Application of pre-contoured anatomic locking plate for treatment of humerus split type greater tuberosity fractures: A prospective review of 68 cases with an average follow-up of 2.5 years.
Although various implants exist for 3- and 4-part proximal humerus fractures, few implants are appropriate for humerus split type greater tuberosity fractures. The goal of this study was to assess the efficacy of pre-contoured anatomic locking plate for humerus split type greater tuberosity fractures. A retrospective review of 68 patients with humerus split type greater tuberosity fractures treated with open reduction and internal fixation using anatomic locking plates between January 2014 and October 2016. Postoperatively, patient radiographs, functional results, and complications were reviewed. All patients got a mean follow-up of 30.5 months (range 14-46 months). Average fracture healing time was 9.4 weeks (range, 8-14 weeks). Overall mean Constant score was 86.8% (range, 70%-96%). The result was rated as excellent in 25 patients (Constant score: 92.1%), good in 38 patients (Constant score: 85.3%) moderate in 5 patients (Constant score: 71.8%) and poor in 0 cases. The excellent-good rate was 92.6%. No recurrence of dislocation occurred in the 30 cases with shoulder dislocation. All fractures healed without the complications of wound infection, subacromial impingement syndrome, nonunion, secondary displacement, and implant loosening. Pre-contoured anatomic locking plate is a reliable option in treating humerus split type greater tuberosity fractures as it provides stable fixation with an early return to function. The surgical technique is easy and efficient.


Flattening of the cornea after collagen crosslinking for keratoconus.
To identify preoperative parameters that may predict flattening of the keratoconic cornea after collagen crosslinking (CXL). Institut für Refraktive und Ophthalmo-Chirurgie (IROC), Zurich, Switzerland. Cohort study. Patients with verified progressive primary keratectasia received standard corneal CXL. Factors such as corrected distance visual acuity (CDVA) and Scheimpflug tomography (Pentacam) were used to follow the evolution from preoperatively to 12 months after CXL. Statistical analysis included U tests and Spearman rank correlation tests to detect risk factors for flattening of the keratoconus. The study enrolled 151 eyes of 151 patients; more than 80% completed the 12-month follow-up. The flattening rate (flattening of the maximum curvature >1.00 diopter [D]) was 37.7%. A preoperative maximum keratometry (K) reading of more than 54.00 D was identified as the only significant risk factor for this effect (odds ratio, 1.88; 95% confidence interval, 1.01-3.51). A restriction to corneas with a maximum K value greater than 54.00 D would have resulted in a significant flattening in 51% of the cases. Statistically significant flattening occurred during 1 year after CXL in more than 50% of cases when the preoperative maximum K reading was more than 54.00 D. None of the other preoperative parameters evaluated (eg, age, sex, diagnosis, CDVA, corneal shape factors) had a statistically significant impact on corneal flattening after CXL.


Cytomegalovirus ileitis with protein-losing enteropathy in an immunocompetent adult.
Symptomatic cytomegalovirus (CMV) infection in immunocompetent hosts has traditionally been considered to have a benign, self-limited course, and those who need intensive therapy are rare. Moreover, there are few reports of CMV infection with protein-losing enteropathy (PLE). We present an immunocompetent 74-year-old woman with CMV ileitis with PLE, which was diagnosed due to severe hypoalbuminemia and edema of the lower extremities. The patient was not immunocompromised, because a human immunodeficiency virus (HIV) antibody test was negative and she had not been taking immunosuppressants. Imaging tests including colonoscopy revealed ileitis with shallow widespread ulcers. 99mTc-human serum albumin (HAS-D) scintigraphy suggested a possibility of protein loss in the ileum based on selective accumulation of nuclides in the right abdomen. Histological findings of the biopsy showed ulcerative mucosa with abnormal cells, which had enlarged nuclei with intranuclear inclusion bodies, including typical Cowdry A type. In immunohistochemistry, these cells were positive for anti-CMV staining. She was successfully treated with medical treatments including intravenous injection of ganciclovir (GCV) (500 mg/day). We described an extremely rare case of CMV ileitis with PLE in an immunocompetent adult who was treated successfully with medical treatments, including GCV.


Hyperbaric nitrous oxide as a sole anesthetic agent in humans.
Nitrous oxide (N2O) has been used to produce analgesia and anesthesia for more than 100 yr. However, because of its high MAC value (1.04), general anesthesia with N2O can usually be attained only in a hyperbaric environment. Because of the sparsity of documentation for human physiologic responses to hyperbaric N2O, we studied eight male volunteers at 2 ATA (1520 mm Hg) anesthetized with N2O only for periods of 2-4 h. N2O partial pressures ranged from 836 to 1368 mm Hg. The anesthetic state was associated with tachypnea, tachycardia, increases in systemic blood pressure, mydriasis, diaphoresis, and at times, clonus and opisthotonus. A stable level of physiologic activity was difficult to maintain.


The association of prescription opioid use with incident cancer: A Surveillance, Epidemiology, and End Results-Medicare population-based case-control study.
Cancer is the second leading cause of death globally, and researchers seek to identify modifiable risk factors Over the past several decades, there has been ongoing debate whether opioids are associated with cancer development, metastasis, or recurrence. Basic science, clinical, and observational studies have produced conflicting results. The authors examined the association between prescription opioids and incident cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. A complex relation was observed between prescription opioids and incident cancer, and cancer site may be an important determinant. By using linked SEER cancer registry and Medicare claims from 2008 through 2013, a case-control study was conducted examining the relation between cancer onset and prior opioid exposure. Logistic regression was used to account for differences between cases and controls for 10 cancer sites. Of the population studied (n = 348,319), 34% were prescribed opioids, 79.5% were white, 36.9% were dually eligible (for both Medicare and Medicaid), 13% lived in a rural area, 52.7% had ≥1 comorbidity, and 16% had a smoking-related diagnosis. Patients exposed to opioids had a lower odds ratio (OR) associated with breast cancer (adjusted OR, 0.96; 95% CI, 0.92-0.99) and colon cancer (adjusted OR, 0.90; 95% CI, 0.86-0.93) compared with controls. Higher ORs for kidney cancer, leukemia, liver cancer, lung cancer, and lymphoma, ranging from lung cancer (OR, 1.04; 95% CI, 1.01-1.07) to liver cancer (OR, 1.19; 95% CI, 1.08-1.31), were present in the exposed population. The current results suggest that an association exists between prescription opioids and incident cancer and that cancer site may play an important role. These findings can direct future research on specific patient populations that may benefit or be harmed by prescription opioid exposure.


Better industrial vision testing and safety.
In no sense should an industrial vision program be considered a means of providing visual ease, comfort for off-the-job activities such as viewing television.


Prediction of giant and ideal Rashba-type splitting in ordered alloy monolayers grown on a polar surface.
A large and ideal Rashba-type spin-orbit splitting is desired for the applications of materials in spintronic devices and the detection of Majorana fermions in solids. Here, we propose an approach to achieve giant and ideal spin-orbit splittings through a combination of ordered surface alloying and interface engineering, that is, growing alloy monolayers on an insulating polar surface. We illustrate this unique strategy by means of first-principle calculations of buckled hexagonal monolayers of SbBi and PbBi supported on Al2O3(0001). Both systems display ideal Rashba-type states with giant spin-orbit splittings, characterized with energy offsets over 600 meV and momentum offsets over 0.3 Å-1, respectively. Our study thus points to an effective way of tuning spin-orbit splitting in low-dimensional materials to draw immediate experimental interest.


Separation and purification of magnoflorine, spinosin, and 6‴-feruloyspinosin from Ziziphi Spinosae Semen by high-speed counter-current chromatography.
In the study, high-speed counter-current chromatography was used for separation and purification of magnoflorine, spinosin, and 6‴-feruloyspinosin from Ziziphi Spinosae Semen. With n-butanol-ethyl acetate-water (2:3:5, v/v) as the optimum solvent system, about 75 mg of magnoflorine, 110 mg of spinosin, and 40 mg of 6‴-feruloyspinosin were isolated from 0.5 g of crude extract of Z. Spinosae Semen, with the purity of 95.7, 97.2, and 96.4%, respectively. The chemical structures were identified by MS and NMR spectroscopy. In addition, the antidepressant activity of the isolated components was evaluated by PC12 cells injury model and chronic unpredictable mild stress depression mouse model. The results showed that high-speed counter-current chromatography could be used to realize the one-time rapid preparation and separation of magnoflorine, spinosin, and 6‴-feruloyspinosin from Z. Spinosae Semen and compatibility of these isolated components has certain antidepressant activity.


A Review of the Anaerobic Digestion of Fruit and Vegetable Waste.
Fruit and vegetable waste is an ever-growing global question. Anaerobic digestion techniques have been developed that facilitate turning such waste into possible sources for energy and fertilizer, simultaneously helping to reduce environmental pollution. However, various problems are encountered in applying these techniques. The purpose of this study is to review local and overseas studies, which focus on the use of anaerobic digestion to dispose fruit and vegetable wastes, discuss the acidification problems and solutions in applying anaerobic digestion for fruit and vegetable wastes and investigate the reactor design (comparing single phase with two phase) and the thermal pre-treatment for processing raw wastes. Furthermore, it analyses the dominant microorganisms involved at different stages of digestion and suggests a focus for future studies.


Molecular modeling and simulation study of homoserine kinase as an effective leishmanial drug target.
Leishmaniasis is a tropical neglected disease that imposes major health concerns in many endemic countries worldwide and requires urgent attention to the identification of new drug targets as well as drug candidates. In the current study, we propose homoserine kinase (HSK) inhibition as a strategy to induce pathogen mortality via generating threonine deficiency. We introduce a homology-based molecular model of leishmanial HSK that appears to possess all conserved structural as well as functional features in the GHMP kinase family. Furthermore, 200 ns molecular dynamics data of the enzyme in open and closed state attempts to provide the mechanistic details involved in the substrate as well as phosphate binding to this enzyme. We discuss the structural and functional significance of movements involved in various loops (motif 1, 2, 3) and lips (upper and lower) in the transition of leishmanial HSK from closed to open state. Virtual screening data of more than 40,000 compounds from the present investigation tries to identify a few potential HSK inhibitors that possess important features to act as efficient HSK inhibitors. These compounds can be considered an effective starting point for the identification of novel drug-like scaffolds. We hope the structural wealth that is offered in this report will be utilized in designing competent experimental and therapeutic interventions for leishmaniasis management. Graphical abstract.


[Gender aspects in anesthesia : modified approach in research and treatment?].
Gender differences can have a relevant influence on the perioperative outcome as male and female patients are affected differently by adverse events, e.g. side effects of drugs. Furthermore, differences relating to specific drug effects, comorbidities and outcome after anesthesia or intensive care have been demonstrated. There seems to be a gender bias in diagnosis and therapy. While the knowledge regarding this field is still growing certain aspects have already been integrated into clinical practice: prevention of postoperative nausea and vomiting (PONV), target controlled infusion (TCI) model and male only policy with production of blood products. There is a need to study the influence of gender, age and race in order to optimize treatment towards a more individualized therapy. This article highlights already identified differences and discusses potential underlying mechanisms.


Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells.
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor or rictor enhanced rapamycin's suppression of hsBAFF-induced survivin expression and proliferation/viability in B cells. Also, PP242, an mTORC1/2 kinase inhibitor, repressed survivin expression, and cell proliferation/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Of interest, ectopic expression of constitutively active Akt (myr-Akt) or constitutively active S6K1 (S6K1-ca), or downregulation of 4E-BP1 conferred resistance to rapamycin's attenuation of hsBAFF-induced survivin expression and B-cell proliferation/viability, whereas overexpression of dominant negative Akt (dn-Akt) or constitutively hypophosphorylated 4E-BP1 (4EBP1-5A), or downregulation of S6K1, or co-treatment with Akt inhibitor potentiated the inhibitory effects of rapamycin. The findings indicate that rapamycin attenuates excessive hsBAFF-induced cell proliferation/survival via blocking mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. Our data underscore that rapamycin may be a potential agent for preventing excessive BAFF-evoked aggressive B-cell malignancies and autoimmune diseases.


Heterogeneous Do-Do model of water adsorption on carbons.
The model of water adsorption on carbons proposed five years ago by Do and Do is analyzed and improved. Following the experimental evidence that for activated carbons surface active groups differ in the value of the energy of interaction with water molecules, we propose to extend the original model to take this fundamental feature into account. For the original DD model, as well as proposed new heterogeneous one (HDDM), we develop also the corresponding isosteric enthalpy of adsorption formulas. The features of the HDDM are studied via simulations. It is shown that the new model predicts the shapes of adsorption isotherm as well as corresponding enthalpy observed for real experimental systems. Finally, the HDDM is successfully applied to description of arbitrarily chosen adsorption and enthalpy of adsorption data. Up to our knowledge, HDDM is the first model describing satisfactorily water adsorption isotherms and corresponding enthalpy data measured on different microporous activated carbons in the whole relative pressure range.


Glycobiotechnology: enzymes for the synthesis of nucleotide sugars.
Complex carbohydrates, as constituting part of glycoconjugates such as glycoproteins, glycolipids, hormones, antibiotics and other secondary metabolites, play an active role in inter- and intracellular communication. The aim of "glycobiotechnology" as an upcoming interdisciplinary research field is to develop highly efficient synthesis strategies, including in vivo and in vitro approaches, in order to bring such complex molecules into analytical and therapeutic studies. The enzymatic synthesis of glycosidic bonds by Leloir-glycosyltransferases is an efficient strategy for obtaining saccharides with absolute stereo- and regioselectivity in high yields and under mild conditions. There are, however, two obstacles hindering the realization of this process on a biotechnological scale, namely the production of recombinant Leloir-glycosyltransferases and the availability of enzymes for the synthesis of nucleotide sugars (the glycosyltransferase donor substrates). The present review surveys some synthetic targets which have attracted the interest of glycobiologists as well as recombinant expression systems which give Leloir-glycosyltransferase activities in the mU and U range. The main part summarizes publications concerned with the complex pathways of primary and secondary nucleotide sugars and the availability and use of these enzymes for synthesis applications. In this context, a survey of our work will demonstrate how enzymes from different sources and pathways can be combined for the synthesis of nucleotide deoxysugars and oligosaccharides.


Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC.
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype among breast tumors and remains a challenge even for the most current therapeutic regimes. Here, we demonstrate that oncolytic alphavirus M1 effectively kills both TNBC and non-TNBC. ER-stress and apoptosis pathways are responsible for the cell death in non-TNBC as reported in other cancer types, yet the cell death in TNBC does not depend on these pathways. Transcriptomic analysis reveals that the M1 virus activates necroptosis in TNBC, which can be pharmacologically blocked by necroptosis inhibitors. By screening a library of clinically available compounds commonly used for breast cancer treatment, we find that Doxorubicin enhances the oncolytic effect of the M1 virus by up to 100-fold specifically in TNBC in vitro, and significantly stalls the tumor growth of TNBC in vivo, through promoting intratumoral virus replication and further triggering apoptosis in addition to necroptosis. These findings reveal a novel antitumor mechanism and a new combination regimen of the M1 oncolytic virus in TNBC, and highlight a need to bridge molecular diagnosis with virotherapy.


Skin self-examination practices in a convenience sample of U.S. university students.
Melanoma skin cancer affects many young adults, yet few practice skin self-examination (SSE). We collected detailed information about young adult SSE practices, which can be used to guide the development of SSE interventions that target this age group. We surveyed 190 US university students to assess their SSE practices, including thoroughness of self-exams and reasons for not performing SSE. Just 33.2% of respondents had ever performed SSE, and only 5.8% had checked their entire body. The three most commonly cited reasons for failing to practice SSE were not knowing what to look for (55.9%), never thinking of it (54.3%), and not knowing it should be done (33.1%). Interventions to promote early melanoma detection must raise awareness about the importance of beginning SSE practice in young adulthood and conducting thorough self-exams. They should target all young adults, including those who already practice SSE.


Increased m6A-RNA methylation and FTO suppression is associated with myocardial inflammation and dysfunction during endotoxemia in mice.
Endotoxemia triggers life-threatening immune and cardiovascular response that leads to tissue damage, multi-organ failure, and death. The understanding of underlying molecular mechanisms is still evolving. N6-methyladenosine (m6A)-RNA modification plays key regulatory role in numerous biological processes. However, it remains unclear whether endotoxemia alters RNA methylation in the myocardium. In the current study, we investigated the effect of lipopolysaccharide (LPS)-induced endotoxemia on m6A-RNA methylation and its implications on myocardial inflammation and left ventricular (LV) function. Following LPS administration, mice showed increases in m6A-RNA methylation in the myocardium with a corresponding decrease in the expression of fat mass and obesity-associated protein (FTO, an m6A eraser/demethylase). The changes were associated with a significant increase in expression of myocardial inflammatory cytokine genes, such as IL-6, TNF-α, IL-1β, and reduced LV function. Moreover, rat cardiomyoblasts (H9c2) exposed to LPS showed similar changes (with increase in m6A-RNA methylation and inflammatory cytokine genes, whereas downregulation of FTO). Furthermore, methylated RNA immunoprecipitation assay showed hypermethylation and increase in the expression of IL-6 and TNF-α genes in LPS-treated H9c2 cells as compared to untreated cells. Interestingly, FTO knockdown in cardiomyocytes mimicked the above effects. Taken together, these data suggest that endotoxemia-induced m6A methylation might play a critical role in expression of cardiac proinflammatory cytokines, and modulation of m6A methylation might limit myocardial inflammation and dysfunction during endotoxemia.


Risk factors for and prognosis of carboplatin-related hypersensitivity in patients with epithelial ovarian cancer.
We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 - 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.


Effect of silica on iron oxidation and floc formation.
Silicates can greatly affect the characteristics of iron oxidation products, and thereby floc formation, in water treatment. This study investigated the effects of silicate on iron oxidation in six groundwaters from the west coast of Finland. The waters contained 13-29 mg SiO(2)/L, were soft and acidic, and had high contents of iron, manganese, and organic matter. Sample pH was adjusted to 6.9 or 7.9, and a known concentration, 0-80 mg SiO(2)/L, of silicate was added. After oxidation with hydrogen peroxide, the sample was filtered to determine the iron size fractions. The results showed that even small amounts of added silicon decreased the iron particle size. The critical silicon:iron molar ratio was 1.3-2.5, above which fine iron particles, <0.1 μm, were formed. Increasing pH weakened the effect of silicon. Addition of silicon did not affect iron that was already in oxidized form.


Synthesis and crystal structures of N-H, N-phenyl and N-benzyl-2-(4-hexyl-oxyphen-yl)benzimidazoles.
The title compounds, 2-(4-hexyl-oxyphen-yl)-1H-benzimidazole (C19H22N2O; 1), 2-(4-hexyl-oxyphen-yl)-1-phenyl-1H-benzimidazole (C25H26N2O; 2) and 1-benzyl-2-(4-hexyl-oxyphen-yl)-1H-benzimidazole (C26H28N2O; 3) were synthesized and their structures were determined by single-crystal X-ray analysis. The N-substituent at the imidazole moiety slightly affects the inter-planar angle between the 4-hexyl-oxyphenyl ring and the benzimidazole system. The unsubstituted benzimidazole (1) forms inter-molecular N-H⋯N bonds while in the crystal structures of 2 and 3, the mol-ecules are assembled only through π-π and C-H⋯π inter-actions.


Exploring new strategies for ozone-risk assessment: A dynamic-threshold case study.
Tropospheric ozone is a dangerous atmospheric pollutant for forest ecosystems when it penetrates stomata. Thresholds for ozone-risk assessment are based on accumulated stomatal ozone fluxes such as the Phytotoxic Ozone Dose (POD). In order to identify the effect of ozone on a Holm oak forest in central Italy, four flux-based ozone impact response functions were implemented and tested in a multi-layer canopy model AIRTREE and evaluated against Gross Primary Productivity (GPP) obtained from observations of Eddy Covariance fluxes of CO2. To evaluate if a clear phytotoxic threshold exists and if it changes during the year, six different detoxifying thresholds ranging between 0 and 5 nmol O3 m-2 s-1 were tested. The use of species-specific rather than more general response functions based on plant functional types (PFT) increased model accuracy (RMSE reduced by up to 8.5%). In the case of linear response functions, a threshold of 1 nmol m-2 s-2 produced the best results for simulations of the whole year, although the tolerance to ozone changed seasonally, with higher tolerance (5 nmol m-2 s-1 or no ozone impact) for Winter and Spring and lower thresholds in Summer and Fall (0-1 nmol m-2 s-1). A "dynamic threshold" obtained by extracting the best daily threshold values from a range of different simulations helped reduce model overestimation of GPP by 213 g C m-2 y-1 and reduce RMSE up to 7.7%. Finally, a nonlinear ozone correction based on manipulative experiments produced the best results when no detoxifying threshold was applied (0 nmol O3 m-2 s-1), suggesting that nonlinear functions fully account for ozone detoxification. The evidence of seasonal changes in ozone tolerance points to the need for seasonal thresholds to predict ozone damage and highlights the importance of performing more species-specific manipulative experiments to derive response functions for a broad range of plant species.


[Histotopochemical investigations on elastic membranes of blood vessels with special regard to diabetes mellitus. III. Lipids (author's transl)].
Lipids have been investigated in the light microscope with Scarlet-Blue and for the fluorescentmicroscopy with rhodamine B and sulforhodamine B. Both of these reactions gave weak results. After using nilblue-sulfate for the detecting of acid and neutral lipids the presence of acid lipids could be shown in the walls of the vessels of normoglycemic men and animals. In the asymptomatical diabetes the tinction of elastic membranes was more intensive. Both acid and neutral lipids are present in a higher concentration in this stadium of diabetes mellitus as well as in the manifest diabetes of man.


[Dental pulp reactions and pulp protection: traditional underlayers versus dentin adhesive lacquer].
The dental pulp possesses an intrinsic healing capacity, by which pulpal reactions remain initially localised; they are often completely reversible. The younger and healthier the pulp is, the greater its healing capacity will be. Only in case of bacterial infection will the sterile pulpal inflammation convert into a local necrosis of the pulpal tissue that gradually will expand apically until the whole pulp is contaminated. The profit-effect of pulpal protection by means of traditional calcium hydroxide medicaments is compared with a more modern adhesive dentin sealing. Potential pulpal response to restorative materials and procedures are reviewed. Finally, clinical guidelines for optimal pulpal protection and dentinal sealing are formulated.


Chemical constitution of polyfurfuryl alcohol investigated by FTIR and Resonant Raman spectroscopy.
The actual chemical structure of polyfurfuryl alcohol (PFA) is still uncertain in spite of several studies on the topic, variations during the polymerization processes being one reason that must be addressed. The use of a limited set of analytical techniques is often insufficient to provide an exhaustive chemical characterization. Moreover, it is still not possible to exactly determine presence and amount of each specific functional group in the polymeric structure. We employed both Fourier Transform Infrared Spectroscopy (FTIR) and Resonant Raman spectroscopy (RR), corroborated by quantum mechanically aided analysis of the experimental spectra, to infer about the chemical structure of two samples of PFAs, synthetized in different ways and appearing macroscopically different, the first one being a liquid and viscous commercial sample, the second one being a self-prepared solid and rigid sample produced following a thermosetting procedure. The vibrational spectroscopic analysis confirms the presence of differences in their chemical structures. The viscous form of PFA is mainly composed by short polymeric chains, and is characterized by the presence of isolated furfuryl alcohol and furfural residues similar to 5-hydroxymethylfurfural; the thermosetted PFA is formed by more cross-linked structures, characterized by several ketones and alkene double bonds, as well as a significant presence of Diels-Alder structures. In summary, the present study evidences how the use of both FTIR and RR spectroscopy, the latter carried out at several laser excitation wavelengths, indicates an accurate way to spectroscopically investigate complex polymers enabling to satisfactorily infer about their peculiar chemical structure.


Stimulated X-ray Resonant Raman Spectroscopy of Conical Intersections in Thiophenol.
The conical intersection dynamics of thiophenol is studied by computing the stimulated X-ray resonant Raman spectroscopy signals. The hybrid probing field is constructed of a hard X-ray narrowband femtosecond pulse combined with an attosecond broadband X-ray pulse to provide optimal spectral and temporal resolutions for electronic coherences in the level crossing region. The signal carries phase information about the valence-core electronic coupling in the vicinity of conical intersections. Two conical intersections occurring during the course of the S-H dissociation dynamics can be distinguished by their valence-core transition frequencies computed at the complete active space self-consistent field level. The X-ray pulse is tuned such that the Raman transition at the first conical intersection between 1πσ* and 11ππ* involves higher core levels, while the Raman transition at the second conical intersection between 1πσ* and S0 involves the lowest core level in the sulfur K-edge.


A stability study of an opacity standard.
Three procedures were adopted to increase the stability of the Chinese National Opacity Standard so that the change in opacity was within a range of +/- 5%.


Comparison of sandwich enzyme-linked immunoadsorbent assay and radioimmunoassay for determination of exogenous glucagon-like peptide-1(7-36)amide in plasma.
A sensitive sandwich enzyme-linked immunoadsorbent assay (ELISA) for determination of exogenous glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) in plasma samples from pharmacokinetic studies is described. The assay employs an N-terminally directed antibody and a C-terminally directed antibody. The ELISA has a working range from 10 to 500 pmol l-1, and can be applied to plasma samples from humans, dogs, pigs, minipigs, cats, rabbits, and rats. The assay was compared to a validated radioimmunoassay (RIA), employing an antibody directed against the mid-region of GLP-1. After s.c. administration of GLP-1(7-36)amide, the plasma immunoreactivity of GLP-1 (P-GLP-1-IR) measured by ELISA was markedly lower than P-GLP-1-IR measured by RIA. After HPLC fractionation of plasma samples with subsequent RIA and ELISA analyses of the fractions, this difference was shown to be due to cross reaction with biologically inactive fragments of GLP-1(7-36)amide in the RIA but not in the ELISA.


Plasmid Transfer Detection in Soil using the Inducible lPR System Fused to Eukaryotic Luciferase Genes.
We report a model system for plasmid transfer analysis using the regulated lambda phage right promoter, lPR, fused to luc and lucOR as reporter genes. We have demonstrated that the systems cI857-lPR::luc and cI857-lPR::lucOR are temperature-inducible in Escherichia coli but not in other Gram-negative bacteria analyzed, enabling detection of luminescence when plasmids were mobilized from E. coli to those Gram-negative backgrounds. Using light for the detection, we have observed plasmid transfer from E. coli harboring RK2 and R388 derived plasmids to Pseudomonas putida KT2440 (co-introduced with donors) and to indigenous microorganisms, in vitro and in nonsterile soil microcosms. The importance of nutrients for an efficient plasmid transfer in nonsterile soil microcosms has been confirmed. When plasmid transfer experiments were carried out into nonsterile soil microcosms, significant populations of indigenous transconjugants arose. This system provides efficient marker genes and avoids the use of antibiotics for the selection of transconjugants.


Restoring E-cadherin-mediated cell-cell adhesion increases PTEN protein level and stability in human breast carcinoma cells.
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well-characterized tumor suppressor that negatively regulates cell growth and survival. Despite the critical role of PTEN in cell signaling, the mechanisms of its regulation are still under investigation. We reported here that PTEN expression could be controlled by overexpression or knock-down of E-cadherin in several mammary carcinoma cell lines. Furthermore, we showed that the accumulation of PTEN protein in E-cadherin overexpressing cells was due to increased PTEN protein stability rather than the regulation of its transcription. The proteasome-dependent PTEN degradation pathway was impaired after restoring E-cadherin expression. Moreover, maintenance of E-cadherin mediated cell-cell adhesion was necessary for its regulating PTEN. Altogether, our results suggested that E-cadherin mediated cell-cell adhesion was essential for preventing the proteasome degradation of PTEN, which might explain how breast carcinoma cells which lost cell-cell contact proliferate rapidly and are prone to metastasis.


C4/5 foraminal stenosis predicts C5 palsy after expansive open-door laminoplasty.
Laminoplasty is frequently performed in cervical myelopathy patients, but can lead to unexpected postoperative C5 palsy. Although several studies have examined the pathogenesis and prevention of postoperative C5 palsy, many controversies remain and some radiological findings identified as risk factors were not correlated with our outcomes. This study sought reliable radiological findings that predict C5 palsy after laminoplasty and examined why the predictors of C5 palsy did not apply in our series. This study reviewed 116 patients who underwent open-door laminoplasty for cervical spondylotic myelopathy between January 2014 and April 2016, retrospectively. C5 palsy was defined as weakness of the deltoid muscle. We evaluated the incidence of C5 palsy, the preoperative C2-7 Cobb's angle, and Pavlov ratio at the C4/C5 level using simple cervical lateral radiographs. We also evaluated the existence of an ossified posterior longitudinal ligament, the transverse diameter of the C4/5 foramen, and increases in the anteroposterior diameter of the spinal canal at the C4/5 levels after surgery. Furthermore, a high signal intensity on T2-weighted images of the cervical spinal cord preoperatively was noted. Of the 116 patients, 16 cases were excluded and 100 cases were analyzed; postoperative C5 palsy occurred in 8 patients (8%). There were no significant differences between the two groups except the average diameter of the C4/5 foramen. A diameter of the C4/5 foramen of less than 2 mm was significantly related to C5 palsy in the binary logistic regression test. A smaller diameter of the C4/5 foramen was the only factor significantly correlated with C5 palsy after laminoplasty. The results suggest that C4/5 foraminal stenosis is one of the best predictors of C5 palsy, which might be related to ischemic/reperfusion injury of the C5 root nerve after laminoplasty.


TET2 is required for Type I IFN-mediated inhibition of bat-origin swine acute diarrhea syndrome coronavirus.
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered bat-origin coronavirus with fatal pathogenicity for neonatal piglets. There is no vaccine to prevent SADS-CoV infection or clinically approved drugs targeting SADS-CoV. Therefore, unraveling cellular factors that regulate SADS-CoV for cell entry is critical to understanding the viral transmission mechanism and provides a potential therapeutic target for SADS-CoV cure. Here, we showed that Type I interferon (IFN-I) pretreatment potently blocks SADS-CoV entry into cells using lentiviral pseudo-virions as targets whose entry is driven by the SADS-CoV Spike glycoprotein. IFN-I-mediated inhibition of SADS-CoV entry and replication was dramatically impaired in the absence of TET2. These results suggest TET2 is found to serve as a checkpoint of IFN-I-meditated inhibition on the cell entry of SADS-CoV, and our discovery might constitute a novel treatment option to combat against SADS-CoV.


What does the patient have to say? Valuing the patient experience to improve the patient journey.
Patient-reported data-satisfaction, preferences, outcomes and experience-are increasingly studied to provide excellent patient-centred care. In particular, healthcare professionals need to understand whether and how patient experience data can more pertinently inform the design of service delivery from a patient-centred perspective when compared with other indicators. This study aims to explore whether timely patient-reported data could capture relevant issues to improve the hospital patient journey. Between January and February 2019, a longitudinal survey was conducted in the orthopaedics department of a 250-bed Italian university hospital with patients admitted for surgery; the aim was to analyse the patient journey from the first outpatient visit to discharge. The same patients completed a paper-and-pencil questionnaire, which was created to collect timely preference, experience and main outcomes data, and the hospital patient satisfaction questionnaire. The first was completed at the time of admission to the hospital and at the end of hospitalisation, and the second questionnaire was completed at the end of hospitalisation. A total of 254 patients completed the three questionnaires. The results show the specific value of patient-reported data. Greater or less negative satisfaction may not reveal pathology-related needs, but patient experience data can detect important areas of improvement along the hospital journey. As clinical conditions and the context of care change rapidly within a single hospital stay for surgery, collecting data at two different moments of the patient journey enables researchers to capture areas of potential improvement in the patient journey that are linked to the context, clinical conditions and emotions experienced by the patient. By contributing to the literature on how patient-reported data could be collected and used in hospital quality improvement, this study opens the debate about the use of real-time focused data. Further studies should explore how to use patient-reported data effectively (including what the patient reports are working well) and how to improve hospital processes by profiling patients' needs and defining the appropriate methodologies to capture the experiences of vulnerable patients. These topics may offer new frontiers of research to achieve a patient-centred healthcare system.


Airway obstruction caused by penicilliosis: a case report and review of the literature.
Penicilliosis is an opportunistic infection in HIV-infected and other immunocompromised patients mostly in Southeast Asia, Southern China, Hong Kong, and Taiwan, with respiratory manifestations in about one-third of patients. We report the case of a 26-year-old non-HIV immunocompromised patient presenting with an airway obstruction caused by penicilliosis, together with a review of the literature of this rare condition.


Macrophage migration inhibitory factor activates cyclooxygenase 2-prostaglandin E2 in cultured spinal microglia.
In our previous study, peripheral inflammatory stimulation evoked production of macrophage migration inhibitory factor (MIF) in the spinal cord and found spinal microglia are the major source of MIF in this context. Given the contribution of the activated-microglia to the inflammatory neuropathy plus the role for upregulated COX 2 expression and PGE(2) production in the severity of clinical manifestations of these neuroinflammatory conditions, we herein tested the hypothesis that in vitro MIF stimulation to spinal microglia could result in an activation of COX 2-PGE(2) system by MIF-CD74 interaction. We found MIF played roles in evoking COX 2 mRNA and protein expression in a dose-dependent manner correspondingly in changes in PGE(2) level in the cultured rat microglia, but these changes could be inhibited by genetic deletion of CD74. Finally, MIF-induced COX 2-PGE(2) activation could be blocked by selective inhibitors of p44/p42 and p38 MAPKs. These data highlight MIF/CD74 interaction induces upregulation of COX 2 expression and PGE(2) secretion in primary rodent microglia, and further this effect is associated with downstream activation of p38 and p44/p42 signaling cascades, and favors the role of MIF as a novel pathway for microglia-associated neuroinflammation.


Gender identity disorder in a girl with autism--a case report.
A girl with high functioning autism who developed transsexualism is described. The literature to date has, to the authors' knowledge, not documented any similar case. The diagnosis of a coexisting psychiatric disorder in transsexualism has implications for the evaluation, prognosis, and appropriate management of the patient. The question of a possible relationship between autism and transsexualism and whether there is a predisposition to gender dysphoria in autism, is discussed.


Tumor-associated Macrophages Mediate Gefitinib Resistance in Lung Cancer through HGF/c-met Signaling Pathway.
The biological behavior of cells changes after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. In this study, we aimed to study the effects of M2 macrophages on gefitinib resistance. We polarized THP-1 cells into M0 and M2 macrophages, and conducted various experiments to investigate the effects of M2 macrophages on gefitinib resistance in lung cancer. We found that M2 macrophages promote gefitinib resistance in HCC827 and PC9 cells. In addition, we used ELISA to measure the secretion level of HGF. HGF secretion levels were significantly increased in M2 macrophages. Exogenous HGF remarkably increased the proliferation and invasion in HCC827 and PC9 cells. However, the addition of anti-HGF antibodies abolished the proliferation and invasion of both HCC827 and PC9 cells promoted by M2 macrophages. Furthermore, M2 macrophages or exogenous HGF significantly increased the expression of p-met and p- ERK in HCC827 and PC9 cells, while anti-HGF antibodies diminished the expression of p-met and p-ERK by neutralizing HGF in M2 macrophages. Our results revealed that M2 macrophages promote gefitinib resistance by activating ERK and HGF/cmet signaling pathways in HCC827 and PC9 cells. Our findings provide a new therapeutic strategy for gefitinib resistance in lung cancer.


Quantitative pulsed CEST-MRI at a clinical 3T MRI system.
The goal of this study was to quantify CEST related parameters such as chemical exchange rate and fractional concentration of exchanging protons at a clinical 3T scanner. For this purpose, two CEST quantification approaches-the AREX metric (for 'apparent exchange dependent relaxation'), and the AREX-based Ω-plot method were used. In addition, two different pulsed RF irradiation schemes, using Gaussian-shaped and spin-lock pulses, were compared. Numerical simulations as well as MRI measurements in phantoms were performed. For simulations, the Bloch-McConnell equations were solved using a two-pool exchange model. MR experiments were performed on a clinical 3T MRI scanner using a cylindrical phantom filled with creatine solution at different pH values and different concentrations. The validity of the Ω-plot method and the AREX approach using spin-lock preparation for determination of the quantitative CEST parameters was demonstrated. Especially promising results were achieved for the Ω-plot method when the spin-lock preparation was employed. Pulsed CEST at 3T could be used to quantify parameters such as exchange rate constants and concentrations of protons exchanging with free water. In the future this technique might be used to estimate the exchange rates and concentrations of biochemical substances in human tissues in vivo.


The Enigma of AHR Activation in the Skin: Interplay among Ligands, Metabolism, and Bioavailability.
AHR is expressed in a variety of skin cell types and contributes to skin homeostasis. Therapeutic targeting of AHR in dermatology was first described for the treatment of inflammatory skin diseases using coal tar ointment. In addition to therapies involving active ligands such as coal tar and tapinarof, the inhibition of AHR-dependent enzymatic activities in the skin may be an alternative approach to resolving skin inflammation.


Transcriptional activation of the mouse Mx gene by type I interferon.
Mouse cells of the Mx+ genotype accumulate Mx mRNA in response to type I interferon (IFN). Nuclear runoff experiments show that IFN stringently regulates Mx gene expression at the level of transcription. Mx mRNA synthesis peaks about 3 h after IFN treatment, and within 5 h, Mx mRNA concentration rises from undetectable levels to about 0.1% of polyadenylated RNA.


Ring models of binocular rivalry and fusion.
When similar visual stimuli are presented binocularly to both eyes, one perceives a fused single image. However, when the two stimuli are distinct, one does not perceive a single image; instead, one perceives binocular rivalry. That is, one perceives one of the stimulated patterns for a few seconds, then the other for few seconds, and so on - with random transitions between the two percepts. Most theoretical studies focus on rivalry, with few considering the coexistence of fusion and rivalry. Here we develop three distinct computational neuronal network models which capture binocular rivalry with realistic stochastic properties, fusion, and the hysteretic transition between. Each is a conductance-based point neuron model, which is multi-layer with two ocular dominance columns (L & R) and with an idealized "ring" architecture where the orientation preference of each neuron labels its location on a ring. In each model, the primary mechanism initiating binocular rivalry is cross-column inhibition, with firing rate adaptation governing the temporal properties of the transitions between percepts. Under stimulation by similar visual patterns, each of three models uses its own mechanism to overcome cross-column inhibition, and thus to prevent rivalry and allow the fusion of similar images: The first model uses cross-column feedforward inhibition from the opposite eye to "shut off" the cross-column feedback inhibition; the second model "turns on" a second layer of monocular neurons as a parallel pathway to the binocular neurons, rivaling out of phase with the first layer, and together these two pathways represent fusion; and the third model uses cross-column excitation to overcome the cross-column inhibition and enable fusion. Thus, each of the idealized ring models depends upon a different mechanism for fusion that might emerge as an underlying mechanism present in real visual cortex.


The teacher as coach: An innovative, longitudinal training for (bio)medical educators.
In order to be impactful, to support students to become resilient, adaptive, and collaborative lifelong learning professionals in an ever-changing environment requires the teachers to have a specific set of skills and abilities. Teachers who are not taught these competencies struggle empirically and cannot coach students effectively in the modern professional world. We developed a longitudinal programme for teachers, combining theory and skills training, and performed nine half-day hands-on training modules on campus. Special attention was paid to a common frame of mind, coaching techniques, and dealing with students' emotions and resistance. All 16 participating teachers indicated their learning goals beforehand and their learning outcomes afterwards. Before and after finishing the course, participants completed a questionnaire in which they evaluated their own evolving coaching competencies. In the next academic year, students of both participants and non-participants evaluated their teachers' coaching competencies. Participants experienced the added value of coaching and understood how to coach. They reported being able to focus on fostering the student's development instead of being knowledge-transferring and advising mentors. Students recognised that coaching teachers (participants) provided less advice and focused more on students' responsibility. To prepare teachers for coaching students in their professional development, early investment is recommended. A dedicated coach training programme, as outlined by us, can facilitate and stimulate the desired transition from a role-modelling, knowledge-transferring academic teacher, mentor, or adviser to a professional development coaching teacher. When translating to other curricula, we recommend to take into account the adaptation of generic content in the local learning environment.


Efficacy of hybrid therapy using prior administration of bepridil hydrochloride and cryoballoon ablation in patients with persistent atrial fibrillation.
Rhythm control before catheter ablation for persistent atrial fibrillation (PeAF) can improve clinical outcomes. We sought to investigate the efficacy of pretreatment with bepridil prior to cryoballoon ablation (CBA) with respect to clinical outcomes in patients with PeAF. We retrospectively analyzed 65 consecutive patients with PeAF who underwent CBA following pretreatment with bepridil hydrochloride (bepridil). Electrical cardioversion was additionally performed in cases involving failure of pharmacological sinus restoration before CBA. The primary endpoint was survival free from atrial tachyarrhythmia at the one-year follow-up, and the secondary endpoints were changes in P-wave morphology and left atrium diameter (LAD) before CBA. At the one-year follow-up, 51 patients (78.5%) achieved the primary endpoint (non-recurrence group). Compared to the P-wave duration (Pdur) and dispersion at the time of sinus restoration, they significantly shortened at the time of CBA in the non-recurrence group, while they did not change in the recurrence group. There were no changes in LAD in both groups. Multivariate analysis revealed that refractoriness of bepridil (p = 0.03, odds ratio = 4.72, 95% confidence interval = 1.18-18.92), and longer Pdur at admission for CBA (p = 0.003, odds ratio = 1.08, 95% confidence interval = 1.01-1.14) were independent predictors of recurrence. Rhythm control with bepridil induced electrical reverse remodeling; bepridil may improve clinical outcomes after CBA.


Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools.
Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool. We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance. High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004). We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.


Giant steps: adhesion and locomotion in theraphosid tarantulas.
Theraphosid tarantulas are large spiders that bear dense hairy adhesive pads on the distal parts of their legs: scopula and claw tufts. These structures allow them to climb on vertical smooth surfaces and contribute to prey capture. While adult females and juveniles remain most of the time in their burrows, adult males actively walk searching for females during the reproductive period. Adhesion and locomotion thus play important roles in the ecology and reproduction of these animals. In this paper, we review the current state of the knowledge on adhesion and locomotion in tarantulas, focusing on functional and evolutionary morphology.


Arsenic co-exposure potentiates benzo[a]pyrene genotoxicity.
Co-exposures to complex mixtures of arsenic and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) are common in the environment. These two environmental pollutants are carcinogenic, but the nature of their molecular interactions in the induction of cancer is not well understood. Additive or synergistic interactions have been proposed to explain why arsenic, which is not a potent mutagen itself, is comutagenic with a variety of DNA-damaging agents. We have examined the genotoxicity of BaP-arsenic mixtures. We find that exposure of mouse hepatoma Hepa-1 cells to low concentrations of arsenite increases BaP-DNA adduct levels by as much as 18-fold. This effect requires the activation of BaP by cytochrome p450 1A1 (CYP1A1), although arsenite does not alter BaP-inducible CYP1A1 enzymatic activity, suggesting that arsenite acts downstream of metabolic BaP activation. Glutathione homeostasis was important in modulating the potency of arsenite. In cells depleted of reduced glutathione, arsenite increased BaP-DNA adduct formation by an even greater degree than in cells co-treated with BaP and arsenite in control medium. Although arsenic comutagenicity has been attributed to inhibition of DNA repair, arsenite treatment did not alter adduct removal kinetics in BaP-treated cells, suggesting that mechanisms upstream of DNA repair are responsible for increased adduct levels. Concentrations of arsenite and BaP that had no measurable mutagenic effect alone, increased mutation frequency at the Hprt locus by eight-fold when given in combination, demonstrating a comutagenic response between BaP and arsenite. These results provide strong support for the positive interaction between arsenic and PAH-induced cancer observed in epidemiology studies, and help to identify additional mechanistic steps likely to be involved in arsenic comutagenesis.


ERK1/2 activation is involved in the neuroprotective action of P2Y13 and P2X7 receptors against glutamate excitotoxicity in cerebellar granule neurons.
Cerebellar granule neurons express several types of nucleotide receptors, with the metabotropic P2Y(13) and the ionotropic P2X7 being the most relevant in this model. In the present study we investigated the role of P2Y(13) and P2X7 nucleotide receptors in ERK1/2 signalling. The nucleotidic agonists 2MeSADP (2-methylthioadenosine-5'-diphosphate) for P2Y(13) and BzATP (2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate) for P2X7 receptors were coupled to ERK1/2 activation in granule neurons, being able to increase around two-fold the levels of ERK1/2 phosphorylation. These effects were sensitive to the inhibitory action of the antagonists MRS-2211 and A-438079, specific for P2Y(13) and P2X7 receptors, respectively. Although both receptor subtypes shared the same pattern of transient ERK1/2 phosphorylation, they differed in the intracellular cascades they triggered, being PI3K-dependent for P2Y(13) and calcium/calmodulin kinase II (CaMKII)-dependent for P2X7. These two different ERK-mediated pathways were involved in the neuroprotective effects displayed by both P2Y(13) and P2X7 receptors against apoptosis induced by an excitotoxic concentration of glutamate, in a similar manner to the neurotrophin, BDNF. In addition, P2Y(13) and P2X7 receptor agonists were also able to phosphorylate and activate the ERK-dependent target CREB, which could be involved in their neuroprotective effect. These results indicate that nucleotide receptors share with trophic factors the same survival routes in neurons, such as the ERK signalling route, and therefore, can contribute to the maintenance of granule neurons in conditions in which survival is being compromised.


Characterization of molecular genetics and clinicopathology in thymic MALT lymphoma.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a type of low-grade malignant B-cell lymphoma. The aim of this study was to investigate the clinicopathological characteristics of thymic MALT lymphoma. We analyzed the clinical, morphological, immunophenotypical, cytogenetic, and molecular characteristics of 11 cases of thymic MALT lymphoma. The relevant literature was also reviewed. The median age of the 11 patients was 50 (range: 33-60). There was a female predominance with a female-to-male ratio of 10:1. Three patients presented with Sjögren syndrome, autoimmune thrombocytopenia purpura, and type B1 thymoma, respectively. Microscopically, thymic MALT lymphoma was characterized by epithelium-lined cysts that were surrounded by small lymphocytes, centrocyte-like cells, and monocytoid B-cells. Plasmacytic differentiation was observed in two cases. The tumor cells expressed CD20, CD79α, and BCL2. Clonal immunoglobulin genes were detected in all 8 examined cases. Fluorescence in situ hybridization (FISH) for 18q21 was performed in 7 cases, and no translocations involving 18q21 were found. Targeted gene sequencing was performed in five cases with available DNA samples, and TNFAIP3, CARD11, IGLL5, and CCND3 mutations were identified. Thymic MALT lymphoma is a rare type of B cell malignancy with a female predominance and excellent clinical outcomes. Molecular aberrations involving the NF-κB pathway are frequent in thymic MALT lymphoma, suggesting that dysregulation of the NF-κB pathway is an important mechanism underlying the pathogenesis of thymic MALT lymphoma.


Cross section and parity-violating spin asymmetries of W± boson production in polarized p + p collisions at sqrt[s] = 500 GeV.
Large parity-violating longitudinal single-spin asymmetries A(L)(e+) = -0.86(-0.14) (+0.30) and A(L)(e-) = 0.88(-0.71) (+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p+p collisions at a center-of-mass energy of sqrt[s] = 500 GeV with the PHENIX detector at RHIC. These e± come mainly from the decay of W± and Z0 bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W± to the light quarks. The observed electron and positron yields were used to estimate W± boson production cross sections for the e± channels of σ(pp → W+ X) × BR(W+ → e+ ν(e)) = 144.1 ± 21.2(stat)(-10.3) (+3.4) (syst) ± 21.6(norm) pb, and σ(pp → W- X) × BR(W- → e- ν[over ¯](e)) = 31.7 ± 12.1(stat)(-8.2) (+10.1) (syst) ± 4.8(norm) pb.


Anti-infective-treated central venous catheters: a systematic review of randomized controlled trials.
This systematic review assesses the effect of anti-infective-treated central venous catheters (CVCs) on catheter-related bloodstream infection (CRBSI) in the acute care setting. Randomized controlled trials were retrieved from Medline and the Cochrane Library up to 15 January 2007. Two reviewers independently assessed trial quality and extracted data. Data for CRBSI were combined where appropriate, using a random effects model. The impact of the risk for CRBSI in the control group (baseline risk) on the benefit of anti-infective CVCs was studied by using meta-regression based on the binomial normal bivariate meta-analysis model. Twenty-one trials were included in the review. Mainly intensive care (IC) patients were studied. Eighteen trials showed that anti-infective CVCs reduced the risk of CRBSI. The number needed to treat (NNT) varied from 182 to 12, with baseline risks ranging from 1% to 10%. Nearly all trials had serious methodological shortcomings. Three trials comparing minocycline-rifampicin-treated catheters with antiseptic-treated catheters showed inconsistent results. One trial suggested that there is not any difference in CRBSI between heparin- and antiseptic-treated CVCs. Because the NNT is large when the baseline risk is low, the use of anti-infective-treated CVCs in the acute care setting should only be considered in situations in which background rates of CRBSI are high. The magnitude of benefit as calculated in this review should be interpreted with caution because of strong arguments in favor of a systematic overestimation of the effect. Which type of anti-infective catheter is most effective could not be established from the available data.


Targeting HIV entry through interaction with envelope glycoprotein 120 (gp120): synthesis and antiviral evaluation of 1,3,5-triazines with aromatic amino acids.
On the basis of the interesting inhibitory properties that lectins show against HIV-replication through their interaction with glycoprotein 120 (gp120), we here describe the design, synthesis, and anti-HIV evaluation of three series of 1,3,5-triazine derivatives (monomers, dimers, and trimers) functionalized with aromatic amino acids meant to mimic interactions that lectins establish with gp120. While monomers were inactive against HIV replication, dimers showed limited anti-HIV activity that is, however, considerably more significant in the trimers series, with EC(50) values in the lower μM range. These findings most likely reflect the requirement of multivalency of the 1,3,5-triazine derivatives to display anti-HIV activity, as lectins do. The pronounced anti-HIV activity (EC(50) ∼ 20 μM) is accompanied by the absence of toxicity in CEM T-cell line (CC(50) > 250 μM). Moreover, SPR experiments revealed that the prototype trimers with a central core of 2,4,6-triethylbenzene and six l-Trp or six l-Tyr residues at the periphery were efficient binders of CXCR4- and CCR5-tropic HIV-1 gp120 (estimated K(D): lower micromolar range). The collected data support the interest of this novel family of anti-HIV agents and qualify them as potential novel microbicide lead compounds.


Short-term exposure to a treated sewage effluent alters reproductive behaviour in the three-spined stickleback (Gasterosteus aculeatus).
Some UK sewage treatment work (STW) effluents have been found to contain high levels of anti-androgenic activity, but the biological significance of this activity to fish has not been determined. The aim of this study was to investigate the effects of exposure to a STW effluent with anti-androgenic activity on the reproductive physiology and behaviour of three-spined sticklebacks (Gasterosteus aculeatus). Fish were exposed to a STW effluent (50 and 100%, v/v) with a strong anti-androgenic activity (328.56±36.83 μgl(-1) flutamide equivalent, as quantified in a recombinant yeast assay containing the human androgen receptor) and a low level of oestrogenic activity (3.32±0.66 ngl(-1) oestradiol equivalent, quantified in a recombinant yeast assay containing the human oestrogen receptor) for a period of 21 days in a flow-through system in the laboratory. Levels of spiggin, an androgen-regulated protein, were not affected by the STW effluent exposure, nor were levels of vitellogenin (a biomarker of oestrogen exposure), but the reproductive behaviour of the males was impacted. Males exposed to full strength STW effluent built fewer nests and there was a significant reduction in male courtship behaviour for exposures to both the 50 and 100% STW effluent treatments compared with controls. The effect seen on the reproduction of male sticklebacks may not necessarily have been as a consequence of the endocrine active chemicals present in the STW effluent alone, but could relate to other features of the effluent, such as turbidity that can impair visual signalling important for courtship interactions. Regardless the specific causation, the data presented show that effluents from STW have an impact on reproductive behaviour in male sticklebacks which in turn affects reproductive performance/outcome. The study further highlights the use of fish behaviour as a sensitive endpoint for assessing potential effects of contaminated water bodies on fish reproduction.


Brain dynamics of recommendation-based social influence on preference change: A magnetoencephalography study.
People change their preferences when exposed to others' opinions. We examine the neural basis of how peer feedback influences an individual's recommendation behavior. In addition, we investigate if the personality trait of 'agreeableness' modulates behavioral change and neural responses. In our experiment, participants with low and high agreeableness indicated their degree of recommendation of commercial brands, while subjected to peer group feedback. The associated neural responses were recorded with concurrent magnetoencephalography. After a delay, the participants were asked to reevaluate the brands. Recommendations changed consistently with conflicting feedback only when peer recommendation was lower than the initial recommendation. On the neural level, feedback evoked neural responses in the medial frontal and lateral parietal cortices, which were stronger for conflicting peer opinions. Conflict also increased neural oscillations in 4-10 Hz and decreased oscillations in 13-30 Hz in medial frontal and parietal cortices§. The change in recommendation behavior was not different between the low and high agreeableness groups. However, the groups differed in neural oscillations in the alpha and beta bands, when recommendation matched with feedback. In addition to corroborating earlier findings on the role of conflict monitoring in feedback processing, our results suggest that agreeableness modulates neural processing of peer feedback.


Increase in the Colorectal Cancer Screening Rate by a Round-Mailed Fecal Immunochemical Testing Kit and Associated Factors in Underserved Regions of Korea: A Community-Based Intervention Study.
Postal distribution of a fecal immunochemical test (FIT) kit has been recommended as an effective method of increasing participation in colorectal cancer (CRC) screening. The present study was performed to assess the impact of the round-mailed FIT kit on screening participation in underserved regions of Korea and to identify factors related to nonparticipation. Residents were recruited from three rural regions of Korea that lack screening units for the National Cancer Screening Program. A package containing a FIT kit for stool self-sampling and a return envelope addressed to the local health center was postally distributed to each subject. Thirty days after the kits were mailed, nonresponders were reminded via telephone as the second intervention. The participation rates and odds ratios with 95% confidence intervals (CIs) for each intervention response were calculated to evaluate the effect of the interventions and factors related to screening participation in response to the interventions. CRC screening participation rates increased from 24.5% (95% CI, 21.6% to 27.4%) to 42.6% (95% CI, 39.3% to 46.0%) as a result of postal screening and increased further to 51.4% (95% CI, 48.0% to 54.9%) after the telephone reminder. After controlling for the sex, age, and household type of each subject, factors associated with poor response to postal screening were identified as low educational attainment and poor previous participation in the National Cancer Screening Program. Round-mailed FIT kits with phone call reminders were an effective intervention, nearly doubling the screening rate in underserved regions of Korea.


Joint evolution of sex ratio and reproductive group size under local mate competition with inbreeding depression.
Local mate competition (LMC) may involve some amount of inbreeding between siblings. Because sib-mating is generally accompanied by inbreeding depression, natural selection may favor a reduced rate of sib-mating, possibly affecting the evolution of sex ratio and reproductive group size. The present study theoretically investigated the evolution of these traits under LMC in the presence of inbreeding depression. When the reproductive group size evolves, the determination mechanism of sex ratio is important because the timescale of the sex ratio response to reproductive group size can affect the evolutionary process. We consider a spectrum of sex ratio determination mechanisms from purely unconditional to purely conditional, including intermediate modes with various relative strengths of unconditional and conditional effects. This analysis revealed that both the evolutionarily stable reproductive group size and ratio of males increase with higher inbreeding depression and with a larger relative strength of an unconditional effect in sex ratio determination. Unexpectedly, when the sex ratio is controlled purely conditionally, the reproductive group size cannot exceed three even under the severest level of inbreeding depression (i.e., lethal effect). The present study reveals the conditions for LMC to evolve through the analysis of the joint evolution of reproductive group size and sex ratio.


Pediatric skeletal diffusion-weighted magnetic resonance imaging, part 2: current and emerging applications.
Diffusion-weighted imaging (DWI) complements the more established T1, fluid-sensitive and gadolinium-enhanced magnetic resonance pulse sequences used to assess several pediatric skeletal pathologies. There is optimism that the technique might not just be complementary but could serve as an alternative to gadolinium and radiopharmaceuticals for several indications. As a non-contrast, free-breathing and noninvasive technique, DWI is especially valuable in children and is readily incorporated into existing MRI protocols. The indications for skeletal DWI in children include distinguishing between benign and malignant skeletal processes, initial assessment and treatment response assessment for osseous sarcomas, and assessment of inflammatory arthropathies and femoral head ischemia, among others. A notable challenge of diffusion MRI is the dynamic nature of the growing pediatric skeleton. It is important to consider the child's age when placing DWI findings in context with potential marrow pathology. This review article summarizes the current and evolving applications of DWI for assessing the pediatric skeleton, rounding off the discussion with evolving directions for further research in this realm.


Intraoperative MRI-derived volumetric ablation margins and initial correlation with local outcome after MRI-guided cryoablation of renal tumors.
To assess volumetric ablation margins derived from intraoperative pre- and post-ablation MRI after magnetic resonance imaging (MRI)-guided percutaneous cryoablation of renal tumors and explore its correlation with local treatment success. Retrospective analysis was performed on 30 patients (mean age 69y) who underwent percutaneous MRI-guided cryoablation between May 2014 and May 2020 for 32 renal tumors (size: 1.6-5.1 cm). Tumor and ice-ball volumes were segmented on intraprocedural pre- and post-ablation MR images using Software Assistant for Interventional Radiology (SAFIR) software. After MRI-MRI co-registration, the software automatically quantified the minimal treatment margin (MTM),defined as the smallest 3D distance between the tumor and ice-ball surface. Local tumor progression (LTP) after cryoablation was assessed on follow-up imaging. Median follow-up was 16 months (range: 1-58). Local control after cryoablation was achieved in 26 cases (81%) while LTP occurred in 6 (19%). The intended MTM of ≥5 mm was achieved in 3/32 (9%) cases. Median MTM was significantly smaller for cases with (- 7 mm; IQR:-10 to - 5) vs. without LTP (3 mm; IQR:2 to 4) (P < .001). All cases of LTP had a negative MTM. All negative treatment margins occurred in tumors > 3 cm. Determination of volumetric ablation margins from intraoperative MRI was feasible and may be useful in predicting local outcome after MRI-guided renal cryoablation. In our preliminary data, an intraoperative MRI-derived minimal margin extending at least 1 mm beyond the MRI-visible tumor led to local control and this was more difficult to achieve in tumors > 3 cm. Ultimately, online margin analysis may be a valuable tool to intraoperatively assess therapy success, but larger prospective studies are needed to establish a reliable threshold for clinical use.


Characterization of alpha-1-antitrypsin by isoelectric focusing on an ultrathin polyacrylamide gel layer. An economic high-resolution system for determining PiM subtypes.
Through the use of ultrathin layer polyacrylamide gel isoelectric focusing it is possible to obtain a resolution of the bands of alpha 1AT so as to be able to easily recognize all six PiM subtypes. The optimal resolution of the PiM subtypes is obtained without deforming the pattern of the Pi phenotypes. In addition to high resolution, ultrathin layer polyacrylamide gel isoelectric focusing permits a notable reduction of fees to 1/5 of the usual.


Efficacy of homeopathic intervention in subclinical hypothyroidism with or without autoimmune thyroiditis in children: an exploratory randomized control study.
The decision to treat subclinical hypothyroidism (SCH) with or without autoimmune thyroiditis (AIT) in children, presents a clinical dilemma. This study was undertaken to evaluate the efficacy of individualized homeopathy in these cases. The study is an exploratory, randomized, placebo controlled, single blind trial. Out of 5059 school children (06-18 years) screened for thyroid disorders, 537 children had SCH/AIT and 194 consented to participate. Based on primary outcome measures (TSH and/or antiTPOab) three major groups were formed: Group A - SCH + AIT (n = 38; high TSH with antiTPOab+), Group B - AIT (n = 47; normal TSH with antiTPOab+) and Group C - SCH (n = 109; only high TSH) and were further randomized to two subgroups-verum and control. Individualized homeopathy or identical placebo was given to respective subgroup. 162 patients completed 18 months of study. Baseline characteristics were similar in all the subgroups. The post treatment serum TSH (Group A and C) returned to normal limits in 85.94% of verum and 64.29% of controls (p < 0.006), while serum AntiTPOab titers (Group A and B) returned within normal limits in 70.27%of verum and 27.02%controls (p < 0.05). Eight children (10.5%) progressed to overt hypothyroidism (OH) from control group. A statistically significant decline in serum TSH values and antiTPOab titers indicates that the homeopathic intervention has not only the potential to treat SCH with or without antiTPOab but may also prevent progression to OH.


The cyclic AMP second messenger system in man: the effects of heredity, hormones, drugs, aluminum, age and disease on signal amplification.
The intracellular effects of a number of hormonal signals are mediated by the cyclic AMP second messenger system in man and the ubiquitous distribution of hormone-stimulated adenylate cyclase suggests the importance of this enzyme complex in normal aging and pathophysiological states. Various vectors including heredity, endogenous catecholamines, steroid hormones, and drugs affect the activity of hormone-stimulated adenylate cyclase in man. The effect of heredity was studied using lymphocytes obtained from monozygotic twin pairs and age and sex-matched sib pairs. Only for forskolin-stimulated activity is a significant proportion of individual variance attributable to heredity, suggesting the relative stability of the catalytic subunit. Beta-adrenergic and prostaglandin E-1 activity are "state" characteristics and their activities are controlled by environmental parameters. A significant reduction in isoproterenol-stimulated cyclic AMP accumulation between the menses and luteal phase of the menstrual cycle is observed in lymphocytes obtained from 11 female subjects. The lowest level of beta-adrenergic receptor activity is associated with the highest levels of progesterone and estradiol hormone levels in blood. Lithium at therapeutic concentrations markedly inhibits adenylate cyclase activity in platelet membranes. Moreover, marked individual differences are observed in sensitivity to lithium as determined by Dixon plot derived Ki values for 9 normal, healthy subjects. Human adenylate cyclase obtained from platelets and lymphocytes is activated by micromolar amounts of aluminum in the presence of NaF. Irreversible activation of adenylate cyclase by aluminum is suggested as a possible mechanism of this metal's neurotoxicity. The biochemical basis for the age-associated decline in beta-adrenergic responsiveness in man is discussed. Several investigations suggest a deficit at two levels in the adenylate cyclase complex: an impaired coupling of the receptor/N protein subunits and an additional lesion distal to the receptor at the level of N/C coupling. Perfusion studies with salbutamol suggest that the decline in beta-adrenergic sensitivity is general and not restricted to lymphocytes. Possible abnormalities in cyclic AMP signal amplification and recognition in various disease states is discussed. Increased prostaglandin E-1-stimulated cyclic AMP accumulation is observed in lymphocytes obtained from patients with Alzheimer's disease compared to age-matched controls and correlated with severity of the disease state.(ABSTRACT TRUNCATED AT 400 WORDS)


Nanosized flower-like ZnO synthesized by a simple hydrothermal method and applied as matrix for horseradish peroxidase immobilization for electro-biosensing.
Nanosized flower-like ZnO was synthesized by a simple hydrothermal method which is a convenient, environment friendly, inexpensive and efficient process. Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to confirm the material structure and the crystallite microstructure. Then ZnO was dispersed in the chitosan solution to form a ZnO/chitosan composite matrix for the fabrication of H2O2 biosensor. This composite combined the advantages of inorganic species (ZnO) and organic polymer (chitosan). The parameters affecting the fabrication and experimental conditions of biosensors were optimized. Using hydroquinone as the mediator, the biosensor showed a fast response of less than 5s with the linear range of 1.0x10(-5) to 1.8x10(-3) M H2O2 with a correlation coefficient of 0.995 (n=20). The detection limit of the sensor was found to be 2.0 microM, based on a signal-to-noise ratio of 3. The biosensor exhibited satisfactory reproducibility and stability and retained about 78% of its original response after 40 days storage in a phosphate buffer at 4 degrees C.


Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes.
High-grade neuroendocrine lung malignancies (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are among the most deadly lung cancer conditions with no optimal clinical management. The biological relationships between SCLC and LCNEC are still largely unknown and a current matter of debate as growing molecular data reveal high heterogeneity with potential therapeutic consequences. Here we describe murine models of high-grade neuroendocrine lung carcinomas generated by the loss of 4 tumor suppressors. In an Rbl1-null background, deletion of Rb1, Pten, and Trp53 floxed alleles after Ad-CMVcre infection in a wide variety of lung epithelial cells produces LCNEC. Meanwhile, inactivation of these genes using Ad-K5cre in basal cells leads to the development of SCLC, thus differentially influencing the lung cancer type developed. So far, a defined model of LCNEC has not been reported. Molecular and transcriptomic analyses of both models revealed strong similarities to their human counterparts. In addition, a 68Ga-DOTATOC-based molecular-imaging method provides a tool for detection and monitoring the progression of the cancer. These data offer insight into the biology of SCLC and LCNEC, providing a useful framework for development of compounds and preclinical investigations in accurate immunocompetent models.


A Philosophical Review of School Nursing Framed by the Holistic Nursing Theory of Barbara Dossey.
This article is a philosophical review of school nursing and its constructs framed by Barbara Dossey's holistic nursing theory. The author describes the application of holistic nursing theory within the school nurse's area of activity. The review suggests that holistic nursing theory can be applied in several areas of school nursing. School nurses have a multifaceted occupation that includes meetings with students, parents, and school staff. Barbara Dossey's holistic nursing theory offers the school nurse tools to deal with people's varied experiences, feelings, and needs.


Monoclonal antibodies against large oval aggregates of Aβ1-42.
Abnormal cerebral accumulation of amyloid beta protein(1-42) (Aβ(1-42)) is one of the hallmarks of Alzheimer's disease (AD). Aβ(1-42) aggregates exist in two distinct forms: fibrils that are composed of highly ordered β-sheets and amorphous aggregates that differ in size and toxicity. Here, we generated large oval aggregates (LOA) 369 ± 81 nm and 224 ± 92 nm in size on their major and minor axes, respectively, as measured by tapping-mode atomic force microscopy. LOA were produced by slow rotation of high concentrations (0.22 mM, 1.0 mg/mL) of Aβ(1-42) for 16 h at 37°C in the presence of 2.2 mM Aβ(16-20), which prevents the fibril formation, and purified with 0.22-μm filters. Analysis with thioflavin T showed that LOA have little β-sheet structure on their surfaces. Monoclonal antibodies that react with LOA, but not the fibril forms, were screened from 960 mouse hybridoma cell lines, and seven antibodies consisting of four IgG and three IgM antibodies were obtained. Four IgG monoclonal antibodies showed cross-reactivity of <10% against the monomer and fibril forms and amorphous aggregates that passed through 0.22-μm filters. Among the four antibodies, the antibody that was designated as 31-2 exhibited the highest reactivity against LOA and showed the lowest reactivity against the fibril forms. On the basis of these results, a unique epitope on the surface of LOA was suggested. The 31-2 antibody may be useful for future basic research and therapeutic applications for AD.


Liver prenylated methylated protein methyl esterase is an organophosphate-sensitive enzyme.
Prenylation and subsequent methylation are essential modifications on a significant proportion of eucaryotic proteins. Proteins such as the G-gamma subunits of G-protein coupled receptors, nuclear lamins, and guanine nucleotide-binding proteins such as Ras are prenylated and undergo methylation. Prenylated methylated protein methyl esterase (PMPMEase) readily hydrolyses the prenylated protein methyl esters, thus making this step reversible and possibly regulatory. Benzoyl-glycyl-farnesyl-cysteine methyl ester (BzGFCM) was developed as a specific PMPMEase substrate and characterized by electron spray ionization mass spectrometry (ESI-MS) to be of the calculated molecular mass. Rat liver and brain PMPMEase hydrolyzed BzGFCM, forming benzoyl-glycyl-farnesyl-cysteine (BzGFC) in a time- and concentration-dependent manner. Both enzymes cleaved BzGFCM with K(m) values of 4.58 +/- 0.30 and 25.57 +/- 2.36 microM and V(max) values of 2.21 +/- 0.03 and 0.17 +/- 0.003 nmol/min/mg, respectively. The liver enzyme eluted from a gel-filtration column as a single peak of apparent size, 89 kDa. The brain enzyme eluted as two main peaks of 53 and 890 kDa. Organophosphorus pesticides (OPs), which are suspected to be involved in human disorders such as parkinsonism, neuronal, and retinal degeneration, inhibited the liver enzyme with IC(50) values from 4.77 muM for parathion to 0.04 microM for paraoxon, respectively. Only about 25% of the brain enzyme was inhibited by 0.5-1 mM solutions of mipafox, while 0.1 and 1 mM paraoxon inhibited over 50% and 95% of the enzyme, respectively. Paraoxon is thus about 2,250 times less potent against the brain than the liver PMPMEase. BzGFCM was not hydrolyzed by various cholinesterases, indicating its specificity for PMPMEase. Perturbations in prenylated protein metabolism might play a role in noncholinergic OPs-induced toxicity, since prenylated proteins play such important roles in cell signaling, proliferation, differentiation, and apoptosis.


Restoration of fractured and hypoplastic incisors by the acid etch resin technique: a three-year report.
A total of 724 fractured and hypoplastic incisors were restored using an acid etch resin technique in combination with a newly developed "chamfer shoulder" preparation. The retention rate of the restorations, as observed over a three-year period, was 97.1% for the incisal restorations and 94.4% for the labial veneer restorations. According to evidence reported here, the use of pins for such cases is not recommended.


A novel bifunctional-group salamo-like multi-purpose dye probe based on ESIPT and RAHB effect: Distinction of cyanide and hydrazine through optical signal differential protocol.
A novel bifunctional-group multi-purpose dye probe p-TNS has been designed and synthesized. The probe p-TNS has unique excited-state intramolecular proton transfer (ESIPT) and resonance-assisted hydrogen bonding (RAHB) coupled system, was confirmed to detect cyanide and hydrazine by blocking the ESIPT effect. Cyanide can change the fluorescence of the solution from bright green to orange-red (116 nm Stokes shift), while hydrazine causes the bright green fluorescence to be quenched. The recognition mechanism of the probe p-TNS to CN- and N2H4 was proposed reasonably through spectral characterizations and theoretical calculations. Combined with theoretical calculations, it was speculated that the solvent dependence may be caused by the ICT effect in the molecule. The probe p-TNS could be prepared into test strips for the detection of cyanide and hydrazine. In addition, the probe molecule can also be used to detect trace amounts of cyanide in agricultural products, and respond to gaseous hydrazine by direct contact, indicating that the probe p-TNS has good practical application prospects. Therefore, this molecular framework provides a new way of thinking about detecting multiple target substances.


Induction of revertant fibres in the mdx mouse using antisense oligonucleotides.
Duchenne muscular dystrophy is a fatal genetic disorder caused by dystrophin gene mutations that result in premature termination of translation and the absence of functional protein. Despite the primary dystrophin gene lesion, immunostaining studies have shown that at least 50% of DMD patients, mdx mice and a canine model of DMD have rare dystrophin-positive or 'revertant' fibres. Fine epitope mapping has shown that the majority of transcripts responsible for revertant fibres exclude multiple exons, one of which includes the dystrophin mutation. The mdx mouse model of muscular dystrophy has a nonsense mutation in exon 23 of the dystrophin gene. We have shown that antisense oligonucleotides (AOs) can induce the removal of this exon, resulting in an in-frame mRNA transcript encoding a shortened but functional dystrophin protein. To emulate one exonic combination associated with revertant fibres, we target multiple exons for removal by the application of a group of AOs combined as a "cocktail". Exons 19-25 were consistently excluded from the dystrophin gene transcript using a cocktail of AOs. This corresponds to an alternatively processed gene transcript that has been sporadically detected in untreated dystrophic mouse muscle, and is presumed to give rise to a revertant dystrophin isoform. The transcript and the resultant correctly localised smaller protein were confirmed by RT-PCR, immunohistochemistry and western blot analysis. This work demonstrates the feasibility of AO cocktails to by-pass dystrophin mutation hotspots through multi-exon skipping. Multi-exon skipping could be important in expediting an exon skipping therapy to treat DMD, so that the same AO formulations may be applied to several different mutations within particular domains of the dystrophin gene.


Prevalence of Dysphonia in Children with Adenotonsillar Problems and the Impact of Surgery on Voice.
Adenotonsillar problems might affect the voices of patients with pediatric dysphonia, which is very common. This study aimed to evaluate the prevalence of dysphonia in patients with adenotonsillar problems and to demonstrate the impact of tonsillectomy and adenoidectomy (T & A) on their voice postoperatively. Single-institution retrospective study. Subjects were recruited from those children admitted for the purpose of T & A, and all underwent the auditory-perceptual assessment by speech therapists preoperatively. If children demonstrated scores >2 in the G parameter, we performed subjective (pediatric voice handicap index [pVHI], severity, talkativeness scale) and objective (Multi-Dimensional Voice Program) voice analyses preoperatively and 1 and 3 months postoperatively. Among the 1,197 patients, 91 (7.6%) patients showed dysphonia with a score >2 in the G parameter preoperatively. The follow-up voice analysis was completed in 51 and 22 patients after 1 and 3 months, respectively. Although there were no significant differences in the amount of speech preoperatively and postoperatively, the average visual analog scale score for dysphonia severity was significantly decreased at postoperative 1 month and postoperative 3 months. The average total pVHI score, jitter, shimmer, noise-to-harmonic ratio, and soft phonation index were significantly decreased at 1 and 3 months postoperatively. Subjective scores given by parents did not correlate with the acoustic parameters; however, the postoperative subjective parameters were significantly correlated with objective parameters. Voice problems were significantly improved after T & A in the short term and long term. In those with pediatric dysphonia, decreased mouth breathing and compliance with vocal hygiene would be helpful for voice improvement. 4 Laryngoscope, 131:2369-2375, 2021.


Why People Keep an Intimate Relationship : Investigating Ultimate and Proximate Reasons.
Forming long-term intimate relationships constitutes an important aspect of human nature. Within the context of an evolutionary theoretical framework, the current research has attempted to investigate what motivates people to keep an intimate relationship. Using a combination of qualitative research methods in a sample of 131 Greek-speaking participants, 58 reasons that motivated individuals to keep their intimate relationship were identified. Using quantitative research methods in a sample of 789 Greek-speaking participants who were in an intimate relationship, these reasons were classified in nine broad factors and two broader domains. Having a supporting and compatible partner with whom one shares similar goals, and with whom one has good sex and a strong emotional attachment, were rated among the most important factors motivating participants to keep their relationship. Moreover, as indicated by the domain means, participants were more strongly motivated to keep their intimate relationship if their partners had desirable attributes, such as providing them with support, and less so by their own attributes, such as fear of loneliness. Significant effects of sex, age, marital status, presence of children, and years in a relationship were found for several factors.


Effect of temperature on acoustic communication: sound production in the croaking gourami (labyrinth fishes).
Sound communication comprising the production and detection of acoustic signals is affected by ambient temperature in ectothermic animals. In the present study we investigated the effects of temperature on sound production and characteristics in the croaking gourami Trichopsis vittata, a freshwater fish from Southeast Asia possessing a highly specialized sound-generating mechanism found only in a single genus. The croaking gourami produces pulsed sounds by stretching and plucking two enhanced pectoral fin tendons during rapid pectoral fin beating. Croaking sounds typically consist of a series of double-pulsed bursts with main energies between 1 and 1.5 kHz. Sounds were recorded during dyadic contests between two males at three different temperatures (25°, 30° and 35°C). The mean dominant frequency increased with rising temperature from 1.18 to 1.33 kHz, whereas temporal characteristics decreased. The sound interval dropped from 492 to 259 ms, the burst period from 51 to 35 ms and the pulse period from 5.8 to 5.1 ms. In contrast, the number of sounds and number of bursts within a sound were not affected by temperature. The current study shows that spectral and temporal characteristics of sounds are affected in different ways by temperature in the croaking gourami, whereas the numbers of sounds and bursts remain unaffected. We conclude that acoustic communication in gouramis is affected by changes in ambient temperature.


Head motion during fMRI tasks is reduced in children and adults if participants take breaks.
Head motion remains a challenging confound in functional magnetic resonance imaging (fMRI) studies of both children and adults. Most pediatric neuroimaging labs have developed experience-based, child-friendly standards concerning e.g. the maximum length of a session or the time between mock scanner training and actual scanning. However, it is unclear which factors of child-friendly neuroimaging approaches are effective in reducing head motion. Here, we investigate three main factors including (i) time lag of mock scanner training to the actual scan, (ii) prior scan time, and (iii) task engagement in a dataset of 77 children (aged 6-13) and 64 adults (aged 18-35) using a multilevel modeling approach. In children, distributing fMRI data acquisition across multiple same-day sessions reduces head motion. In adults, motion is reduced after inside-scanner breaks. Despite these positive effects of splitting up data acquisition, motion increases over the course of a study as well as over the course of a run in both children and adults. Our results suggest that splitting up fMRI data acquisition is an effective tool to reduce head motion in general. At the same time, different ways of splitting up data acquisition benefit children and adults.