HUBNET: Wide Area Network utilization of Local Area Network medical reference and communication resources.
The State University of New York at Buffalo School of Medicine and Biomedical Sciences and its associated teaching sites have developed and partially implemented a regional Wide Area Network (WAN) in Buffalo and Western New York. The school wishes to use this WAN to deliver reference and communication resources to students, residents and faculty. The richest pool of easy to use reference and communication resources are PC software programs that are intended for individual workstations or at best, client-server, Local Area Network (LAN) implementation. HUBNET (Hospitals and University at Buffalo Library Resource Network), a project of the School of Medicine and the Library Consortium of Health Institutions in Buffalo offers integrated presentation of many such LAN resources over this regional WAN. The system crosses many institutional boundaries and reaches physically remote sites in a complex mix of information systems environments with few issues related to performance. The system design provides a level of ease of use that has brought many new users into active computer use while addressing integration into diverse information systems settings and networking environments.


Hydrogen peroxide-independent generation of superoxide catalyzed by soybean peroxidase in response to ferrous ion.
It is well documented that extracellular alkalization occurs in plants under the challenges by pathogenic microbes. This may eventually induce the pH-dependent extracellular peroxidase-mediated oxidative burst at the site of microbial challenges. By employing the purified proteins of horseradish peroxidase as a model, we have recently proposed a likely role for free Fe(2+) in reduction of ferric enzyme of plant peroxidases into ferrous intermediate and oxygen-bound form of enzyme known as Compound III which may eventually releases superoxide anion radical (O2(•-)), especially under alkaline condition, possibly contributing to the plant defense mechanism. In the present study, we employed the purified protein of soybean peroxidase (SBP) as an additional model, and examined the changes in the redox status of enzyme accompanying the generation of O2(•-) in response to Fe(2+) under alkaline condition.


The genes for perforin, granzymes A-C and IFN-gamma are differentially expressed in single CD8(+) T cells during primary activation.
Here we show that the genes for perforin, the three major T cell granzymes (A-C) and IFN-gamma are differentially expressed during primary activation of naive CD8(+) T cells, kinetically and at the single-cell level. When CD44(low)CD62L(high)CD8(+) lymph node T cells were activated with IL-2 and immobilized antibodies to CD3, CD8 and CD11a, expression of perforin, granzyme B and IFN-gamma mRNAs was induced by day 2, and increased in parallel with perforin-dependent cytolytic activity. Granzyme C and A transcripts were not detected until 1 and 3 days later respectively. Single-cell PCR showed that expression frequencies rose in parallel with total levels of each mRNA, but that individual cells expressed diverse combinations of perforin, granzyme A-C and IFN-gamma mRNAs. These expression patterns indicated that the delayed expression of granzymes A and C was not due to late activation of distinct cell subpopulations. Statistical analysis of the data suggested that each gene was differentially regulated at the single-cell level. Individual naive CD8(+) T cells gave rise over 7 days to clones that expressed all five products at the clonal level, but also expressed diverse combinations at the single-cell level. We conclude that, during primary activation, CD8(+) T cells progressively acquired the ability to express most or all of these genes, and that the variable expression patterns observed among single cells within clones and populations reflected transient rather than heritable differences in expression profile.


RNA editing of the human herpesvirus 8 kaposin transcript eliminates its transforming activity and is induced during lytic replication.
Human herpesvirus 8 is the etiologic agent associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The K12 RNA, which produces as many as three variants of the kaposin protein, as well as a microRNA, is the most abundant transcript expressed in latent Kaposi's sarcoma-associated herpesvirus infection, and yet it is also induced during lytic replication. The portion of the transcript that includes the microRNA and the kaposin A sequence has been shown to have tumorigenic potential. Genome coordinate 117990, which is within this transcript, has been found to be heterogeneous, primarily in RNAs but also among viral DNA sequences. This sequence heterogeneity affects an amino acid in kaposins A and C and the microRNA. The functional effects of this sequence heterogeneity have not been studied, and its origin has not been definitively settled; both RNA editing and heterogeneity at the level of the viral genome have been proposed. Here, we show that transcripts containing A at position 117990 are tumorigenic, while those with G at this position are not. Using a highly sensitive quantitative assay, we observed that, in PEL cells under conditions where more than 60% of cDNAs derived from K12 RNA transcripts have G at coordinate 117990, there is no detectable G in the viral DNA sequence at this position, only A. This result is consistent with RNA editing by one of the host RNA adenosine deaminases (ADARs). Indeed, we observed that purified human ADAR1 efficiently edits K12 RNA in vitro. Remarkably, the amount of editing correlated with the replicative state of the virus; editing levels were nearly 10-fold higher in cells treated to induce lytic viral replication. These results suggest that RNA editing controls the function of one segment of the kaposin transcript, such that it has transforming activity during latent replication and possibly another, as-yet-undetermined, function during lytic replication.


Size-dependent enthalpy of condensation.
A thermodynamic model for the size dependence of enthalpy of condensation, DeltaH(con), is discussed. The model is valid over a range of radii where the arrangement of surface layer and surface tension remain invariable; it provides a way of calculating enthalpy and entropy changes and equilibrium vapor pressures. The difference between DeltaH(con) for two liquid bodies of the same chemical nature is equal to the variation of the autoadsorption energies on their surfaces.


Cloned piglets born after nuclear transplantation of embryonic blastomeres into porcine oocytes matured in vivo.
Nuclear transplantation in the pig is more difficult than in other domestic animals and only one embryonic nuclear transplantation (NT) pig has been born to date. In this study, reconstituted porcine embryos were produced by electrofusion of blastomeres from in vivo four-cell embryos to enucleated in vivo or in vitro matured (IVM) oocytes. Nuclear transfer using cumulus cells as nuclear donors was also conducted. When blastomeres were used as donors, the electrofusion rate was significantly higher in oocytes matured in vivo (91.5%) than in those matured in vitro (66.1%) (p < 0.01). After fusion, the NT embryos reconstituted from in vivo matured oocytes developed to blastocysts at a rate of 10.3% after culture in rabbit oviducts for up to 5 days, while only 5.9% of the NT embryos reconstructed from in vitro matured oocytes developed to blastocyst stage. Electrofusion rate of cumulus cell nuclei with enucleated IVM oocytes was lower (47.6%) and only 1.5% (2/136) of the reconstituted eggs developed in vitro to morula stage, and 1.9% developed to blastocysts when cultured in the ligated rabbit oviducts. Transfer of 94 embryos reconstructed by blastomere NT with in vivo matured oocytes to five synchronous recipients resulted in the birth of two cloned piglets. No piglet was born following transfer to two recipients of embryos (n = 39) derived from NT with in vitro matured oocytes. The results demonstrate that in vivo matured oocytes are better recipients than those matured in vitro for pig cloning.


An association between the natural course of shoulder joint destruction in rheumatoid arthritis and HLA-DRB1*0405 in Japanese patients.
To assess the association between HLA-DRB1 alleles and shoulder destruction due to rheumatoid arthritis (RA) in Japanese, we typed for HLA-DRB1 alleles in 100 Japanese RA patients who could be classified into 5 groups: non-progressive (N) with normal radiographs; erosive (E) showing marginal erosion but no collapse; collapse (C) showing subchondral cysts followed by collapse; arthrosis-like (A) showing osteoarthrotic features; and the mutilating (M) showing mutilating bone destruction. The HLA-DRB1*0405 antigen frequency in N, E, C, A, and M types was 55%, 61%, 33%, 71%, 100%, respectively. That in the M type (100%) was significantly higher than that in the others (the N, E, C, and A types; 57%). These findings suggest that the most severe shoulder joint destruction pattern in RA, the M type, is associated with HLA-DRB1*0405.


Fe2O3 nanoparticles anchored on 2D kaolinite with enhanced antibacterial activity.
An enhanced antibacterial activity of Fe2O3 nanoparticles was achieved by controlling the distribution density of Fe2O3 nanoparticles on modified kaolinite nanosheets (Fe2O3-KlnKAc) by adjusting the pH value of the reaction system. A proper distribution density of Fe2O3 nanoparticles generating higher levels of hydroxyl radicals led to a higher antibacterial activity.


Nanospheres formulated from L-tyrosine polyphosphate as a potential intracellular delivery device.
Current delivery devices for drugs and genes such as films and microspheres are usually formulated from polymers that degrade over a period of months. In general, these delivery systems are designed to achieve an extracellular release of their encapsulated drugs. For drugs that require interaction with cellular machinery, the efficacies of both macroscopic and microscopic delivery systems are normally low. In contrast, nano-sized drug delivery vehicles could achieve high delivery efficiencies, but they must degrade quickly, and the delivery system itself should be nontoxic to cells. In this aspect, biodegradable nanospheres formulated from l-tyrosine polyphosphate (LTP) have been produced from an emulsion of oil and water for the potential use as an intracellular delivery device. Scanning electron microscopy (SEM) and dynamic laser light scattering (DLS) show that LTP nanospheres possess a diameter range between 100 and 600 nm. SEM reveals nanospheres formulated from LTP are spherical and smooth. Additionally, DLS studies demonstrate that nanospheres degrade hydrolytically in 7 days. Confocal microscopy reveals LTP nanospheres are internalized within human fibroblasts. Finally, the cell viability after exposure to LTP nanospheres and determined with a LIVE/DEAD Cell Viability Assay is comparable to a buffer control. In conclusion, our nanospheres have been shown to be nontoxic to human cells, possess the appropriate size for endocytosis by human cells, and degrade within 7 days. Therefore LTP nanospheres can be used for a sustained intracellular delivery device.


Identification of genetic markers linked to anthracnose resistance in sorghum using association analysis.
Anthracnose in sorghum caused by Colletotrichum sublineolum is one of the most destructive diseases affecting sorghum production under warm and humid conditions. Markers and genes linked to resistance to the disease are important for plant breeding. Using 14,739 SNP markers, we have mapped eight loci linked to resistance in sorghum through association analysis of a sorghum mini-core collection consisting of 242 diverse accessions evaluated for anthracnose resistance for 2 years in the field. The mini-core was representative of the International Crops Research Institute for the Semi-Arid Tropics' world-wide sorghum landrace collection. Eight marker loci were associated with anthracnose resistance in both years. Except locus 8, disease resistance-related genes were found in all loci based on their physical distance from linked SNP markers. These include two NB-ARC class of R genes on chromosome 10 that were partially homologous to the rice blast resistance gene Pib, two hypersensitive response-related genes: autophagy-related protein 3 on chromosome 1 and 4 harpin-induced 1 (Hin1) homologs on chromosome 8, a RAV transcription factor that is also part of R gene pathway, an oxysterol-binding protein that functions in the non-specific host resistance, and homologs of menthone:neomenthol reductase (MNR) that catalyzes a menthone reduction to produce the antimicrobial neomenthol. These genes and markers may be developed into molecular tools for genetic improvement of anthracnose resistance in sorghum.


Discrimination of relative distance in the auditory modality: the success and failure of the loudness discrimination hypothesis.
Difference limens for auditory distance discrimination were determined using the method of limits. Eight untrained subjects were tested across a wide range of distances (49 to 4876 cm) using broadband noise sources. For sources in excess of 304 cm, the Weber ratios observed approximated the function predicted by the inverse first power loss equation. At the longer distances, the subjects appear to be judging distance on the basis of the loudness difference cue. At the shorter distances (49 to 304 cm), the Weber ratios were considerably larger than would be predicted from the inverse first power loss equation. In this range, distance discrimination becomes increasingly degraded as the referent source approaches the subject.


Changes in mercury levels in Great Lakes fish between 1970s and 2007.
A number of initiatives have curtailed anthropogenic mercury emissions in North America over the last two decades; however, various factors, including long-range transport of global emissions, may complicate the response of fish mercury levels to remedial actions. Since the Great Lakes of North America are together the largest surface freshwater body in the world and are under the influence of many complicating factors, trends of mercury in fish from the Great Lakes can reflect the overall impact of mercury management actions at local, regional, and perhaps global scales. Here we present a comprehensive view of mercury trends in Canadian Great Lakes fish using two large (total 5807 samples), different (fillet and whole fish), and long-term (1970s-2007) monitoring data sets. The spatial differences in lake trout and walleye mercury levels during this period have generally been within a factor of 2-3 with Lakes Erie and Superior having the lowest and highest concentrations, respectively. These spatial differences have diminished in the recent years (2000-2007). The concentrations have generally declined over the three decades (mid-1970s to 2007); however, in recent years, the concentration trends are flat in Lake Ontario walleye and appear to be increasing in Lake Erie walleye. There was a mismatch in the Lake Ontario lake trout and walleye temporal trends, which shows the importance of considering more than one fish species for proper spatial/temporal trend assessments.


The Utility of Renal Mass Biopsy in Large Renal Masses.
The role of needle core renal biopsy in large renal masses, defined as lesions larger than 4 cm, is debatable, as larger renal masses are associated with malignant histology. We aim to review the safety and impact of renal biopsy on the management of large renal masses. A retrospective, single-center review of all renal biopsies performed between January 2011 and December 2020 at Royal Perth Hospital was conducted. Indications for biopsy, complications and final management plans were correlated to assess the value of biopsies in large renal masses. In total, 126 biopsies were performed. Indeterminate imaging findings and comorbidities were the main indications for biopsies. We identified 116 (92.1%) diagnostic biopsies and 10 (8.0%) non-diagnostic biopsies due to insufficient samples or inflammatory tissue. Of the diagnostic biopsies, 99 (78.6%) were malignant and 17 (13.5%) were benign. Unnecessary extirpative surgery was avoided in 17 patients. Histology included renal cell carcinoma (96%) and other malignancies such as urothelial carcinoma (3%) and non-Hodgkin's lymphoma (1%). Benign biopsies identified histology including angiomyolipoma (35.3%) and oncocytoma (52.5%). The median follow-up time was 68 months (range 19-132 months). Renal biopsies in large renal masses may aid in preventing unnecessary surgery, especially in situations where imaging findings are equivocal or in patients with many comorbidities.


Active specific T-cell-based immunotherapy for cancer: nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell-based vaccines. Principles and future prospects.
Whereas tumor cells are poor immunogens, recombinant tumor cells or dendritic cells as well as engineered viruses have been demonstrated to elicit specific antitumor immune responses leading to tumor growth suppression and long-lasting immunity in mouse tumor models. Single cytotoxic T lymphocyte-defined epitope-based strategies have proved useful for immunization in tumor-bearing mice. This strategy is under investigation in human melanoma, along with adjuvants such as cytokines or dendritic cells. Flt3L is an in vivo dendritic-cell growth factor that offers new prospects in the field of active specific immunotherapy. These immunotherapeutic approaches are being tested in clinical trials, and may open up novel avenues for disease-free patients with poor prognostic factors.


The Prediction of Students' Academic Performance With Fluid Intelligence in Giving Special Consideration to the Contribution of Learning.
The present study provides a new account of how fluid intelligence influences academic performance. In this account a complex learning component of fluid intelligence tests is proposed to play a major role in predicting academic performance. A sample of 2, 277 secondary school students completed two reasoning tests that were assumed to represent fluid intelligence and standardized math and verbal tests assessing academic performance. The fluid intelligence data were decomposed into a learning component that was associated with the position effect of intelligence items and a constant component that was independent of the position effect. Results showed that the learning component contributed significantly more to the prediction of math and verbal performance than the constant component. The link from the learning component to math performance was especially strong. These results indicated that fluid intelligence, which has so far been considered as homogeneous, could be decomposed in such a way that the resulting components showed different properties and contributed differently to the prediction of academic performance. Furthermore, the results were in line with the expectation that learning was a predictor of performance in school.


Evaluation of scattered radiation dose received by medical staff during uterine artery embolization in the operating room.
The air kerma radiation doses have gained much attention since the operating room interventional radiology is a place where medical staff are exposed to a fluoroscopy environment and gain a cumulative dose during the uterine artery embolization procedure. We aimed to evaluate the radiation dose received by medical staff by applying a flat X-ray machine in the surgical room during uterine artery embolization. An ATOM humanoid model was laid on the operating table and simulated a patient. The scattered radiation dose received by the radiologist, anesthetist and radiologic technologist was evaluated. The scintillation detector was adopted. The measurement points were 50 cm, 100 cm and 150 cm above the floor, representing the limbs, abdomen and thyroid level, respectively. We compared the X-rays under different tube voltages of 70, 80, and 90, respectively and frames per second (FPS) of 30, 15, and 7.5, respectively. We configured the dose level per pulse of 40 nGy with a fixed detector. In Section 1, when the tube voltage was 70 kVp and 7.5 FPS, the average radiation doses of limbs, abdomen and thyroid level was 0.48, 1.3 and 1.9 μSv/min respectively. When the tube voltage was 80 kVp and the fluoroscopy decreases from 30 FPS to 7.5 FPS, 58% of the radiation dose was reduced. When the tube voltage was 90 kVp, the radiation dose in the lead garment increased 31-177% in comparison to when the tube voltage was 80 kVp. Sections 2 and 3 were far away from the central ray, so the highest radiation dose 100 cm above the floor were 0.05 and 0.02 μSv/min. Lead garment can effectively reduce medical staff from occupational doses with an average attenuation rate of 90%. 80 kVp was most commonly used. Fluoroscopy 7.5 FPS was used 100 cm above the floor in A section and the lowest radiation dose was 1.33 μSv/min. The operator should decrease the duration of X-rays or adopt suspended lead shielding to decrease the radiation dose received by the operator. When kVp increases, the penetration increases. Decreasing FPS cannot decrease occupational doses of medical staff.


Effect of different concentrations of acetic, citric, and propionic acid dipping solutions on bacterial contamination of raw chicken skin.
Bacterial contamination of raw, processed poultry may include spoilage bacteria and foodborne pathogens. We evaluated different combinations of organic acid (OA) wash solutions for their ability to reduce bacterial contamination of raw chicken skin and to inhibit growth of spoilage bacteria and pathogens on skin during refrigerated storage. In experiment 1, raw chicken skin samples were dipped into a suspension of either 10(8) cfu/mL of Salmonella Typhimurium, Escherichia coli O157:H7, or Listeria monocytogenes for 30 s and then immersed in PBS or an OA wash solution mixture of 0.8% citric, 0.8% acetic, and 0.8% propionic acid (at equal wt/vol concentrations) for an additional 30 s. In experiment 2, three different concentrations of the OA wash solution (0.2, 0.4, and 0.6% at equal wt/vol concentrations) were tested against chicken skin samples contaminated with Salmonella Typhimurium. Viable pathogenic bacteria on each skin sample were enumerated after 1 and 24 h of storage at 4°C in both experiments. In experiment 3, skin samples were initially treated on d 1 with PBS or 2 concentrations of the OA mixture (0.4 and 0.8%), and total aerobic bacteria were enumerated during a 2-wk storage period. In all experiments, significant (P < 0.05) differences were observed when skin samples were treated with the OA wash solution and no spoilage organisms were recovered at any given time point, whereas increasing log10 numbers of spoilage organisms were recovered over time in PBS-treated skin samples. These results suggest that 0.2 to 0.8% concentrations of an equal-percentage mixture of this OA combination may reduce pathogens and spoilage organisms and improve food safety properties of raw poultry.


Circadian protein CLK suppresses transforming growth factor-β expression in peripheral B cells of nurses with day-night shift rotation.
The mechanism of dysfunction of regulatory B cells is unclear. The circadian locomotor output cycles kaput (CLK) regulates immune responses. CLK expression can be increased by alteration of the circadian rhythm. This study tests a hypothesis that alteration of the circadian rhythm, such as engaging the day-night shift rotation (DNSR), interferes with the expression of transforming growth factor (TGF)-β in B cells (TGFbB cell). Peripheral blood samples were collected from DNSR nurses and persons with the regular circadian clock life style (RC). The frequency of TGFbB cells in the blood samples was assessed by flow cytometry. The expression of TGF-beta in B cells was assessed with real time RT-PCR. We observed that the frequency of peripheral TGFbB cells was less in DNSR nurses as compared to RC subjects. The expression of CLK and histone deacetylase 11 in peripheral B cells was higher, the TGF-β expression was lower, in peripheral B cells of DNSR nurses. Over-expression of CLK repressed the expression of TGF-β in B cells, which was mediated by HDAC11. The CLK expression in peripheral B cells is higher in DNSR nurses, which suppresses the expression of TGF-β in B cells. To regulate the expression of CLK during the circadian clock alteration needs to be further investigated.


Phylogenetic signal and rate of evolutionary change in language structures.
Within linguistics, there is an ongoing debate about whether some language structures remain stable over time, which structures these are and whether they can be used to uncover the relationships between languages. However, there is no consensus on the definition of the term 'stability'. I define 'stability' as a high phylogenetic signal and a low rate of change. I use metric D to measure the phylogenetic signal and Hidden Markov Model to calculate the evolutionary rate for 171 structural features coded for 12 Japonic, 2 Koreanic, 14 Mongolic, 11 Tungusic and 21 Turkic languages. To more deeply investigate the differences in evolutionary dynamics of structural features across areas of grammar, I divide the features into 4 language domains, 13 functional categories and 9 parts of speech. My results suggest that there is a correlation between the phylogenetic signal and evolutionary rate and that, overall, two-thirds of the features have a high phylogenetic signal and over a half of the features evolve at a slow rate. Specifically, argument marking (flagging and indexing), derivation and valency appear to be the most stable functional categories, pronouns and nouns the most stable parts of speech, and phonological and morphological levels the most stable language domains.


Physiological and Anatomical Outputs of Rat Genital Cortex.
Rat somatosensory genital cortex contains a large sexually monomorphic representation of the penis in males and the clitoris in females. Genital cortex microstimulation-evoked movements of legs, trunk and genitals, which showed sex-specific differences related to mating behaviors and included thrusting in males and lordosis-like movements in females. Erections/tumescence of penis or clitoris could not be evoked, however. Anterograde tracer injections into penis/clitoris cortex revealed eleven corticocortical and 10 subcortical projection targets, which were qualitatively similar in both sexes. Corticocortical genital-cortex-projections innervated about 3% of the cortical surface and most were analog to other somatosensory projections targeting motor cortex, secondary somatosensory cortex, parietal cortex and perirhinal cortex. Corticocortical projections that differed from other parts of somatosensory cortex targeted male scrotum cortex, female vulva cortex, the somatosensory-ear-auditory-cortex-region and the caudal parietal area. Aligning cytoarchitectonic borders with motor topography, sensory genital responses and corticocortical projections identified a candidate region for genital motor cortex. Most subcortical genital-cortex-projections were analog to other thalamic, tectal or pontine projections of somatosensory cortex. Genital-cortex-specific subcortical projections targeted amygdala and nucleus submedius and accumbens. Microstimulation-effects and projections support a sexual function of genital cortex and suggest that genital cortex is a major hub of sexual sensorimotor processing in rodents.


Learning from extremism in the history of mental health. The example of multiple personality disorder.
This article reviews some of the history of the cultural forces that shaped the diagnosis of multiple personality disorder/dissociative identity disorder and the subsequent abuses that occurred at the time of its popularization. Some of the implications that can be drawn from these kinds of historical excesses in the field of mental health will be discussed. The article concludes by underscoring the ethical obligation inherent in maintaining healthy professional skepticism toward ideas driven by ideology and fad, rather than scientific empiricism.


An extended single-index multiplexed 16S rRNA sequencing for microbial community analysis on MiSeq illumina platforms.
The primary 16S rRNA sequencing protocol for microbial community analysis using Illumina platforms includes a single-indexing approach that allows pooling of hundreds of samples in each sequencing run. The protocol targets the V4 hypervariable region (HVR) of 16S rRNA using 150 bp paired-end (PE) sequencing. However, the latest improvement in Illumina chemistry has increased the read length up to 600 bp using 300 bp PE sequencing. To take advantage of the longer read length, a dual-indexing approach was previously developed for targeting different HVRs. However, due to simple working protocols, the single-index 150 bp PE approach still continues to be attractive to many researchers. Here, we described an extended single-indexing protocol for 300 bp PE illumina sequencing that targets the V3-V4 HVRs of 16S rRNA. The new primer set led to increased read length and alignment resolution, as well as increased richness and diversity of resulting microbial profile compared to that obtained from150 bp PE protocol for V4 sequencing. The β-diversity profile also differed qualitatively and quantitatively between the two approaches. Both primer sets had high coverage rates and specificity to detect dominant phyla; however, their coverage rate with regards to the rare biosphere varied. Our data further confirms that the choice of primer is the most deterministic factor in sequencing coverage and specificity.


Nail Analysis for Drugs: A Role in Workplace Testing?
Analysis of nail clippings may be a useful back-up for hair analysis when hair is unavailable. One aspect of using nails or hair is the ability to analyze whether drug present is from ingestion or from contamination. A common method of three 15-s rinses in methanol failed to remove drug from nails that had been soaked in either 5 or 50 μg/mL cocaine, methamphetamine or morphine for 1 h. While methanol rinsing did not remove contaminating drug, washing the nails soaked with 5 and 50 μg/mL of these drugs with an extended wash, a method developed for hair analysis and consisting of a 15-min isopropanol wash, and three 30-min and two 60-min phosphate buffer-0.1% albumin washes, when applied to nails did remove most of the contaminating drug. The drug left in the nails after extended washing could be interpreted as contamination by applying a wash criterion that is routinely applied in hair analysis. Successful decontamination of the soaked contaminated nail model was followed by applying this extended wash method to presumptive positive nail samples identified in workplace testing. While the extended buffer wash and wash criterion distinguish contamination from ingestion with hair, we failed to demonstrate that the method effectively differentiates contamination from ingestion with nails.


Dynamic hemodynamic energy loss in normal and stenosed aortic valves.
Aortic valve (AV) stenosis, if untreated, leads to heart failure. From a mechanics standpoint, heart failure can be interpreted as the failure of the heart to generate sufficient power to overcome energy losses in the circulation. Thus, energy efficiency-based measures for evaluating AV performance and disease severity have the advantage of being a direct measure of the contribution of the AV hydrodynamic characteristics toward heart failure. We present a new method for computing the rate of energy dissipation as a function of systolic time, by modifying the Navier-Stokes momentum equation. This method preserves the dynamic term of the Navier-Stokes momentum equation, and allows the investigation of the trend of the rate of energy dissipation over time. This method is applied to a series of in vitro experiments, where a trimmed porcine valve is exposed to various conditions: varying stroke volumes (50 ml to 90 ml) at the fixed heart rate; varying heart rates (60-80 beats/min) at fixed stroke volume; and varying stenosis levels (normal, mild stenosis, moderate stenosis). The results are: (1) energy dissipation waveform has a distinctive pattern of being skewed toward late systole, due to flow instabilities during deceleration phases; (2) increasing heart rate and stroke volume increases energy dissipation, but the normalized shape of the energy dissipation waveform is preserved across heart rates and stroke volumes; (3) increasing stenosis level increases energy dissipation, and also alters the normalized shape of the energy dissipation waveform. Since stenosis produces a signature energy dissipation waveform shape, dynamic energy dissipation analysis can potentially be extended into a clinical tool for AV evaluation.


Considering Uterus Transplantation for a Same-Sex Couple: A Case Study.
A woman with congenital absence of a uterus applied for participation in a clinical trial for uterus transplantation. She was married to a woman who had the potential to carry a child without the need for aggressive medical intervention. Thus, the question arose regarding whether the infertile partner should be considered for uterus transplantation. In this article we discuss the ethical issues with uterus transplantation for a member of a same-sex couple, whose partner could carry a pregnancy. We review the medical criteria for uterus transplantation, discuss the additional options for parenthood in same-sex couples, examine how to determine if this meets the criteria of just distribution of uterus grafts, and ultimately argue that the value of gestation is at the level of the individual rather than the couple.


Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression: a pilot study.
The impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method that provides a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). It has recently been demonstrated that TRD is associated with increased inflammatory process. In the present study, we investigated whether a relationship exists between changes in cognitive function and those in inflammatory cytokines before and after rTMS treatment. Eleven patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and serum concentration of inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α) were measured at baseline and at the endpoint of rTMS treatment. rTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that partial changes in cognitive function and changes in IL-1β were significantly correlated. The partial improvement of cognitive dysfunction by rTMS in the present study might be attributable to the reduction of peripheral IL-1β levels. The present results should be replicated for verification in future studies.


The association between diabetes and abdominal aortic aneurysms in men: results of two Danish screening studies, a systematic review, and a meta-analysis of population-based screening studies.
A paradoxical protective effect of diabetes on the development and progression of abdominal aortic aneurysms (AAA) has been known for years. This study aimed to investigate whether the protective role of diabetes on AAAs has evolved over the years. A cross-sectional study, a systematic review and meta-analysis. This study was based on two large, population-based, randomised screening trials of men aged 65-74; VIVA (2008-2011) and DANCAVAS (2014-2018), including measurement of the abdominal aorta by ultrasound or CT, respectively. Analyses were performed using multiple logistic regressions to estimate the odds ratios (ORs) for AAAs in men with diabetes compared to those not having diabetes. Moreover, a systematic review and meta-analysis of population-based screening studies of AAAs to visualise a potential change of the association between diabetes and AAAs. Studies reporting only on women or Asian populations were excluded. In VIVA, the prevalence of AAA was 3.3%, crude OR for AAA in men with diabetes 1.04 (95% confidence interval, CI, 0.80-1.34), and adjusted OR 0.64 (CI 0.48-0.84). In DANCAVAS, the prevalence of AAA was 4.2%, crude OR 1.44 (CI 1.11-1.87), and adjusted OR 0.78 (CI 0.59-1.04). Twenty-three studies were identified for the meta-analysis (N = 224 766). The overall crude OR was 0.90 (CI 0.77-1.05) before 2000 and 1.16 (CI 1.03-1.30) after 1999. The overall adjusted OR was 0.63 (CI 0.59-0.69) before 2000 and 0.69 (CI 0.57-0.84) after 1999. Both the crude and adjusted OR showed a statistically non-significant trend towards an increased risk of AAA by the presence of diabetes. If this represents an actual trend, it could be due to a change in the diabetes population. DANCAVAS: Current Controlled Trials: ISRCTN12157806. VIVA: ClinicalTrials.gov NCT00662480.


Essential Oils for the Conservation of Paper Items.
Archival documents and artworks stored in libraries frequently undergo degradative processes promoted by the so-called "biodeteriogens" that inhabit these places. A renewed interest in plant-derived products has arisen in those research groups focusing on cultural heritage preservation and looking for new and safe disinfection techniques. In this view, essential oils (EOs) and their volatile organic constituents are very appealing thanks to their versatility of action. A literature survey of the scientific publications involving EOs and/or their major constituents related to the conservation of paper items of cultural heritage interest is presented here, aiming to reveal benefits and limitations of such peculiar plant-derived compounds.


Hetero-oligomerization of the P2Y11 receptor with the P2Y1 receptor controls the internalization and ligand selectivity of the P2Y11 receptor.
Nucleotides signal through purinergic receptors such as the P2 receptors, which are subdivided into the ionotropic P2X receptors and the metabotropic P2Y receptors. The diversity of functions within the purinergic receptor family is required for the tissue-specificity of nucleotide signalling. In the present study, hetero-oligomerization between two metabotropic P2Y receptor subtypes is established. These receptors, P2Y1 and P2Y11, were found to associate together when co-expressed in HEK293 cells. This association was detected by co-pull-down, immunoprecipitation and FRET (fluorescence resonance energy transfer) experiments. We found a striking functional consequence of the interaction between the P2Y11 receptor and the P2Y1 receptor where this interaction promotes agonist-induced internalization of the P2Y11 receptor. This is remarkable because the P2Y11 receptor by itself is not able to undergo endocytosis. Co-internalization of these receptors was also seen in 1321N1 astrocytoma cells co-expressing both P2Y11 and P2Y1 receptors, upon stimulation with ATP or the P2Y1 receptor-specific agonist 2-MeS-ADP. 1321N1 astrocytoma cells do not express endogenous P2Y receptors. Moreover, in HEK293 cells, the P2Y11 receptor was found to functionally associate with endogenous P2Y1 receptors. Treatment of HEK293 cells with siRNA (small interfering RNA) directed against the P2Y1 receptor diminished the agonist-induced endocytosis of the heterologously expressed GFP-P2Y11 receptor. Pharmacological characteristics of the P2Y11 receptor expressed in HEK293 cells were determined by recording Ca2+ responses after nucleotide stimulation. This analysis revealed a ligand specificity which was different from the agonist profile established in cells expressing the P2Y11 receptor as the only metabotropic nucleotide receptor. Thus the hetero-oligomerization of the P2Y1 and P2Y11 receptors allows novel functions of the P2Y11 receptor in response to extracellular nucleotides.


Consortium management structures, processes, and approaches: The DELTAS Africa example.
Background: Global efforts to strengthen health research capacity in low- and middle-income countries (LMICs) have intensified in the past few decades, and these efforts are often implemented by consortia. Our review of the literature indicated that reports on health research capacity strengthening (HRCS) consortia have primarily focused on programme outputs and outcomes while management processes and their contributions to consortia goals have received little attention. This qualitative study sought to identify the consortium management processes employed by 10 DELTAS Africa consortia, factors influencing these processes, and leaders' consortium management experiences. Methods: We conducted 24 key informant interviews with the directors and programme managers of all the 10 DELTAS Africa consortia, and funding actors who worked closely with the consortia. The interviews were supplemented by reviews of DELTAS and consortium-specific documents. Data were analysed using the content analysis approach. Results: The consortia studied employed similar management processes but adopted different strategies in executing these processes. Study results indicate that decision-making in consortia is not always a straightforward process as leaders were often faced with dilemmas when determining management strategies to adopt, and often tried to balance multiple factors which were not always aligned. This was demonstrated as consortia selected partners, determined goals and activities, assigned roles and responsibilities, allocated resources, established governance and partner management systems, and coordinated and monitored consortia activities. Factors that influenced the choice of processes and approaches included previous experiences, funders expectations, and the pressure to deliver research outputs. Consortia's unique approaches to management were due to varying contexts and influences and indicate that management decisions are nuanced and cannot easily be formularized. Conclusion: The study has highlighted the importance of flexibility in consortium management and the need to generate research capacity strengthening (RCS)-specific guidance that can assist consortia in resolving dilemmas and making appropriate management decisions.


Interaction between amylose and beta-cyclodextrin investigated by complexing with conjugated linoleic acid.
Interaction between amylose, a common food component, and beta-cyclodextrin (betaCD), an often used food additive, was investigated by incorporating a third component of bioactive conjugated linoleic acid (CLA) that could form an inclusion complex with both amylose and betaCD. The existence of an amylose-betaCD interaction was first evidenced by a reduced thermal stability of amylose in the amylose-betaCD complex and a decrease of extractable betaCD from 60 to 51.40% after their complexation. The way of their interaction was then explored in a three-component system, in which the amount of CLA is high enough to oversaturate both amylose and betaCD. In comparison to the amylose-CLA and betaCD-CLA complexes, a self-assemblied amylose-CLA-betaCD three-component complex confirmed by differential scanning calorimetry (DSC), X-ray diffraction, and thermogravimetric analyses showed an in-between thermal stability, high acid stability, and the highest amylolytic digestibility (74.43%), which suggests that betaCD is likely sandwiched between the helical amylose chains in the amylose-betaCD complex. Therefore, betaCD can be used to manipulate the crystallization process of amylose to modulate food product quality, and the amylose-betaCD complex could also be applied to improve the delivery efficiency of CLA and other bioactive compounds.


The Walking Recovery One Year after Surgical Management of Thoracolumbar Burst Fracture in Paraplegic Patients.
The aim of this study was to highlight the walking recovery after surgical management of traumatic burst fractures at the thoracolumbar junction (T10 or T11 or T12 or L1) in paraplegic patients to decide what surgeons should tell their patients to help them develop realistic expectations and potentially improve their outcome. This is a series of adult patients presented with paraplegia from isolated thoracolumbar fracture and underwent surgical intervention from August 2009 to August 2015. Patients with preexisting disability from previous neurologic condition, patients with associated severe head injury or major medical comorbidities or life-threatening injuries were excluded. Neurological status was assessed on admission using the American Spinal Injury Association (ASIA) impairment scale (AIS). The walking ability was assessed 12 months after surgery using the modified Benzel scale. This study included 53 patients with a mean age of 39.4 years (ranging from 18 years to 58 years). Patients presented with AIS grade A are 6, 18 patients with AIS grade B, and 29 patients with AIS grade C. All the patients with L1 fracture and 70.96% of the patients with T12 fracture regained the ability to walk, but unfortunately all the patients with T10 and T11 fractures didn't regain the walking ability 12 months after surgery. The severity of spinal cord injury and hence the walking recovery were related to the spinal level of fracture. A prospectively controlled study with more patients is needed to reevaluate the walking recovery in paraplegic patients with T10 and T11 fractures.


Soft tissue sarcomas of the distal lower extremities: A single-institutional analysis of the prognostic significance of surgical margins in 120 patients.
Soft tissue sarcomas (STS) arising in the distal lower extremities pose a therapeutic challenge due to concerns of functional morbidity. The impact of surgical margins on local recurrence‑free survival (LRFS) and overall survival (OS) still remains controversial. The aim of this study was to identify prognostic indicators of survival and functional outcome in patients with STS of the distal lower extremities through a long‑term follow‑up. Between 1999 and 2014, 120 patients with STS of the foot, ankle and lower leg were treated surgically at our institution. The median follow‑up was 6.3 years. The results reveal that the 5‑year estimate of the OS rate was 80.0% [95% confidence interval (CI): 69.6‑87.1] for the entire series. Surgical margins attained at the resection of the primary tumor did not influence OS significantly [5‑year OS: R0 80.5% (69.7‑87.9) vs. R1 74.1% (28.9‑93.0); P=0.318]. Within the R0 subgroup, negative surgical margin widths ≤1 and >1 mm led to similar outcomes, as well as ≤5 and >5 mm, respectively. In the multivariate analysis, significant adverse prognostic features included male gender and age >60 years at the time point of primary diagnosis. In conclusion, the data from this study could not underscore the long‑term benefit of negative margins achieved at the resection of the primary tumor. Surgical efforts should aim at function‑sparing resections when feasible with negative margins. Here, close negative margins seem to be adequate.


Methods for cell-attached capacitance measurements in mouse adrenal chromaffin cell.
Neuronal transmission is an integral part of cellular communication within the brain. Depolarization of the presynaptic membrane leads to vesicle fusion known as exocytosis that mediates synaptic transmission. Subsequent retrieval of synaptic vesicles is necessary to generate new neurotransmitter-filled vesicles in a process identified as endocytosis. During exocytosis, fusing vesicle membranes will result in an increase in surface area and subsequent endocytosis results in a decrease in the surface area. Here, our lab demonstrates a basic introduction to cell-attached capacitance recordings of single endocytic events in the mouse adrenal chromaffin cell. This type of electrical recording is useful for high-resolution recordings of exocytosis and endocytosis at the single vesicle level. While this technique can detect both vesicle exocytosis and endocytosis, the focus of our lab is vesicle endocytosis. Moreover, this technique allows us to analyze the kinetics of single endocytic events. Here the methods for mouse adrenal gland tissue dissection, chromaffin cell culture, basic cell-attached techniques, and subsequent examples of individual traces measuring singular endocytic event are described.


Crucible-Free Preparation of Transition-Metal Borides: HfB2.
This study gives an account of an innovative, crucible-free technique for the synthesis of single-phase borides at relatively moderate temperatures. A metal wire heated by an electrical current reacts with a chosen gaseous boron halide in a gas/solid reaction yielding a single-phase, oxygen- and carbon-free product, as evidenced by X-ray powder diffraction and chemical analysis. This method is demonstrated using the example of hafnium reacting with boron tribromide. Preliminary thermodynamic considerations show that this kind of crucible-free synthesis specifically enables the preparation of borides of transition metals and similar elements.


Screening at school entry: vision, hearing and growth.
Tam Fry of the Child Growth Foundation criticises the new recommendations for screening at school entry in the 2003 edition of Health for all Children. He argues that proposals to reduce preschool surveillance make the school entry screening even more important for detecting deviations from the normal, especially in vision, hearing and growth. This surveillance needs to be rigorously performed, yet a shortage of school nurses and optometrists makes this less likely to happen. The author argues that even though there may be insufficient evidence for retaining current preschool screening programmes, there is also insufficient evidence to show that severely curtailing them will not cause harm.


Social cognition and social functioning in nonclinical paranoia.
Persons with nonclinical paranoia show many of the same biases as those with clinical paranoia, suggesting that paranoia exists on a continuum. However, little is known about the various social cognitive processes found in paranoia and how these relate to social functioning and social behaviours in general. This study will examine performance on emotion perception and attributional style measures and their relationship to social functioning, social problem solving, and social skill. A key element in this study will be the incorporation of ambiguity in the perception of emotional expressions and the assignment of attributional blame, which appears to be an important, yet neglected, construct in paranoia. Twenty-six persons with high levels of nonclinical paranoia and 31 persons with low levels of paranoia completed measures of emotion perception, attributional style, social functioning, and social problem solving. Salient and subtle emotional expressions were used to examine how ambiguity impacts emotion perception in paranoia. The group high in nonclinical paranoia showed reduced accuracy for subtle negative emotional expressions and showed more perceived hostility and blame for ambiguous social situations as compared to the group low in nonclinical paranoia. Also, the high nonclinical paranoia group reported less social engagement, fewer social contacts, and more problems in social perception and social skill than the group low in nonclinical paranoia. Social cognitive and social functioning biases are found in persons with high levels of nonclinical paranoia. Possible mechanisms of these biases and relevance for treatment approaches are discussed.


Comparison of human polycystic and medullary cystic kidney disease with diphenylamine-induced cystic disease.
Because of difficulty in obtaining cystic human kidneys for functional and morphologic study, animal models are receiving increasing attention. Most prominent among them is the renal cystic disease that is induced in rats through feeding of the antioxidant, diphenylamine, The present study examined the morphology of adult polycystic and medullary cystic kidney disease in man using scanning electron microscopy and compared them with diphenylamine-induced cystic kidney disease in rats. Diphenylamine nephropathy was induced by feeding rats 1 per cent diphenylamine for 12 to 18 months. All types of cystic disease showed changes in the renal corpuscles, including dilation of Bowman's space, podocyte fusion and degeneration, and basement membrane thickening. Cysts were noted along the entire nephron in polycystic and diphenylamine-induced cystic disease but only along the collecting ducts in medullary cystic disease. Cysts in polycystic disease were large and lined by flattened epithelium. Collecting duct cysts in diphenylamine cystic disease were lined by cells of irregular size and shape suggestive of cell hypertrophy and/or hyperplasia, whereas cysts of medullary cystic disease were lined by flattened epithelium except where the nephron entered or left the cyst. Cast material was generally found in the cysts of diphenylamine-induced and polycystic kidney disease but not medullary cystic disease. Atrophic glomeruli and tubules were found in all three diseases. Complete tubular obstruction was found in none; however, larger cysts frequently impinged on adjacent tubules and narrowed their lumina. The results of this study show that, in the terminal stages, cellular as well as gross morphologic differences exist between polycystic and medullary cystic kidney disease and that diphenylamine-induced cystic disease more closely resembles human polycystic than medullary cystic kidney disease.


Multi-criteria decision-making methods applied in health-insurance underwriting.
This study attempts to structure methodologically the health insurance underwriting process by applying Multi-criteria Decision-making (MCDM) analysis in health insurance underwriting. This is done by assigning a score to each health insurance applicant which can be used to determine whether he or she is accepted, rejected or accepted with special terms and conditions (such as exclusions, additional waiting periods and/ or surcharge). The introduction of MCDM approaches in health insurance underwriting enables the quantification of the selection criteria, the increased standardization and automation of the process and its alignment through quantitative indicators with the risk tolerance/ risk appetite of the insurer, and there lie the novelties of this research. The proposed methodology can be readily implemented by insurers with added value in the underwriting, risk management and distribution (sales & marketing) functions, as well as in the profitability of the company or the level of premium paid by the insured.


Compartment-Specific Importance of Ascorbate During Environmental Stress in Plants.
Ascorbate is an essential antioxidant in plants. Total contents and its redox state in organelles are crucial to fight and signal oxidative stress. Recent Advances: With quantitative immunoelectron microscopy and biochemical methods, highest ascorbate contents have recently been measured in peroxisomes (23 mM) and the cytosol (22 mM), lowest ones in vacuoles (2 mM), and intermediate concentrations (4-16 mM) in all other organelles. The accumulation of ascorbate in chloroplasts and peroxisomes is crucial for plant defense. Its depletion in chloroplasts, peroxisomes, and mitochondria during biotic stress leads to the accumulation of reactive oxygen species (ROS) and the development of chlorosis and necrosis. In the apoplast and vacuoles, ascorbate is the most important antioxidant for the detoxification of ROS. The cytosol acts as a hub for ascorbate metabolism as it reduces its oxidized forms that are produced in the cytosol or imported from other cell compartments. It is a sink for ascorbate that is produced in mitochondria, distributes ascorbate to all organelles, and uses ascorbate to detoxify ROS. As ascorbate and its redox state are involved in protein synthesis and modifications, it can be concluded that ascorbate in the cytosol senses oxidative stress and regulates plant growth, development, and defense. Future research should focus on (1) dissecting roles of ascorbate in vacuoles and the lumen of the endoplasmic reticulum, (2) identifying the physiological relevance of ascorbate transporters, and (3) correlating current data with changes in the subcellular distribution of related enzymes, ROS, and gene expression patterns.


Surface-induced unfolding of human lactoferrin.
We have determined the structural conformations of human lactoferrin adsorbed at the air/water interface by neutron reflectivity (NR) and its solution structure by small angle neutron scattering (SANS). The neutron reflectivity measurements revealed a strong structural unfolding of the molecule when adsorbed at the interface from a pH 7 phosphate buffer solution (PBS with a total ionic strength at 4.5 mM) over a wide concentration range. Two distinct regions, a top dense layer of 15-20 angstroms on the air side and a bottom diffuse layer of some 50 angstroms into the aqueous subphase, characterized the unfolded interfacial layer. At a concentration around 1 g dm(-3), close to the physiological concentration of lactoferrin in biological fluids, the adsorbed amount was 5.5 x 10(-8) mol m(-2) in the absence of NaCl, but the addition of 0.3 M NaCl reduced protein adsorption to 3.5 x 10(-8) mol m(-2). Although the polypeptide distributions at the interface remained similar, quantitative analysis showed that the addition of NaCl reduced the layer thickness. Parallel measurements of lactoferrin adsorption in D2O instead of null reflecting water confirmed the unfolded structure at the interface. Furthermore, the D2O data indicated that the polypeptide in the top layer was predominantly protruded out of water, consistent with it being hydrophobic. In contrast, the scattering intensity profiles from SANS were well described by a cylindrical model with a diameter of 47 angstroms and a length of 105 angstroms in the presence of 0.3 M NaCl, indicating a retention of the globular framework in the bulk solution. In the absence of NaCl but with the same amount of phosphate buffer, the length of the cylinder increased to some 190 angstroms and the diameter remained constant. The length increase is indicative of changes in distance and orientation between the bilobal monomers due to the change in charge interactions. The results thus demonstrate that the surface structural unfolding was caused by the exposure of the protein molecule to the unsymmetrical energetic balance following surface adsorption.


CbgA, a protein involved in cortex formation and stress resistance in Myxococcus xanthus spores.
CbgA plays a role in cortex formation and the acquisition of a subset of stress resistance properties in Myxococcus xanthus spores. The cbgA mutant produces spores with thin or no cortex layers, and these spores are more sensitive to heat and sodium dodecyl sulfate than their wild-type counterparts.


Conductive silver paste smeared glass substrates for label-free Raman spectroscopic detection of HIV-1 and HIV-1 p24 antigen in blood plasma.
We report on application of conductive silver paste smeared glass slides as Raman spectroscopy sample substrates for label-free detection of HIV-1 p24 antigen in blood plasma. We also show that the same substrates can be applied in Raman spectroscopic screening of blood plasma for presence of HIV. The characteristic Raman spectrum of HIV-1 p24 antigen displayed prominent bands that were assigned to ribonucleic acids (RNA) and proteins that constitute the antigen. This spectrum can be used as reference during Raman spectroscopic screening for HIV in plasma within the first few days after exposure (<7 days). The Raman spectra obtained from HIV+ plasma displayed unique peaks centered at wavenumbers 928, 990, 1270, 1397, and 1446 cm-1 attributed to the Raman active vibrations in the virion carbohydrates, lipids, and proteins. Other bands similar to those reported in literature were also seen and assignments made. The attachment of the HIV virions to silver nanoparticles via gp120 glycoprotein knobs was thought to be responsible for the enhanced Raman signals of proteins associated with the virus. The principal component analysis (PCA) applied on the combined spectral data showed that HIV- and HIV+ spectra had differing spectral patterns. This indicated the great power of Raman spectroscopy in HIV detection when plasma samples are deposited onto silver paste smeared glass substrates. The Raman peaks responsible for the segregation of the spectral data in PCA were mainly those assigned to the viral proteins (645, 725, 813, 1270, and 1658 cm-1). Excellent results were obtained from Artificial Neural Network (ANN) applied on the HIV+ Raman spectral data around the prominent peak centered at 1270 cm-1 with R (coefficient of correlation) and R 2 (coefficient of determination) values of 0.9958 and 0.9895, respectively. The method has the potential of being used as quick blood screening for HIV before blood transfusion with the Raman peaks assigned to the virion proteins acting as reference. Graphical Abstract The HIV type 1 virus particle gets attached to the silver nanoparticle contained in the conductive silver paste smear onto a glass slide. This results in strong Raman signals associated with the components of the virion. The signals are collected, dispersed in a spectrometer and displayed on a computer screen. Method can be used as a label-free and rapid HIV screening in blood plasma.


Evaluation of a Preclerkship Learning Community Model for Delivering Clinical Skills Curriculum.
Medical schools are increasingly using learning communities (LCs) for clinical skills curriculum delivery despite little research on LCs employed for this purpose. We evaluated an LC model compared with a non-LC model for preclerkship clinical skills curriculum using Kirkpatrick's hierarchy as an evaluation framework. The first LC cohort's (N = 101; matriculating Fall 2013) reaction to the LC model was assessed with self-reported surveys. Change in skills and learning transfer to clerkships was measured with objective structured clinical examinations (OSCEs) at the end of years 2 and 3 and first and last clerkship preceptor evaluations; the LC cohort and the prior cohort (N = 86; matriculating Fall 2012) that received clinical skills instruction in a non-LC format were compared with Mann-Whitney U tests. The LC model for preclerkship clinical skills curriculum was rated as excellent or good by 96% of respondents in Semesters 1 to 3 (N = 95). Across multiple performance domains, 96% to 99% of students were satisfied to very satisfied with their LC faculty preceptors (N varied by item). For the end of preclerkship OSCE, the LC cohort scored higher than the non-LC cohort in history gathering (P = .003, d = 0.50), physical examination (P = .019, d = 0.32), and encounter documentation (P ⩽ .001, d = 0.47); the non-LC cohort scored higher than the LC cohort in communication (P = .001, d = 0.43). For the end of year 3 OSCE, the LC cohort scored higher than the non-LC cohort in history gathering (P = .006, d = 0.50) and encounter note documentation (P = .027, d = 0.24); there was no difference in physical examination or communication scores between cohorts. There was no detectable difference between LC and non-LC student performance on the preceptor evaluation forms at either the beginning or end of the clerkship curriculum. We observed limited performance improvements for LC compared with non-LC students on the end of the preclerkship OSCE but not on the clerkship preceptor evaluations. Additional studies of LC models for clinical skills curriculum delivery are needed to further elucidate their impact on the professional development of medical students.


[Effect of Drought and Subsequent Re-wetting Cycles on Transferable Nitrogen and Its Form Distribution in the Sediment of Water Level Fluctuating Zone in the Tributary of Three Gorge Reservoir Areas].
Nitrogen is the most comment source of eutrophication in freshwater systems. In current study, we investigated the various forms of transferable nitrogen in sediments, which potentially contributed to the nitrogen output into waters. Sediments samples were collected in the water level fluctuating zone of Pengxi River crossing three hydrological sections, e. g. upstream, midstream and downstream and two water level altitudes, 160 m and 170 m, with multiple depths for each site, 0-20, 20-40, 40-60, 60-80, 80-100 cm. To characterize the response of transformation of nitrogen in sediment of the water level fluctuating zone towards cycles of drought and re-wetting processes, we analyzed the content and distribution of transferable nitrogen (TF-N) and its forms. The result showed that the changing of the amount of total nitrogen followed the pattern of upstream > midstream > downstream, the mean value was in the range of 313.02-3 255.53 mg. kg-1, while the content of total transferable nitrogen was on an average of 639.40 mg . kg-1 and coincided with the pattern of total nitrogen. In addition, TF-N followed the pattern of OSF-N > IMOF-N > OSF-N > IEF-N. It indicated that both OSF-N and IMOF-N dominated the form of TF-N in sediments by proportions of 50. 9% and 33. 3%, respectively. Since the transformation rate of OSF-N into dissolved phase was relatively slow, its contribution as a source of nitrogen to eutrophication was limited. We, thus, concluded that IMOF-N was the most important fraction which could be potentially affected by water fluctuation and contributed as dissolved nitrogen into water phase. This study indicated that the manner of manipulating water resource in the Three Gorges Reservoir area has raised the potential risk of transforming IMOF-N from sediment into water phase.


Imaging findings predicting the outcome of cervical facet joint blocks.
To determine which cross-sectional imaging findings predict the short-term outcome of cervical facet joint blocks (FJB) and to evaluate the effect of combined intra-/periarticular versus periarticular injection on pain. Fifty facet joints in 37 patients were included in the study. Single, unilateral FJBs in 24 patients, and bilateral single level FJBs in 13 patients were performed, respectively. In all patients, pain relief was assessed using a visual analogue scale. All computed tomography (CT) examinations were blindly reviewed by two radiologists. Osteoarthritis was rated using the Kellgren classification. The presence of combined intra-/periarticular vs. sole periarticular injection of contrast was evaluated. Kellgren Grades 0 (n=23), 1 (n=5), 2 (n=3), 3 (n=9), and 4 (n=10) were found. Mean pain relief after injection was 35% (range: 0-100%). 40% of all injections were combined intra-/periarticular. There was neither a statistically significant difference between pain relief and combined intra-/periarticular versus sole periarticular injection (p=0.64) nor the grade of osteoarthritis (p=0.49). Pain relief after cervical FJBs does not correlate with morphologic alterations seen on CT. Periarticular FJBs are not less successful than combined intra-/periarticular FJBs.


Short-term, intensive neurodevelopmental treatment program experiences of parents and their children with disabilities.
Parents' perspectives on intervention and functional changes in children were investigated following an intensive neurodevelopmental treatment (NDT) program of 1 to 2 weeks (5 consecutive days per week; 2-4 h/d). Thirteen parents and their children (aged 1-17 years) with neuromotor conditions participated in a short-term, intensive program conducted by NDT certified pediatric therapists. A mixed-method design was used: a qualitative phenomenological approach of inquiry for parent perspectives and a pre/posttest quasi-experimental design for weekly intervention changes using Goal Attainment Scaling and the Canadian Occupational Performance Measure. Through interviews, parents reported positive experiences with the intensive NDT program. Child participants demonstrated significant improvements in Goal Attainment Scaling (P < .001) and Canadian Occupational Performance Measure (P < .001) scores pre- to postintervention. A short-term, intensive NDT program was perceived by parents as beneficial and supported functional improvements. Valued were expert, compassionate therapists; collaboration; objective goals; home programming; and individualized intervention. Scheduling, financial support, and fatigue were difficulties.


Combination of MiR-378 and MiR-210 Serum Levels Enables Sensitive Detection of Renal Cell Carcinoma.
Serum microRNAs are emerging as a clinically useful tool for early and non-invasive detection of various cancer types including renal cell carcinoma (RCC). Based on our previous results, we performed the study to analyze circulating serum miR-378 and miR-210 in patients with various histological subtypes of RCC. RNA was purified from blood serum samples of 195 RCC patients and 100 healthy controls. The levels of miR-378 and miR-210 in serum were determined absolutely using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs were compared in 20 RCC patients. Significantly increased serum levels of both miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy controls with 80% sensitivity and 78% specificity if analyzed in combination (p<0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p<0.0001). Increased level of miR-378 positively correlates with disease-free survival (p=0.036) and clinical stage (p=0.0476). The analysis of serum miR-378 and miR-210 proved their potential to serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.


Pd Nanocluster/Monolayer MoS2 Heterojunctions for Light-Induced Room-Temperature Hydrogen Sensing.
Developing sensing approaches that can exploit visible light for the detection of low-concentration hydrogen at room temperatures has become increasingly important for the safe use of hydrogen in many applications. In this study, heterostructures composed of monolayer MoS2 and Pd nanoclusters (Pd/MoS2) acting as photo- and hydrogen-sensitizers are successfully fabricated in a facile and scalable manner. The uniform deposition of morphologically isotropic Pd nanoclusters (11.5 ± 2.2 nm) on monolayer MoS2 produces a plethora of active heterojunctions, effectively suppressing charge carrier recombination under light illumination. The dual photo- and hydrogen-sensitizing functionality of Pd/MoS2 can enable its use as an active sensing layer in optoelectronic hydrogen sensors. Gas-sensing examinations reveal that the sensing performance of Pd/MoS2 is enhanced three-fold under visible light illumination (17% for 140 ppm of H2) in comparison with dark light (5% for 140 ppm of H2). Photoactivation is also found to enable excellent sensing reversibility and reproducibility in the obtained sensor. As a proof-of-concept, the integration of Pd nanoclusters and monolayer MoS2 can open a new avenue for light-induced hydrogen gas sensing at room temperature.


Alleviating Cellular Oxidative Stress through Treatment with Superoxide-Triggered Persulfide Prodrugs.
Overproduction of superoxide anion (O2.- ), the primary cellular reactive oxygen species (ROS), is implicated in various human diseases. To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O2.- to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H2 S). Termed SOPD-NAC, this persulfide donor reacts specifically with O2.- , decomposing to generate N-acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self-assembling peptide (Bz-CFFE-NH2 ) to make a superoxide-responsive, persulfide-donating peptide (SOPD-Pep). Both SOPD-NAC and SOPD-Pep delivered persulfides/H2 S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that SOPD-Pep mitigated toxicity induced by phorbol 12-myristate 13-acetate (PMA) more effectively than SOPD-NAC and several control compounds, including common H2 S donors.


Antimicrobial Selection for the Equine Practitioner.
Antimicrobial drugs play an important, often central, role in the therapeutic management of mature horses and foals with a variety of illnesses, including those requiring critical care. Antimicrobial use must be based on rational principles involving thorough patient evaluation and sound clinical judgment that indicate a high likelihood that the patient has a bacterial infection and that antimicrobials are indicated to promote recovery. The aim of antimicrobial treatment is to inflict an insult on infecting bacteria sufficient to kill the organism or render it susceptible to inactivation by natural host defenses or the local microenvironment without adversely affecting the patient.


Adjuvant tamoxifen prescription in women 65 years and older with primary breast cancer.
We examined patterns of adjuvant tamoxifen discussion and prescription among breast cancer patients age 65 years and older. We selected from women diagnosed with primary breast cancer those with (1) stage I (tumor diameter > or = 1 cm), stage II, or stage IIIa disease; (2) age 65 years or older on the date of diagnosis; and (3) permission from the attending physician to contact. Data were collected from consenting patients' medical records, telephone interviews with patients, and mailed questionnaires completed by their physicians. We obtained medical record and interview data for 698 patients. The oldest patients (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.23 to 0.87 for those aged 80+ relative to those aged 65 to 69 years old), those with more comorbid conditions (each additional comorbid condition reduced the odds of discussion by 0.84; 95% CI, 0.73 to 0.96), and those who were estrogen receptor-negative (OR, 0.56; 95% CI, 0.32 to 0.99) were less likely to report discussion of tamoxifen therapy with a physician. Older patients (OR, 2.17; 95% CI, 1.18 to 4.01 for 70- to 79-year-olds relative to 65- to 69-year-olds; OR, 2.44; 95% CI, 1.11 to 5.34 for those aged 80+ relative to those aged 65 to 69 years old), those who reported a greater influence of information about tamoxifen on decision-making (an increase in 1 SD increased the odds by 7.43; 95% CI, 4.36 to 12.65), and those whose physicians believed that the benefits of tamoxifen outweighed its risks (an increase in 1 SD increased the odds by 1.87; 95% CI, 1.34 to 2.62) were more likely to be prescribed tamoxifen. These findings highlight the key role of communication in the care of older women with breast cancer and its ultimate influence on the receipt of therapy.


Design, synthesis and biological evaluation of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines as antiplasmodial antifolates.
The design, synthesis and biological evaluation of a series of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines is described. These compounds exhibited in vitro antiplasmodial activity in the low nanomolar range against both drug sensitive and drug resistant strains of P. falciparum, with 1-(3-(2,4-dichlorophenoxy)propyl)-6-phenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride identified as the most potent compound from this series against the drug resistant FCR-3 strain (IC50 2.66 nM). The compounds were not toxic to mammalian cells at therapeutic concentrations and were shown to be inhibitors of parasitic DHFR in a biochemical enzyme assay.


Elution Is a Critical Step for Recovering Human Adenovirus 40 from Tap Water and Surface Water by Cross-Flow Ultrafiltration.
This paper examines the recovery of the enteric adenovirus human adenovirus 40 (HAdV 40) by cross-flow ultrafiltration and interprets recovery values in terms of physicochemical interactions of virions during sample concentration. Prior to ultrafiltration, membranes were either blocked by exposure to calf serum (CS) or coated with a polyelectrolyte multilayer (PEM). HAdV 40 is a hydrophobic virus with a point of zero charge between pH 4.0 and pH 4.3. In accordance with predictions from the extended Derjaguin-Landau-Verwey-Overbeek theory, the preelution recovery of HAdV (rpre) from deionized water was higher with PEM-coated membranes (rpre (PEM) = 74.8% ± 9.7%) than with CS-blocked membranes (rpre (CS) = 54.1% ± 6.2%). With either membrane type, the total virion recovery after elution (rpost) was high for both deionized water (rpost (PEM) = 99.5% ± 6.6% and rpost (CS) = 98.8% ± 7.7%) and tap water (rpost (PEM) = 89% ± 15% and rpost (CS) = 93.7% ± 6.9%). The nearly 100% recoveries suggest that the polyanion (sodium polyphosphate) and surfactant (Tween 80) in the eluent disrupt electrostatic and hydrophobic interactions between the virion and the membrane. Addition of EDTA to the eluent greatly improved the elution efficacy (rpost (CS) = 88.6% ± 4.3% and rpost (PEM) = 87.0% ± 6.9%) with surface water, even when the organic carbon concentration in the water was high (9.4 ± 0.1 mg/liter). EDTA likely disrupts cation bridging between virions and particles in the feed water matrix or the fouling layer on the membrane surface. For complex water matrices, the eluent composition is the most important factor for achieving high virion recovery. Herein we present the results of a comprehensive physicochemical characterization of HAdV 40, an important human pathogen. The data on HAdV 40 surface properties enabled rigorous modeling to gain an understanding of the energetics of virion-virion and virion-filter interactions. Cross-flow filtration for concentration and recovery of HAdV 40 was evaluated, with postelution recoveries from ultrapure water (99%), tap water (∼91%), and high-carbon-content surface water (∼84%) being demonstrated. These results are significant because of the very low adenovirus recoveries that have been reported, to date, for other methods. The recovery data were interpreted in terms of specific interactions, and the eluent composition was designed accordingly to maximize HAdV 40 recovery.


Supportive short-term family therapy by nursing staff in the inpatient unit: preventing dependence and rehospitalization in the acutely ill and suicidal adolescent.
Adolescents with acute mental illness or suicidal behavior are almost always hospitalized for safety and evaluation purposes. The tendency towards long-term or repeated hospitalizations has many adverse effects such as dependency on the mental health care system and increased chronicity of illness. The causes for these phenomena may be prevented in the early stages of hospitalization. We suggest a therapeutic model of supportive short-term family therapy. The family therapy component aims to enhance the quality of interaction and the level of support among family members. The therapy component dealing with the individual targets the patient's anxiety symptoms and coping strategies, and focuses on return to a healthy state. The child is encouraged to return home to a supportive family as soon as the treatment team feels this to be advisable. This paper discusses a case which highlights how a patient reacts in crisis, and ways in which a supportive environment can help bring about therapeutic success with reduced hospitalization.


Genetic IGF1R defects: new cases expand the spectrum of clinical features.
We aimed to identify the phenotypic variability of IGF1R defects in a cohort of short children with normal GH secretion gathered through the last decade. Fifty children (25 girls) with short stature and a basal/stimulated growth hormone (GH) over 10 ng/ml having either a low birth weight or microcephaly were enrolled. MLPA and then Sanger sequence analysis were performed to detect IGF1R defects. The auxological and metabolic evaluation were carried out in index cases and their first degree family members whenever available. A total of seven (14%) IGF1R defects were detected. Two IGF1R deletions and five heterozygous variants (one frameshift, four missense) were identified. Three (likely) pathogenic, one VUS and one likely benign were classified by using ACMG. All children with IGF1R defects had a height < - 2.5SDS, birth weight < - 1.4SDS, and head circumference < - 1.36SDS. IGF-1 ranged from - 2.44 to 2.13 SDS. One child with a 15q terminal deletion had a normal phenotype and intelligence, whereas low IQ is a finding in a case with missense variant. Two parents who carried IGF1R mutations had diabetes mellitus, hypertension and hyperlipidemia, one of whom also had hypergonadotropic hypogonadism. We found a deletion or variant in IGF1R in 14% of short children. Birth weight, head circumference, intelligence, dysmorphic features, IGF-1 levels and even height are not consistent among patients. Additionally, metabolic and gonadal complications may appear during adulthood, suggesting that patients should be followed into adulthood to monitor for these late complications.


Targeting inflammation in diabetic kidney disease: early clinical trials.
The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials. The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action. Agents mainly targeting other pathways, such as endothelin receptor or mineralocorticoid receptor blockers and vitamin D receptor activators are not discussed. Agents targeting inflammation have shown promising results in the treatment of diabetic kidney disease when added on top of RAS blockade. The success of pentoxifylline in open label trials supports the concept of targeting inflammation. In early clinical trials, the pentoxifylline derivative CTP-499, the CCR2 inhibitor CCX140-B, the CCL2 inhibitor emapticap pegol and the JAK1/JAK2 inhibitor baricitinib were the most promising drugs for diabetic kidney disease. The termination of trials testing the anti-IL-1β antibody gevokizumab in 2015 will postpone the evaluation of therapies targeting inflammatory cytokines.


Effect of cellular quiescence on the success of targeted CML therapy.
Similar to tissue stem cells, primitive tumor cells in chronic myelogenous leukemia have been observed to undergo quiescence; that is, the cells can temporarily stop dividing. Using mathematical models, we investigate the effect of cellular quiescence on the outcome of therapy with targeted small molecule inhibitors. According to the models, the initiation of treatment can result in different patterns of tumor cell decline: a biphasic decline, a one-phase decline, and a reverse biphasic decline. A biphasic decline involves a fast initial phase (which roughly corresponds to the eradication of cycling cells by the drug), followed by a second and slower phase of exponential decline (corresponding to awakening and death of quiescent cells), which helps explain clinical data. We define the time when the switch to the second phase occurs, and identify parameters that determine whether therapy can drive the tumor extinct in a reasonable period of time or not. We further ask how cellular quiescence affects the evolution of drug resistance. We find that it has no effect on the probability that resistant mutants exist before therapy if treatment occurs with a single drug, but that quiescence increases the probability of having resistant mutants if patients are treated with a combination of two or more drugs with different targets. Interestingly, while quiescence prolongs the time until therapy reduces the number of cells to low levels or extinction, the therapy phase is irrelevant for the evolution of drug resistant mutants. If treatment fails as a result of resistance, the mutants will have evolved during the tumor growth phase, before the start of therapy. Thus, prevention of resistance is not promoted by reducing the quiescent cell population during therapy (e.g., by a combination of cell activation and drug-mediated killing). The mathematical models provide insights into the effect of quiescence on the basic kinetics of the response to targeted treatment of CML. They identify determinants of success in the absence of drug resistant mutants, and elucidate how quiescence influences the emergence of drug resistant mutants.


Augmentation with transcortical wiring of an onlay-type prosthesis for a deficient patella during revision total knee arthroplasty.
The management of patellae with a severe bony deficiency during revision total knee arthroplasty is a challenging problem. However, using a technique of augmentation with transcortical wiring of an onlay-type prosthesis allowed the authors to revise a deficient patellae successfully. After making the decision to revise the existing patellar component, the procedure was found to be technically straightforward. Furthermore, the procedure does not require sophisticated instruments, only an onlay-type prosthesis, cement and wires. This technique entails fixing wires to the three pegs of the patellar component, passing the wires through drill holes in the anterior cortex and, after compression of a cemented prosthesis, augmenting the fixation by twisting the wires anteriorly. We believe that stable fixation and painless articulation will be obtained with the described technique for deficient patellae.


First record of the genus Venanus (Hymenoptera: Braconidae: Microgastrinae) in Mesoamerica, with the description of two new species from Costa Rica.
The New World genus Venanus (Hymenoptera: Braconidae: Microgastrinae) is a small group of parasitoid wasps that includes two Nearctic and seven Neotropical species. Here two additional species, authored by Fernández-Triana & Whitfield, are described from Costa Rica: V.johnnyrosalesi sp. n. from Area de Conservación Guanacaste (ACG) and V.randallgarciai sp. n. from Area de Conservación Cordillera Volcanica Central. They represent the first record of the genus for Mesoamerica. A previous key to all known Venanus (Whitfield et al. 2011) is modified to include the new species. The Costa Rican species were collected at altitudes of 1,400-1,460 m, but nothing is known of their biology. DNA barcodes were obtained for both species and are included as part of the description along with extensive photos. This paper is part of a series inventorying the diversity of Microgastrinae in ACG.


[Verapamil-responsive ventricular tachycardia in small children: a case report and review of the literature].
A case of verapamil-responsive incessant ventricular tachycardia in a 4-year-old girl is reported. Oral verapamil alone failed in maintaining stable sinus rhythm. With association of oral verapamil and betablockers (nadolol) the patient remained asymptomatic without recurrence of ventricular tachycardia over a follow-up of 1 year. In case of failure of monotherapy with verapamil or betablockers alone, an association of both can be effective and safe also in pediatric age. Radiofrequency catheter ablation should be reserved, especially in pediatric age, only to patients with impaired ventricular function who are not responsive to medical therapy.


Chaos-induced coherence in two independent food chains.
Coherence evolution of two food web models can be obtained under the stirring effect of chaotic advection. Each food web model sustains a three-level trophic system composed of interacting predators, consumers, and vegetation. These populations compete for a common limiting resource in open flows with chaotic advection dynamics. Here we show that two species (the top predators) of different colonies chaotically advected by a jetlike flow can synchronize their evolution even without migration interaction. The evolution is characterized as a phase synchronization. The phase differences (determined through the Hilbert transform) of the variables representing those species show a coherent evolution.


Association between XRCC1 single-nucleotide polymorphisms and susceptibility to nasopharyngeal carcinoma: An update meta-analysis.
Many studies have investigated polymorphisms of X-ray repair cross-complementing protein 1 (XRCC1) and risk of nasopharyngeal carcinoma (NPC), but the results are somewhat contradictory in different studies. There is an urgent need to keep in step with the relevant observational studies to more comprehend the effects of XRCC1 variants on the NPC risk. A systematic literature search accompanied with meta-analysis was carried out to obtain a detailed evaluation on the association between XRCC1 polymorphisms and NPC risk. Meta-analyses showed that there was no statistically significant association observed between Arg194Trp/Arg280His variants in the XRCC1 gene and NPC risk with all genetic models, when relatively larger samples were pooled into the update meta-analysis. The reassessment suggested NPC risk was significantly increased with Arg399Gln polymorphism. The significant association was identified in homozygous, recessive, and allelic models, more than previously reported. We confirmed that Arg399Gln polymorphism of XRCC1 gene is a potential predictor for susceptibility to NPC, especially for Asians. More studies are required to evaluate the association in different populations.


Exchange of an imido ligand in bis(imido) complexes of uranium.
Addition of B(C6H5)3.H2O to U(NtBu)2I2(THF)2 provides U(NtBu)(O)I2(THF)2, a complex with a trans arrangement of the oxo and imido ligands. A DFT study on the Ph3PO adduct, U(NtBu)(O)I2(Ph3PO)2, reveals that there are six bonding orbitals in the O=U=N interaction, much like the bis(imido) N=U=N interaction. However, the calculations suggest that the multiple bonding in the oxo imido complexes is less covalent than that in the bis(imido) analogues.


Ambulatory insulin infusion pumps.
We evaluated nine ambulatory insulin infusion pumps from seven manufacturers, basing our ratings primarily on human factors--size, weight, battery type, and adequate reservoir capacity (i.e., 48 hr insulin supply). Of these, seven were rated Acceptable, and two were rated Acceptable-Not Recommended.


The adenylate kinase of human plasma, erythrocytes and platelets in relation to the degradation of adenosine diphosphate in plasma.
1. Adenylate kinase (EC 22.214.171.124) has been shown to be present in human plasma obtained by conventional means and the adenylate-kinase activities of plasma and of lysed and intact human platelets and erythrocytes have been measured at 37 degrees by sensitive spectrophotometric methods. 2. The activities found in plasma ranged from 2.7 to 22.9mumoles of ADP formed/min./l. and in lysed platelets and lysed erythrocytes mean values of 0.79 and 12.0mumoles of ADP formed/min./10(9) cells respectively were found. Intact platelets and erythrocytes showed little or no activity. 3. The apparent K(m) of plasma adenylate kinase for ADP was found to be 1.4-1.6mm. 4. The adenylate-kinase activity of plasma was correlated with the free haemoglobin present and the larger part of the activity could be accounted for by haemolysis occurring either during the withdrawal of the blood or in vivo. 5. Aggregation of platelets by ADP, collagen fibres or thrombin released up to 16% of the platelet adenylate kinase into the suspending medium. 6. Measurement of the rate of breakdown of 1.6mum-ADP in plasma gave values of about 0.1mmu-mole/min./ml. This was not increased by addition of sufficient erythrocyte lysate to increase the activity of plasma adenylate kinase five to ten times. 7. It was concluded that the activity of adenylate kinase found in plasma, even after aggregation of the platelets, is insufficient to account for the rate of breakdown of low concentrations of ADP usually observed, and that another enzyme is responsible for this process.


Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration.
Neovascular age-related macular degeneration (AMD) is associated with rapid vision loss due to choroidal neovascularization (CNV), leakage, and scarring. Steroids have gained attention in their role for the treatment of neovascular AMD for their antiangiogenic and anti-inflammatory properties. This review aims to examine effects of steroids with antiangiogenic properties in the treatment of neovascular AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2012), EMBASE (January 1980 to November 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2012. We included randomized controlled clinical trials of intra- and peri-ocular antiangiogenic steroids in people diagnosed with neovascular AMD. Two authors independently screened abstracts and full-text articles, assessed risk of bias in the included trials, and extracted data. We did not conduct a meta-analysis. We included three trials after screening a total of 1503 abstracts and 21 full-text articles. The three trials included a total of 809 participants. One trial compared different doses of acetonide anecortave acetate with placebo, a second trial compared triamcinolone acetonide versus placebo, and the third trial compared anecortave acetate against photodynamic therapy (PDT). We did not conduct a meta-analysis owing to heterogeneity of interventions and comparisons. The risk ratio for loss of 3 or more lines of vision at 12 months follow-up was 0.8 (95% confidence interval (CI) 0.45 to 1.45) with 3 mg anecortave acetate, 0.45 (95% CI = 0.21 to 0.97) with 15 mg anecortave acetate, 0.91 (0.52 to 1.58) with 30 mg anecortave acetate, 0.97 (95% CI 0.74 to 1.26) with triamcinolone acetonide, all compared to placebo and 1.08 (95% CI 0.91 to 1.29) with anecortave acetate compared with PDT. Based on the included trials, we found no evidence that antiangiogenic steroids prevent visual loss in patients with neovascular AMD. With the emergence of anti-vascular endothelial growth factor modalities, based on evidence summarized in this review, it is unclear what role steroids have in treating patients with neovascular AMD.


[Expression of caspase-8, receptor interacting protein and nuclear factor-kappaBp65 in oral lichen planus].
To investigate the expressions of caspase-8, receptor interacting protein (RIP) and nuclear factor (NF)-kappaBp65 in oral lichen planus (OLP) and their relationship with cell apoptosis. Immunohistochemical technique with SP method was used to detect the expressions of caspase-8, RIP and NF-kappaBp65 in 30 OLP cases and 15 normal oral mucosa specimens. Terminal deoxynucleotidyl transferase-mediated nucleotide shift enzyme (TdT) mediated d-UTP end labeling (TUNEL) was used for detecting the cell apoptotic index (AI) in 15 OLP cases and 5 nomal oral mucosa specimens. Compared with the control group, the AI of epithelial cells (6.76 +/- 2.32) increased and the AI of lymphocytes (1.75 +/- 0.74)decreased in OLP (P < 0.01). The positive rate of caspase-8, RIP and NF-kappaBp65 of epithelial cells were 97% (29/30), 87% (26/30) and 93% (28/30) respectively, significantly higher in OLP than in normal control (P < 0.05). The positive rate of caspase-8, RIP and NF-kappaBp65 of lymphocytes were 100% (30/30, 90% (27/30) and 80% (24/30) respectively, significantly higher in OLP than in normal control (P < 0.01). A positive correlation was also observed between NF-kappaBp65 expression of lymphocytes and AI of epithelial cells. Accelerated apoptosis of the keratinocytes and inhibition of lymphocyte apoptosis may coexist and contribute to the formation and progression of OLP. The over expression of caspase-8, RIP and NF-kappaBp65 in OLP may play a role in the pathogenesis of OLP.


Enhanced Capacity Retention of Li3V2(PO4)3-Cathode-Based Lithium Metal Battery Using SiO2-Scaffold-Confined Ionic Liquid as Hybrid Solid-State Electrolyte.
Li3V2(PO4)3 (LVP) is one of the candidates for high-energy-density cathode materials matching lithium metal batteries due to its high operating voltage and theoretical capacity. However, the inevitable side reactions of LVP with a traditional liquid-state electrolyte under high voltage, as well as the uncontrollable growth of lithium dendrites, worsen the cycling performance. Herein, a hybrid solid-state electrolyte is prepared by the confinement of a lithium-containing ionic liquid with a mesoporous SiO2 scaffold, and used for a LVP-cathode-based lithium metal battery. The solid-state electrolyte not only exhibits a high ionic conductivity of 3.14 × 10-4 S cm-1 at 30 °C and a wide electrochemical window of about 5 V, but also has good compatibility with the LVP cathode material. Moreover, the cell paired with a solid-state electrolyte exhibits good reversibility and can realize a stable operation at a voltage of up to 4.8 V, and the discharge capacity is well-maintained after 100 cycles, which demonstrates excellent capacity retention. As a contrast, the cell paired with a conventional liquid-state electrolyte shows only an 87.6% discharge capacity retention after 100 cycles. In addition, the effectiveness of a hybrid solid-state electrolyte in suppressing dendritic lithium is demonstrated. The work presents a possible choice for the use of a hybrid solid-state electrolyte compatible with high-performance cathode materials in lithium metal batteries.