Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia.
Erythropoietin (EPO) improves cognitive performance in clinical studies and rodent experiments. We hypothesized that an intrinsic role of EPO for cognition exists, with particular relevance in situations of cognitive decline, which is reflected by associations of EPO and EPO receptor (EPOR) genotypes with cognitive functions. To prove this hypothesis, schizophrenic patients (N > 1000) were genotyped for 5' upstream-located gene variants, EPO SNP rs1617640 (T/G) and EPORSTR(GA)(n). Associations of these variants were obtained for cognitive processing speed, fine motor skills and short-term memory readouts, with one particular combination of genotypes superior to all others (p < 0.0001). In an independent healthy control sample (N > 800), these associations were confirmed. A matching preclinical study with mice demonstrated cognitive processing speed and memory enhanced upon transgenic expression of constitutively active EPOR in pyramidal neurons of cortex and hippocampus. We thus predicted that the human genotypes associated with better cognition would reflect gain-of-function effects. Indeed, reporter gene assays and quantitative transcriptional analysis of peripheral blood mononuclear cells showed genotype-dependent EPO/EPOR expression differences. Together, these findings reveal a role of endogenous EPO/EPOR for cognition, at least in schizophrenic patients.


Delayed Recovery of Idiopathic Common Peroneal Nerve Palsy After Total Knee Arthroplasty: A Rare Case Report.
Common peroneal nerve palsy (CPNP) is a rare complication post total knee arthroplasty (TKA). Even though it is diagnosed acutely, the recovery potential is just over 50%. The average period for complete recovery in such cases is 5 months; however, the management remains controversial. Through this report, we present one such case of left sided complete CPNP after bilateral TKA who was conserved with various modalities. Even though the recovery was delayed, the patient made full recovery. A 70-year-old female patient was diagnosed to have bilateral tricompartmental knee osteoarthritis with varus deformity, both clinically and radiologically (Kellgren-Lawrence grade 4). She underwent bilateral TKA in a single sitting as per the standard protocols practiced by the primary author. On post-operative day 1, she had left-sided foot drop with a complete sensory deficit. The patient underwent routine rehabilitation with an ankle foot orthosis splint in the immediate post-operative period, with simultaneous faradic current stimulation for the left lower limb. Periodic electromyography and nerve conduction study was done at the end of 4-week and 3-month post-TKA. At 6.5-month post-surgery, she made a full clinical recovery. The surgical maneuvers and full neurovascular examination before and after every TKA surgery should be carefully performed. Despite this, if a patient presents with CPNP, the surgeon need not take an aggressive approach, unlike fracture fixation cases. These patients can be managed conservatively using appropriate orthosis, physical therapy, and faradic current stimulation. Through this case, we attempt to report that CPNP patient can recover even after 6 months of surgery when there is no tangible cause for the palsy.


Micro-Membrane Electrode Assembly Design to Precisely Measure the in Situ Activity of Oxygen Reduction Reaction Electrocatalysts for PEMFC.
An in situ micro-MEA technique, which could precisely measure the performance of ORR electrocatalyst using Nafion as electrolyte, was designed and compared with regular thin-film rotating-disk electrode (TFRDE) (0.1 M HClO4) and normal in situ membrane electrode assembly (MEA) tests. Compared to the traditional TFRDE method, the micro-MEA technique makes the acquisition of catalysts' behavior at low potential values easily achieved without being limited by the solubility of O2 in water. At the same time, it successfully mimics the structure of regular MEAs and obtains similar results to a regular MEA, thus providing a new technique to simply measure the electrode activity without being bothered by complicated fabrication of regular MEA. In order to further understand the importance of in situ measurement, Fe-N-C as a typical oxygen reduction reaction (ORR) free-Pt catalyst was evaluated by TFRDE and micro-MEA. The results show that the half wave potential of Fe-N-C only shifted negatively by -135 mV in comparison with state-of-the-art Pt/C catalysts from TFRDE tests. However, the active site density, mass transfer of O2, and the proton transfer conductivity are found to strongly influence the catalyst activity in the micro-MEA, thereby resulting in a much lower limiting current density than Pt/C (8.7 times lower). Hence, it is suggested that the micro-MEA is better in evaluating the in situ ORR performance, where the catalysts are characterized more thoroughly in terms of intrinsic activity, active site density, proton transfer, and mass transfer properties.


Legal abortion: the impending obsolescence of the trimester framework.
Women who wish to terminate a pregnancy, and physicians willing to perform abortions, are subject to increasing harassment from groups which challenge the constitutional abortion right upheld by the Supreme Court in Roe v. Wade. Their vulnerability, in fact, parallels the vulnerability of the abortion right. This Article analyzes the inherent weakness and impending obsolescence of the trimester framework established in Roe. Present medical evidence of maternal health risks and fetal viability demonstrates that the trimester framework is inconsistent with current medical knowledge, and will likely be rendered obsolete by developments in medical technology. The Article suggests that adoption of an alternative constitutional basis for legal abortion is necessary to preserve the abortion right, and explores the utility of two arguments grounded in the equal protection doctrine. Finally, it discusses means of preserving legal abortion within the confines of the trimester framework established in Roe v. Wade.


Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-RAS status for unresectable colorectal liver metastasis (BECK study): Long-term results of survival.
To investigate the long-term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. Recurrence and survival data with long-term follow-up were analyzed in the cohort of a multi-institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). A total of 22/12 patients with K-RAS wild-type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left-sided primary tumors than in right-sided tumors (75.0% vs 30.0%, P = .022). The median follow-up was 72.6 months. The 5-year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5-year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow-up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5-year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1-4). Conversion hepatectomy achieved a similar long-term survival to the results of previous studies in initially resectable patients, although many of them experienced several post-hepatectomy recurrences. Left-sided primary was found to be the predictor for conversion hepatectomy.


Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung.
Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN activation. The aim of this study was to examine the effect of a PDE type 4 inhibitor, rolipram, on the functional changes and the retention of PMN in the lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN deformability was evaluated using silicon microchannels. Rolipram reduced the increase of F-actin and CD11b but did not change the decrease of L-selectin. Rolipram inhibited the increase of the transit time of PMN through the microchannel. We evaluated the retention of PMN in the lung in vivo by infusing labeled blood into the vena cava and examining the recovery into aortic root samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of PMN in the lung by reducing deformability change and CD11b upregulation of PMN.


Unusual CoS2 ellipsoids with anisotropic tube-like cavities and their application in supercapacitors.
Unusual CoS(2) ellipsoids with anisotropic tube-like cavities have been synthesized from the simultaneous thermal decomposition and sulfidation of a preformed cobalt carbonate precursor. The as-prepared CoS(2) ellipsoids show interesting supercapacitive properties with high capacitance and good cycling performance.


Migration of metallic ions from screwposts into dentin and surrounding tissues.
Previous investigations have shown htat corrosion and other electrochemical processes occure when different alloys or metals are found together in the same mouth. In the present report, when teeth were restored using non-noble metallic posts, the metals diffused out to surrounding hard and soft connective tissues. The material consisted of extracted teeth with screw posts and surrounding discolored connective tissues. The screwposts had been cemented to the teeth 3--10 years earlier. The distribution of metal ions was determined by means of energy-dispersive X-ray microanalysis. Copper and zinc were found in both hard and soft tissues. Relatively high concentrations of copper ions were identified in areas of the teeth with blue-green discolorations. Zinc ions were detected in the dentin; they most probably originated from the screwposts and the cement, but zinc is also found in normal human dentin. Copper, zinc, silver and iron were found in the dark discolorations of the gingiva adjacent to the extracted teeth.


Activities in a social networking-based discussion group by endoscopic retrograde cholangiopancreatography doctors.
Online social networking is increasingly being used among medical practitioners. However, few studies have evaluated its use in therapeutic endoscopy. Here, we aimed to analyze the shared topics and activities of a group of endoscopic retrograde cholangiopancreatography (ERCP) doctors in a social networking-based endoscopic retrograde cholangiopancreatography discussion group (EDG). Six ERCP trainers working in Xijing Hospital and 48 graduated endoscopists who had finished ERCP training in the same hospital were invited to join in EDG. All group members were informed not to divulge any private information of patients when using EDG. The activities of group members on EDG were retrospectively extracted. The individual data of the graduated endoscopists were collected by a questionnaire. From June 2014 to May 2015, 6924 messages were posted on EDG, half of which were ERCP related. In total, 214 ERCP-related topics were shared, which could be categorized into three types: sharing experience/cases (52.3%), asking questions (38.3%), and sharing literatures/advances (9.3%). Among the 48 graduated endoscopists, 21 had a low case volume of less than 50 per year and 27 had a high volume case volume of 50 or more. High-volume graduated endoscopists posted more ERCP-related messages (P=0.008) and shared more discussion topics (P=0.003) compared with low-volume graduated endoscopists. A survey showed that EDG was useful for graduated endoscopists in ERCP performance and management of post-ERCP complications, etc. A wide range of ERCP-related topics were shared on the social networking-based EDG. The ERCP-related behaviors on EDG were more active in graduated endoscopists with an ERCP case volume of more than 50 per year.


Disease activity-guided rituximab therapy in rheumatoid arthritis: the effects of re-treatment in initial nonresponders versus initial responders.
To explore the efficacy of re-treatment with rituximab in patients with rheumatoid arthritis (RA) who were initial nonresponders to treatment, and to evaluate the effects of rituximab in RA when re-treatment is given in a standardized way based on the Disease Activity Score in 28 joints (DAS28), according to the international consensus statement. Patients with RA who had a DAS28 of > or =3.2 received up to 3 courses of rituximab at intervals of at least 6 months, regardless of whether the patient had responded to the first course of treatment with rituximab. Of the 30 patients with RA who were included in the study, 26 could be evaluated for the efficacy of treatment after 6 months. Eighteen patients qualified for re-treatment at 6 months, 6 patients were re-treated at a later time point because of a disease relapse, and 2 other patients were not re-treated because they had low disease activity. Seven of the 24 patients who qualified for re-treatment had not exhibited clinical improvement after the first treatment course. These patients typically did not respond to subsequent courses of rituximab. Of interest, in the 17 patients who had exhibited a clinical response to the first course of rituximab, the second and third treatment courses resulted in European League Against Rheumatism responses similar to those observed after the first course, and no major relapses occurred before re-treatment. Rituximab re-treatment is not effective in patients who do not exhibit clinical improvement after the first treatment course, which is consistent with the notion that such patients represent a different pathogenetic subset of RA. Patients who initially responded to rituximab treatment experienced sustained benefit from DAS28-based systematic re-treatment according to the international consensus statement.


Visual responses of neurons in the Clare-Bishop area of the cat.
Single unit responses in the Clare-Bishop area of the pretrigeminal cat were analyzed using stationary and moving visual stimuli. Of the units responding, 80 percent could be influenced by a 0.5 s diffuse flash, most displaying inhibition or excitation to both "on" and "off". In most units responses to stationary shapes were not very specific. Responses to moving stimuli were strong and directional preference was usually present. For the majority of cells the optimal speed of movement was in the range from 100 to 800 deg/s, and some cells preserved their direction preferences when the speed was over 1,500 deg/s. The direction preference could be reversed depending on the speed of movement, location in the receptive field or the shape of stimulus.


Why targeted therapy hasn't worked in advanced cancer.
In this issue of the JCI, Nissen et al. report that a reciprocal interaction exists between the growth factors FGF2 and PDGF-BB, causing tumors to exhibit increased angiogenesis and metastatic potential. Both FGF2 and PDGF-BB signal through tyrosine kinase receptors, which have been the target of tyrosine kinase inhibitors for cancer therapies. These inhibitors are usually small molecules that inhibit the kinase activity of a receptor or nonreceptor tyrosine kinase, preventing downstream signaling. The results of this study shed light on why tyrosine kinase inhibitors have been useful for the treatment of only a small number of advanced cancers. Currently, a major focus of pharmaceutical companies is to develop ever more potent and specific tyrosine kinases. The results presented here suggest that this approach may not be successful.


Insights from zebrafish on human pigment cell disease and treatment.
Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes, and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans. This review discusses our current knowledge of melanophore biology and how zebrafish are contributing to improving how diseases of melanocytes are understood and treated in humans. Developmental Dynamics 246:889-896, 2017. © 2017 Wiley Periodicals, Inc.


A new stability--indicating RP-HPLC method to determine assay and known impurity of Celecoxib API.
A simple, rapid and accurate Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method was developed to determine assay and known impurity of Celecoxib API. The chromatographic separation was performed on reversed-phase C-18 column. Eluents were monitored on photo-diode array detector at a wavelength of 254 nm using a mixture (40:60) of buffer and acetonitrile. Solution concentrations were measured on a weight basis to avoid the use of an internal standard. The method was statistically validated for forced-degradation study, linearity and range, accuracy, precision, stability of analytical solutions, and selectivity. Due to its simplicity, rapid, and accuracy, we believe that the method will be useful to determine assay and known impurity of Celecoxib.


Supramolecular enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate mediated by capped gamma-cyclodextrins: critical control of enantioselectivity by cap rigidity.
A series of gamma-cyclodextrins (CDs) modified with capping and noncapping aromatic group(s) were synthesized to mediate the enantiodifferentiating [4 + 4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these gamma-CDs with AC was studied by circular dichroism, UV-vis, and NMR spectroscopy to reveal the formation of stable 1:2 host-guest complexes in all cases. The capped gamma-CD with a biphenyl group bridging the A and D glucose units was shown to confine the included AC molecules most strictly among the capped and noncapped gamma-CDs examined. Photocyclodimerization of AC mediated by capped gamma-CDs considerably improved the yield and enantiomeric excess (ee) of the head-to-head photodimer 3. The ee and the absolute configuration of syn-head-to-tail photodimer 2 critically depended on the rigidity of capping. Thus, the flexibly capped and rim-substituted gamma-CDs afforded 2 in moderate ee's of around 40%, whereas gamma-CD with a rigid biphenyl cap gave the antipodal 2 in -58% ee. Interestingly, the ee of 2 mediated by flexibly capped gamma-CDs was highly sensitive to the temperature variation as a consequence of large differential entropy changes in the enantiodifferentiation process. In contrast, the entropy effect does not appear to play a significant role in the photocyclodimerization of AC with rigidly capped gamma-CDs. The differential enthalpy and entropy changes obtained for the enantiodifferentiating photocyclodimerization mediated by native and most of the modified gamma-CDs gave an excellent enthalpy-entropy compensation plot with an exception of the biphenyl-capped gamma-CD, indicating the operation of significantly different enantiodifferentiation mechanism within the rigidly capped cyclodextrin cavity.


Chemotherapy of advanced prostatic cancer with peplomycin.
Peplomycin, a new anticancer agent, was produced as a side-chain derivative of bleomycin to reduce the incidence of pulmonary complications. Intramuscular injections of 5-10 mg of peplomycin were given 3 times a week to 35 patients with stages C and D disease. Patients were evaluated at the end of 12 weeks using the National Prostatic Cancer Project criteria. A response rate of 26% was achieved when peplomycin was used as the primary treatment. Prostatic cancer patients resistant to standard endocrine therapy had a 17% response rate to peplomycin therapy. Bone metastases were not influenced by this agent. The main side effects of peplomycin are fever and respiratory disturbances, but the incidence of these conditions is lower than that experience with bleomycin.


Variations in brain DNA.
It is assumed that DNA sequences are conserved in the diverse cell types present in a multicellular organism like the human being. Thus, in order to compare the sequences in the genome of DNA from different individuals, nucleic acid is commonly isolated from a single tissue. In this regard, blood cells are widely used for this purpose because of their availability. Thus blood DNA has been used to study genetic familiar diseases that affect other tissues and organs, such as the liver, heart, and brain. While this approach is valid for the identification of familial diseases in which mutations are present in parental germinal cells and, therefore, in all the cells of a given organism, it is not suitable to identify sporadic diseases in which mutations might occur in specific somatic cells. This review addresses somatic DNA variations in different tissues or cells (mainly in the brain) of single individuals and discusses whether the dogma of DNA invariance between cell types is indeed correct. We will also discuss how single nucleotide somatic variations arise, focusing on the presence of specific DNA mutations in the brain.


[Overview of the allergens from several feeder regions of Czechoslovakia. Incidence and prevalence of contact hypersensitivity caused by the allergens spread by the population of the feeder areas of Bratislava, Trnava and Banská Bystrica 1978-1980].
With the aid of patch tests an investigation involving 3060 patients was carried out to register the incidence and prevalence of allergens of the standard and supplementary test series. The standard series with 16 allergens was selected in cooperation with the work group for curtailing contact dermatitis and occupational dermatoses in the socialist countries. The Czechoslovakian supplementary test series included three allergens: neomycin sulfate, extr . chamomillae and resorcinol. In 22.6% of the 693 patients the skin tests were positive for at least one allergen. The most frequent eczematogenic among men was potassium dichromate (resulting from contact with cement), among women nickel sulfate, and in the group as a whole Peruvian balm. The age groups most affected were between 41 and 50 years and between 51 and 60 years, respectively, for men, between 21 and 30 years for women, and between 21 and 30 years for the group as a whole. In registering the prevalence, chamomillae extract caused the highest occurrence among men, cobalt nitrate among the women, and also cobalt nitrate for the group as a whole. The age group affected most was between 51 and 60 years. In the complete investigative study of incidence and prevalence, Peruvian balm topped the list for the group as a whole, potassium dichromate for the men, and nickel sulfate for the women. Among the men and for the group as a whole the most affected age group was between 51 and 60 years, and among the women between 21 and 30 years.(ABSTRACT TRUNCATED AT 250 WORDS)


Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do.
The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha-delta ratio and relative alpha variability are needed before an automated EEG-based early delayed cerebral ischemia detection system is ready for clinical use.


Identification of the mitophagy-related diagnostic biomarkers in hepatocellular carcinoma based on machine learning algorithm and construction of prognostic model.
As a result of increasing numbers of studies most recently, mitophagy plays a vital function in the genesis of cancer. However, research on the predictive potential and clinical importance of mitophagy-related genes (MRGs) in hepatocellular carcinoma (HCC) is currently lacking. This study aimed to uncover and analyze the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. In our research, by using Least absolute shrinkage and selection operator (LASSO) regression and support vector machine- (SVM-) recursive feature elimination (RFE) algorithm, six mitophagy genes (ATG12, CSNK2B, MTERF3, TOMM20, TOMM22, and TOMM40) were identified from twenty-nine mitophagy genes, next, the algorithm of non-negative matrix factorization (NMF) was used to separate the HCC patients into cluster A and B based on the six mitophagy genes. And there was evidence from multi-analysis that cluster A and B were associated with tumor immune microenvironment (TIME), clinicopathological features, and prognosis. After then, based on the DEGs (differentially expressed genes) between cluster A and cluster B, the prognostic model (riskScore) of mitophagy was constructed, including ten mitophagy-related genes (G6PD, KIF20A, SLC1A5, TPX2, ANXA10, TRNP1, ADH4, CYP2C9, CFHR3, and SPP1). This study uncovered and analyzed the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Based on the mitophagy-related diagnostic biomarkers, we constructed a prognostic model(riskScore). Furthermore, we discovered that the riskScore was associated with somatic mutation, TIME, chemotherapy efficacy, TACE and immunotherapy effectiveness in HCC patients. Mitophagy may play an important role in the development of HCC, and further research on this issue is necessary. Furthermore, the riskScore performed well as a standalone prognostic marker in terms of accuracy and stability. It can provide some guidance for the diagnosis and treatment of HCC patients.


Leukocyte migration inhibition in amiodarone-associated pneumonitis.
Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.


Noninvasive blood perfusion measurements of an isolated rat liver and an anesthetized rat kidney.
A simple, cost effective, and noninvasive blood perfusion system is tested in animal models. The system uses a small sensor to measure the heat transfer response to a thermal event (convective cooling) imposed on the tissue surface. Heat flux data are compared with a mathematical model of the tissue to estimate both blood perfusion and thermal contact resistance between the tissue and the probe. The perfusion system was evaluated for repeatability and sensitivity using isolated rat liver and exposed rat kidney tests. Perfusion in the isolated liver tests was varied by controlling the flow of the perfusate into the liver, and the perfusion in the exposed kidney tests was varied by temporarily occluding blood flow through the renal artery and vein. The perfusion estimated by the convective perfusion probe was in good agreement with that of the metered flow of the perfusate into the liver model. The liver tests indicated that the probe can be used to detect small changes in perfusion (0.005 ml/ml/s). The probe qualitatively tracked the changes in the perfusion in the kidney model due to occlusion of the renal artery and vein.


Sodium intake and exchangeable sodium in hypertensive rats.
Exchangeable sodium, extracellular fluid volume and sodium intake were significantly higher in spontaneously hypertensive rats (SHR) than in normotensive controls. The increased exchangeable sodium was due to the expanded extracellular fluid sodium content. Two kidney one clip Goldblatt renal hypertensive rats develop thirst and high renin levels. When drinking saline the rats have markedly increased exchangeable sodium levels, but those drinking water did not. It is proposed that the exaggerated saline intake leads to a volume dependent component of the hypertension in both models. In the SHR both the salt appetite and the hypertension may be induced by angiotensin acting via central mechanisms.


Statistical tools for linkage analysis and genetic association studies.
Genetic mapping by linkage analysis has been an invaluable tool in the positional strategy to identify the molecular basis of many rare Mendelian disorders. With the attention of the scientific and medical community shifting towards the analysis of more common, complex traits, it has become necessary to develop new approaches that take into account the complexity of the genetic basis of these disorders and their possible interaction with other, nongenetic factors. Linkage disequilibrium studies are now becoming increasingly popular thanks to the advent of genotyping platforms that allow genome-wide searching for association between hundreds of thousands of random polymorphisms and disease phenotypes in large samples of unrelated individuals. Moreover, the definition of the disease phenotype itself is being reconsidered to include quantitative traits that may better define the underlying biologic mechanisms for many pathologic conditions. This article will review classic and new approaches to genetic mapping by linkage and association analysis and discuss the directions this field is likely to take in the near future.


Characterization of epoxy resin-based anion-responsive polymers: applicability to chloride sensing in physiological samples.
The potentiometric properties of an epoxy resin-based anion-responsive polymer and its feasibility as a chloride sensing membrane are described. The response mechanism of the epoxy resin-based membrane is studied by varying the types and contents of epoxy components (e.g., resin, hardener, diluent, and plasticizer). It is found that epoxy resins cured with polyamine-type hardeners have excellent characteristics as chloride-sensing membranes, in terms of their selectivity, stability, sensor lifetime, and adhesion for constructing an all-solid-state sensing device. In addition, effects of the diluent or plasticizer added in an epoxy resin/hardener system on the potentiometric behaviors are investigated. To demonstrate the practical analytical utility of the epoxy resin-based electrodes, chloride levels in various controls and biological specimens (e.g., human sera and whole blood) are determined with a flow-cell system.


A colorimetric sensor based on catechol-terminated mixed self-assembled monolayers modified gold nanoparticles for ultrasensitive detections of copper ions.
A colorimetric sensor for Cu(II) ions has been developed based on mixed self-assembled monolayers (SAMs) modified gold nanoparticles (AuNPs). The AuNPs were modified with mixed SAMs consisting of mercaptosuccinic acid and the product of electrochemically triggered Michael addition reaction of 4-thiouracil and catechol. In the presence of Cu(II) ions, the coordination of Cu(2+) to catechol-terminated AuNPs leads to aggregation-induced changes of surface plasmon resonance. The cost-effective chemical sensor allows rapid, sensitive and selective detection of Cu(2+) ions, indicating its potential application in environmental field.


Role of some biogenic amines in the pathomechanism of glomerulonephritis. II. Adrenaline, noradrenaline and serotonin in acute serum sickness in rabbits.
In acute serum sickness induced with one intravenous dose of bovine serum albumin (BSA) in 40 rabbits the patterns of excretion of adrenaline (A), noradrenaline (NA), serotonin (5HT) and 5-hydroxyindole-acetic acid (5HIAA) were studied in 24-hour urine, and the 5HT level was determined at intervals of three days. The urinary levels of biogenic amines were determined daily. Some rabbits immunized with BSA received also additionally 5HT, reserpine or parachlorphenylalanine (PCPA). Administration of BSA to rabbits caused a significant increase in the excretion of A and NA and a less evident increase in 5HT level in the blood. The greatest correlation with the course of the immune reaction was shown by the increase in NA excretion observed on the 2nd and 3rd days after BSA administration, and then between the 5th and the 12th days of the experiment. Daily subcutaneous injections of 5HT during 15 days caused a significant rise of its level in the blood and urine, and an increase of 5HIAA excretion. After reserpine or PCPA administration a significant decrease of the levels of all these amines was observed. Taking into account the results of histological examination of the kidneys, that is intensification of the inflammatory changes after 5HT administration and evident inhibition of the inflammatory process after administration of reserpine and PCPA it must be accepted that the studied amines have an important role in the pathomechanism of glomerulonephritis in acute serum sickness.


Determinants of preventable stroke-Ankara ACROSS stroke preventability study.
Unhealthy lifestyle and inadequate control of vascular risk factors are the major contributors of stroke burden. Failure in achieving the target levels in control of these factors, not only designate missed opportunities contributing to the preventability of an incident stroke, but also set the post-stroke treatment goals in a case wise basis. In this study, we analyzed pre-event clinical features that play a role in stroke preventability, and determined the cumulative burden of risk factors that necessitate optimization following the ischemic insult. Information about the pre-stroke optimal control of seven major modifiable risk factors (Life's Simple 7: hypertension, diabetes mellitus, hyperlipidemia, smoking, obesity, diet, and physical activity) was prospectively collected in ischemic stroke patients admitted to three tertiary academic centers in Ankara. Stroke preventability was evaluated by the overall number of factors requiring optimization with patients ≥4 risk factor conditions categorized as those suffering from a preventable stroke. Bivariate and multivariate analyzes were performed to uncover predictors of stroke preventability. Among 787 patients, 386 (49.0%) had ≥4 risk factor conditions requiring optimization. Preventable stroke was more common in younger patients, and patients with small artery occlusion. Multivariate analyses taking into account the pre-stroke antithrombotic treatment regimen, have highlighted age (OR: 0.99, 95%CI 0.98-1.00), female gender (1.59, 95%CI 1.17-2.16), coronary artery disease (1.54, 95%CI 1.10-2.14), small artery occlusion (1.90, 95%CI 1.13-3.18), and cardio-aortic embolism (0.53, 95%CI 0.35-0.82) as significant factors associated with preventability. Approximately half of the ischemic stroke patients have preventable stroke from the perspective of risk factor control. Extra care should be given to strategies directed to risk factor control and lifestyle interventions in certain high-risk groups for the prevention of future complications.


The ELISA-based detection of anti-Opisthorchis viverrini IgG and IgG4 in samples of human urine and serum from an endemic area of north-eastern Thailand.
The levels of correlation between the number of Opisthorchis viverrini eggs excreted in the faeces and levels of anti-Opisthorchis IgG and IgG(4) in the serum and urine (as indicated by absorbances in ELISA) have recently been evaluated in north-eastern Thailand. The 225 subjects investigated in detail, all of whom came from an endemic village in Chaiyaphum province, were selected on the basis of the numbers of O. viverrini eggs that they were excreting. ELISA based on a crude antigen extract of the trematode were then used to determine the levels of specific IgG and IgG(4) in serum and urine samples. Compared with the egg-negative, the villagers who were found to be egg-positive for O. viverrini had significantly higher levels of specific IgG in their urine and serum and significantly higher levels of specific IgG(4) in their serum. The serum levels of specific IgG and IgG(4) and the urine levels of specific IgG all correlated with the numbers of O. viverrini eggs/g faeces [with correlation coefficients (r) of 0.251, 0.121 and 0.142, respectively]. Although the serum levels of IgG were positively correlated with the urine levels of IgG (r=0.098), there was no significant relationship between the serum and urine levels of specific IgG(4) (r=0.051). When the 225 subjects investigated in the ELISA were divided according to whether they had no detectable Opisthorchis eggs in their faeces (N=57), or 1-100 (N=154), 101-1000 (N=5), 1001-1500 (N=5) or >1501 (N=4) eggs/g faeces, the serum and urine levels of specific IgG and the serum (but not urine) levels of specific IgG4 were also found to correlate significantly with the infection-intensity categories (with r-values of 0.550, 0.146 and 0.578, respectively). When the results of the faecal examinations were treated as the 'gold standard', the ELISA for the detection of (Opisthorchis-specific) serum IgG, serum IgG(4), urine IgG and urine IgG(4) had sensitivities of 99.2%, 23.1%, 43.0% and 45.9% and specificities of 93.0%, 29.6%, 45.9% and 67.2%, respectively. Although the study was limited by the small number of subjects with intense infections, it appears worth investigating urine samples for subclasses of specific IgG other than IgG(4).


[Effects of spinal cord decompression in patients with cervical spondylotic myelopathy oncortical brain activations].
The aim of this project was to compare and evaluate cortical sensorimotor adaptations as measured by brain fMRI (functional magnetic resonance imaging) in patients before and after surgery for cervical spondylotic myelopathy (CSM), i.e., after spinal cord decompression. Study inclusion required evidence of CSM on MRI of the cervical spine, anterior compression of the spinal cord by osteophytes, or disc herniation. We measured the antero-posterior diameter of the spinal canal stenosis before and 3 months after surgery. Surgery was performed at one or two levels from the anterior approach with implantation of radiolucent spacers, without plate fixation. Each participant underwent two fMRI brain examinations, the first one preoperatively and the second one 6 months following surgery. Subjects performed acoustically paced repetitive wrist flexion and extension of each upper extremity according to block design. MRI data were acquired using 1.5 Tesla scanners. Statistical analysis was carried out using the general linear model implemented in FEAT 6.00 (FMRI Expert Analysis Tool), part of the FSL 5.0 package (FMRIB Software Library). The group differences were evaluated using paired t-test and the resulting statistical maps evaluated as Z-score (standardised value of the t-test) were thresholded at a corrected significance level of p <0.05. The study group consisted of 7 patients including 5 female and 2 male patients, with the average age of 55.7 years. Patients with cervical spondylogenous radiculopathy were evaluated as a control group. The analysis of mean group effects in brain fMRI during flexion and extension of both wrists revealed significant activation in dorsal primary motor cortex contralaterally to the active extremity and in adjacent secondary motor and sensory areas, bilaterally in supplementary motor areas, the anterior cingulum, primary auditory cortex, in the region of the basal ganglia, thalamus and cerebellum. After surgery, the cortical activations and maximum Z-scores decreased in most areas. Analysis of differences between sessions before and after surgery showed a statistically significant activation decrease during movement of both extremities in the right parietal operculum and the posterior temporal lobe. During left wrist movement, there was additional activation decrease in the right superior parietal lobe, the supramarginal gyrus, insular cortex, and the central operculum. In contrast, an activation decrease was detected in the left middle temporal gyrus during right wrist movement. An average difference of anteroposterior cervical spinal canal distance before and after surgery of CSM was 2.67 millimetres, representing a 40% increase; the cross-sectional area of the spinal canal increased by 37% and that of the spinal cord by 36%. Functional MRI of the brain revealed significant activation especially in primary and secondary motor cortex and sensory areas in patients with CSM. After surgical decompression of the spinal cord, cortical activations and maximum Z-score decreased in the majority of areas. We proved decreased cortical activation on functional MRI of the brain after surgery in patients with CSM (evaluated according to MRI of cervical spine), even at an initial stage of the disease.


[Functionally stable fixation in severe midface fractures using an external cranial fixator].
With the external Cranial-fixator we can achieve a stable fixation of the severe maxillofacial injuries. In a period of 10 years (1973-1982) 61 patients were treated with a external cranial fixation, which is tolerated very well by the patients. The intermaxillary fixation is not necessary, the application is easy, the morbidity rate is low and the results are good (table 3 und 4).


Applications of open-path Fourier transform infrared for identification of volatile organic compound pollution sources and characterization of source emission behaviors.
An open-path Fourier transform infrared spectroscopy (OP-FTIR) system was set up for 3-day continuous line-averaged volatile organic compound (VOC) monitoring in a paint manufacturing plant. Seven VOCs (toluene, m-xylene, p-xylene, styrene, methanol, acetone, and 2-butanone) were identified in the ambient environment. Daytime-only batch operation mode was well explained by the time-series concentration plots. Major sources of methanol, m-xylene, acetone, and 2-butanone were identified in the southeast direction where paint solvent manufacturing processes are located. However, an attempt to uncover sources of styrene was not successful because the method detection limit (MDL) of the OP-FTIR system was not sensitive enough to produce conclusive data. In the second scenario, the OP-FTIR system was set up in an industrial complex to distinguish the origins of several VOCs. Eight major VOCs were identified in the ambient environment. The pollutant detected wind-rose percentage plots that clearly showed that ethylene, propylene, 2-butanone, and toluene mainly originated from the tank storage area, whereas the source of n-butane was mainly from the butadiene manufacturing processes of the refinery plant, and ammonia was identified as an accompanying reduction product in the gasoline desulfuration process. Advantages of OP-FTIR include its ability to simultaneously and continuously analyze many compounds, and its long path length monitoring has also shown advantages in obtaining more comprehensive data than the traditional multiple, single-point monitoring methods.


Sugar, Spice, and Bleeding.
Brodifacoum (BDF), otherwise known as superwarfarin, is a long-acting anticoagulant rodenticide (LAAR) which acts as a vitamin K antagonist. Much like warfarin, BDF's mechanism of action is to irreversibly inhibit the enzyme vitamin K epoxide reductase, thus reducing the recycling of vitamin K and, therefore, reducing the activation of clotting factors two, seven, nine, and 10. Although BDF is usually found in rodenticides, it has been recently used as an additive in synthetic cannabinoids. We present a case of a young male with a history of synthetic cannabinoid use who presented with hematuria and epistaxis and was ultimately found to have BDF poisoning.


Temperature gradient interaction chromatography and MALDI-TOF mass spectrometry analysis of stereoregular poly(ethyl methacrylate)s.
Temperature gradient interaction chromatography (TGIC) was applied for the separation of stereoregular poly(ethyl methacrylate) (PEMA) according to the tacticity. The three PEMA samples with differing tacticity (rr triad content 0, 53, and 91%) prepared by anionic polymerization were used. C18 bonded silica and a mixture of CH2Cl2 and CH3CN (30/70, v/v) were used as stationary and mobile phase, respectively. TGIC was able to separate the PEMA samples, showing the increasing retention in the order of decreasing rr triad contents; however TGIC elution peaks of the three PEMAs were not fully resolved but, rather, were partially overlapped. To isolate the tacticity effect from the molecular weight effect on the TGIC retention, the PEMA samples were fractionated by TGIC, and the accurate molecular weight of the fractions was determined by MALDI-TOF mass spectrometry. The fractions showed a much narrower molecular weight distribution than the mother PEMAs. The TGIC fractions of similar molecular weight but with different tacticity were fully resolved by TGIC, but mother PEMAs were not. These results indicate that the retention in TGIC is affected by both tacticity and molecular weight.


Depression by relaxin of neurally induced contractile responses in the mouse gastric fundus.
The peptide hormone relaxin, which attains high circulating levels during pregnancy, has been shown to depress small-bowel motility through a nitric oxide (NO)-mediated mechanism. In the present study we investigated whether relaxin also influences gastric contractile responses in mice. Female mice in proestrus or estrus were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Mechanical responses of gastric fundal strips were recorded via force-displacement transducers. Evaluation of the expression of nitric oxide synthase (NOS) isoforms was performed by immunohistochemistry and Western blot. In control mice, neurally induced contractile responses elicited by electrical field stimulation (EFS) were reduced in amplitude by addition of relaxin to the organ bath medium. In the presence of the NO synthesis inhibitor l-NNA, relaxin was ineffective. Direct smooth muscle contractile responses were not influenced by relaxin or l-NNA. In strips from relaxin-pretreated mice, the amplitude of neurally induced contractile responses was also reduced in respect to the controls, while that of direct smooth muscle contractions was not. Further addition of relaxin to the bath medium did not influence EFS-induced responses, whereas l-NNA did. An increased expression of NOS I and NOS III was observed in gastric tissues from relaxin-pretreated mice. In conclusion, the peptide hormone relaxin depresses cholinergic contractile responses in the mouse gastric fundus by up-regulating NO biosynthesis at the neural level.


Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization.
In a previous study, we showed that various low-molecular-weight compounds in follicular fluid (FF) samples of control fertile females (CFF) have different concentrations compared to those found in FF of infertile females (IF), before and after their categorization into different subgroups, according to their clinical diagnosis of infertility. Using the same FF samples of this previous study, we here analyzed the FF concentrations of free and bound bilirubin and compared the results obtained in CFF, IF and the different subgroups of IF (endometriosis, EM, polycystic ovary syndrome, PCOS, age-related reduced ovarian reserve, AR-ROR, reduced ovarian reserve, ROR, genetic infertility, GI and unexplained infertility, UI). The results clearly indicated that CFF had lower values of free, bound and total bilirubin compared to the respective values measured in pooled IF. These differences were observed even when IF were categorized into EM, PCOS, AR-ROR, ROR, GI and UI, with EM and PCOS showing the highest values of free, bound and total bilirubin among the six subgroups. Using previous results of ascorbic acid, GSH and nitrite + nitrate measured in the same FF samples of the same FF donors, we found that total bilirubin in FF increased as a function of decreased values of ascorbic acid and GSH, and increased concentrations of nitrite + nitrate. The values of total bilirubin negatively correlated with the clinical parameters of fertilization procedures (number of retrieved oocytes, mature oocytes, fertilized oocytes, blastocysts, high-quality blastocysts) and with clinical pregnancies and birth rates. Bilirubin concentrations in FF were not linked to those found in serum samples of FF donors, thereby strongly suggesting that its over production was due to higher activity of heme oxygenase-1 (HO-1), the key enzyme responsible for bilirubin formation, in granulosa cells, or cumulus cells or oocytes of IF and ultimately leading to bilirubin accumulation in FF. Since increased activity of HO-1 is one of the main enzymatic intracellular mechanisms of defense towards external insults (oxidative/nitrosative stress, inflammation), and since we found correlations among bilirubin and oxidative/nitrosative stress in these FF samples, it may reasonably be supposed that bilirubin increase in FF of IF is the result of protracted exposures to the aforementioned insults evidently playing relevant roles in female infertility.


'PJ paralysis' campaign gets patients up and trusts moving.
The aims of the #EndPJparalysis campaign are simple: get patients out of bed and dressed during the day, and then into chairs, activity rooms or to dining rooms for meals. Increased activity can help recovery, reduce muscle wastage, maintain independence and lead to patients being discharged sooner.


Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells.
The increasing incidence of hypercholesterolemia-related diseases even in the presence of the currently available cholesterol-lowering drugs indicates a need to discover new therapeutic drugs. This study aimed to investigate the hypocholesterolemic potential of two triterpenoids isolated from Protorhus longifolia stem bark. In silico techniques and in vitro enzyme assays were used to evaluate the potential inhibition of cholesterol esterase and HMG-CoA reductase by the triterpenoids (ARM-2 and RA-5). The toxicity, modulation of low-density lipoprotein (LDL) uptake, and associated gene expression were determined in HepG2 hepatocytes. In silico molecular docking revealed that ARM-2 compared with RA-5 has a relatively stronger binding affinity for both enzymes. Both triterpenoids further demonstrated promising in silico drug-likeness properties and favorable ADMET profiles characterized by high intestinal absorption and lack of CYP450 enzyme inhibition. The compounds further showed, to varying degrees of efficacy, inhibition of cholesterol micellization as well as both cholesterol esterase and HMG-CoA reductase activities with IC50 values ranging from 16.4 to 41.1 μM. Moreover, enhanced hepatic cellular LDL uptake and the associated upregulation of the LDL-R and SREBP-2 gene expression were observed in the triterpenoid-treated HepG2 cells. It is evident that the triterpenoids, especially ARM-2, possess hypocholesterolemic properties, and these molecules can serve as leads or structural templates for the development of new hypocholesterolemic drugs.


Effect of ribose-glycated BSA on histone demethylation.
A reducing sugar reacts with the protein, resulting in advanced glycation end-products (AGEs), which have been implicated in diabetes-related complications. Recently, it has been found that both type 1 and type 2 diabetic patients suffer from not only glucose but also ribose dysmetabolism. Here, we compared the effects of ribose and glucose glycation on epigenetics, such as histone methylation and demethylation. To prepare ribose-glycated (riboglycated) proteins, we incubated 150 μM bovine serum albumin (BSA) with 1 M ribose at different time periods, and we evaluated the samples by ELISAs, Western blot analysis, and cellular experiments. Riboglycated BSA, which was incubated with ribose for approximately 7 days, showed the strongest cytotoxicity, leading to a significant decrease in the viability of SH-SY5Y cells cultured for 24 h (IC50 = 1.5 μM). A global demethylation of histone 3 (H3K4) was observed in SH-SY5Y cells accompanied with significant increases in lysine-specific demethylase-1 (LSD1) and plant homeodomain finger protein 8 (PHF8) after treatment with riboglycated BSA (1.5 μM), but demethylation did not occur after treatment with glucose-glycated (glucoglycated) proteins or the ribose, glucose, BSA, and Tris-HCl controls. Moreover, a significant demethylation of H3K4, H3K4me3, and H3K4me2, but not H3K4me1, occurred in the presence of riboglycated proteins. A significant increase of formaldehyde was also detected in the medium of SH-SY5Y cells cultured with riboglycated BSA, further indicating the occurrence of histone demethylation. The present study provides a new insight into understanding an epigenetic mechanism of diabetes mellitus (DM) related to ribose metabolic disorders.


A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.
Ras proteins are membrane-bound GTPases that regulate essential cellular processes at the plasma membrane (PM). Constitutively active mutations of K-Ras, one of the three Ras isoforms in mammalian cells, are frequently found in human cancers. Ferrocene derivatives, which elevate cellular reactive oxygen species (ROS), have shown to block the growth of non-small cell lung cancers harboring oncogenic mutant K-Ras. Here, we tested a novel ferrocene derivative on the growth of pancreatic ductal adenocarcinoma and non-small cell lung cancer. Our compound, which elevated cellular ROS levels, inhibited the growth of K-Ras-driven cancers, and abrogated the PM binding and signaling of K-Ras in an isoform-specific manner. These effects were reversed upon antioxidant supplementation, suggesting a ROS-mediated mechanism. We further identified that K-Ras His95 residue plays an important role in this process, and it is putatively oxidized by cellular ROS. Together, our study demonstrates that the redox system directly regulates K-Ras/PM binding and signaling via oxidative modification at the His95, and proposes a role of oncogenic mutant K-Ras in the recently described antioxidant-induced growth and metastasis of K-Ras-driven cancers.


The pancreas of the naked mole-rat (Heterocephalus glaber): an ultrastructural and immunocytochemical study of the endocrine component of thermoneutral and cold acclimated animals.
Endocrine cell distribution within the islets of Langerhans may vary both between species and under different energetically demanding conditions such as cold acclimation. The naked mole-rat, Heterocephalus glaber, lacking an effective insulatory pelage, is effectively a poikilotherm, yet it shows a typical mammalian cold-acclimation response by substantially increasing food intake to meet higher energy requirements when housed at lower temperatures. The endocrine component of the pancreas of thermoneutral and cold-acclimated naked mole-rats was thus characterized using immunocytochemistry and ultrastructural analyses. Four distinct endocrine cells were identified: alpha (glucagon-producing), beta (insulin-producing), delta (somatostatin-producing), and PP (pancreatic polypeptide-producing) cells. Distribution of these cells differed from that of other rodents, in that beta cells formed the mantle while alpha cells formed the core of the islets. This distribution may contribute to the observed insulin insensitivity of this species, as indicated in abnormal responses to glucose tolerance tests. Insulin-producing cells, however, were more numerous than glucagon-producing cells. This ratio was unchanged with cold acclimation. Immunoreactivity of alpha and beta cells was more intense in cold-acclimated than in thermoneutral animals, possibly indicative of a change in hormonal production in animals housed at a lower temperature.


Mechanism of azithromycin in airway diseases.
Azithromycin (AZM) has been used to treat chronic inflammatory airway diseases because it regulates cell-cell contact between airway epithelial cells. Airway mucus hypersecretion is an important component of chronic respiratory diseases. Mucin 5AC (MUC5AC) is the major mucin produced by airway epithelial cells, and hypersecretion of MUC5AC is a sign of various pulmonary inflammatory diseases. Recently, it was found that matrix metallopeptidase 9 is involved in mucus hypersecretion. Moreover, AZM can inhibit the ability of TNF-α-to induce interleukin (IL)-8 production. This review focuses on the effects on AZM that may be beneficial in inhibiting MUC5AC, matrix metalloprotease-9 and IL-8 production in airway epithelial cells. In addition, recent studies have begun to assess activation of mitogen-activated protein kinase (MAPK) signaling pathways in response to AZM. Understanding these new developments may be helpful for clinicians.


From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform.
Alternative pre-mRNA splicing is a crucial process that allows the generation of diversified RNA and protein products from a multi-exon gene. In tumor cells, this mechanism can facilitate cancer development and progression through both creating oncogenic isoforms and reducing the expression of normal or controllable protein species. We recently demonstrated that an alternative cyclin D-binding myb-like transcription factor 1 (DMTF1) pre-mRNA splicing isoform, DMTF1β, is increasingly expressed in breast cancer and promotes mammary tumorigenesis in a transgenic mouse model. Aberrant pre-mRNA splicing is a typical event occurring for many cancer-related functional proteins. In this review, we introduce general aberrant pre-mRNA splicing in cancers and discuss its therapeutic application using our recent discovery of the oncogenic DMTF1 isoform as an example. We also summarize new insights in designing novel targeting strategies of cancer therapies based on the understanding of deregulated pre-mRNA splicing mechanisms.


Herpes zoster induced neuropathic bladder--a case report.
Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.


Extractable work in quantum electromechanics.
Recent experiments have demonstrated the generation of coherent mechanical oscillations in a suspended carbon nanotube, which are driven by an electric current through the device above a certain voltage threshold, in close analogy with a lasing transition. We investigate this phenomenon from the perspective of work extraction, by modeling a nanoelectromechanical device as a quantum flywheel or battery that converts electrical power into stored mechanical energy. We introduce a microscopic model that qualitatively matches the experimental finding, and we compute the Wigner function of the quantum vibrational mode in its nonequilibrium steady state. We characterize the threshold for self-sustained oscillations using two approaches to quantifying work deposition in nonequilibrium quantum thermodynamics: the ergotropy and the nonequilibrium free energy. We find that ergotropy serves as an order parameter for the phonon lasing transition. The framework we employ to describe work extraction is general and widely transferable to other mesoscopic quantum devices.


[The application of trajectory model in epidemiological research].
This article introduced the application of trajectory model in epidemiological study on fat development in sixty teenagers. Results showed that fat developing trend on three trajectories-normal fat group, high fat group and very high fat group, with independently different developing trend. Trajectory model seemed a suitable model for fitting the longitudinal data with heterogeneity.


[Medical treatment of urothelial tumors of the bladder].
Intravesical chemotherapy is widely used in the management of superficial urinary bladder tumors. A complete response rate of 30 to 50% is observed in unresected tumors. Prophylactic instillations of the drugs after transurethral resection of the tumors seem able to delay recurrences. BCG can also be as effective, particularly in carcinoma in situ. Confirmation of efficacy of retinoids needs further studies. Invasive or metastatic bladder carcinoma can be responsive to systemic chemotherapy in about 40% of the cases for a period of 6 to 12 months. The value of adjuvant chemotherapy remains to be proved. Enhancement of radiation therapeutic effects by CisPlatinum in an interesting field of clinical research.


Unraveling new therapeutic targets of coronary artery disease by genetic approaches.
Coronary artery disease (CAD) is the most common cause of death and physical disabilities in developed countries, even though efforts to identify and target causal factors such as hypertension and dyslipidemia have brought tremendous improvements in prevention and treatment. A rapid advance in technology has unraveled new genetic variants associated with CAD and also provided great opportunities to identify novel pathogenic mechanisms and to develop new drugs with higher specificity. Whole-genome sequencing and whole-exome sequencing has made it possible to find rare alleles that are responsible for CAD in small, affected families and case-control studies in a very efficient manner. At present, genome-wide association studies have identified more than 50 loci that explain approximately 10% of the heritability of CAD, most of which is unrelated to traditional risk factors. Mendelian randomization studies enable identification of causal factors among numerous biomarkers and to narrow down promising therapeutic targets. This review highlights new genetic approaches and demonstrates the extent to which the outcome contributes to the finding of new therapeutic targets.


Changes in the hypothalamic-hypophyseal axis of mares associated with seasonal reproductive recrudescence.
Four groups of mares, representing anestrus (AN; n = 8), early transition (ET; n = 7), late transition (LT; n = 8) and estrus (EST; n = 12) were used to examine changes in the hypothalamus and anterior pituitary during the period of transition from winter anestrus into the breeding season. Mares were of mixed breeding, between the ages of 3 and 20 years, and had shown normal patterns of estrous behavior and ovulation during the breeding season previous to this experiment. Hypothalamic content of gonadotropin-releasing hormone (GnRH) and anterior pituitary content of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. The number of receptors for GnRH in anterior pituitary tissue was also determined. There was no effect of stage of transition into the breeding season on receptors for GnRH or content of FSH (p greater than 0.05). Likewise, content of GnRH in the hypothalamus did not differ between the four groups (p greater than 0.05). However, pituitary content of LH increased progressively from anestrus to the breeding season (p less than 0.05). Means for the AN, ET, LT and EST groups were 1.1 +/- 0.2, 2.2 +/- 0.3, 6.3 +/- 1.4 and 15.2 +/- 1.8 micrograms LH/mg pituitary, respectively. In addition, serum concentrations of LH associated with the first ovulation of the year for 5 of the EST mares were significantly lower (p less than 0.01) than those associated with the second ovulation of the year.(ABSTRACT TRUNCATED AT 250 WORDS)


Regional solutions to the physician workforce shortage: the WWAMI experience.
With major medical organizations predicting a national shortage of physicians in coming years, a number of institutional models are being considered to increase the numbers of medical students. At a time when the cost of building new medical schools is extremely expensive, many medical schools are considering alternative methods for expansion. One method is regional expansion. The University of Washington School of Medicine (UWSOM) has used regional expansion to extend medical education across five states without the need to build new medical schools or campuses. The WWAMI program (the acronym for Washington, Wyoming, Alaska, Montana, Idaho), which was developed in the early 1970s, uses existing state universities in five states for first-year education, the Seattle campus for second-year education, and clinical sites across all five states for clinical education. Advantages of regional expansion include increasing enrollment in a cost-effective fashion, increasing clinical training opportunities, responding to health care needs of surrounding regions and underserved populations, and providing new opportunities for community-based physicians to enhance their practice satisfaction. Challenges include finding basic-science faculty at regional sites with backgrounds appropriate to medical students, achieving educational equivalence across sites, and initiating new research programs. UWSOM's successful long-term regional development, recent expansion to Wyoming in 1997, and current consideration of adding a first-year site in Spokane, Washington, indicate that regional expansion is a viable option for expanding medical education.


Ironing out Macrophage Immunometabolism.
Over the last decade, increasing evidence has reinforced the key role of metabolic reprogramming in macrophage activation. In addition to supporting the specific immune response of different subsets of macrophages, intracellular metabolic pathways also directly control the specialized effector functions of immune cells. In this context, iron metabolism has been recognized as an important component of macrophage plasticity. Since macrophages control the availability of this essential metal, changes in the expression of genes coding for the major proteins of iron metabolism may result in different iron availability for the macrophage itself and for other cells in the microenvironment. In this review, we discuss how macrophage iron can also play a role in immunometabolism.


Quantitative determination of conformational, dynamic, and kinetic parameters of a ligand-protein/DNA complex from a complete relaxation and conformational exchange matrix analysis of intermolecular transferred NOESY.
We report a quantitative analysis of the 13C-edited intermolecular transferred NOESY (inter-TrNOESY) spectrum of the trp-repressor/operator complex (trp-rep/op) with [ul-13C/15N]-L-tryptophan corepressor using a computer program implementing complete relaxation and conformational exchange matrix (CORCEMA) methodology [Moseley et al. (1995) J. Magn. Reson. 108B, 243-261]. Using complete mixing time curves of three inter-TrNOESY peaks between the tryptophan and the Trp-rep/op, this self-consistent analysis determined the correlation time of the bound species (tauB = 13.5 ns) and the exchange off-rate (k(off) = 3.6 s(-1)) of the corepressor. In addition, the analysis estimated the correlation time of the free species (tauF approximately 0.15 ns). Also, we demonstrate the sensitivity of these inter-TrNOESY peaks to several factors including the k(off) and orientation of the tryptophan corepressor within the binding site. The analysis indicates that the crystal structure orientation for the corepressor is compatible with the solution NMR data.


[Development of a diabetes risk prediction sheet for specific health guidance].
To develop diabetes risk scores and to produce a diabetes risk prediction sheet that can be used throughout Japan as a tool for health guidance. A total of 16,289 men and 37,099 women aged 40-69 years who had underwent health check-ups in Ibaraki prefecture, Japan, in 1993, were followed through 2003 (mean follow-up duration; 5.0 yr in men, 5.5 yr in women). Relative risk (RR) of newly developed diabetes (determined by fasting blood glucose > / = 126 mg/dL, resting blood glucose > / = 200 mg/dL, or treatment of diabetes) was calculated according to blood glucose, triglycerides (log-transformed), systolic blood pressure, body mass index (BMI), treatment for hypertension, dyslipidemia, smoking habits, alcohol consumption, and fasting status using Cox's proportional hazards model. Diabetes risk scores were calculated by multiplying RRs of individual variables. In addition, we attempted to develop a diabetes risk prediction sheets for specific health guidance of the larger general Japanese population. During the follow-up, there were 3,654 new cases of diabetes in 1,667 men and 1,987 women. In both men and women, the significant factors included in the risk scores were BMI, blood glucose, systolic blood pressure, treatment for hypertension, triglycerides and smoking habits. Based on the computed risk scores, a 12-page diabetes risk prediction sheet was produced. The sheet includes a scoring protocol for diabetes risk scores consisting of a representative value and RR for each risk factor as well as advice for achieving a healthy lifestyle. The diabetes risk prediction sheet developed in this study may be an effective tool to guide individuals at high risk for lifestyle-related disease such as diabetes.


Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats.
Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes.In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK), which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change the nociceptive response (visceral pain sensitivity) and anterior cingulate cortex neuronal responses to CRD. CCK activating vagal afferent C fibers enhances memory consolidation and retention involved in long-term visceral negative affective state. Thus, in a number of gastrointestinal disorders, such as irritable bowel syndrome, nutrient content may contribute to painful visceral perception by enhancing visceral aversive memory via acts on vagal afferent pathway.


Competency categorization and roles of online teachers from the perspective of university students.
The teaching and learning process is facing many unprecedented challenges that require innovative solutions in the short life of knowledge and the abrupt development of technology. Some of these challenges are the new roles of teachers who are the main constituents in the online teaching process. The main aim of this study revolved around determining and analyzing university students' priorities concerning the competency categorization and roles of online teachers. The research was based on Moodle and Google classroom to validate the competency elements with the final aim of improving teaching and learning processes. The data were collected by using an online questionnaire that evaluated eight dimensions of competencies and roles of online teachers. The research sample consisted of 430 participants (aged between 19 and 30) from Iraq and Oman. The results obtained from these two countries were very similar as the respondents highlighted professional, pedagogical and social competencies in their teachers. It further shows that though the applications used in the two contexts were different (Google classroom with Google Meet or Moodle), it did not affect the final results gained. The results of this survey could be important for further analysis of online teaching practice and bring several important insights regarding the possibilities of online teaching.


Triploid bridge and role of parthenogenesis in the evolution of autopolyploidy.
Autopolyploidization is considered to play an important role in plant evolution. In polyploidization, the polyploid evolves from the original diploid cytotype, in which the triploid state is considered to mediate the process (triploid bridge). Nevertheless, the fitness of triploid individuals seems to be too low to facilitate the polyploidization process (triploid block). The evolutionary condition of autopolyploidy was analyzed using a mathematical model focusing on the role of parthenogenesis in triploid and tetraploid individuals. In addition, offspring were assumed to arise by sexual reproduction by conjugations between haploid, diploid, and triploid gametes produced by diploid, tetraploid, and triploid individuals. According to the analysis, even if triploid block suppresses the fitness of sexually produced triploids, the polyploidization process can proceed when parthenogenesis occurs frequently. If only triploids frequently reproduce parthenogenetically, the evolutionary consequences tend to depend on the fitness of the tetraploid individuals. On the basis of a predetermined parameter set, if tetraploid fitness is relatively low, all three ploidies can coexist. Otherwise, tetraploidization occurs. In this case, triploid parthenogenesis promotes not only triploidization but also tetraploidization. However, if both triploids and tetraploids frequently reproduce parthenogenetically, the ploidy levels with the highest fitness are likely to dominate in the population through direct competition among cytotypes.


Physical Status and Parent-Child Feeding Behaviours in Children and Adolescents with Down Syndrome in The United Arab Emirates.
The prevalence of Down syndrome (DS) in the United Arab Emirates (UAE) is high in comparison to the global statistics. The aim of this study is to assess the physical status, feeding problems, parent-child feeding relationship and weight outcome in children and adolescents with DS in the UAE. In this cross-sectional study, 83 individuals aged between 2-19 years with DS were recruited from three humanitarian centres for differently abled in the Emirates of Sharjah and Dubai, UAE. Socio-demographic characteristics; height, weight, BMI and body composition; feeding problems (STEP-CHILD screening tool); and parent-child feeding relationship (child feeding questionnaire-CFQ) were assessed. Correlations and regression analyses were used to determine the relationships and the best predictor of weight outcome (BMI) in DS participants. The median age of the participants was 9 (8) years. Fifty-five (66.3%) males and twenty-eight (33.7%) females constituted a sex ratio of 1.96:1. Five (6.2%) participants were short for their age, and 20.6% were overweight/obese compared to the growth charts for DS population. Body composition of females showed significantly higher percent body fat than males (25.5 (14.3)% vs. 18.2 (4.0)%, p = 0.03; 29.9 (2.8)% vs. 16.3 (12.2)%, p = 0.006) in 5-8.99 years and 12-19.99 years, respectively. The most common feeding difficulties on STEP-CHILD tool were food selectivity (62.2%), continued eating in the presence of food (57.7%) and swallowing without sufficient chewing (50%). Median score of total-CFQ for the parent-child feeding behaviour was 3.2 (1.9); parental restriction 3.3 (1.0); pressure to eat 3.0 (0.8); concern about child weight 3.7 (2.3). Parent-child feeding relationship was significantly positively correlated with feeding problems, and body weight of the participants. The best predictor for BMI was the parental concern about child weight (OR: 1.4, p = 0.02). The findings can be valuable for the health care professionals, parents and caretakers of children and adolescents with DS in emphasizing the need for regular monitoring of their physical status, and feeding behaviours. In addition, it reinforces the role of parents in mindfully managing their child feeding relationship in promoting healthy eating behaviours and weight of their youth with DS.


Systemic cytokine response to hepatic resections under total vascular exclusion.
To investigate the systemic cytokine response to major liver surgery as the basis for assessing potential new treatments. Open prospective study. University hospital, UK. Thirteen patients undergoing elective hepatic resections that involved total vascular exclusion of the liver. Blood samples were taken preoperatively, during the operation, and during the first four postoperative days. Concentrations of endotoxin, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were measured. Endotoxin concentrations were raised in 3/13 patients before operation and in 6 patients during the postoperative period. TNFalpha concentrations were undetectable. IFN-gamma and IL-1 responses followed a low and inconclusive pattern. IL-6 was significantly increased from 6 hours after operation to the third postoperative day, peaking at 699 (+/-277) pg/ml at 24 hours (p < 0.01). The two patients who died had the highest postoperative concentrations of IL-6. There is a pronounced systemic response to hepatic resection under total vascular exclusion that is reflected by the increase in IL-6 concentration and correlates with the operative blood loss and postoperative outcome. This might be used as an indicator of the response to specific treatments in this type of surgery. Treatments that minimise the IL-6 response to major hepatic resection may be of value.


Highly Reversible Zn Metal Anodes Enabled by Freestanding, Lightweight, and Zincophilic MXene/Nanoporous Oxide Heterostructure Engineered Separator for Flexible Zn-MnO2 Batteries.
Aqueous zinc (Zn)-ion batteries are regarded as promising candidates for large-scale energy storage systems because of their high safety, low cost, and environmental benignity. However, the dendrite issue of Zn anode hinders their practical application. Herein, a freestanding, lightweight, and zincophilic MXene/nanoporous oxide heterostructure engineered separator is designed to stabilize a Zn metal anode. The nanoporous oxides prepared by a one-step vacuum distillation technique afford the advantages of large surface area, high porosity, and homogeneous porous structure. The zincophilic MXene@oxides layer can homogenize the electric field distribution, facilitate ion diffusion kinetics, reduce local current density, and promote even Zn ionic flux, which will regulate uniform Zn deposition and suppress side reactions. Accordingly, dendrite-free Zn anodes with stable cyclability are achieved for over 500 h at an ultrahigh area capacity of 10 mAh cm-2. Besides, flexible, long-lifespan, and high-rate N/S-doped three-dimensional MXene@MnO2||Zn full cells are constructed with the engineered separator. Moreover, this strategy can be successfully extended to lithium, sodium, potassium, and magnesium metal batteries, indicating that separator regulation is a universal approach to overcome the challenges of metal batteries.


Quantifying the impact of COVID-19 on e-bike safety in China via multi-output and clustering-based regression models.
The impacts of COVID-19 on travel demand, traffic congestion, and traffic safety are attracting heated attention. However, the influence of the pandemic on electric bike (e-bike) safety has not been investigated. This paper fills the research gap by analyzing how COVID-19 affects China's e-bike safety based on a province-level dataset containing e-bike safety metrics, socioeconomic information, and COVID-19 cases from 2017 to 2020. Multi-output regression models are adopted to investigate the overall impact of COVID-19 on e-bike safety in China. Clustering-based regression models are used to examine the heterogeneous effects of COVID-19 and the other explanatory variables in different provinces/municipalities. This paper confirms the high relevance between COVID-19 and the e-bike safety condition in China. The number of COVID-19 cases has a significant negative effect on the number of e-bike fatalities/injuries at the country level. Moreover, two clusters of provinces/municipalities are identified: one (cluster 1) with lower and the other (cluster 2 that includes Hubei province) higher number of e-bike fatalities/injuries. In the clustering-based regressions, the absolute coefficients of the COVID-19 feature for cluster 2 are much larger than those for cluster 1, indicating that the pandemic could significantly reduce e-bike safety issues in provinces with more e-bike fatalities/injuries.


Coexistence of Normal and Auxetic Behavior in a Thermally and Chemically Stable sp3 Nanothread: Poly[5]asterane.
A one-dimensional nanostructure with sp3 -hybridized carbon atoms, namely, poly[5]asterane (PA), is predicted by means of electronic structure calculations and reactive molecular dynamics simulations. Thermochemical analysis based on homodesmotic reactions showed that the formation of poly[5]asterane is more favorable than that of polytriangulane and comparable to that of polytwistane. A plane-wave DFT approach gave a computed Young's modulus of about 0.84 TPa, which is quite promising and comparable to those of other sp3 -hybridized nanothreads. Simulations of the desorption of hydrogen atoms from PA showed a high activation energy (Ea ≈52 kcal mol-1 ), which again indicates substantial chemical stability. Interestingly, PA was shown to exhibit auxetic behavior (negative Poisson's ratio). Thus, PA is advocated as a new mechanically and chemically stable nanothread with exotic auxetic behavior.


Activity of combination chemotherapy in brain metastases from breast and lung adenocarcinoma.
Brain metastases represent a common complication of breast and lung cancer, with an overall incidence exceeding 30-40% of cases. Results achieved with radiotherapy are disappointing, with a median survival of a few months, and no clear activity has been observed with chemotherapy. The aims of this study were to assess the activity and feasibility of a new chemotherapeutic approach according to the following schedule: lomustine, 80 mg/m2 day 1; carboplatin, 80 mg/m2 days 1, 8, 15, 22; vinorelbine, 20 mg/m2 days 1, 8, 15, 22; L-leucovorin 250 mg/m2 days 1, 8, 15, 22; and fluorouracil, 500 mg/m2 days 1, 8, 15, 22. Cycles were repeated every 6 weeks. Since January 1994, 28 patients have been enrolled and 26 are evaluable for response and side effects. Major patient characteristics were median age, 55 years (range 31-72); men/women 15/11; lung primary, 20; breast primary, 6; performance status Eastern Cooperative Oncology Group, 0-2. A total of 64 cycles were administered (median/patient, two cycles). Nine partial remissions have been observed (35%, 95% confidence interval 17-56%), 6 disease stabilizations, and 11 disease progressions. Median duration of response was 3 months, and median time to progression for the whole group was 3.7 months (range 1-7). Treatment was well tolerated. Mild or moderate side effects included neutropenia, thrombocytopenia, mucositis, and nausea/vomiting; grade III-IV toxicity included neutropenia and thrombocytopenia. In conclusion, our results indicate that the schedule proposed is feasible and effective in this subset of patients.


The NCEP-ATPIII but not the IDF criteria for the metabolic syndrome identify Type 2 diabetic patients at increased risk of chronic kidney disease.
To examine the association between chronic kidney disease (CKD) and the metabolic syndrome (MetS) using both International Diabetes Federation (IDF) and National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATPIII) definitions in Chinese subjects with Type 2 diabetes. Subjects with Type 2 diabetes were categorized according to the presence or absence of MetS by IDF or NCEP-ATPIII criteria. CKD was considered present if glomerular filtration rate, calculated using the abbreviated equation developed by the Modification of Diet in Renal Disease study with Chinese modification, was < 60 ml/min per 1.73 m2. Multivariate logistic regression analysis of the association between CKD and MetS by either definition was performed. Of 6350 subjects (mean age 55.1 +/- 13.3 years), 3439 (54.2%) and 3204 (50.5%) had MetS by IDF and NCEP-ATPIII definitions, respectively. Using the IDF definition, the presence of MetS was not associated with CKD [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.71, 1.29, P = 0.784]. In contrast, the association with CKD was significant when MetS was defined by the NCEP-ATPIII definition (OR 1.75, 95% CI 1.37, 2.24, P < 0.001). In subjects who did not have MetS (n = 2911) as defined by IDF criteria, 997 fulfilled the MetS criteria of NCEP-ATP III. The association with CKD was stronger, after adjustment for covariates, in these subjects (OR 1.42, 95% CI 1.03, 1.97, P = 0.032) compared with subjects who met IDF criteria of MetS. In Type 2 diabetes, NCEP-ATPIII, but not the IDF definition of MetS, identifies a subgroup of patients who have a higher risk of CKD.


Evaluation of DNA metabarcoding for identifying fish eggs: a case study on the West Florida Shelf.
A critical factor in fisheries management is the protection of spawning sites for ecologically and economically important fish species. DNA barcoding (i.e., amplification and sequencing of the mitochondrial cytochrome c oxidase I (COI) gene) of fish eggs has emerged as a powerful technique for identifying spawning sites. However, DNA barcoding of individual fish eggs is time-consuming and expensive. In an attempt to reduce costs and effort for long-term fisheries monitoring programs, here we used DNA metabarcoding, in which DNA is extracted and amplified from a composited sample containing all the fish eggs collected at a given site, to identify fish eggs from 49 stations on the West Florida Shelf. A total of 37 taxa were recovered from 4,719 fish eggs. Egg distributions on the West Florida Shelf corresponded with the known habitat types occupied by these taxa, which included burrower, coastal pelagic, epipelagic, mesopelagic, demersal, deep demersal, commensal, and reef-associated taxa. Metabarcoding of fish eggs was faster and far less expensive than barcoding individual eggs; however, this method cannot provide absolute taxon proportions due to variable copy numbers of mitochondrial DNA in different taxa, different numbers of cells within eggs depending on developmental stage, and PCR amplification biases. In addition, some samples yielded sequences from more taxa than the number of eggs present, demonstrating the presence of contaminating DNA and requiring the application of a threshold proportion of sequences required for counting a taxon as present. Finally, we review the advantages and disadvantages of using metabarcoding vs. individual fish egg barcoding for long-term monitoring programs.


Complexation of Manganese with Glutarimidedioxime: Implication for Extraction Uranium from Seawater.
The molecule of glutaroimidedioxime, a cyclic imidedioxime moiety that can form during the synthesis of the poly(amidoxime)sorbent and is reputedly responsible for the extraction of uranium from seawater. Complexation of manganese (II) with glutarimidedioxime in aqueous solutions was investigated with potentiometry, calorimetry, ESI-mass spectrometry, electrochemical measurements and quantum chemical calculations. Results show that complexation reactions of manganese with glutarimidedioxime are both enthalpy and entropy driven processes, implying that the sorption of manganese on the glutarimidedioxime-functionalized sorbent would be enhanced at higher temperatures. Complex formation of manganese with glutarimidedioxime can assist redox of Mn(II/III). There are about ~15% of equilibrium manganese complex with the ligand in seawater pH(8.3), indicating that manganese could compete to some degree with uranium for sorption sites.


[Synthesis, 13C-NMR and CD study of the N-terminal tridecapeptide sequence of human fibroblast interferon].
The N-terminal sequence H-Met-Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-OH (FIF[1-13]) of human fibroblast interferon HuIFN-beta(Fi) has been synthesized using the solid-phase method. After esterification of N-tert-butyloxycarbonyl-O-benzyl-L-serine cesium salt with chloromethylated polystyrene-1% divinylbenzene (loading 0.25 mmol/g) the tridecapeptide was built up stepwise. Coupling reagents and N-tert-butyloxycarbonylamino acids were used in a six-fold excess. For the second coupling 1-hydroxybenzotriazole was added during carbodiimide and 4-nitrophenyl glutaminate or asparaginate couplings. Side chain functions were masked: O-benzylserine, O-(2,6-dichlorobenzyl)tyrosine and Ng-tosylarginine. After an acetylation step the N-protection was removed by trifluoroacetic acid/dichloromethane 1:1, and for neutralisation triethylamine/-chloroform 1:9 were used, both steps with a prewash. The Ng-tosyltridecapeptide was split-off from the resin by HBr in trifluoroacetic acid and purified by repetitive precipitations. After deprotection of the guanidino group of arginine with sodium in liquid ammonia, the peptide was precipitated from acetic acid/water, chromatographed on Sephadex G-25 coarse in acetic acid/water 1:1 and precipitated from acetic acid/ether and dimethylformamide/acetone. After purification by multiplicative counter-current distribution in butanol/-5% acetic acid/propanol 5:5:1 the tridecapeptide was pure according to chromatographic, electrophoretic, enzymatic and instrumental analyses. The peptide was investigated by circular dichroism in trifluoroethanol and hexafluoroacetonesesquihydrate and 13C-nuclear magnetic resonance, which revealed an alpha-helical conformation. In order to obtain a suitable antigen the tridecapeptide was coupled to poly(L-lysine) (molecular mass 37300) via N,N'-dicyclohexylcarbodiimide followed by dialysis. The resulting poly(L-lysine)-FIF[1-13] conjugate showed a loading of 17.8 mol FIF[1-13] per mol poly(L-lysine).


[Temporal and Spatial Variations in Water Quality of Hanjiang River and Its Influencing Factors in Recent Years].
Hanjiang River is the main water source and influence area of the Middle Route of the South to North Water Transfer Project. In recent years, the water quality and ecological environment in the middle and lower reaches of the Hanjiang River has become seriously degraded and water blooms occur frequently. Scientific identification of the temporal and spatial variations in water environment quality (and the main driving factors) has become an important management requirement for optimizing the upstream water transfer project. The temporal and spatial variations and influencing factors of water quality in the Hanjiang River basin were systematically analyzed, based on multi-source data and using the Daniel trend test, Mann Kendall test, K-means cluster analysis, dissimilarity analysis, and redundancy analysis. Results showed that: ① in recent years, the main stream of the Hanjiang River had generally good water quality, which was generally classified as class Ⅱ of GB 3838-2002, while the water quality of some sections in the middle and lower reaches was classified as class Ⅲ. However, the total phosphorus (TP) and total nitrogen (TN) load was relatively high, with 10 stations in the Hanjiang River basin showing averaged concentrations of 0.028-0.263 mg·L-1 and 0.630-1.852 mg·L-1, respectively, during 2014-2018. ② From 2004 to 2018, TP and TN at Zongguan station did not show significant variation, and other water quality indexes did not exhibit any regular patterns. The concentrations of TN, NH4+-N, and BOD5 in the dry season were higher than those in the wet season. In the wet season. the permanganate index showed different variation patterns, while TP concentration did not decrease significantly. ③ Different sections showed obvious differences in the variation of water quality indexes. However, the ten stations can be clustered into three categories: the upstream stations showed the best water quality, followed by the middle reaches, and the downstream stations showed the worst. The water quality at Xiaohe station improved significantly over the study period, which may be related to protection measures implemented in recent years, such as source control, emission reduction, and removal of aquaculture. ④ Water discharge and temperature were important factors affecting the water quality of the three regions in Hanjiang River. According to redundancy analysis, the contribution of discharge to water quality in the upstream and downstream areas was much larger, while the contribution of water temperature was greatest in the middle reaches of the river.


DeepMap+: Recognizing High-Level Indoor Semantics Using Virtual Features and Samples Based on a Multi-Length Window Framework.
Existing indoor semantic recognition schemes are mostly capable of discovering patterns through smartphone sensing, but it is hard to recognize rich enough high-level indoor semantics for map enhancement. In this work we present DeepMap+, an automatical inference system for recognizing high-level indoor semantics using complex human activities with wrist-worn sensing. DeepMap+ is the first deep computation system using deep learning (DL) based on a multi-length window framework to enrich the data source. Furthermore, we propose novel methods of increasing virtual features and virtual samples for DeepMap+ to better discover hidden patterns of complex hand gestures. We have performed 23 high-level indoor semantics (including public facilities and functional zones) and collected wrist-worn data at a Wal-Mart supermarket. The experimental results show that our proposed methods can effectively improve the classification accuracy.


Substituted 6-(1-pyrrolidine)quinolin-2(1H)-ones as novel selective androgen receptor modulators.
The androgen receptor is a ligand inducible transcription factor that is involved in a broad range of physiological functions. Here we describe the discovery of a new class of orally available selective androgen receptor modulators. The lead compound, 6-[(2R,5R)-2-methyl-5-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-4-trifluoromethylquinolin-2(1H)-one (6a), showed excellent anabolic activity in muscle with reduced effect on the prostate in a rat model of hypogonadism. The compound also improved bone strength in a rat model of post-menopausal osteoporosis.