Fast algorithm for detecting community structure in networks.
Many networks display community structure--groups of vertices within which connections are dense but between which they are sparser--and sensitive computer algorithms have in recent years been developed for detecting this structure. These algorithms, however, are computationally demanding, which limits their application to small networks. Here we describe an algorithm which gives excellent results when tested on both computer-generated and real-world networks and is much faster, typically thousands of times faster, than previous algorithms. We give several example applications, including one to a collaboration network of more than 50,000 physicists.


Basic mechanisms underlying prenylamine-induced 'torsade de pointes': differences between prenylamine and fendiline due to basic actions of the isomers.
The calcium antagonists prenylamine and fendiline both bind with rather low affinity to the dihydropyridine (nifedipine) binding site. As calmodulin (CaM) antagonists, they both inhibit CaM-dependent enzymes and relax smooth muscle preparation in nearly the same concentration range. If compared with other calcium antagonists, their action on smooth muscle develops rather slowly and cannot be inhibited by the calcium agonist Bay k 8644. In contrast, basic pharmacology reveals major differences of the actions of prenylamine and fendiline in heart muscle, indicating that, after all, the change in structure close to the asymmetric carbon strongly influences the molecular action of the compounds and their respective isomers. The negative inotropic effect of racemic prenylamine is rather independent of stimulation rate, whereas fendiline preferably depresses contraction at high rate stimulation. The negative inotropic potencies are determined by the (-)-isomers, but only in the case of prenylamine the isomeric ratio of 6 reveals a considerable stereoselectivity of action. In low concentrations and preferably at low rate stimulation, (+)-prenylamine exerts a strong positive inotropic effect. At low rate stimulation, total duration of transmembrane action potential is prolonged by (+/-)- and (+)-prenylamine, but discretely shortened by (+/-)- and (+)-fendiline. At high rate stimulation, it is shortened by (+/-)- and (-)-prenylamine, but prolonged (only) at the very final repolarization level by (+/-)- and (-)-fendiline. The positive inotropic action of prenylamine and the prolongation of action potential at low stimulation rate can be interpreted as a calcium agonistic side-effect due to the action of the (+)-isomer. It seems possible that, under the condition of low heart rate, prenylamine (as reported for the calcium agonist Bay k 8644) increases the potential-dependent transmembrane calcium current. In addition, it is argued that during the long-lasting action potential, a reactivation of the calcium current induces early after-depolarizations. These effects are postulated to represent the main mechanisms triggering torsade de pointes during therapy with prenylamine. Though fendiline, from a chemical point of view, rather resembles prenylamine, its pharmacological profile is different. In particular, in regard to electrophysiology, torsade de pointes are not expected to be induced by fendiline.


From Pong to Pokemon Go, catching the essence of the Internet Gaming Disorder diagnosis.
Taking as a starting point, this commentary proposes some issues regarding the diagnosis of Internet Gaming Disorder discussed in Kuss et al. (2016). In our opinion, the confusion in DSM-5 diagnosis could be due to the weak starting point in building the criteria. The criteria such as functional impairment and stability of the dysfunctional behavior are considered. It is suggested that avatar identification, playing motivations, and types of video games should be considered for diagnosis. The diagnostic process is highly influenced by social context and the rapid development of video game industry. The commentary ends by considering the distinction between online and offline video gaming and the critical consideration of everyday behaviors as being addictive.


Remediation of spatial processing disorder (SPD).
To determine the efficacy of deficit-specific remediation for spatial processing disorder, quantify effects of remediation on functional listening, and determine if remediation is maintained. Participants had SPD, diagnosed using the Listening in Spatialised Noise-Sentences test. The LiSN and Learn software was provided as auditory training. Post-training, repeat LiSN-S testing was conducted. Questionnaires pre- and post-training acted as subjective measures of remediation. A late-outcome assessment established long-term effects of remediation. Sixteen children aged between 6;3 [years; months] and 10;0 completed between 20 and 146 training games. Post-training LiSN-S improved in measures containing spatial cues (p ≤ 0.001) by 2.0 SDs (3.6 dB) for DV90, 1.8 SDs for SV90 (3.2 dB), 1.4 SDs for spatial advantage (2.9 dB) and 1.6 SDs for total advantage (3.3 dB). Improvement was also found in the DV0 condition (1.4 dB or 0.5 SDs). Post-training changes were not significant in the talker advantage measure (1.0 dB or 0.4 SDs) or the SV0 condition (0.3 dB or 0.1 SDs). The late-outcome assessment demonstrated improvement was maintained. Subjective improvement post-remediation was observed using the parent questionnaire. Children with SPD had improved ability to utilise spatial cues following deficit-specific remediation, with the parent questionnaire sensitive to remediation. Effects of the remediation also appear to be sustained.


Humidity-controlled preparation of frozen-hydrated biological samples for cryogenic coherent x-ray diffraction microscopy.
Coherent x-ray diffraction microscopy (CXDM) has the potential to visualize the structures of micro- to sub-micrometer-sized biological particles, such as cells and organelles, at high resolution. Toward advancing structural studies on the functional states of such particles, here, we developed a system for the preparation of frozen-hydrated biological samples for cryogenic CXDM experiments. The system, which comprised a moist air generator, microscope, micro-injector mounted on a micromanipulator, custom-made sample preparation chamber, and flash-cooling device, allowed for the manipulation of sample particles in the relative humidity range of 20%-94%rh at 293 K to maintain their hydrated and functional states. Here, we report the details of the system and the operation procedure, including its application to the preparation of a frozen-hydrated chloroplast sample. Sample quality was evaluated through a cryogenic CXDM experiment conducted at BL29XUL of SPring-8. Taking the performance of the system and the quality of the sample, the system was suitable to prepare frozen-hydrated biological samples for cryogenic CXDM experiments.


Density-dependent effects on establishment of Necator americanus and Ancylostoma ceylanicum.
The relationships between the number of infective larvae (L3s) to which animals were exposed and the establishment of A. ceylanicum and N. americanus in hamsters were examined. There was no evidence of density-dependent constraints on the establishment of A. ceylanicum in the range 10-1000 larvae, but an experiment in which the range was extended to 1500 L3s gave a significant negative correlation between the magnitude of the infecting dose and percentage establishment. Even so the percentage reduction was relatively small, approximating to 0.89% per 100 larvae administered, and in practice density-dependent constrains on establishment are unlikely to affect experiments with this species in which much lower doses (< 250 L3) are generally employed. The range of doses for N. americanus L3s was smaller (10-400). Of the four experiments reported, two gave a significant reduction of establishment with increasing dose and two did not. When the data was split into low doses (< 100 L3s) and high doses (> 100 L3s), falling establishment with increasing dose was only detected in the lower dose range. There was no difference in the establishment when doses of 100 L3s were compared with 250 or 400 L3s. On balance, it was concluded that density-dependent constraints on establishment of N. americanus in hamsters were not marked and would have little significant effect on experiments utilizing fewer than 200 L3s (approximately 7.6% reduction between 10 and 200 L3s). These results are discussed in relation to host regulation of hookworm burdens.


[Henry's law constant measurement for hydrogen peroxide using oxidative decoloration of BPR].
The temperature-dependent Henry's Law Constant for hydrogen peroxide was measured. The gas phase of hydrogen peroxide from the vapor saturator collected in a cryogenic trap was analyzed by a spectrophotometric determination, based on the oxidative decoloration of BPR (bromopryogallol red) reaction with hydrogen peroxide under the catalysis of hemin. At 10 degrees C - 35 degrees C, the relationship between Henry's Law constant K(H) (mol x L(-1) x atm(-1)) of hydrogen peroxide and temperature T (K) can be expressed as ln K(H) = a/T - b, where a = 7 269+/-22, and b = 13.26+/-0.08. The standard heat of hydrogen peroxide aqueous solution is 60.43+/-0.18 kJ x K(-1) x mol(-1).


Bioremediation of hexavalent chromium by endophytic fungi; safe and improved production of Lactuca sativa L.
One of the main problems of the industrialized world is the accumulation of chromium (Cr) in soil, which is a serious threat to the crops. Complete removal of Cr from the contaminated soils poses a great challenge. However, this issue can be minimised by using plant growth promoting microbes as a bioremediation tool. In the present study, healthy plants established near the University campus in Mardan were selected for the isolation of Cr resistant endophytes. From the designated plants, 114 species of endophytic fungi were isolated. Among the 114 isolated strains, 4 strains have induced resistance in L. sativa against Cr. The strains were identified as Aspergillus fumigatus, Rhizopus sp., Penicillium radicum and Fusarium proliferatum based on ITS region (18 S rDNA) homology. The isolates have removed Cr from soil and culture media as well as bio-transformed it from highly toxic hexavalent to least toxic trivalent form, thus helped the Cr stressed L. sativa to restore its normal growth. The Rhizopus Sp. CUC23 has mainly accrued Cr and detoxified intracellularly, whereas A. fumigatus ML43 and P. radicum PL17 has detoxified up to 95% of Cr extracellularly. From the results, it is concluded that the selected endophytic strains might be used as biofertilizer for healthy and safe crop production in Cr contaminated soils.


SUMOylation in the control of cholesterol homeostasis.
SUMOylation-protein modification by the small ubiquitin-related modifier (SUMO)-affects several cellular processes by modulating the activity, stability, interactions or subcellular localization of a variety of substrates. SUMO modification is involved in most cellular processes required for the maintenance of metabolic homeostasis. Cholesterol is one of the main lipids required to preserve the correct cellular function, contributing to the composition of the plasma membrane and participating in transmembrane receptor signalling. Besides these functions, cholesterol is required for the synthesis of steroid hormones, bile acids, oxysterols and vitamin D. Cholesterol levels need to be tightly regulated: in excess, it is toxic to the cell, and the disruption of its homeostasis is associated with various disorders like atherosclerosis and cardiovascular diseases. This review focuses on the role of SUMO in the regulation of proteins involved in the metabolism of cholesterol.


Characterization of Antibacterial Cell-Free Supernatant from Oral Care Probiotic Weissella cibaria, CMU.
Recently, studies have explored the use of probiotics like the Weissella cibaria strain, CMU (oraCMU), for use as preventive dental medicine instead of chemical oral care methods. The present study was conducted to investigate the antibacterial properties of the cell-free supernatant (CFS) from this bacterium. Cell morphology using the scanning electron microscope, and the antibacterial effect of CFS under various growth conditions were evaluated. The production of hydrogen peroxide, organic acids, fatty acids, and secretory proteins was also studied. Most of the antibacterial effects of oraCMU against periodontal pathogens were found to be acid- and hydrogen peroxide-dose-dependent effects. Lactic acid, acetic acid, and citric acid were the most common organic acids. Among the 37 fatty acids, only 0.02% of oleic acid (C18:1n-9, cis) was detected. Proteomic analysis of the oraCMU secretome identified a total of 19 secreted proteins, including N-acetylmuramidase. This protein may be a potential anti-microbial agent effective against Porphyromonas gingivalis.


There is no moral authority in medicine: response to Cowdin and Tuohey.
Central to the Cowdin-Tuohey paper is the concept of a moral authority proper to medical practitioners. Much as I agree with the authors in refusing to degrade doctors to the status of mere technicians, I argue that one does not succeed in retrieving the moral dimension of medical practice by investing doctors with moral authority. I show that none of the cases brought forth by Cowdin-Tuohey really amounts to a case of moral authority. Then I try to explain why no such cases can be found. Developing an insight that is common to all the major moral thinkers in the philosophia perennis, I show that doctors are professionally competent with respect only to a part of the human good; morally wise persons are competent with respect to that which makes man good as man. I try to show why it follows that a) professional expertise has no natural tendency to pass over into moral understanding, and that b) doctor and non-doctor alike start from the same point in developing their understanding of medical morality. It follows that the authors fail in their attempt to de-center the moral magisterium of the Church by setting up centers of moral authority outside of the Church.


Generating entangled two-photon states with coincident frequencies.
It is shown that parametric down-conversion, with a short-duration pump pulse and a long nonlinear crystal that is appropriately phase matched, can produce a frequency-entangled biphoton state whose individual photons are coincident in frequency. Quantum interference experiments which distinguish this state from the familiar time-coincident biphoton state are described.


A novel binding pocket in the D2 domain of protein tyrosine phosphatase mu (PTPmu) guides AI screen to identify small molecules that modulate tumour cell adhesion, growth and migration.
Approximately 40% of people will get cancer in their lifetime in the US, and 20% are predicted to die from the condition when it is invasive and metastatic. Targeted screening for drugs that interact with proteins that drive cancer cell growth and migration can lead to new therapies. We screened molecular libraries with the AtomNet® AI-based drug design tool to identify compounds predicted to interact with the cytoplasmic domain of protein tyrosine phosphatase mu. Protein tyrosine phosphatase mu (PTPmu) is proteolytically downregulated in cancers such as glioblastoma generating fragments that stimulate cell survival and migration. Aberrant nuclear localization of PTPmu intracellular fragments drives cancer progression, so we targeted a predicted drug-binding site between the two cytoplasmic phosphatase domains we termed a D2 binding pocket. The function of the D2 domain is controversial with various proposed regulatory functions, making the D2 domain an attractive target for the development of allosteric drugs. Seventy-five of the best-scoring and chemically diverse computational hits predicted to interact with the D2 binding pocket were screened for effects on tumour cell motility and growth in 3D culture as well as in a direct assay for PTPmu-dependent adhesion. We identified two high-priority hits that inhibited the migration and glioma cell sphere formation of multiple glioma tumour cell lines as well as aggregation. We also identified one activator of PTPmu-dependent aggregation, which was able to stimulate cell migration. We propose that the PTPmu D2 binding pocket represents a novel regulatory site and that inhibitors targeting this region may have therapeutic potential for treating cancer.


Comprehensive Analysis of Key Genes and Regulatory Elements in Osteosarcoma Affected by Bone Matrix Mineral With Prognostic Values.
Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis. However, genes involved in the mineral metabolism in the microenvironment of the bone affected by osteosarcoma are, to date, largely unknown. A public data series (GSE114237) was used to identify differentially expressed genes (DEGs) between osteosarcoma cells adhering to demineralized osseous surfaces and mineralized osseous surfaces. Functional enrichment analysis of DEGs and hub genes, protein-protein interaction network of DEGs and regulatory network (miRNA-mRNA network and transcription factor (TF)-mRNA network), survival analysis of hub genes was visualized. The prognostic hub genes were considered as candidate genes and their functional predictions were analyzed. A total of 207 DEGs were mainly enriched in extracellular space and thirteen hub genes were mainly enriched in the function of epithelial to mesenchymal transition. However, out of these, only one candidate gene was found to be suitable as a candidate gene. Besides that, 297 miRNAs and 349 TFs interacting with the hub genes were screened. In conclusion, the DEGs, hub genes, miRNAs and TFs screened out in this research could contribute to comprehend the latent mechanisms in osteosarcoma affected by matrix mineral and provide potential research molecular for further study.


Design and psychometric testing of instruments to measure qualified intensive care nurses' attitudes toward obese intensive care patients.
The purpose of this pilot study was to design and test research instruments to measure qualified intensive care nurses' implicit and explicit attitudes and behavioral intentions toward obese intensive care patients. In previous studies researchers have demonstrated that some health professionals hold negative attitudes toward obese patients; however, little is known about qualified intensive care nurses' attitudes toward these patients. Our cross-sectional pilot study involved Implicit Association Tests, the Anti-fat Attitude questionnaire, an explicit bias scale comprising ratings of explicit beliefs and feelings, assessment of behavioral intentions based on vignettes, and demographic questions. Thirty qualified intensive care nurses from a general intensive care unit in Norway (80% female; age range 31-62 years) completed the study. Nurses reported implicit and explicit preferences for thin over thick patients and found obese patients lazier than normal-weight patients. Measures of behavioral intentions and anti-fat attitudes were reliable. Generally, the nurses intended to help obese patients immediately. Nevertheless, explicit anti-fat attitudes (rho = -0.49) as well as implicit anti-obese stereotypes (rho = -0.40) were negatively correlated with such intentions. Data supported satisfactory face validity, and convergent and discriminant validity within and between implicit and explicit attitudes and stereotypes. The set of research instruments were reliable, valid, and suitable tools to measure qualified intensive care nurses' implicit and explicit attitudes; however, the present findings need to be replicated in a larger-scale study.


Surface Geometry Processing: An Efficient Normal-Based Detail Representation.
With the rapid development of high-resolution 3D vision applications, the traditional way of manipulating surface detail requires considerable memory and computing time. To address these problems, we introduce an efficient surface detail processing framework in 2D normal domain, which extracts new normal feature representations as the carrier of micro geometry structures that are illustrated both theoretically and empirically in this article. Compared with the existing state of the arts, we verify and demonstrate that the proposed normal-based representation has three important properties, including detail separability, detail transferability and detail idempotence. Finally, three new schemes are further designed for geometric surface detail processing applications, including geometric texture synthesis, geometry detail transfer, and 3D surface super-resolution. Theoretical analysis and experimental results on the latest benchmark dataset verify the effectiveness and versatility of our normal-based representation, which accepts 30 times of the input surface vertices but at the same time only takes 6.5% memory cost and 14.0% running time in comparison with existing competing algorithms.


Differentiation of the emerging human pathogens Trichosporon asahii and Trichosporon asteroides from other pathogenic yeasts and moulds by using species-specific monoclonal antibodies.
The fungal genus Trichosporon contains emerging opportunistic pathogens of humans, and is the third most commonly isolated non-candidal yeast from humans. Trichosporon asahii and T. asteroides are the most important species causing disseminated disease in immunocompromised patients, while inhalation of T. asahii spores is the most important cause of summer-type hypersensitivity pneumonitis in healthy individuals. Trichosporonosis is misdiagnosed as candidiasis or cryptococcosis due to a lack of awareness and the ambiguity of diagnostic tests for these pathogens. In this study, hybridoma technology was used to produce two murine monoclonal antibodies (MAbs), CA7 and TH1, for detection and differentiation of Trichosporon from other human pathogenic yeasts and moulds. The MAbs react with extracellular antigens from T. asahii and T. asteroides, but do not recognise other related Trichosporon spp., or unrelated pathogenic yeasts and moulds including Candida, Cryptococcus, Aspergillus, Fusarium, and Scedosporium spp., or the etiologic agents of mucormycosis. Immunofluorescence and Western blotting studies show that MAb CA7, an immunoglobulin G1 (IgG1), binds to a major 60 kDa glycoprotein antigen produced on the surface of hyphae, while TH1, an immunoglobulin M (IgM), binds to an antigen produced on the surface of conidia. The MAbs were used in combination with a standard mycological growth medium (Sabouraud Dextrose Agar) to develop an enzyme-linked immunosorbent assay (ELISA) for differentiation of T. asahii from Candida albicans and Cryptococcus neoformans in single and mixed species cultures. The MAbs represent a major advance in the identification of T. asahii and T. asteroides using standard mycological identification methods.


Facile Method to Reduce Surface Defects and Trap Densities in Perovskite Photovoltaics.
Owing to improvements in film morphology, crystallization process optimization, and compositional design, the power conversion efficiency of perovskite solar cells has increased from 3.8 to 22.1% in a period of 5 years. Nearly defect-free crystalline films and slow recombination rates enable polycrystalline perovskite to boast efficiencies comparable to those of multicrystalline silicon solar cells. However, volatile low melting point components and antisolvent treatments essential for the processing of dense and smooth films often lead to surface defects that hamper charge extraction. In this study, we investigate methylammonium bromide (MABr) surface treatments on perovskite films to compensate for the loss of volatile cation during the annealing process for surface defect passivation, grain growth, and a bromide-rich top layer. This facile method did not change the phase or bandgap of perovskite films yet resulted in a significant increase in the open circuit voltages of devices. The devices with 10 mM MABr treatment show 2% improvement in absolute power conversion efficiency over the control sample.


The Effect of Calcium Pre-Rinse on Salivary Fluoride After 900 ppm Fluoride Mouthwash: A Randomized Clinical Trial.
Calcium fluoride deposit during fluoride application. Uptake and retention of fluoride by saliva depends generally on the concentration of calcium. In this study, the effect of calcium pre-rinse on salivary fluoride concentration after a 900 ppm fluoride mouthwash was investigated. This cross-over double-blind randomized clinical trial was conducted in a girls' dormitory in Zahedan University of Medical Sciences, southeast Iran. In this study, 42 female dental students were chosen using simple randomization. During the first phase, 21 subjects (group A) used fluoride rinse (F regimen) and the remaining (group B) used calcium pre-rinse followed immediately by fluoride rinse (Ca + F regimen). In the second phase, participants rinsed using the mouthwashes not previously used. Prior to each phase prophylaxis was performed and no fluoridated product was used during a two-week interval between the phases. Salivary samples were taken immediately before (baseline), 1 and 12 hours after rinsing. The salivary fluoride concentration was determined using fluoride sensitive electrode. Repeated measures ANOVA was used for statistical analysis and the significance level was set at P<0.05. There was significant difference between fluoride concentrations at different time points (P< 0.001). Significant differences were observed when the different time points of two regimens were examined. In contrast to this, the baseline before using F regimen and the baseline before using Ca + F regimen did not show any significance (P= 0.070). Pre-rinsing with calcium before fluoride is recommended because of significant increases in salivary fluoride concentration.


[Organization of surgical work in hospitals under special conditions].
A check-list consisting all the importants measures in hospital care for handling all sorts of disasters is described. In those situations the management of organization is primarily more important than medical attendance. The doctor educated in individual medicine overestimates the medical problems. In every hospital a disaster plan should be step up as a precuation. The importance of triage has been confirmed, and several aspects of its planning have been stressed. Excercise and test alarm are necessary to check the set upa organization.


Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection.
Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that Pseudomonas N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-homoserine lactone, 3-oxo-C12-HSL), but not N-butanoyl-L-homoserine lactone (C4-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C12-HSL-carrier protein conjugate on acute P. aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12-HSL-BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3 x 10(6) c.f.u. P. aeruginosa PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)-alpha in the immunized mice were significantly lower than those of control mice (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated apoptosis in macrophages in vitro. These results demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.


Resolving alternative structure determinations of indapamide using 13C solid-state NMR.
The conflict between alternative crystal structures in the Cambridge Structural Database for the diuretic drug indapamide hemihydrate (IND) has been resolved with the aid of 13C solid-state NMR. IND is seen to contain multiple distinct molecules in the asymmetric unit (Z' = 4) rather than exhibiting disorder in the orientation of sulfonamide groups. The NMR crystallographic approach is a more effective tool for distinguishing between alternative structures than naïve judgements of quality based on crystallographic refinement agreement factors.


Mouse effector functions involved in the antibody-dependent cellular cytotoxicity to xenogeneic erythrocytes.
Mouse spleen cell populations were fractionated by carbonyl iron depletion and nylon wool column separation. The fractions were tested for phagocytic and lytic activity against antibody-coated 51Cr-labeled sheep red blood cells. Carbonyl iron resistant cells had no phagocytic activity but caused lysis at a relatively slow rate. Nylon wool column nonadherent cells had a similar effect. In contrast with the slow lytic action of these cells, nylon wool adherent cells or non-carbonyl iron-treated cells had phagocytic as well as rapid lytic action. Under the conditions studied, both rapid and slow lytic functions were saturable whereas the phagocytic function was not.


An excited state ab initio and multidimensional Franck-Condon analysis of the A (1)B2 <-- X (1)A1 band system of fluorobenzene.
This work combines high level ab initio calculations with multidimensional Franck-Condon calculations to refine and augment previous assignments of the lower wavenumber region of the A (1)B(2) <-- X (1)A(1) band system of fluorobenzene. The strength of the assignment has been greatly assisted by the use of zero electron kinetic energy spectroscopy in a series of pump-probe experiments where the response of the molecule to selective excitation in specific modes prior to ionization has been studied. The net result of this analysis is the reassignment of 7 of the 12 previously assigned bands in the region below about 1000 cm(-1) using a strategy that aims to trace the origins of excited state normal modes of fluorobenzene to the well-known Wilson modes of benzene by taking full account of the Duschinsky mixing that accompanies electronic excitation. Duschinsky normal mode analyses of the ground and first excited states of fluorobenzene as well as the electronic ground state of fluorobenzene cation have shown that the common use of the benzene Wilson notation to describe normal modes of this prototypical benzene derivative is highly questionable, particularly following electronic excitation and ionization.


Genetic Algorithm for TMS Coil Position Optimization in Stroke Treatment.
Transcranial magnetic stimulation (TMS), a non-invasive technique to stimulate human brain, has been widely used in stroke treatment for its capability of regulating synaptic plasticity and promoting cortical functional reconstruction. As shown in previous studies, the high electric field (E-field) intensity around the lesion helps in the recovery of brain function, thus the spatial location and angle of coil truly matter for the significant correlation with therapeutic effect of TMS. But, the error caused by coil placement in current clinical setting is still non-negligible and a more precise coil positioning method needs to be proposed. In this study, two kinds of real brain stroke models of ischemic stroke and hemorrhagic stroke were established by inserting relative lesions into three human head models. A coil position optimization algorithm, based on the genetic algorithm (GA), was developed to search the spatial location and rotation angle of the coil in four 4 × 4 cm search domains around the lesion. It maximized the average intensity of the E-field in the voxel of interest (VOI). In this way, maximum 17.48% higher E-field intensity than that of clinical TMS stimulation was obtained. Besides, our method also shows the potential to avoid unnecessary exposure to the non-target regions. The proposed algorithm was verified to provide an optimal position after nine iterations and displayed good robustness for coil location optimization between different stroke models. To conclude, the optimized spatial location and rotation angle of the coil for TMS stroke treatment could be obtained through our algorithm, reducing the intensity and duration of human electromagnetic exposure and presenting a significant therapeutic potential of TMS for stroke.


Valence electronic properties of n-channel organic materials based on fluorinated derivatives of perylene diimides.
The valence electronic states of three kinds of fluorinated derivatives of perylene diimides, D2MFPP, D3MFPP, and D4MFPP, on Cu(110) and SiO(2)Si surface were studied by photoemission and density functional calculations. When these organic molecules were deposited on the Cu(110) and thermally oxidized SiO(2) surfaces, five well-resolved photoemission features originating from the molecules were observed. On Cu(110) surface, two emission features with pi-like character increased their binding energy with increasing the coverage of organic molecule, indicating a strong interaction between the organic molecules and Cu substrate. The density functional calculations suggest flat-lying adsorption geometry for D3MFPP and D4MFPP on Cu(110) surface.


The effectiveness of prophylactic closed incision negative pressure wound therapy compared to conventional dressings in the prevention of periprosthetic joint infection post hip and knee revision arthroplasty surgery: A systematic review.
To evaluate the effectiveness of prophylactic closed incision negative pressure wound therapy (ciNPWT) compared to conventional dressings in the prevention of periprosthetic joint infection (PJI) post hip and knee revision arthroplasty surgery. Five databases (MEDLINE, Embase., Emcare, CINAHL and Scopus) were searched with no date or language limits. Two independent reviewers assessed articles against the inclusion criteria and methodological quality of the 3 included studies. Data was extracted using a customised data tool and included the intervention, study methods and outcomes of interest. A meta-analysis was performed, and results presented in narrative form with forest plots. The three studies, one randomized control trial and two quasi-experimental studies, included 136 intervention and 228 control participants (Sample 364). The PJI rate decreased in the ciNPWT cohort compared to the conservative dressing cohort (2 [1.47%] vs 27 [11.84%]). The reoperation rate was lower in the ciNPWT cohort versus the conventional cohort (4 [2.94%] vs 35 [15.35%]). The rate of wound complications was significantly decreased in the ciNPWT cohort compared to the conventional dressing cohort (14 [10.29%] v 85 [37.28), p=<0.001). Prophylactic application of ciNPWT may be effective in reducing wound complications, PJI and reoperation post hip and knee revision arthroplasty surgery. The added cost of ciNPWT may be justified in the reduction of wound complications, PJI and reoperation. Ongoing trials determining if the prophylactic application of ciNPWT post hip and knee revision arthroplasty surgery is beneficial in preventing PJI particularly in high risk patients with additional comorbidities are warranted.


MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.
Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.


Assessing positivity and circulating levels of NS1 in samples from a 2012 dengue outbreak in Rio de Janeiro, Brazil.
Dengue virus (DENV) represents a major threat to public health worldwide. Early DENV diagnosis should not only detect the infection but also identify patients with a higher likelihood to develop severe cases. Previous studies have suggested the potential for NS1 to serve as a viral marker for dengue severity. However, further studies using different sera panels are required to confirm this hypothesis. In this context, we developed a lab-based ELISA to detect and quantitate NS1 protein from the four DENV serotypes and from primary and secondary cases. This approach was used to calculate the circulating NS1 concentration in positive samples. We also tested the NS1 positivity of DENV-positive samples according to the Platelia Dengue NS1 Ag assay. A total of 128 samples were positive for DENV infection and were classified according to the WHO guidelines. The overall NS1 positivity was 68% according to the Platelia assay, whereas all samples were NS1-positive when analyzed with our lab-based ELISA. Fifty-four samples were positive by PCR, revealing a co-circulation of DENV1 and DENV4, and the NS1 positivity for DENV4 samples was lower than that for DENV1. The circulating NS1 concentration ranged from 7 to 284 ng/mL. Our results support previous data indicating the low efficiency of the Platelia assay to detect DENV4 infection. Moreover, this work is the first to analyze NS1 antigenemia using retrospective samples from a Brazilian outbreak.


Synthesis and evaluation of multisubstrate bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase.
A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been implicated in angiogenesis and plays a significant role in tumor progression and metastasis. The presence and orientation of the phosphonate moiety (acting as a phosphate mimic) in these derivatives were critical for inhibitory activity. The most active compounds possessed a phosphonate group in an endo orientation. This was consistent with molecular modeling results that showed the endo isomer protein-ligand complex to be lower in energy than the exo complex.


MOTION PICTURE STUDIES ON DEGRANULATION OF HORSE EOSINOPHILS DURING PHAGOCYTOSIS.
Horse eosinophil function has been studied in vitro by means of phase contrast cinemicrophotography. Locomotion of horse eosinophils was inhibited by serum factors reacting with glass surfaces. Under appropriate conditions which eliminated this inhibitory effect, eosinophils moved about and ingested some particles as rapidly as did neutrophils. Eosinophils were attracted to and readily engulfed such diverse materials as yeast cell walls, foreign erythrocytes, and antigen-antibody precipitates. Specific antibody was required for phagocytosis of red cells, and greatly accelerated the uptake of yeast cell walls. Horse eosinophil granules situated adjacent to material being engulfed disrupted with discharge of granule contents into or alongside the phagocytic vacuole. Granule disruption resulted in a clear zone and deposition of amorphous, phase-dense material. A heat-labile serum factor was required for degranulation of eosinophils ingesting foreign red cells, but not for degranulation during engulfment of yeast cell walls or antigen-antibody precipitates. Horse eosinophils were incapable under these conditions of engulfing an entire human red cell. The eosinophil commonly put out a large pseudopod to surround about half the red cell, and then appeared to constrict this pseudopod distally to cut the erythrocyte in half. It is concluded that eosinophils are phagocytic cells, resembling neutrophils in many of their properties. Any specific functions of eosinophils, distinguishing them from other phagocytes, remain to be discovered.


Severe thyrotoxicosis induced by tislelizumab: a case report and literature review.
Immune checkpoint inhibitors (ICIs) have made significant breakthroughs in the treatment of a variety of malignancies. As its use increases, the unique immune-mediated toxicity profile of ICls are becoming apparent. We report a case of immune-related endocrine adverse events (irAE) in a patient with hepatocellular carcinoma treated with anti-programmed cell death protein 1 (PD-1) (tislelizumab). Although many irAEs have been reported, few cases of severe thyrotoxicosis have been described after immunotherapy in the literature. We present the case of a 49-year-old male who experienced a Grade 3 tislelizumab-related adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE5.0) and received methylprednisolone, thiamazole, and levothyroxine sodium tablets. Early identification of irAEs, risk factors, regular monitoring, use of steroids and/or immunoglobulins, and adjuvant supportive care are critical to the clinical prognosis of patients. It should be underlined that the tumor benefits of ICI therapy outweigh the risks associated with ICI-induced endocrine disorders, and ICI treatment should not be stopped or delayed except in rare cases (adrenal crisis, severe thyrotoxicosis). The familiarity of healthcare professionals with irAEs of the thyroid when thyrotoxicosis occurs is important to facilitate an effective diagnosis and appropriate treatment of this increasingly common thyroid disorder.


Combined detection of serum UL16-binding protein 2 and macrophage inhibitory cytokine-1 improves early diagnosis and prognostic prediction of pancreatic cancer.
Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ≥1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.


Thyroid cancer post radioactive iodine treatment for hyperthyroidism - case series and review of the literature.
To assess the rate of thyroid cancer and mortality rate in a cohort of patients who received RAI¹³¹ treatment for hyperthyroidism and to report the index cases' characteristics and management MATERIAL AND METHODS: A cohort of 264 patients who received RAI¹³¹ treatment for different causes of thyrotoxicosis were followed up over a period of 18 years (1996-2014) by physical exam, radiological evaluation and serial thyroid function tests. During the follow up period, three cases of thyroid cancer were identified. The prevalence of thyroid cancer was 1.136% of cases who received RAI¹³¹. The relative risk was 378.79 (95% CI: 76.8 < RR < 1868.23). The P value was < 0.0000004 and the SMR is 1.99/1000. The prevalence of thyroid cancer was 1.136% in the cohort of patients treated with RAI¹³¹. Despite the fact that no direct cause-effect relationship between RAI and thyroid cancer could be established, these cases highlights the importance of life-long surveillance of patients who receive RAI¹³¹.


The role of apurinic/apyrimidinic endonuclease DNA repair gene in endometriosis.
The altered cellular repair capacity plays a critical role in genomic instability and carcinogenesis. We aimed at evaluating the contribution of the polymorphic variant in apurinic/apyriminidinic endonuclease (APEX1) gene to its mRNA and protein levels and the risk of endometriosis. In the current case-control study, 153 endometriosis patients and 636 non-endometriosis controls were recruited. APEX1 Asp(148)Glu (rs1130409) genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). At the same time, twenty eight endometriosis tissue samples with different genotypes were examined regarding their expression levels of APEX1 mRNA and protein by quantitative reverse transcription-polymerase chain reaction (q-PCR) and western blotting, respectively. Compared with wild-type TT genotype, TG and GG genotypes of APEX1 Asp(148)Glu had a risk of endometriosis of 0.93- and 0.87-fold. The results from in vivo transcriptional (RNA) and translational (protein) level analysis revealed that the APEX1 mRNA and protein were of similar levels among the endometriosis tissues of people carrying TT, TG, or GG genotypes. There was no joint effect of APEX1 Asp(148)Glu genotype with menarche, pregnancy, smoking or alcohol drinking lifestyles on endometriosis risk. The APEX1 Asp(148)Glu genotype correlates well with its mRNA and protein expression among endometriosis patients and may not serve as a sensitive marker for prediction of endometriosis risk in Taiwan.


Taxonomic Review of Eumenes Latreille, 1802 (Hymenoptera, Vespidae, Eumeninae) from the New World.
The genus Eumenes Latreille, 1802, from the New World, is revised based on external morphology and male genitalia. New synonymy is proposed as follows: E. aureus Isely, 1917 = E. americanus de Saussure, 1852; E. bollii oregonensis Bequaert, 1838, and E. b. ehrenbergi Zavattari, 1912 = E. bollii Cresson, 1872; E. consobrinus pedalis Fox, 1894 = E. consobrinus de Saussure, 1855; E. crucifera bolliformis Viereck, 1908, E. c. nearcticus de Saussure, 1855 and E. c. stricklandi Bequaert, 1944 = E. crucifera Provancher, 1888; E. smithii belfragei Cresson, 1872 = E. smithii de Saussure, 1852; E. verticalis coloradensis Cresson, 1875, E. v. neoboreus Bequaert, 1944, E. v. tricinctus Isely, 1917 = E. verticalis Say, 1824. Eumenes flavitinctus Bohart, 1950, revised status, is no longer a subspecies of E. crucifera but elevated to specific level. Eumenes brunneus is elevated to the specific level and a new name is proposed because of homonymy, E. bequaerti Grandinete Carpenter nom. nov. An identification key for all the species of the genus from the New World is provided and the geographical distributions are updated.


Ion cum molecularly dual imprinted polymer for simultaneous removal of cadmium and salicylic acid.
Ion cum molecularly dual imprinted polymer (DMIP) was synthesized for the simultaneous removal of salicylic acid (SA) and cadmium (Cd) by suspension polymerization method using chitosan (CTS) as functional polymer, epichlorohydrin as cross-linker, and 4-hydroxy benzoic acid (4HBA) as well as Cd as organic and inorganic templates, respectively. Use of the dummy template 4HBA during the synthesis of DMIP had the advantage of creating imprinted cavities in DMIP, which depicted good uptake for SA. Scanning electron microscopy and Fourier transform infrared spectroscopy indicated successful preparation of DMIP. Particle size analysis confirmed polydispersity, and thermal and swelling studies indicated the mechanical stability in DMIP. The rebinding capacities of the DMIP for Cd and SA were found to be 38.46 and 23.81 mgg-1 , respectively, under the optimize condition of the time, dose, and concentration. Adsorption isotherm results fitted into Langmuir adsorption isotherm model with the R2 values of 0.994 and 0.995 for Cd and SA, respectively. The presence of intramolecular hydrogen bonding in SA, stability of the template-monomer complexes (CTS-SA and CTS-4HBA), and the involvement of the hydroxyl groups on DMIP for the uptake of SA has been supported by molecular modeling studies using Gaussian 03 software. The electron doublet of the amino groups of DMIP was involved for the uptake of Cd. Lower binding efficiency of DMIP for SA as compared to Cd may be due to the partial participation of hydroxyl group in cross-linking with epichlorohydrin during the synthesis of DMIP.


The type 2 CD10/neutral endopeptidase 24.11 promoter: functional characterization and tissue-specific regulation by CBF/NF-Y isoforms.
The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 ([NEP] neprilysin) functions as part of a regulatory loop to control local concentrations of peptide substrates and associated peptide-mediated signal transduction. The physiologic role of the enzyme depends on available substrates in specific organs and cell types. Although CD10/NEP is expressed on a restricted subset of normal and malignant lymphoid progenitors, the enzyme is also expressed by a variety of epithelial cells. To explore the mechanism of tissue-specific expression of this regulatory enzyme, we characterized the major (type 2) CD10/NEP promoter and identified three functionally active transcription factor binding sites (regions I to III). CBF/NF-Y binds to the inverted CCAAT box in region I, whereas a second positive and a third negative factor bind to regions II and III, respectively. Although region I is required for maximal CD10/NEP-driven luciferase activity in the examined epithelial cell lines, this region is not required for maximal activity in the evaluated lymphoid cell lines. The apparent tissue-specific differences in requirements for region I (and CBF/NF-Y) are of particular interest because lymphoid and epithelial cells express alternatively spliced versions of CBF/NF-Y that differ in biologic activity.


Task analysis of the preincision period in a pediatric operating suite: an independent observer-based study of 656 cases.
We designed this cross-sectional investigation to assess anesthesia release time (ART = patient-on-table until release for surgical preparation) and surgical preparation time (start of surgical preparation to incision) of children undergoing anesthesia and surgery (n = 656). Data collected by trained independent observers included variables such as age, ASA physical status, anesthetic technique, and placement of invasive monitoring. We found that mean ART was 11.0 +/- 9.7 min and the mean surgical preparation time was 11.1 +/- 10.0 min. Also, ART ranged from 7 +/- 7 min (for mask anesthesia) to 52 +/- 18 min (general anesthesia/endotracheal tube and invasive hemodynamic monitoring). The percentage of ART of the total case length was 15% +/- 7%, with a wide variability depending on the total case length. We also found that there is a significant variability in ART as a function of the surgical service involved (analysis of variance; P = 0.0001), ASA physical status (P = 0.0001), and age. For example, younger children had a significantly longer ART as compared with older children (P = 0.001). Room coverage ratio by the attending anesthesiologist and training level of the anesthesia resident did not impact ART (P = not significant). We conclude that ART in children undergoing surgery is highly variable and is a function of factors such as the surgical service involved, age of the child, and ASA physical status of the child. These factors should be considered when scheduling a surgical case.


Acute nasal breathing lowers diastolic blood pressure and increases parasympathetic contributions to heart rate variability in young adults.
There is growing interest in how breathing pace, pattern, and training (e.g., device-guided or -resisted breathing) affect cardiovascular health. It is unknown whether the route of breathing (nasal vs. oral) affects prognostic cardiovascular variables. Because nasal breathing can improve other physiological variables (e.g., airway dilation), we hypothesized that nasal compared with oral breathing would acutely lower blood pressure (BP) and improve heart rate variability (HRV) metrics. We tested 20 adults in this study [13 females/7 males; age: 18(1) years, median (IQR); body mass index: 23 ± 2 kg·m-2, means ± SD]. We compared variables between nasal- and oral-only breathing (random order, five min each) using paired, two-tailed t tests or Wilcoxon signed-rank paired tests with significance set to P < 0.05. We report the median (interquartile range) for diastolic BP and means ± SD for all other variables. We found that nasal breathing was associated with a lower mean BP (nasal: 84 ± 7 vs. oral: 86 ± 5 mmHg, P = 0.006, Cohen's d = 0.70) and diastolic BP [nasal: 68(8) vs. oral: 72(5) mmHg, P < 0.001, Rank-biserial correlation = 0.89] but not systolic BP (nasal: 116 ± 11 vs. oral: 117 ± 9 mmHg, P = 0.48, Cohen's d = 0.16) or heart rate (HR; nasal: 74 ± 10 vs. oral: 75 ± 8 beats·min-1, P = 0.90, Cohen's d = 0.03). We also found that nasal breathing was associated with a higher high-frequency (HF) contribution to HRV (nasal: 59 ± 19 vs. oral: 52 ± 21%, P = 0.04, Cohen's d = 0.50) and a lower low frequency-to-HF ratio at rest (nasal: 0.9 ± 0.8 vs. oral: 1.2 ± 0.9, P = 0.04, Cohen's d = 0.49). These data suggest that nasal compared with oral breathing acutely 1) lowers mean and diastolic BP, 2) does not affect systolic BP or heart rate, and 3) increases parasympathetic contributions to HRV.NEW & NOTEWORTHY There is growing interest in how breathing pace, pattern, and training (e.g., device-guided or -resisted breathing) affect prognostic cardiovascular variables. However, the potential effects of the breathing route on prognostic cardiovascular variables are unclear. These data suggest that nasal compared with oral breathing 1) lowers mean and diastolic blood pressure (BP), 2) does not affect systolic BP or heart rate (HR), and 3) increases parasympathetic contributions to heart rate variability (HRV). These data suggest that acute nasal breathing improves several prognostic cardiovascular variables.


Ultrasound evaluation of costochondral abnormalities in children presenting with anterior chest wall mass.
The purpose of this article is to summarize our experience with the use of ultrasound for evaluation of costochondral cartilage deformity in patients presenting with an anterior chest wall mass. From 2007 to 2012, we identified all patients at our tertiary care children's hospital younger than 18 years old who underwent ultrasound for a clinical indication of anterior chest wall mass of unknown cause. A pediatric radiologist reviewed all ultrasound examinations and other pertinent radiology examinations as well as prior and follow-up clinical history and determined the final clinical cause of the mass. We identified 16 patients (nine girls and seven boys; age range, 11 months to 16.1 years; mean, 7.5 years). All patients presented with a firm anterior chest wall mass. Three patients had pain. Thirteen patients had prior imaging studies, including chest radiography (n = 13), CT of the chest (n = 1), MRI of the breast (n = 1), and ultrasound of the chest wall (n = 1). In all prior studies the cause of the anterior chest wall mass was missed. Ultrasound showed an angular deformity of a single-level (n = 13) or multilevel (n = 1) costal cartilage, hypertrophy and elongation with mild angulation of the costal cartilage (n = 1), and osteochondroma (n = 1). Targeted chest ultrasound is a useful diagnostic tool in the evaluation of costochondral cartilage deformities and should be considered in children with a firm anterior chest wall mass and negative radiography.


Vasopressin receptors influencing the secretion of ACTH by the rat adenohypophysis.
The effects of selective agonists and antagonists of type 1 (V1) and type 2 (V2) vasopressin receptors on the secretion of ACTH in vitro by segments of adenohypophysial tissue and in vivo in rats pretreated with pentobarbitone and chlorpromazine were studied in the presence and absence of the 41 amino acid-containing peptide, corticotrophin-releasing factor-41 (CRF-41). The non-selective vasopressin receptor agonist, arginine vasopressin (AVP) and the V1-receptor agonist, felypressin caused dose-related increases in ACTH release in vivo and in vitro but the V2-receptor agonist, desmopressin was only weakly active in this respect. Their actions in vitro were antagonized competitively by the V1-receptor antagonist, d(C2H5)2-AVP, but were unaffected by the V2-receptor antagonist, d(CH2)5-D-Iso2-Thr4-AVP. Arginine vasopressin, felypressin and desmopressins in concentrations considerably lower than those necessary to elicit directly the release of ACTH, potentiated, in a dose-related manner, the activity of CRF-41 in vitro. The potentiating effects were not antagonized by the V2-receptor antagonist or by low concentrations of the V1-receptor antagonist. At a higher concentration, the V1-receptor antagonist reduced, but did not abolish, the potentiating effects of AVP and its analogues. However, at this concentration, it also exhibited weak intrinsic activity and, like the agonists, potentiated the response to CRF-41. The results suggest that the direct effect of AVP on ACTH release is mediated by V1-like receptors. The vasopressin receptors involved in the potentiation of CRF-41 activity appear to be different.


Comparative population structure of two dominant species, Shinkaia crosnieri (Munidopsidae: Shinkaia) and Bathymodiolus platifrons (Mytilidae: Bathymodiolus), inhabiting both deep-sea vent and cold seep inferred from mitochondrial multi-genes.
Deep-sea hydrothermal vents and cold seeps, limited environments without sunlight, are two types of extreme habitat for marine organisms. The differences between vents and cold seeps may facilitate genetic isolation and produce population heterogeneity. However, information on such chemosynthetic fauna taxa is rare, especially regarding the population diversity of species inhabiting both vents and cold seeps. In this study, three mitochondrial DNA fragments (the cytochrome c oxidase submit I (COI), cytochrome b gene (Cytb), and 16S) were concatenated as a mitochondrial concatenated dataset (MCD) to examine the genetic diversity, population structure, and demographic history of Shinkaia crosnieri and Bathymodiolus platifrons. The genetic diversity differences between vent and seep populations were statistically significant for S. crosnieri but not for B. platifrons. S. crosnieri showed less gene flow and higher levels of genetic differentiation between the vent and seep populations than B. platifrons. In addition, the results suggest that all the B. platifrons populations, but only the S. crosnieri vent populations, passed through a recent expansion or bottleneck. Therefore, different population distribution patterns for the two dominant species were detected; a pattern of population differentiation for S. crosnieri and a homogeneity pattern for B. platifrons. These different population distribution patterns were related to both extrinsic restrictive factors and intrinsic factors. Based on the fact that the two species were collected in almost identical or adjacent sampling sites, we speculated that the primary factors underlying the differences in the population distribution patterns were intrinsic. The historical demographics, dispersal ability, and the tolerance level of environmental heterogeneity are most likely responsible for the different distribution patterns.


Kappa and lambda rearrangement occur simultaneously in transformed pre-B cells.
Murine B-lineage cells can express either kappa or lambda Ig light chains. However, most of these cells express kappa protein, a phenomenon that appears to be controlled in part at the level of gene rearrangement. This feature may reflect a preference for the kappa locus by the recombinase machinery, or it may indicate that kappa rearrangement begins before lambda rearrangement. These possibilities can be distinguished by measuring the kinetics with which light chain gene rearrangement at both loci actually occurs. To this end, we have used pre-B cells transformed by temperature-sensitive mutants of Abelson virus that undergo kappa and lambda gene rearrangement when shifted to the nonpermissive temperature. Competitive PCR analyses of rearrangement kinetics demonstrate that the kappa and lambda loci rearrange at about the same time in these cells. Consistent with this, some clones isolated from cells induced for a short period of time have rearranged only the lambda locus. However, the frequency with which lambda genes are rearranged is three- to sixfold lower than that with which kappa genes rearrange. These data indicate that the recombinase machinery targets both light chain loci at the same time, but acts preferentially at the kappa locus. The reduced ability of the recombinase machinery to target the lambda locus and selection pressures occurring during B cell development probably both contribute to the preferential usage of kappa genes in normal murine B lineage cells.


Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis.
Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a therapeutic modality for severe systemic sclerosis (SSc). We set out to systematically review and meta-analyze the efficacy and safety of AHSCT in SSc. Randomized controlled trials (RCTs) and retrospective studies comparing AHSCT with standard immunosuppressive therapy were included. Of 363 titles screened from multiple databases, 15 were extracted for further investigation, and 4 met inclusion criteria (3 RCTs and 1 retrospective analysis). The control arm was monthly cyclophosphamide in all the RCTs and the majority of patients in the retrospective analysis (69%). Compared with the control, AHSCT reduced all-cause mortality (risk ratio [RR], .5 [95% confidence interval, .33 to .75]) and improved skin thickness (modified Rodnan skin score mean difference [MD], 10.62 [95% CI, -14.21 to 7.03]), forced vital capacity (MD, 9.58 [95% CI, 3.89 to 15.18]), total lung capacity (MD, 6.36 [95% CI, 1.23 to 11.49]), and quality of life (physical 36-Item Short Form Health Survey [MD, 6.99 (95% CI, 2.79 to 11.18)]). Treatment-related mortality considerably varied between trials but was overall higher with AHSCT (RR, 9.00 [95% CI, 1.57 to 51.69]). The risk of bias for studies included in the analysis was low. Overall, AHSCT reduces the risk of all-cause mortality and has properties of a disease-modifying antirheumatic treatment in SSc. Further investigation is warranted for refining patient selection and timing of transplantation.


Biomarkers as proxies for cognitive reserve: The role of high density lipoprotein cholesterol in first episode of psychosis.
The proxies used to compose cognitive reserve (CR) for patients of a first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to peripheral pathways of the central nervous system, yet despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Meanwhile, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP. We included 668 FEP patients and 217 healthy controls. Participants were assessed for sociodemographic information, years of education, employment status, premorbid IQ and biological parameters: waist circumference, hypertension, and levels of HDL, triglycerides, and glucose. The findings suggest that the years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b=0.185) and controls (r=0.31, b=0.342). We found that the CR index composed of years of education and HDL levels showed a higher explanatory power for the phenomenon than the classic CR index composed of years of education, employment status and premorbid IQ. This article proposes an objective and quantifiable method to measure CR that is more the multifactorial nature of FEP.


[Evaluation of QuEchERS methods for the analysis of 66 organophosphorus pesticide residues in vegetables by liquid chromatography-tandem mass spectrometry].
A comparison was made between the two versions of QuEChERS sample preparation method for the extraction of 66 organophosphorus pesticides (OPPS) in vegetables. The two QuEChERS methods were the original method without buffer published in 2003, and the AOAC Official Method 2007. 01 with acetate buffer. The adsorption behaviors of primary secondary amine (PSA) sorbent and C18 sorbent on the OPPS were studied. The method of after-extraction addition was used to evaluate matrix effects for OPPS in matrix of broccoli, tomato, green soybean, radish and shallot during liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. As a result, the QuEChERS method with acetate buffer gave higher and more consistent recoveries for some of OPPS. The PSA sorbent and C18 sorbent can adsorb dibrom, so the QuEChERS method was not suitable for the analysis of dibrom. The maximum matrix effects were in the extracts of broccoli during LC-MS/MS analysis. In this article, OPPS were extracted using the QuEChERS method with acetate buffer, and analysed by LC-MS/MS under the optimized conditions with monitoring 132 MS/MS transitions of precursor ions (two for each pesticide) in one single run. Recoveries for all but dibrom at fortification levels of 10, 40, 80 microg/kg in broccoli, tomato, green soybean, radish and shallot ranged from 55% to 122% with relative standard deviations of 1.6% - 18%. The limits of quantification (S/N > or = 10) were 0.1 - 8 microg/kg. Based on these results, the analytical method was proven to be highly efficient, robust and sensitive, and suitable for the monitoring of the maximum residue limits (MRLs) of 66 OPPS in vegetables.


[Endothelial cell proliferation stimulated by basic fibroblast growth factor].
To determine the influence of basic fibroblast growth factor (bFGF) on endothelial cell (EC) proliferation in vitro and its possible mechanisms, and to examine the effect of both TNP-470 and dexamethasone (Dex) on the EC proliferation induced by bFGF. Human umbilical vein endothelial cells were cultured and the proliferation of EC was quantified by a colorimetric assay using MTT reagent. The expression of nuclear factor-kappa B (NF-kappa B) and ki-67 was detected with SABC immunohistochemical method. bFGF stimulated the EC proliferation and enhanced the expression of NF-kappa B and ki-67 in nucleus; TNP-470 and Dex suppressed EC proliferation induced by bFGF, and reduced the expression of NF-kappa B and ki-67 in nucleus. The above results indicate that the possible mechanisms of EC proliferation stimulated by bFGF come from that bFGF can activate NF-kappa B to promote the synthesis of DNA and EC mitosis. TNP-470 and Dex inhibited EC proliferation stimulated by bFGF by inhibiting NF-kappa B.


Elephantiasis nostras verrucosa.
Swelling of the leg is a frequent finding in podiatric medicine. Unless the patient draws notice to the condition or the physician is diligent in asking questions and examining the extremity, the condition may be viewed as minor and given little attention. Swelling of the leg can be a clinical sign of certain systemic diseases, lymphatic and venous disorders, or other miscellaneous causes. Dermatologic consequences linked to many of these causes of swelling are well documented. What is not as well chronicled is a dramatic skin alteration associated with chronic lymphedema. This article provides an overview and a case presentation of the unusual and debilitating skin condition related to chronic lymphedema of the lower extremity known as elephantiasis nostras verrucosa.


Effectiveness of a cranberry (Vaccinium macrocarpon) preparation in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty.
Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty. Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry (Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control. Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1-93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13-60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment. Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies.


The Microbiome Colorectal Cancer Puzzle: Initiator, Propagator, and Avenue for Treatment and Research.
The human gut microbiome has an ever-increasing role in the instigation and progression of colorectal cancer (CRC). Recent investigations have focused on identifying the key causative bacterial species and the composition and structure of the microbiome as a whole that ultimately lead to tumorigenesis in the colon. Understanding the bacterial mechanisms that promote CRC provides a rich area for the development of new screening modalities and therapeutics that may improve patient outcomes. This article reviews the various mechanisms that bacteria in the gut use to induce and/or promote tumor formation, discusses the application of the microbiome in the prevention and therapy of CRC, and provides directions for future research endeavors aiming to develop a more complete understanding of this complex phenomenon.


Energy metabolism and alginate biosynthesis in Pseudomonas aeruginosa: role of the tricarboxylic acid cycle.
Infection with mucoid, alginate-producing strains of Pseudomonas aeruginosa is the leading cause of mortality among patients with cystic fibrosis. Alginate production by P. aeruginosa is not constitutive but is triggered by stresses such as starvation. The algR2 (also termed algQ) gene has been previously identified as being necessary for mucoidy; an algR2 mutant strain is unable to produce alginate when grown at 37 degrees C. We show here that the levels of phosphorylated succinyl coenzyme A synthetase (Scs) and nucleoside diphosphate kinase (Ndk), which form a complex in P. aeruginosa, are reduced in the algR2 mutant. We were able to correlate the lower level of phosphorylated Scs with a decrease in Scs activity. Western blots (immunoblots) also showed a decreased level of Ndk in the algR2 mutant, but the presence of another kinase activity sensitive to Tween 20 provides the missing Ndk function. The effect of AlgR2 on tricarboxylic acid (TCA) cycle enzymes appears to be specific for Scs, since none of the other TCA cycle enzymes measured showed a significant decrease in activity. Furthermore, the ability of the algR2 mutant to grow on TCA cycle intermediates, but not glucose, is impaired. These data indicate that AlgR2 is responsible for maintaining proper operation of the TCA cycle and energy metabolism.


[Meaning of ghrelin and leptin in gastrointestinal tract diseases].
Ghrelin and leptin are newly discovered, still very mysterious, hormones. Beside the energy balance, they regulate endocrine and immune system, growth and maturate processes. Fluctuations of both hormones concentration are observed in many gastrointestinal tract diseases. In this publication is presented current knowledge about meaning ghrelin and leptin in choosen diseases, like malabsorption syndromes, inflammatory diseases and tumors of gastrointestinal tract.


CC3/TIP30 regulates metabolic adaptation of tumor cells to glucose limitation.
CC3/TIP30 is a metastasis and tumor suppressor, with reduced or absent expression in a variety of aggressive tumors. Overexpression of CC3 in tumor cells predisposes them to apoptosis in response to different death signals. We found that silencing of CC3 expression does not increase apoptotic resistance of cells. However, it strongly improves survival of tumor cells in response to glucose limitation. HeLa cells with silenced CC3 survive long-term in low glucose, and, in comparison to control HeLa cells, show superior metabolic adaptation to glucose limitation. First, unlike the parental HeLa cells, HeLa with silenced CC3 activate and maintain high levels of mitochondrial respiration that is critical for their ability to thrive in low glucose. Second, silencing of CC3 leads to higher expression levels of mitochondrial proteins in respiration complexes when cells are continuously cultured in limiting glucose. Third, HeLa cells with silenced CC3 maintain higher levels of c-MYC and the M2 isoform of pyruvate kinase in low glucose, contributing to more efficient glycolysis. Fourth, HeLa cells with silenced CC3 fail to fully activate AMPK in response to glucose limitation. Inhibition of AMPK, either pharmacologic or via siRNA, protects control HeLa cells from death in low glucose. The metabolic flexibility acquired by cells after silencing of CC3 could be directly relevant to the development of metastatic and aggressive human tumors that frequently have low or absent expression of CC3.


Antibiotic control of Mycoplasma in tissue culture.
Seven of eight strains of Mycoplasma (PPLO) were found to be sensitive to the deoxystreptamines, certain macrolides, and the tetracyclines. These antibiotics are relative noncytotoxic. Kanamycin and tetracycline were useful in eliminating PPLO (pleuropneumonia-like organisms) strain Squibb no. 1 from a HeLa cell line which was deliberately contaminated with PPLO. Repeated exposure of M. laidlawii type B cells to neomycin resulted in a 50-fold increase in resistance, and the resistant strain was also resistant to gentamicin, kanamycin, neomycin, and paromomycin. A tetracycline-resistant strain of this culture was found to be resistant to 7-chlortetracycline, 7-chlor-6-demethyltetracycline, and 5-hydroxytetracycline. One PPLO strain, Squibb no. 2, derived from a contaminated HeLa cell culture, was resistant to all antibiotics studied.


Evaluating waiting time effect on health outcomes at admission: a prospective randomized study on patients with osteoarthritis of the knee joint.
To evaluate the effect of waiting on health-related quality of life (HRQoL), pain and physical function in patients awaiting primary total knee replacement (TKR) due to osteoarthritis. Some 438 patients awaiting TKR were randomized to a short waiting time (WT) group (< or =3 months) or a non-fixed WT group. In the final assessment, 310 patients (213 women) with a mean age of 68 years were included. HRQoL was measured on being placed on the waiting list and again at hospital admission using the generic 15D. Patients' self-report pain and physical function were evaluated using a scale modified from the Knee Society Clinical Rating System. The median WTs for patients with short and non-fixed WT were 73 days (range 8-600 days) and 266 days (range 28-818 days), respectively. At admission, as assessed by the intention-to-treat analysis, there were no statistically significant differences between the groups in the 15D total score and disease-specific pain and function. Our study showed that longer WT did not result in worse pre-operative HRQoL.


Expression of CdDHN4, a Novel YSK2-Type Dehydrin Gene from Bermudagrass, Responses to Drought Stress through the ABA-Dependent Signal Pathway.
Dehydrin improves plant resistance to many abiotic stresses. In this study, the expression profiles of a dehydrin gene, CdDHN4, were estimated under various stresses and abscisic acid (ABA) treatments in two bermudagrasses (Cynodon dactylon L.): Tifway (drought-tolerant) and C299 (drought-sensitive). The expression of CdDHN4 was up-regulated by high temperatures, low temperatures, drought, salt and ABA. The sensitivity of CdDHN4 to ABA and the expression of CdDHN4 under drought conditions were higher in Tifway than in C299. A 1239-bp fragment, CdDHN4-P, the partial upstream sequence of the CdDHN4 gene, was cloned by genomic walking from Tifway. Bioinformatic analysis showed that the CdDHN4-P sequence possessed features typical of a plant promoter and contained many typical cis elements, including a transcription initiation site, a TATA-box, an ABRE, an MBS, a MYC, an LTRE, a TATC-box and a GT1-motif. Transient expression in tobacco leaves demonstrated that the promoter CdDHN4-P can be activated by ABA, drought and cold. These results indicate that CdDHN4 is regulated by an ABA-dependent signal pathway and that the high sensitivity of CdDHN4 to ABA might be an important mechanism enhancing the drought tolerance of bermudagrass.


Cardioprotective role of APIP in myocardial infarction through ADORA2B.
In ischemic human hearts, the induction of adenosine receptor A2B (ADORA2B) is associated with cardioprotection against ischemic heart damage, but the mechanism underlying this association remains unclear. Apaf-1-interacting protein (APIP) and ADORA2B transcript levels in human hearts are substantially higher in patients with heart failure than in controls. Interestingly, the APIP and ADORA2B mRNA levels are highly correlated with each other (R = 0.912). APIP expression was significantly increased in primary neonatal cardiomyocytes under hypoxic conditions and this induction reduced myocardial cell death via the activation of the AKT-HIF1α pathway. Accordingly, infarct sizes of APIP transgenic mice after left anterior descending artery ligation were significantly reduced compared to those of wild-type mice. Strikingly, knockdown of APIP expression impaired the cytoprotective effects of ADORA2B during hypoxic damage. Immunoprecipitation and proximity ligation assays revealed that APIP interacts with ADORA2B, leading to the stabilization of both proteins by interfering with lysosomal degradation, and to the activation of the downstream PKA-CREB signaling pathways. ADORA2B levels in the hearts of APIPTg/Tg, APIPTg/+, and Apip+/- mice were proportionally downregulated. In addition, ADORA2B D296G derived from the rs200741295 polymorphism failed to bind to APIP and did not exert cardioprotective activity during hypoxia. Moreover, Adora2b D296G knock-in mice were more vulnerable than control mice to myocardial infarction and intentional increases in APIP levels overcame the defective protection of the ADORA2B SNP against ischemic injury. Collectively, APIP is crucial for cardioprotection against myocardial infarction by virtue of binding to and stabilizing ADORA2B, thereby dampening ischemic heart injury.


Contrast-induced acute kidney injury in kidney transplant recipients: A systematic review and meta-analysis.
To evaluate the incidence of contrast-induced acute kidney injury (CIAKI) in kidney transplant recipients. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from the inception of the databases through July 2016. Studies assessing the incidence of CIAKI in kidney transplant recipients were included. We applied a random-effects model to estimate the incidence of CIAKI. Six studies of 431 kidney transplant recipients were included in the analyses to assess the incidence of CIAKI in kidney transplant recipients. The estimated incidence of CIAKI and CIAKI-requiring dialysis were 9.6% (95%CI: 4.5%-16.3%) and 0.4% (95%CI: 0.0%-1.2%), respectively. A sensitivity analysis limited only to the studies that used low-osmolar or iso-osmolar contrast showed the estimated incidence of CIAKI was 8.0% (95%CI: 3.5%-14.2%). The estimated incidences of CIAKI in recipients who received contrast media with cardiac catheterization, other types of angiogram, and CT scan were 16.1% (95%CI: 6.6%-28.4%), 10.1% (95%CI: 4.2%-18.0%), and 6.1% (95%CI: 1.8%-12.4%), respectively. No graft losses were reported within 30 d post-contrast media administration. However, data on the effects of CIAKI on long-term graft function were limited. The estimated incidence of CIAKI in kidney transplant recipients is 9.6%. The risk stratification should be considered based on allograft function, indication, and type of procedure.


Boechera microsatellite website: an online portal for species identification and determination of hybrid parentage.
Boechera (Brassicaceae) has many features to recommend it as a model genus for ecological and evolutionary research, including species richness, ecological diversity, experimental tractability and close phylogenetic proximity to Arabidopsis . However, efforts to realize the full potential of this model system have been thwarted by the frequent inability of researchers to identify their samples and place them in a broader evolutionary context. Here we present the Boechera Microsatellite Website (BMW), a portal that archives over 55 000 microsatellite allele calls from 4471 specimens (including 133 nomenclatural types). The portal includes analytical tools that utilize data from 15 microsatellite loci as a highly effective DNA barcoding system. The BMW facilitates the accurate identification of Boechera samples and the investigation of reticulate evolution among the ±83 sexual diploid taxa in the genus, thereby greatly enhancing Boechera 's potential as a model system. http://sites.biology.duke.edu/windhamlab/.


A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell.
Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage.


The use of lithium in the treatment of thyrotoxicosis.
Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed (131)I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of (131)I from the thyroid, led to a fall in serum (131)I levels and diminished urinary (131)I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. NEITHER INHIBITION OF RELEASE NOR OF HORMONE DISAPPEARANCE SEEMED TO BE AFFECTED BY METHIMAZOLE (RELEASE: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: approximately 60% decrease in both). When Li(+) was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li(+) values. When Li(+) is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li(+). The similarity of inhibition of iodine release from the thyroid produced by Li(+) and iodides is discussed.


Temperature Sensing in Plants: On the Dawn of Molecular Thermosensor Research.
Although many studies on plant growth and development focus on the effects of light, a growing number of studies dissect plant responses to temperature and the underlying signaling pathways. The identity of plant thermosensing molecules (thermosensors) acting upstream of the signaling cascades in temperature responses was elusive until recently. During the past six years, a set of plant thermosensors has been discovered, representing a major turning point in the research on plant temperature responses and signaling. Here, we review these newly discovered plant thermosensors, which can be classified as sensors of warmth or cold. We compare between plant thermosensors and those from other organisms and attempt to define the subcellular thermosensing compartments in plants. In addition, we discuss the notion that photoreceptive thermosensors represent a novel class of thermosensors, the roles of which have yet to be described in non-plant systems.


The Role of Non-Typeable Haemophilus influenzae Biofilms in Chronic Obstructive Pulmonary Disease.
Non-typeable Haemophilus influenzae (NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD). COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation. Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD. NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts. However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa as the cause. NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility. There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD. NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes. These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix. These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including S. pneumoniae and M. catarrhalis. Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or in-vitro bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied. This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung. Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets.


Influence of exercise training and exhaustion on 45Ca++ content of skeletal muscle mitochondria and fragmented sarcoplasmic reticulum.
Following a 25 muCi/Kg i/p. injection, 45Ca++ activity from the mitochondria and fragmented sarcoplasmic reticulum (FSR) of the superficial rectus femoris (FG-fibers) and combined soleus muscle (SO-fibers) of trained (T, N = 9) and untrained (UT, N = 8) male Wistar rats was determined. The FG mitochondrial 45Ca++ activity from rested animals was 3.9 (T) and 5.3 (UT) times greater than the FSR from this muscle group while the so-mitochondrial 45Ca++ activity was 13.2 (T) and 20.5 (UT) times greater when compared with the respective SO-FSR (p less than .01). The mitochondrial 45Ca++ content of the SO-fibers from rested animals was 58% UT, p less than .01) and 148% (T, p less than .001) greater than that of the FG mitochondria. After 20-26 weeks of exercise training the SO-mitochondrial 45Ca++ content of the rested-T animals was approximately 18% lower (p less than .05) while the T-FG-mitochondrial 45Ca++ content was 48% less than that of UT animals (p less than .01) with a concomitant 28% greater 45Ca++ activity in SO-FSR for the T-group as compared to UT (p less than .01). Following a rapidly exhaustive treadmill run the mitochondrial 45Ca++ content in the UT group was depressed by 21% in SO-fibers and 37% in FG-fibers (p less than .01) with no changes occurring in the T-group. Exhaustion produced no significant changes in the 45Ca++ activity of the FSR from either group of animals.


Utility of Non-Invasive Monitoring of Cardiac Output and Cerebral Oximetry during Pain Management of Children with Sickle Cell Disease in the Pediatric Emergency Department.
Pain crisis in children with sickle cell disease (SCD) is typically managed with intravenous fluids and parenteral opioids in the pediatric emergency department. Electrical cardiometry (EC) can be utilized to measure cardiac output (CO) and cardiac index (CI) non-invasively. Near-infrared spectroscopy (NIRS) measuring cerebral (rCO₂) and splanchnic regional (rSO₂) mixed venous oxygenation non-invasively has been utilized for monitoring children with SCD. We studied the value and correlation of NIRS and EC in monitoring hemodynamic status in children with SCD during pain crisis. We monitored EC and NIRS continuously for 2 h after presentation and during management. Forty-five children participated in the study. CO (D = 1.72), CI (D = 1.31), rSO₂ (D = 11.6), and rCO₂ (D = 9.3), all increased over time. CO max and CI max were achieved 1 h after starting resuscitation. rCO₂ max attainment was quicker than rSO₂, as monitored by NIRS. CI max correlated with rCO₂ max (r = -0.350) and rSO₂ max (r = -0.359). In adjustment models, initial CI significantly impacted initial rCO₂ (p = 0.045) and rCO₂ max (p = 0.043), while initial CO impacted rCO₂ max (p = 0.030). Cardiac output monitoring and NIRS monitoring for cerebral and splanchnic oxygenation were feasible and improved the monitoring of therapeutic interventions for children with SCD during pain crisis.


Keratinophilic fungi from Orissa, India, II: Isolations from feathers of wild birds and domestic fowls.
Feather samples from 117 birds, representing 11 species, were examined for keratinophilic fungi. Of these, 63 (53.8%) were found to be positive. Nine species of fungi classified in 6 genera were isolated: Aphanoascus terreus (1.7%), Chrysosporium indicum (26.4%), Chrys. tropicum (11.1%) the Chrysosporium state of Aphanoascus spp. (2.5%), the Chrysosporium state of Arthroderma tuberculatum (3.4%), Ctenomyces serratus (0.8%), Gymnoascoideus petalosporus (7.6%), Malbranchea spp. (6.8%), Rollandina hyalinospora (6.8%). Passer domesticus (the house sparrow) harboured the largest varieties of keratinophilic fungi: the Chrysosporium state of Arthroderma tuberculatum was found to be associated with it selectively. The associations of these keratinophilic fungi with birds were non-clinical in nature.


Detection of anti-endoplasmic reticulum antibody-positive autoimmune hepatitis in children, using an ELISA technique.
Anti-endoplasmic reticulum antibody positive autoimmune hepatitis in children is characterized by the recognition of a single 50,000 MW protein of the endoplasmic reticulum in liver microsomal fractions by their sera. We have developed an enzyme-linked immunosorbent assay technique with rat liver microsomal preparations as the antigen to be used for detection of this disease. Titers obtained may be useful in following the course of the disease and as an aid in determining when therapy can be discontinued. The technique is rapid, sensitive, reproducible, and simple to perform and is easier to manipulate than immunofluorescence or radioimmunoassay techniques.


Extension of organised cervical cancer screening programmes in Italy and their process indicators.
Since 1996, Italian national guidelines have recommended to regions the implementation of organised screening programmes for cervical cancer. As in the previous years, starting from 1998, we collected aggregated tables of data from Italian organised cervical screening programmes in order to centrally compute process indicators. In 2005, the target population of Italian organised screening programmes included 10,969,571 women, corresponding to 66.7% of Italian women aged 25-64 years. However, these programmes invited only 24.8% of their target population in 2005, vs. 33.3% expected in order to invite the entire target population in the 3-year recommended interval. Compliance to invitation was 36.7%, with a clear North-South decreasing trend. It must however be considered that many women are screened outside the organised programmes. The remaining process indicators deal with women invited during 2004 and screened up to April 2005. Unsatisfactory smears were 3.1%. It was recommended to 6.1% of women to repeat cytology, and 61% of them complied. Some (2.5%) of screened women were referred to colposcopy. Compliance to colposcopy was 84.7% among women referred because of ASCUS or more severe cytology and 88.2% among those referred because of HSIL or more severe cytology. The Positive Predictive Value (PPV) of referral because of ASCUS or more severe cytology for CIN2 or more severe histology was 15.5%. There was a relevant variability of both referral rate and PPV, that were inversely related, and 10 % ofprogrammes referred > 5% of women, suggesting too broad criteria of interpretation of cytology. The unadjusted detection rate ofhistologically confirmed CIN2 or more severe was 2.7 per 1000 screened women (3.0 per 1000, standardised on the Italian population, truncated 25-64).


Neurotensin-induced modulation of dopamine D2 receptors and their function in rat striatum: counteraction by a NTR1-like receptor antagonist.
The present study investigated the neurotensin (NT) receptor subtype (NTR) involved in the antagonistic neurotensin modulation of striatal dopamine D2 receptors observed in vitro and in vivo. The NT induced increase of the IC50 values of dopamine (DA) competition for [125I]iodosulpiride binding sites was counteracted by the NTR1-like antagonist SR48692 in rat striatal slices. Intrastriatal perfusion of pergolide induced in the awake rat an inhibition of striatal DA release that was antagonized by NT. This action of NT was counteracted by co-perfusion with the NTR1 like antagonist SR48692. These data indicate that there exists in the striatum at the prejunctional level an intramembrane antagonistic NT receptor/DA D2 receptor-receptor interaction where NTR1 like receptor activation reduces the DA D2 autoreceptor function.