMP-7 expression was significantly higher in biopsies of patients infected with H .pylori compared to uninfected individuals. In addition, mucosal MMP-7 mRNA expression in H. pylori-infected patients significantly associated with the cagA status and the types of disease. Our results suggest that MMP-7 might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated with cag pathogenicity island-dependent MMP-7 upregulation.


Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris).
Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.


Alternative oxygen therapeutics: products, status of clinical trials, and future prospects.
Alternative oxygen therapeutics are oxygen carriers that can potentially replace red blood cell transfusion in clinical instances in which banked blood is unavailable or unsafe. Most of the candidate solutions have been based on hemoglobin, derived from animals, outdated banked human blood, or recombinant systems. Other solutions are based on perfluorocarbons. In contrast to hemoglobin, which chemically binds oxygen, perfluorocarbons carry oxygen as a dissolved gas. Most of the products of either category developed over the past two decades have failed attempts at regulatory approval for clinical use, but their development has led to a large body of research that has defined the way oxygen is normally delivered to tissues. From this research, a new generation of products is emerging, designed specifically to target oxygen to the tissues in most need. It is possible that one or more of the earlier products may be approved by regulatory agencies in 1 or 2 years. However, a universally compatible and safe product most likely will be unavailable for several more years.


Lung function before and after oxygen diving: a randomized crossover study.
Breathing oxygen with a partial pressure of > 50 kPa can cause pulmonary oxygen toxicity (POT). Diffusing capacity for carbon monoxide (DL(CO)) is thought to be a more sensitive indicator of POT than vital capacity (VC). Because diffusing capacity can be measured more specifically using nitric oxide (DL(NO)), we hypothesized that DL(NO) is better able to monitor and exclude POT than DL(CO). To compare changes in lung function after oxygen and air dives which include measurement of DL(NO) and DL(CO). Eleven healthy male divers (mean age 27.5 +/- 3.1 years) made two immersed dives to 150 kPa for three hours on two separate days, during which they randomly breathed 100% oxygen or air. VC, DL(NO) and DL(CO) were measured six times during a 26-hour period on both days and on a third non-diving day. There were no significant changes in DL(CO), DL(NO) or other diffusing capacity or spirometric parameters after either type of dive. Lung function after a single three-hour oxygen dive at a pO2 of approximately 150 kPa is comparable to that after an air dive at the same depth and duration. This suggests that such an oxygen dive does not induce detectable signs of POT. Our hypothesis that DL(NO) is more sensitive than DL(CO) for detection of POT could not be tested because the oxygen exposure did not affect either parameter.


In vitro and clinical studies of image acquisition in breath-hold MR cholangiopancreatography: single-shot projection technique versus multislice technique.
This study was undertaken to compare the in vitro and clinical value of two-dimensional multislice breath-hold MR cholangiopancreatography (MRCP) with a single-shot projection technique using a half-Fourier acquisition single-shot turbo spin-echo sequence. We examined 108 patients with pancreaticobiliary diseases, using breath-hold MRCP and a half-Fourier acquisition single-shot turbo spin-echo sequence on a 1.5-T MR unit with a body phased-array coil. Two data acquisition techniques were employed: multislice acquisition postprocessed by maximum intensity projection (MIP) (multislice technique) and single-shot projection with a thick slice (projection technique). In the multislice technique, nine contiguous slices were obtained with a thickness of 5 mm (acquisition time. 18 sec). In the projection technique, a single slice was obtained with a thickness of 30, 50, or 70 mm (acquisition time. 2 sec). Contrast-to-noise ratio (CNR) between the common bile duct and the liver as well as detectability of normal structures and diseases were compared for these two acquisition techniques. In the multislice technique, source images were also evaluated. ERCP or percutaneous transhepatic cholangiography images were used as the gold standard. Most of the pancreatic duct and common bile duct was revealed on 54% and 100% of the projection images, respectively, and on 35% and 98% of the MIP images, respectively, CNR was significantly higher with the multislice technique than with the projection technique (p < .01). With the projection technique, CNR decreased as slice thickness increased. Dilatation and occlusion of the pancreaticobiliary tree were equally well revealed by the two imaging techniques. However, abnormalities in the periampullary region and anomalies in the pancreaticobiliary tree were more clearly seen on projection images than on MIP images (p < .05). Stones in the common bile duct, gallbladder, or intrahepatic bile duct were best seen on source images acquired by the multislice technique (83% sensitivity). Because of the absence of misregistration and the speed of image acquisition, breath-hold single-shot MRCP using the projection technique with a slice thickness of 30 or 50 mm consistently revealed the pancreaticobiliary tree and periampullary region with an acceptable CNR. Stones in the bile duct were best seen on the source images acquired by the MIP technique.


Values of applying white blood cell counts in the prognostic evaluation of resectable colorectal cancer.
The count and classification of white blood cells (WBCs) may be used as prognostic markers in certain types of cancer. The present study investigated the prognostic potential of the counts of WBCs, including lymphocytes (LYs), monocytes (MOs), neutrophils (NEs), eosinophils (EOs) and basophils (BAs), in the prognosis of resectable colorectal cancer. The present study recruited 153 resectable colorectal cancer cases retrospectively, which were pathologically confirmed. All patients were divided into two groups, according to the median value of LY (low LY, ≤1.632x109/l or high LY, >1.632x109/l), MO (low MO, ≤0.330x109/l or high MO, >0.330x109/l), NE (low NE, ≤3.600x109/l or high NE, >3.600x109/l), EO (low EO, ≤0.085x109/l or high EO, >0.085x109/l), BA (low BA, ≤0.010x109/l or high BA, >0.010x109/l), or WBC (low WBC, ≤5.780x109/l or high WBC, >5.780x109/l). To evaluate the alterations in WBC counts following surgery and adjuvant chemotherapy; all samples received oxiplatin and capecitabine (XELOX) for 6‑8 cycles or 5‑fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for 10‑12 cycles. XELOX included oxaliplatin administered intravenously at a dose of 130 mg/m2 on day 1 and 850‑1,250 mg/m2 capecitabine twice daily for days 1‑14, repeated every 3 weeks. mFOLFOX6 included oxaliplatin administered intravenously at a dose of 85 mg/m2, 400 mg/m2 leucovorin and 400 mg/m2 5‑FU on day 1 followed by 1,200 mg/m2/days continuous infusion for 2 days (in total, 2,400 mg/m2 over 46‑48 h), repeated every 2 weeks. The present study investigated the post/pre‑treatment of LY, MO, NE, EO, BA and WBC ratios (≤1 indicated that LY, MO, NE, EO, BA and WBC counts were not increased following therapy; whereas, >1 suggested increased counts). Kaplan‑Meier curves were constructed to demonstrate overall survival (OS). A multivariate and univariate logistic regression analyses model was employed to identify the independent risk factors. Low pre‑treatment BA counts were associated with larger tumor size (>5 cm); pre‑treatment BA levels were positively associated with OS. Surgery significantly decreased the count of BAs and increased the count of EOs; whereas, no effect was observed on LYs, MOs, NEs or WBCs. Adjuvant chemotherapy markedly decreased the counts of LY, NE and WBC; whereas, no notable effects on MOs, EOs or BAs were observed. Whole course treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of LY, NE and WBC; however, increased the value of EO; no effects on the MO or BA counts were observed. An increased post‑/pre‑treatment NE ratio suggested poorer prognosis. Multivariate Cox regression analysis revealed that sex, tumor size, pre‑treatment BA count and the post‑/pre‑treatment NE ratio were independent prognostic factors affecting OS. The results of the present study suggested that the pre‑treatment BA count and post‑/pre‑treatment NE ratio may be potential prognostic factors for resectable colorectal cancer.


Design and Evaluation of the Kinect-Wheelchair Interface Controlled (KWIC) Smart Wheelchair for Pediatric Powered Mobility Training.
Children with severe disabilities are sometimes unable to access powered mobility training. Thus, we developed the Kinect-Wheelchair Interface Controlled (KWIC) smart wheelchair trainer that converts a manual wheelchair into a powered wheelchair. The KWIC Trainer uses computer vision to create a virtual tether with adaptive shared-control between the wheelchair and a therapist during training. It also includes a mixed-reality video game system. We performed a year-long usability study of the KWIC Trainer at a local clinic, soliciting qualitative and quantitative feedback on the device after extended use. Eight therapists used the KWIC Trainer for over 50 hours with 8 different children. Two of the children obtained their own powered wheelchair as a result of the training. The therapists indicated the device allowed them to provide mobility training for more children than would have been possible with a demo wheelchair, and they found use of the device to be as safe as or safer than conventional training. They viewed the shared control algorithm as counter-productive because it made it difficult for the child to discern when he or she was controlling the chair. They were enthusiastic about the video game integration for increasing motivation and engagement during training. They emphasized the need for additional access methods for controlling the device. The therapists confirmed that the KWIC Trainer is a useful tool for increasing access to powered mobility training and for engaging children during training sessions. However, some improvements would enhance its applicability for routine clinical use.


Rationale for the surgical treatment of pulmonary metastases.
In a twenty-six year period, 90 patients underwent surgical treatment for metastatic malignant disease of the lung. The primary tumour had apparently been completely removed and there was no evidence of other metastatic spread. Thirty patients enjoyed a survival of more than five years. In 22 cases of the lung lesion was multiple and in 17, the lesions were bilateral. In patients with pulmonary metastases, but without evidence of other dissemination of the disease, resection of the lesions provided useful palliation, and 33% survived for five years of more.


Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo.
The 3.2-kb hepatitis B virus (HBV) genome encodes a single regulatory protein termed HBx. While multiple functions have been identified for HBx in cell culture, its role in virus replication remains undefined. In the present study, we combined an HBV plasmid-based replication assay with the hydrodynamic tail vein injection model to investigate the function(s) of HBx in vivo. Using a greater-than-unit-length HBV plasmid DNA construct (payw1.2) and a similar construct with a stop codon at position 7 of the HBx open reading frame (payw1.2*7), we showed that HBV replication in transfected HepG2 cells was reduced 65% in the absence of HBx. These plasmids were next introduced into the livers of outbred ICR mice via hydrodynamic tail vein injection. At the peak of virus replication, at 4 days postinjection, intrahepatic markers of HBV replication were reduced 72% to 83% in mice injected with HBx-deficient payw1.2*7 compared to those measured in mice receiving wild-type payw1.2. A second plasmid encoding HBx was able to restore virus replication from payw1.2*7 to wild-type levels. Finally, viremia was monitored over the course of acute virus replication, and at 4 days postinjection, it was reduced by nearly 2 logs in the absence of HBx. These studies establish that the role for HBx in virus replication previously shown in transfected HepG2 cells is also apparent in the mouse liver within the context of acute hepatitis. Importantly, the function of HBx can now be studied in an in vivo setting that more closely approximates the cellular environment for HBV replication.


Development and evaluation of a real-time RT-qPCR for detection of Crimean-Congo hemorrhagic fever virus representing different genotypes.
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by a nairovirus belonging to family Bunyaviridae. The CCHF virus (CCHFV) can be transmitted to humans by Hyalomma ticks as well as by direct contact with infected body fluids or tissues from viremic livestock or humans. Our aim was to set up a fast RT-qPCR for detection of the different CCHFV genotypes in clinical samples, including an inactivation step to make the sample handling possible in lower biosafety levels (BSL) than BSL-4. This method was evaluated against commercial reference assays and international External Quality Assessment (EQA) samples. The analytical limit of detection for the developed CCHFV-S RT-qPCR was 11 CCHFV genomes per reaction. After exclusion of four dubious samples, we studied 38 CCHFV-positive samples (using reference tests) of which 38 were found positive by CCHFV-S RT-qPCR, suggesting a sensitivity of 100%. CCHFV-S RT q-PCR detected all eight different CCHFV strains representing five different CCHFV genotypes. In conclusion, the CCHFV-S RT-qPCR described in this study was evaluated using various sources of CCHFV samples and shown to be an accurate tool to detect human CCHFV infection caused by different genotypes of the virus.


Fiber post adhesion to radicular dentin: The use of acid etching prior to a one-step self-etching adhesive.
The aim of this study was to evaluate the bond strength of fiber posts luted with a one-step self-etching adhesive with the push-out test after phosphoric acid conditioning of the root dentin. Thirty-six single-rooted teeth were endodontically treated. Teeth were sectioned perpendicularly to the cementoenamel junction, and a 10-mm post space was prepared with a calibrated bur. Specimens were then divided into three groups according to the adhesive protocol: A, total-etch three steps; B, self-etch one step; and C, 32% phosphoric acid conditioning and self-etch one step. Fiber posts were luted with self-curing resin-based cement. Teeth were cut in 1-mm slices and pushed until failure with an Instron machine. Results were statistically analyzed with the ANOVA and Bonferroni tests (P < .05). Two additional specimens from each group were examined under the scanning electron microscope (SEM). The 32% phosphoric acid significantly influenced the push-out bond strength of fiber posts luted with self-etch adhesives (P < .05). SEM analysis showed a continuous hybrid layer with resin tags and lateral branches in groups A and C, while group B showed smear layer dissolution with poor infiltration of the tubules.


Clean indoor air: advances in California, 1990-1999.
This study assessed progress in achieving clean indoor air in California. Data were from large, cross-sectional population-based surveys (1990-1999). Indoor workers reporting smoke-free workplaces increased from 35.0% (95% confidence interval [CI] = 33.7, 36.3) in 1990 to 93.4% (95% CI = 92.6, 94.2) in 1999. Exposure of nonsmoking indoor workers to secondhand tobacco smoke decreased from 29.0% (95% CI = 27.2, 30.8) to 15.6% (95% CI = 14.1, 17.1). Adults with smoke-free homes increased from 37.6 % (95% CI = 35.1, 40.1) in 1992 to 73.7% (95% CI = 73.2, 74.2) in 1999; nearly half of smokers in 1999 had smoke-free homes. In 1999, 82.2% (95% CI = 81.5, 82.9) of children and adolescents (0-17 years) had smoke-free homes, up from 38.0% (95% CI = 35.1, 40.9) in 1992. California's advances highlight an important opportunity for tobacco control.


Intensivists' perceptions and attitudes towards infectious diseases management in the ICU: An international survey.
Exploring infectious diseases (ID) practice in Intensive Care Unit (ICU) to identify gaps and opportunities. Online international survey (PRACT-INF-ICU) endorsed by the ESICM and open from July 30, 2019 to October 19, 2019. International study conducted in 78 countries. Physicians working in ICU. None. Practice variations were assessed according to respondents' countries income class, training, and years of practice. Univariate and multivariate ordinal logistic regression were used to estimate associations between respondents' characteristics and their perceptions regarding adequacy of training. 466 intensivists with a median practice of 10 years (interquartile range, 5-19) completed the survey. A third reported no antimicrobial stewardship program and 40% had no regular microbiological rounds in their ICUs. Intensivists were mostly the decision makers for the initial antimicrobial therapy which in 70% of cases were based on guidelines or protocols. Non-ICU expertise were sought more frequently on reviewing (48/72h, culture adjustment and discontinuation in 32%, 39% and 21% respectively) rather than antimicrobial therapy initiation (16%). Only 42% described ID training as adequate. Multivariate ordinal logistic regression showed that low- to middle-income countries (OR: 0.41, 95% CI: 0.28-0.61), ICU practice ≤10 years (OR: 0.55, 95% CI: 0.39-0.79), and dual training with anaesthesia (OR: 0.52, 95% CI: 0.34-0.79) or medicine (OR: 0.49, 95% CI: 0.32-0.76) were associated with less training satisfaction. ID practice is heterogeneous across ICUs while antimicrobial stewardship program is not universally implemented. From intensivists' perspective, ID training and knowledge need improvement.


Intelligent Decision-Support System for Epidemiological Diagnostics. II. Information Technologies Development*, *.
The article projects the components of the intelligent decision support system for epidemiological diagnostics and investigates their interaction with the user. The system includes a bank of models and machine learning methods, a bank of population dynamics models, visualization and reporting tools, and management decision-making unit. The concept of information technology to ensure biosafety of the population is provided. A model of specified information technology use cases is developed and a sequence diagram is constructed. A model of information technology components and ways of their deployment on a server are proposed.


Holmium laser fulguration of superficial urothelial carcinoma of the pendulous urethra.
Urothelial carcinoma may occur anywhere in the urinary tract including the pendulous urethra. To prevent urethral stricture after resection and monopolor fulguration we describe the use of the holmium laser to fulgurate recurrent pTa UC from the urethra. The surgical approach was staged and provided excellent long term results for management of superficial UC.


Irrigation of port sites: prevention of port site metastases?
Port site metastases can occur when free viable tumor cells implant at trocar wounds. Irrigation of port sites with cytotoxic agents has been suggested to prevent port site metastases. The objective of this study is to assess whether tumor growth at port sites can be reduced by irrigation of these port sites. WAG rats were insufflated with CO(2) for 20 minutes and 5 x 10(5) CC531 tumor cells were injected intraperitoneally. Port sites were irrigated after completion of the pneumoperitoneum with povidone-iodine, a mixture of taurolidine and heparin, or sodium chloride. Controls did not undergo any irrigation of port sites. In experiment 1, all 16 rats had all 4 irrigation modalities. In experiment 2, four groups of 20 rats had one type of irrigation on two trocar wounds. Tumor growth was evaluated 4 weeks after the procedure. No difference in tumor growth at trocar wounds was found between any type of irrigation and controls in both experiments. In this experimental model, no beneficial or adverse effects of irrigation of port sites could be shown.


Helix-Induced Asymmetric Self-Assembly of π-Conjugated Block Copolymers: From Controlled Syntheses to Distinct Properties.
Conspectusπ-Conjugated polymers have gained significant interest because of their potential applications in optoelectronics, bioelectronics, and other domains. The controlled synthesis of π-conjugated block polymers optimizes their performance and enables novel properties and functions. However, precise control of the self-assembled architectures of π-conjugated polymers remains a formidable challenge. Inspired by the precise helical architectures of biomacromolecules, the helical polymers and the supramolecular helical assemblies have gained significant attention. Helical polymers with an excess of one-handed helicity can be optically active with a strong tendency toward self-assembly. Incorporating a helical polymer into a π-conjugated polymer can induce asymmetric helical assemblies, leading to novel chiral materials with unique functionalities.To control the self-assembly of architectures, π-conjugated polymers are usually synthesized into block copolymers by incorporating a polymer with self-assembling characteristics. Although various π-conjugated block copolymers have been produced, precise and asymmetric self-assembly is still challenging and has rarely been addressed. Incorporating helical polymers into the π-conjugated polymers can induce a precise and asymmetric self-assembly, which transfers the chirality of the helical polymer block to the π-conjugated polymer, resulting in chiral supramolecular architectures with unique chiroptical properties and functionalities. However, synthesizing hybrid block copolymers containing two distinct polymer blocks is complicated. Some general strategies such as connecting the chain ends of two preformed homopolymers and extending the chain of a prefabricated π-conjugated polymer with a second monomer are time-consuming and require complex synthetic protocols. Therefore, developing novel strategies for the facile synthesis of π-conjugated block copolymers with a predictable molar mass, low dispersity, and tunable composition is of practical importance.Recently, we investigated a controlled synthesis of helical polyisocyanides, helical polyallenes, and helical polycarbenes by developing advanced Pd(II) and Ni(II) catalysts. These helical polymers were successfully incorporated into π-conjugated polymers, including polythiophene, polyfluorene, and poly(phenyleneethynylene), via a one-pot sequential living block polymerization of the two distinct monomers using Pd(II)- or Ni(II)-complexes as catalysts. As a result, a variety of well-defined π-conjugated block copolymers containing helical polymeric blocks were readily synthesized. Although the copolymerized monomers possess different structures and polymerization mechanisms, the one-pot block copolymerization followed a living polymerization mechanism and provided the desired π-conjugated block copolymers in high yields with controlled molar mass, narrow size distribution, and tunable composition.Remarkably, the helical polymeric block induces the π-conjugated block copolymer asymmetric self-assembly into a supramolecular, one-handed helical architecture resulting in distinct optical properties. More interestingly, by utilizing the crystallization of conjugated blocks and one-handed helical blocks, the crystallization-driven and helix-induced precise asymmetric living self-assembly yielded a family of uniform and single-handed helical architectures with controlled dimensions, narrow distribution, and well-defined helicity. The transfer of helical chirality to the supramolecular architectures rendered the achiral π-conjugated blocks with unique chiroptical properties such as the emission of white light over a broad optical spectrum and the circularly polarized luminescence.


Interaction of sperm with the zona pellucida during fertilization.
In order to achieve fertilization sperm cells, first need to successfully interact with the zona pellucida. To this end, the sperm surface is extensively remodeled during capacitation and the resulting sperm cells also possess hyperactivated motility. Together, this serves to mediate optimal recognition of the zona pellucida in the oviduct or after in vitro fertilization incubations (primary zona pellucida binding). When the sperm cell attaches to the zona pellucida, it will be triggered to undergo the acrosome reaction which allows the hyperactivated motile sperm cell to drill through the zona pellucida (secondary zona pellucida binding coinciding with sequential local zona pellucida digestion and rebinding). After successful zona penetration, some sperm cells may enter the perivitelline space. This delaying strategy of the oocyte allows only one sperm cell at a given time to bind and fuse with the oocyte (fertilization) and thus minimizes the risk of polyspermy. The fertilization fusion between the oocyte and the first sperm cell is immediately followed by a polyspermic fertilization block, in which the content of the oocyte's cortical granules is released into the perivitelline space. The cortical reaction blocks further sperm-oocyte fusion either by sticking at the oolemma or by the induction of a biochemical reaction of the zona pellucida (zona pellucida hardening). The cortical reaction thus blocks sperm-zona pellucida binding and/or sperm-zona pellucida penetration. This review summarizes the current understanding of sperm-zona pellucida interactions in relation to mammalian fertilization. The lack of knowledge about sperm-zona pellucida binding in ruminants will be critically discussed.


Dietary intake of vitamin B12 in relation to diet and lifestyle characteristics in a population at high risk for colorectal cancer.
Besides irreplaceable role in health, vitamin B12 is proposed to have cytoprotective role in colorectal cancer (CRC). So far, studies are inconclusive on the role dietary intake of vitamin B12 has in CRC. The aim of this study was to determine whether total dietary intake of vitamin B12 and contribution from its food sources relates to a low-risk diet and lifestyle in a population at high risk for CRC. An observational study on 200 healthy adults from Eastern Croatia was conducted during April-May 2013. A typical diet of this population in this region is characterized with all known major dietary risk factors for CRC placing the population at high risk for CRC, yet the incidence of CRC remains relatively low. Diet and lifestyle characteristics of 52.2% of participants can be classified as the high-risk for CRC. Women, people in lower BMI category, and urban residents have significantly lower risk of the high-risk diet and lifestyle. Higher intake of vitamin B12 shows positive association with the low-risk diet and lifestyle. Intake of vitamin B12 from milk, dairy and fish represent independent factors for the low-risk diet and lifestyle in this population at high-risk for CRC. Higher intake of vitamin B12, especially intake from milk, dairy and fish are associated with the low-risk diet and lifestyle in a population at high risk for CRC. Further studies should focus on interplay between vitamin B12 and other nutrients that share the same food sources to elucidate their role in the aetiology and pathology of CRC.


Fluid intelligence and gross structural properties of the cerebral cortex in middle-aged and older adults: A multi-occasion longitudinal study.
According to Parieto-Frontal Integration Theory (P-FIT, Jung and Haier, 2007), individual differences in a circumscribed set of brain regions account for variations in general intelligence (g). The components of g, fluid (Gf) and crystallized (Gc) reasoning, exhibit distinct trajectories of age-related change. Because the brain also ages differentially, we hypothesized that age-related cognitive and neural changes would be coupled. In a sample of healthy middle-aged and older adults, we examined changes in Gf (operationalized by Cattell Culture Fair Test) and Gc (indexed by two vocabulary tests) as well as in structural properties of 19 brain regions. We fitted linear mixed models to the data collected on 73 healthy adults who participated in baseline assessment, with 43 returning for at least one follow-up, and 16 of them contributing four repeated assessments over seven years. We observed age differences as well as longitudinal decline in Gf, contrasted to a lack of age differences and stability in Gc. Cortical thickness and cortical volume exhibited significant age differences and longitudinal declines, which were accelerated in P-FIT regions. Gf (but not Gc) was associated with cortical thickness, but no such relationship was found for cortical volume. Uniformity of cognitive change (lack of reliable individual differences) precluded examination of the coupling between cognitive and brain changes. Cortical shrinkage was greater in high-Gc individuals, whereas in participants with higher Gf cortical volume slower volume shrinkage was observed.


Purification and characterization of a novel levanoctaose-producing levanase from Pseudomonas strain K-52.
Levan-assimilating micro-organisms from soil samples were screened for levanoligosaccharide-generating enzyme production. The isolated strain K-52 produced an extracellular levanoctaose-generating enzyme and was identified as belonging to genus Pseudomonas. The levanase was purified to homogeneity by (NH4)2SO4 fractionation and successive column chromatography on DEAE-cellulose, phenyl-Toyopearl 650 M, Sephadex G-100 and hydroxyapatite. The molecular mass of the enzyme was estimated as approx. 38 kDa by both SDS/PAGE and gel filtration, and its isoelectric point was approx. pH 4.8. The optimum temperature and pH for the enzyme reaction were 35 and 7.0 respectively. The enzyme was stable at a pH range of 6.0-9.0 at 4 degrees C and up to 40 degrees C at pH 6.8. The enzyme activity was inhibited by Fe2+, Cu2+, Hg2+ and Ag2+. The levanase was specific toward 2,6-beta-D-fructosidic linkages of levan and did not hydrolyse other polysaccharides such as inulin and dextran. Chemical modification on the levanase suggested that cysteine and histidine residues are essential for enzyme activity. The levanoctaose liberated by levanase reaction was used selectively only by the intestinal beneficial micro-organisms, such as Bifidobacterium and Lactobacillus spp.


[Preparation and application of CuS/Cu2+ nanoparticles as a resonance light scattering probe].
Cuprum-enriched cuprum sulfide nanoparticles (CuS/Cu2+) were prepared. The nanoparticles are water-soluble. They could be used as a resonance light scattering (RLS) probe in the determination of human gamma globulin, which was proved to be a simple, rapid and specific method. In comparison with organic dye probes, these nanoparticles probes are brighter, more stable against photobleaching, and do not suffer from blinking. Under optimum conditions, the response is linearly proportional to the concentration of gamma globulin between 0.1 and 1.5 mg x L(-1), and the detection limit is 0.064 6 mg x L(-1).


New insight into the importance of formulation variables on parenteral growth hormone preparations: potential effect on the injection-site pain.
Reducing injection-site pain (ISP) in patients with chronic conditions such as growth hormone deficiency is a valuable strategy to improve patient compliance and therapeutic efficiency. Thus understanding different aspects of pain induction following subcutaneous injection of biotherapeutics and identifying the responsible factors are vital. Here we have discussed the effects of formulation's viscosity, concentration, osmolality, buffering agents, pH, and temperature as well as injection volume, dosing frequency, and different excipients on ISP following subcutaneous injection of commercially available recombinant human growth hormone products. Our literature review found limited available data on the effects of different components of parenteral rhGH products on ISP. This may be due to high cost associated with conducting various clinical trials to assess each excipient in the formulation or to determine the complex interactions of different components and its impact on ISP. Recently, conducting molecular dynamics simulation studies before formulation design has been recommended as an alternative and less-expensive approach. On the other hand, the observed inconsistencies in the available data is mainly due to different pain measurement approaches used in each study. Moreover, it is difficult to translate data obtained from animal studies to human subjects. Despite all these limitations, our investigation showed that components of parenteral rhGH products can significantly contribute to ISP. We suggest further investigation is required for development of long acting, buffer-free, preservative-free formulations. Besides, various excipients are currently being investigated for reducing ISP which can be used as alternatives for common buffers, surfactants or preservatives in designing future rhGH formulations.


Clinical Value of Metagenomics Next-Generation Sequencing in Antibiotic Resistance of a Patient with Severe Refractory Mycoplasma pneumoniae Pneumonia: A Case Report.
Mycoplasma pneumoniae is an important infectious pathogen of lower respiratory tract infection in children and adolescents. Macrolide resistant M. pneumoniae (MRMP) has become increasingly prevalent, and identifying pathogen resistance genes is crucial for treatment. We report a patient with severe refractory M. pneumoniae pneumonia (MPP). The failure of initial clinical treatment prompted the re-analysis of metagenomic next-generation sequencing (mNGS) data for macrolide-resistant gene. Macrolide-resistance 23S ribosomal RNA gene was confirmed with read depth of 64 X for the A2063G mutation, which can decrease the affinity of macrolide with M. pneumoniae ribosome resulting in macrolide resistance. Furthermore, antimicrobial susceptibility testing demonstrated that M. pneumoniae was resistant to macrolide. PCR confirmatory test about M. pneumoniae resistance A2063G mutation, clinical treatment course and prognosis with altered treatment strategy, and M. pneumoniae antimicrobial susceptibility confirmed that the severe refractory MPP was due to macrolide resistant M. pneumoniae. As a new molecular level detection, mNGS is an effective method for detecting M. pneumoniae resistance genes. Early recognition of macrolide resistance and suitable antibiotics strategy is of vital importance for the prognosis of severe refractory MPP.


Surgical Management of Gout in the Foot and Ankle A Systematic Review.
The surgical management of tophaceous gout has been well documented in the literature, including its effect on foot pain and disability. To date, there have been no systematic reviews assessing the quality of the literature relating to the operative management of tophaceous gout and the outcomes in the foot and ankle. The following electronic databases were searched (1980-2014): Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Scopus, and the Cochrane Library. The articles identified were published in English and included adult participants (age ≥18 years) with diagnosed gout and surgical intervention to the foot and ankle. The Downs and Black Quality Index was modified to assess the quality of the articles being reviewed. Six articles were reviewed and were of moderate quality (mean quality score of 71%). Surgical management was conducted on men (88%) with a mean age of 52 years. There was wide variation in the types of surgical procedures performed, with 28% of studies reporting surgery to the first metatarsophalangeal joint. Most studies were retrospective. A wide range of outcome measures were reported: foot pain, function, preoperative and postoperative activity levels, monitoring of uric acid levels, and patient satisfaction after surgery. The review demonstrated a limited number of good-quality studies. Several surgical procedures for the foot and ankle in people with chronic tophaceous gout were reported. Future studies should include prospective observational studies using validated and reliable patient-reported outcome measures.


Intracellular microlasers.
Optical microresonators1 which confine light within a small cavity are widely exploited for various applications ranging from the realization of lasers2 and nonlinear devices3, 4, 5 to biochemical and optomechanical sensing6, 7, 8, 9, 10, 11. Here we employ microresonators and suitable optical gain materials inside biological cells to demonstrate various optical functions in vitro including lasing. We explored two distinct types of microresonators: soft and hard, that support whispering-gallery modes (WGM). Soft droplets formed by injecting oil or using natural lipid droplets support intracellular laser action. The laser spectra from oil-droplet microlasers can chart cytoplasmic internal stress (~500 pN/μm2) and its dynamic fluctuations at a sensitivity of 20 pN/μm2 (20 Pa). In a second form, WGMs within phagocytized polystyrene beads of different sizes enable individual tagging of thousands of cells easily and, in principle, a much larger number by multiplexing with different dyes.


Budd-Chiari syndrome computed tomographic imaging: Elucidating the devil in the details.
Hepatic venous outflow obstruction, due to hepatic venous thrombosis is the hallmark of Budd-Chiari Syndrome (BCS), a relatively uncommon disorder. The aim of this study was to explore imaging details and causes, and define invasive and non-invasive interventions for achieving successful portosystemic shunting (PSS). The variations in imaging topology and associated risk factors in BCS cases, diagnosed during the past 20 months, were studied. Of the 53 cases (32 males, 21 females; mean age: 34.4±13.5 years), 5 (9%) were Hepatitis-B virus (HBV) positive, 12 (23%) were HCV positive and 6 (11%) were co-infected, rest were negative. Imaging features included mottled cirrhotic hepatic parenchyma, thrombosed hepatic and portal-vein with or without IVC thrombosis, left lobe atrophy, caudate hypertrophy, splenomegaly, portosystemic varices and ascites. Three cases had subacute onset; two had acute while the rest were chronic BCS. The aetiology was: protein C, S and anti-thrombin deficiency in 24 (45%), JAK2 mutation in 3 (6%), lupus antibody with increased homocysteine levels in 5 (9%) and cryptogenic in 21 (40%) cases. Twelve cases were planned for liver transplantation, 20 were prepared to undergo TIPS, and the rest were optimised medically.


Quantitative articular cartilage sub-surface defect assessment using optical coherence tomography: An in-vitro study.
Assessment of structural cartilage damage is of high scientific and clinical interest. Optical Coherence Tomography (OCT) is a light-based cross-sectional imaging modality that allows the real-time assessment of articular cartilage at near-histological resolution. Algorithm routines for the detection, parameterization and quantification of sub-surface defects as assessed by OCT were implemented and validated in this study. Standard defects of 0.9mm, 1.1mm and 1.3mm diameter were created in the sub-surface regions of macroscopically intact human articular cartilage samples (n=60 defects of variable sizes in n=20 samples). Subsequently, samples were scanned by 3D OCT and defect size, height, width and distance to the surface were determined based on the algorithm and related to manual measurements. Histology served as the standard-of-reference. Statistical analysis included one-way ANOVA's and Tukey's post-hoc test. All defects were correctly identified by the algorithm, while five structural tissue inhomogeneities were erroneously marked as defects (sensitivity 100%, specificity: 92.3%). Inter-modality analysis revealed no significant differences in terms of defect area, height or width within the different defect sizes, while the distance to the surface was significantly different. The comprehensive algorithm-based characterization of cartilage defects is consistent and reliable and allows their more objective evaluation. Given further research in this field, OCT and OCT-based quantitative measures may become clinically useful in the arthroscopic detection and evaluation of sub-surface cartilage defects.


Prevalence and trends in urinary incontinence among women in the United States, 2005-2018.
Women are disproportionately affected by urinary incontinence compared with men. Urinary incontinence results in physical and psychological adverse consequences and impaired quality of life and contributes to significant societal and economic burden. Previous studies reported high urinary incontinence burden in the United States. However, the current prevalence and recent trends in urinary incontinence and its subtypes among US women have not been described. In addition, correlates of urinary incontinence among US women have not been systematically evaluated in the contemporary population. The purpose of this study was to determine the prevalence and trends in urinary incontinence among adult women in the United States from 2005 to 2018. In addition, this study aimed to investigate the relationship of urinary incontinence subtypes with several sociodemographic, lifestyle, health-related, and gynecologic factors. We used data from the National Health and Nutrition Examination Survey, a nationally representative series of surveys that was designed to evaluate the health status of the US population. Data on urinary incontinence from 7 consecutive 2-year cycles (2005-2006 to 2017-2018) were used for this study. A total of 19,791 participants aged ≥20 years were included. Weighted prevalence estimates and 95% confidence intervals were calculated in each study cycle for stress, urgency, and mixed urinary incontinence. Multivariate-adjusted weighted logistic regression was used to investigate the temporal trends in urinary incontinence, in addition to determining the association between urinary incontinence subtypes with several participants' factors. In the 2017-2018 cycle, stress urinary incontinence was the most prevalent subtype (45.9%; 95% confidence interval, 42.1-49.7), followed by urgency urinary incontinence (31.1%; 95% confidence interval, 28.6-33.6) and mixed urinary incontinence (18.1%; 95% confidence interval, 15.7-20.5). The prevalence rates of urgency and mixed urinary incontinence were higher in women aged 60 years and older (urgency, 49.5% [95% confidence interval, 43.9-55.2]; mixed, 31.4% [95% confidence interval, 26.2-36.6]) than in those aged 40 to 59 years (urgency, 27.9% [95% confidence interval, 23.6-32.1]; mixed, 15.9% [95% confidence interval, 12.9-19.0]) and those aged 20 to 39 years (urgency, 17.6% [95% confidence interval, 13.8-21.5]; mixed, 8.3% [95% confidence interval, 5.4-11.3]). The overall prevalence of stress and mixed urinary incontinence was stable throughout 2005 to 2018 (both Ptrend=.3), with increases in mixed urinary incontinence among women aged 60 years and older (P=.001). The prevalence of urgency urinary incontinence significantly increased, particularly among women aged 60 years and older (both P=.002). Age, obesity, smoking, comorbidities, and postmenopausal hormone therapy were associated with higher prevalence of all types of urinary incontinence. Black women were less likely to report stress urinary incontinence but more likely to report urgency urinary incontinence. Although the estimated overall prevalence of stress and mixed urinary incontinence remained stable from 2005 to 2018, the prevalence of urgency and mixed urinary incontinence significantly increased among women aged 60 years and older. All subtypes of urinary incontinence were higher among women with obesity and comorbidities, those who used postmenopausal hormone therapy, and those who smoke.