Burnout in orthopedic surgeons.
Burnout corresponds to a state of exhaustion (emotional, physical, mental) that can result in complete psychological and/or physical breakdown. Burnout is a result of how our society has evolved. A recent phenomenon, it affects all strata of society, all corporations, and all countries. Physicians are not immune to it, whether they are in public or private practice and whether they are residents in training or seasoned practitioners. The orthopedic world is particularly affected because of multiple risk factors such as sustained work demands, increased malpractice lawsuits, patients no longer placing physicians on a pedestal, greater bureaucratic demands from hospitals and large practices, institutional control policies, reduced autonomy and aggressive media. This is a highly topical issue, hence this study. We sought to answer the following questions: What is burnout? Burnout has three components: emotional exhaustion, depersonalization, loss of personal accomplishment. Its manifestations are psychological, emotional and also physical. Six psychosocial risk factors have been described. The most relevant to our specialty are the intensity and complexity of the work, and the substantial emotional requirements. What is the frequency of burnout and the risk factors in the medical field? Burnout affects the healthcare sector, especially surgeons with a mean of 40% rate. All age groups, all types of practices and all countries are impacted. The mean suicide rate among surgeons (13.3%) is double that of the general population. The primary risk factors are physical and emotional overload, growing bureaucracy, the burden of malpractice lawsuits and regulatory bodies. How does burnout impact orthopedic and trauma surgery specifically? The burnout rate has been reported to be 30% to 40%, and greater than 50% in residents. The stress level is graded at more than 8/10 in 31% of us, with 40% of practitioners deeming this current stress level unacceptable. Administrative factors and the regulatory burden are said to be the most difficult to handle; consequently, orthopedic surgeons feel the best when they are operating. How can burnout be prevented and treated? The main elements of individual and collective prevention appear to be stress management seminars where surgeons can share their experiences, hear from others in the same situation and adjust their practices. We believe the priority should be placed on managing the work time and number of patients.


Prospective memory in bilinguals and monolinguals: ERP and behavioural correlates of prospective processing in bilinguals.
Prospective memory (PM) allows us to form intentions and execute them in the future. Successful retrieval of prospective intentions depends on adequate context monitoring and disengagement from the ongoing task. These processes are also central in predicting incoming language information and guiding language production in bilinguals. We investigated if different bilingual experiences (early/late bilinguals, monolinguals) modulate performance in PM tasks that varied in attentional requirements (focal vs. non-focal). Behavioural and event-related potential (ERP) results indicated that early bilinguals differed from late bilinguals and monolinguals in how they performed the prospective task. Specifically, they showed larger differences between the ongoing activity and the prospective task in the N300 and P3b components when performing the more difficult non-focal PM task, indicating that they engaged in monitoring/updating to adapt to the task's demands. These differences were not observed in late bilinguals and monolinguals, suggesting that prospective processing is dependent on the bilingual experience.


Optimizing the Exposure Indicator as a Dose Management Strategy in Computed Radiography.
To investigate a technique for optimizing radiation dose and image quality for a computed radiography system. Entrance skin doses were measured for phantom models of the pelvis and lumbar spine imaged using the vendor's recommended exposure settings (ie, the reference doses) as well as doses above and below the vendor's recommended settings for both body parts. Images were assessed using visual grading analysis (VGA). The phantom dosimetry results revealed strong positive linear relationships between dose and milliampere seconds (mAs), mAs and inverse exposure indicator (EI), and dose and inverse EI for both body parts. The VGA showed that optimized values of 16 mAs/EI = 136 for the anteroposterior (AP) pelvis and 32 mAs/EI = 139 for the AP lumbar spine did not compromise image quality. Selecting optimized mAs reduced dose by 36% compared with the vendor's recommended mAs (dose) values. Optimizing the mAs and associated EIs can be an effective dose management strategy.


The potential of self-activated carbon for adsorptive removal of toxic phenoxyacetic acid herbicide from water.
Phenoxyacetic acid herbicides are widely used in agriculture for controlling weeds. These organic compounds are persistent and recalcitrant, often contaminating water and soil. Therefore, we studied five pristine biochars (BCs), and southern yellow pine (SYP) based self-activated carbon (SAC) for the adsorptive removal of 2,4-Dichlorophenoxyacetic acid (2,4-D) herbicide. Among the tested adsorbents, SYP-SAC-15 demonstrated higher (>90%) 2,4-D removal from water. The SYP-SAC-15 was produced using a facile and green route where the biomass pyrolysis gases worked as activating agents creating a highly porous structure with a surface area of 1499.79 m2/g. Different adsorption kinetics and isotherm models were assessed for 2,4-D adsorption on SYP-SAC-15, where the data fitted best to pseudo-second order (R2 > 0.999) and Langmuir (R2 > 0.991) models, respectively. Consequently, the adsorption process was mainly dominated by the chemisorption mechanism with monolayer coverage of SYP-SAC-15 surface with 2,4-D molecules. At the optimum pH of 2, the maximum 2,4-D adsorption capacity of SYP-SAC-15 reached 471.70 mg/g. Furthermore, an increase in the water salinity demonstrated a positive influence on 2,4-D adsorption, whereas humic acid (HA) showed a negative impact on 2,4-D adsorption. The regeneration ability of SYP-SAC-15 showed excellent performance by retaining 71.09% adsorption capability at the seventh adsorption-desorption cycle. Based on the operating pH, surface area, spectroscopic data, kinetics, and isotherm modeling, the adsorption mechanism was speculated. The 2,4-D adsorption on SYP-SAC-15 was mainly governed by pore filling, electrostatic interactions, hydrogen bonding, hydrophobic and π-π interactions.


Applicability of factory calibrated optical particle counters for high-density air quality monitoring networks in Ghana.
In this study, we demonstrate the feasibility of using miniaturised optical particle counters (OPCs) for understanding AQ in Sub-Saharan Africa. Specifically, the potential use of OPCs for high-density ground-based air pollution networks and the use of derived data for quantification of atmospheric emissions were investigated. Correlation and trend analysis for particulate matters (PM), including PM10, PM2.5 and PM1 were undertaken on hourly basis alongside modelled meteorological parameters. Hourly averaged PM values were 500 μg/m3, 90 μg/m3 and 60 μg/m3 for PM10, PM2.5 and PM1, respectively and Pearson's correlation coefficient ranged between 0.97 and 0.98. These levels are in the agreement with range of PM emission reported for these types of environmental settings. PM was locally associated with low wind speeds (<= 2 ms-1) and was closely linked to anthropogenic activities. This study provides a benchmark for future AQ and demonstrates the feasibility of the current generation of OPCs for AQ monitoring in environments typical of large parts of West and Sub Saharan Africa.


A study of "white spotted kidneys" in cattle.
A study was performed at an abattoir in Australia, in an attempt to correlate focal chronic interstitial nephritis (FCIN) producing the so-called "white spotted kidney", with Leptospira spp. and other pathogens in cattle. Samples of kidneys, urine and blood were collected immediately after slaughter from 46 two-year-old heifers, and 72 cows and bulls with gross lesions consistent with FCIN. The same samples were also collected from nine heifers and 12 cows with no gross kidney lesions. Aqueous humour was also collected from the eye of 17 of the adult animals. The sera were processed by a microscopic agglutination test for leptospira antibodies, while all the other samples were cultured for Leptospira spp. and also processed for routine aerobic and anaerobic culture for other pathogens. Sub-samples from all the kidneys were fixed in 10% buffered formalin and processed histologically. Antibody titers of 1:400 or higher for Lepstospira borgpeterseni serovar hardjo were found in six adult animals with FCIN and in one adult animal with no gross kidney changes, while antibody titers of 1:400 to L. borgpeterseni serovar tarassovi were found in only one animal with FCIN. L. borgpeterseni serovar hardjo was isolated from the urine and kidney of one adult animal and from the urine of another adult animal, both with FCIN. No pathogens were isolated from any of the other samples. The histological lesions were consistent in most cases with FCIN. The results suggest that neither Leptospira spp. nor active infection by other bacteria are associated with the so-called "white spotted kidneys".


Digital PCR After MALDI-Mass Spectrometry Imaging to Combine Proteomic Mapping and Identification of Activating Mutations in Pulmonary Adenocarcinoma.
Matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-MSI) is a powerful tool to analyze the spatial distribution of peptides in tissues. Digital PCR (dPCR) is a method to reliably detect genetic mutations. Biopsy material is often limited due to minimally invasive techniques, but information on diagnosis, prognosis, and prediction is required for subsequent clinical decision making. Thus, saving tissue material during diagnostic workup is highly warranted for best patient care. The possibility to combine proteomic analysis by MALDI-MSI and mutational analysis by dPCR from the same tissue section is evaluated. Ten 0.5 × 0.5 cm formalin-fixed paraffin embedded tissue samples of pulmonary adenocarcinomas with known EGFR or KRAS mutations are analyzed by MALDI-MSI. Subsequently, DNA is extracted from the analyzed tissue material and tested for the respective driver mutation by dPCR. Detection of driver gene mutations after MALDI MSI analysis is successful in all analyzed samples. Determined mutant allele frequencies are in good agreement with values assessed from untreated serial tissue sections with a mean absolute deviation of 0.16. It has been demonstrated that MALDI-MSI can be combined with genetic analysis, like dPCR. Workflows enabling the subsequent analysis of proteomic and genetic markers are particularly promising for the analysis of limited sample material such as biopsy specimen.


Static equilibrium configurations of a model red blood cell.
The membrane of the red blood cell is modeled as a fluid shell which resists bending and changes in area. The differential equations governing the mechanical equilibrium of such a membrane are derived and axisymmetric solutions are obtained numerically.


The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study.
To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. The mean decreases in the total symptom score at 4 weeks were estimated to be -18.1±13.8 in the combination therapy group and -15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were -8.4±6.6 in the combination therapy group and -6.8±5.9 in the monotherapy group (p=0.009). Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.


Cytochemical reaction for cationic proteins as a marker of primary granules during development in chick heterophilis.
The ammoniacal silver reaction (ASR) for cationic proteins was used as a cytochemical marker for the primary or A granules in the cytoplasm of developing heterophils of chick bone marrow. The presence of the electron-dense particulate reaction product of silver, which is localized in the fully formed rod-shaped A granules, provides a marker by which the A granules could be distinguished from the B granules of similar size and by which the formation and maturation of both granule types could be followed through the developmental stages. Progressive developmental stages were ascertained on the basis of decreasing cell size, increasing condensation and margination of the chromatin, and the number and morphology of the granules; the stages were divided into promyelocyte, myelocyte, metamyelocyte and heterophil. During the promyelocyte stage, the first appearance of the electron-dense, membrane-bound, spherical granules (0.3--1.0 micrometer in diameter) is observed in the vicinity of an extensive Golgi complex. They occur in a cytoplasm containing rough-surfaced endoplasmic reticulum, ribosomal clusters, centrioles, mitochondria, microtubules, as well as the membranes, saccules, vesicles and vacuoles of the Golgi complex. These granules are considered as primary but their presence as the only granule type appears very brief. The ASR reaction product is first detected on the surface of these primary granules in late promyelocytes or myelocytes. The secondary or B granule, devoid of reaction for cationic protein at all stages, appears as a condensing vacuole in promyelocytes, but after some A granules are already present. The vacuole contents condense to form the B granules which are 0.1--0.6 micrometer in diameter, often oval-shaped, and contain a loose filamentous material surrounded by a membrane. Tertiary C granules or lysosomes appear during the myelocyte stage as dense core vesicles (0.1--0.2 micrometer in diameter) negative for cationic protein.


Scientific publications in obstetrics and gynecology journals from China, 2000-2009.
To analyze the output of scientific publications in obstetrics and gynecology journals from 3 principal regions of China: mainland China, Taiwan, and Hong Kong. Information on article numbers, impact factors, citation reports, and publication in high-impact obstetrics and gynecology journals by Chinese authors between January 1, 2000, and December 31, 2009, was extracted from PubMed and WoS databases. Comparisons of quantity and quality were done by Kruskal-Wallis and rank-sum tests. There were 3044 articles from mainland China (n=1042), Taiwan (n=1304), and Hong Kong (n=698). The cumulative impact factors and citations of articles from Taiwan were highest among the 3 regions. In terms of average impact factor and number of citations per article, Hong Kong exceeded mainland China and Taiwan. Fertility and Sterility, Human Reproduction and Gynecologic Oncology were among the most popular obstetrics and gynecology journals used by authors in the 3 regions. The annual number of articles published in obstetrics and gynecology journals from the 3 regions of China increased during the past decade, especially for mainland China. However, the quality of articles from mainland China arouses attention because the average citation of articles from Hong Kong and Taiwan was higher than that of articles from the mainland.


Immunological characterization of factor VIII inhibitors by a sensitive micro-ELISA method.
A micro-ELISA method for the immunological characterization of factor VIII (F. VIII) inhibitors is described. Microplates sensitized with purified monospecific anti-von Willebrand factor (vWF) IgG were firstly incubated with a commercial F. VIII concentrate and then with the samples containing the F. VIII inhibitors to be characterized. Peroxidase conjugated monospecific antisera were used to determine the Ig class and the light chain type. Alkaline phosphatase conjugated monoclonal antibodies were employed to investigate the IgG subclasses. The F. VIII inhibitors from 8 hemophiliacs and 1 patient with systemic lupus erythematosus (SLE) were characterized. All of them belonged to the IgG class but one case simultaneously exhibited another inhibitor of the IgA class. Eight inhibitors analyzed for light chains resulted to be polyclonal. In 7 cases the inhibitors belonged solely to the IgG4 subclass while in the other 2 cases contained all the 4 IgG subclasses. The method appears to be simple, accurate and highly sensitive (detecting as low as 0.156 Bethesda Units/ml) for the immunological characterization of F. VIII inhibitors.


Engel's law in the commodity composition of exports.
Different shares of distinct commodity sectors in production, trade, and consumption illustrate how resources and capital are allocated and invested. Economic progress has been claimed to change the share distribution in a universal manner as exemplified by the Engel's law for the household expenditure and the shift from primary to manufacturing and service sector in the three sector model. Searching for large-scale quantitative evidence of such correlation, we analyze the gross-domestic product (GDP) and international trade data based on the standard international trade classification (SITC) in the period 1962 to 2000. Three categories, among ten in the SITC, are found to have their export shares significantly correlated with the GDP over countries and time; The machinery category has positive and food and crude materials have negative correlations. The export shares of commodity categories of a country are related to its GDP by a power-law with the exponents characterizing the GDP-elasticity of their export shares. The distance between two countries in terms of their export portfolios is measured to identify several clusters of countries sharing similar portfolios in 1962 and 2000. We show that the countries whose GDP is increased significantly in the period are likely to transit to the clusters displaying large share of the machinery category.


Rapid diagnosis of thalassemias and other hemoglobinopathies by capillary electrophoresis system.
Basic diagnosis of hemoglobinopathies can be performed by analysis of erythrocyte indices as well as by the separation and quantification of the common hemoglobin (Hb) fractions Hb A(2), Hb S, Hb C, Hb D, Hb E, and Hb F. This study used an automatic capillary zone electrophoresis system to diagnose various types of hemoglobinopathies common in the Thai population. A total of 459 adults were recruited, which consisted of normal, various types of thalassemia carriers, and thalassemia patients with different genotypes. Hb types and quantification of all Hb components were determined by an automated capillary zone electrophoresis. The automatic capillary electrophoresis system can separate and quantitate Hbs A, F, E, A(2), Constant Spring (CS), H, and Bart's in a way that is comparable with other Hb analysis methods. Moreover, the Hb A(2) peak can be distinguished clearly from the Hb E peak in individuals who carry Hb E. The slightly increased levels of Hb A(2), 3.5% +/- 0.4%, which is shown in the carriers of Hb E, confirm that Hb E is the silent phenotype of beta(+)-thalassemia.


Supplementing retention through crown/preparation modification: an in vitro study.
The best treatment for a crown that has come loose but has appropriate marginal fit and form is not clear. This study was designed to determine whether the retention of such crowns can be increased without remaking the crown or by extensively modifying the tooth preparation. Ninety cast metal complete crowns, divided into 9 groups of 10, were fabricated to be slightly loose in their internal adaptation to metal dies with an optimal tooth preparation. Horizontal grooves were formed around the circumference of the internal crown surface and the external surface of the metal die, the control being the unaltered crown and die. The crowns were cemented with resin-modified glass ionomer cement and then subjected to a tensile force until they were dislodged. The data were subjected to a 2-way ANOVA to determine the significance of the differences between crowns and dies, and 2 t tests were then used to compare each crown/die combination to the control (α=.05). The mean retention was significantly higher when 1 horizontal groove was placed inside the crowns (P<.001) and was even higher when 2 grooves were placed inside the crowns (P<.001). Placing 1 or 2 grooves in the metal die or in both the crown and die was not significantly more retentive than placing grooves only in the crown. Placing 1 or 2 horizontal circumferential grooves into the internal surface increased the retention of metal complete crowns made for optimal tooth preparations. Grooves placed into the crown were as effective as or more effective than grooves placed into the tooth / die.


Setting up an ancient DNA laboratory.
Entering into the world of ancient DNA research is nontrivial. Because the DNA in most ancient specimens is degraded to some extent, the potential for contamination of ancient samples and DNA extracts with modern DNA is considerable. To minimize the risk associated with working with ancient DNA, experimental protocols specific to handling ancient specimens have been introduced. Here, I outline the challenges associated with working with ancient DNA and describe guidelines for setting up a new ancient DNA laboratory. I also discuss steps that can be taken at the sample collection and preparation stage to minimize the potential for contamination with exogenous sources of DNA.


Evolution of microRNAs and their targets: are all microRNAs biologically relevant?
MicroRNAs (miRNAs) are defined by their precise processing from a longer stem-loop precursor and by their subsequent ability to direct the regulation of target RNAs distinct from the miRNA precursor. Several lines of evidence suggest that miRNAs arose at least twice during eukaryotic evolution from an ancestral, pan-eukaryotic small RNA producing molecular machinery, though alternative scenarios cannot be ruled out. A handful of plant miRNAs are strongly expressed, widely conserved among plants, and have identical targets in long-diverged species; most of these very well conserved miRNA-target relationships involve DNA-binding transcription factors with suspected roles in developmental control. In contrast, a much greater number of plant miRNAs are weakly expressed, poorly conserved, and have few if any readily identifiable targets. These miRNAs appear to be evolutionarily "transient", and many of them may be of little to no selective value. However, this ever-changing cast of transient miRNAs could provide a reservoir of potentially useful miRNAs from which new regulatory interactions sometimes are selected.


DNA and RNA amplification in urology: the polymerase chain reaction.
Polymerase chain reaction (PCR) technology is a promising molecular approach for diagnosis of genitourinary tract infections, inherited disorders, tumor-associated genetic alterations and tumor markers. Because it is based on exponential amplification, the technology is capable of ultimate theoretical sensitivity. Although not entirely free of technical limitations, PCR holds advantages over other diagnostic tests, including exquisite sensitivity, specificity, interchangeability and speed.


Transvaginal laparo-endoscopic single-site sigmoidectomy.
We report a case of sigmoid colon resection by single-incision laparoscopic surgery using transvaginal access. The patient was a 54-year-old woman with early stage sigmoid cancer who had no previous surgery and had a body mass index of 23.5 kg/m(2). The operative time was 270 min, and the blood loss was negligible. We used only transvaginal access, since no transabdominal assistance was required. No complications occurred. Minimal postoperative pain and a rapid recovery of gastrointestinal function were observed. As novel equipment is introduced into clinical practice, transvaginal laparoscopic procedures will most likely become increasingly popular in abdominal surgery. In particular, this type of procedure will have a more defined role in colorectal surgery. Indeed, in the future, it may become an alternative for natural orifice transluminal endoscopic surgery.


Improved fluoroquinolone detection in ELISA through engineering of a broad-specific single-chain variable fragment binding simultaneously to 20 fluoroquinolones.
Fluoroquinolones (FQs) are a group of synthetic, broad-spectrum antibacterial agents. Due to its extensive use in animal industry and aquaculture, residues of these antibiotics and the emergence of bacteria resistant to FQs have become a major public health issue. To prepare a generic antibody capable of recognizing nearly all FQs, a single-chain variable fragment (scFv) was generated from the murine hybridoma cells C49H1 producing a FQ-specific monoclonal antibody. This scFv was characterized by indirect competitive enzyme-linked immunosorbent assay (ciELISA), and it showed identical binding properties to parental monoclonal antibody: it was capable of recognizing 17 of 20 targeted FQs below maximum residue limits, except for sarafloxacin (SAR), difloxacin (DIF), and trovafloxacin (TRO) which are highly concerned members in the FQs family. In order to broaden the specificity of this scFv to SAR and its analogues (DIF and TRO), protein homology modeling and antibody-ligands docking analysis were employed to identify the potential key amino acid residues involved in hapten antibody. A mutagenesis phage display library was generated by site directed mutagenesis randomizing five aminoacid residues in the third heavy-chain complementarity determining region. After one round of panning against biotinylated norfloxacin (NOR) and four rounds of panning against biotinylated SAR, scFv variants we screened showed up to 10-fold improved IC(50) against SAR, DIF, and TRO in ciELISA while the specificity against other FQs was fully retained.


Disks solid phase extraction based polypyrrole functionalized core-shell nanofibers mat.
A novel disks solid phase extraction (SPE) based on polypyrrole (PPy) functionalized core-shell electrospun nanofibers mat was proposed. The performance of the established disks SPE technique was evaluated in the extraction of trace polar analytes from environmental water samples. Disulphonated (acid yellow 9) and monosulphonated azo dyes (acid orange 7 and metanil yellow) were selected as typical model analytes. Under the optimum conditions, detection limits were 0.15-0.3 μg/L for all target analytes and the enrichment coefficients were 106-121. The recoveries of sulfonated azo dyes added to typical environmental water samples were 87.6-112.3%, suggesting that the interferences of the sample matrix did not affect the enrichment. Compared with existing methods, the device in this study showed higher recovery, lower detection limit and better precision. Moreover, the miniaturized disks SPE technique for sample preparation is simple and fast, with significantly reduced sorbent bed mass (2.5 mg) and eluent volume (500 μL). These results indicate that PPy nanofibers mat-based disks SPE may be a promising device that can effectively extract the polar species in water samples.


Critical review of the epidemiological literature on occupational exposure to perchloroethylene and cancer.
Of an estimated 500,000 workers in the USA potentially exposed to perchloroethylene (PCE), the largest share is employed in the dry-cleaning industry. PCE, a non-flammable solvent, has commercial applications as a chemical intermediate, metal degreaser and, since the 1950s, primary solvent in the dry-cleaning industry. The International Agency for Research on Cancer (IARC) currently finds sufficient evidence to designate PCE as carcinogenic in animals, with limited evidence in humans. With regard to occupational exposure through dry-cleaning, PCE is considered to be possibly carcinogenic to humans. This review was conducted to assess the current epidemiological literature on PCE and specific cancers. A comprehensive search was conducted to identify all available epidemiological literature pertaining to the carcinogenic effects of PCE. Forty-four papers that provided reasonable data on up to 17 cancer sites were critically reviewed in the context of the available background literature for each cancer site and were assessed on the basis of specified methodological and scientific quality criteria. While all the epidemiological studies selected for review investigated similar exposure-health outcome relationships, there was a broad diversity of proxy measurements of exposure to PCE, as well as numerous specific cancer outcomes of interest. The widespread lack of valid exposure measurements or other adequate indicators of potential for exposure were consistent limitations. We found no evidence of an association between breast, prostate, skin or brain cancer and exposure to PCE. A relationship between PCE and cancer of the following sites was considered unlikely: oral cavity, liver, pancreas, cervix lung. Scientific evidence was inadequate for laryngeal, kidney, esophageal and bladder cancers. The current epidemiological evidence does not support a conclusion that occupational exposure to PCE is a risk factor for cancer of any specific site. Priority areas in which additional data are most needed include cancers of the esophagus and bladder.


Regional ischemia distal to a critical coronary stenosis during prolonged fibrillation--improvement with pulsatile perfusion.
In a previous study from this laboratory, regional myocardial ischemia developed distal to a critical coronary stenosis in the fibrillating heart on cardiopulmonary bypass when myocardial perfusion was non-pulsatile. To assess the effect of pulsatile perfusion on the development of the fibrillation-induced ischemia, 10 dogs were placed on total cardiopulmonary bypass with the heart in the vented fibrillating state. A critical stenosis was applied to the left anterior descending artery (LAD). Pulsatile perfusion with a pulse pressure of 35 mm Hg and a pulse rate of 100/min was produced by a new method developed in this laboratory. During the 2 hours of bypass, ischemia in the LAD-supplied myocardium was assessed by changes in intramyocardial oxygen (PmO2) and carbon dioxide (PmCO2) tensions and by regional arterial-coronary venous lactate difference. With linear perfusion, regional ischemia in the LAD myocardium had been evidenced by a low PmO2 (8 +/- 3 mm Hg), a high PmCO2 (170 +/- 25 mm Hg) and regional lactate production (9.2 +/- 4.2 mg/100 ml). In contrast with pulsatile perfusion intramyocardial gas tensions remained stable during the 2 hours on bypass (PmO2 = 21 +/- 3 mm Hg, PmCO2 = 65 +/- 5 mm Hg, P less than 0.05 vs linear flow study) and lactate consumption was demonstrated (+17.7 +/- 2.9 mg/100 ml, P less than 0.001 vs linear flow group). With linear perfusion, myocardial blood flow to the LAD area had decreased 56 +/- 8% in the subendocardial layer and 46 +/- 7% in the subepicardial layer. In the dogs receiving pulsatile flow during bypass, regional LAD blood flow remained unchanged over the 2-hour bypass period and was significantly higher than the flow with linear flow (P less than 0.05). These data indicate that fibrillation-induced regional myocardial ischemia distal to a critical stenosis can be prevented by maintaining pulsatile perfusion during cardiopulmonary bypass.


Assessing the cost of cystic fibrosis diagnosis and treatment.
To extend previous evaluations of costs of cystic fibrosis (CF) diagnosis and examine key issues in assessing the CF cost of care. Costs for CF newborn screening (NBS) including CF multi-mutation testing are analyzed by using data from the Wisconsin State Laboratory of Hygiene. Electronic data from 2 Wisconsin CF centers are used to illustrate the complexity of analyzing CF health care utilization and costs. The current cost-per-newborn of a CF multi-mutation test is 50% higher than testing for a single mutation. Data collection for the cost-of-care study requires a combination of electronic and manual data collection; modeling of cost data requires consideration of any censoring. Hospitalizations are shown to have a large impact on costs and show high variability at the individual level. Sixty-nine percent of children with meconium ileus had some hospitalization versus 56% of children without meconium ileus. A cost-benefit analysis of CF multi-mutation testing is warranted. The study of health care cost data is complex and utilization varies between children. Individual-level modeling of CF costs must include factors contributing to the severity of the disease and allow for consideration of individual-level utilization, such as the number of hospitalizations.


Pigmentary changes in acquired retinoschisis.
We reviewed retrospectively the records of patients referred for retinal examination and found 375 eyes (233 patients) with acquired retinoschisis. Of the 375 eyes, 85 had outer layer retinal breaks, 27 had retinal detachments, and 29 had pigmentary lines. Twenty-five of the 29 pigmentary lines (86.2%) demarcated either retinal detachment or outer retinal layer breaks.


An integrated WebGIS framework for volunteered geographic information and social media in soil and water conservation.
Volunteered geographic information and social networking in a WebGIS has the potential to increase public participation in soil and water conservation, promote environmental awareness and change, and provide timely data that may be otherwise unavailable to policymakers in soil and water conservation management. The objectives of this study were: (1) to develop a framework for combining current technologies, computing advances, data sources, and social media; and (2) develop and test an online web mapping interface. The mapping interface integrates Microsoft Silverlight, Bing Maps, ArcGIS Server, Google Picasa Web Albums Data API, RSS, Google Analytics, and Facebook to create a rich user experience. The website allows the public to upload photos and attributes of their own subdivisions or sites they have identified and explore other submissions. The website was made available to the public in early February 2011 at http://www.AbandonedDevelopments.com and evaluated for its potential long-term success in a pilot study.


Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects.
Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.


Immunotherapies in ovarian cancer.
Ovarian cancer is the leading cause of death for gynaecological cancer, and new therapies are urgently awaited. Although the presence of tumour-infiltrating lymphocytes has been confirmed to be associated to a better prognosis, immunotherapy is not yet incorporated to the armamentarium in ovarian cancer. This review briefly summarises the strategies that have been tested or are under study for the three different groups of tumours: immune desert, inflamed and immune-excluded ovarian tumours. Finally, a better knowledge of the biology and immune microenvironment is needed for successfully developing new immunotherapy strategies.


Promotion of protocell self-assembly from mixed amphiphiles at the origin of life.
Vesicles formed from single-chain amphiphiles (SCAs) such as fatty acids probably played an important role in the origin of life. A major criticism of the hypothesis that life arose in an early ocean hydrothermal environment is that hot temperatures, large pH gradients, high salinity and abundant divalent cations should preclude vesicle formation. However, these arguments are based on model vesicles using 1-3 SCAs, even though Fischer-Tropsch-type synthesis under hydrothermal conditions produces a wide array of fatty acids and 1-alkanols, including abundant C10-C15 compounds. Here, we show that mixtures of these C10-C15 SCAs form vesicles in aqueous solutions between pH ~6.5 and >12 at modern seawater concentrations of NaCl, Mg2+ and Ca2+. Adding C10 isoprenoids improves vesicle stability even further. Vesicles form most readily at temperatures of ~70 °C and require salinity and strongly alkaline conditions to self-assemble. Thus, alkaline hydrothermal conditions not only permit protocell formation at the origin of life but actively favour it.


Transcriptional profiles of benzo(a)pyrene exposure in normal human mammary epithelial cells in the absence or presence of chlorophyllin.
Benzo(a)pyrene (BP) exposure causes alterations in gene expression in normal human mammary epithelial cells (NHMECs). This study used Affymetrix Hu-Gene133A arrays, with 14,500 genes represented, to evaluate modulation of BP-induced gene expression by chlorophyllin in six NHMEC strains derived from different donors. A major goal was to seek potential biomarkers of carcinogen exposure and how they behave in the presence of a chemopreventive agent. NHMECs (passage 6 and 70% confluence) were exposed for 24h to either vehicle control, or BP, or chlorophyllin followed by BP and chlorophyllin together. BP exposure resulted in approximately 3-fold altered expression of 49 genes in at least one of the six NHMEC strains. When cells were exposed to chlorophyllin pre-treatment followed by BP plus chlorophyllin, expression of 125 genes was similarly altered. Genes in the functional categories of xenobiotic metabolism, cell signaling, cell motility, cell proliferation, cellular transcription, metabolism, cell cycle control, apoptosis and DNA repair were identified. Only CYP1B1 and ALDH1A3 were consistently up-regulated by approximately 3-fold in most of the cell strains (at least 4) when exposed to BP. Cluster analysis identified a suite of 13 genes induced by BP where induction was mitigated in the presence of chlorophyllin. Additionally, cluster analysis identified a suite of 16 genes down-regulated by BP where induction was partially restored in the presence of chlorophyllin.


Ion-exchange-immunoaffinity purification of a recombinant baculovirus Plasmodium falciparum apical membrane antigen, PF83/AMA-1.
A two-step purification regime has been developed for a quantitatively minor, putatively transmembrane, M(r) 83,000, apical membrane blood stage vaccine candidate antigen of Plasmodium falciparum (PF83/AMA-1), that has been expressed as a full-length baculovirus recombinant protein, PF83-7G8-1. The first step utilizes a new approach to high-performance ion-exchange chromatography (HPIEC) in which elution conditions are not only defined by charge, but also by hydrophobicity. HPIEC fractionation involves successive sodium chloride gradient anion-exchange elutions (A and B), where a change in the non-ionic detergent polyoxyethylenealkylether C10E5 concentration between elutions A and B (from 0.01% to 0.1% (w/v) respectively), results in a fraction that comprises from 2% to 9% PF83-7G8-1. Subsequent column immunoaffinity purification of this fraction on Q-Sepharose CL 4B-28G2dc1 mAb yields a PF83-7G8-1 preparation that is 56% pure. Rat mAb 28G2dc1 recognizes a C-terminal region that is conserved and cross reactive within the AMA-1 family, thus permitting recombinant and native full-length AMA-1 molecules from other species to be purified for molecular analysis. Immunological and molecular characterisation of the vaccine-related characteristics of purified PF83/AMA-1 are now underway.


Enhanced health risks from exposure to environmentally persistent free radicals and the oxidative stress of PM2.5 from Asian dust storms in Erenhot, Zhangbei and Jinan, China.
Asian dust storms can increase the level of atmospheric pollution over regions downwind of dust storms and may have adverse health effects on residents along the sandstorm transmission route. This study was the first to report the concentration levels, properties and possible sources of environmentally persistent free radicals (EPFRs) and oxidative potential in atmospheric PM2.5 at the three sites of Erenhot, Zhangbei, and Jinan along the transport route of Asian dust storms during the occurrence of Asian dust storms in the spring of 2016. Under non-sandstorm weather conditions, the average EPFR concentrations at the three sites were Zhangbei>Jinan>Erenhot, while the PM-induced oxidative potential levels were Erenhot>Jinan>Zhangbei. The PM2.5 concentration increased significantly during dust storm events, and the total atmospheric concentration of EPFRs (spins/m3) and total oxidation potential (a.u./m3) of PM2.5 simultaneously increased. However, the EPFR concentration in PM2.5 (spins/g) and the unit mass of the PM oxidation potential (a.u./g) were significantly reduced. Electron paramagnetic resonance analysis combined with backward trajectory analysis and MODIS products showed that Asian dust storms can carry EPFRs over long distances. Correlation analysis showed that the atmospheric concentrations of EPFRs were positively correlated with elemental carbon (EC) for the Zhangbei and Jinan samples but were not significantly correlated with EC for the Erenhot samples, indicating that combustion may be an important source of EPFRs for the Zhangbei and Jinan samples. In contrast, the EPFRs in the Erenhot samples were more affected by dust/sand. The EPFR concentration levels showed a significant positive correlation with the oxidation potentials for the Erenhot and Zhangbei samples and showed negative correlations for the Jinan samples, suggesting that the EPFRs in the Erenhot and Zhangbei samples may provide an important contribution to the oxidative stress in PM2.5. In contrast, the oxidation potential for the Jinan samples was mainly caused by substances other than EPFRs. This study presents a basic understanding of the potential health effects of Asian dust storms, and this information can be used to assess the health risks of Asian dust storms in future studies.


Assessing Sus scrofa diversity among continental United States, and Pacific islands populations using molecular markers from a gene banks collection.
Human migration and trade facilitated domesticated livestock movement, gene flow and development of diverse populations upon which agriculture is based. In addition, varying USA ecological conditions has led to a diverse set of livestock populations to utilize. Quantifying genetic diversity of these populations is incomplete. This paper quantifies genetic diversity captured by the National Animal Germplasm Program and explores genetic structure and differences among 19 pig populations (feral populations from Pacific islands, continental US, and Chinese breeds) using 70,231 SNP from 500 animal samples. Among continental US breeds Fis was consistently low suggesting genetic variability is sufficiently available for breeders to use. A unique population structure using principal component analysis illustrated clear distinctions between Duroc, Yorkshire, Hampshire, breeds of Chinese origin, and feral Pacific Island populations were identified. Five Y chromosome haplotypes were evaluated and demonstrated migration patterns from European, central Asia, and potentially Polynesian waves of gene flow. Quantifying diversity and potential origin of Pacific populations provides insight for future uses, and the need for preservation. Viewing gene bank holdings in context of diversity measures we found a lack of inbreeding within breeds, suggesting the collection represents a wide sampling of individual breeds.


Ultrahigh-Loading Manganese-Based Electrodes for Aqueous Batteries via Polymorph Tuning.
Manganese-based aqueous batteries utilizing Mn2+ /MnO2 redox reactions are promising choices for grid-scale energy storage due to their high theoretical specific capacity, high power capability, low-cost, and intrinsic safety with water-based electrolytes. However, the application of such systems is hindered by the insulating nature of deposited MnO2 , resulting in low normalized areal loading (0.005-0.05 mAh cm-2 ) during the charge/discharge cycle. In this work, the electrochemical performance of various MnO2 polymorphs in Mn2+ /MnO2 redox reactions is investigated, and ɛ-MnO2 with low conductivity is determined to be the primary electrochemically deposited phase in normal acidic aqueous electrolyte. It is found that increasing the temperature can change the deposited phase from ɛ-MnO2 with low conductivity to γ-MnO2 with two order of magnitude increase in conductivity. It is demonstrated that the highly conductive γ-MnO2 can be effectively exploited for ultrahigh areal loading electrode, and a normalized areal loading of 33 mAh cm-2 is achieved. At a mild temperature of 50 °C, cells are cycled with an ultrahigh areal loading of 20 mAh cm-2 (1-2 orders of magnitude higher than previous studies) for over 200 cycles with only 13% capacity loss.


Characterization of rat and human steroid sulfatases.
Rat and human steroid sulfatases were purified from liver and placenta, respectively, by the same procedure. The rat and human enzymes were solubilized with Triton X-100, and purified by immunoaffinity chromatography with a monoclonal antibody showing high binding activities to both the enzymes. They were further purified by high-pressure anion-exchange chromatography to compare their structural and catalytic properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that both enzymes had a molecular weight of 62,000. The enzymes had similar amino acid compositions and amino-terminal amino acid sequences. Significant differences of the optimum pH, Michaelis constant and maximum velocity were observed between these enzymes. The optimum pH of each enzyme varied from 6.0 to 8.0, depending on substrates and with or without Triton X-100. In detergent-free media, steroid sulfates competitively inhibited the ability of these enzymes to hydrolyze 4-nitrophenyl sulfate. In media containing Triton X-100, on the other hand, the inhibition types of the steroid sulfates on the hydrolyzing activities of the rat and human enzymes were noncompetitive- and mixed-types, respectively.


Immuno-enzymatic detection of fibronectin in normal and pathological haematopoietic tissue.
Cryostat sections of bone marrow biopsies were stained immuno-enzymatically for fibronectin using the alkaline phosphatase: anti-alkaline phosphatase (APAAP) technique. In normal marrow fibronectin was present only in megakaryocytes and the walls of blood vessels. In contrast, myelofibrotic bone marrow possessed an extensive distribution of fibronectin which did not correspond to the distribution of reticulin. Infiltrated and hypercellular marrows showed an increase in fibronectin which appeared to be related to increased marrow vascularity. Again no correlation with the reticulin pattern was evident. In contrast to platelets, other circulating blood cells had no demonstrable fibronectin. This study suggests that fibronectin does not act as a mediator of haemopoiesis in vivo as has been suggested by the results of experiments in non-human models.


Prognostic significance of heart rate turbulence following ventricular premature beats in patients with idiopathic dilated cardiomyopathy.
Heart Rate Turbulence in Dilated Cardiomyopathy. The aim of this study was to investigate the prognostic significance of heart rate turbulence (HRT) characterized by HRT onset and slope after ventricular premature beats in patients with idiopathic dilated cardiomyopathy (IDC). Blinded HRT analysis was performed in 242 patients with IDC who were enrolled in the Marburg Cardiomyopathy database between 1992 and 2000. During 41 +/- 23 months of follow-up, 54 patients (22%) died or underwent heart transplant. On Cox univariate regression analysis, abnormal HRT onset, HRT slope, HRT onset combined with HRT slope, left ventricular (LV) ejection fraction, LV size, and New York Heart Association (NYHA) functional class III showed a significant association with total mortality or the need for heart transplant. On multivariate analysis, abnormal HRT onset identified patients without transplant-free survival, as did LV size and NYHA class III heart failure. Major arrhythmic events were observed in 42 patients (17%) during follow-up. On univariate analysis, abnormal HRT onset, HRT onset combined with HRT slope, male sex, NYHA class III, LV ejection fraction, and LV size were associated with a higher incidence of major arrhythmic events. On multivariate analysis, only LV ejection fraction remained as a significant arrhythmia risk predictor, with a relative risk of 2.2 per 10% decrease in ejection fraction (95% confidence interval 1.5-3.2). In this selected patient population with IDC, HRT onset is a significant predictor of transplant-free survival, as are LV size and NYHA class. For arrhythmia risk stratification, however, only LV ejection fraction remained a significant risk predictor on multivariate analysis.


Sulfonamide metformin derivatives induce mitochondrial-associated apoptosis and cell cycle arrest in breast cancer cells.
Metformin, an oral anti-diabetic drug, has attracted scientific attention due to its anti-cancer effects. This biguanide exerts preventive effects against cancer, and interferes with cancer-promoting signaling pathways at the cellular level. However, the direct cytotoxic or anti-proliferative effect of the drug is observed at very high concentrations, often exceeding 5-10 mM. This paper presents the synthesis of eight novel sulfonamide-based biguanides with improved cellular uptake in two breast cancer cell lines (MCF-7 and MDA-MB-231), and evaluates their effects on cancer cell growth. The synthesized sulfonamide-based analogues of metformin (1-5) were efficiently taken up in MCF-7 and MDA-MB-231 cells, and were characterized by stronger cytotoxic properties than those of metformin. Generally, compounds were more effective in MCF-7 than in MDA-MB-231. Compound 2, with an n-octyl chain, was the most active molecule with IC50 = 114.0 μmol/L in MCF-7 cells. The cytotoxicity of compound 2 partially results from its ability to induce early and late apoptosis. Increased intracellular reactive oxygen species (ROS) production and reduced mitochondrial membrane potential suggest that compound 2 promotes mitochondrial dysfunction and activates the mitochondrial-associated apoptosis-signaling pathway. In addition, compound 2 was also found to arrest cell cycle in the G0/G1 and G2/M phase and significantly inhibit cancer cell migration. In conclusion, this study supports the hypothesis that improved transporter-mediated cellular uptake of potential drug molecule is accompanied by its increased cytotoxicity. Therefore, compound 2 is a very good example of how chemical modification of a biguanide scaffold can affect its biological properties and improve anti-neoplastic potential.


Characteristics and trends of spontaneous reporting of therapeutic ineffectiveness in South Korea from 2000 to 2016.
Therapeutic ineffectiveness involves drug-related therapeutic failure, inefficacy or resistance and has not been sufficiently studied. Objective of our study was to evaluate reporting trends in therapeutic ineffectiveness by year and describe factors affecting therapeutic ineffectiveness using the Korea Adverse Event Reporting System. Proportion of therapeutic ineffectiveness reports was based on total submitted reports between 2000 and 2016. Utilizing 2016 alone, we compared the characteristics of therapeutic ineffectiveness with age group and gender matching by random extraction. We conducted a logistic regression analysis to estimate reporting odds ratios (ROR) and its 95% confidence intervals (CI) for reports by type of reporters, e.g., doctors, pharmacists, or consumers. We presented most frequent reports by the anatomical main groups and therapeutic subgroups according to the Anatomical Therapeutic Chemical (ATC) classification system. For the 17-years, the proportion of therapeutic ineffectiveness adverse drug reactions reporting ranged from 0.0% to 3.7% between 2000 and 2016. Of 228,939 reports, 2,797 (1.2%) were submitted in 2016. Consumers accounted for 6.92% of reports and doctors accounted for 45.49%, in which, consumers were more likely to report therapeutic ineffectiveness than doctors (adjusted ROR 3.98; 95% CI, 2.92 to 5.41). According to the ATC classification system, "nervous system" was the most frequently reported anatomical group (18.7%) and "parathyroid hormones and analogues" was reported most frequently in the pharmacological subgroup (23.7%). Teriparatide, a drug used to treat osteoporosis, had the most reports (11.0%). Therapeutic ineffectiveness reports may be used as a scientific tool for the reevaluation of respective drugs in order to confirm of its therapeutic effects.


Molecular Cytogenetic and Y Copy Number Analysis of a Reciprocal ECAY-ECA13 Translocation in a Stallion with Complete Meiotic Arrest.
We present a detailed molecular cytogenetic analysis of a reciprocal translocation between horse (ECA) chromosomes Y and 13 in a Friesian stallion with complete meiotic arrest and azoospermia. We use dual-color fluorescence in situ hybridization with select ECAY and ECA13 markers and show that the translocation breakpoint in ECAY is in the multicopy region and in ECA13, at the centromere. One resulting derivative chromosome, Y;13p, comprises of ECAY heterochromatin (ETSTY7 array), a small single copy and partial Y multicopy region, and ECA13p. Another derivative chromosome 13q;Y comprises of ECA13q and most of the single copy ECAY, the pseudoautosomal region and a small part of the Y multicopy region. A copy number (CN) analysis of select ECAY multicopy genes shows that the Friesian stallion has significantly (p < 0.05) reduced CNs of TSPY, ETSTY1, and ETSTY5, suggesting that the translocation may not be completely balanced, and genetic material is lost. We discuss likely meiotic behavior of abnormal chromosomes and theorize about the possible effect of the aberration on Y regulation and the progression of meiosis. The study adds a unique case to equine clinical cytogenetics and contributes to understanding the role of the Y chromosome in male meiosis.


Effect of albendazole on the metacestodes of Taenia saginata in calves.
Albendazole, a benzimadazole-carbamate anthelmintic, has been shown to effectively cause destruction of the metacestodes of Taenia saginata in calves.


Yes. No. Maybe. That's about as firm as the guidance gets over launching a provider-sponsored health plan. Strategy roundtable.
Few participants in our roundtable on provider-sponsored health plans see them the same way. Some are gearing up new products, others are scaling back or getting out. Yet they agreed on one thing: The financial risks are tremendous.


Language impairment in motor neurone disease.
Evidence from recent neuropsychological studies of patients with motor neurone disease (MND) has demonstrated that some patients have cognitive impairment. This challenges traditional teaching that MND is a disease with only motor symptoms. Language processing in MND patients has so far not been studied in any depth, but has only been touched upon as a part of general cognition. This study has assessed nine MND subjects on a range of standardised language assessments and compared their performance to that of nine control subjects. Although this is a small experimental sample of subjects, the results of this study indicate that language impairment is present in some patients with MND. The deficits are subtle and only exposed on formal testing. It is not possible to define the nature of the language impairment from this restricted set of data, but there was evidence of some deficits in a sub-group of MND patients on tasks involving naming, auditory comprehension of complex sentences, some semantic tests and spelling. The implications of these findings are discussed in relationship to the clinical management of patients with MND.


Pretreatment characteristics of waste oak wood by ammonia percolation.
A log of waste oak wood collected from a Korean mushroom farm has been tested for ammonia percolation pretreatment. The waste log has different physical characteristics from that of virgin oak wood. The density of the waste wood was 30% lower than that of virgin oak wood. However, there is little difference in the chemical compositions between the woods. Due to the difference in physical characteristics, the optimal pretreatment conditions were also quite different. While for waste oak the optimum temperature was determined to be 130 degrees C, for virgin oak wood the optimum pretreatment was only achieved at 170 degrees C. Presoaking for 12 h with ammonia solution before pretreatment was helpful to increase the delignification efficiency.


Validation and Clinical Utility of a Prediction Model for the Risk of Upstaging to Invasive Breast Cancer After a Biopsy Diagnosis Ductal Carcinoma In Situ.
This study aimed to validate the DCIS-upstage model, a previously developed model to predict the risk of upstaging to invasive breast cancer in patients with biopsy-proven ductal carcinoma in situ (DCIS) in a more recent cohort and to assess the model's clinical utility. The model was validated in a registry cohort (n = 2269) and in an institution cohort (n = 302). A calibration plot was made, followed by a decision curve analysis (DCA). The model's area under the curve (AUC) was compared with the AUC of another published model and with the AUCs of new models using the risk factors of the DCIS-upstage model and additional risk factors. The DCIS-upstage model had an AUC of 0.67 at development; in the validation, the AUC was 0.65 in the registry cohort and 0.73 in the institution cohort. The DCA showed that the model has clinical utility. The other published model had an AUC of 0.66 in the institution cohort. Adding risk factors to the DCIS-upstage model slightly increased the AUC. The DCIS-upstage prediction model is valid in other cohorts. The model has clinical utility and may be used to select patients with biopsy-proven DCIS for sentinel lymph node biopsy.


Let Their Voices Be Seen.
The mutual distrust, in part caused by misunderstanding and bias, between sickle cell disease (SCD) patients and their emergency department (ED) providers has been widely documented in the SCD literature. This study seeks to illustrate the perceptions and experiences of adult sickle cell patients who have had at least 1 ED experience in the last 2 years. Qsource, a nonprofit health care consultancy based in Tennessee, used photovoice, a qualitative research method, to facilitate the representation of patients' experiences in living with SCD. Photovoice has participants document their experiences through photography and then, as a group, discuss and analyze the emotional state behind the photographs. Eight participants with SCD took 25 photographs during 4 weeks. Then, in a 2-hour critical dialogue, participants identified recurring themes through consensus. Participants identified 6 themes that emerged from their discussion: unpredictability of SCD, fickleness of time, coping with pain, proximity to death, avoidance of the ED, and need for improved communication. They expressed their wish to be active participants in their care, and many described a fear of death, which is exacerbated by a lack of control in the ED setting. Factors such as poor patient experience and misunderstanding may contribute to delays in seeking care for SCD patients. This may, in turn, escalate pain crises and increase the likelihood of hospital admission. We believe that photovoice may be a new means to educate ED providers on SCD patient perceptions, ultimately resulting in better ED care.


Is self-assessment of skin type a valid method for adolescents?
Self-assessed sun sensitivity (skin type) according to Fitzpatrick's classification has been reported to have drawbacks. Data from a cross-sectional study of tanning habits in Stockholm, Sweden, showed an underestimation of sun sensitivity among adolescents. Cautionary advice regarding sun and sun bed exposure, and sunscreen use versus skin type may have to be revised.


Diagnostic utility of touch imprint cytology for intraoperative assessment of surgical margins and sentinel lymph nodes in oral squamous cell carcinoma patients using four different cytological stains.
OSCC is most commonly associated with positive surgical margins. The important cause of loco regional recurrence is histologically positive or closed margins. Clear surgical margins might favor the patient with a better prognosis and prevent repetitive surgeries. The present study was designed to the diagnostic utility of touch imprint (TI) smears using H and E, Pap, Giemsa and Feulgen stains, so that they can be used on a routine basis. A total of 720 smears from 130 margins resected from 32 patients who underwent surgical resection of OSCC were prospectively evaluated. The slides were fixed in alcohol and randomly divided into four different batches for staining with H&E, rapid Pap, Giemsa, Feulgen stain. TI of 30 sentinel lymph node were fixed in 95% alcohol, stained by (H&E) and evaluated by two independent observers. The results were compared with gold standard histopathology. H&E stain showed sensitivity 44%, rapid Pap 35%, Giemsa 29% and Feulgen stain 25%. Positive predictive value-100% for all the four stains. NPV-H&E 70%, Pap 66%, Giemsa 62%, Feulgen 59%. Diagnostic test accuracy of H&E stained smears was higher 72%, compared to Pap 67%. Giemsa 65%, and Feulgen 63%. In lymph nodes, Specificity was 94.74%, PPV 90.91%, NPV 94.74%, diagnostic accuracy 93.33%. TIC is effective in identifying an inadequate or severe dysplasia margin comparable to gold standard histopathology. It might be used to intraoperatively identify metastases in sentinel lymph nodes in clinically N0 Patients.


Groin infections following vascular surgery: obturator bypass (BYP) versus "biologic coverage" (TRP)--a comparative analysis.
Deep infections in the groin complicating vascular surgical procedures pose a serious problem, in the treatment of which two alternative methods are available: (1) Removal of the graft and the construction of an extra anatomic bypass (obturator canal bypass, BYP), or (2) retaining the graft and achieving healing of the infected wound by various biological materials, such as omentum or an inferior rectus abdominis muscle flap (TRP). The probability of patient and limb survival was estimated by the Kaplan-Meier method and possible differences between both groups checked using Breslow's and Mantel's tests. No statistically significant differences were found and a variety of factors with potential influence on the outcome were considered equally balanced. However, as soon as the catastrophic event of infection plus haemorrhage enforced emergency surgery, the incidence of success differed markedly: in the BYP group 6 infections healed out of 8 and in the TRP group 1 out of 6.


Crossed ectopic testis: a case report and review of the literature.
Crossed or transverse ectopic testis is a rare anomaly of testicular descent. It has been noted that fewer than 100 cases have been reported in the world literature. In this paper, we report a new case found in a 6-month-old infant operated on in West Africa for an obstructed right inguinoscrotal hernia.


Visfatin Exerts Immunotherapeutic Effects in Lipopolysaccharide-Induced Acute Lung Injury in Murine Model.
Visfatin acts as a significant regulator of inflammatory cytokines. However, the immunological response and therapeutic effects of visfatin under bacterial stress in murine lung tissue are still not clear. To investigate the role of visfatin on lipopolysaccharide (LPS)-induced acute lung injury (ALI), thirty Kunming mice were divided into Saline, LPS, and LPS + visfatin groups. After routine blood examination, the effects of visfatin on inflammatory cytokines, lung tissue structure, and expression of inflammatory mediators were explored through hematoxylin-eosin (H&E), Masson and immunohistochemical staining, quantitative polymerase chain reaction (Q-PCR), and Western blotting. Compared with the Saline group, neutrophil percentage, peripheral blood neutrophil count, and the ratio of lymphocyte count (NLR) were upregulated in LPS group. Moreover, Masson staining showed alterations in lung tissue structure; the mRNA level of different cytokines (IL-6, IL-1β, TNF-α, IL-10, TLR4, IFN-γ) was upregulated; and the protein expression of interleukin (IL)-6, myeloperoxidase (MPO), and transforming growth factor-β1 (TGF-β) was significantly (p < 0.05) different in LPS group. Compared with LPS group, neutrophil percentage significantly decreased (p < 0.01), the numbers of lymphocytes significantly (p < 0.05) increased, NLR decreased, Masson staining of the lung was extremely different (p < 0.01), the structure of the lung was slightly damaged, and the myeloperoxidase values of lung showed no differences in LPS + visfatin. Hence, visfatin inhibits the lung inflammation induced by ALI. During the ALI, visfatin acts by decreasing NLR, downregulated the expression of MPO, enhanced antioxidant capacity, and regulated the inflammatory factors IL-1β, IL-6, IL-10, and TNF-α to reduce the lung injury.


Small vessel disease and collaterals in ischemic stroke patients treated with thrombectomy.
To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS). Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals' adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0-2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores. A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52-0.89] and aOR 0.66; 95%CI [0.5-0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20-0.79]). Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals.


Hypoxic-ischemic brain injury induces an acute microglial reaction in perinatal rats.
Activated microglia may contribute to the progression of neuronal injury after a wide range of CNS insults. In this study, we used two complementary methods to evaluate acute changes in the morphology and regional distribution of microglia induced by a focal hypoxic-ischemic insult in 7-d-old (P7) rats. To elicit injury, P7 rats underwent right carotid ligation followed by 3 h of 8% O2 exposure; rats were killed 10 min to 5 d later (n > or = 3/group). A histochemical assay using Griffonia simplicifolia B4-isolectin enabled detection of both resting and activated microglia in tissue sections; vascular cells were also reactive. Activated microglia were also identified immunocytochemically using a macrophage-specific MAb, ED-1. In normal P7-12 brain, lectin, and ED-1 immunoreactive-activated microglia were concentrated in white matter; lectin-positive resting, ramified microglia were also detected throughout the gray and white matter. Subtle morphologic evidence of microglial activation was noted 10 min posthypoxia-ischemia in the lesioned right cerebral hemisphere; activated microglia began to accumulate within the next 4 h. Accumulation of lectin-positive activated microglia peaked at 2-4 d posthypoxia-ischemia. ED-1 immunoreactive-microglia were first noted 4 h after hypoxic-ischemic injury in the lesioned right hemisphere, and there was a corresponding increase in accumulation over the first 48 h posthypoxia-ischemia. In the left hemisphere, contralateral to the ligation, no increase in activated microglia were detected with either method. In brain sections where no neuronal injury was evident, activated microglia did not accumulate. These data demonstrate that perinatal hypoxic-ischemic brain injury induced rapid accumulation of activated microglia in hypoxic-ischemic forebrain.


Cognitive processing therapy versus supportive counseling for acute stress disorder following assault: a randomized pilot trial.
The study tested the efficacy and tolerability of cognitive processing therapy (CPT) for survivors of assault with acute stress disorder. Participants (N=30) were randomly allocated to CPT or supportive counseling. Therapy comprised six individual weekly sessions of 90-min duration. Independent diagnostic assessment for PTSD was conducted at posttreatment. Participants completed self-report measures of posttraumatic stress, depression, and negative trauma-related beliefs at pre-, posttreatment, and 6-month follow-up. Results indicated that both interventions were successful in reducing symptoms at posttreatment with no statistical difference between the two; within and between-group effect sizes and the proportion of participants not meeting PTSD criteria was greater in CPT. Treatment gains were maintained for both groups at 6-month follow-up.


Ultrastructure of a model basement membrane lacking type IV collagen.
Basement membranes (BMs) are specialized extracellular matrices which have important roles in cell attachment, migration, growth, and differentiation. The major components of these matrices include type IV collagen, laminin, entactin, and heparan sulfate proteoglycan. The framework or scaffold of BMs has been proposed to be type IV collagen (Yurchenco et al., 1986, J. Histochem. Cytochem., 34:93-102). However, a murine teratocarcinoma cell-line, M1536-B3, has been described which produces an extracellular matrix (ECM) composed of some of the known components of BM, e.g., laminin, entactin, and sulfated proteoglycan, but lacking type IV collagen (Chung et al., 1979, Cell, 16:277-287). With the use of morphological techniques, we have found that the ECM assembled by these cells is composed of multiple layers of electron-dense cords arranged in an interweaving meshwork with short 2-4 nm-diameter cylindrical rods embedded throughout. This organization closely resembles that reported for naturally occurring BMs, e.g., Reichert's membrane (Inoué et al., 1983, J. Cell Biol., 97: 1524-1537). The previous identification of known in vivo BM components in M1536-B3 ECM and the correspondence in morphological appearance of M1536-B3 ECM with that present in naturally occurring BMs suggests that a BM-type of ECM can be assembled without a type IV collagen framework, thus indicating that other components of BMs have a critical role in BM organization and assembly.


Apical TLR ligation of intestinal epithelial cells drives a Th1-polarized regulatory or inflammatory type effector response in vitro.
Intestinal epithelial cells (IEC) separate the mucosal immune system from the external milieu. Under inflammatory conditions, Toll-like receptor (TLR) expression by IEC is increased. In a transwell co-culture model immune modulation by IEC upon TLR ligation was studied. Human IEC (HT-29 and T84) grown on filters were apically or basolaterally exposed to TLR4 or TLR9 ligands and co-cultured with CD3/CD28-activated healthy donor PBMC in the basolateral compartment. TLR4 ligation of IEC (HT-29) enhanced the production of TNF-α and IEC-derived MDC and decreased numbers of Foxp3(+) regulatory T cells. Neutralization of TSLP abrogated TLR4-induced TNF-α secretion. In contrast, apical TLR9 ligation of IEC (HT-29 and T84) enhanced IFN-γ and IL-10 secretion and increased the number of activated T(h)1 cells. The increase in IFN-γ secretion depended on the presence of IEC. Furthermore, CD14 expression on monocytes was reduced coinciding with enhanced intracellular IL-10 and decreased TNF-α production. However, basolateral TLR9 ligand exposure of HT-29 cells resulted in enhanced IFN-γ, IL-6 and TNF-α, while IL-10 secretion remained unaltered. TLR4 and TLR9 ligands reduced IL-13 secretion in presence and absence of apically exposed IEC and enhanced IL-12 secretion in presence of IEC. These data suggest that TLR4 ligation of IEC drives an inflammatory, while apical TLR9 ligation drives a regulatory T(h)1 effector immune response in vitro in a polarized manner. IEC may be important modulators of the mucosal effector immune response.


Impact of STZ-induced hyperglycemia and insulin-induced hypoglycemia in plasma amino acids and cortical synaptosomal neurotransmitters.
In this work, we evaluated the effects of streptozotocin (STZ)-induced hyperglycemia and an acute episode of insulin-induced hypoglycemia in plasma amino acids and cortical neurotransmitters. For that purpose, we used citrate (vehicle)-treated Wistar rats, STZ-treated rats [i.p., 50 mg/kg body weight], and STZ-treated rats injected with insulin [s.c., dose adjusted with blood glucose levels] 1 h prior to sacrifice to induce an acute episode of hypoglycemia. Plasma was collected for determination of amino acids levels. In addition, cortical synaptosomal preparations were obtained and the total levels of neurotransmitters, levels of aspartate, glutamate, taurine, and GABA released by the action of KCl, iodoacetic acid (IAA), ouabain, and veratridine, membrane potential and ATP levels were evaluated. Compared with control rats, plasma from hypoglycemic rats presented increased levels of aspartate, glutamate, glutamine, and taurine whereas GABA levels were decreased in STZ and hypoglycemic rats. Similarly, glutamate and taurine levels were increased in hypoglycemic synaptosomes while GABA decreased in hypoglycemic and STZ-diabetic synaptosomes. The depolarizing agent KCl promoted an increase in aspartate, glutamate, and taurine release from hypoglycemic synaptosomes. The highest release of neurotransmitters occurred in the presence of veratridine and ouabain, two other depolarizing agents, in all groups of experimental animals. However, a higher release of glutamate was observed in the diabetic and hypoglycemic synaptosomes. No alterations were observed in synaptosomal membrane potential and ATP levels. These results show that in the presence of a metabolic insult a higher release of excitatory amino acids occurs, which may underlay the neuronal injury observed in type 1 diabetic patients under insulin therapy.


The evolution of loan volume and non-performing loans under COVID-19 innovations: The Colombian case.
Financial institutions' scale of total and non-performing loans are important figures signaling economic activity and its risk level. COVID-19 created an external shock with overarching effects on the global economy, impacting the credit activity and debtors' ability to repay their obligations. We study how Colombia's loans and non-performing loans market ratios could react to an external shock (absent of any relief measures) by developing a vector autoregressive model with exogenous variables (VARX) with the Central Bank intervention rate as an exogenous variable. We use impulse response functions to simulate the impact of the COVID-19 pandemic on the market of loans and default levels in Colombia. Our results show that the effects remain significant over long periods.


The prevalence of high blood pressure and its determinants among Tunisian adolescents.
Hypertension can originate in childhood and remain undetected unless special screening is performed. The burden of hypertension in adolescents in Tunisia is unknown. The aim of this study was to investigate the prevalence of blood pressure (BP) within the hypertension range and its association with other risk factors among Tunisian adolescents. A cross-sectional study that included 1385 secondary school students in Sousse, Tunisia, was performed during 2017-2018. A two-stage cluster sampling strategy was used to obtain a representative sample of the study population. BP within the hypertension range (HBP)was classified following the European guideline recommendations for measuring BP in children and adolescents. Anthropometric indices were measured using a standard protocol. A structured questionnaire collected information about sociodemographic characteristics, lifestyle, mental health status, and addictions. Adjusted logistic regression models were used to assess hypertension-related risk factors. Our study included 39.5% boys and 60.5% girls. The mean age of our population was 17 ± 1.5 years. The prevalence of HBP was 15.4% (13.1-18.0%), and it was significantly higher in boys (22.8%) than in girls (10.6%, p value < 0.001). In the multivariate logistic regression model, overweight [OR = 1.72(1.18-2.51)] and obesity [OR = 3.73(2.55-5.41)] were independent risk factors for HBPrange, (p value < 0.001), whereas female sex [OR = 0.41(0.29-0.56), p value < 0.001] and depression [OR = 0.67(0.51-0.88), p value = 0.008] were independent protective factors. Among Tunisian secondary school adolescents, the prevalence of HBP was high and associated with excess body weight. A comprehensive strategy for the prevention of hypertension and its risk factors among youth is urgently needed.


Predictors of functional disability with focus on activities of daily living: A community based follow-up study in older adults in India.
Disability in activities of daily living is a growing concern among older populations all over the world. India has one of the rapidly ageing populations and predicted burden of functional disability is higher for Indian older adults as compared to other ageing Asian countries. Total 1140 aged 60 years and over participated in a baseline study. 560 of them participated in the prospective cohort study conducted in the city of Pune, India. An interview and functional assessment using a questionnaire and Pune-FAAT tool was carried out in 2013-14. Binary logistic regression was used to obtain the factors that increased the odds of having ADL disability at follow-up. The mean age of the study population was 69.73±5.48years. Squatting, walking and climbing functions were affected significantly. Total 376 participants (67.1%) reported difficulties and/or disability in performing activities of daily living (ADL) at follow-up. Hospitalization (OR=3.6; 95% CI: 1.9-6.7), being female (OR=2.3; 95% CI: 1.5-3.5), presence of two or more chronic diseases (OR=1.7; 95% CI: 1.1-2.7), experience of memory loss (OR=1.9; 95% CI: 1.2-3.0) and feeling of loneliness (OR=2.3; 95% CI: 1.0-5.3) increased the odds of being in the "With disability" group at follow-up. Apart from this, self-rated health and self-reported depression were associated with limitations in ADL. Hospitalization and being female appeared to be the most significant risk factors for disability in urban older adults in India. Rehabilitation services after hospitalization, physical exercise, effective control on chronic illness, and social participation to reduce loneliness is recommended.


Photoinduced Multiple Effects to Enhance Uranium Extraction from Natural Seawater by Black Phosphorus Nanosheets.
Based on the photoinduced photothermal, photoelectric, and photocatalytic effects of black phosphorus (BP) nanosheets, a BP-PAO fiber with enhanced uranium extraction capacity and high antibiofouling activity is fabricated by compositing BP nanosheets into polyacrylamidoxime (PAO). The photothermal effect increases the coordination interaction between UO2 2+ and the functional amidoxime group, and the photoelectric effect produces the surface positive electric field that exhibits electrostatic attraction to the negative [UO2 (CO3 )3 ]4- , which all increase the capacity for uranium adsorption. The photocatalytic effect endows the adsorbent with high antibiofouling activity by producing biotoxic reactive oxygen species. Owing to these three photoinduced effects, the photoinduced BP-PAO fiber shows a high uranium adsorption capacity of 11.76 mg g-1 , which is 1.50 times of the PAO fiber, in bacteria-containing natural seawater.


K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111), the inhibitor of CHI3L1, has the inhibitory effect on memory impairment in Αβ infusion mouse model and on LPS-induced neuroinflammation in the murine BV-2 microglia and primary cultured astrocyte. In the present study, we investigated the inhibitory effect of K284-6111 on memory dysfunction and neuroinflammation in Tg2576 transgenic mice, and a more detailed correlation of CHI3L1 and AD. To investigate the effects of K284-6111 on memory dysfunction, we administered K284-6111 (3 mg/kg, p.o.) daily for 4 weeks to Tg2576 mice, followed by behavioral tests of water maze test, probe test, and passive avoidance test. Administration of K284-6111 alleviated memory impairment in Tg2576 mice and had the effect of reducing the accumulation of Aβ and neuroinflammatory responses in the mouse brain. K284-6111 treatment also selectively inactivated ERK and NF-κB pathways, which were activated when CHI3L1 was overexpressed, in the mouse brain and in BV-2 cells. Web-based gene network analysis and our results of gene expression level in BV-2 cells showed that CHI3L1 is closely correlated with PTX3. Our result revealed that knockdown of PTX3 has an inhibitory effect on the production of inflammatory proteins and cytokines, and on the phosphorylation of ERK and IκBα. These results suggest that K284-6111 could improve memory dysfunction by alleviating neuroinflammation through inhibiting CHI3L1 enhancing ERK-dependent PTX3 pathway.


Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth.
Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hippel-Lindau tumour suppressor gene and clear cell subtype RCC. We examined the overexpression of several growth factor receptors immunohistochemically and analyzed their relationship to the cytomorphological characters in 120 cases of RCCs. These receptors included c-met proto-oncogene product (c-MET), epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor II (TGFbetaR). The overexpression of c-MET was detected in all cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of chromophilic cell subtype, resulting in a very significant associations between c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EGFR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpression of TGFbetaR (P<0.0001). These results strongly suggest a close correlation between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely related to the pathogenesis of the clear cell subtype of RCC with compact growth pattern. The overexpression of c-MET, EGFR, and TGFbetaR may have roles that are individually significant in the morphogenesis of RCC.


Thyroid carcinoma in children and adolescents-systematic review of the literature.
Thyroid cancer in children and adolescents is usually a major concern for physicians, patients, and parents. Controversies regarding the aggressiveness of the clinical presentation and the ideal therapeutic approach remain among the scientific community. The current recommendations and staging systems are based on data generated by studies in adults, and this might lead to overtreating in some cases as well as undertreating in others. Understanding the differences in the biology, clinical course, and outcomes in this population is crucial for therapeutic decisions. This paper evaluates the biology, clinical presentation, recurrences, and overall survival as well as the staging systems in children and adolescents with differentiated thyroid cancer.


Factors driving the change of household CO2 emissions through 2040 in China: based on decomposition and scenario analyses.
With China's economic transformation into a consumption-driven model, household CO2 emissions (HCEs) become an increasingly essential part of China's CO2 emissions. However, how will the HCEs change in urban and rural areas and what are the driving forces of HCEs through 2040 are not clear. In this paper, we project nation-level HCEs up to 2040 by the scenario analysis, and analyze the drivers of HCEs during 1997-2040 by the decomposition analysis. We find that the HCEs kept a persistent growth during 1997-2017 as energy intensity reduction and energy structure optimization cannot offset the rapid growth of consumption and population. During 2017-2040, in the current policy scenario, the rural HCEs will decrease, while the peaking of the total HCEs and urban HCEs would not be achieved. In the sustainable development scenario, the total HCEs, urban HCEs and rural HCEs will peak before 2030 and afterward decrease, because the energy intensity will induce a 51% and 76% reduction in the total HCEs and urban HCEs, respectively. Moreover, the decrease in the share of coal consumption due to the development of non-fossil fuels and natural gas will cause a more than 25% reduction in HCEs in the sustainable development scenario.


Getting a line on CVAD. Central vascular access devices.
Covering all types of central lines, these practical guidelines explain how you can protect your patients from complications--and protect yourself from malpractice accusations.


Facile Synthesis of CeO₂-LaFeO₃ Perovskite Composite and Its Application for 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) Degradation.
A facile and environmentally friendly surface-ion adsorption method using CeCO₃OH@C as template was demonstrated to synthesize CeO₂-LaFeO₃ perovskite composite material. The obtained composite was characterized by X-ray diffraction (XRD), fourier transform infrared spectra (FT-IR), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), thermo-gravimetric analysis and differential scanning calorimetry (TG-DSC), N₂ adsorption/desorption isotherms and X-ray photoelectron spectra (XPS) measurements. The catalytic degradation of nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was tested to evaluate catalytic activity of the CeO₂-LaFeO₃ composite. Much better activity was observed for the CeO₂-LaFeO₃ composite comparing with CeO₂ and LaFeO₃. These results suggested that perovskite composite materials are a promising candidate for the degradation of tobacco-specific nitrosamines (TSNAs).


Spatial navigation: Alzheimer's pathology disrupts movement-based navigation.
All animals use two different strategies to navigate: idiothetic or movement-based navigation, and allothetic or landmark-based navigation. A new study reveals that compromised idiothetic navigation underlies disrupted grid cell coding in an early stage Alzheimer's disease mouse model.


A water-infusion system with two reservoirs at different levels.
To provide a continuous supply of fluid during arthroscopic surgery, we suggest an infusion system with 2 reservoirs placed at different heights. The lower bag serves as a water reservoir, which allows more time for the circulating nurse to complete the task of exchanging the emptied water bag.


Discrepancies between fluorescein angiography and optical coherence tomography in macular edema in uveitis.
To assess the frequency and characteristics of discrepant findings between fluorescein angiography (FA) and optical coherence tomography (OCT) in uveitic macular edema (ME). Retrospective cross-sectional study of 112 eyes of 78 patients with uveitic ME on FA, OCT, or both. ME was graded on OCT and FA of uveitis patients attending the University Medical Center Utrecht. The frequency and severity of discrepant findings were analyzed, and the clinical findings at the time of imaging were assessed. The imaging studies were compared with the clinical characteristics. Positive results of both imaging methods (FA+/OCT+) were observed in 61 (54%) of 112 eyes, whereas discrepant results occurred in 51 (46%) of 112 eyes. The FA+/OCT- discrepancy occurred in 34 (30%) of 112 eyes, and the FA-/OCT+ discrepancy occurred in 17 (15%) of 112 eyes. No correlations between the discrepant imaging results and age, gender, duration of uveitis or ME, visual acuity, or cause of uveitis were identified. FA+/OCT- and FA-/OCT+ discrepancies comprised typically mild degrees of ME. The FA+/OCT- discrepancy occurred in 50% of eyes with birdshot chorioretinopathy (7/14), and the FA-/OCT+ discrepancy occurred more often in intermediate uveitis than in other anatomic locations. Although the FA+/OCT+ consistency was noted frequently in active uveitis, the FA-/OCT+ discrepancy was common in eyes with inactive uveitis (8/18; 44% of inactive eyes). Our results emphasize that FA and OCT are complementary investigations, each revealing different aspects of the pathophysiology of uveitic ME.


Parity and endometrial cancer risk: a meta-analysis of epidemiological studies.
The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case-control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65-0.74; I(2) = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64-0.84, I(2) = 88.3%; RR = 0.62, 95% CI 0.53-0.74, I(2) = 92.1%; and RR = 0.68, 95% CI 0.65-0.70, I(2) = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings.


Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer.
Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor response. Adding ipilimumab 10 mg/kg to paclitaxel (PTX) and carboplatin (CBDCA) in a phased schedule improved progression-free survival in a phase II non-small-cell lung cancer (NSCLC) study. This dose-escalating, phase I study was designed to identify the recommended dose of ipilimumab (3 or 10 mg/kg) by evaluating dose-limiting toxicity (DLT; Cycles 3 and 4) in phased combination with PTX (175 mg/m(2)) and CBDCA (area under the curve = 6) in Japanese patients with advanced NSCLC. Treatment was administered intravenously every 3 weeks initially, followed by some eligible patients receiving maintenance ipilimumab once every 12 weeks. Additional endpoints included safety, tumor response, pharmacokinetics, and immunogenicity. Fifteen patients were enrolled and 12 received ipilimumab (n = 6, 3 mg/kg; n = 6, 10 mg/kg) in combination with PTX and CBDCA. DLTs occurred in 2 patients (ipilimumab 3 mg/kg) and 1 patient (ipilimumab 10 mg/kg). The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, leukopenia, and neutropenia. The most common immune-related AEs affected the skin, gastrointestinal, and nervous system. The safety profile was similar in both cohorts. Three patients in each cohort achieved a partial response. The pharmacokinetic (PK) profile of ipilimumab in Japanese patients was similar to that observed in previous studies in non-Japanese patients. Conclusions The recommended dose of ipilimumab in phased combination with PTX and CBDCA in Japanese patients with NSCLC was identified as 10 mg/kg. The safety profile was consistent with the previously defined AE profile.


'Split and splayed C3'-traumatic lateral C2-3 dislocation without neurological deficits: unique case and its management.
Traumatic C2-3 dislocation has been often described in the antero-posterior plane but is extremely rare in the lateral plane. Such dislocations have been described in thoraco-lumbar and C1-2. The need to study the imaging in multiple planes has been highlighted to plan proper realignment. A young male presented with neck pain alone following a train accident. The imaging showed a fracture of C3 splaying it. The C2-3 showed lateral dislocation in the lateral plane with locked C2-3 facets on one side and C3-4 facets on the other. Through the posterior approach, the dislocation was corrected by manipulating (distraction and rotation) the lateral mass screws and rods. Curvilinear rods helped to maintain realignment after reduction. Residual lateral rotation was corrected by subsequent anterior approach. Compression, distraction and lateral force possibly resulted in such fracture dislocation. Using the technique, the fracture fragments could be realigned perfectly and the reduction was maintained. The saddle shape of the sub-axial cervical spine prevents such lateral dislocations. It is imperative to study the radiology in multiple planes to assess the 'multiplanar dislocation'. Correction is possible with proper planning and manipulation of facets and bodies using the available instrumentation. Though not obtained in this case, a preoperative MRI and a CT angiogram are important in surgery planning.


[Thygeson's superficial punctate keratitis (author's transl)].
Thygeson's keratitis is characterized by a coarse punctate epithelial keratitis with almost no hyperaemia of the conjunctiva. It is a bilateral disease with frequent recurrences. The prognosis is good.


Do Vestibular Physiotherapy and a Clinical Pathway in the Emergency Department Improve Management of Vertigo?
Determine the effects of a vertigo/dizziness emergency department (ED) clinical pathway incorporating vestibular physiotherapy on quality and efficiency of care. A multisite retrospective study investigated differences between cohorts before and after a vertigo clinical pathway and cohorts who did and did not receive vestibular physiotherapy assessment. Adults presenting to 2 Australian EDs with symptoms clinically consistent with vestibular disorder were captured via ED diagnostic code screening and subsequent medical record review. Medical record audits obtained quality of care indicators: diagnosis, HINTS (head impulse-nystagmus-test of skew), and vestibular physiotherapy management. Linked hospital administrative data sets provided efficiency measures: time from ED presentation to assessments, hospital admission rates, and ED and total hospital length of stay. Postpathway cohorts (n = 329) showed greater use of HINTS (by 27%; 95% CI, 21%-33%), more frequent vestibular physiotherapy assessment (by 27%; 95% CI, 20%-33%), reduced wait time to assessment (25.0 to 4.6 hours; 95% CI, -27.1 to -14.1), and reduced ED length of stay (3.9 to 3.2 hours; 95% CI, -0.3 to -1.0) as compared with prepathway cohorts (n = 214). When compared with those not receiving vestibular physiotherapy assessment, patients assessed by a vestibular physiotherapist (n = 150) received a specific diagnosis more frequently (65% vs 34%; 95% CI, 22%-40%) but were admitted more often (79% vs 49%; 95% CI, 22%-38%) with longer total hospital length of stay (13.0 vs 5.0 hours; 95% CI, 6.1-10.6). An ED vertigo clinical pathway was associated with improved quality and efficiency of care, including reduced ED time. Vestibular physiotherapist assessment was associated with greater diagnostic specificity but higher hospital admissions.