Determination of acquired immunodeficiency syndrome (AIDS) after renal transplantation.
Diagnosing the acquired immunodeficiency syndrome (AIDS) in transplant recipients can be difficult due to the patient's medication-induced immunosuppressed state. We report two renal allograft recipients who acquired HIV infection at the time of transplantation and later went on to develop multiple opportunistic infections. Careful documentation of HIV antibody status of the donor and recipient, when available, the nature of immunosuppressive therapy used, the type of infections and their timing after transplantation, as well as the patient's absolute T4 lymphocyte count, T cell ratio, and B cell humoral response to infection were used as factors to distinguish between infection related to immunosuppressive therapy and that seen in HIV-induced immunodeficiency. Reduction in immunosuppressive therapy because of the HIV-related immunodeficiency state did not result in allograft rejection. Both patients died of their multiple infections. The determination of AIDS in the transplant recipient has both therapeutic and prognostic significance. This diagnosis should be considered when transplant patients develop unusual infections in relationship to their posttransplant course.


Stabilisation of human interferon beta synthesis in Escherichia coli by zinc ions.
Human interferon beta synthesized in Escherichia coli is unstable and toxic for the bacterial cell. Zinc ions are able to stabilise interferon beta in E. coli probably by inhibiting the action of cell internal proteinase(s) which affect the half-life of this foreign protein. As a result up to one order of magnitude more active IFN-beta can be detected in Zn2+-treated E. coli cells.


A bibliometric analysis on the research trends of climate change effects on economic vulnerability.
The climate change effect has received a crucial concern from global policymakers as well as academic researchers. The climate change effect is a real-world issue threatening the existence of species and human beings, thus causing the economic vulnerability. Apart from policymakers, academic researchers are showing their concern on the effect of climate change on economic and socioeconomic vulnerability through publishing research articles in the recent decade. In light of the revolution of research articles, this study applied a bibliometric analysis on the academic research articles to explore the publication trends, themes, impacts, and potential scopes for further studies. Both the Scopus and the Web of Science online databases were used to search for journal articles linked to climate change effects and economic vulnerability. The final data of 229 journal articles were analyzed using bibliometric and visualization tools "Biblioshiny" and "VOSViewer." The findings unveiled an uprising trend in publications and posited several themes, mainly exposure, sensitivity, drought, and flood by means of climate change effects that affect economic vulnerability. Based on the findings and review of literature, several research gaps were identified and offered opportunities for further studies. The policymakers can attribute attention to encouraging more research in several areas in addition to agriculture and coastal regions.


Current Trends and Perspectives in Microbial Bioconversions of Steroids.
The microbiological transformation of sterols is currently the technological basis for the industrial production of valuable steroid precursors, the so-called synthons, from which a wide range of steroid and indane isoprenoids are obtained by combined chemical and enzymatic routes. These compounds include value-added corticoids, neurosteroids, sex hormones, bile acids, and other terpenoid lipids required by the medicine, pharmaceutical, food, veterinary, and agricultural industries.Progress in understanding the molecular mechanisms of microbial degradation of steroids, and the development and implementation of genetic technologies, opened a new era in steroid biotechnology. Metabolic engineering of microbial producers makes it possible not only to improve the biocatalytic properties of industrial strains by enhancing their target activity and/or suppressing undesirable activities in order to avoid the formation of by-products or degradation of the steroid core, but also to redirect metabolic fluxes in cells towards accumulation of new metabolites that may be useful for practical applications. Along with whole-cell catalysis, the interest of researchers is growing in enzymatic methods that make it possible to carry out selective structural modifications of steroids, such as the introduction of double bonds, the oxidation of steroidal alcohols, or the reduction of steroid carbonyl groups. A promising area of research is strain engineering based on the heterologous expression of foreign steroidogenesis systems (bacterial, fungal, or mammalian) that ensure selective formation of demanded hydroxylated steroids.Here, current trends and progress in microbial steroid biotechnology over the past few years are briefly reviewed, with a particular focus on the application of metabolic engineering and synthetic biology techniques to improve existing and create new whole-cell microbial biocatalysts.


Study of the separation limits of continuous solid support free liquid-liquid chromatography: separation of capsaicin and dihydrocapsaicin by centrifugal partition chromatography.
Sequential centrifugal partition chromatography (sCPC) is a cyclic solid support-free liquid-liquid chromatographic process, in which a continuously introduced feed mixture is separated into two sequentially collected product streams. The few experimental demonstrations of this concept already revealed its potential for the preparative separation of pharmaceuticals and fine chemicals. In this work not only the possibilities, but also the limits of the sCPC technology are explored. A feed mixture consisting of capsaicin and dihydrocapsaicin, whose molecular structure differs in only one double bond, was selected for this purpose. The sCPC unit operating parameters needed for a complete separation of the feed mixture were selected using the recently published approach, which uses the partition coefficient of the feed components and the hydrodynamic characteristics of the system as input data. A complete separation of capsaicin and dihydrocapsaicin with the solvent system heptane/ethyl acetate/methanol/water:1/1/1/1 (v/v/v/v) was achieved, although the separation factor was only 1.32. The sCPC unit separation performance was successfully simulated using the cell model.


Underestimating the duration of future events: memory incorrectly used or memory bias?
People frequently underestimate how long it will take them to complete a task. The prevailing view is that during the prediction process, people incorrectly use their memories of how long similar tasks have taken in the past because they take an overly optimistic outlook. A variety of evidence is reviewed in this article that points to a different, although not mutually exclusive, explanation: People base predictions of future duration on their memories of how long past events have taken, but these memories are systematic underestimates of past duration. People appear to underestimate future event duration because they underestimate past event duration.


Belated diagnosis in three patients with rifampicin-induced immune haemolytic anaemia.
We report three patients who developed haemolysis following rifampicin treatment. Initially, autoimmune haemolytic anaemia (AIHA) of the warm type and/or an acute haemolytic transfusion reaction (AHTR) was suggested. The direct antiglobulin tests (DAT) were strongly positive for IgG and C3d, and tests for rifampicin-dependent antibodies were positive in all three cases, featuring C-specificity in one case. The outcome was fatal in two out of the three cases, presumably due to belated diagnosis. This shows that rifampicin may stimulate the production of autoantibodies (aab) and/or drug-dependent antibodies (ddab), and that the resulting haemolytic syndrome bears similarities with AIHA and AHTR.


Bladder cancer: do we need contrast injection for MRI assessment of muscle invasion? A prospective multi-reader VI-RADS approach.
(1) To investigate whether a contrast-free biparametric MRI (bp-MRI) including T2-weighted images (T2W) and diffusion-weighted images (DWI) can be considered an accurate alternative to the standard multiparametric MRI (mp-MRI), consisting of T2, DWI, and dynamic contrast-enhanced (DCE) imaging for the muscle-invasiveness assessment of bladder cancer (BC), and (2) to evaluate how the diagnostic performance of differently experienced readers is affected according to the type of MRI protocol. Thirty-eight patients who underwent a clinically indicated bladder mp-MRI on a 3-T scanner were prospectively enrolled. Trans-urethral resection of bladder was the gold standard. Two sets of images, set 1 (bp-MRI) and set 2 (mp-MRI), were independently reviewed by four readers. Descriptive statistics, including sensitivity and specificity, were calculated for each reader. Receiver operating characteristic (ROC) analysis was performed, and the areas under the curve (AUCs) were calculated for the bp-MRI and the standard mp-MRI. Pairwise comparison of the ROC curves was performed. The AUCs for bp- and mp-MRI were respectively 0.91-0.92 (reader 1), 0.90 (reader 2), 0.95-0.90 (reader 3), and 0.90-0.87 (reader 4). Sensitivity was 100% for both protocols and specificity ranged between 79.31 and 89.66% and between 79.31 and 83.33% for bp-MRI and mp-MRI, respectively. No significant differences were shown between the two MRI protocols (p > 0.05). No significant differences were shown accordingly to the reader's experience (p > 0.05). A bp-MRI protocol consisting of T2W and DWI has comparable diagnostic accuracy to the standard mp-MRI protocol for the detection of muscle-invasive bladder cancer. The experience of the reader does not significantly affect the diagnostic performance using VI-RADS. • The contrast-free MRI protocol shows a comparable accuracy to the standard multiparametric MRI protocol in the bladder cancer muscle-invasiveness assessment. • VI-RADS classification helps non-expert radiologists to assess the muscle-invasiveness of bladder cancer. • DCE should be carefully interpreted by less experienced readers due to inflammatory changes representing a potential pitfall.


Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database.
Little is known about pediatric spinal cord high grade gliomas (SCHGG) beyond their dismal prognosis. Here, we analyzed the HIT-GBM(®) database for the influence of surgical resection on survival. Between 1991 and 2010 the HIT-GBM group collected data from European children diagnosed with high grade glioma. Patients with the following inclusion criteria were analyzed in this study: astrocytic histology, WHO grade III or IV, age at diagnosis <18 years, and tumor localized to the spinal cord. 28 patients (mean age 11.28 years, 14 male) with primary SCHGG were identified. The tumor sizes were measured by the span across adjacent vertebrae and varied greatly (range: 1-20, median: 4). Histology was classified as WHO grade III in 15 and grade IV in 13 tumors. Of note, the four largest tumors identified were WHO grade III. Surgery was classified as complete resection (n = 6), subtotal resection (STR) (n = 7), partial resection (n = 12) or biopsy only (n = 3). 27 patients received chemotherapy, 22 of which also received radiation. With the mean follow-up time of 2.88 (SD ± 2.95) years, 14 patients were still alive resulting in a median overall survival of 2.5 years (SE ± 1.6). The positive prognostic indicators for overall survival were: age younger than 5 years (P = 0.047), WHO grade III (P = 0.046), absence of necrosis (P = 0.025) and gross total resection (GTR) (P = 0.012). The prognosis of SCHGG might not be as miserable as generally assumed. GTR is of benefit. Larger data sets and meta-analysis are necessary to identify patient sub-groups.


The long-term strength of Europe and its implications for plate-forming processes.
Field-based geological studies show that continental deformation preferentially occurs in young tectonic provinces rather than in old cratons. This partitioning of deformation suggests that the cratons are stronger than surrounding younger Phanerozoic provinces. However, although Archaean and Phanerozoic lithosphere differ in their thickness and composition, their relative strength is a matter of much debate. One proxy of strength is the effective elastic thickness of the lithosphere, Te. Unfortunately, spatial variations in Te are not well understood, as different methods yield different results. The differences are most apparent in cratons, where the 'Bouguer coherence' method yields large Te values (> 60 km) whereas the 'free-air admittance' method yields low values (< 25 km). Here we present estimates of the variability of Te in Europe using both methods. We show that when they are consistently formulated, both methods yield comparable Te values that correlate with geology, and that the strength of old lithosphere (> or = 1.5 Gyr old) is much larger (mean Te > 60 km) than that of younger lithosphere (mean Te < 30 km). We propose that this strength difference reflects changes in lithospheric plate structure (thickness, geothermal gradient and composition) that result from mantle temperature and volatile content decrease through Earth's history.


Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG.
Patients with antibody deficiency suffer chronic respiratory symptoms, recurrent exacerbations, and progressive airways disease despite systemic replacement of IgG. Little is known about the respiratory tract biology of these patients. We sought to measure immunoglobulin levels, inflammatory cytokines, and mediators of tissue damage in serum and sputum from patients with antibody deficiency and healthy controls; to analyze the respiratory microbiome in the same cohorts. We obtained paired sputum and serum samples from 31 immunocompetent subjects and 67 antibody-deficient patients, the latter divided on computed tomography scan appearance into "abnormal airways" (bronchiectasis or airway thickening) or "normal airways." We measured inflammatory cytokines, immunoglobulin levels, neutrophil elastase, matrix-metalloproteinase-9, urea, albumin, and total protein levels using standard assays. We used V3-V4 region 16S sequencing for microbiome analysis. Immunodeficient patients had markedly reduced IgA in sputum but higher concentrations of IgG compared with healthy controls. Inflammatory cytokines and tissue damage markers were higher in immunodeficient patients, who also exhibited dysbiosis with overrepresentation of pathogenic taxa and significantly reduced alpha diversity compared with immunocompetent individuals. These differences were seen regardless of airway morphology. Sputum matrix-metalloproteinase-9 and elastase correlated inversely with alpha diversity in the antibody-deficient group, as did sputum IgG, which correlated positively with several inflammatory markers, even after correction for albumin levels. Patients with antibody deficiency, even with normal lung imaging, exhibit inflammation and dysbiosis in their airways despite higher levels of IgG compared with healthy controls.


Alcohol induced structural and dynamic changes in β-lactoglobulin in aqueous solution: a neutron scattering study.
Structural and dynamic properties of β-lactoglobulin (β-LG) were revealed as a function of alcohol concentration in ethanol- and trifluoroethanol(TFE)-water mixtures with circular dichroism (CD), small-angle neutron scattering (SANS) and quasi-elastic neutron scattering (QENS). The CD spectra showed that an increase in TFE concentration promotes the formation of the β-sheet structure of β-LG. The SANS-intensities were fitted using form factors for two attached spheres for the native and native-like states of the protein. At higher alcohol concentrations, where aggregation takes place, a form factor modelling diffusion limited colloidal aggregation (DLCA) was employed. The QENS-data were analyzed in terms of internal motions for all alcohol concentrations. While low concentrations of TFE (10% (v/v)) lead to an increase of the mean square amplitudes of vibrations <u(2)> and a retention of a native-like structure - but not to an increase of the characteristic radius of proton diffusion processes a. Addition of 20% (v/v) of TFE induces aggregation, going along with a further increase of <u(2)>. Further increase of TFE concentration to 30% (v/v) changes the nanoscale structure of the oligomeric nucleate, but induces no further significant changes in <u(2)>. The present study underlines the necessity of methods sensitive to the dynamics of a system to obtain a complete picture of a molecular process.


Impact of outcome adjudication in kidney disease trials: observations from the Study of Heart and Renal Protection (SHARP).
We aimed to assess opportunities for trial streamlining and the scientific impact of adjudication on kidney and cardiovascular outcomes in CKD. We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data. For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00). These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.


Protein-protein interaction of HP137 with histidine kinase HP244 does not contribute to flagellar regulation in Helicobacter pylori.
Flagellar motility is essential for the ability of Helicobacter pylori to colonize the gastric mucosa. Expression of the flagella is controlled by a complex regulatory cascade involving the two-component system FlgR-HP244, the sigma factors sigma54 and sigma28 and the anti-sigma28 factor FlgM. The protein-protein interaction map of H. pylori, which is based on a high-throughput two-hybrid screen (Rain et al., 2001. Nature 409, 211-215) indicated a protein-protein interaction between the gene product of ORF hp137 and both the histidine kinase HP244 and the flagellar hook protein HP908. We hypothesized that HP137 might be involved in a feedback regulatory mechanism controlling the activity of histidine kinase HP244. Here we demonstrate that HP137 does not participate in the regulation of flagellar gene expression, neither in H. pylori nor in the closely related bacterium Campylobacter jejuni.


Effect of ionic interaction on the mechanochromic properties of pyridinium modified tetraphenylethene.
A pyridinium modified tetraphenylethene-based salt shows aggregation-induced emission enhancement properties and irreversible mechanochromic behaviours.


Incidence of primary tissue valve failure in porcine bioprosthetic heart valves.
This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group.


Disruption of the iron-sulfur cluster of aconitase by myeloperoxidase-derived oxidants.
Oxidative damage catalysed by the heme enzyme myeloperoxidase (MPO) has been linked with multiple inflammatory pathologies. The major oxidant species generated by MPO are hypochlorous (HOCl) and hypothiocyanous acids (HOSCN). The damage induced by HOCl is well characterized and has been linked to multiple diseases, however the role of HOSCN is less well understood. It is known that HOSCN can cause selective damage, as this oxidant selectively targets thiol (e.g. Cys) residues and selenium-containing species. The aim of the current study was to assess whether HOCl and HOSCN can disrupt the [4Fe-4S] cluster of aconitase causing iron release and loss of activity. It is shown that HOSCN induces rapid and efficient release of iron from aconitase, with 80% removed at an oxidant concentration of 3 micromoles/mg protein; this is markedly more efficient than HOCl. In contrast the extent of loss of enzymatic activity was comparable between the two oxidants at the same concentration. Blocking the [4Fe-4S] cluster inhibited HOSCN-mediated inactivation, but did not have dramatic effects on HOCl-mediated damage, consistent with HOSCN, but not HOCl, interacting with the cluster. This data is supported by peptide mass mapping studies that indicate that HOSCN oxidises Cys385 of the [4Fe-4S] cluster. In contrast HOCl damaged multiple sites. Exposure of human coronary artery endothelial cells (HCAEC) to 0-50 micromolar HOCl or 0-150 micromolar HOSCN resulted in an increase in intracellular iron, loss of aconitase activity and a loss of mitochondrial aconitase protein. In contrast cytosolic aconitase was not affected. These data indicate that aconitase - and particularly the mitochondrial form - is a target for MPO-mediated damage with HOSCN showing a selectivity for the [4Fe-4S] cluster and inducing greater iron release. This damage, and the release of iron, may exacerbate oxidative stress in cells at sites of inflammation where active MPO is present.


Silicone implant arthroplasty in patients with idiopathic osteoarthritis of the metacarpophalangeal joint.
The outcome of silicone metacarpophalangeal (MCP) joint implant arthroplasty in the osteoarthritic patient population has not been well established. Typically patients with idiopathic osteoarthritis have no history of underlying systemic disease and may respond well to treatment with MCP joint implant arthroplasty. This study examined the efficacy of silicone MCP joint implant arthroplasty for patients with idiopathic osteoarthritis for whom nonsurgical treatment had failed. Of 14 patients (15 arthroplasties) who had silicone MCP joint implant arthroplasty for idiopathic osteoarthritis 12 (13 arthroplasties) returned for follow-up evaluation at an average of 40 months after surgery. There were 9 index finger and 4 middle finger arthroplasties. The average age at the time of surgery was 62 years. Patients completed a subjective questionnaire and were examined by a certified therapist. Range of motion and strength were recorded and the Jebsen-Taylor examination was administered to assess function. Range of motion values at final follow-up evaluation were compared with preoperative and early postoperative values. Radiographs were taken at final follow-up evaluation and compared with preoperative and early postoperative films to assess joint position, wear, and radioulnar alignment. At final follow-up evaluation excellent (9 patients) and good (3 patients) overall improvement were reported. Nine patients (10 implants) reported greater than 75% functional improvement. A notable increase was seen in MCP joint flexion. Grip and lateral pinch strengths were below age-matched normative data. Of the 11 patients (12 implants) who came in for follow-up evaluation 7 performed all tasks of the Jebsen-Taylor examination within the allotted time. At final follow-up evaluation all silicone implants were located and showed no signs of subluxation. Radiographic radioulnar alignment was maintained. One implant was revised at 35 months secondary to fracture. Silicone implant arthroplasty is a motion-sparing procedure that provides good pain relief and maintenance of function at intermediate follow-up evaluation in patients with idiopathic osteoarthritis of the MCP joint.


Implications of Escherichia coli community diversity in free-ranging Australian pinniped pups.
Escherichia coli is a widely studied bacterium, commonly used as an indicator of faecal contamination. Investigations into the structure and diversity of E. coli in free-ranging wildlife species has been limited. The objective of this study was to characterise intra-individual and inter-species E. coli phylotype and B2 sub-type diversity in free-ranging Australian pinniped pups, to determine whether a single E. coli colony is representative of the phylotype and B2 sub-type diversity in these hosts. Faecal samples were collected from free-ranging Australian fur seal (Arctocephalus pusillus doriferus), Australian sea lion (Neophoca cinerea) and long-nosed fur seal (Arctocephalus forsteri) pups from three breeding colonies between 2018 and 2021. Faecal swabs from thirty randomly selected pups (n = 10 from each species) were cultured and ten E. coli colonies were selected from each culture based on morphology and separation between colonies on agar plates. Molecular screening techniques were utilised to assign isolates to phylotypes and B2 sub-types. There was no significant difference (p > 0.05) in either intra-individual or inter-species E. coli phylotype and B2 sub-type diversity. The B2 phylotype was the most dominant, with 78% of isolates (n = 234) assigned to this phylotype. Host factors (species, weight [kg] and standard length [cm]) did not significantly affect phylotype diversity. The absence of intra-individual and inter-species differences in E. coli diversity at a phylotype level suggests that a single E. coli colony could be used as an indicator of overall diversity of E. coli at a phylotype level in A. p. doriferus, N. cinerea and A. forsteri pups. These findings can be used to simplify and improve the efficiency of sampling protocols for ongoing monitoring of human-associated E. coli phylotypes in free-ranging pinniped populations.


Endocannabinoid signaling in the spinal locomotor circuitry.
To understand how the spinal central pattern generators produce locomotor movements, it is necessary to characterize the network's connectivity, the intrinsic properties of the constituent neurons and the modulatory mechanisms. Modulation operating within spinal locomotor networks is required for the generation of the final motor output. In this review, we have summarized how endocannabinoids released by locomotor network neurons contribute to setting the baseline locomotor frequency. They are synthesized on demand as a result of activation of mGluR1 and act as retrograde messengers to depress inhibitory synaptic transmission. We also discuss how endogenous activation of mGluR1 contributes to the normal operation of the spinal locomotor network and the underlying cellular and synaptic mechanisms.


Glutathione S-transferase in human hepatocellular carcinoma.
Qualitative and quantitative changes in glutathione S-transferase (GSH-T) were studied in human hepatocellular carcinoma. GSH-T specific activity (mumoles per min per mg protein) was variably reduced in hepatocellular carcinoma. Similar changes were seen in "cationic" GSH-T (ligandin) concentration determined by radioimmunoassay. Immunohistochemical studies with antihuman liver ligandin suggest that positive staining was more frequently found in well-differentiated tumors. The relative activities of "cationic," "neutral," and "anionic" transferases (pI greater than 7.5) activity ranged from virtually absent to near normal values. "Neutral" (pI 6 to 6.5) and "anionic" (pI less than 5.4) species were present more often in tumors than in normal liver. In two cases, normal liver tissue and tumor were obtained from the same patient. In one, only quantitative differences were present, while in the other "cationic" and "neutral" GSH-Ts were present in the normal liver tissue while both "cationic" and "anionic" species were found in the tumor. Our studies indicate that qualitative as well as quantitative changes of GSH-T occur in human hepatocellular carcinoma.


Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines.
Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase.


Peptide prodrugs: improved oral absorption of lopinavir, a HIV protease inhibitor.
Lopinavir (LVR) is extensively metabolized by CYP3A4 and is prevented from entering the cells by membrane efflux pumps such as P-gp and MRP2. In an approach to evade the first-pass metabolism and efflux of LVR, peptide prodrugs of LVR [valine-valine-lopinavir (VVL) and glycine-valine-lopinavir (GVL)] were synthesized. Prodrugs were identified with 1H and 13C NMR spectra and LC/MS/MS was employed to evaluate their mass and purity. Solubility studies indicated that the prodrugs have enhanced aqueous solubilities relative to parent LVR. Accumulation and transport data of VVL and GVL across MDCKII-MDR1 and MDCKII-MRP2 cells indicated evasion of prodrugs' efflux by P-gp and MRP2 significantly. Permeability studies across Caco-2 cells indicated that the prodrugs are transported by peptide transporters and have increased permeability as compared with LVR. VVL and GVL exhibited significantly better degradation rate constants as compared with LVR in rat liver microsomes. Enzymatic stability studies in Caco-2 cell homogenate indicated that the peptide prodrugs are first converted to the ester intermediate (amino acid prodrug VL) and then finally to the parent drug. Overall, the advantages of utilizing peptide prodrugs include chemical modification of the compound to achieve targeted delivery via peptide transporters present across the intestinal epithelium, significant evasion of efflux and CYP3A4 mediated metabolism and significantly better solubility profiles. Therefore, in vitro studies demonstrated that peptide prodrug derivatization of LVR may be an effective strategy for evading its efflux and enhancing its systemic concentrations.


Burkholderia vietnamiensis G4 as a biological agent in bioremediation processes of polycyclic aromatic hydrocarbons in sludge farms.
Polycyclic aromatic hydrocarbons (PAHs) are one of the main pollutants generated by the refining and use of oil. To search bioremediation alternatives for these compounds, mainly in situ, considering the biotic and abiotic variables that affect the contaminated sites is determinant for the success of bioremediation techniques. In this study, bioremediation strategies were evaluated in situ, including biostimulation and bioaugmentation for 16 priority PAHs present in activated sludge farms. B. vietnamiensis G4 was used as a biodegradation agent for bioaugmentation tests. The analyses occurred for 12 months, and temperature and humidity were measured to verify the effects of these factors on the biodegradation. We used the technique GC-MS to evaluate and quantify the degradation of PAHs over the time of the experiment. Of the four treatments applied, bioaugmentation with quarterly application proved to be the best strategy, showing the degradation of compounds of high (34.4% annual average) and low (21.9% annual average) molecular weight. A high degradation rate for high molecular weight compounds demonstrates that this technique can be successfully applied in bioremediation of areas with compounds considered toxic and stable in nature, contributing to the mitigation of impacts generated by PAHs.


A developmental change in the content of parvalbumin in normal and dystrophic mouse (mdx) muscle.
A highly sensitive enzyme immunoassay for mouse parvalbumin was developed in this study. The amount of parvalbumin was determined by a sandwich enzyme immunoassay method using anti-parvalbumin IgG-coated polystyrene balls and an anti-parvalbumin Fab'-horseradish peroxidase conjugate. Parvalbumin could not be detected in normal and dystrophic skeletal muscles of newborn mice. In normal mice, it appeared in the first postnatal week and increased linearly thereafter until the 12th week in fast twitch muscle. Rapid increase in parvalbumin was seen during 3rd and 8th week. On the other hand, parvalbumin detected in the first postnatal week increased gradually, but did not yet reach the adult level at the 16th postnatal week in slow twitch muscle. In mdx mice, fast twitch muscles such as the gastrocnemius and tibialis anterior were found to contain significantly decreased amounts of parvalbumin, compared with those in control mice. In fast twitch muscle parvalbumin in mdx mice could not be detected in the newborn, increased until 4th week and thereafter did not increase as that in normal mice. In slow twitch muscle the postnatal increase in parvalbumin content was not different from that in control mice. These results suggest that the decrease in the content of parvalbumin in dystrophic muscle may contribute to the elevation of the level of sarcoplasmic free Ca2+ and the activated Ca2(+)-dependent proteolysis.


Quality of Life in Chronic Venous Disease: Bridging the Gap Between Patients and Physicians.
Chronic venous disease (CVD) has a negative impact on patients' quality of life (QoL). This was demonstrated in the recent Patient Journey on CVD study, which examined QoL in patients with early- and advanced-stage CVD (Clinical, Etiological, Anatomical and Pathophysiological classification C0 to C4), and the gaps between the way in which physicians and patients viewed the impact of CVD on QoL. The study was conducted in five countries (Brazil, China, Czech Republic, Italy and Russia) and included 100 patients with CVD and 60 CVD specialists. Patients completed the 14-item Chronic Venous Insufficiency Questionnaire (CIVIQ-14) to assess their QoL, and all patients and physicians were questioned during a 60-minute qualitative structured interview, focusing on four key dimensions-physical symptoms, aesthetics/appearance, emotional impact and impact on relationships. The study found that physicians tended to focus more on physical symptoms than on other impacts of CVD and rarely measured QoL in clinical practice. Patients were significantly less satisfied with the management of their QoL than physicians perceived them to be. About 25% of patients with CVD reported disturbed sleep, but physicians did not routinely ask them how CVD affected their sleep. These data reinforce the importance of physicians obtaining information about the impact of CVD on all aspects of the patient's life, including sleep and QoL. Evidence from randomised controlled trials and real-world studies demonstrates that some veno-active drugs, particularly micronised purified flavonoid fraction, can positively impact QoL in patients with CVD.


Topical anesthetic abuse keratitis secondary to floppy eyelid syndrome.
To report the diagnosis and management of a patient with chronic ophthalmic topical anesthetic abuse and floppy eyelid syndrome. We describe the case of a 47-year-old man suffering from persistent bilateral ocular irritation and chronic corneal erosions. The patient was hospitalized in our ophthalmology department and underwent thorough ophthalmic, systemic, and psychiatric evaluation. Chronic topical anesthetic abuse was discovered. Removal of abused drops and copious lubricating treatment lead to partial improvement further permitting diagnosis of floppy eyelid syndrome. Definitive surgical treatment by horizontal eyelid tightening combined with continuous lubrication resulted in remission of symptoms. Uncommon conditions may coexist in 1 patient. In this case, floppy eyelid syndrome resulted in topical anesthetic abuse. Ophthalmologists should keep both these conditions in mind when treating patients with otherwise unexplained chronic persistent corneal erosions.


Comparing supervised and unsupervised approaches to emotion categorization in the human brain, body, and subjective experience.
Machine learning methods provide powerful tools to map physical measurements to scientific categories. But are such methods suitable for discovering the ground truth about psychological categories? We use the science of emotion as a test case to explore this question. In studies of emotion, researchers use supervised classifiers, guided by emotion labels, to attempt to discover biomarkers in the brain or body for the corresponding emotion categories. This practice relies on the assumption that the labels refer to objective categories that can be discovered. Here, we critically examine this approach across three distinct datasets collected during emotional episodes-measuring the human brain, body, and subjective experience-and compare supervised classification solutions with those from unsupervised clustering in which no labels are assigned to the data. We conclude with a set of recommendations to guide researchers towards meaningful, data-driven discoveries in the science of emotion and beyond.


Bioavailability of norethindrone in human subjects.
A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.


Bladder leiomyosarcoma and pelvic fibroblastic tumor following cyclophosphamide therapy.
We report a case of leiomyosarcoma in the bladder 8 years after completion of 45 months of cyclophosphamide chemotherapy for Hodgkin's disease. One year after cystoprostatectomy a large fibroblastic tumor arose in the soft tissues of the pelvis.


Withdrawal of immunosuppression in liver transplantation and the mechanism of tolerance.
Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient's immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients. We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in PubMed. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed. Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in dendritic cells is associated with rejection after liver transplantation. Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.


Endovascular stent grafting of the descending thoracic aorta after arch repair in acute type A dissection.
An endovascular stent graft was successfully deployed to the primary entry site in the proximal descending thoracic aorta after total aortic arch replacement using the "elephant trunk" technique in acute type A aortic dissection. The residual false lumen of the descending aorta was thrombosed completely after stent grafting. The elephant trunk was feasible for a proximal landing zone for stent grafting of the descending aorta. Stent grafting in combination with aortic arch replacement was a safe and effective procedure, and may be an alternative choice in carefully selected patients with type A aortic dissection.


Lean body mass and risk of incident atrial fibrillation in post-menopausal women.
High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.


Application of porous foams for size-selective measurements of airborne wheat allergen.
Exposure to airborne wheat allergen is a well-known cause of bakers' allergy and asthma. Airborne wheat allergen can be measured by enzyme immunoassays (EIAs) in extracts of inhalable dust samples, but only limited knowledge is available on the size distribution of wheat allergen-carrying particles. Recently, a new sampling medium, porous polyurethane foam, has been introduced for the size-selective sampling of airborne dust in various occupational settings. We investigated the applicability of these foams for size-selective wheat allergen measurements. Personal and stationary measurements were performed in a flour mill, using respirable and thoracic foams inserted into the conventional IOM inhalable sampler, together with PTFE (Teflon) filters. Foams and filters were eluted and wheat allergen levels determined by human IgG4 inhibition EIA. Wheat allergen levels could be determined in both filter and foam eluates. Inhalable dust levels from filters and foams ranged from 1.4 to 53 mg m(-3), and wheat allergen levels from 15 to 580 microg m(-3). The allergen was mainly borne on particles with D(ae) (particle aerodynamic diameter) > 10 microm and particles with 4 microm < D(ae) < or = 10 microm, accounting for 54.5-77.5% and 18.9-43.2% of the total allergen yield, respectively. Less than 4% of airborne wheat allergen was carried by particles smaller than 4 mum (respirable fraction). Measurement of wheat allergen in dust fractions trapped in respirable and thoracic foams is technically feasible. Both wheat flour dust and wheat allergen are mainly concentrated in larger particle-size fractions (extrathoracic and tracheobronchial).


Cholesterol granuloma presenting with facial nerve paralysis following translabyrinthine surgery: A case report.
Cholesterol granuloma (CG) is a foreign body giant cell inflammatory reaction to blood degradation products, and clinically presents as a cyst with a thick fibrous lining filled with brownish-yellow fluid. We report an unusual case of CG with facial nerve paralysis 9 years after translabyrinthine (TL) surgery for vestibular schwannoma (VS) removal. A 70-year-old woman, who underwent TL surgery previously, presented with left facial palsy (FP). CT findings revealed devastated cochlea and uncovered facial nerve, and progression of FP up to House-Brackmann grade 6 was observed. Therefore, we suspected recurrence of cystic VS or facial schwannoma, although MRI was inconsistent with that of schwannoma. The cyst was completely surgically excised, and histopathology confirmed CG diagnosis. Postoperatively her facial movement improved to grade 4. Recurrence has not been encountered since 7 years. During follow-up after TL surgery for VS, care should be taken for possibility of CG occurring.


A sensitive TSH assay in spot-coated microwells utilizing recombinant antibody fragments.
We have developed a novel TSH immunoassay based on a simplified test protocol suitable for point-of-care testing yet providing 3rd generation TSH assay sensitivity. The antibody density and the functional solid phase capacity were improved up to six-fold by capturing the site-specifically biotinylated recombinant Fab fragment or single chain antibody fragment onto the surface of immobilized streptavidin. An important mechanism for obtaining a low limit of detection (0.003 mIU/l) was the reduction of the coated area to a size ("spot") more closely coinciding with the excitation beam. The reporter technology was based on time-resolved fluorometric detection of inherently fluorescent europium chelates of high quantum yield. The ready-to-use assay concept employed the all-in-one (Aio!) principle--holding all assay components in a dry form in the microtitration well--to provide a simple assay protocol. Direct signal measurement from the surface was done after the washing step without a separate development step. It is concluded that size reduction and site-specific labeling of the antibodies to create a surface with high functional capacity provides a rapid, highly sensitive immunoassay.


Gene nomenclature by default, or BLASTing to Babel.
The current proliferation of mammalian genomes is creating a nomenclature issue caused by naming genes based on their best BLAST hit to a gene in another annotated genome. The rat genome is relying heavily on the mouse genome for nomenclature, but not all rat genes have direct orthologues in the mouse; often, there are paralogous groups of genes--due to expansions of that gene subfamily in one or the other genome. Many of these genes have already been assigned names in the rat, so that renaming them based on BLAST scores leads to duplicate sets of names. The supposed orthology created by name sharing across genomes is not always found. These inaccurate names are appearing in frequently used sites, such as the University of California Santa Cruz Genome Browser. The example of rat cytochrome P450 (Cyp) genes is presented here, but other gene families are also likely to be affected.


Multi-parameter optimization of a neutron backscattering landmine detection system.
A study was performed to enhance the neutron moderation and investigate the response of a landmine detection system based on measuring backscattered neutrons with a (3)He detector. Parameters affecting the system's response were simultaneously optimized to improve the sensitivity of the detection system. The optimized sensitivity of the detection system was analyzed for different horizontal and lateral positions of a landmine.


MRI-based vertebral bone quality score: relationship with age and reproducibility.
Vertebral bone quality (VBQ) score is an opportunistic measure of bone mineral density using routine preoperative MRI in spine surgery. VBQ score positively correlates with age and is reproducible across serial scans. However, extrinsic factors, including MRI machine and protocol, affect the VBQ score and must be standardized. The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3 months. This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3 months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5 years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.


Coombs-negative Autoimmune Hemolytic Anemia Followed by Anti-erythropoetin Receptor Antibody-associated Pure Red Cell Aplasia: A Case Report and Review of Literature.
A 76-year-old woman was referred to our hospital because of anemia. The laboratory findings revealed hemolysis. Although a direct Coombs test was negative, a high titer of RBC-bound IgG was detected, and a diagnosis of Coombs-negative autoimmune hemolytic anemia was made. She was successfully treated with prednisolone. One year and five months later, she again presented anemia and was diagnosed with pure red cell aplasia. Anti-erythropoietin receptor antibody was detected in the serum. She was treated with cyclosporine and obtained prompt recovery. We herein report this rare case and review the pertinent literature.


Changes in the choroidal circulation of rabbit following RPE removal.
To examine the effects of surgical removal of the retinal pigment epithelium (RPE) on the choroidal circulation of the rabbit. The retina and choroid were examined by biomicroscopy, scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography and histology at various times after the surgical removal of the RPE by gentle aspiration following a prior local vitrectomy and bleb detachment. Comparison was made between small and large areas of RPE removal, or only slight pressure to the retina without removal of RPE. Removal of the RPE layer causes transient leakage of vascular fluid into the subretinal space for at least a week after surgery and loss of perfusion in the underlying choroidal vessels and choriocapillaris at the débridement site. This reduction in local choroidal blood flow can occur within 15 min after RPE débridement and can be transient or permanent. Histology indicates that permanent changes are due to fibroblastic infiltration that compresses the choroidal vessels. Permanent changes tend to occur after removal of relatively large areas of RPE. The removal of small areas of RPE or slight pressure on the retina causes a transient loss of local choroidal perfusion, and fibroblastic infiltration into the choroid does not occur. Removal of the RPE causes changes throughout the underlying choroid. It reduces the circulation in the large choroidal vessels as well as the choriocapillaris. If large areas of RPE are removed, this choroidal non-perfusion can be permanent due to fibroblastic infiltration. Small areas of RPE removal or slight pressure on the retina lead to only transient reduction of the choroidal flow. The rapidity with which the choroidal blood flow can be reduced implies a reflex mechanism that responds to sudden RPE pressure and/or trauma. These changes are best observed with ICG angiography.


Exploratory study to evaluate plasma vasopressin and apelin-13 levels in children with attention-deficit hyperactivity disorder.
Vasopressin exerts robust influences on social communication and behavior in humans. Apelin is a relatively novel neuropeptide that could counteract vasopressin's actions and has been shown to be closely related with a broad range of physiological functions. Abnormalities in vasopressin and apelin have been detected in a variety of psychiatric disorders, but their relation to attention-deficit hyperactivity disorder (ADHD) is unknown. In the present study, we explored the plasma levels of vasopressin and apelin-13 in children with ADHD. Thirty-four children with ADHD and 36 healthy controls were enrolled in this study. The severity of ADHD symptoms was assessed via Conners' Parent Rating Scale and Conners' Teacher Rating Scale. Plasma levels of vasopressin and apelin-13 were measured using commercial enzyme-linked immunosorbent assay kits. The mean plasma apelin-13 levels were significantly higher in male children with ADHD than in male control subjects; no significant difference was found between the groups for plasma apelin-13 levels in girls or in the entire subject cohort. Plasma vasopressin levels did not show any significant differences between groups. There were no significant correlations between plasma levels of these neuropeptides and scores for Conners' Parent Rating Scale and Conners' Teacher Rating Scale. Our results suggest a sex-specific association between plasma apelin-13 levels and ADHD. Apelin-13 may play a role in the etiopathogenesis of ADHD either with a direct impact on the apelin receptor or via its opposing effect on the vasopressinergic system.


Retransplantation of human bone marrow. Two immunosuppressive drug regimens.
A 15-year-old boy with aplastic anemia was successfully retransplanted with matched sibling bone marrow after failure of a first transplant from the same donor. Cyclophosphamide was used as immunosuppression for the first transplant, and cyclophosphamide plus procarbazine plus antithymocyte globulin were used for the second transplant. Laboratory studies of peripheral blood and bone marrow karyotypes and T and B lymphocytes supported the conclusion that immunosuppression was inadequate for the first transplant, but adequate for the second transplant.


Use of the NIH consensus criteria in cellular and soluble biomarker research in chronic graft-versus-host disease: A systematic review.
Chronic graft-versus-host disease (cGvHD) is the most frequent cause of late non-relapse mortality after allogeneic haematopoietic stem cell transplantation (alloHCT). Nevertheless, established biomarkers of cGvHD are still missing. The National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGvHD provided recommendations for biomarker research. We evaluated to which extent studies on cellular and soluble biomarkers in cGvHD published in the last 10 years complied with these recommendations. Also, we highlight the most promising biomarker candidates, verified in independent cohorts and/or repeatedly identified by separate studies. We searched Medline and EMBASE for "cGvHD", "biomarkers", "soluble" and "cells" as MeSH terms or emtree subject headings, and their variations on July 28th, 2021, limited to human subjects, English language and last ten years. Reviews, case reports, conference abstracts and single nucleotide polymorphism studies were excluded. Criteria based on the set of recommendations from the NIH group for biomarker research in cGvHD were used for scoring and ranking the references. A total of 91 references encompassing 15,089 participants were included, 54 prospective, 17 retrospective, 18 cross-sectional, and 2 studies included both prospective and retrospective cohorts. Thirty-five papers included time-matched controls without cGvHD and 20 studies did not have any control subjects. Only 9 studies were randomized, and 8 were multicentric. Test and verification cohorts were included in 11 studies. Predominantly, diagnostic biomarkers were explored (n=54). Assigned scores ranged from 5-34. None of the studies fulfilled all 24 criteria (48 points). Nevertheless, the scores improved during the last years. Three cell subsets (CXCR3+CD56bright NK cells, CD19+CD21low and BAFF/CD19+ B cells) and several soluble factors (BAFF, IL-15, CD163, DKK3, CXCL10 and the panel of ST2, CXCL9, MMP3 and OPN) had the highest potential as diagnostic and/or prognostic biomarkers in cGvHD. Despite several limitations of this review (limited applicability for paediatric population, definition of verification, missing data on comorbidities), we identified promising candidate biomarkers for further evaluation in multicentre collaborative studies. This review confirms the importance of the NIH consensus group criteria for improving the quality and reproducibility of cGvHD biomarker research.


Genotoxicity, oxidative stress, and biochemical biomarkers of exposure to green synthesized cadmium nanoparticles in Oreochromis niloticus (L.).
The considerable increment in the use of Nanoparticles in the industry has been recognized as an environmental concern today. Therefore, this study aimed to investigate the toxicity effects of green synthesized cadmium nanoparticles [Cd]NPs using Moringa oleifera leaves extract on multi-biomarkers in Oreochromis niloticus after four weeks of exposure. The results showed that LC50 values of [Cd]NPs for 24, 48, 72 and 96 h were 2.17, 1.75, 1.49 and 1.22 mg l-1, respectively. There was a significant decrease in the number of white and red blood cells, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration value in fish exposed to [Cd]NPs. The mean corpuscular volume and neutrophils were increased. [Cd]NPs exposure to fish has led to cytotoxic and genotoxic changes in the erythrocytes. Significant changes were observed in the cortisol, triiodothyronine, and thyroxine levels of the fish exposed to [Cd]NPs. The activities of aspartate aminotransferase and alanine aminotransferase increased. Glucose, total lipids, urea, and creatinine levels increased in the serum of fish exposed to [Cd]NPs, whereas total protein contents and alkaline phosphatase activity decreased. A significant reduction was observed in glycogen, total antioxidant levels, and superoxide dismutase, catalase and glutathione S-transferase activities of fish exposed to [Cd]NPs. In contrast, the [Cd]NPs exposure resulted in a significant increase in DNA fragmentation percentages, lipid peroxidation, and carbonyl protein levels in different tissues. The results of the present study confirmed that [Cd]NPs has the toxicity potential to cause Cyto-genotoxicity, oxidative damages, changes in the hematological and biochemical changes, and endocrine disruptor in the fish.


Simultaneous subtyping of group specific component and esterase D by isoelectric focusing on agarose gels.
A quick, sensitive and economical technique has been developed to subtype GC and ESD simultaneously on the same agarose IEF gel. This method could be a useful tool for forensic application.


Variation in the relative abundance of gamma-crystallin gene transcripts during development and ageing.
The transcripts of gamma-crystallin mRNA were examined during adulthood. The mRNA transcripts were detected by Northern blot technique. Although the total RNA per lens measured remains constant during adulthood, the mRNA transcript size was observed to decline with ageing, specifically for the gamma-crystallin and not for alpha- and beta-crystallins. We could show that the relative amount of mRNA transcripts detected with the four probes decreased with ageing, with gamma 1 and gamma 2 transcripts being found at a higher level than the gamma 3 and gamma 4 transcripts.


Prevalence of Deleterious Oral Habits among 3- to 5-year-old Preschool Children in Bhubaneswar, Odisha, India.
Oral habits during and beyond preschool age are one of the important etiological factors in developing malocclusion and other ill effects on orofacial structures. The objective of the present study was to know the prevalence of deleterious oral habits among 3- to 5-year-old preschool children in Bhubaneswar, Odisha, India. This cross-sectional study was conducted among preschool children, in the age group of 3 to 5 years in the city of Bhubaneswar, Odisha, India. To carry out this study, six private schools, two from each of the three electoral constituency, were selected using cluster sampling technique. A total of 500 students, studying in LKG and UKG and their respective mothers/caregivers were selected for the study as per the inclusion/exclusion criteria. Prevalence of different oral habits in children was calculated from the data obtained. Using Statistical Package for the Social Sciences (SPSS), version 17.0 software, Chi-square test was applied to compare the differences present between boys and girls and their significant values (p < 0.05). The result of this study showed a high prevalence of oral habits (36%) among preschool children in Bhubaneswar, Odisha, India. Lip biting was found to be the most prevalent habit (13.4%), followed closely by thumb sucking (12.8%), bruxism (12.8%), and mouth breathing (11%). The study revealed a great dearth of a well-established dental education program for preschool children as well as their parents, caretakers, teachers, and pediatricians in order to provide an effective and timely care to the children.How to cite this article: Dhull KS, Verma T, Dutta B. Prevalence of Deleterious Oral Habits among 3- to 5-year-old Preschool Children in Bhubaneswar, Odisha, India. Int J Clin Pediatr Dent 2018;11(3):210-213.


Origin of tumor recurrence after intensity modulated radiation therapy for oropharyngeal squamous cell carcinoma.
To model locoregional recurrences of oropharyngeal squamous cell carcinomas (OSCC) treated with primary intensity modulated radiation therapy (IMRT) in order to find the origins from which recurrences grow and relate their location to original target volume borders. This was a retrospective analysis of OSCC treated with primary IMRT between January 2002 and December 2009. Locoregional recurrence volumes were delineated on diagnostic scans and coregistered rigidly with treatment planning computed tomography scans. Each recurrence was analyzed with two methods. First, overlapping volumes of a recurrence and original target were measured ('volumetric approach') and assessed as 'in-field', 'marginal', or 'out-field'. Then, the center of mass (COM) of a recurrence volume was assumed as the origin from where a recurrence expanded, the COM location was compared with original target volume borders and assessed as 'in-field', 'marginal', or 'out-field'. One hundred thirty-one OSCC were assessed. For all patients alive at the end of follow-up, the mean follow-up time was 40 months (range, 12-83 months); 2 patients were lost to follow-up. The locoregional recurrence rate was 27%. Of all recurrences, 51% were local, 23% were regional, and 26% had both local and regional recurrences. Of all recurrences, 74% had imaging available for assessment. Regarding volumetric analysis of local recurrences, 15% were in-field gross tumor volume (GTV), and 65% were in-field clinical tumor volume (CTV). Using the COM approach, we found that 70% of local recurrences were in-field GTV and 90% were in-field CTV. Of the regional recurrences, 25% were volumetrically in-field GTV, and using the COM approach, we found 54% were in-field GTV. The COM of local out-field CTV recurrences were maximally 16 mm outside CTV borders, whereas for regional recurrences, this was 17 mm. The COM model is practical and specific for recurrence assessment. Most recurrences originated in the GTV. This suggests radioresistance in certain tumor parts.


Left Atrial Deformation Imaging and Atrial Fibrillation in Patients with Rheumatic Mitral Stenosis.
Atrial fibrillation (AF) is a frequent complication of rheumatic mitral stenosis (MS) and is associated with worse outcomes. Prediction of new-onset AF by assessing left atrial (LA) mechanics with speckle-tracking echocardiography might be useful for risk stratification and guiding therapeutic strategies. Therefore, the aim of this study was to assess the association of LA reservoir strain (LASr) and strain rate (LASRr) with AF at follow-up in patients with rheumatic MS. Left atrial reservoir strain and LASRr measured by speckle-tracking echocardiography were assessed in 125 patients (mean age, 50 ± 15 years; 80.8% female) with rheumatic MS and without a history of AF. Patients were followed up for the occurrence of a first episode of AF after the index echocardiogram. During a median follow-up of 32 (9.5-70) months, 41 patients (32.8%) developed new-onset AF. Patients who developed AF had significantly more impaired LASr (13.4% ± 5.2% vs 18.9% ± 8.2%; P < .001) and LASRr (0.72 ± 0.26 s-1 vs 0.98 ± 0.36 s-1;P < .001) compared with patients who remained in sinus rhythm. On multivariable Cox regression analysis, LASr < 21% and LASRr < 0.8 s-1 were independently associated with the development of AF at follow-up (hazard ratio = 7.03, 95% CI, 2.08-23.77, P = .002; and hazard ratio = 3.42, 95% CI, 1.59-7.34, P = .002, respectively). LASr and LASRr are impaired in patients with rheumatic MS, and the degree of impairment is associated with new-onset AF at follow-up.


ESEM-EDX characterisation of airborne particles from an industrialised area of northern Greece.
The aim of this study was to characterise individual airborne particles collected from the Ptolemais-Kozani region (Western Macedonia), northern Greece. Throughout a 1-year period (March 2003 to February 2004), we collected several filters that captured airborne particles at seven sampling sites distributed throughout the area. The airborne particles captured on the filters were then characterised by environmental scanning electron microscopy (ESEM) coupled with energy-dispersive X-ray analysis (EDX). The particles were categorised as geogenic, biogenic and anthropogenic. The main anthropogenic airborne particles were fly ash (released from lignite-fired power plants) and carbonaceous (soot and char) and metalliferous (mainly iron- and copper-enriched) particulates. We present here characteristic ESEM and EDX spectra for the airborne particles and underline the presence of characteristic primary and secondary sulphates.


Construction of chimeric beta-glucosidases with improved enzymatic properties.
The amino acid sequences of beta-glucosidases from Cellvibrio gilvus and Agrobacterium tumefaciens show about 40% similarity. The pH/temperature optima and stabilities and substrate specificities of the two enzymes are quite different. C. gilvus beta-glucosidase exhibits an optimum pH of 6.2-6.4 and temperature of 35 degrees C, whereas the corresponding values for A. tumefaciens are 7.2-7.4 and 60 degrees C, respectively. The substrate specificity of A. tumefaciens enzyme toward different aryl glycosides is broader than C. gilvus enzyme. To analyze these properties further, three chimeric beta-glucosidases were constructed by substituting segments from the C-terminal homologous region of C. gilvus beta-glucosidase gene with that of A. tumefaciens. The chimeric enzymes were characterized with respect to pH/temperature activity and stability and substrate specificity. Chimeric enzymes exhibited chromatographic behavior similar to that of C. gilvus enzyme. However, enzymatic properties of chimeras were admixtures of those of the two parents. The chimeric enzymes were optimally active at 45-50 degrees C and pH 6.6-7.0. Km values of chimeric enzymes for the various saccharides were admixtures of both parental enzymes. These results suggest that the two domains of C. gilvus and A. tumefaciens enzymes probably can fold independently. The homologous C-terminal region in beta-glucosidase appears to play an important role in determining enzyme characteristics. Changes in the properties on substitution of segments in this region might be related to the enzyme specificity, and beta-glucosidases with improved properties can be prepared by manipulating this region.


Expression of VP2 gene protein of infectious bursal disease virus detected in Korea.
The VP2 gene DNA (1.4 kb in approximate) of a very virulent infectious bursal disease virus (vvIBDV) Chinju strain detected in Chinju, Korea was cloned into the bacmid, a baculovirus shuttle vector, through transposition of the gene from initially cloned pFastBacHTa plasmid, a baculovirus expression vector, and was subsequently expressed in Spodoptera frugiperda (Sf) cells. Biological properties of the expressed VP2 subunit protein were characterized to aid in the development of genetically engineered diagnostic reagents and vaccines against the vvIVDV. When the VP2 DNA-recombinant bacmid was transfected and propagated in the Sf cells, the cells showed no occlusion formation, which is a positive evidence for the insertion of the VP2 DNA into the polyhedrin gene of the bacmid, whereas the occlusions were observed in the cells infected by the Autographa californica nuclear polyhedrosis virus, a wild baculovirus. The expression of VP2 DNA was identified by strong positive reaction in fluorescent antibody test using chicken anti-IBDV serum. The VP2 protein was determined as a polypeptide band with Mr of 48 kDa by the sodium dodecyl-polyacrylamide gel electrophoresis for the lysate of the Sf cells infected with the recombinant bacmid. The VP2 protein was successfully purified from the cell lysate by Ni-NTA affinity chromatography. The expressed VP2 subunit protein reacted specifically with chicken anti-IBDV serum in Western blotting.


Efficient and recyclable dendritic Buchwald-type catalyst for the Suzuki reaction.
A Buchwald-type ligand attached to a star-shape molecule was synthesized in high yield, and its catalytic properties for the Suzuki reactions are shown to be excellent (down to 50 ppm with a simple chloroarene) including recovery/re-use of this hexa ligand.


Preparing to strike: Acute events in signaling by the serpentine receptor for thromboxane A2.
Over the last two decades, awareness of the (patho)physiological roles of thromboxane A2 signaling has been greatly extended. From humble beginnings as a short-lived stimulus that activates platelets and causes vasoconstriction to a dichotomous receptor system involving multiple endogenous ligands capable of modifying tissue homeostasis and disease generation in almost every tissue of the body. Thromboxane A2 receptor (TP) signal transduction is associated with the pathogenesis of cancer, atherosclerosis, heart disease, asthma, and host response to parasitic infection amongst others. The two receptors mediating these cellular responses (TPα and TPβ) are derived from a single gene (TBXA2R) through alternative splicing. Recently, knowledge about the mechanism(s) of signal propagation by the two receptors has undergone a revolution in understanding. Not only have the structural relationships associated with G-protein coupling been established but the modulation of that signaling by post-translational modification to the receptor has come sharply into focus. Moreover, the signaling of the receptor unrelated to G-protein coupling has become a burgeoning field of endeavor with over 70 interacting proteins currently identified. These data are reshaping the concept of TP signaling from a mere guanine nucleotide exchange factors for Gα activation to a nexus for the convergence of diverse and poorly characterized signaling pathways. This review summarizes the advances in understanding in TP signaling, and the potential for new growth in a field that after almost 50 years is finally coming of age.


Archaea from the gut microbiota of humans: Could be linked to chronic diseases?
Archaea comprise a unique domain of organisms with distinct biochemical and genetic differences from bacteria. Methane-forming archaea, methanogens, constitute the predominant group of archaea in the human gut microbiota, with Methanobrevibacter smithii being the most prevalent. However, the effect of methanogenic archaea and their methane production on chronic disease remains controversial. As perturbation of the microbiota is a feature of chronic conditions, such as cardiovascular disease, neurodegenerative diseases and chronic kidney disease, assessing the influence of archaea could provide a new clue to mitigating adverse effects associated with dysbiosis. In this review, we will discuss the putative role of archaea in the gut microbiota in humans and the possible link to chronic diseases.


Staphylococcus aureus osteitis of the dens: a rare location.
An immunocompetent 84-year-old woman was admitted for severe neck pain with a fever. Magnetic resonance imaging showed osteitis of the dens. She had methicillin-susceptible Staphylococcus aureus bacteremia related to a dental extraction. She then developed an infection of a hip prosthesis due to the same organism. Her treatment consisted in intravenous antibiotics followed by oral suppressive antibiotic therapy for 2 years. Exchange arthroplasty was not performed given the advanced age of the patient, her unwillingness to undergo the procedure, and the risk of neurological complications during endotracheal intubation. The outcome was favorable at last follow-up more than 2 years after antibiotic treatment initiation.


Cerebral palsy.
In a prospective study it was found that cerebral palsy constituted 0.29% of total paediatric outdoor cases during the study period of 1988-1990. Seventy-five children suffering from cerebral palsy were studied at SN Children Hospital, Allahabad. Male to female ratio was 1:2. There were 42.8% cases who belonged to the age between one and 2 years. Hypertonic cases were predominant over hypotonic cases (3:1). Hemiplegia was commonest (68%) while triplegia was least common (2.7%). There were 24.5% cases who were mentally retarded. Hypertonic cases improved more frequently than hypotonic cases. An early management by paediatric physiotherapy may play an important role in the treatment of cerebral palsy.


Effectiveness of an mHealth intervention to increase adherence to triage of HPV DNA positive women who have performed self-collection (the ATICA study): A hybrid type I cluster randomised effectiveness-implementation trial.
Human Papillomavirus (HPV) self-collection offered by community health workers (CHWs) during home visits has been hampered by low levels of triage Pap among HPV-positive women. We investigated effectiveness of a mHealth intervention to increase adherence to triage Pap. We conducted a hybrid type I cluster randomised effectiveness-implementation trial in Jujuy, Argentina. CHWs (clusters) were eligible if actively offering HPV self-collection and served at least 26 women aged 30 years and over. Women were eligible if they conducted self-collection and provided a mobile phone number. 260 CHWs were randomly allocated (3:2 ratio) to a multi-component intervention (Up to four SMS messages sent to HPV-positive women, and one SMS message to CHWs to prompt a visit of women with no triage Pap 60 days after a positive-test), or control group (Usual care: Women instructed to attend their health centre 30 days after HPV self-collection to pick-up results). The primary effectiveness outcome was percentage of HPV-positive women with triage 120 days after the HPV-test result. We evaluated implementation of the intervention using the RE-AIM framework. 221 CHWs (132 intervention, 89 control group) contacted 5389 women; and 5351 agreed to participate (3241 intervention, 2110 control group). In total 314/445 (70·5%) HPV-positive women of the intervention group had triage at 120 days after the HPV result, compared to 163/292 (55·1%) in the control group: 15·5% point improvement; 95%CI: 6·8-24·1; relative risk: 1·28; 95%CI: 1·11-1·48. 97·2% of women accepted the intervention and 86·9% of CHWs agreed to its adoption. The multicomponent mHealth intervention was effective in increasing the percentage of HPV-positive women who had triage Pap, allowing for many more women at risk of cervical cancer to receive timely follow-up. National Cancer Institute of the National Institutes of Health (USA) under Award Number R01CA218306.


[ACUTE KIDNEY INJURY SECONDARY TO URINARY TRACT OBSTRUCTION - A RARE COMPLICATION OF CIRCUMCISION].
Approximately a third of men worldwide and over 90% of Israeli men are circumcised. The procedure carries a low rate of complication, mainly including surgical and infectious complications. Urinary tract obstruction (UTO) is a rare complication of circumcision. The aim of this study was to define the incidence of UTO following circumcision in the last 20 years and describe the characteristics of the affected babies. Study participants were identified from a list consisting of all male babies aged 7-30 days treated at the Shaare Zedek Medical Center during the years 2000-2020. Files of patients with serum creatinine ≥ 1 mg/dl were reviewed. Clinical and laboratory data were collected from patients' records. Ten babies with acute kidney injury due to UTO after circumcision were identified. Average age at admission was 10.1 days (8-13). Only two babies had an uncomplicated postnatal course. The main findings on physical examination were distended abdomen, abdominal wall discoloration and leg edema. Average creatinine on admission was 1.76 mg/dl (1.0-3.28). Additional findings were hyperkalemia 6.2 mEq/L (4.5-7.6) and hyponatremia 125 mEq/L (118-134). All hospitalized patients developed post-obstructive diuresis. Kidney function and laboratory abnormalities completely resolved in all of our patients. There was no evidence of kidney damage in six children with long-term follow up. UTO with acute kidney injury is a rare severe complication of circumcision. Prompt identification and proper treatment can result in complete resolution of kidney function.


Synthesis and crystal structure of poly[[bis-(aqua-κO)tetra-kis-(μ-4,4'-bi-pyridine-κ2 N:N')hexa-kis-(3-chloro-benzoato)-κ5 O;κ2 O:O'-tricobalt(II)] methanol disolvate].
A novel ladder-chain cobalt(II) coordination polymer, {[Co3(C7H4ClO2)6(C10H8N2)4(H2O)2]·2CH3OH} n , was synthesized and characterized. The structure contains two CoII centres with different octa-hedral environments, [Co(1)N3O3] and [Co(2)N2O4]. The O-donating 3-chloro-benzoate anions (3-Clbenz) act as the terminal ligands, while the N-donating 4,4'-bipy mol-ecules play the role of linkers. The Co(1) ions are linked by 4,4'-bipy mol-ecules into linear chains. Two such chains are joined by [Co(2)(3-Clbenz)2(H2O)2] units via two 4,4'-bipy bridging ligands, thus forming the ladder-chain structure. The crystal packing of the title compound is stabilized by supra-molecular inter-actions, such as hydrogen bonding, π-π and halogen⋯π contacts, giving a three-dimensional framework. The spectroscopic and thermal properties of the title compound have also been investigated.


Effect of forced locomotion on the rest-activity cycle of the cockroach.
Many insects are known to exhibit clear circadian rest-activity rhythms. Attention has focussed more on active behaviors such as locomotion than on rest. I investigated the consequences of disturbances of the rest period on activity states of the cockroach Leucophea maderae. The 24-h rest-activity rhythm of individual animals maintained under a 12 h light-12 h dark schedule was continuously recorded by timelapse video recording. Three activity states were scored: locomotion, immobility, and limb or antenna movements without locomotion. The effect of (i) 3 h forced activity; and of (ii) handling and a new environment was studied. Forced activity during the last 3 h of the light period caused a significant reduction of locomotion, and of limb or antenna movements; and an enhancement of immobility in the first hours of the dark period. However, over the entire 12 h dark period, these parameters did not differ from control. Brief handling in conjunction with a change in environment during the last 3 h of the dark period, was followed by similar, though smaller changes in locomotion as seen after forced locomotion. The results indicate that the time spent in immobility corresponds to a resting state which is regulated as a function of prior activity. Thus immobility in an invertebrate may exhibit similar regulating mechanisms as rest or sleep in vertebrates.


Cultural construction of the menopausal syndrome: the Japanese case.
Europe and North America have been the focus of most research on the menopause and its symptoms. In this study, in the course of in-depth interviews Japanese physicians and women were asked to describe the menopausal experience. A cross-sectional survey concerning women and their health at midlife was then distributed to 1738 women. The analysis in this paper is based on the replies received from 1141 non-hysterectomized women aged 45-55. Factor analysis was used to group the symptoms these women had experienced in the previous 2 wk. After constructing an index based on the factor scores, one-way analysis of variance was used to examine the relationship between symptom experience and the epidemiological menopausal status as well as the self-defined menopausal status. Symptom experience was always significantly related to self-defined menopausal status.


Data security and protection in cross-institutional electronic patient records.
This paper aims at identifying the specific legal requirements concerning data security and data protection of patient health data that apply to a cross-institutional electronic patient record (EPR) and describes possible solutions for meeting these requirements. In Germany, the legal framework for such records provide that disclosure of patient health information to physicians of third-party institutions is only allowed in case that it is necessary for the joint treatment of the patient, i.e. in case of a "treatment connection". As a first step, the functionality of a remote-access architecture was proven allowing a one-way connection between the EPR systems of two health institutions in Germany, which jointly treat tumor patients. Besides, a signature system model for ensuring the integrity and authenticity of medical documents was developed and implemented in the existing information system architecture of the University Medical Center of Heidelberg. Especially in Germany, the legal framework for cross-institutional EPRs is very complex and has a considerable influence on the development and implementation of cross-institutional EPRs. However, its introduction is thought to be valuable, since a cross-institutional EPR will improve communication within shared care processes, and thus improve the quality of patient care.


Differential effects of fluoride during initiation and progression of mineralization of osteoid nodules formed in vitro.
Osteoid nodules form in cultures of fetal rat calvarial (RC) cells grown in medium containing 10% FBS and 50 micrograms/ml of ascorbic acid. When 10 mM beta-glycerophosphate (beta-GP) is added, osteoid nodules mineralize in two phases: an initiation phase, which is dependent upon alkaline phosphatase activity for conversion of beta-GP to P(i), and a progression phase that proceeds independently of alkaline phosphatase activity and does not require exogenous phosphate. We have now used this system to investigate the effects of fluoride (F-) on mineralization. In cultures in which osteoid was formed and mineralization initiated in the presence of F-, a dose-dependent inhibition of the initiation of mineralization occurred over a concentration range of 25-500 microM F- (p < 0.001 in all cases). The initiation of mineralization was not inhibited if F- was removed from the cultures at the time when mineralization was initiated with beta-GP. In osteoid nodules grown in the absence of F-, addition of F- resulted in a dose-dependent inhibition of the initiation of mineralization, with significant decreases in 45Ca uptake occurring at F- concentrations of 3 microM (p < 0.01) and higher. However, if F- was added to cultures after mineralization was initiated in the absence of F-, a stimulation of 45Ca uptake was observed at F- concentrations of 250 microM and above (p < 0.001). F- (1-1000 microM) did not affect the conversion of beta-GP to P(i) or alkaline phosphatase activity in the cultures.(ABSTRACT TRUNCATED AT 250 WORDS)


[History and contemporary state of hygienic regulation for chemicals in air of workplace in Russian Federation].
The article covers state of hygienic regulation of chemicals in air of workplace in Russian Federation from 1991 to date.


Testicular sarcoidosis.
A 20 year old black man presented with shortness of breath, hilar adenopathy, monoarticular arthritis, polydipsia and polyuria, and bilateral testicular masses. Transbronchial biopsy revealed noncaseating granulomas consistent with sarcoidosis. Subsequent work-up demonstrated hypothalamic dysfunction, and joint fluid analysis was consistent with sarcoid arthropathy. Concern over the possibility of a testicular neoplasm led to right testicular biopsy which revealed noncaseating granulomas consistent with testicular sarcoidosis. A short course of steroid therapy resulted in clinical improvement and complete resolution of the remaining left testicular mass.


Incidence and risk factors for pneumonia following anterior cervical decompression and fusion procedures: an ACS-NSQIP study.
Postoperative pneumonia has important clinical consequences for both patients and the health-care system. Few studies have examined pneumonia following anterior cervical decompression and fusion (ACDF) procedures. This study aimed to determine the incidence and risk factors for development of pneumonia following ACDF procedures. A retrospective cohort study of data collected prospectively by the American College of Surgeons National Surgical Quality Improvement Program was carried out. This study comprised 11,353 patients undergoing ACDF procedures during 2011-2013. The primary outcome was diagnosis of pneumonia in the first 30 postoperative days. Independent risk factors for the development of pneumonia were identified using multivariate regression. Readmission rates were compared between patients who did and did not develop pneumonia using multivariate regression that adjusted for all demographic, comorbidity, and procedural characteristics. The incidence of pneumonia was 0.45% (95% confidence interval=0.33%-0.57%). In the multivariate analysis, independent risk factors for the development of pneumonia were greater age (p<.001), dependent functional status (relative risk [RR]=5.3, p<.001), chronic obstructive pulmonary disease (RR=4.4, p<.001), and greater operative duration (p=.020). Patients who developed pneumonia following discharge had a higher readmission rate than other patients (72.7% vs. 2.4%, adjusted RR=24.5, p<.001). In total, 10.2% of all readmissions were caused by pneumonia. Pneumonia occurs in approximately 1 in 200 patients following ACDF procedures. Patients who are older, are functionally dependent, or have chronic obstructive pulmonary disease are at greater risk. These patients should be counseled, monitored, and targeted with preventative interventions accordingly. Greater operative duration is also an independent risk factor. Approximately three in four patients who develop pneumonia following hospitalization for ACDF procedures are readmitted. This elevated readmission rate has implications for bundled payments and hospital performance reports.


In vivo formation of IRF-1 homodimers.
Interferon regulatory factor 1 (IRF-1) is a transcriptional activator which exerts different biological activities. IRF-1 activates interferon induced genes as well as genes which are not directly linked to the interferon system, such as the ICE protease gene. IRF-1 activity is post-transcriptionally regulated in addition to transcriptional regulation by interferons, cytokines, hormones and many other factors. This includes heterodimerisation with activators and repressors of transcription. These protein interactions modulate the transactivating capacity of IRF-1. By using a two-hybrid system, we demonstrate that IRF-1 forms homodimers in vivo. The homodimerization domain was determined to be located in the N-terminal part of IRF-1 which belongs to the DNA-binding domain. Since this sequence is highly conserved between members of the IRF-family, our observation raises the question of homodimerization of other IRFs through this domain.


Perioral force measurement by a radiotelemetry device.
A telemetric method was developed to monitor the active and passive perioral forces exerted on the maxillary dental arch. The system consists of intraoral and extraoral units. An electromagnetic coupling between intraoral and extraoral coils supplies the power of the intraoral unit and transmits the signals induced by variations in perioral forces. The force sensor has a diameter of 6 mm, a thickness of 1 mm, and is constructed of an 0.08 mm thick cantilever beam to which semiconductor strain gauges are cemented. Clinical application of the system was tested in four adult subjects. The forces on the labial surface of an upper central incisor were 1.5 gm/cm2 during rest, 10.9 gm/cm2 during swallowing, and 5.0 gm/cm2 during speech; the corresponding lingual forces were 4.0 gm/cm2, 19.1 gm/cm2, and 13.9 gm/cm2, respectively. Lingual forces were always higher than labial forces. The telemetry system can be used to monitor up to 6 hours of continual variations in perioral forces.


Impaired processing of binaural temporal cues to auditory scene analysis in schizophrenia.
It is well established that individuals with schizophrenia demonstrate alterations in auditory perception beginning at the very earliest stages of information processing. However, it is not clear how these impairments in basic information processing translate into high-order cognitive deficits. Auditory scene analysis allows listeners to group auditory information into meaningful objects, and as such provides an important link between low-level auditory processing and higher cognitive abilities. In the present study we investigated whether low-level impairments in the processing of binaural temporal information impact upon auditory scene analysis ability. Binaural temporal processing ability was investigated in 19 individuals with schizophrenia and 19 matched controls. Individuals with schizophrenia showed impaired binaural temporal processing ability on an inter-aural time difference (ITD) discrimination task. In addition, patients demonstrated impairment in two measures of auditory scene analysis. Specifically, patients had reduced ability to use binaural temporal cues to extract signal from noise in a masking level difference paradigm, and to separate the location of a source sound in the presence of an echo in the precedence effect paradigm. These findings demonstrate that individuals with schizophrenia have impairments in the accuracy with which simple binaural temporal information is encoded in the auditory system, and furthermore, this impairment has functional consequences in terms of the use of these cues to extract information in complex auditory environments.


Experienced surgeons versus novice surgery residents: Validating a novel knot tying simulator for vessel ligation.
Vessel ligation with a knot is one of the most fundamental tasks surgeons must master. We developed a simulator designed to enable novices to acquire and refine gentle knot tying capabilities. A bench-top, knot-tying simulator with computer-acquired assessment was tested on expert surgeons and surgery residents at an academic medical center during the years 2016 to 2018. Each participant tied a total of 8 knots in different settings (superficial versus deep) and techniques (1-handed versus 2 hands). The simulator measured vertical forces and task completion time. Fifteen experienced surgeons and 30 surgery residents were recruited. The expert group exerted considerably less total force during placement of the knots than the novice residents (3.8 ± 2.0 vs 9.2 ± 6.1 N, respectively; P = .0005) and the peak force exerted upward was less in the expert group (1.31 ± 0.6 vs 1.75 ± 0.84 N; P = .02). The experts also completed the task in less time (10.9 ± 3.4 vs 18.3 ± 7.2 seconds; P = 0.001). The simulator can offer residency programs a low-cost, bench-top platform to train and assess objectively the knot-tying capabilities of surgery residents.


Involvement of the ipsilateral rostral ventrolateral medulla in the pressor response to L-glutamate microinjection into the nucleus tractus solitarii of awake rats.
Microinjection of L-glutamate into the lateral commissural nucleus tractus solitarii (NTS) of unanesthetized rats evokes increases in mean arterial pressure (MAP) and a bradycardia. In a previous study we verified that this increase in MAP is mediated sympathetically because prazosin (i.v.) blocks this response. The aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the pressor response produced by L-glutamate microinjected into the NTS of unanesthetized rats. L-Glutamate was microinjected into the NTS before and 15 and 90 min after microinjection of kynurenic acid into the ipsilateral RVLM. Pressor (+24+/-3 vs. +6+/-3 mm Hg) and bradycardic (-101+/-10 vs. -3+/-12 bpm) responses to L-glutamate microinjected into the NTS (n = 8) were almost abolished 15 min after microinjection of kynurenic acid into the RVLM when compared with control responses. Both pressor (+23+/-6 mm Hg) and bradycardic (-93+/-16 bpm) responses to L-glutamate into the NTS returned to control values 90 min after microinjection of kynurenic acid into the RVLM. These data indicate that the pressor response to L-glutamate into the NTS is essentially dependent on the ipsilateral RVLM and also that this sympatho-excitatory response is mediated by excitatory amino acid receptors in RVLM neurons.


Chemoprevention Uptake for Breast Cancer Risk Reduction Varies by Risk Factor.
The efficacy of chemoprevention for breast cancer risk reduction has been demonstrated in randomized controlled trials; however, use remains low. We sought to determine whether uptake differed by risk factors, and to identify reasons for refusal and termination. Women seen in a high-risk clinic from October 2014 to June 2017 considered eligible for chemoprevention (history of lobular carcinoma in situ, atypia, family history of breast/ovarian cancer, genetic mutation, or history of chest wall radiation) were retrospectively identified. Breast cancer risk factors were compared among those with and without chemoprevention use, and compliance was noted. Overall, 1506 women were identified, 24% with prior/current chemoprevention use. Women ≥ 50 years of age were more likely to use chemoprevention than women < 50 years of age (28% vs. 11%, p < 0.001). Chemoprevention use by risk factor ranged from 7 to 40%. Having multiple risk factors did not increase use. Significant variation by risk factor was present among women ≥ 50 years of age (p < 0.001), but not among women < 50 years of age (p = 0.1). Among women with a documented discussion regarding chemoprevention (575/1141), fear of adverse effects was the most common refusal reason (57/156; 36%). The majority of women (61%) who initiated chemoprevention completed 5 years. Chemoprevention use among women at increased risk for breast cancer remains low, with more frequent use among women ≥ 50 years of age. These data highlight the need for ongoing educational efforts and counseling, as the majority who begin therapy complete 5 years of use. Given the fear of adverse effects as well as low uptake, particularly among women < 50 years of age, alternative risk-reducing strategies are needed.