Highly efficient and stable tandem luminescent solar concentrators based on carbon dots and CuInSe2-xSx/ZnS quantum dots.
Semi-transparent large-area luminescent solar concentrators (LSCs) have been considered an essential part of zero-energy or low-energy consuming buildings in the future. Inorganic colloidal quantum dots (QDs) are promising candidates for LSCs due to the advantages of a tunable bandgap, engineered large Stokes shift, and relatively high photoluminescence (PL) quantum yield. However, LSCs that are fabricated using colloidal quantum dots exhibited an inferior stability under long-term illumination, demanding great efforts to explore the highly stable LSCs. Herein, we fabricated large-area (∼100 cm2) tandem LSCs based on highly stable carbon dots (CDs) and highly luminescent near-infrared emitting CuInSe2-xSx/ZnS (CuInSeS/ZnS) QDs. Coupled with a Si diode as a reference, the power conversion efficiency of the corresponding tandem (dimensions: 10 × 10 × 0.5 cm3) and single LSCs (dimensions: 10 × 10 × 0.3 cm3) based on CuInSeS/ZnS QDs under one sun illumination are 0.46% and 0.5%, respectively. For single CuInSeS/ZnS QD based LSCs at a low concentration (0.039 wt%), external and internal quantum efficiencies reach up to 2.87% and 36.37%, respectively. After UV illumination for 8 h, bottom LSCs based on CuInSeS/ZnS QDs retain 93.22% of the initial PL emission, which is higher than that of LSCs (∼80%) without the CD protection. The highly efficient and stable tandem LSCs employing green CDs and NIR CuInSeS/ZnS QDs as PL emitters pave the way for the realization of large area building-integrated photovoltaic (BIPV) devices.


Prevention of mechanical stretch-induced endothelial and smooth muscle cell injury in experimental vein grafts.
Vein grafts are subject to increased tensile stress due to exposure to arterial blood pressure, which has been hypothesized to induce endothelial cell (EC) and smooth muscle cell (SMC) injury. This study was designed to verify this hypothesis and to develop a tissue engineering approach that can be used to prevent these pathological events. Two experimental models were created in rats to achieve these goals: (1) a nonengineered vein graft with increased tensile stress, which was created by grafting a jugular vein into the abdominal aorta using a conventional end-to-end anastomotic technique; and (2) an engineered vein graft with reduced tensile stress, which was created by restricting a vein graft into a cylindrical sheath constructed using a polytetrafluoroethylene membrane. The integrity of ECs in these models was examined by using a silver nitrate staining method, and the integrity of SMCs was assessed by using a fluorescein phalloidin-labeling technique. It was found that nonengineered vein grafts were associated with early EC denudation with a change in EC coverage from 100 percent in normal jugular veins to 36 +/- 10, 28 +/- 12, 18 +/- 9, 44 +/- 15, 80 +/- 13, and 97 +/- 6 percent at 1 and 6 hours and 1, 5, 10, and 30 days, respectively. Similarly, rapid SMC actin filament degradation was found during the early period with a change in SMC coverage from approximately 94 percent in normal jugular veins to 80 +/- 10, 41 +/- 17, 25 +/- 9, 51 +/- 15, 79 +/- 15, 98 +/- 2 percent at 1 and 6 hours and 1, 5, 10, and 30 days, respectively, in nonengineered vein grafts. In engineered vein grafts with reduced tensile stress, EC denudation and SMC actin filament degradation were prevented significantly. These results suggested that mechanical stretch due to increased tensile stress contributed to EC and SMC injury in experimental vein grafts, and these pathological events could be partially prevented when tensile stress was reduced by using a biomechanical engineering approach.


Chronic post-traumatic headache in pediatrics.
Both primary headaches and minor head injuries are common in children. If headache presents for the first time or becomes exacerbated soon after head injury it is described as post-traumatic headache (PTH). Acute PTH resolves within 3 months from injury, but chronic PTH continues beyond 3 months. The pathogenesis of PTH is not well understood. Several mechanisms were proposed such as axonal injuries and disturbances of cerebral metabolic processes. The clinical features of PTH are those of primary headache disorders such as migraine and tension-type headache and usually follow a favorable prognosis. Investigations and management should therefore be relevant to the type of headache and focused on clinical needs of the child.


[Regulatory influence of hippocampus CA1 and CA3 areas on bulbar respiratory neurons under hypoxia].
We studied the influence of stimulation of the CA1 and CA3 areas of the hippocampus on the impulse activity of respiratory neurons (RN) of the medulla oblongata under normal and oxygen deficiency conditions. Under conditions of normal atmospheric pressure, the electrical stimulation of the CA1 and CA3 areas of the hippocampus had mainly an inhibiting influence. In the initial phase, at a 4-5-thousand meter altitude, activation of frequent discharge of neurons occurred. In this situation, stimulation of the CA1 and CA3 areas was more accentuated than under conditions of normoxia. In the second phase (an altitude of 7.5-8 thousand meters), on the reduction of the impulse activity of neurons, stimulation of the CA1 and CA3 areas of the hippocampus induced untypical responses of these neurons.


Experimental validation of the solar aureole technique for determining aerosol size distributions.
This paper describes the inversion procedures by including multiple scattering contributions to almucantar radiance in the solar aureole region and discusses the retrieved size distribution results by comparing them with ground truth measurements. The agreement between the two sets of results is good and provides yet another experimental validation to show that the solar aureole technique is a simple, practical, and accurate method for obtaining the columnar size distribution of atmospheric aerosols. Comparisons between the results obtained by the two approximations--single and multiple scattering--show that the size distribution retrievals obtained by the latter are more accurate than those obtained by the former. Retrieved estimates of surface albedo show that even though surface albedo cannot be accurately determined from solar aureole measurements, these measurements can provide reasonable estimates. A recommendation is made for the use of solar aureole measurements from satellites to retrieve the size distribution and concentration of stratospheric and upper tropospheric aerosols.


Alternate exon in the 5'-untranslated region of the human ACTH receptor gene.
The human ACTH receptor (ACTH-R) gene consists of two exons; the first encodes the 5'-untranslated region (UTR) and the second encodes part of the 5'-UTR, the entire coding region, and the whole of the 3'-UTR. While investigating the transcription initiation site of the human ACTH-R gene by 5'-rapid amplification of cDNA ends, we found a 157-bp alternate exon in the 5'-UTR. This newly identified exon was irrelevant to the alternate exon in the mouse ACTH-R gene which we reported previously.


Pharmacogenomics in a community pharmacy: ACT now.
To highlight the opportunity for community pharmacists to provide pharmacogenomic testing and counseling. Peer-reviewed pharmacy literature. Pharmacists practicing in community pharmacy are accustomed to optimizing drug therapy through various medication therapy management programs. They use patient-specific information obtained from the patient and their prescribers to cater patient-specific drug regimens. Pharmacogenomics is rapidly evolving, and this field can help optimize medication therapy using an individual's genetic code to identify opportunities for increased or decreased adverse effects or changes in efficacy. Pharmacogenomic testing technology has made conducting pharmacogenomic testing in community pharmacies possible. Pharmacists must arm themselves with the knowledge and skills specific to pharmacogenomics in order to fully integrate this expanding area into patient care and turn this into a great opportunity. Advances in knowledge and technology regarding pharmacogenomics coupled with the overwhelming access and use of a community pharmacist by patients provides a tremendous opportunity for community pharmacists to lay claim to the field of pharmacogenomics. Pharmacists are able and needed to provide testing, evaluate results, and offer patient and prescriber education for pharmacogenomics. Pharmacists must take steps to assess the entire clinical picture and use pharmacogenomics where appropriate to optimize drug therapy.


Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana.
Nucleosomes package eukaryotic DNA and are composed of four different histone proteins, designated H3, H4, H2A, and H2B. Histone H3 has two main variants, H3.1 and H3.3, which show different genomic localization patterns in animals. We profiled H3.1 and H3.3 variants in the genome of the plant Arabidopsis thaliana and found that the localization of these variants shows broad similarity in plants and animals, along with some unique features. H3.1 was enriched in silent areas of the genome, including regions containing the repressive chromatin modifications H3 lysine 27 methylation, H3 lysine 9 methylation, and DNA methylation. In contrast, H3.3 was enriched in actively transcribed genes, especially peaking at the 3' end of genes, and correlated with histone modifications associated with gene activation, such as histone H3 lysine 4 methylation and H2B ubiquitylation, as well as RNA Pol II occupancy. Surprisingly, both H3.1 and H3.3 were enriched on defined origins of replication, as was overall nucleosome density, suggesting a novel characteristic of plant origins. Our results are broadly consistent with the hypothesis that H3.1 acts as the canonical histone that is incorporated during DNA replication, whereas H3.3 acts as the replacement histone that can be incorporated outside of S-phase during chromatin-disrupting processes like transcription.


Self-similarity properties of alpha-crystallin supramolecular aggregates.
The supramolecular aggregation of alpha-crystallin, the major protein of the eye lens, was investigated by means of static and dynamic light scattering. The aggregation was induced by generating heat-modified alpha-crystallin forms and by stabilizing the clusters with calcium ions. The kinetic pattern of the aggregation and the structural features of the clusters can be described according to the reaction limited cluster-cluster aggregation theory previously adopted for the study of colloidal particles aggregation systems. Accordingly, the average mass and the hydrodynamic radius of alpha-crystallin supramolecular aggregates grow exponentially in time. The structure factor of the clusters is typical of fractal aggregates. A fractal dimension df approximately 2.15 was determined, indicating a low probability of sticking together of the primitive aggregating particles. As a consequence, the slow-forming clusters assemble a rather compact structure. The basic units forming the fractal aggregates were found to have a radius about twice (approximately 17 nm) that of the native protein and 5.3 times its size, which is consistent with an intermediate molecular assembly corresponding to the already known high molecular weight forms of alpha-crystallin.


ERP time course of perceptual and post-perceptual mechanisms of spatial selection.
Event-related potentials (ERPs) were recorded from volunteers performing a task requiring simple judgements about the spatial location of a single target that could appear with equal probability to the left or right of fixation. A robust finding in the ERP literature is a dichotomy between attentional selection for spatial and non-spatial features. Visual spatial selection is manifest as a modulation of early components (P1, N1) that reveal exogenous processes, while non-spatial selection is revealed by the presence of longer latency endogenous components (N2). We present an analysis of several conditions that require different degrees of visual analysis to confirm the location of the single target, and show that spatial selection can be manifest at early (N1) or later (N2) stages. Observers identified the location of targets that were more salient (2D line drawings with abrupt onset) or less salient (2D line drawings without abrupt onset or 3D objects embedded in random-dot stereograms). We examined differences in amplitude, latency, and topography of early ERP components (P1, N1, P2, N2), and compared responses measured over the left and right hemispheres in response to left and right targets. The results support the hypothesis that the processes involved in spatial selection can be manifest at early or late stages, dependent on the quality of the incoming data. Moreover, the iterative process by which the percept is established benefits from a change in the visual input that is specific to the target.


Cost-effectiveness of strategies for diagnosing pulmonary embolism among emergency department patients presenting with undifferentiated symptoms.
Symptoms associated with pulmonary embolism can be nonspecific and similar to many competing diagnoses, leading to excessive costly testing and treatment, as well as missed diagnoses. Objective studies are essential for diagnosis. This study evaluates the cost-effectiveness of different diagnostic strategies in an emergency department (ED) for patients presenting with undifferentiated symptoms suggestive of pulmonary embolism. Using a probabilistic decision model, we evaluated the incremental costs and effectiveness (quality-adjusted life-years gained) of 60 testing strategies for 5 patient pretest categories (distinguished by Wells score [high, moderate, or low] and whether deep venous thrombosis is clinically suspected). We performed deterministic and probabilistic sensitivity analyses. In the base case, for all patient pretest categories, the most cost-effective diagnostic strategy is to use an initial enzyme-linked immunosorbent assay D-dimer test, followed by compression ultrasonography of the lower extremities if the D-dimer is above a specified cutoff. The level of the preferred cutoff varies with the Wells pretest category and whether a deep venous thrombosis is clinically suspected. D-dimer cutoffs higher than the current recommended cutoff were often preferred for patients with even moderate and high Wells categories. Compression ultrasonography accuracy had to decrease below commonly cited levels in the literature before it was not part of a preferred strategy. When pulmonary embolism is suspected in the ED, use of an enzyme-linked immunosorbent assay D-dimer assay, often at cutoffs higher than those currently in use (for patients in whom deep venous thrombosis is not clinically suspected), followed by compression ultrasonography as appropriate, can reduce costs and improve outcomes.


Effect of educational intervention on adoption of new endodontic technology by general dental practitioners: a questionnaire survey.
To survey the clinical endodontic protocols of general dental practitioners (GDPs) in public dental clinics and to assess the effect of an educational intervention on the adoption of a nickel-titanium (Ni-Ti) rotary system. General dental practitioners in a Swedish Intervention County (IC), underwent an educational programme in endodontics. A follow-up questionnaire was posted to 98 GDPs in the IC and to 97 GDPs in a Control County (CC), where no specific training had been provided. The questionnaire concerned demographics, clinical endodontic protocols and instrumentation techniques. The response rate to the questionnaire was 87%. More than 90% of all GDPs reported they always or generally used rubber dam, determined working length, used the canal irrigant 0.5% buffered NaOCl and calcium hydroxide as an interappointment dressing. Two of three GDPs reported, they generally or always informed the patient of the prognosis. Every second GDP reported routines for postoperative recall and follow-up. The Ni-Ti rotary technique was reported to be completely adopted by 77% of the GDPs in the IC, significantly higher than in the CC (6%), P < 0.001. In the IC 79% of the GDPs reported they completed instrumentation in one treatment session, compared with only 32% in the CC, P < 0.001. The 'single-cone' mode of canal filling was reported to be significantly more frequent amongst GDPs in the IC, P < 0.001. General dental practitioners in both counties reported using contemporary clinical endodontic protocols. GDPs who had undergone an educational programme in Ni-Ti rotary instrumentation reported they had successfully integrated the technique into daily clinical practice.


Injection profiles in liquid chromatography. I. A fundamental investigation.
This is a fundamental experimental and theoretical investigation on how the injection profile depends on important experimental parameters. The experiments revealed that the injection profile becomes more eroded with increased (i) flow rate, (ii) viscosity of the eluent, (iii) size of the solute, (iv) injection volume and (v) inner diameter of the injection loop capillary. These observations cannot be explained by a 1D-convection-diffusion equation, since it does not account for the effect of the parabolic flow and the radial diffusion on the elution profile. Therefore, the 1D model was expanded into a 2D-convection-diffusion equation with cylindrical coordinates, a model that showed a good agreement with the experimental injection profiles dependence on the experimental parameters. For a deeper understanding of the appearance of the injection profile the 2D model is excellent, but to account for injection profiles of various injection volumes and flow rates in preparative and process-chromatography using computer-optimizations, a more pragmatic approach must be developed. The result will give guidelines about how to reduce the extra-column variance caused by the injection profile. This is important both for preparative and analytical chromatography; in particular for modern analytical systems using short and narrow columns.


Normalization of glucose intolerance in first-degree relatives of patients with type 2 diabetes.
The aim of this study was to estimate the conversion rate to normal glucose tolerance (NGT) from a state of abnormal glucose metabolism and to identify characteristics predicting the conversion rate in first-degree relatives (FDRs) of patients with type 2 diabetes with glucose intolerance. A total of 2368 (614 men and 1754 women) FDRs of consecutive patients with type 2 diabetes aged 20-70 years in 2003-2005 were followed through 2007. Glucose tolerance classification was based on the criteria of the American Diabetes Association base on standard 75 g 2-h oral glucose tolerance test. The study group consisted of 370 participants with glucose intolerance at baseline. The conversion rates to normal glucose tolerance from impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were 16.2% (95% confidence interval (CI) 13.30, 19.10) and 10.9% (95% CI: 5.7, 16.1) per year after an average of 2 years, respectively. Lower baseline fasting plasma glucose (HR 1.02, 95% CI: 1.01, 1.04) and 2-h (HR 1.02, 95% CI: 1.01, 1.04) glucose predicted conversion to NGT, as did changes in body mass index (BMI), waist circumference (WC), and lipids. This is the first estimate of conversion rate and predictors from IFG and IGT to NGT in FDRs of people with type 2 diabetes in Iran. Lower baseline fasting, 2-h plasma glucose and changes in BMI, WC, and lipids predicted reversal to NGT at 24 months follow-up.


Antibody response to low-molecular-weight antigens of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis.
Sera from patients with allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma and normal sera were analyzed for specific antibodies by Western (immuno-) blotting with Aspergillus fumigatus antigens transferred electrophoretically onto polyvinylidene difluoride membranes. Western blot analysis demonstrated consistent reactivity of low-molecular-weight A. fumigatus antigens against ABPA sera but not against uncomplicated aspergilloma or normal sera. None of these low-molecular-weight components had any lectin-binding activity. Sera from patients with aspergilloma, however, frequently reacted with high-molecular-weight components of A. fumigatus. The majority of these high-molecular-weight antigenic components demonstrated concanavalin A-binding activity. The low-molecular-weight bands were discernible in Western blots with sera from all ABPA patients irrespective of disease activities, such as relapse, flare, or treatment. Antibodies detected by methods such as immunodiffusion or enzyme-linked immunosorbent assays demonstrated total antibody responses to most or all antigenic components, while Western blots demonstrated the reactivities of the individual components with the specific antibodies. Western blot analysis thus provided more information for immunodiagnosis of ABPA than other methods, especially when only crude antigens were available.


[Social and healthy circumstances of women's decision about applying hormonal replacement therapy].
The aim of the study was to evaluate the frequency of hormonal replacement therapy (HRT) application among Polish women aged 40-65, patients of five selected health care institutions located in south-eastern Poland and to determine the most significant factors that influence women's decision to initiate HRT. The next purpose was to establish how the women learned about the possibility of receiving HRT. Women, who never decided to take sex hormones, were asked about the reasons of such decision. The study comprised a group of 1033 women aged 40-65 years living in south-eastern Poland, the patients of various hospital wards and outpatient clinics. The study was conducted from January 2003 to December 2004 using categorized interview technique. The interview questionnaire was constructed by the authors. The statistical analysis was performed on the basis of the chi2 test of independence; log-linear analysis and Pareto's analysis were also used. Research result analysis proves that 30.5% of the examined women have used HRT currently or in the past. The sociodemographic and healthy variables that showed positive correlation with receiving hormonal treatment by midlife women were: age 51-65 years, the presence of climacteric ailments, the absence of monthly bleedings, possessing of permanent life partner and good self-estimation of one's financial status. It was not revealed that better educated women more frequently decide to take HRT. The main sources of women's knowledge about HRT were the mass media and health service employees. Among the reasons for not taking up hormonal treatment the most significant were: lack or small intensification of menopausal ailments as well as the fear of side effects of hormonal replacement therapy.


Human 18 S ribosomal RNA sequence inferred from DNA sequence. Variations in 18 S sequences and secondary modification patterns between vertebrates.
We have determined the DNA sequences encoding 18 S ribosomal RNA in man and in the frog, Xenopus borealis. We have also corrected the Xenopus laevis 18 S sequence: an A residue follows G-684 in the sequence. These and other available data provide a number of representative examples of variation in primary structure and secondary modification of 18 S ribosomal RNA between different groups of vertebrates. First, Xenopus laevis and Xenopus borealis 18 S ribosomal genes differ from each other by only two base substitutions, and we have found no evidence of intraspecies heterogeneity within the 18 S ribosomal DNA of Xenopus (in contrast to the Xenopus transcribed spacers). Second, the human 18 S sequence differs from that of Xenopus by approx. 6.5%. About 4% of the differences are single base changes; the remainder comprise insertions in the human sequence and other changes affecting several nucleotides. Most of these more extensive changes are clustered in a relatively short region between nucleotides 190 and 280 in the human sequence. Third, the human 18 S sequence differs from non-primate mammalian sequences by only about 1%. Fourth, nearly all of the 47 methyl groups in mammalian 18 S ribosomal RNA can be located in the sequence. The methyl group distribution corresponds closely to that in Xenopus, but there are several extra methyl groups in mammalian 18 S ribosomal RNA. Finally, minor revisions are made to the estimated numbers of pseudouridines in human and Xenopus 18 S ribosomal RNA.


Association between diagnostic criteria for severe acute malnutrition and hospital mortality in children aged 6-59 months in the eastern Democratic Republic of Congo: the Lwiro cohort study.
Few studies have assessed the relationship between weight-for-height (WHZ) and mid-upper arm circumference (MUAC) with hospital mortality considering confounders. The particularity of MUAC for age (MUACZ) is less documented. This study aims to investigate this relationship in a region endemic for severe acute malnutrition (SAM). This is a retrospective cohort based on a database of children admitted from 1987 to 2008 in South Kivu, eastern DRC. Our outcome was hospital mortality. To estimate the strength of the association between mortality and nutritional indices, the relative risk (RR) with its 95% confidence interval (95% CI) was calculated. In addition to univariate analyses, we constructed multivariate models from binomial regression. A total of 9,969 children aged 6 to 59 months were selected with a median age of 23 months. 40.9% had SAM (according to the criteria WHZ < -3 and/or MUAC<115 mm and/or the presence of nutritional edema) including 30.2% with nutritional edema and 35.2% had both SAM and chronic malnutrition. The overall hospital mortality was 8.0% and was higher at the beginning of data collection (17.9% in 1987). In univariate analyses, children with a WHZ < -3 had a risk almost 3 times higher of dying than children without SAM. WHZ was more associated with in-hospital mortality than MUAC or MUACZ. Multivariate models confirmed the univariate results. The risk of death was also increased by the presence of edema. In our study, WHZ was the indicator more associated with hospital death compared with MUAC or MUACZ. As such, we recommend that all criteria shall continue to be used for admission to therapeutic SAM programs. Efforts should be encouraged to find simple tools allowing the community to accurately measure WHZ and MUACZ.


Viable cervical pregnancy managed with systemic Methotrexate, uterine artery embolization, and local tamponade with inflated Foley catheter balloon.
We present an unusual case of a primigravida with a viable cervical pregnancy diagnosed by transvaginal ultrasound and magnetic resonance imaging. Staggered conservative therapeutic measures included systemic high-dose Methotrexate with Folinic acid rescue followed by bilateral embolization of the uterine arteries in response to active cervical bleeding despite declining serum beta-human chorionic gonadotropin levels. Continued active cervical bleeding responded to local tamponade with an inflated Foley catheter balloon positioned within the cervical canal. Conservative treatment was successful, with complete resolution of the cervical pregnancy, resumption of normal menstrual cycles, and a normal transvaginal ultrasonographic appearance of the cervical canal, documented 8 weeks after the initial diagnosis. This case and review of the literature support that various staggered conservative hemostatic measures may be used at various points in which bleeding may occur in the conservative management algorithm of cervical pregnancy.


Transfer across the human gut of environmental technetium in lobsters (Homarus gammarus L.) from the Irish Sea.
Few data are available on the uptake by the human gut of the element technetium. Of current radiological interest in connection with discharges of technetium-99 in liquid discharges from BNFL, Sellafield, is uptake from European lobsters (Homarus gammarus), whose edible parts are known to concentrate technetium. In this study, a group of eight adult volunteers (six males and two females) ate samples of edible flesh from lobsters caught off the west Cumbrian coast and provided 24 h samples of urine and faeces for analysis. Detection of uptake from the gut by difference between intake and faecal measurements proved insensitive, suggesting a low value of the gut transfer factor (f1 value) of up to 0.1 with a maximum (two standard deviations) level of about 0.3. In urine, technetium was detectable at a relatively low level compared with the intakes, consistent with a low absorption across the gut. Values for f1 were derived with the aid of literature data for excretion following intravenous administration of technetium-95 m as pertechnetate, and gave averaged data for f1 in the range 0.046 to 0.23. These results are in broad conformity with those derived from the faecal measurements, and suggest a lower value than the 0.5 used by ICRP.


Refining neural network predictions for helical transmembrane proteins by dynamic programming.
For transmembrane proteins experimental determination of three-dimensional structure is problematic. However, membrane proteins have important impact for molecular biology in general, and for drug design in particular. Thus, prediction method are needed. Here we introduce a method that started from the output of the profile-based neural network system PHDhtm (Rost, et al. 1995). Instead of choosing the neural network output unit with maximal value as prediction, we implemented a dynamic programming-like refinement procedure that aimed at producing the best model for all transmembrane helices compatible with the neural network output. The refined prediction was used successfully to predict transmembrane topology based on an empirical rule for the charge difference between extra- and intra-cytoplasmic regions (positive-inside rule). Preliminary results suggest that the refinement was clearly superior to the initial neural network system; and that the method predicted all transmembrane helices correctly for more proteins than a previously applied empirical filter. The resulting accuracy in predicting topology was better than 80%. Although a more thorough evaluation of the method on a larger data set will be required, the results compared favourably with alternative methods. The results reflected the strength of the refinement procedure which was the successful incorporation of global information: whereas the residue preferences output by the neural network were derived from stretches of 17 adjacent residues, the refinement procedure involved constraints on the level of the entire protein.


Pulmonary Surfactant: A Mighty Thin Film.
Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.


Customised spatiotemporal temperature gradients created by a liquid metal enabled vortex generator.
Generating customised temperature gradients in miniaturised flow-free liquid chambers is challenging due to the dominance of diffusion. Inducing internal flows in the form of vortices is an effective strategy for overcoming the limitations of diffusion in such environments. Vortices can be produced by applying pressure, temperature and electric potential gradients via miniaturised actuators. However, the difficulties associated with the fabrication, integration, maintenance and operation of such actuators hinder their utility. Here, we utilise liquid metal enabled pumps to induce vortices inside a miniaturised liquid chamber. The configuration and rotational velocity of these vortices can be controlled by tuning the polarity and frequency of the energising electrical signal. This allows creation of customised spatial temperature gradients inside the chamber. The absence of conventional moving elements in the pumps facilitates the rapid reconfiguration of vortices. This enables quick transition from one temperature profile to another, and creates customised spatiotemporal temperature gradients. This allows temperature oscillation from 35 to 62 °C at the hot spot, and from 25 to 27 °C at the centre of the vortex within 15 seconds. Our liquid metal enabled vortex generator can be fabricated, integrated and operated easily, and offers opportunities for studying thermo-responsive materials and biological samples.


CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.
4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.


Incidence of Clostridium difficile associated diarrhoea in a tertiary care hospital.
Rampant and injudicious use of broad spectrum antibiotics in hospitalized patients has increased the incidence of Clostridium difficile associated diarrhoea (CDAD). Though antibiotic use is the best known risk factor for CDAD, the occurrence of community acquired C. difficile suggests the presence of other risk factors too. However CDAD is still under-recognized in India and Asia. Therefore we undertook a prospective study to determine the incidence of Clostridium difficile associated diarrhoea in our hospital. 50 patients of antibiotic associated diarrhoea (AAD) and 50 age and sex matched controls were studied prospectively over a period of 1 year. Controls were patients on antibiotics who did not have diarrhoea. All other causes of diarrhoea were ruled out. Fresh stool samples were examined for the presence of C. difficile toxin A and B by the enzyme-linked immunofluorescence assay. 5 patients in the AAD group (10%) and 3 patients in the control group (6%) were positive for C. difficile toxin A and B. 5 (10%) patients in the control group showed equivocal results. Out of the 5 CDAD patients, 4 (80%) were males and 1 was a female (p = 2, not significant). 3 patients were from the MICU and 2 were from the medical wards. The median age of the patients was 39 years. Only 1 male patient was > 60 years old (p = 0.781, not significant). All 5 CDAD patients were on proton pump inhibitors (PPIs) and 2 had Ryle's tube inserted (p = 0.22, not significant). Only 2 patients had leucocytosis (p = 1.67, not significant) and none showed faecal leucocytosis. So out of 100 patients on antibiotics, 8 (8%) tested positive for C. difficile toxins in their stools. However, only 5 (5%) had diarrhoea (CDAD) whereas 3 (3%) were asymptomatic carriers. The incidence of CDAD in our hospital was 10% of the 50 patients with AAD. The asymptomatic carriage rate was 6%. All the cases had mild to moderate diarrhoea and were responsive to metronidazole unlike the west where the incidence is higher and the disease more severe.


Associations of tibia lead, DMSA-chelatable lead, and blood lead with measures of peripheral nervous system function in former organolead manufacturing workers.
The goals of the present study were to compare and contrast associations of blood lead, DMSA-chelatable lead, current tibia lead, and back-extrapolated "peak" tibia lead with four peripheral nervous system (PNS) sensory and motor function measures in older males with past exposure to organic and inorganic lead. Data were collected from former organolead manufacturing workers with an average of 16 years since last occupational lead exposure. Current tibia lead levels were measured by (109)Cd x-ray fluorescence. Sensory pressure thresholds (index and pinky fingers) and pinch and grip strength were measured with the Pressure-Specified Sensory Device (PSSD). In adjusted analyses, none of the four lead biomarkers was associated with sensory pressure threshold of the index finger or pinch or grip strength. In contrast, all four biomarkers were associated (P < or = 0.10) with pressure threshold of the pinky finger. The final linear regression models accounted for a small proportion of the variance in the sensory (1-3%) and motor measures (10-21%). This study found no strong association between lead biomarkers and selected PNS sensory or motor function measures among former organolead manufacturing workers with no recent occupational exposure to lead. Previously reported CNS findings in this cohort suggest that the PNS may be less sensitive to the chronic toxic effects of lead in this dose range among adults. It is also possible that the PNS has a greater capacity for repair than does the CNS, or that the PNS measures were less sensitive for detection of lead-related health outcomes than were the CNS measures.


Publication bias, statistical power and reporting practices in the Journal of Sports Sciences: potential barriers to replicability.
Two factors that decrease the replicability of studies in the scientific literature are publication bias and studies with underpowered desgins. One way to ensure that studies have adequate statistical power to detect the effect size of interest is by conducting a-priori power analyses. Yet, a previous editorial published in the Journal of Sports Sciences reported a median sample size of 19 and the scarce usage of a-priori power analyses. We meta-analysed 89 studies from the same journal to assess the presence and extent of publication bias, as well as the average statistical power, by conducting a z-curve analysis. In a larger sample of 174 studies, we also examined a) the usage, reporting practices and reproducibility of a-priori power analyses; and b) the prevalence of reporting practices of t-statistic or F-ratio, degrees of freedom, exact p-values, effect sizes and confidence intervals. Our results indicate that there was some indication of publication bias and the average observed power was low (53% for significant and non-significant findings and 61% for only significant findings). Finally, the usage and reporting practices of a-priori power analyses as well as statistical results including test statistics, effect sizes and confidence intervals were suboptimal.


CD95 (Fas) and CD95L (FasL)-mediated non-canonical signaling pathways.
Although the interaction of CD95L (also known as FasL) with its so-called death receptor CD95 (Fas) induces an apoptotic signal responsible for the elimination of infected and cancer cells and maintenance of tissue homeostasis, this receptor can also implement non apoptotic signaling pathways. This latter signaling is involved in metastatic dissemination in certain cancers and the severity of auto-immune disorders. The signaling complexity of this pair is increased by the fact that CD95 expression itself seems to contribute to oncogenesis via a CD95L-independent manner and, that both ligand and receptor might interact with other partners modulating their pathophysiological functions. Finally, CD95L itself can trigger cell signaling in immune cells rendering complex the interpretation of mouse models in which CD95 or CD95L are knocked out. Herein, we discuss these non-canonical responses and their biological functions.


Changes in Segmental Impedances and Selected Body Composition Parameters Assessed by Multi-Frequency Bioimpedance Analysis after Fluid Consumption in Healthy Young Population.
Objectives: Body composition (BC) analysis is a routine part of comprehensive public health care. Assessment of BC is more important source of information than BMI. Adherence to the standard measurement conditions is essential for the correct results. Our study aimed to examine the effect of acute fluid consumption on measures of body mass (BM), percentage of body fat (%BF), visceral fat (VF), percentage of body water (%BW), and impedance at 100 kHz (I100) and 20 kHz (I20) using segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) in a general healthy population. Methods: 95 consecutive healthy normal-weight adults (42 men; 53 women) were involved in the study (mean ± s.d.; age 23.9±1.6 years; body mass 68.3±14.1 kg). All subjects underwent two separate series of body composition (BC) measurements at 0 (BASELINE), 30, 60, 90 min (POST): the first series after drinking 600 ml of isotonic carbohydrate/electrolyte drink (IST) and the second after no fluid administration (CON). Individual measurements were performed in the morning on two consecutive days. Results: In the IST group, BM, VF (both P<0.001), and %BF (P<0.05) increased significantly at 30 min POST compared to BASELINE. BM and VF remained elevated at 90 min POST (both P<0.001). %BW decreased significantly at 30 min POST (P<0.01) then increased at 60 min (P<0.001) and 90 min (P<0.01) POST. There were no significant changes in I100. I20 increased significantly at 30 min POST (P<0.001) then decreased at 60 min (P<0.001) and 90 min POST (P<0.01) compared to BASELINE. In the CON group, BM and VF decreased below BASELINE at 90 min POST (P<0.001), %BF, %BW and I100 did not change significantly. The difference between IST and CON was statistically significant for all POST measurement times only in BM and VF (both P<0.001). The VF results are also underlined by the detected impedance changes in the trunk area at 20 kHz (B20) and 100 kHz (B100) at 60 min and 90 min (both P<0.001). Conclusions: Our study suggests that segmental impedances and BC measurement in healthy young normal-weight adults requires strict adherence to fluid restriction at least 90 min before the measurement to avoid false impedance values and overestimation of BM and VF.


Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid.
Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.


Rabies trend in China (1990-2007) and post-exposure prophylaxis in the Guangdong province.
Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990-1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.


Texas H.B. 810: Increased Access to Stem Cell Interventions or an Increase in Unproven Treatments?
Born of the expectations and hype associated with regenerative medicine, there are now numerous clinics around the world selling stem cell-based interventions (SCBI) that have yet to be proven effective or safe, with little to no accounting of the outcomes being collected. In the United States, SCBI are overseen by the U.S. Food and Drug Administration (FDA), but several SCBI clinics have been pushing for policies to expand access and circumvent FDA oversight. Related to this effort, in 2017, Texas passed a bill, HB 810, which allows clinics to provide "investigational stem cell treatments to patients with certain severe chronic diseases or terminal illnesses." In this article, we describe how the new law relates to another deregulation movement, state and federal, the Right to Try laws, the content of HB 810, and the state legislators' intent in passing HB 810.


Effects of ethanol drinking on central nervous system functional activity of alcohol-preferring rats.
The [(14)C]-2-deoxyglucose (2-DG) technique was used to assess the rates of local cerebral glucose utilization (LCGU) in key limbic, cerebral cortical, hippocampal, basal ganglionic, and subcortical regions of alcohol-preferring (P) rats following chronic 24-h free-choice ethanol drinking. Adult male P rats were submitted to (1) 8 continuous weeks of two-bottle access to 15% ethanol and water (E-C group); (2) 8 weeks of identical two-bottle access followed by 2 weeks of ethanol deprivation (E-D group); (3) cycles of 2 weeks of two-bottle ethanol access and 2 weeks of deprivation, repeated for four cycles (E-RD group); or (4) water only treatment [ethanol-naive group (E-N group)]. A single pulse of [(14)C]-2-DG (125 microCi/kg) was administered via a venous catheter, and timed arterial blood samples were collected over 45 min and later assayed for plasma glucose and [(14)C]-2-DG concentrations. Quantitative autoradiography was used to determine [(14)C] densities, and LCGU values were calculated. With the exception of a few small differences in the hippocampus, no significant differences were found in any of the central nervous system (CNS) regions examined among the four experimental groups of P rats. Animals in the E-D group had lower LCGU rates in the anterior hippocampal CA1 subregion than animals in the E-N, E-C, and E-RD groups. In the anterior hippocampal CA3 subregion and the anterior hippocampal dentate gyrus, the E-D group had significantly lower LCGU rates than the E-RD group. Overall, the results of this study indicate that 24-h ethanol-drinking experience has little effect on CNS functional neuronal activity in P rats.


Site Selectivity of Hydride in Early-Transition-Metal Ruddlesden-Popper Oxyhydrides.
Layered perovskite titanium oxyhydrides have been prepared by low-temperature topochemical CaH2 reduction from Ruddlesden-Popper Sr n+1Ti nO3 n+1 phases ( n = 1, 2) and structurally characterized by combined synchrotron X-ray and neutron diffraction data refinements. In the single-layered Sr2TiO3.91(2)D0.14(1) material, hydride anions are statistically disordered with oxides on the apical site only, as opposed to known transition-metal oxyhydrides exhibiting a preferred occupation of the equatorial site. This unprecedented site selectivity of H- has been reproduced by periodic DFT+ U calculations, emphasizing for the hydride defect a difference in formation energy of 0.24 eV between equatorial and apical sites. In terms of electronic structure, the model system Sr2TiO3.875H0.125 is found to be slightly metallic and the released electron remains mostly delocalized over several Ti atoms. On the other hand, hydride anions in the double-layered Sr3Ti2O6.20H0.12 material show a clear preference for the bridging apical site within the perovskite slabs, as confirmed by DFT calculations on the Sr3Ti2O6.875H0.125 model system. Finally, the influence of the B-site chemical nature on the hydride site selectivity for early 3d transition metals is theoretically explored in the single-layered system by substituting vanadium for titanium. The V3+ electronic polaron is suggested to play a role in stabilizing H- on the equatorial site in Sr2VO4- xH x for x = 0.125.


Chronic exposure to synthetic food colorant Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice.
Chemicals in food are widely used leading to significant human exposure. Allura Red AC (AR) is a highly common synthetic colorant; however, little is known about its impact on colitis. Here, we show chronic exposure of AR at a dose found in commonly consumed dietary products exacerbates experimental models of colitis in mice. While intermittent exposure is more akin to a typical human exposure, intermittent exposure to AR in mice for 12 weeks, does not influence susceptibility to colitis. However, exposure to AR during early life primes mice to heightened susceptibility to colitis. In addition, chronic exposure to AR induces mild colitis, which is associated with elevated colonic serotonin (5-hydroxytryptamine; 5-HT) levels and impairment of the epithelial barrier function via myosin light chain kinase (MLCK). Importantly, chronic exposure to AR does not influence colitis susceptibility in mice lacking tryptophan hydroxylase 1 (TPH1), the rate limiting enzyme for 5-HT biosynthesis. Cecal transfer of the perturbed gut microbiota by AR exposure worsens colitis severity in the recipient germ-free (GF) mice. Furthermore, chronic AR exposure elevates colonic 5-HT levels in naïve GF mice. Though it remains unknown whether AR has similar effects in humans, our study reveals that chronic long-term exposure to a common synthetic colorant promotes experimental colitis via colonic 5-HT in gut microbiota-dependent and -independent pathway in mice.


Laparoscopic management of impalpable undescended testes: 20 years' experience.
Laparoscopy is the best available method to manage impalpable undescended testes. We performed our first laparoscopic orchiopexy in June 1992 and found good results in consecutive cases with laparoscopic orchiopexy over last 20 years. From June 1992 to May 2012, 241 patients with 296 impalpable testes were operated upon by laparoscopic approach. One-stage laparoscopic orchiopexy was performed in 152 cases, while two-stage Fowler - Stephens laparoscopic orchiopexy was performed in 55 cases. Laparoscopic orchiectomy was required in 20, and in 21 patients testes were absent. One-sided laparoscopic orchiopexy was performed in a male pseudo hermaphrodite. None of the testis atrophied after two-stage Fowler - Stephens laparoscopic orchiopexy, while in 152 cases of single-stage orchiopexies one testes atrophied. One patient developed malignant change in the testis, 6 years after orchiopexy. Laparoscopy is the best way to diagnose impalpable undescended testes. No other imaging investigation was required. Single-stage laparoscopic orchiopexy for low level undescended testis has very good results. For high-level undescended testis and when one-stage mobilisation is difficult, two-stage Fowler - Stephens orchiopexy has excellent results. Minimum 4 months should separate first and second stage of laparoscopic Fowler - Stephens procedure. Even when open orchiopexy is being done for intra-canalicular testes in a child, it is advisable to be ready with laparoscopy if necessary, at the same time, in case open surgery fails to mobilise the testicular vessels adequately.


The Community Integration Questionnaire - Revised: Australian normative data and measurement of electronic social networking.
Consideration of the relationship between meaningful participation, health and wellbeing underpins occupational therapy intervention, and drives measurement of community integration following acquired brain injury (ABI). However, utility of community integration measures has been limited to date by lack of normative data against which to compare outcomes, and none examine the growing use of electronic social networking (ESN) for social participation. This research had four aims: (i) develop and pilot items assessing ESN to add to the Community Integration Questionnaire, producing the Community Integration Questionnaire-Revised (CIQ-R); (ii) examine factor structure of the CIQ-R; (iii) collect Australian CIQ-R normative data; and (iv) assess test-retest reliability of the revised measure. Australia. A convenience sample of adults without ABI (N = 124) was used to develop and pilot ESN items. A representative general population sample of adults without ABI aged 18-64 years (N = 1973) was recruited to gather normative CIQ-R data. Cross-sectional survey. Demographic items and the CIQ-R. The CIQ-R demonstrated acceptable psychometric properties, with minor modification to the original scoring based on the factor analyses provided. Large representative general population CIQ-R normative data have been established, detailing contribution of a range of independent demographic variables to community integration. The addition of electronic social networking items to the CIQ-R offers a contemporary method of assessing community integration following ABI. Normative CIQ-R data enhance the understanding of community integration in the general population, allowing occupational therapists and other clinicians to make more meaningful comparisons between groups.


Effects of calmodulin and lipoxygenase inhibitors on LH (lutropin)- and LHRH (luliberin)-agonist-stimulated steroidogenesis in rat Leydig cells.
The results of this study, carried out with purified rat Leydig cells, indicate that there are no major differences in the stimulating effects of lutropin (LH) and luliberin (LHRH) agonists on steroidogenesis via mechanisms that are dependent on Ca2+. This was demonstrated by using inhibitors of calmodulin and the lipoxygenase pathways of arachidonic acid metabolism. All three calmodulin inhibitors used (calmidazolium, trifluoperazine and chlorpromazine) were shown to block LH- and LHRH-agonist-stimulated steroidogenesis. This probably occurred at the step of cholesterol transport to the mitochondria. Similarly, three lipoxygenase inhibitors (nordihydroguaiaretic acid, BW755c and benoxaprofen), inhibited both LH- and LHRH-agonist-stimulated steroidogenesis. The amounts of the inhibitors required were similar for LH- and LHRH-agonist-stimulated steroidogenesis. Steroidogenesis stimulated by the Ca2+ ionophore A23187 was also inhibited, but higher concentrations of the inhibitors were required. Indomethacin (a cyclo-oxygenase inhibitor) increased LHRH-agonist-stimulated steroidogenesis;this is consistent with the role of the products of arachidonic acid metabolism via the alternative, lipoxygenase, pathway. The potentiation of LH-stimulated testosterone production by LHRH agonist was unaffected by indomethacin or by lipoxygenase inhibitors at concentrations that inhibited LH-stimulated testosterone production by 75-100%. It was not possible to eliminate a role of calmodulin in modulating the potentiation, although higher concentrations of the inhibitors were generally required to negate the potentiation than to inhibit LH- or LHRH-agonist-stimulated testosterone production.


Brine-Soluble Zwitterionic Copolymers with Tunable Adsorption on Rocks.
Injection of aqueous fluids into reservoirs as an enhanced oil recovery (EOR) tool has been of great interest in petroleum engineering. EOR using viscous polymer solutions improves the volumetric sweep efficiency. However, significant polymer adsorption on reservoir rock surfaces is one of the greatest challenges in polymer-flooding EOR. We have synthesized and characterized five zwitterionic copolymers and studied their static adsorption on limestone surfaces in seawater at high temperatures and salinities. Our results indicate that polymer adsorption directly correlates to a small percentage of functional co-monomers on the polymer backbone. One particular copolymer shows negligible static adsorption on limestone surfaces.


BetaIg-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells.
HAb18G/CD147, a new hepatoma-associated antigen cloned and screened from human hepatocellular carcinoma cDNA library, is closely correlated with metastasis process in human hepatoma cells. In the present study we aimed to identify the pivotal molecules of the HAb18G/CD147 signal transduction pathway. The investigation showed that betaig-h3, a secretory extracellular matrix (ECM) protein, was upregulated in HAb18G/CD147-expressing human hepatoma T7721 cells and was downregulated by depressing HAb18G/CD147 expression. The expression of betaig-h3, upregulated in human hepatoma cells, was positively relative to the expression of HAb18G/CD147 in different human hepatoma cell lines. By overexpressing betaig-h3 in human SMMC-7721 hepatoma cells, we discovered that betaig-h3 promoted cell adhesion, invasion, and matrix metalloproteinase (MMP) secretion potential. HAb18G/CD147-induced invasion and metastasis potential of human hepatoma cells can be attenuated by antibodies specific for betaig-h3, and no significant differences on inhibitory effects were observed among T7721 cells incubated with antibodies for betaig-h3 or HAb18G/CD147 or both types together. Taken together, our study suggests that betaig-h3, regulated by the expression of HAb18G/CD147, is involved in the HAb18G/CD147 signal transduction pathway and mediates the HAb18G/CD147-induced invasion and metastasis process of human hepatoma cells.


Ligation independent cloning (LIC) as a rapid route to families of recombinant biocatalysts from sequenced prokaryotic genomes.
A technique is presented for the high throughput generation of families of recombinant biocatalysts sourced from prokaryotic genomes, providing rapid access to the naturally evolved diversity of enzyme specificity for biocatalyst discovery. The method exploits a novel ligation independent cloning strategy, based on the locally engineered vector pET-YSBLIC and has been used for the rapid generation of a suite of expression plasmids containing genes encoding a family of six Baeyer-Villiger monooxygenases (BVMOs) from Mycobacterium tuberculosis H37Rv (MTb). The six resultant recombinant strains of E. coli B834 (DE3) expressing the genes were assayed for oxygenating activity in respect of the target reaction; the resolution of bicyclo[3.2.0]hept-2-en-6-one. The analysis of biotransformations catalysed by growing cells of E. coli was complicated by the production of indole in the reaction mixtures, possibly resulting from the in vivo activity of E. coli tryptophanase. Four of the recombinant strains expressing different BVMOs catalysed the oxidation of one or more of four screening substrates, well above controls that had been transformed with the re-ligated parent vector. One of the recombinant strains, E. coli B834 (DE3) pDB5, expressing the Rv3049c gene from MTb, was found to effectively resolve the target substrate, yielding a 19% yield of (1R, 5S)-(+)-bicyclo[3.2.0]hept-2-en-6-one with >95% enantiomeric excess in a 4 L fermentation reaction.


Do quality indicators for general practice teaching practices predict good outcomes for students?
Keele medical students spend 113 days in general practices over our five-year programme. We collect practice data thought to indicate good quality teaching. We explored the relationships between these data and two outcomes for students; Objective Structured Clinical Examination (OSCE) scores and feedback regarding the placements. Though both are surrogate markers of good teaching, they are widely used. We collated practice and outcome data for one academic year. Two separate statistical analyses were carried out: (1) to determine how much of the variation seen in the OSCE scores was due to the effect of the practice and how much to the individual student. (2) to identify practice characteristics with a relationship to student feedback scores. (1) OSCE performance: 268 students in 90 practices: six quality indicators independently influenced the OSCE score, though without linear relationships and not to statistical significance. (2) Student satisfaction: 144 students in 69 practices: student feedback scores are not influenced by practice characteristics. The relationships between the quality indicators we collect for practices and outcomes for students are not clear. It may be that neither the quality indicators nor the outcome measures are reliable enough to inform decisions about practices' suitability for teaching.


RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND GAMMA-GLOBULINS.
Admixture of separated L and H polypeptide chains of 7S gamma-globulins under appropriate conditions has been found to result in the reconstitution of 7S molecules. The chains were mixed in 0.5 N propionic acid and when dialyzed into neutral aqueous buffers interacted to form reconstituted material in greater than 30 per cent yield. This material had sedimentation coefficients of 6S to 7S, a weight average molecular weight of 160,000, and its antigenic structure and electrophoretic properties were the same as those of 7S gamma-globulin. By the use of I(131) and I(125) labels on the different types of chains, combined with ultracentrifugation of chain mixtures in sucrose density gradients, the 7S product was found to contain both isotopes in ratios consistent with the presence of two L and two H chains. After hydrolysis with papain, the reconstituted material yielded products resembling S and F fragments. All of the isotope corresponding to L chains was found in the counterpart of the S fragment; the isotope corresponding to the H chain fraction was present in both fragments. The activity reconstituted from chains of a purified guinea pig antibody to f1 phage was found to be associated mainly with the 7S material. Hybrid molecules containing rabbit L chains and human H chains and of human L chains and rabbit H chains were formed by the same techniques of reconstitution. It was found that the interchain disulfide bonds of native 7S gamma-globulins could be broken and reoxidized, as could those of reconstituted 7S material. Reduced L and H chains mixed in propionic acid, dialyzed against neutral buffers containing mercaptan, then against neutral buffers in the absence of mercaptan, formed stable 7S molecules of molecular weight 160,000, which were dissociable only after reduction.


Enzyme cycling contributes to efficient induction of genome mutagenesis by the cytidine deaminase APOBEC3B.
The single-stranded DNA cytidine deaminases APOBEC3B, APOBEC3H haplotype I, and APOBEC3A can contribute to cancer through deamination of cytosine to form promutagenic uracil in genomic DNA. The enzymes must access single-stranded DNA during the dynamic processes of DNA replication or transcription, but the enzymatic mechanisms enabling this activity are not known. To study this, we developed a method to purify full length APOBEC3B and characterized it in comparison to APOBEC3A and APOBEC3H on substrates relevant to cancer mutagenesis. We found that the ability of an APOBEC3 to cycle between DNA substrates determined whether it was able to efficiently deaminate single-stranded DNA produced by replication and single-stranded DNA bound by replication protein A (RPA). APOBEC3 deaminase activity during transcription had a size limitation that inhibited APOBEC3B tetramers, but not APOBEC3A monomers or APOBEC3H dimers. Altogether, the data support a model in which the availability of single-stranded DNA is necessary, but alone not sufficient for APOBEC3-induced mutagenesis in cells because there is also a dependence on the inherent biochemical properties of the enzymes. The biochemical properties identified in this study can be used to measure the mutagenic potential of other APOBEC enzymes in the genome.


Adrenal medullary opiate receptors. Pharmacological characterization in bovine adrenal medulla and a human pheochromocytoma.
We have characterized the opiate binding sites on the membranes of bovine adrenal medulla and human pheochromocytoma, using 3H-labeled D-Ala2-D-Leu5-enkephalin ( [3H]DADLE), [3H]etorphine, and [3H]ethylketocyclazocine ( [3H]EKC). Binding was stereoselective in both membrane preparations. Association and dissociation kinetics showed that steady state was achieved after 20-25 min of incubation at 37 degrees. Saturation experiments were performed in the absence or in the presence of morphiceptin (1 microM), which masks the mu sites, D-Ser2-Leu-enkephalin-Thr6 (100 nM), which masks delta sites, or DADLE (5 microM), which was found to mask the delta, mu, and benzomorphan receptor. Taking into consideration the affinities of the three radioligands used (DADLE identifying the delta and mu sites when used in the nanomolar range; etorphine identifying the delta, mu, and benzomorphan sites; EKC identifying the delta, mu, kappa, and benzomorphan receptors) we have characterized pharmacologically the opiate sites present on bovine and human membranes. Human pheochromocytoma membranes contained (a) mu binding sites (15 fmoles/mg of protein, KD [3H]etorphine 1.0 nM, [3H]EKC 5.4 nM, [3H]DADLE 5.6 nM); (b) kappa sites (41 fmoles/mg of protein, KD [3H]EKC 1.0 nM); (c) benzomorphan sites (115 fmoles/mg of protein, KD [3H]etorphine and [3H]EKC 1.0 nM). On bovine membranes we have detected (a) delta binding sites (10 fmoles/mg of protein, KD [3H]DADLE 0.7 nM); (b) mu sites (24 fmoles/mg of protein, KD [3H]DADLE 2.9 nM, [3H]etorphine 0.2 nM, [3H]EKC 3.4 nM); (c) kappa sites (12 fmoles/mg of protein, KD [3H]EKC 0.4 nM); (d) benzomorphan sites (80 fmoles/mg of protein, KD [3H]etorphine 0.2 nM, [3H]EKC 1.3 nM); (e) a residual high-affinity (20 fmoles/mg of protein, KD 0.2 nM) site identified by [3H]etorphine in the presence of 5 microM DADLE. The relative proportions of benzomorphan sites were equal in both tissues (65% of the high-affinity sites) whereas kappa receptors were more abundant on human membranes (25%) than on bovine membranes (9% of the high-affinity sites).


Influence of Methylphenidate on Long-Term Neuropsychological and Everyday Executive Functioning After Traumatic Brain Injury in Children with Secondary Attention Problems.
To investigate the effects of methylphenidate on long-term executive and neuropsychological functioning in children with attention problems following TBI, as well as the relationship between methylphenidate associated changes in lab-based neuropsychological measures of attentional control, processing speed, and executive functioning and parent- or self-report measures of everyday executive functioning. 26 children aged 6-17 years, who were hospitalized for moderate-to-severe blunt head trauma 6 or more months previously, were recruited from a large children's hospital medical center. Participants were randomized into a double-masked, placebo-controlled cross-over clinical trial. Participants completed a comprehensive neuropsychological battery and parent- and self-report ratings of everyday executive functioning at baseline, and at 4 weeks and 8 weeks following upward titration of medication to an optimal dose or while administered a placebo. Methylphenidate was associated with significant improvements in processing speed, sustained attention, and both lab-based and everyday executive functioning. Significant treatment-by-period interactions were found on a task of sustained attention. Participants who were randomized to the methylphenidate condition for the first treatment period demonstrated random or erratic responding, with slower and more variable response times when given placebo during the second period. Results indicate that methylphenidate treatment is associated with positive outcomes in processing speed, sustained attention, and both lab-based and everyday measures of executive functioning compared to placebo group. Additionally, results suggest sustained attention worsens when discontinuing medication. (JINS, 2019, 25, 740-749).


Impact of glyphosate on the Bradyrhizobium japonicum symbiosis with glyphosate-resistant transgenic soybean: a minireview.
Glyphosate-resistant (GR) soybean [Glycine max (L.) Merr.] expressing an insensitive 5-enolpyruvylshikimic acid-3-phosphate synthase (EPSPS) gene has revolutionized weed control in soybean production. The soybean nitrogen fixing symbiont, Bradyrhizobium japonicum, possesses a glyphosate-sensitive enzyme and upon exposure to glyphosate accumulates shikimic acid and hydroxybenzoic acids such as protocatechuic acid (PCA), accompanied with B. japonicum growth inhibition and death at high concentrations. In a series of greenhouse and field experiments, glyphosate inhibited nodulation and nodule leghemoglobin content of GR soybean. Glyphosate accumulated in nodules of field-grown GR soybean, but its effect on nitrogenase activity of GR soybean was inconsistent in field studies. In greenhouse studies, nitrogenase activity of GR soybean following glyphosate application was transiently inhibited especially in early growth stages, with the greatest inhibition occurring under moisture stress. Studies using bacteroid preparations showed that the level of glyphosate inhibition of bacteroid nitrogenase activity was related to in vitro glyphosate sensitivity of the B. japonicum strains. These studies indicate the potential for reduced nitrogen fixation in the GR soybean system; however, yield reductions due to this reduced N2 fixation in early stages of growth have not been demonstrated.


New Genomes from the Congo Basin Expand History of CRF01_AE Origin and Dissemination.
Although the first HIV circulating recombinant form (CRF01_AE) is the predominant strain in many Asian countries, it is uncommonly found in the Congo Basin from where it first originated. To fill the gap in the evolutionary history of this important strain, we sequenced near complete genomes from HIV samples with subgenomic CRF01_AE regions collected in Cameroon and the Democratic Republic of the Congo from 2001 to 2006. HIV genomes were generated from N = 13 plasma specimens by next-generation sequencing of metagenomic libraries prepared with spiked primers targeting HIV, followed by Sanger gap-filling. Genome sequences were aligned to reference strains, including Asian and African CRF01_AE sequences, and evaluated by phylogenetic and recombinant analysis to identify four CRF01_AE strains from Cameroon. We also identified two CRF02, one CRF27, and six unique recombinant form genomes (01|A1|G, 01|02|F|U, F|G|01, A1|D|01, F|G|01, and A1|G|01). Phylogenetic analysis, including the four new African CRF01_AE genomes, placed these samples as a bridge between basal Central African Republic CRF01_AE strains and all Asian, European, and American CRF01_AE strains. Molecular dating confirmed previous estimates indicating that the most recent common CRF01_AE ancestor emerged in the early 1970s (1968-1970) and spread beyond Africa around 1980 to Asia. The new sequences and analysis presented in this study expand the molecular history of the CRF01_AE clade, and are illustrated in an interactive Next Strain phylogenetic tree, map, and timeline at (https://nextstrain.org/community/EduanWilkinson/hiv-1_crf01).


New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease.
Novel peroxisome proliferator-activated receptor (PPAR) modulators (selective PPAR modulators [SPPARMs]) and dual PPAR agonists may have an important role in the treatment of cardiometabolic disorders owing to lipid-modifying, insulin-sensitizing and anti-inflammatory effects. This review summarizes the efficacy of new PPAR agonists and SPPARMs that are under development for the treatment of atherogenic dyslipidemia and non-alcoholic fatty liver disease (NAFLD). ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH.


Psychometric performance of the NEI VFQ-25 in visually normal Latinos: the Los Angeles Latino Eye Study.
To characterize the psychometric performance of the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) in visually normal Latinos (Mexican Americans). The Los Angeles Latino Eye Study (LALES) is a population-based study to assess the prevalence of eye disease and self-reported visual functioning in Latinos aged 40 or more years. Self-reported visual functioning was assessed by using English and Spanish versions of the NEI VFQ-25. Psychometric properties of the NEI VFQ-25, including internal consistency of the subscales and the individual items, were assessed through the Multi-trait Analysis Program-Revised (MAP-R) analysis. Adjusted mean and median subscale scores were compared between English and Spanish speakers to identify any systematic differences. Of the 1917 participants from two census tracts, 1171 participants with no visual impairment were included in this analysis. The mean age of the participants was 52.3 years, 57% of the participants were female, and 67.5% of the participants were Spanish speaking. Median scores for Spanish-speaking participants were significantly lower than those of the English-speaking participants on four subscales: Ocular Pain, General Vision, Vision-Specific Mental Health, and General Health (P < 0.05). Internal consistency for three of eight measurable subscales for the study group was poor (Cronbach alpha < 0.6). This study reveals psychometric inconsistencies in the NEI VFQ-25 when administered to visually normal Latinos. The difference in mean subscale scores between Spanish and English speakers must be integrated into the development of population norms of visual function. Further detailed psychometric evaluation is needed to determine the validity of this instrument in Latino populations.


Degenerative mitral regurgitation: when should we operate?
Left untreated, severe mitral regurgitation in asymptomatic patients can lead to irreversible cardiac damage, which can develop with little warning. Over the period of this study, we have tended to operate earlier in the disease process and on less symptomatic patients. We report here our experience. Between January 1985 and June 1996, 710 patients with mitral regurgitation underwent operations. Three hundred twenty-nine (213 male and 116 female with a mean age of 65.5 years) had degenerative mitral valve disease and of this group, 169 patients underwent repair and 160, replacement. The overall operative mortality was 4 patients (1.2%). There were no operative deaths among patients having isolated mitral valve repair. Survival at 1 year, 5 years, and 10 years was 94%+/-1.4% (+/- the standard error of the mean), 77%+/-2.9%, and 41%+/-5.8%, respectively. Survival was significantly better in the group having repair (p < 0.05). Ten patients (6%) in the repair group and 13 (8%) in the replacement group required reoperation. Increased age, worse left ventricular function, type of operation (replacement worse than repair), and increased left ventricular size were significantly associated with poorer survival. These data confirm the superior results achieved with mitral valve repair and support early mitral valve repair before functional deterioration.


Exploring salivary lipid profile changes in COVID-19 patients: Insights from mass spectrometry analysis.
The most common COVID-19 testing relies on the use of nasopharyngeal swabs. However, this sampling step is very uncomfortable and is one of the biggest challenges regarding population testing. In the present study, the use of saliva as an alternative sample for COVID-19 diagnosis was investigated. Therefore, high-resolution mass spectrometry analysis and chemometric approaches were applied to salivary lipid extracts. Two data organizations were used: classical MS data and pseudo-MS image datasets. The latter transformed MS data into pseudo-images, simplifying data interpretation. Classification models achieved high accuracy, with pseudo-MS image data performing exceptionally well. PLS-DA with OPSDA successfully separated COVID-19 and healthy groups, serving as a potential diagnostic tool. The most important lipids for COVID-19 classification were elucidated and include sphingolipids, ceramides, phospholipids, and glycerolipids. These lipids play a crucial role in viral replication and the inflammatory response. While pseudo-MS image data excelled in classification, it lacked the ability to annotate important variables, which was performed using classical MS data. These findings have the potential to improve clinical diagnosis using rapid, non-invasive testing methods and accurate high-volume results.


Genomic Prediction of Complex Phenotypes Using Genic Similarity Based Relatedness Matrix.
In the last years, a series of methods for genomic prediction (GP) have been established, and the advantages of GP over pedigree best linear unbiased prediction (BLUP) have been reported. However, the majority of previously proposed GP models are purely based on mathematical considerations while seldom take the abundant biological knowledge into account. Prediction ability of those models largely depends on the consistency between the statistical assumptions and the underlying genetic architectures of traits of interest. In this study, gene annotation information was incorporated into GP models by constructing haplotypes with SNPs mapped to genic regions. Haplotype allele similarity between pairs of individuals was measured through different approaches at single gene level and then converted into whole genome level, which was then treated as a special kernel and used in kernel based GP models. Results shown that the gene annotation guided methods gave higher or at least comparable predictive ability in some traits, especially in the Arabidopsis dataset and the rice breeding population. Compared to SNP models and haplotype models without gene annotation, the gene annotation based models improved the predictive ability by 0.56~26.67% in the Arabidopsis and 1.62~16.53% in the rice breeding population, respectively. However, incorporating gene annotation slightly improved the predictive ability for several traits but did not show any extra gain for the rest traits in a chicken population. In conclusion, integrating gene annotation into GP models could be beneficial for some traits, species, and populations compared to SNP models and haplotype models without gene annotation. However, more studies are yet to be conducted to implicitly investigate the characteristics of these gene annotation guided models.


[Surgical results in lung cancer in women].
The paper deals with the immediate and long-term results of treatment of 173 female and 1,330 male patients with lung cancer operated on at the Department of Lung and Mediastinal Tumors of the Institute in 1960-1979. The results of radical surgery were better in females: 5-year survival rate was 1.5 times that in males (44.4% vs 31.4%) whereas at 10 years it was twice as high (35.5 vs 17.2%).


Hodgkin Lymphoma: A disease shaped by the tumor micro- and macroenvironment.
The tumor microenvironment (TMicroE) and tumor macroenvironment (TMacroE) are defining features of classical Hodgkin lymphoma (cHL). They are of critical importance to clinicians since they explain the common signs and symptoms, allow us to classify these neoplasms, develop prognostic and predictive biomarkers, bioimaging and novel treatments. The TMicroE is defined by effects of cancer cells to their immediate surrounding and within the tumor. Effects of cancer cells at a distance or outside of the tumor define the TMacroE. Paraneoplastic syndromes are signs and symptoms due to effects of cancer at a distance or the TMacroE, which are not due to direct cancer cell infiltration. The most common paraneoplastic symptoms are B-symptoms, which manifest as fevers, chills, drenching night sweats, and/or weight loss. Less common paraneoplastic syndromes include those that affect the central nervous system, skin, kidney, and hematological autoimmune phenomena including hemophagocytic lymphohistiocytosis (HLH). Paraneoplastic signs such as leukocytosis, lymphopenia, anemia, and hypoalbuminemia are prognostic biomarkers. The neoplastic cells in cHL are the Hodgkin and Reed Sternberg (HRS) cells, which are preapoptotic germinal center B cells with a high mutational burden and almost universal genetic alterations at the 9p24.1 locus primarily through copy gain and amplification with strong activation of signaling via PD-L1, JAK-STAT, NFkB, and c-MYC. In the majority of cases of cHL over 95% of the tumor cells are non-neoplastic. In the TMicroE, HRS cells recruit and mold non-neoplastic cells vigorously via extracellular vesicles, chemokines, cytokines and growth factors such as CCL5, CCL17, IL6, and TGF-β to promote a feed-forward inflammatory loop, which drives cancer aggressiveness and anti-cancer immune evasion. Novel single cell profiling techniques provide critical information on the role in cHL of monocytes-macrophages, neutrophils, T helper, Tregs, cytotoxic CD8+ T cells, eosinophils, mast cells and fibroblasts. Here, we summarize the effects of EBV on the TMicroE and TMacroE. In addition, how the metabolism of the TMicroE of cHL affects bioimaging and contributes to cancer aggressiveness is reviewed. Finally, we discuss how the TMicroE is being leveraged for risk adapted treatment strategies based on bioimaging results and novel immune therapies. In sum, it is clear that we cannot effectively manage patients with cHL without understanding the TMicroE and TMacroE and its clinical importance is expected to continue to grow rapidly.


Incremental value of clinical data beyond claims data in predicting 30-day outcomes after heart failure hospitalization.
Administrative claims data are used routinely for risk adjustment and hospital profiling for heart failure outcomes. As clinical data become more readily available, the incremental value of adding clinical data to claims-based models of mortality and readmission is unclear. We linked heart failure hospitalizations from the Get With The Guidelines-Heart Failure registry with Medicare claims data for patients discharged between January 1, 2004, and December 31, 2006. We evaluated the performance of claims-only and claims-clinical regression models for 30-day mortality and readmission, and compared hospital rankings from both models. There were 25 766 patients from 308 hospitals in the mortality analysis, and 24 163 patients from 307 hospitals in the readmission analysis. The claims-clinical mortality model (area under the curve [AUC], 0.761; generalized R(2)=0.172) had better fit than the claims-only mortality model (AUC, 0.718; R(2)=0.113). The claims-only readmission model (AUC, 0.587; R(2)=0.025) and the claims-clinical readmission model (AUC, 0.599; R(2)=0.031) had similar performance. Among hospitals ranked as top or bottom performers by the claims-only mortality model, 12% were not ranked similarly by the claims-clinical model. For the claims-only readmission model, 3% of top or bottom performers were not ranked similarly by the claims-clinical model. Adding clinical data to claims data for heart failure hospitalizations significantly improved prediction of mortality, and shifted mortality performance rankings for a substantial proportion of hospitals. Clinical data did not meaningfully improve the discrimination of the readmission model, and had little effect on performance rankings.


Impact of adiponectin on left ventricular mass index in non-complicated obese subjects.
To evaluate the relationship between the adiponectin levels and left ventricular mass index (LVMI) in uncomplicated obese subjects. Fifty-nine subjects were assigned to the obese (BMI> or =30 kg/m(2)) and 58 to the lean (BMI<30 kg/m (2) ) group. Plasma glucose, insulin, serum total cholesterol and high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides and adiponectin were measured. Insulin resistance was determined by the Homeostasis Assessment Model (HOMA-IR). The left ventricular functions of all subjects were determined by 2D and pulse wave Doppler echocardiography. LVMI was calculated as left ventricular mass (LVM) normalized for height in m (2.7) . The obese group displayed significantly higher LVMI and late mitral inflow velocity. Thirty-three obese subjects met the criteria for left ventricular hypertrophy (LVH) and had lower serum adiponectin levels compared with obese subjects without LVH and lean subjects (p<0.05). Adiponectin was negatively correlated with LVMI (R: -0.277, p: 0.002). Furthermore, during the partial correlation analysis where HOMA-IR was controlled, the negative correlation between adiponectin and LVMI progressed (r: -0.283, p: 0.002). The linear regression analysis showed an independent relationship between LVMI and adiponectin. (beta: -0.214, p: 0.01) Obesity is associated with LVH. This study showed direct influence of adiponectin on LVMI.


Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis.
To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials. For GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations. Addition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.


Cell-free protein synthesis enables one-pot cascade biotransformation in an aqueous-organic biphasic system.
Biocatalytic cascade reactions have become increasingly important and useful for chemical synthesis. However, biocatalysts are often incompatible with organic solvents, which prohibits many cascade reactions involving nonpolar substrates. In this study, we used cell-free protein synthesis (CFPS) to express enzymes in an aqueous-organic biphasic system for the construction of an artificial enzymatic pathway. CFPS-expressed enzymes without purification performed efficiently to convert styrene (below 20 mM) to (S)-1-phenyl-1,2-ethanediol (two steps in one pot) with 100% conversion. In addition, our CFPS system showed great tolerance to different organic solvents, and, importantly, the entire biocatalytic system can be consistently scaled up without a reduction of the substrate conversion rate. We, therefore, anticipate that our cell-free approach will make a possible cost-effective, high-yielding synthesis of valuable chemicals.


Marine Tar Residues: a Review.
Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean environment indefinitely, decomposing or becoming buried in the sea floor. However, in many cases, they are transported ashore via currents and waves where they pose a concern to coastal recreation activities, the seafood industry and may have negative effects on wildlife. This review summarizes the current state of knowledge on marine tar residue formation, transport, degradation, and distribution. Methods of detection and removal of marine tar residues and their possible ecological effects are discussed, in addition to topics of marine tar research that warrant further investigation. Emphasis is placed on benthic tar residues, with a focus on the remnants of the Deepwater Horizon oil spill in particular, which are still affecting the northern Gulf of Mexico shores years after the leaking submarine well was capped.


Advances in CT assessment of metabolic and endocrine disorders.
Advances in diagnostic imaging of endocrine disorders are occurring rapidly. In certain disease entities, such as Cushing's disease, pheochromocytoma, primary aldosteronism, and islet cell tumors, noninvasive imaging techniques like CT have become the initial diagnostic imaging procedures of choice. In other disorders, such as hyperparathyroidism, carcinoid, and thyroid disease, CT is making important contributions, and further advances can be anticipated.


Adenoid Cystic Carcinoma- A rare Differential Diagnosis for a mass in the External Auditory Canal.
Primary external auditory canal malignancies are very rare; in which, adenoid cystic carcinoma is extremely rare tumour accounting for approximately 5%. Majority of the patients presents with unilateral severe or dull aching constant ear pain of prolonged duration, reduced hearing and mass in the External Ear. These tumours are treated with aggressive surgical excision and adjuvant radiotherapy. Despite this, the overall prognosis is poor due to recurrences and distant metastasis. We report a rare case of adenoid cystic carcinoma in a 36-year-old female, who presented with right ear pain for the last one year. She was treated with wide local excision of the mass followed by adjuvant radiotherapy.


A family with abdominal aortic aneurysms.
This investigation focused on 7 siblings to 2 brothers with abdominal aortic aneurysm (AAA), with respect to AAA, Chlamydia pneumoniae (CP) serology, serum cholesterol, and smoking habits. Five male and 4 female siblings were included. All siblings underwent ultrasonography, and surgical specimens from the aorta were prepared for immunohistochemical (IHC) analysis. Blood was obtained from all living siblings and serum cholesterol level was analyzed. Serologic analysis was done by microimmunofluorescence (MIF). Smoking habits were recorded. In addition to the 2 known siblings with AAA, 2 other brothers with AAA were found. Four of 8 siblings had IgG 1/512 or greater and 7 of 8 had IgA 1/64 or greater. Two of 3 were positive for CP in IHC obtained from aortic specimens. Two of 8 had hypercholesterolemia; 7 of 9 were smokers. C. pneumoniae as well as smoking seems to be important in the pathogenesis of AAA in this small cohort; however, larger patient cohorts are needed.


Design and synthesis of new enzymes based on the lactate dehydrogenase framework.
Analysis of the mechanism and structure of lactate dehydrogenases is summarized in a map of the catalytic pathway. Chemical probes, single tryptophan residues inserted at specific sites and a crystal structure reveal slow movements of the protein framework that discriminate between closely related small substrates. Only small and correctly charged substrates allow the protein to engulf the substrate in an internal vacuole that is isolated from solvent protons, in which water is frozen and hydride transfer is rapid. The closed vacuole is very sensitive to the size and charge of the substrate and provides discrimination between small substrates that otherwise have too few functional groups to be distinguished at a solvated protein surface. This model was tested against its ability to successfully predict the design and synthesis of new enzymes such as L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase. Solvent friction limits the rate of forming the vacuole and thus the maximum rate of catalysis.