Cationic rare-earth metal trimethylsilylmethyl complexes supported by THF and 12-crown-4 ligands: synthesis and structural characterization.
To expand the limited range of rare-earth metal cationic alkyl complexes known, a series of mono- and dicationic trimethylsilylmethyl complexes supported by THF and 12-crown-4 ligands with [BPh4]-, [BPh3(CH2SiMe3)]-, [B(C6F5)4]-, [B(C6F5)3(CH2SiMe3)]-, and [Al(CH2SiMe3)4]- anions were prepared from corresponding neutral precursors [Ln(CH2SiMe3)3Ln] (Ln = Sc, Y, Lu; L = THF, n = 2 or 3; L = 12-crown-4, n = 1) as solvent-separated ion pairs. The syntheses of the monocationic derivatives [Ln(CH2SiMe3)2(12-crown-4)n(THF)m]+[A]- are all high yielding and proceed rapidly in THF solution at room temperature. A "one pot" procedure using the neutral species directly for the syntheses of a number of lutetium and yttrium dicationic derivatives [Ln(CH2SiMe3)(12-crown-4)n(THF)m]2+[A]-2 with a variety of different anions, a class of compounds previously limited to just a few examples, is presented. When BPh3 is used to generate the ion triple, the presence of 12-crown-4 is required for complete conversion. Addition of a second equiv of 12-crown-4 and a third equiv of [NMe2PhH]+[B(C6F5)4]- abstracts a third alkyl group from [Ln(CH2SiMe3)(12-crown-4)2(THF)x]2+[B(C6F5)4]-2 (Ln = Y, Lu). X-ray crystallography and variable-temperature (VT) NMR spectroscopy reveal a structural diversity within the known series of neutral 12-crown-4 supported tris(trimethylsilylmethyl) complexes [Ln(CH2SiMe3)3(12-crown-4)] (Ln = Sc, Y, Sm, Gd-Lu) in the solid and solution states. The X-ray structure of [Sc(CH2SiMe3)3(12-crown-4)] exhibits incomplete 12-crown-4 coordination. VT NMR spectroscopy indicates fluxional 12-crown-4 coordination on the NMR time scale. X-ray crystallography of only the second structurally characterized dicationic rare-earth metal alkyl complex [Y(CH2SiMe3)(12-crown-4)(THF)3]2+[BPh4]-2 shows exocyclic 12-crown-4 coordination at the 8-coordinate metal center with well separated counteranions. 11B and 19F NMR spectroscopy of all mono- and dicationic rare-earth metal complexes reported demonstrate that the anions are symmetrical and noncoordinating on the NMR time scale. A series of trends within the 1H and 13C{1H} NMR resonances arising from the Ln-CH2 groups and, in the case of yttrium, the 1JYC coupling constants at the Y-CH2 group and the 89Y chemical shift values are discussed.


Deficiency in p38β MAPK fails to inhibit cytokine production or protect neurons against inflammatory insult in in vitro and in vivo mouse models.
The p38 MAPK pathway plays a key role in regulating the production of proinflammatory cytokines, such as TNFα and IL-1β, in peripheral inflammatory disorders. There are four major isoforms of p38 MAPK (p38α, β, δ, γ), with p38α and p38β the targets of most p38 MAPK inhibitor drugs. Our previous studies demonstrated that the p38α MAPK isoform is an important contributor to stressor-induced proinflammatory cytokine up-regulation and neurotoxicity in the brain. However, the potential role of the p38β MAPK isoform in CNS proinflammatory cytokine overproduction and neurotoxicity is poorly understood. In the current studies, we used primary microglia from wild type (WT) and p38β knockout (KO) mice in co-culture with WT neurons, and measured proinflammatory cytokines and neuron death after LPS insult. We also measured neuroinflammatory responses in vivo in WT and p38β KO mice after administration of LPS by intraperitoneal or intracerebroventricular injection. WT and p38β KO microglia/neuron co-cultures showed similar levels of TNFα and IL-1β production in response to LPS treatment, and no differences in LPS-induced neurotoxicity. The in vitro results were confirmed in vivo, where levels of TNFα and IL-1β in the CNS were not significantly different between WT or p38β KO mice after LPS insult. Our results suggest that, similar to peripheral inflammation, p38α is critical but p38β MAPK is dispensable in the brain in regards to proinflammatory cytokine production and neurotoxicity induced by LPS inflammatory insult.


Pharmacists' expectations for entry-level practitioner competency.
Objective. To determine if defined subgroups of pharmacists' have variability in their expectations for competency of entry-level practitioners.Methods. Rating scale data collected from the 2009 National Pharmacy Practice Survey were analyzed to determine to what extent pharmacists' degree, practice setting, and experience as a preceptor were associated with the ratings they assigned to 43 competency statements for entry-level practitioners. The competency statements determine the content on the North American Pharmacist Licensure Examination (NAPLEX).Results. Pharmacists with a doctor of pharmacy (PharmD) degree rated the co mpetency statements higher in terms of criticality to entry-level practice than did those with a bachelor of science (BS) degree (p< 0.05). Pharmacists working in inpatient settings gave slightly higher ratings to the competency statements than did pharmacists working in outpatient settings, pharmacists without direct patient care responsibilities, and those in academia. However, there were no significant differences among practitioner subgroups' criticality ratings with regard to practice setting. Preceptor pharmacists' criticality ratings of the competency statements were not significantly different from those of non-preceptor practitioners. Conclusion. Pharmacists exhibited a fair amount of agreement in their expectations for the competence of entry-level practitioners independent of their practice sites and professional roles. As the pharmacy profession embraces patient-centered clinical practice, evaluating practicing pharmacists' expectations for entry-level practitioners will provide useful information to the practitioners and academicians involved in training future pharmacists. Stakeholders in pharmacy education and regulation have vested interests in the alignment of the education of future practitioners with the needs of the profession.


[Histoplasmosis of the central nervous system in an immunocompetent patient].
Histoplasmosis is a multifaceted condition caused by the dimorphic fungi Histoplasma capsulatum whose infective spores are inhaled and reach the lungs, the primary organ of infection. The meningeal form, considered one of the most serious manifestations of this mycosis, is usually seen in individuals with impaired cellular immunity such as patients with acquired immunodeficiency syndrome, systemic lupus erythematous or solid organ transplantation, and infants given their immunological immaturity. The most common presentation is self-limited and occurs in immunocompetent individuals who have been exposed to high concentrations of conidia and mycelia fragments of the fungi. In those people, the condition is manifested by pulmonary disorders and late dissemination to other organs and systems. We report a case of central nervous system histoplasmosis in an immunocompetent child.


Water dependence of the dielectric β-relaxation in poly(ε-caprolactone).
Water dependent secondary relaxations are well known in glass formers. In Poly(ε-caprolactone) (PCL) both the dielectric and mechanical β-relaxation have a water dependent relaxation strength, whose molecular reasons are still unclear. By systematically varying the water content of the samples, a linear dependency between the dielectric relaxation strength and the number of absorbed water molecules was found, leading to a vanishing relaxation for completely dried samples. Neither the α-relaxation nor the secondary β-relaxation showed water dependent relaxation times and also the glass transition temperature determined by differential scanning microscopy (DSC) is not affected by the water absorption. So far the molecular origins of the dielectric β-relaxation in PCL are not consistent with the observations in other glass formers.


Vaccine research and development capacity in Central and West Asia: A path toward sustainable vaccine R&D programs.
The ability to support a comprehensive vaccine research and development (R&D) portfolio from a health security perspective has taken on enhanced significance over the past 3 years whereby countries that had existing vaccine R&D infrastructure (G7, Russia and China) have been at the forefront of global efforts to combat COVID-19. Few countries outside of these key players have the infrastructure necessary to develop national vaccine programs, though this is beginning to change with investment across many low- and middle-income countries. These same opportunities exist for countries in Central and West Asia, and in this perspective, we highlight the existing infrastructure and expertise across seven countries (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan) and propose opportunities for enhanced collaboration along with a bold proposal for establishing a new-build, regional vaccine translational research institute to facilitate the development of a robust, regional vaccine R&D environment to combat existing and future health challenges.


A study of the anatomy, histology and ultrastructure of the digestive tract of Orthrias angorae Steindachner, 1897.
The anatomy, histology and ultrastructure of the digestive tract of Orthrias angorae (Steindachner, 1897) were investigated using light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The histological structure consists of four layers: mucosa, submucosa, muscularis and serosa. The esophageal mucosa consists of undifferentiated basal epithelial cells, mucous cells and surface epithelial cells. It was observed that the J-shaped stomach had a meshwork of folds in the cardiac region, and longitudinal folds in the fundic and pyloric regions. A single layer of columnar cells, PAS positive only in their apical portions, forms the epithelium. The convoluted tube-shape intestine is lined by simple columnar epithelial cells, which have microvilli at the apical surface. The wall of the esophagus and stomach are thicker than that of the intestine because of the thick muscle layer. There were numerous goblet cells in the intestine. There were numerous gastric glands in the submucosa layer ofthe cardiac stomach, but none were present in the pyloric region of the stomach. There were no pyloric caeca between the stomach and intestine. The enterocytes with microvilli contained rough endoplasmic reticulum, ribosomes and rounded bodies, and the gastric cells contained a well-developed Golgi apparatus.


The precautionary principle, toxicological science, and European-U.S. scientific cooperation.
Although it is an ages old concept, the precautionary principle is only a few decades old as a formal expression of a philosophy guiding protection of the environment and of human health. The emergence of the precautionary principle in the European Community and its relatively slower acceptance in the United States reflects differences in underlying social, cultural, and legal approaches to environmental and public health protection. Unfortunately, this poorly defined principle in some of its manifestations can lead to a loss of the toxicological scientific base that is necessary for short-term and long-term protection of the environment and public health. Examples of problems caused by using the precautionary principle include trade barriers erected by the European Community, and the loss of the impetus to develop understanding of the toxicity of hazardous air pollutants due to precautionary aspects of the 1990 U.S. Clean Air Act amendments. There are other U.S.-European differences in the organization and funding of science that are threatening the legacy of Herbert Remmer which was built on close trans-Atlantic scientific cooperation to the benefit of all.


Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.
The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223). Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo. Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients. These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.


Use of the fluorescence probe 1-anilino-8-naphthalenesulfonate in predicting interindividual differences in the plasma protein binding of acidic drugs in rats.
The possibility that the fluorescence probe, 1-anilino-8-naphthalenesulfonate (I), might be used for predicting the interindividual differences in the plasma protein binding of acidic drugs was examined. The interindividual differences in the free fraction of I (fI) were found not to be due to corresponding differences in plasma albumin concentration, but to those differences in binding constant. The binding constant of I to the plasma of 18 individual rats ranged from 1.75 X 10(6) M-1 to 2.3 X 10(7) M-1. The free fraction of I had a highly significant statistical correlation with plasma concentration of free fatty acids, but had no significant correlation with the infinite fluorescence of I or the degree of the polarization of I. Each free fraction of five acidic drugs (warfarin, phenylbutazone, salicylic acid, indomethacin, and sulfaphenazole ) was correlated with fI with high statistical significance. Therefore, the simple and convenient method using I may predict the interindividual differences in the plasma protein binding of acidic drugs in rats.


Transient global left ventricular dysfunction in a localized myocardial infarction related to occlusion of the distal left anterior descending artery.
In some patients with acute myocardial infarction (MI), wall motion in the noninfarcted area declines globally despite localized myocardial damage. In most, an infarct-related lesion is the proximal part of the left anterior descending artery (LAD). Previous studies have reported that hypokinesis of remote myocardium may be related to multivessel disease, impaired coronary flow, or coronary flow reserve in nonculprit arteries. This report describes the case of a 53-year-old man who presented with severe global left ventricular (LV) dysfunction after an acute MI associated with distal LAD occlusion. Follow-up echocardiographic examination revealed nearly normalized LV function 5 days after the episode. We discuss a plausible mechanism of dysfunction of noninfarcted myocardium.


Palmitic acid effect on lipoprotein profiles and endogenous cholesterol synthesis or clearance in humans.
The effect of palmitic acid (C16:0) on serum lipoprotein cholesterol levels is debatable. If C16:0 is hypercholesterolaemic, then it may increase the endogenous synthesis or decrease clearance of cholesterol. Four diets were formulated to provide combinations of two levels of C16:0 in relation to two levels of PUFA. Healthy male subjects received each of the four diet treatments for 21 days, followed by washout periods of 21 days. On day 21 of each diet treatment, a fasting blood sample was drawn for lipoprotein determination and to provide a measure of the background level of deuterium. A priming dose of deuterium was consumed and a second blood sample obtained 24 hours after the first sample. Isotope Ratio Mass Spectrometry was used to determine the incorporation of deuterium into the newly synthesised cholesterol molecule, and fractional synthetic rates calculated. Serum total cholesterol and LDL-cholesterol was not significantly affected by the high level of C16:0 when diets also contained the high level of PUFA. There was no effect of C16:0 on HDL-cholesterol at either the high or low levels of intake. The fractional synthetic rates of cholesterol observed for each of the diet treatments did not significantly differ from one another, suggesting no relationship between the endogenous synthesis of cholesterol and diet C16:0 content. These results indicate that C16:0 had no effect on serum lipoprotein profiles in the presence of recommended intakes for PUFA, nor did it increase rates of cholesterol synthesis in healthy males.


The Hysteroflator 1000S.
A new electrical apparatus for CO2 hysteroscopy is described. It adds an electric suction pump to the insufflator to fix the cervical cup securely and maintain the seal indefinitely. The apparatus was used in 257 patients without any untoward effects.


The function of the upstream region of the sigma 54-dependent Klebsiella pneumoniae nifL promoter is sensitive to DNA supercoiling.
The positive control protein NTRC activates transcription from the sigma 54-dependent nifL and glnAp2 promoters of Klebsiella pneumoniae by binding to upstream enhancer-like sequences and contacting downstream bound sigma 54-RNA polymerase via looping of the intervening DNA. In contrast to the glnAp2 promoter, the activity of the nifL promoter is very sensitive to changes in DNA supercoiling both in vivo and in vitro. We have shown previously that the downstream elements of the nifL promoter are involved in the supercoiling response. In this study we find that the upstream region of nifL influences the supercoiling response of a hybrid nifL-glnAp2 promoter both in vivo and in vitro, demonstrating that the nifL upstream region also confers supercoiling sensitivity. DNA supercoiling did not appear to influence binding of NTRC to its sites in the nifL upstream region, suggesting that another function of this region, most probably DNA loop formation, is sensitive to changes in DNA topology.


Performance of a genetic algorithm for mass spectrometry proteomics.
Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated.


Online-2D NanoLC-MS for Crude Serum Proteome Profiling: Assessing Sample Preparation Impact on Proteome Composition.
Although current LC-MS technology permits scientists to efficiently screen clinical samples in translational research, e.g., steroids, biogenic amines, and even plasma or serum proteomes, in a daily routine, maintaining the balance between throughput and analytical depth is still a limiting factor. A typical approach to enhance the proteome depth is employing offline two-dimensional (2D) fractionation techniques before reversed-phase nanoLC-MS/MS analysis (1D-nanoLC-MS). These additional sample preparation steps usually require extensive sample manipulation, which could result in sample alteration and sample loss. Here, we present and compare 1D-nanoLC-MS with an automated online-2D high-pH RP × low pH RP separation method for deep proteome profiling using a nanoLC system coupled to a high-resolution accurate-mass mass spectrometer. The proof-of-principle study permitted the identification of ca. 500 proteins with ∼10,000 peptides in 15 enzymatically digested crude serum samples collected from healthy donors in 3 laboratories across Europe. The developed method identified 60% more peptides in comparison with conventional 1D nanoLC-MS/MS analysis with ca. 4 times lower throughput while retaining the quantitative information. Serum sample preparation related changes were revealed by applying unsupervised classification techniques and, therefore, must be taken into account while planning multicentric biomarker discovery and validation studies. Overall, this novel method reduces sample complexity and boosts the number of peptide and protein identifications without the need for extra sample handling procedures for samples equivalent to less than 1 μL of blood, which expands the space for potential biomarker discovery by looking deeper into the composition of biofluids.


Abnormalities of Brain White Matter in Type 2 Diabetes Mellitus: A Meta-Analysis of Diffusion Tensor Imaging.
Aims: The study aimed to conduct a meta-analysis to determine the abnormalities of white matter in patients with type 2 diabetes mellitus (T2DM) by identifying the consistency of diffusion tensor imaging (DTI). Method: The literature for DTI comparing patients with T2DM with controls published before October 30, 2020, were reviewed in PubMed, Web of Science, Embase, CNKI, and Wan Fang databases. The meta-analysis was performed using the activation likelihood estimation (ALE) method, including 12 reports and 381 patients with T2DM. Results: The meta-analysis identified 10 white matter regions that showed a consistent reduction of fractional anisotropy (FA) in patients with T2DM, including genu of the corpus callosum, the body of corpus callosum, bilateral anterior corona radiata, bilateral superior corona radiata, bilateral cingulum, and bilateral superior fronto-occipital fasciculus. Conclusion: This study revealed the abnormal characteristics of white matter in T2DM, which would be helpful to understand the underlying neuropathological and physiological mechanisms of T2DM and provide evidence for clinical diagnosis and treatment.


[Determination of 17 pyrethroid pesticide residues in vegetables by gas chromatography-mass spectrometry with negative chemical ionization].
A method was established for the determination of 17 pyrethroid pesticide residues in vegetables using QuEChERS (quick, easy, cheap, effective, rugged and safe) clean-up method and gas chromatography-mass spectrometry (GC-MS) with negative chemical ionization (NCI). The pyrethroid pesticides in the sample were extracted with acetonitrile. After QuEChERS clean-up with a mixture of primary secondary amine and graphitized carbon black packings, the extract was analyzed by GC-NCI-MS in selected ion monitoring (SIM) mode. An isotope internal standard of cypermethrin was employed to the quantification. The limits of quantification ranged from 0.02 to 5 microg/kg. The recoveries of the pyrethroid pesticides spiked in three different matrixes (peas, broccoli and Chinese onion green) at four spiked levels of 10, 20, 30 and 100 microg/kg were from 71.0% to 139.0%, and the relative standard deviations were less than 12.8%. This method can be used as a conclusive evidence method of the 17 pyrethroid pesticide residues in vegetables.


Sulphasalazine-induced reversible hypersensitivity pneumonitis and fatal fibrosing alveolitis: report of two cases.
The cases of two patients with ulcerative colitis are described who developed pulmonary infiltrates during the early months of treatment with sulphasalazine. The first patient had a hypersensitivity pneumonitis, which was confirmed by challenge. Recovery was complete. The second patient developed a fibrosing alveolitis type reaction, with fatal outcome.


Regional differences between nuclear concentration of (3H) estradiol and (3H) progesterone and their action on the uterus of rat during delayed implantation.
The cellular and subcellular localization of radioactivity by dry-mount autoradiography was studied at 5, 15 and 30 minutes after intraluminal or at 5, 15, and 60 minutes after subcutaneous administration of (3H) estradiol or (3H) progesterone to rats in which implantation was delayed by ovariectomy on day 3 post-coitum, followed by treatment with progesterone. After intraluminal instillation of (3H) estradiol or (3H) progesterone, radioactivity was cleared from the uterine lumen at 5 minutes. After intraluminal as well as subcutaneous injection of (3H) estradiol, radioactivity was concentrated at all time intervals in the nuclei of cells of the substantia propria, glands and muscularis, but not in the luminal epithelium. White blood cells and endothelial cells were unlabeled, while perivascular cells showed concentration of radioactivity. After intraluminal instillation of (3H) progesterone, radioactivity was retained in the cytoplasm of the luminal epithelium at 5 and 15 minutes, while no such concentration appeared after subcutaneous injection. No selective nuclear retention was observed in the luminal epithelium, in contrast to the substantia propria and muscularis. The autoradiographic results indicate that progesterone treatment simulating the conditions of early pregnancy, changes the uptake affinity of uterine tissues for (3H) estradiol. The lack of a detectable concentration of estrogen within nuclei of the luminal epithelium does not preclude hormone action. Possible mechanisms of metabolic activation of the uterine luminal epithelium in the apparent absence of concentration of (3H) estradiol to nuclei of the luminal epithelium are discussed.


Real-time analysis of the telegrapher's equation for tunneling processes.
Based on a close analogy with an RLC circuit, a model for interpreting delay times in forbidden regimes (tunneling) is formulated, avoiding the analytical continuation into imaginary time. In this way, a reasonable description of experimental data, which were previously reported for a waveguide propagation below the cutoff frequency at approximately 9.5 GHz, is obtained.


Ultrafast vibrational excitation transfer on resonant antenna lattices revealed by two-dimensional infrared spectroscopy.
High-quality lattice resonances in arrays of infrared antennas operating in an open-cavity regime form polariton states by means of strong coupling to molecular vibrations. We studied polaritons formed by carbonyl stretching modes of (poly)methyl methacrylate on resonant antenna arrays using femtosecond 2DIR spectroscopy. At a normal incidence of excitation light, doubly degenerate antenna-lattice resonances (ALRs) form two polariton states: a lower polariton and an upper polariton. At an off-normal incidence geometry of 2DIR experiments, the ALR degeneracy is lifted and, consequently, the polariton energies are split. We spectrally resolved and tracked the time-dependent evolution of a cross-peak signal associated with the excitation of reservoir states and the unidirectional transfer of the excess energy to lower polaritons. Bi-exponential decay of the cross-peak suggests that a reversible energy exchange between the bright and dark lower polaritons occurs with a characteristic transfer time of ∼200 fs. The cross-peak signal further decays within ∼800 fs, which is consistent with the relaxation time of the carbonyl stretching vibration and with the dephasing time of the ALR. An increase in the excitation pulse intensity leads to saturation of the cross-peak amplitude and a modification of the relaxation dynamics. Using quantum-mechanical modeling, we found that the kinetic scheme that captures all the experimental observations implies that only the bright lower polariton accepts the energy from the reservoir, suggesting that transfer occurs via a mechanism involving dipole-dipole interaction. An efficient reservoir-to-polariton transfer can play an important role in developing novel room-temperature quantum optical devices in the mid-infrared wavelength region.


[Detection of RAS genes mutation using the Cobas® method in a private laboratory of pathology: Medical and economical study in comparison to a public platform of molecular biology of cancer].
In France, determination of the mutation status of RAS genes for predictive response to anti-EGFR targeted treatments is carried out by public platforms of molecular biology of cancer created by the French National Cancer Institute. This study aims to demonstrate the feasibility of these analyses by a private pathology laboratory (MEDIPATH) as per the requirements of accreditation. We retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases of colorectal metastatic cancer using the Cobas® technique. We compared our results to those prospectively obtained through pyrosequencing and allelic discrimination by the genetic laboratory of solid tumors at the Nice University Hospital (PACA-EST regional platform). The results of both series were identical: 98.7% positive correlation; negative correlation of 93.1%; overall correlation of 95.7% (Kappa=0.92). This study demonstrates the feasibility of molecular analysis in a private pathology laboratory. As this practice requires a high level of guarantee, its accreditation, according to the NF-EN-ISO15189 quality compliance French standard, is essential. Conducting molecular analysis in this context avoids the steps of routing the sample and the result between the pathology laboratory and the platform, which reduces the overall time of rendering the result. In conclusion, the transfer of some analysis from these platforms to private pathology laboratories would allow the platforms to be discharged from a part of routine testing and therefore concentrate their efforts to the development of new analyses constantly required to access personalized medicine.


Renaissance of Sandmeyer-Type Reactions: Conversion of Aromatic C-N Bonds into C-X Bonds (X = B, Sn, P, or CF3).
The Sandmeyer reaction represents an important organic transformation that converts an arylamine to an aryl halide using Cu(I) halide via a diazonium salt intermediate. The reaction was first reported by Sandmeyer in 1884, and a number of named reactions closely related to it have been developed and widely applied in organic synthesis throughout the 20th century. These include the Pschorr reaction for the synthesis of biaryl tricycles, the Gomberg-Bachmann reaction for biaryl formations, the Balz-Schiemann reaction for C-F bond formations, and the Meerwein reaction for arylation of α,β-unsaturated carbonyl compounds. However, all these reactions were discovered before 1940. In 1977, Doyle and co-workers reported an organic phase diazotization process, and Kikukawa and Matsuda used aryldiazonium salts in transition metal-catalyzed cross-coupling reactions. However, completely new processes involving diazonium salts have been seldom reported since then, although aryldiazonium salts are widely utilized in modern organic synthesis. In the past few years, diazonium salt chemistry has been revisited and become a fast-growing research topic. Several novel transformations based on diazonium salts have been developed and have been practiced in organic synthesis. In 2010, we reported a direct conversion of arylamines to pinacol boronates through the reaction of in situ generated aryl diazonium salts with B2pin2. This new strategy is under metal-free conditions and thus completely avoids contamination by transition metals in the boron products. From readily available arylamines various functionalized arylboronates, some of which are difficult to access by other methods, can be easily obtained with this reaction. Mechanistic investigations indicate the reaction likely follows a radical mechanism, which is similar to traditional Sandmeyer-type reactions. Subsequently, modified reaction conditions for this transformation appeared in the literature, which include light-induced reactions, aqueous-phase diazotization methods, and reactions with aryltriazenes as the arene diazonium salt surrogates. In addition to the borylation, we have also demonstrated the corresponding stannylation and phosphorylation of arylamines with similar Sandmeyer-type approaches. The stannylation of arylamines was achieved by the reaction of in situ generated diazonium salts with a distannane reagent, while phosphorylation is the reaction of arylamines with trimethyl phosphite in the presence of tert-butyl nitrite (t-BuONO). With the sequential borylation and stannylation approaches, the aromatic compounds bearing two amino groups are easily converted into trimethylstannyl arylboronates, which can be further used in consecutive Stille and Suzuki-Miyaura cross-couplings. Finally, direct conversion of the amino group of arylamines to the trifluoromethyl group has been developed through aryl diazonium salts almost simultaneously by several groups. These reactions represent a novel strategy to achieve trifluoromethylation of aromatic compounds. These developments show the revivification of this age-old chemistry, and this Account will summarize the Sandmeyer reaction-related transformations that have been developed since 2010.


Respiratory syncytial virus prophylaxis--the story so far.
Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations. Therapy is sub-optimal for RSV, thus treatment focuses on ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have been ongoing to develop a safe and effective vaccine. These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-risk children in the United States; EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects. Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.


[The effects of electrical stimulation of posterior hypothalamus on activity of the nucleus pontis oralis' neurons].
The nucleus pontis oralis' neurons were responsive to electrical stimulation of posterior hypothalamus. PS-on neurons showed an inhibitory response, and PS-off cells demonstrated an excitatory response. Neurons that discharged in association with phasic paradoxical sleep phenomena were found to have both the excitatory and the inhibitory responses. Evoked responses changed across sleep-waking cycle. The findings suggest that posterior hypothalamus is involved in the control of paradoxical sleep generation mechanisms located in the nucleus pontis oralis.


[Tapentadol prolonged release for the treatment of severe chronic tumor pain in routine clinical practice].
This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol prolonged release (Palexia retard) for the treatment of severe chronic tumor pain in routine clinical practice in Germany. Data of all patients in the study cohort who were exclusively diagnosed with tumor pain (n = 143) were included in this analysis. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. A total of 96.5% of all patients with tumor pain had already received analgesic long-term treatment prior to initiation of tapentadol PR therapy, 49.0% of those strong opioids. Switching to tapentadol PR resulted in a mean pain reduction of 3.8 points from 7.1 +/- 1.4 at baseline to 3.3 +/- 1.9 at end of observation (NRS-11, 11-point pain scale; descriptive pvalue < or = 0.001). At end of observation, 67.4% of the patients had experienced a clinically relevant pain relief of > or = 50%, and 89.9% of the patients attained either their intended pain reduction and/or an additional individual treatment goal; both goals had been predefined at start of tapentadol PR treatment. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life (descriptive p value < or = 0.001) with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Treatment with tapentadol PR resulted in marked effective and well tolerated relief of severe tumor pain accompanied by an improvement of pain-related impairments of daily activities and quality of life in this routine clinical practice non-interventional study. Tapentadol PR--an innovative effective analgesic--might thus provide an alternative treatment option in the management of tumor pain.


High throughput discovery of thermo-responsive materials using water contact angle measurements and time-of-flight secondary ion mass spectrometry.
Switchable materials that alter their chemical or physical properties in response to external stimuli allow for temporal control of material-biological interactions, thus, are of interest for many biomaterial applications. Our interest is the discovery of new materials suitable to the specific requirements of certain biological systems. A high throughput methodology has been developed to screen a library of polymers for thermo-responsiveness, which has resulted in the identification of novel switchable materials. To elucidate the mechanism by which the materials switch, time-of-flight secondary ion mass spectrometry has been employed to analyse the top 2 nm of the polymer samples at different temperatures. The surface enrichment of certain molecular fragments has been identified by time-of-flight secondary ion mass spectrometry analysis at different temperatures, suggesting an altered molecular conformation. In one example, a switch between an extended and collapsed conformation is inferred. Copyright © 2012 John Wiley & Sons, Ltd.


Prediction of impacts on liver enzymes from the exposure of low-dose medical radiations through artificial intelligence algorithms.
This study aimed to develop artificial intelligence and machine learning-based models to predict alterations in liver enzymes from the exposure of low annual average effective doses in radiology and nuclear medicine personnel of Institute of Nuclear Medicine and Oncology Hospital. Ninety workers from the Radiology and Nuclear Medicine departments were included. A high-capacity thermoluminescent was used for annual average effective radiation dose measurements. The liver function tests were conducted for all subjects and controls. Three supervised learning models (multilayer precentron; logistic regression; and random forest) were applied and cross-validated to predict any alteration in liver enzymes. The t-test was applied to see if subjects and controls were significantly different in liver function tests. The annual average effective doses were in the range of 0.07-1.15 mSv. Alanine transaminase was 50% high and aspartate transaminase was 20% high in radiation workers. There existed a significant difference (p=0.0008) in Alanine-aminotransferase between radiation-exposed and radiation-unexposed workers. Random forest model achieved 90-96.6% accuracies in Alanine-aminotransferase and Aspartate-aminotransferase predictions. The second best classifier model was the Multilayer perceptron (65.5-80% accuracies). As there is a need of regular monitoring of hepatic function in radiation-exposed people, our artificial intelligence-based predicting model random forest is proved accurate in prediagnosing alterations in liver enzymes.


Endoplasmic Reticulum Stress: A New Research Direction for Polycystic Ovary Syndrome?
Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders, with sporadic ovulation, excessive androgens, and polycystic ovarian changes as the main clinical manifestations. Due to the high heterogeneity of its clinical manifestations, the discussion on its pathogenesis has not been unified. Current research has found that genetic factors, hyperandrogenism, chronic inflammation and oxidative stress, insulin resistance, and obesity are strongly associated with PCOS. Recently, when studying the specific mechanisms of the abovementioned factors in PCOS, the biological response process of endoplasmic reticulum stress (ERS) has gradually come to researchers' attention, and several studies have confirmed the involvement of ERS in the pathogenesis of PCOS and the improvement of a series of pathological manifestations of PCOS after the application of ERS inhibitors, which may be a new entry point for the treatment of PCOS. In this article, we review the relationship between ERS and various pathogenic factors of PCOS.


Mitochondrial phylogeny of the endemic mouthbrooding lineages of cichlid fishes from Lake Tanganyika in eastern Africa.
Of the three cichlid species flocks in eastern Africa, Lake Tanganyika harbors the oldest species assemblage, which is also the most diverse morphologically and behaviorally. For 12 species (20 individuals) of 12 genera of the tribe Ectodini, 852 bp from two segments (cytochrome b and control region) of the mitochondrial genome were sequenced. In addition, orthologous sequences were obtained from eight species (11 individuals) representing other mouthbrooding lineages from Lake Tanganyika. Comparisons of sequence divergences revealed that the single Tanganyikan tribe Ectodini appears to be approximately five times older than the whole Lake Malawi cichlid species flock, suggesting that the radiation of the Tanganyikan mouthbrooding lineages took place long before the species flocks of Lakes Malawi and Victoria evolved. Seven of nine surveyed tribes of Tanganyikan cichlids appear to be approximately equally divergent, and this seems to corroborate the hypothesis of a rapid simultaneous formation of lineages at an early stage in the history of the Lake Tanganyika species flock. The close genetic relationship between the endemic Tropheus lineage and a nonendemic "Haplochromine," Astatotilapia burtoni, indicates that members of the tribe Tropheini may be the sister group of the cichlid flocks of Lakes Malawi and Victoria. The phylogenetic analyses demonstrate the monophyly of the Ectodini and identify the Cyprichromini as their sister group among the Tanganyikan cichlids. Within the tribe Ectodini the molecular data suggest both a branching pattern different than that previously proposed and a subdivision of the Ectodini into four clades, instead of the two originally described. The previously postulated model of morphological transformations believed to be responsible for the drastically different types of ecological specialization found among the Ectodini might therefore be in need of reinterpretation. Characters immediately related to foraging and nutrition seem to be particularly prone to homoplasy, even among members of a single lineage of cichlid fishes.


Comparing the effects of fatigue and alcohol consumption on locomotive engineers' performance in a rail simulator.
Laboratory studies have established that the performance impairments due to fatigue and alcohol consumption are quantitatively similar. However, the generalisability of this phenomenon is not clear because comparisons have not been made in realistic work settings with experienced shiftworkers. The aim of the current study was to quantify the effects of fatigue on performance in a simulated work environment (i.e. rail simulator) and compare them with the effects of alcohol consumption. It was hypothesised that fatigue would significantly impair driving performance, and that this impairment would be quantitatively similar to that associated with moderate levels of alcohol consumption. Twenty locomotive engineers participated in the study with a randomised cross-over design and three conditions: baseline, fatigue, and alcohol. During each 8-hour condition, participants completed four driving sessions in the rail simulator. The results indicate that fatigue caused participants to disengage from operating the simulator such that safety was traded off, not necessarily deliberately, against efficiency. The impairment in safety due to fatigue was in a range similar to the impairment associated with moderate levels of alcohol consumption. In summary, the study demonstrated that the effects of fatigue in a simulated work environment can be quantified and may be considerable.


Cytosolic NADPH metabolism in penicillin-G producing and non-producing chemostat cultures of Penicillium chrysogenum.
This study addresses the relation between NADPH supply and penicillin synthesis, by comparing the flux through the oxidative branch of the pentose phosphate pathway (PPP; the main source of cytosolic NADPH) in penicillin-G producing and non-producing chemostat cultures of Penicillium chrysogenum. The fluxes through the oxidative part of the PPP were determined using the recently introduced gluconate-tracer method. Significantly higher oxidative PPP fluxes were observed in penicillin-G producing chemostat cultures, indicating that penicillin production puts a major burden on the supply of cytosolic NADPH. To our knowledge this is the first time direct experimental proof is presented for the causal relationship between penicillin production and NADPH supply. Additional insight in the metabolism of P. chrysogenum was obtained by comparing the PPP fluxes from the gluconate-tracer experiment to oxidative PPP fluxes derived via metabolic flux analysis, using different assumptions for the stoichiometry of NADPH consumption and production.


Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States.
Vitamin D sufficiency is required for optimal health, and solar ultraviolet B (UVB) irradiance is an important source of vitamin D. UVB and/or vitamin D have been found in observational studies to be associated with reduced risk for over a dozen forms of cancer, multiple sclerosis, osteoporotic fractures, and several other diseases. On the other hand, excess UV irradiance is associated with adverse health outcomes such as cataracts, melanoma, and nonmelanoma skin cancer. Ecologic analyses are used to estimate the fraction of cancer mortality, multiple sclerosis prevalence, and cataract formation that can be prevented or delayed. Estimates from the literature are used for other diseases attributed to excess UV irradiation, additional cancer estimates, and osteoporotic fractures. These results are used to estimate the economic burdens of insufficient UVB irradiation and vitamin D insufficiency as well as excess UV irradiation in the United States for these diseases and conditions. We estimate that 50,000-63,000 individuals in the United States and 19,000-25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D. The U.S. economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet, and supplements was estimated at $40-56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6-7 billion. These results suggest that increased vitamin D through UVB irradiance, fortification of food, and supplementation could reduce the health care burden in the United States, UK, and elsewhere. Further research is required to confirm these estimates.


Not in wilderness: African vulture strongholds remain in areas with high human density.
Vultures constitute an important functional group in many ecosystems, providing crucial ecosystem services both in natural and humanized environments. These scavengers are facing massive declines worldwide, but in several African countries virtually nothing is known on populations' status and threats, hampering the development of adequate conservation strategies. In Guinea-Bissau, globally important populations of Hooded Necrosyrtes monachus and African white-backed vultures Gyps africanus were recently reported. Using the country as a study area, we aim to characterize human-vulture interactions in West Africa applying a multidisciplinary approach. We assessed the status and distribution of vulture populations using data from 1711 km of roadside transects, examined predictors of their distribution, and produced a nationwide population estimate for the Hooded Vulture, using an innovative method based on the relationship between the size of human population in settlements and vulture numbers. We conducted 47 stakeholder interviews to assess perceived roles played by vultures, and to investigate potential anthropogenic threats. Hooded vultures were strongly associated with high human population densities, whereas no relation was found between African white-backed and Rüppell's vultures and any of the tested predictors, which included cattle density, precipitation and Normalized Difference Vegetation Index, among others. We estimate a national population of 43347 Hooded vultures, the largest population reported in the species range. Respondents were generally aware of the services provided by vultures, especially waste and carcass removal, including in urban areas. Hunting for witchcraft and traditional medicine was the most frequently recognised threat, while poisoning was ranked as having the highest impact. We hypothesise that poisoning-related mortality may be affecting African white-backed and Rüppell's vultures' distribution and explain their scarcity in apparently highly suitable habitats. Our results suggest a mutualistic rather than a commensalistic relationship between vultures and humans, with important implications for designing and implementing conservation strategies.


Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation.
A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions. Six early life immune causal networks, each compromising a different time period in early life (the 1st, 2nd, 3rd trimester of gestations, birth, newborn, and infant period), were generated. Thereto information was extracted and structured from early life literature using the automated text mining and machine learning tool: Integrated Network and Dynamical Reasoning Assembler (INDRA). The tool identified relevant entities (e.g., genes/proteins/metabolites/processes/diseases), extracted causal relationships among these entities, and assembled them into early life-immune causal networks. These causal early life immune networks were denoised using GeneMania, enriched with data from the gene-disease association database DisGeNET and Gene Ontology resource tools (GO/GO-SLIM), inferred missing relationships and added expert knowledge to generate information-dense early life immune networks. Analysis of the six early life immune networks by PageRank, not only confirmed the central role of the "commonly used immune markers" (e.g., chemokines, interleukins, IFN, TNF, TGFB, and other immune activation regulators (e.g., CD55, FOXP3, GATA3, CD79A, C4BPA), but also identified less obvious candidates (e.g., CYP1A2, FOXK2, NELFCD, RENBP). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (TNF, IL6, IL10, CD4, FOXP3, IL4, NELFCD, CD79A, IL5, RENBP, and IFNG), and also genes that were only described in certain early life period(s). Concluding, here we describe a network-based approach that provides a science-based and systematical method to explore the functional development of the early life immune system through time. This systems approach aids the generation of a testing strategy for the safety and efficacy of early life immune modulation by predicting the key candidate markers during different phases of early life immune development.


Genetic Counselling and Narrative Practices: A Model of Support following a "Negative" Predictive Test for Huntington's Disease.
Predictive testing for Huntington's disease (HD) has been available for individuals at risk of HD by direct mutation analysis since 1993. International Predictive test guidelines recommend that support is offered following the result regardless of test outcome. However, there is lack of an evidence base regarding what this support should look like and how it might work in practice. A service improvement initiative looked at the feasibility of offering a narrative group session co-facilitated by a genetic counsellor and clinical psychologist, to individuals who had tested mutation negative for HD. The narrative session was evaluated from the perspective of group participants. Individuals who tested mutation negative at a genetic centre in the North of England over a 5-year period were invited to attend a narrative group session. 52 people were contacted and 9 people agreed to participate. Participants completed standardised questionnaires (PHQ-9 and GAD-7) before and after the session and a detailed written evaluation. Participants' comments were analysed thematically. Participants were overwhelmingly positive about the narrative session finding it a safe and enjoyable way to explore difficult life experiences. Reported benefits included feeling less isolated, being inspired by other people's stories and connecting as a group. All 9 participants said they would recommend the narrative session to anyone impacted by HD. The narrative group session was considered an interesting and useful approach to facilitating adaptation following a negative predictive test result for HD.


Establishment of a Murine Chronic Anorexia Nervosa Model.
Anorexia nervosa (AN) is associated with hyperactivity, amenorrhea, and brain atrophy. The underlying pathophysiology is mostly unknown, and new targets for therapeutic interventions are needed. This study aimed to systematically establish a murine AN model with the parameter extent of starvation, animal age, and length of starvation for functional studies. The activity-based anorexia (ABA) model combines food restriction with running wheel access. Early adolescent and adolescent mice received 40% of their baseline food intake until a 20% or 25% weight reduction was reached (acute starvation). To mimic chronic starvation, body weight loss was maintained for another two weeks. Running activity was examined using wheel sensors, while amenorrhea was investigated by analysis of vaginal smears. Brain sections were used to analyze cerebral cortex volumes. Acute starvation did not lead to either AN-related symptoms, whereas chronic starvation led to hyperactivity and amenorrhea except in the adolescent cohort with 20% weight reduction. Only ABA mice with 25% weight reduction revealed a cortex volume reduction. The optimal parameters to mirror AN-related symptoms included a 25% weight reduction, early adolescent or adolescent mice, and chronic starvation. The ABA model enables functional analysis of the impact of chronic AN on the underlying hormonal, behavioral, and brain pathophysiology.


Fluorescence in situ hybridization: a multitarget approach in diagnosis and management of urothelial cancer.
Noninvasive tests for detecting genetic or molecular alterations in urine indicative of urothelial cancer are increasingly becoming the focus of urological cancer research. Since its approval by the US FDA in 2001, the fluorescence in situ hybridization test (Vysis UroVysion) has been widely evaluated. In general, published data demonstrate better sensitivity and equal or better specificity compared with routine cytology, which is still considered the 'gold standard' in diagnosing and monitoring bladder tumors. However, the fluorescence in situ hybridization test seems to provide not only a useful tool in bladder cancer detection, but also in the diagnosis of upper urinary tract tumors, surveillance and determining therapy effectiveness. This multitarget assay that detects four different chromosomal aberrations in tumor cells is a kind of objective molecular cytology and has proven advantages over routinely used cytology.


Carbapenem-resistant Gram-negative bacteria - analysis of the data obtained through a mandatory reporting system in the Rhine-Main region, Germany, 2012-2015.
Multidrug-resistant Gram-negative bacteria (MRGN) and the infections they cause are a serious threat and a challenge to the healthcare system. This particularly applies to carbapenem-resistant Gram-negative bacteria (CRGN). Currently, the introduction of a nationwide mandatory notification system for CRGN in Germany is under consideration. Against this background, this paper presents an analysis of the mandatory reporting system for CRGN in effect since November 2011 in the federal state of Hesse (Germany). All carbapenem-resistant Gram-negative bacteria and the detected carbapenemases reported to the public health department of the city of Frankfurt am Main, Hesse, Germany, on the basis of the mandatory notification system were analyzed. 827 CRGN cases were reported to the public health department of Frankfurt/Main between April 2012 and December 2015. The following bacterial species were reported: Pseudomonas spp. (n=268), Acinetobacter spp. (n=183), Klebsiella spp. (n=195), Enterobacter spp. (n=77), Escherichia coli (n=75) and others (n=29). Between 2012 and 2015, a reduction of the CRGN reports was noticed, mainly due to changes in the reporting of Pseudomonas spp. Between 2012 and 2015, the total number of notifications decreased slightly, although the number of reported CRGN in screening samples increased, thus giving no indication of a decreased testing frequency. For 10.5% of the patients, the place of residence was not Germany, 18.0% of the patients had previously stayed in hospitals abroad, often in countries with a high CRGN prevalence. CRGN bacteria were reported from all of Frankfurt's hospitals, and 3.9% were reported from out-patient care facilities. Carbapenemases were detected and reported in 251 CRGN bacteria, including 73 OXA-48, 76 OXA-23, 56 NDM subtypes, and 21 KPC subtypes. There have been no major epidemiological signs of outbreak scenarios. CRGN bacteria are already widespread in patients from hospitals and out-patient care facilities. Clearly, infection control measurements should therefore not only include hospital patients but also those receiving out-patient care. Screening strategies focused on patients from foreign countries with high MRGN prevalence is not sufficient, as only 10.5% of MRGN patients resided in those countries, and only 18% of the patients had been previously treated in a foreign hospital. In a public health context, infection control measures should therefore encompass broader screening strategies.


Cognitive-behavioural predictors of children's tolerance of laboratory-induced pain: implications for clinical assessment and future directions.
This study sought to investigate cognitive-behavioural predictors of children's tolerance for laboratory-induced cold-pressor pain. It was hypothesised that pain tolerance, as measured by immersion time, would be greater in children who were high in self-efficacy for pain, high in self-reported use of cognitive-coping strategies, and low in emotion-focused coping strategies such as catastrophising. Age and sex differences were also examined in post hoc analyses. Children between the ages of 7 and 14 years (N = 53) participated in the study. Offering partial support for the hypotheses, use of cognitive distraction was found to be associated with greater pain tolerance, while use of internalising/catastrophising was associated with lower pain tolerance. Older boys tended to have greater pain tolerance than younger boys, whereas younger and older girls had intermediate pain tolerance levels. Self-efficacy for pain, in general, was found to be positively correlated with age. The results support efforts to identify children who, because they have lower confidence or lower skills in coping with distress, may need extra support and preparation for painful procedures. Further research is needed to investigate these findings within a clinical pain context.


Treatment of ununited fractures of the scaphoid by iliac bone grafts and Kirschner-wire fixation.
Of 151 ununited fractures of the scaphoid that were treated with iliac bone grafts and Kirschner-wire fixation through a volar approach, all but four (97 per cent) healed in an average of seventeen weeks, Three of the four failures resulted from obvious technical errors. Neither the preoperative existence of necrosis of the proximal fragment nor the location of the fracture affected the results. When there was mild radiocarpal arthritis preoperatively, it did not progress postoperatively; if there was moderate radiocarpal arthritis preoperatively, progression seldom was seen if a radial styloidectomy was done. Displaced and unstable ununited fractures healed even if the deformity was not corrected completely. The principal benefit of the procedure was relief of pain rather than an increase either in motion of the wrist or in strength of grip.


Gonadotropins and sex hormones in healthy Chinese infants.
This study was conducted to investigate the infantile changing regularity of gonadotropins and sex hormones. Serum samples were obtained from 416 healthy infants (male: 215; females: 201). In male infants, peaks in serum gonadotropins and testosterone concentrations were observed at 2-4 months. In female infants, serum FSH concentrations reached peak at 2-3 months. Before 6 months, serum testosterone and LH concentrations were higher in male, while FSH was on the contrary. Peaks in serum gonadotropins and sex hormones concentrations are reached and sexual dimorphism appears in the early infancy. Defining the range of mean values and the trends for infantile gonadotropins and sex hormones could be helpful for clinical evaluation.


Rescue of disabled infectious single-cycle (DISC) equine arteritis virus by using complementing cell lines that express minor structural glycoproteins.
Equine arteritis virus (EAV) contains seven structural proteins that are all required to produce infectious progeny. Alphavirus-based expression vectors have been generated for each of these proteins to explore the possibilities for their constitutive expression in cell lines. This approach was successful for minor glycoproteins GP(2b), GP(3) and GP(4) and for the E protein. Subsequently, it was demonstrated that cell lines expressing these proteins could rescue EAV mutants that were disabled in the expression of the corresponding gene, resulting in the production of virus particles carrying the mutant genome. This system was particularly efficient for GP(2b)- and GP(4)-knockout mutants. Upon infection of non-complementing cells with these mutants, a self-limiting single cycle of replication was initiated, resulting in the expression of all but one of the viral proteins. These disabled infectious single-cycle (DISC) arteriviruses can also be used to express foreign sequences and are potentially useful in both fundamental research and vaccine development.


Chlamydia trachomatis OmcB protein is a surface-exposed glycosaminoglycan-dependent adhesin.
The OmcB protein of Chlamydia trachomatis is a cysteine-rich outer membrane polypeptide with important functional, structural and antigenic properties. The entire gene encoding the OmcB protein from C. trachomatis serovar LGV1 was cloned and expressed in Escherichia coli and the full-length protein used to raise polyclonal antibodies. Recombinant OmcB was used to show that OmcB is a surface-exposed protein that functions as a chlamydial adhesin. Infectivity inhibition assays carried out using HeLa cells with serovar LGV1 in the presence of purified anti-OmcB serum showed inhibition of infectivity, suggesting that some of the OmcB was surface exposed. Moreover, using recombinant OmcB in infectivity inhibition assays resulted in 70% inhibition of infectivity, confirming that OmcB plays a role as an adhesin in C. trachomatis. Furthermore, recombinant OmcB protein bound to the surface of HeLa and Hec1B cells, but binding to glycosaminoglycan (GAG)-deficient cells (pgsA-745 and pgsD-677) was markedly reduced, indicating that OmcB binds to GAG-like receptors on host cells.


The opinion of the production sector on the role of vaccines in the control and eradication of livestock diseases in Argentina.
Research by a number of international organisations indicates that world demand for red meat protein is set to increase significantly in the coming years. However, faced with the risk of infectious animal diseases and zoonoses--factors that could limit the growth of this production sector--the fight against livestock diseases must continue, especially against those that affect food safety or pose a threat to human life. The use of vaccination to prevent infectious animal diseases is of key importance, not only because it helps to control and effectively eradicate infectious livestock diseases, but also because it makes it possible to introduce new technologies for intensive or semi-intensive production, to protect the environment, to care for animal welfare and to guarantee the safety of animal-derived foodstuffs. As part of their professional culture, livestock producers have come to fully appreciate the advantages of using vaccination to prevent disease rather than curative measures, which are more costly to implement and in some cases not very effective. The control of anthrax and rabies by means of effective vaccines was a factor in the widespread development of livestock in Argentina and other parts of Latin America. Recent results in the control and eradication of foot and mouth disease have made producers even more convinced of the merits of this technology. Animal disease prevention has proven to be highly conducive to the production of healthy foodstuffs. It is the responsibility of international organisations to draw up appropriate regulations to protect trade, supply safe and healthy products and prevent the application of unjustified non-tariff measures.


Transforming negative parent-adolescent interactions: from impasse to dialogue.
This treatment development, process research study focuses on resolving in-session, parent-adolescent conflicts characterized by negative exchanges, emotional disengagement, and poor problem solving. These processes have been empirically linked to poor developmental outcomes, and clinically linked to poor therapeutic progress. Specifically, we examined how a shift of therapeutic focus from behavior management to interpersonal relationship failures could resolve this impasse and resuscitate therapeutic momentum. A task analysis approach was used to verify the presence of the impasse, to illuminate its core features, and to define the therapist and client behaviors associated with resolving it. In Part 1 of this two-part series, we presented the final performance map that represented that family's cognitive, emotional and behavioral interactions necessary to resolve the impasse. This article, Part II, focuses on the theoretical foundation of the intervention strategies, the phenomenology of the impasse, and the therapist's skills needed to facilitate it.


Accuracy of Ultrasound-Guided and Non-ultrasound-Guided Botulinum Toxin Injection Into Cadaver Salivary Glands.
To compare the accuracy of ultrasound (US)-guided and non-US-guided botulinum toxin (BTX) injection into the salivary glands (parotid and submandibular glands) of cadavers. Two rehabilitation physician injected dye into three sites in the salivary glands (two sites in the parotid gland and one site in the submandibular gland) on one side of each cadaver (one was injected on the right side, while the other was injected on the left side), using either a non-US-guided injection procedure based on superficial landmarks or a US-guided procedure. Orange dye was used for the US-guided procedure, and green dye was used for the blind procedure. Two physicians uninvolved with the injection procedures and who were blinded to the method of injection dissected the cadavers to identify whether the dye was accurately injected into each target site. The accuracies of the blind and US-guided injections into the parotid gland were 79.17% and 95.83%, respectively. In the submandibular gland, the accuracies of the blind and US-guided injections were 50.00% and 91.67%, respectively. The difference in accuracy between the two procedures was statistically significant only in the submandibular gland (p=0.025). There were no significant differences in the accuracy of US-guided and non-US-guided injections between the two physicians for the two sites in the parotid gland (p=0.278 and p=0.146, respectively). US-guided BTX injection into the submandibular gland offers significantly greater accuracy over blind injection. For the treatment of drooling by injecting BTX into the submandibular gland, clinicians should consider using US guidance for improved accuracy.


Isolation and characterization of a novel chalcone synthase gene family from mulberry.
Chalcone synthase (CHS) is the pivotal enzyme that catalyzes the first committed step of the phenylpropanoid pathway leading to flavonoids. Here, five CHS genes were determined in mulberry (Morus atropurpurea Roxb.). Interestingly, phylogenetic analysis tended to group three MaCHSs in the stilbene synthase (STS) family and initially annotated these as MaSTSs. A co-expression system that harbored a 4-coumarate:CoA ligase gene and one of the candidate genes was established to determine the functions of this novel gene family. The fermentation result demonstrated that MaSTS in fact encoded a CHS enzyme, and was consequently retermed MaCHS. Tissue-specific expression analysis indicated that MaCHS1/MaCHS2 was highly abundant in fruit, and MaCHS4 had significant expression in root bark, stem bark and old leaves, while MaCHS3 and MaCHS5 were more expressed in old leaves. Subcellular localization experiments showed that MaCHS was localized to the cytoplasm. Transcription levels suggested MaCHS genes were involved in a series of defense responses. Over-expression of MaCHS in transgenic tobacco modified the metabolite profile, and resulted in elevated tolerance to a series of environmental stresses. This study comprehensively evaluated the function of MaCHS genes and laid the foundation for future research on MaCHS in mulberry.


Vitamin D Status and Related Factors among Korean Stroke Survivors: A Nationwide Population-Based Study.
The aim of this study was to investigate the vitamin D status and related factors in community-dwelling Korean stroke survivors. Data of 23,872 individuals ≥20 y who participated in the Korea National Health and Nutrition Examination Surveys (KNHANES) were analyzed. Participants who had ever been diagnosed with stroke by a doctor were defined as stroke survivors (n=431). The serum 25-hydroxyvitamin D (25(OH)D) level was measured by radioimmunoassay, and vitamin D deficiency was defined as 25(OH)D<20 ng/mL. The association between vitamin D and stroke status was analyzed using multivariable general linear models and logistic regression models adjusted for sociodemographic and clinical covariates. The adjusted mean 25(OH)D level of stroke survivors was significantly lower than that of nonstroke controls; however, after adjustment for systolic blood pressure level and use of antihypertensive medication, the difference was no longer statistically significant. The burden of 25(OH)D deficiency was not higher in stroke survivors than in nonstroke controls (adjusted OR=1.14; 95% CI, 0.81-1.62). Current smoking was independently associated with 25(OH)D deficiency among stroke survivors (adjusted OR=3.17; 95% CI, 1.33-7.55). These findings indicated that treatment of high blood pressure and smoking cessation may be important measures to control vitamin D levels in stroke survivors.


Wisconsin In Situ Penning (WISP) gauge: A versatile neutral pressure gauge to measure partial pressures in strong magnetic fields.
A new type of in-vessel Penning gauge, the Wisconsin In Situ Penning (WISP) gauge, has been developed and successfully operated in the Wendelstein 7-X (W7-X) island divertor baffle and vacuum vessel. The capacity of the quantitative measurements of the neutral reservoir for light impurities, in particular, helium, is important for tokamaks as well as stellarator divertors in order to avoid fuel dilution and radiative energy loss. Penning gauges assisted by spectroscopy are a powerful tool to obtain the total neutral pressure as well as fractional neutral pressures of specific impurities. The WISP gauge is a miniaturized Penning gauge arrangement, which exploits the ambient magnetic field of magnetic confinement fusion experiments to establish the Penning discharge. Then, in situ spectroscopy is conducted to separate the fractional neutral pressures of hydrogen, helium, and possibly also other impurities. The WISP probe head was qualified using the magnetic field of the Magnetized Dusty Plasma Experiment at Auburn University between 0.25 T and 3.5 T [E. Thomas et al., J. Plasma Phys. 81, 345810206 (2015)]. The in-depth quantitative evaluation for hydrogen and helium will be shown as well as an exploration of nitrogen, argon, and neon. A power law scaling between current I and pressure p, I = f(Gas,V) · pn(Gas, B), was shown. The factor f is gas and anode potential dependent, while n is gas and magnetic field strength dependent. Pressure measurements from 0.1 mbar and down to 1 × 10-5 mbar were achieved, demonstrating a reliable operating range for relevant pressure levels in the divertor and main vessel regions in current and future fusion devices, with a time resolution of up to 1 kHz. The lowest achievable pressure measurement increases with an increase in B and can be shifted with the anode potential V. At W7-X, the WISP probe head was mounted on an immersion tube setup that passes through the cryostat and places the probe head close to the plasma. Two probe heads were positioned in different divertor pump gaps, top and bottom, and one close to the plasma on the midplane in one module. The gauges were in situ calibrated together with the ASDEX pressure gauges [G. Haas and H.-S. Bosch, Vacuum 51, 39 (1998)]. Data were taken during the entire operation phase 1.2b, and measurements were coherent with other neutral gas pressure gauges. For the spectroscopic partial pressure measurements, channels of a spectroscopic detection system based on photo-multipliers, a so-called filterscope [R. J. Colchin et al., Rev. Sci. Instrum. 74, 2068 (2003)], provided by the Oak Ridge National Lab were used.


Evaluation of trabecular structure changes in osteoarthritis of the temporomandibular joint with cone beam computed tomography imaging.
To explore the possibility of using 2-dimensional image assessments in combination with cone beam computed tomography (CBCT) in patients with temporomandibular joint osteoarthritis (TMJOA) to enhance the clinical significance and applicability of the CBCT findings on TMJOA changes. Fifty-two patients with unilateral TMJOA and 40 healthy adults who had undergone CBCT in preparation for orthodontic treatment were selected for this study. Temporomandibular joint images were acquired with CBCT. All images were classified into 4 phases (slight erosion, widespread erosion, appearance of bone maintenance, and partial loss of condylar head with a remodeled cortical surface) and 4 levels of severity (absent, slight, moderate, and extensive). Quantitative microstructural analysis, including bone value fraction (BV/TV), trabecular number (Tb.N), trabecular thickness, and trabecular separation (Tb.Sp) of each image, was performed by using a customized software. In patients with unilateral TMJOA, the affected side had significantly higher BV/TV and Tb.N and significantly lower Tb.Sp compared with the unaffected side. Compared with healthy individuals, the affected joints in patients with TMJOA had significantly higher BV/TV and trabecular thickness and significantly lower Tb.N and Tb.Sp. No significant difference was found among different phase groups or different severity levels. CBCT combined with a software investigation protocol for microstructure measurement can be used to provide reliable trabecular parameters in assessing TMJOA.


Erythropoietin Inhibits Hypoxia-Induced Epithelial-To-Mesenchymal Transition via Upregulation of miR-200b in HK-2 Cells.
Renal tubular epithelial-mesenchymal transition (EMT) is regarded as an important factor leading to renal interstitial fibrosis. Erythropoietin (EPO) has been reported to attenuate renal fibrosis. The mechanism underlying this protective effect of EPO remains unclear. In this study, we aim to identify possible mechanisms of the EPO renoprotective effect. Hypoxia was induced in vitro by incubating human proximal tubular epithelial cell line HK-2 cells in 1% O2 and 5% CO2. Western blotting and reverse transcription polymerase chain reaction analyses were used to evaluate the expression of epithelial and mesenchymal markers in the cell samples. The expression of miR-200b in the HK-2 cells under hypoxia or treatment with EPO was examined. EPO represses hypoxia-induced EMT by upregulating miR-200b in HK-2 cells. Overexpression of miR-200b represses the effect of ETS proto-oncogene 1 (Ets-1)-induced EMT in HK-2 cells. miR-200 mediates the protective effects of EPO on EMT in hypoxic HK-2 cells. EPO attenuated hypoxia-induced EMT by increasing miR-200 expression via the repression of Ets-1.


Wireless energizing system for an automated implantable sensor.
The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonant frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.


Selective functionalization of the internal and the external surfaces of mesoporous silicon by liquid masking.
A general approach for selective, differential functionalization of the interior and exterior surfaces of mesoporous Si is reported. The method employs two immiscible liquids, one inert and the other chemically reactive with the porous Si nanostructure. First, a porous Si sample is prepared by electrochemical etch and then it is mildly oxidized, which places a thin layer of silicon oxide at the surface. The inner pore walls of the partially oxidized porous Si film are then infiltrated with an inert liquid (octane). The sample is then immersed in aqueous solution containing hydrogen fluoride (HF), which serves as the reactive liquid. The hydrophobic phase is retained in the interior of the porous nanostructure, and HF(aq) attacks only the exposed surfaces of the oxidized porous Si sample, generating a hydrophobic, hydrogen-terminated (Si-H) outer layer. The reaction is self-limiting due to the immiscibility of octane and water, and the extent of penetration of the Si-H surface into the porous layer is dependent on the time of exposure to HF(aq). The Si-H surface can then be modified by thermal hydrosilylation (1-dodecene or 10-bromo-1-decene) in a subsequent step, resulting in a bifunctional porous Si film containing hydrophobic pore entrances to hydrophilic inner pores. The hydrophobic dodecyl species at the mouths of the pores is found to form a barrier for molecular transport; it decreases the rate of leaching (into water) of a rhodamine test molecule that is preloaded into the sample by >8 fold.


Mindlessly Polite: A Conceptual Replication of the Emotional Seesaw Effect on Compliance and Information Processing.
Recent studies demonstrated that the sequential induction of contrasting negative and positive emotions can be used as a social influence technique. The original field experiments found that whenever a sudden change in the emotional dynamic occurs - from negative to positive or vice versa - an increase in compliant behavior and an impairment in cognitive functioning can be observed. The goal of the present experiments was a conceptual replication and extension of the results in a more controlled and counterbalanced fashion. To this aim a novel emotion induction technique was created using an outcome related expectancy violation to induce and change emotions. In a first experiment, the influence of contrasting emotions (vs. only one emotion) on compliance, message processing and information recall was assessed among 80 undergraduate students. We were able to show that a positive, then negative experience, and vice versa, led to losses in processing efficacy, not only leaving individuals momentarily vulnerable to social influence attempts, but also impairing information recall. We replicated this pattern of findings in a second experiment (N = 41). The implications of this innovative induction technique and its findings for theory and future research on the emerging field on contrasting emotions as social-influence techniques are discussed.


Systematic Review of Outcomes Reporting in Professional Baseball: A Call for Increased Validation and Consistency.
Historically, treatment efficacy of professional baseball injuries has been determined by assessing the return-to-play (RTP) rate or using patient-reported functional outcomes scores; however, these methods may not be sensitive and specific enough for elite athletes. As a consequence, performance-based statistics are increasingly being reported in the medical literature. To (1) assess how treatment efficacy is currently reported in professional baseball players; (2) examine the variability in the reporting of these measures in terms of frequency, length of time followed, and units of measure; and (3) identify any attempts to validate these performance-based statistics. Systematic review. All studies reporting treatment efficacy in professional baseball in PubMed, Embase, and Cochrane were identified. Data collected included frequency and method of reporting: RTP, functional outcomes, and performance-based statistics. Fifty-four studies met all inclusion criteria. Of these, 51 (94%) reported RTP, 12 (22%) utilized functional outcomes, and 18 (33%) provided baseball-specific performance-based statistics to assess treatment efficacy. Great variability was seen in how follow-up was defined (games, seasons, months), duration of follow-up, and which performance-based statistics were utilized. None of the studies validated these performance-based statistics, determined minimal time of follow-up needed, or assessed the baseline variability in these statistics among noninjured players. Most studies reported RTP to determine treatment efficacy, but significant variability was seen in how players were followed. Similarly, great variability was noted in the type and number of performance-based statistics utilized. Additional studies are necessary to validate these measures and determine the appropriate length of time that they should be followed. This study provides a clear overview of the current methods that are used to determine treatment efficacy in professional baseball players.


Transition to synchrony in a three-dimensional swarming model with helical trajectories.
We investigate the transition from incoherence to global collective motion in a three-dimensional swarming model of agents with helical trajectories, subject to noise and global coupling. Without noise this model was recently proposed as a generalization of the Kuramoto model and it was found that alignment of the velocities occurs discontinuously for arbitrarily small attractive coupling. Adding noise to the system resolves this singular limit and leads to a continuous transition, either to a directed collective motion or to center-of-mass rotations.


Ancient vertebrate dermal armor evolved from trunk neural crest.
Bone is an evolutionary novelty of vertebrates, likely to have first emerged as part of ancestral dermal armor that consisted of osteogenic and odontogenic components. Whether these early vertebrate structures arose from mesoderm or neural crest cells has been a matter of considerable debate. To examine the developmental origin of the bony part of the dermal armor, we have performed in vivo lineage tracing in the sterlet sturgeon, a representative of nonteleost ray-finned fish that has retained an extensive postcranial dermal skeleton. The results definitively show that sterlet trunk neural crest cells give rise to osteoblasts of the scutes. Transcriptional profiling further reveals neural crest gene signature in sterlet scutes as well as bichir scales. Finally, histological and microCT analyses of ray-finned fish dermal armor show that their scales and scutes are formed by bone, dentin, and hypermineralized covering tissues, in various combinations, that resemble those of the first armored vertebrates. Taken together, our results support a primitive skeletogenic role for the neural crest along the entire body axis, that was later progressively restricted to the cranial region during vertebrate evolution. Thus, the neural crest was a crucial evolutionary innovation driving the origin and diversification of dermal armor along the entire body axis.


Negative pressure irrigation on water use efficiency, yield and quality of Brassica chinensis L.
Water is critical to the production of crops, especially when faced with seasonal drought or freshwater scarcity. We compared the effect of negative pressure irrigation (NPI) on water use efficiency (WUE), nutrient uptake, yield and quality of Brassica chinensis L. using a greenhouse plot experiment. Three different water supply pressures (-5, -10 and -15 kPa), and a conventional irrigation (CK) treatment, were arranged in a randomized design with three replications. Our results suggest that plant height, leaf area, number of leaves and ratio of root to shoot were significantly correlated with water supply pressure. Specifically, our results show that B. chinensis L. yield was increased 50% with NPI versus CK. Water supply pressure had a significant effect on N and P nutrient uptake and no significant effect on K. The average concentration of vitamin C was greatest with -5 kPa treatment and consecutively declined. According to our results, NPI can save up to 36.8% of water used and improve WUE by 61.3% during growth of B. chinensis L. Our results suggest that the optimum irrigation management strategy is -5 kPa treatment. NPI versus CK can provide more stable irrigation water and retain soil moisture during plant growth, resulting in an increased WUE and yield with suitable water supply pressure. While our results suggest that NPI can enhance B. chinensis L. yield and perhaps also quality, future research should explore the mechanism of NPI in relation to yield and water use efficiency. © 2021 Society of Chemical Industry.


[Research and implementation of picture archiving and communication system (PACS) based on B/S mode].
In this paper, with B/S application and architecture, an integrated solution of PACS is designed, and the function and application of each part of PACS based on the architecture is introduced. The PACS based on this mode is safe, stable, easy to manage and upgrade and convenient for use in telemedicine.


Evaluation of Tear Osmolarity Changes After Photorefractive Keratectomy.
To assess tear film stability, ocular surface disease index (OSDI) score, Schirmer test value, tear film breakup time (TBUT), and tear osmolarity after photorefractive keratectomy (PRK). We enrolled 50 eyes from 25 patients who were PRK candidates (15 men, 10 women). The mean age was 31.9 ± 4.5 years. Dry eye severity was evaluated using OSDI questionnaire, TBUT, Schirmer test, and tear osmolarity preoperatively and in each postoperative follow-up visit during the 4-month follow-up period. Tear osmolarity changed from 302 ± 5.9 mOsm/L preoperatively to 308.8 ± 5.8 mOsm/L (P < 0.0001) and 304.1 ± 9.4 mOsm/L (P = 0.40) after 2 and 4 months, respectively. Schirmer test did not change significantly 4 months after PRK (P = 0.410). TBUT decreased significantly after 2 months and did not return to its preoperative value after 4 months. Subjective complaints measured by OSDI score, improved after 4 months compared with the preoperative level. Although dry eye tests (Schirmer, TBUT, and tear osmolarity) are abnormal 2 months after PRK, they returned to preoperative values after 4 months. We can conclude that post-PRK dry eye is a transient complication which will last less than 4 months with regular use of topical lubricants.


Hydrogen bond and residence dynamics of ion-water and water-water pairs in supercritical aqueous ionic solutions: dependence on ion size and density.
We have carried out a series of molecular dynamics simulations to investigate the hydrogen bond and residence dynamics of X(-)-water (X=F, Cl, and I) and pairs in aqueous solutions at a temperature of 673 K. The calculations are done at six different water densities ranging from 1.0 to 0.15 g cm(-3). The hydrogen bonds are defined by using a set of configurational criteria with respect to the anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)-oxygen-hydrogen angle for an anion(water)-water pair. The F(-)-water hydrogen bonds are found to have a longer lifetime than all other hydrogen bonds considered in the present study. The lifetime of Cl(-)-water hydrogen bonds is shorter than that of F(-)-water hydrogen bonds but longer than the lifetime of water-water hydrogen bonds. The lifetimes of I(-)-water and water-water hydrogen bonds are found to be very similar. Generally, the lifetimes of both anion-water and water-water hydrogen bonds are found to be significantly shorter than those found under ambient conditions. In addition to hydrogen bond lifetimes, we have also calculated the residence times and the orientational relaxation times of water molecules in ion(water) hydration shells and have discussed the correlations of these dynamical quantities with the observed dynamics of anion(water)-water hydrogen bonds as functions of the ion size and density of the supercritical solutions.


Response of plasma adrenal steroids to synthetic ACTH under ketoconazole in man.
We have investigated the effect of a single oral administration of 600 mg ketoconazole, an imidazole derivative used in clinical practice as an antimycotic agent, on the response of plasma adrenocortical steroids to 1-24 ACTH in 5 normal male subjects pretreated with dexamethasone. The 2 mg of dexamethasone was administered orally at 2300 h on the preceding night, and then a rapid ACTH test was started at 0830 h. After a 1 week interval, the ACTH test was repeated in the same manner under the same dexamethasone pretreatment, but 600 mg of ketoconazole was given orally at 0500 h. The absolute plasma concentration and the increase over the basal level of each steroid after ACTH were evaluated and compared in both conditions with and without ketoconazole administration. A single ingestion of ketoconazole caused a decrease in both indices of the responsiveness of plasma dehydroepiandrosterone and a rise in the plasma level of 17 alpha-hydroxypregnenolone. The response of plasma aldosterone was clearly blunted by ketoconazole administration, whereas that of plasma corticosterone was clearly increased. Ketoconazole also blocked the response of plasma cortisol with concomitantly increased responses of plasma 11-deoxycortisol and 11-deoxycorticosterone. The increased response of plasma corticosterone seemed to be likely due to the severe inhibitory action of ketoconazole on the conversion of corticosterone to aldosterone. These results imply the inhibitory effect of ketoconazole on C17-20-lyase activity and on the conversion of corticosterone to aldosterone, and suggest an inhibitory action on 11 beta-hydroxylase activity. The effects of ketoconazole on the other enzyme activities in adrenal steroid biosynthesis were also discussed.


Medicines optimisation.
What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article discussed medicines optimisation, which was defined as a patient-centred approach to safe and effective medicines use to ensure patients achieve the best possible outcomes. It emphasised that involving patients in decisions about their care will assist in ensuring they get the most from their medicines.


The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high affinity IgE receptor.
The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates with FcgammaRIIB and negatively regulates both B-cell and mast cell function. We report here that SHIP was tyrosine-phosphorylated after high affinity IgE receptor (FcepsilonRI) aggregation in rat basophilic leukemia RBL-2H3 cells. The tyrosine phosphorylation of SHIP was an early event after receptor aggregation and was present in cells deficient in the protein-tyrosine kinase Syk. Furthermore it was not secondary to the increase of intracellular calcium or the activation of protein kinase C. SHIP was precipitated by immobilized phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based activation motif (ITAM) of the beta but not the gamma subunit of the high affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with the tyrosine-phosphorylated beta subunit of FcepsilonRI could play an important role in down-regulating receptor-mediated signal transduction in mast cells. Thus, whereas the activation molecule Syk associates with the gamma subunit ITAM, the beta subunit ITAM binds the negative signaling molecule SHIP. Therefore, unlike B cells where the antigen receptor and coreceptors such as FcgammaRIIB or CD22 each recruits molecules with opposite effects, the FcepsilonRI contains subunits which recruit molecules that activate and inhibit signal transduction.


Helicobacter pylori eradication improves the quality of life regardless of the treatment outcome: A multicenter prospective cohort study.
Helicobacter pylori (Hp) eradication is recommended for improving the quality of life (QOL) of patients with epigastric symptoms, especially reflux and dyspepsia. However, no reports have investigated the improvement of QOL after the eradication of Hp irrespective of epigastric symptoms. The aim of this study was to investigate the improvement in the QOL after the eradication of Hp irrespective of epigastric symptoms, and evaluate the factors associated with an improved QOL after the eradication of Hp.This prospective cohort study was performed at 15 referral institutions from September 2013 to December 2014. The patients' QOL and epigastric symptoms were evaluated before and after the eradication of Hp using the 8-item Short-Form Health Survey (SF-8) and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease, respectively.One hundred sixty-five of 184 Hp-infected patients underwent Hp eradication treatment. The treatment was successful in 82.4% (136/165) of the cases. One hundred sixty of the 165 Hp-infected patients were eligible for inclusion in the QOL analysis. In the indices of QOL on the SF-8, the scores on both the mental component summary (MCS) and the physical component summary (PCS) were found to have significantly improved after the eradication of Hp. However, the epigastric symptoms before the eradication of Hp were not correlated with either the MCS or PCS. A low QOL value before the eradication of Hp was the factor what was most strongly associated with the improvement in the QOL.The eradication of Hp improved the QOL, regardless of the outcome of the treatment, especially in patients who had an impaired QOL before the eradication.