Remote near-IR light activation of a hyaluronic acid/poly(l-lysine) multilayered film and film-entrapped microcapsules.
Spontaneous embedding of gold nanoparticle (NP) aggregates or polyelectrolyte microcapsules modified with NPs in biocompatible hyaluronic acid/poly(l-lysine) films is reported. The NPs were adsorbed in the aggregated state to induce near-IR light absorption. The films functionalized with gold NPs become active in response to a "biologically friendly" near-IR laser at a power of about 20 mW. The activation is characterized by a localized temperature increase in the film, allowing conversion of light energy to heat into confined volumes. Microcapsules adsorbed onto the film can release its cargo under stimulation with near-IR light because of localized permeability changes in their walls. This work is aimed at layer-by-layer film-based biomedical coatings and active surfaces with light-sensitive features wherein metal NPs and microcapsules are used as active centers or carriers with remote control of functionalities.


Primary herpetic gingivostomatitis in a 65-year-old patient.
We report a case of primary herpetic gingivostomatitis in a 65 years old patient. Age of onset for this disease is typically 1-5 years, though it may also arise in adolescents and young adults; it is rare in children of less than 6 months, as well as in adults more than 40 years old. Our case is thus, unusual in view of the patient's age. We discuss criteria for diagnosis in cases of this type.


RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications.
Despite being considered the gold standard for brachytherapy dosimetry, Monte Carlo (MC) has yet to be implemented into a software for brachytherapy treatment planning. The purpose of this work is to present RapidBrachyMCTPS, a novel treatment planning system (TPS) for brachytherapy applications equipped with a graphical user interface (GUI), optimization tools and a Geant4-based MC dose calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were implemented in RapidBrachyMC and made available to the user via a source and applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models and were compared against previously validated MC brachytherapy codes. The performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions with a cylindrical shielded/unshielded applicator were validated against film measurements in a Solid WaterTM phantom. TG-43 parameters calculated using RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously published work. For the prostate case, clinical dosimetric indices showed general agreement with Oncentra TPS within 1%. Simulation times were on the order of minutes on a single core to achieve uncertainties below 2% in voxels within the prostate. The calculation time was decreased further using the multithreading features of Geant4. In the comparison between MC-calculated and film-measured dose distributions, at least 95% of points passed the 3%/3 mm gamma index criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This software is especially well suited for the development of new source and applicator models.


Pseudo-spin-orbit-coupling-based manipulation of vector beams using electromagnetically induced transparency.
Based on the electromagnetically induced transparency (EIT) model and the higher-order Poincaré sphere (HOPS) framework, we establish a general paradigm to investigate the paraxial evolution of a vector beam in a tripod EIT system. By quantum-optical analogy, we introduce a formalism with a generalized Pauli-like equation under rotational invariance, in which the pseudo-spin-orbit coupling (PSOC) and the spin-orbit nonseparability of light can coexist. More importantly, we find that both the PSOC-based real and imaginary potentials play a key role in controlling and modulating the nonseparable state of the vector beam to traverse the entire HOPS, where the orientation and ellipticity of the transmitted polarization can be modified by varying the PSOC coefficients. Therefore, an all-optical scheme can be proposed to improve the flexibility for tailoring the space-variant polarization of light in coherent media, where the tunable spatial-polarization multiplexing may be useful in conventional and quantum information processing.


Immediate contact reactions to cow's milk and egg in atopic children.
Forty children (0-5 years old), presented with immediate contact urticaria, rash and often atopic dermatitis (n = 34). Redness or urticaria around the mouth appearing after consuming cow's milk or egg, were the major complaints in all. These symptoms suggested a food-induced immediate contact reaction, which can be immune-mediated or irritative. To reinduce this reaction, a skin provocation test, called SAFT, was performed. SAFT stands for Skin Application Food Test. This test is based on direct skin contact, during a maximum of 30 min with food in its 'ordinary consumptive state'. The SAFT can be regarded as a 'physiological' provocation patch test. If positive, contact urticaria develops most often within a few minutes. The results of SAFT and IgE RAST correlated significantly well. Total IgE values were not informative. The rapid onset of the SAFT reaction, induced by proteins, supported by RAST results, strongly indicates an immune-mediated mechanism. In 52% of the 34 patients with atopic dermatitis, dermatitis was exacerbated following food-to-skin contact. Immune-mediated contact reactions to foods play an important role in (dermal) food allergy.


General Characteristics and Treatment Possibilities of Dairy Wastewater - A Review.
The milk processing industry is one of the world's staple industries, thus the treatment possibilities of dairy effluents have been attracting more and more attention. The purpose of the paper is to review contemporary research on dairy wastewater. The origin, categories, as well as liquid by-products and general indicators of real dairy wastewater are described. Different procedures applied for dairy wastewater management are summarised. Attention is focused on in-factory treatment technologies with the emphasis on biological processes. Aerobic and anaerobic methods with both their advantages and disadvantages are discussed in detail. Consecutive anaerobic and aerobic systems are analysed, too. Finally, future research niches are identified.


[Clinical condition and treatment of combined headache].
Coexistence of migraine with tension-type headache, that is, so-called combined headache is a disabling chronic headache disorder and is often seen in daily practice. Combined headache is a common disease, but it is not so easy to do an accurate diagnosis and adequate treatment because clinical spectrum is wide. For clinician, it is especially important to understand characteristics of patient's headache enough to diagnose correctly by using such as a headache diary and, to educate patients to differentiate between migraine and tension-type headache in order to select the right treatment and to prevent medication-overuse headache.


Gantry triggered x-ray verification during single-isocenter stereotactic radiosurgery: Increased certainty for a no-margin strategy.
Single-isocenter linac-based stereotactic radiosurgery (SRS) has emerged as a dedicated treatment option for multiple brain metastases. Consequently, image-guidance for patient positioning and motion management has become very important. The purpose of this study was to analyze intra-fraction errors measured with stereoscopic x-rays and their impact on the dose distribution. Treatments were planned with non- coplanar dynamic conformal arcs for 33 patients corresponding to 127 brain lesions and 356 arcs. Intra-arc positioning errors were measuredusing stereoscopic x-rays (ExacTrac Dynamic, Brainlab), triggered during arc delivery. Couch corrections above 0.7 mm and 0.5° were always applied. Intra-arc positioning data was analyzed. The dose impact was evaluated by applying the measured errors to the dose given in each arc. Median residual errors were 0.10 mm, 0.13 mm and 0.08 mm for the lateral, longitudinal and vertical directions and 0.10°, 0.08° and 0.13° for the pitch, roll and yaw angles respectively. 90% of the treatment arcs showed shifts of less than 0.4 mm and 0.4°in all directions. Dosimetric impact of motion showed the largest losses in coverage on small targets. All targets achieved at least 95% of the prescription dose to 95% of their volume, even when planned without margins. Intra-fractional errors measured during beam delivery were found to be notably low with a dose impact that showed acceptable target coverage when applying these intra-arc errors to the dose distributions of the individual treatment arcs. Using an adequate immobilization and intra-fraction imaging prior to and during irradiation, no margins need to be added to compensate for intra-fraction motion.


Do Advanced Glycation End Products and Its Receptor Play a Role in Pathophysiology of Hypertension?
There is a close relationship between arterial stiffness and blood pressure. The studies suggest that the advanced glycation end products (AGEs) and its cell receptor (RAGE) are involved in the arterial stiffness in two ways: changes in arterial structure and vascular function. Plasma levels of AGEs and expression of RAGE are elevated, while the levels of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) are lowered in patients with hypertension (HTN). There is a positive correlation between plasma levels of AGEs and arterial stiffness, and an inverse association between arterial stiffness/HTN, and serum levels of sRAGE and esRAGE. Various measures can reduce the levels of AGEs and expression of RAGE, and elevate sRAGE. Arterial stiffness and blood pressure could be reduced by lowering the serum levels of AGEs, and increasing the levels of sRAGE. Levels of AGEs can be lowered by reducing the consumption of AGE-rich diet, short duration of cooking in moist heat at low temperature, and cessation of cigarette smoking. Drugs such as aminoguanidine, vitamins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers, statins, and metformin inhibit AGE formation. Alagebrium, an AGE breakers reduces levels of AGEs. Clinical trials with some drugs tend to reduce stiffness. Systemic administration of sRAGE has beneficial effect in animal studies. In conclusion, AGE-RAGE axis is involved in arterial stiffness and HTN. The studies suggest that inhibition of AGEs formation, reduction of AGE consumption, blockade of AGE-RAGE interaction, suppression of RAGE expression, and exogenous administration of sRAGE may be novel therapeutic strategies for treatment of arterial stiffness and HTN.


Modified Methods of Fabricating Helix and Antihelix in Total Auricular Reconstruction Based on Different Length of Eighth Costal Cartilage.
Attaining an ideal appearance of the reconstructed ear depends primarily on the fabricated cartilaginous ear framework. Despite the role of eighth costal cartilage, the length of the eighth rib cartilage is difficult to anticipate, and growth of the eighth cartilage is variable. The authors discussed modified methods of fabricating helix and antihelix based on different length of eighth costal cartilage. Based on the actual length of the eighth costal cartilage, patients were divided into group A and group B. In group A, the eighth costal cartilage was divided into 2 parts. Part I was used to fashion the helix, whereas part II was used to fabricate the antihelix and superior crus. In group B, the seventh costal cartilage was cut into 3 parts. Part I and part II were used to fashion the helix, antihelix, and superior crus as group A did. Part III was assembled to the lateral part of the framework to form the inferior crus. A total of 56 patients underwent auricular reconstruction adopting the modified techniques between 2015 and 2016. Three cases have been selected to illustrate the favorable result achieved. They revealed that the helix, antihelix, superior crus, and inferior crus all appeared distinct and presented a favorable result of the contour of the reconstructed auricle. Based on different length of eighth costal cartilage, modified methods of fabricating helix and antihelix make full use of the autogenous costal cartilage, elevate anatomical details, and enhance the overall aesthetics of reconstructed ear. The great majority of patients have satisfactory surgical outcomes, demonstrating that personalized treatment is necessary.


Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta-blockers: a randomized controlled trial.
Gastric variceal bleeding is severe and is associated with high mortality. We compared the efficacy of cyanoacrylate injection and beta-blockers in primary prophylaxis of gastric variceal bleeding. Cirrhotics with large gastroesophageal varices type 2 with eradicated esophageal varices or large isolated gastric varix type 1, who had never bled from gastric varix, were randomised to cyanoacrylate injection (Group I, n=30), beta-blockers (Group II, n=29) or no treatment (Group III, n=30). Primary end-points were bleeding from gastric varix or death. The actuarial probability of bleeding from gastric varices over a median follow-up of 26 months was 13% in Group I, 28% in Group II (p=0.039), and 45% in Group III (p=0.003). The actuarial probability of survival was higher in the cyanoacrylate compared to the no-treatment group (90% vs. 72%, p=0.048). The median hepatic venous pressure gradient (HVPG) was increased in Group I (14-15 mm Hg, p=0.001) and III (14-16 mm Hg, p=0.001) but decreased in Group II (14 to 12 mm Hg, p=0.001) during follow-up. Size of gastric varix >20 mm, a MELD score ≥17, and presence of portal hypertensive gastropathy predicted 'high risk' of first bleeding from gastric varices. Primary prophylaxis is recommended in patients with large and high risk gastric varices to reduce the risk of first bleeding and mortality. Cyanoacrylate injection is more effective than beta-blocker therapy in preventing first gastric variceal bleeding.


Identification and quantification of galloyl derivatives, flavonoid glycosides and anthocyanins in leaves of Pistacia lentiscus L.
Separation, identification and quantification of polyphenols was carried out on leaves of Pistacia lentiscus L., an evergreen member of the family Anacardiaceae, using semi-preparative HPLC, HPLC-photodiode array detection and HPLC-MS analysis, together with 1H- and 13C NMR. Three major classes of secondary metabolites were detected: (i) gallic acid and galloyl derivatives of both glucose and quinic acid; (ii) flavonol glycosides, i.e. myricetin and quercetin glycosides; and (iii) anthocyanins, namely delphinidin 3-O-glucoside and cyanidin 3-O-glucoside. Low amounts of catechin were also detected. The concentration of galloyl derivatives was extremely high, representing 5.3% of the leaf dry weight, and appreciable amounts of myricetin derivatives were also detected (1.5% on a dry weight basis). These findings may be useful in establishing a relationship between the chemical composition of the leaf extract and the previously reported biological activity of P. lentiscus, and may also assign a new potential role of P. lentiscus tissue extracts in human health care.


Idiosyncratic and systematic aspects of spatial representations in the macaque parietal cortex.
The sensorimotor transformations for visually guided reaching were originally thought to take place in a series of discrete transitions from one systematic frame of reference to the next with neurons coding location relative to the fixation position (gaze-centered) in occipital and posterior parietal areas, relative to the shoulder in dorsal premotor cortex, and in muscle- or joint-based coordinates in motor output neurons. Recent empirical and theoretical work has suggested that spatial encodings that use a range of idiosyncratic representations may increase computational power and flexibility. We now show that neurons in the parietal reach region use nonuniform and idiosyncratic frames of reference. We also show that these nonsystematic reference frames coexist with a systematic compound gain field that modulates activity proportional to the distance between the eyes and the hand. Thus, systematic and idiosyncratic signals may coexist within individual neurons.


Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells.
The Wnt/β-catenin, EGFR, and PI3K pathways frequently undergo upregulation in head and neck squamous carcinoma (HNSCC) cells. Moreover, the Wnt/β-catenin pathway together with Hedgehog (Hh) signaling regulate the activity of cancer stem cells (CSCs). The aim of this study was to investigate the effects of the combinatorial use of the Wnt/β-catenin and Hh pathway inhibitors on viability, cell cycle progression, apoptosis induction, cell migration, and expression of CSC markers in tongue (CAL 27) and hypopharynx (FaDu) cancer cells. Co-inhibition of Wnt signaling with EGFR or PI3K pathways was additionally tested. The cells were treated with selective inhibitors of signaling pathways: Wnt/β-catenin (PRI-724), Hh (vismodegib), EGFR (erlotinib), and PI3K (HS-173). Cell viability was evaluated by the resazurin assay. Cell cycle progression and apoptosis induction were tested by flow cytometric analysis after staining with propidium iodide and Annexin V, respectively. Cell migration was detected by the scratch assay and CSC marker expression by the R-T PCR method. Mixtures of PRI-724 and vismodegib affected cell cycle distribution, greatly reduced cell migration, and downregulated the transcript level of CSC markers, especially POU5F1 encoding OCT4. Combinations of PRI-724 with erlotinib or HS-173 were more potent in inducing apoptosis.


[Importance of opiate receptor ligands in regulating lymphocyte proliferative activity].
Effects of morphine (10(-12)-10(-6) M), metenkephalin (10(-12)-10(-6) M), beta-endorphin (10(-12)-10(-6) M), dalargin--synthetic analogue of leu-enkephalin (10(-12)-10(-7) M) and naloxone (10(-8)-10(-6) M) on lymphocytes of the human peripheral blood stimulated by polyclonal mitogens were studied. It was shown that morphine (10(-8)-10(-6) M) and dalargin (10(-12)-10(-7) M) inhibited the lymphocyte proliferative activity induced by optimal doses of phytohemagglutinin; effects of morphine and dalargin were blocked by naloxone. It was also found that beta-endorphin (10(-11)-10(9) M) inhibited the proliferative activity of lymphocytes stimulated by pokeweed mitogen; naloxone failed to block beta-endorphin effect.


Progress and Potential of Electron Cryotomography as Illustrated by Its Application to Bacterial Chemoreceptor Arrays.
Electron cryotomography (ECT) can produce three-dimensional images of biological samples such as intact cells in a near-native, frozen-hydrated state to macromolecular resolution (∼4 nm). Because one of its first and most common applications has been to bacterial chemoreceptor arrays, ECT's contributions to this field illustrate well its past, present, and future. While X-ray crystallography and nuclear magnetic resonance spectroscopy have revealed the structures of nearly all the individual components of chemoreceptor arrays, ECT has revealed the mesoscale information about how the components are arranged within cells. Receptors assemble into a universally conserved 12-nm hexagonal lattice linked by CheA/CheW rings. Membrane-bound arrays are single layered; cytoplasmic arrays are double layered. Images of in vitro reconstitutions have led to a model of how arrays assemble, and images of native arrays in different states have shown that the conformational changes associated with signal transduction are subtle, constraining models of activation and system cooperativity. Phase plates, better detectors, and more stable stages promise even higher resolution and broader application in the near future.


Functional interactions of HslV (ClpQ) with the ATPase HslU (ClpY).
HslVU is a bacterial homolog of the proteasome, where HslV is the protease that is activated by HslU, an ATPase and chaperone. Structures of singly and doubly capped HslVU particles have been reported, and different binding modes have been observed. Even among HslVU structures with I-domains distal to HslV, no consensus mode of activation has emerged. A feature in the Haemophilus influenzae HslVU structure, insertion of the C termini of HslU into pockets in HslV, was not seen in all other structures of the enzyme. Here we report site-directed mutagenesis, peptide activation, and fluorescence experiments that strongly support the functional relevance of the C terminus insertion mechanism: we find that mutations in HslV that disrupt the interaction with the C termini of HslU invariably lead to inactive enzyme. Conversely, synthetic peptides derived from the C terminus of HslU bind to HslV with 10(-5) M affinity and can functionally replace full HslU particles for both peptide and casein degradation but fail to support degradation of a folded substrate. Thus, the data can be taken as evidence for separate substrate unfoldase and protease stimulation activities in HslU. Enhanced HslV proteolysis could be due to the opening of a gated channel or allosteric activation of the active sites. To distinguish between these possibilities, we have mutated a series of residues that line the entrance channel into the HslV particle. Our mutational and fluorescence experiments demonstrate that allosteric activation of the catalytic sites is required in HslV, but they do not exclude the possibility of channel opening taking place as well. The present data support the conclusion that the H. influenzae structure with I-domains distal to HslV captures the active species and point to significant differences in the activation mechanism of HslV, ClpP, and the proteasome.


Oligonucleotides conjugated to natural lipids: synthesis of phosphatidyl-anchored antisense oligonucleotides.
Antisense oligonucleotides are promising therapeutic agents against a variety of diseases. Effective delivery of these molecules is critical in view of their clinical application. Despite the richness of synthetic strategies addressed to the lipophilic modification of oligodeoxynucleotides (ODNs) for enhancing their pharmacokinetic behavior and trans-membrane delivery, the phosphatidyl group (1,2-di-O-acyl-sn-glycero-3-phosphoryl) has been never used as the lipophilic moiety of lipid-ODN conjugates. The present paper reports a general procedure for synthesizing 5'-phosphatidyl-ODNs. By this procedure, phosphatidyl conjugates of a VEGF antisense-ODN have been prepared, which differ in the fatty acid composition of their phosphatidyl moiety. These new lipid-ODN conjugates, which have been characterized on the basis of their physicochemical properties, showed an improved resistance to exonucleases and were able to lower the VEGF-mRNA expression in human SH-SY5Y neuroblastoma cells more effectively than the relevant free antisense-ODN did.


NT-3 promotes proprioceptive axon regeneration when combined with activation of the mTor intrinsic growth pathway but not with reduction of myelin extrinsic inhibitors.
Although previous studies have identified several strategies to stimulate regeneration of CNS axons, extensive regeneration and functional recovery have remained a major challenge, particularly for large diameter myelinated axons. Within the CNS, myelin is thought to inhibit axon regeneration, while modulating activity of the mTOR pathway promotes regeneration of injured axons. In this study, we examined NT-3 mediated regeneration of sensory axons through the dorsal root entry zone in a triple knockout of myelin inhibitory proteins or after activation of mTOR using a constitutively active (ca) Rheb in DRG neurons to determine the influence of environmental inhibitory or activation of intrinsic growth pathways could enhance NT-3-mediate regeneration. Loss of myelin inhibitory proteins showed modest enhancement of sensory axon regeneration. In mTOR studies, we found a dramatic age related decrease in the mTOR activation as determined by phosphorylation of the downstream marker S6 ribosomal subunit. Expression of caRheb within adult DRG neurons in vitro increased S6 phosphorylation and doubled the overall length of neurite outgrowth, which was reversed in the presence of rapamycin. In adult female rats, combined expression of caRheb in DRG neurons and NT-3 within the spinal cord increased regeneration of sensory axons almost 3 fold when compared to NT-3 alone. Proprioceptive assessment using a grid runway indicates functionally significant regeneration of large-diameter myelinated sensory afferents. Our results indicate that caRheb-induced increase in mTOR activation enhances neurotrophin-3 induced regeneration of large-diameter myelinated axons.


Burns first aid information on the Internet.
The Internet is an increasingly important source of health-related information. However, the growth of the Internet and its use as a medical delivery tool should be viewed with caution. One of the key concerns is that although the volume of information is huge, the quality, accuracy and completeness of the information is questionable. The aim of this study was to evaluate burns first aid information on the Internet. The search term used was "first aid for burns" and the first 25 hits from each search engine were analysed by one of the observers. We gathered basic information on the web sites--such as the country of origin, language in which the information was offered, accessibility, relevance and whether the site was commercial, organisational or academic. Quality and technicality of the web sites were assessed and scored. The mean quality score was 4.7/15 (31.5%) The mean technical score was 6.1 of 12 (51.1%). When the total score was categorised by percentage, none of the web sites ranked in the excellent category, 1 was very good, 4 were good, 6 were fair and the majority, 36, were poor. Based on the quality score only, two web sites were in the excellent category and two were very good. For technicality one web site was excellent and three were very good. This study has shown first aid information on the Internet is largely of poor quality, that the technical information provided is inadequate and that the sites include a significant amount of grossly inaccurate information. The few sites that contain excellent technical information make up a very small proportion of what is available. Therefore, the average Internet user may not encounter these resources, instead gaining knowledge from sites of questionable value.


Long-acting inhaled bronchodilators for COPD--lack of logic continues.
Long acting inhaled bronchodilators - beta agonists and anti-cholinergic--can improve symptoms, enhance quality of life, increase exercise ability, and reduce exacerbation rates in patients with COPD. PHARMAC needs to change policy so that these patients have easy access to this effective group of drugs.


[Interrelation of the blood kallikrein-kinin and anticoagulation systems in experimental myocardial infarct].
The activity of the kallikrein-kinin and anticoagulation blood systems was studied in dogs with experimental myocardial infarction. Changes were revealed in the kallikrein-kinin system which create conditions for uncontrolled production of kinins in the first 24 hours of the disease. A direct correlation was detected between the activity of kallikrein and plasmin in the first three days of experimental myocardial infarction, which the authors claim to be a pathophysiological reaction of the body because it is conductive to the uncontrolled production of kinins. It is also noted that in this pathological process the depression of the anticoagulation system in the first two days is mainly due to reduced activity of nonenzymatic fibrinolysis, while, beginning with the third day, it is caused by reduced activity of enzymatic fibrinolysis, increased antiplasmin activity in particular.


Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5-fluorouracil and the clinical outcome following definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in patients with esophageal squamous cell carcinoma.
Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU) is believed to be a clinical option for improving clinical responses. Evaluating the potential factors contributing to plasma 5-FU concentration is important to develop TDM of 5-FU. Our aim was to evaluate the association of the circadian and treatment cycle effects on plasma 5-FU concentration with the clinical response. A post hoc population analysis was performed using the plasma concentration of 5-FU and clinical response data, including prognosis from 49 patients with esophageal squamous cell carcinoma after treatment with definitive 5-FU/cisplatin-based chemoradiotherapy, consisting of prolonged infusion of 5-FU at 400 mg/(m2·day) for 5 days. The circadian rhythm and treatment cycle were applied as covariates to the model equation. The plasma 5-FU concentration in the evening was 1.3-fold higher compared with the morning, and in the second cycle, it was 1.5-fold increased compared with the first cycle, with relatively small inter-individual variations (23.3 and 16.8%). Clinical efficacy depended on the plasma 5-FU concentration, excluding the covariate effects (P=0.025), which correlated with age and height but not body surface area. Circadian variation did not contribute to the clinical response, and the increase in 5-FU plasma concentration in the second cycle significantly correlated with leucocyte counts obtained before chemoradiotherapy. The higher plasma concentration of 5-FU in the early phase of treatment may be the key determinant of clinical efficacy, whereas the variations in the plasma concentration of 5-FU owing to the time of day and treatment cycle are small contributors.


Urease and Dental Plaque Microbial Profiles in Children.
Urease enzymes produced by oral bacteria generate ammonia, which can have a significant impact on the oral ecology and, consequently, on oral health. To evaluate the relationship of urease with dental plaque microbial profiles in children as it relates to dental caries, and to identify the main contributors to this activity. 82 supragingival plaque samples were collected from 44 children at baseline and one year later, as part of a longitudinal study on urease and caries in children. DNA was extracted; the V3-V5 region of the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Urease activity was measured using a spectrophotometric assay. Data were analyzed with Qiime. Plaque urease activity was significantly associated with the composition of the microbial communities of the dental plaque (Baseline P = 0.027, One Year P = 0.012). The bacterial taxa whose proportion in dental plaque exhibited significant variation by plaque urease levels in both visits were the family Pasteurellaceae (Baseline P<0.001; One Year P = 0.0148), especially Haemophilus parainfluenzae. No association was observed between these bacteria and dental caries. Bacteria in the genus Leptotrichia were negatively associated with urease and positively associated with dental caries (Bonferroni P<0.001). Alkali production by urease enzymes primarily from species in the family Pasteurellaceae can be an important ecological determinant in children's dental plaque. Further studies are needed to establish the role of urease-associated bacteria in the acid/base homeostasis of the dental plaque, and in the development and prediction of dental caries in children.


Comparison of ridge regression, partial least-squares, pairwise correlation, forward- and best subset selection methods for prediction of retention indices for aliphatic alcohols.
A quantitative structure-retention relationship (QSRR) study based on multiple linear regression (MLR) was performed for the description and prediction of Kováts retention indices (RI) of alcohol compounds. Alcohols were of saturated, linear or branched types and contained a hydroxyl group on the primary, secondary or tertiary carbon atoms. Constitutive and weighted holistic invariant molecular (WHIM) descriptors were used to represent the structure of alcohols in the MLR models. Before the model building, five variable selection methods were applied to select the most relevant variables from a large set of descriptors, respectively. The selected molecular properties were included into the MLR models. The efficiency of the variable selection methods was also compared. The selection methods were as follows: ridge regression (RR), partial least-squares method (PLS), pair-correlation method (PCM), forward selection (FS) and best subset selection (BSS). The stability and the validity of the MLR models were tested by a cross-validation technique using a leave-n-out technique. Neither RR nor PLS selected variables were able to describe the Kováts retention index properly, and PCM gave reliable results in the description but not for prediction. We built models with good predicting ability using FS and BSS as a selection method. The most relevant variables in the description and prediction of RIs were the mean electrotopological state index, the molecular mass, and WHIM indices characterizing size and shape.


Banked bone grafting for bone defect repair--clinical evaluation of bone union and graft incorporation.
One hundred and twenty-four banked bone grafts performed during the past 15 years were studied in respect to union and graft incorporation processes using X-ray, bone scintigraphy and histology. Radiological study of the chip graft showed an absence of cavity contours, and homogenization of the grafted area, followed by development of the trabecular structure. In the block graft, initial union was shown at the junctional area followed by the appearance of mottled shadows throughout the entire graft and finally differentiation of bone marrow and cortex. Bone scintigraphy showed an initial increase in RI uptake at the junction and then a gradual increase in the entire graft. Histological study showed that bone apposition on the trabeculae of the graft starts in the junction and later extends to other areas. The replacement of cancellous bone is more rapid than that of cortical bone. The porous surface seems to promote bone union and incorporation when large block grafts of cortical bone are used.


Calculating census tract-based life expectancy in New York state: a generalizable approach.
Life expectancy at birth (LE) has been calculated for states and counties. LE estimates at these levels mask health disparities in local communities. There are no nationwide estimates at the sub-county level. We present a stepwise approach for calculating LE using census tracts in New York state to identify health disparities. Our study included 2751 census tracts in New York state, but excluded New York City. We used population data from the 2010 United States Census and 2008-2010 mortality data from the state health department. Tracts were assigned to 99.97% of the deaths. We removed tracts which had a majority of people living in group quarters. Deaths in these tracts are often recorded elsewhere. Of the remaining 2679 tracts, 6.6% of the tracts had standard errors ≥ 2 years. A geographic aggregation tool was used to aggregate tracts with fewer than 60 deaths, and then aggregate areas that had standard errors of ≥ 2 years. Aggregation resulted in a 9.9% reduction in the number of areas. Tracts with < 2% of population living below the poverty level had a LE of 82.8 years, while tracts with a poverty level ≥ 25% had a LE of 75.5. We observed differences in LE in border areas, of up to 10.4 years, when excluding or including deaths of study area residents that occurred outside the study area. The range and standard deviation at the county level (77.5-82.8, SD = 1.2 years) were smaller than our final sub-county areas (64.7-92.0, SD = 3.3 years). The correlation between LE and poverty were similar and statistically significant (p < 0.0001) at the county (r = - 0.58) and sub-county level (r = - 0.58). The correlations between LE and percent African-American at the county level were (r = 0.11, p = 0.43) and at the sub-county level (r = - 0.25, p < 0.0001). The proposed approach for geocoding and aggregation of mortality and population data provides a solution for health departments to produce stable empirically-derived LE estimates using data coded to the tract. Reliable estimates within sub-county areas are needed to aid public health officials in focusing preventive health programs in areas where health disparities would be masked by county level estimates.


Structure identification based on steady-state control: experimental results and applications.
We report experimental results on structure identification of nonlinear systems by a steady-state control method. The idea underlying the method is to drive the nonlinear system to steady state by applying a suitable feedback control input. It turns out experimentally that this control-based structure identification method can be used for some applications, such as estimation of initial conditions and state variables of nonlinear systems and structure identification of some special elements. Two attractors of the Chua oscillator are presented to illustrate the reliability of the suggested techniques under the hypotheses of measurable state variables and physical access to the system for implementing the proportional feedback.


Investigating the virulence genes and antibiotic susceptibility patterns of Vibrio cholerae O1 in environmental and clinical isolates in Accra, Ghana.
Cholera has been endemic in Ghana since its detection in 1970. It has been shown that long-term survival of the bacteria may be attained in aquatic environments. Consequently, cholera outbreaks may be triggered predominantly in densely populated urban areas. We investigated clinical and environmental isolates of Vibrio cholerae O1 in Accra to determine their virulence genes, antibiotic susceptibility patterns and environmental factors maintaining their persistence in the environment. Water samples from various sources were analyzed for the presence of V. cholerae O1 using culture methods. Forty clinical isolates from a previous cholera outbreak were included in the study for comparison. Antibiotic susceptibility patterns of the bacteria were determined by disc diffusion. Virulence genes were identified by analyzing genes for ctx, tcpA (tcpAEl Tor tcpACl), zot, ompW, rbfO1 and attRS using PCR. Physicochemical characteristics of water were investigated using standard methods. One-way ANOVA and student t - test were employed to analyze the relationship between physicochemical factors and the occurrence of V. cholerae O1. Eleven V. cholerae O1 strains were successfully isolated from streams, storage tanks and wells during the study period. All isolates were resistant to one or more of the eight antibiotics used. Multidrug resistance was observed in over 97% of the isolates. All isolates had genes for at least one virulence factor. Vibrio cholerae toxin gene was detected in 82.4% of the isolates. Approximately 81.8% of the isolates were positive for tcpAEl Tor gene, but also harbored the tcpAcl gene. Isolates were grouped into thirteen genotypes based on the genes analyzed. High temperature, salinity, total dissolved solids and conductivity was found to significantly correlate positively with isolation of V. cholerae O1. V. cholerae serotype Ogawa biotype El tor is the main biotype circulating in Ghana with the emergence of a hybrid strain. Multidrug resistant V. cholerae O1 with different genotypes and pathogenicity are present in water sources and co-exist with non O1/O139 in the study area.


Longitudinal Tau PET Using 18F-Flortaucipir: The Effect of Relative Cerebral Blood Flow on Quantitative and Semiquantitative Parameters.
Semiquantitative PET measures such as SUV ratio (SUVr) have several advantages over quantitative measures, such as practical applicability and relative computational simplicity. However, SUVr may potentially be affected by changes in blood flow, whereas quantitative measures such as nondisplaceable binding potential (BPND) are not. For 18F-flortaucipir PET, the sensitivity of SUVr for changes in blood flow is currently unknown. Therefore, we compared semiquantitative (SUVr) and quantitative (BPND) parameters of longitudinal 18F-flortaucipir PET scans and assessed their vulnerability to changes in blood flow. Methods: Subjects with subjective cognitive decline (n = 38) and Alzheimer disease patients (n = 24) underwent baseline and 2-y follow-up dynamic 18F-flortaucipir PET scans. BPND and relative tracer delivery were estimated using receptor parametric mapping, and SUVr at 80-100 min was calculated. Regional SUVrs were compared with corresponding distribution volume ratio (BPND + 1) using paired t tests. Additionally, simulations were performed to model effects of larger flow changes in different binding categories. Results: Results in subjective cognitive decline and Alzheimer disease showed only minor differences between SUVr and BPND changes over time. Relative tracer delivery changes were small in all groups. Simulations illustrated a variable bias for SUVr depending on the amount of binding. Conclusion: SUVr provided an accurate estimate of changes in specific binding for 18F-flortaucipir over a 2-y follow-up during which changes in flow were small. Notwithstanding, simulations showed that large(r) flow changes may affect 18F-flortaucipir SUVr. Given that it is currently unknown to what order of magnitude pharmacotherapeutic interventions may induce changes in cerebral blood flow, caution may be warranted when changes in flow are potentially large(r), as in clinical trials.


[Ethical issues in nursing leadership].
Social transition causes shifts and changes in the relationship between health professionals and their patients. In their professional capacity, it is important today for nurses to handle ethical dilemmas properly, in a manner that fosters an ethical environment. This article investigates the ethical concerns and decision processes of nurses from a knowledge construction perspective, and examines such issues as patient needs, staff perceptions, organizational benefits, and professional image. The decision making methods commonly used when facing ethical dilemma explored in this study include the traditional problem solving, nursing process, MORAL model, and Murphy's methods. Although decision making for ethical dilemmas is governed by no universal rule, nurses are responsible to try to foster a trusting relationship between employee and employer, health care providers and patients, and the organization and colleagues. When decision making on ethical dilemmas is properly executed quality care will be delivered and malpractice can be reduced.


Dwell-Time Distribution, Long Pausing and Arrest of Single-Ribosome Translation through the mRNA Duplex.
Proteins in the cell are synthesized by a ribosome translating the genetic information encoded on the single-stranded messenger RNA (mRNA). It has been shown that the ribosome can also translate through the duplex region of the mRNA by unwinding the duplex. Here, based on our proposed model of the ribosome translation through the mRNA duplex we study theoretically the distribution of dwell times of the ribosome translation through the mRNA duplex under the effect of a pulling force externally applied to the ends of the mRNA to unzip the duplex. We provide quantitative explanations of the available single molecule experimental data on the distribution of dwell times with both short and long durations, on rescuing of the long paused ribosomes by raising the pulling force to unzip the duplex, on translational arrests induced by the mRNA duplex and Shine-Dalgarno(SD)-like sequence in the mRNA. The functional consequences of the pauses or arrests caused by the mRNA duplex and the SD sequence are discussed and compared with those obtained from other types of pausing, such as those induced by "hungry" codons or interactions of specific sequences in the nascent chain with the ribosomal exit tunnel.


Tissue engineering using magnetite nanoparticles and magnetic force: heterotypic layers of cocultured hepatocytes and endothelial cells.
Novel technologies to establish three-dimensional, in vivo-like tissue consisting of various types of cells are required for tissue engineering. We applied magnetic force to construct a heterotypic, layered coculture system of rat hepatocytes and human aortic endothelial cells (HAECs) that was not limited by cell type. Magnetite cationic liposomes carrying a positive surface charge to improve adsorption accumulated in HAECs at a concentration of 38 pg of magnetite per cell. Magnetically labeled HAECs specifically accumulated onto hepatocyte monolayers at sites where a magnet (4000 G) was positioned, and then adhered to form a heterotypic, layered construct with tight and close contact. This cocultured construct significantly (p < 0.05) enhanced albumin secretion by hepatocytes compared with that in homotypic cultures of hepatocytes or heterotypic cocultures of hepatocytes and HAECs without magnets. These results suggest that this novel use of magnetite nanoparticles and magnetic force, which we refer to as "magnetic force-based tissue engineering" (Mag-TE), offers a major advancement in tissue engineering.


[Effect of ear mushroom (Auricularia) on functional constipation].
Constipation is one of the most prevalent gastrointestinal complaints. High fiber intake is recommended as an initial therapy for constipation. Ear mushroom is known to have higher fiber contents about 50% than other mushroom. The aim of this study was to evaluate the effect of fiber supplements using ear mushrooms on the improvement of functional constipation. We conducted a double blind study with 3 groups (placebo, ear mushrooms alone, and ear mushrooms with additives including cascara sagrada, etc.), which were randomly assigned out of 34 patients with functional constipation, defined by modified Rome II criteria. Number of bowel movement, straining, sense of incomplete evacuation, stool consistency, satisfactory relief, abdominal pain/discomfort and colon transit time were evaluated and analyzed before, during and after the treatment. Both ear mushrooms alone and ear mushrooms with additives significantly improved number of bowel movement, straining, sense of incomplete evacuation, stool consistency and satisfactory relief in patients with functional chronic constipation (p<0.05). Although the use of ear mushrooms with additives was found to be more effective on the improvement of constipation than ear mushrooms alone, it may induce abdominal discomfort or pain. In patients with functional constipation, fiber supplements using ear mushrooms significantly improved constipation related symptoms without serious side effect.


In search of a pediatric cardiac surgeon's 'Holy Grail': the ideal pulmonary conduit.
The limited lifespan of all currently available conduits leads to repeat operations and interventional procedures in many children. Each reoperation entails considerable risk to life, expenditure and compromised quality of life as the conduit degenerates. The ideal conduit should be available freely, inexpensive, require no anticoagulation, be resistant to infection, free from thromboembolism, have no gradients or regurgitation and have unlimited durability. This review explores various options as surgeons and researchers endeavor to develop the ideal conduit--which will fulfill all of the above-mentioned criteria. Various currently available conduits are analyzed. Special emphasis is given to tissue-engineered valves and percutaneous valve implantations.


DNA methylation of tumor suppressor protein-coding and non-coding genes in multiple myeloma.
Multiple myeloma is an incurable hematological malignancy arising from immortalized plasma cells in the bone marrow. DNA methylation refers to the catalytic addition of a methyl group to the cytosine ring of a CpG dinucleotide. Methylation of a promoter-associated CpG island, a cluster of CpG dinucleotides, may lead to silencing of the associated gene. In carcinogenesis, methylation of protein-coding or non-coding tumor suppressor genes/miRNAs is associated with transcriptional silencing, loss of tumor suppressor function and prognostic significance. This review first introduces pathogenesis of myeloma and DNA methylation in cancer. Then, it summarizes methylation of protein-coding tumor suppressor genes, especially, the latest genome-wide methylation studies in myeloma, followed by the latest findings of methylation of non-coding tumor suppressor miRNAs in myeloma.


Unmet supportive care needs of patients with rare cancer: A systematic review.
Patients with rare cancers may experience different unmet needs than those with common cancer. The objective of this systematic review was to (1) investigate unmet supportive care needs of rare cancer patients throughout the disease trajectory and (2) identify predictive factors for these unmet needs. PubMed, PsycINFO and CINAHL were searched for publications (January 2011 to March 2021) focusing on unmet needs of patients with rare cancer. Two reviewers independently selected studies, extracted data and performed quality assessment. Findings were synthesised. The search yielded 4,598 articles, of which 59 articles met eligibility criteria and 57 were of medium or high quality. Rare cancer patients most frequently reported unmet needs in the healthcare system and information domain (up to 95%), followed by the psychological domain (up to 93%) and the physical and daily living domain (up to 80%). Unmet needs were mainly reported in the posttreatment phase. The most frequently identified predictors were higher anxiety, younger age and higher neuroticism. Patients with rare cancer have unmet needs throughout their disease trajectory. Supportive care needs of rare cancer patients should be addressed individually, depending on the rare cancer subdomain and phase of disease and from diagnosis onwards.


Interactions between new quinolone antibacterials and diagnostic drug containing manganese.
A diagnostic drug containing manganese chloride tetrahydrate as a major ingredient is available since 2006. It is used in magnetic resonance imaging as a negative contrast medium for magnetic resonance cholangiopancreatography of the gastrointestinal tract. However, there is no report regarding interaction between manganese and new quinolone antibacterials. We investigated the interactions between new quinolone antibacterials and a diagnostic drug containing manganese in vitro. We evaluated the rate of formation of chelate complex by reacting new quinolone antibacterials (levofloxacin, ofloxacin, ciprofloxacin) with a diagnostic drug containing manganese. The EC50 values of the formation of chelate complex for levofloxacin, ofloxacin, and ciprofloxacin were 5.14 ± 0.14, 5.29 ± 0.14, and 0.96 ± 0.04 mM, respectively. The rates of formation of chelate complex by levofloxacin, ofloxacin, and ciprofloxacin in a reaction with the diagnostic drug were 17.0, 18.9, and 55.5 % in clinical condition, respectively. Our results suggest that a complex of each antibacterial and manganese was formed, with ciprofloxacin causing the strongest interaction. In addition, our findings indicate that the degree of interaction may be an important problem in clinical settings with concomitant administration of a new quinolone antibacterial and diagnostic drug containing manganese.


Simultaneous determination of sorbic and benzoic acids in milk products using an optimised microextraction technique followed by gas chromatography.
A rapid and reliable method for direct determination of sorbic and benzoic acids in milk products was developed by dispersive liquid-liquid microextraction (DLLME) and gas chromatography with flame ionisation detector (GC-FID). A response surface methodology (RSM) based on a central composite design (CCD) was applied for optimisation of the main variables, such as volume of extraction and dispersive solvents, pH and salt effect. The primary extraction of sorbic and benzoic acids were performed in 8 mL NaOH (0.1 M) in a closed-vessel system. Carrez solutions (potassium hexaferrocyanide and zinc acetate) were used for protein sedimentation. The best simultaneous extraction efficiency was identified using acetone and 1-octanal as dispersive and extraction solvents, respectively. For DLLME, central composite design resulted in the optimised values of microextraction parameters as follows: 475 µL of dispersive and 60 µL of extraction solvents, 2 g NaCl at pH 2.5. Under optimum conditions, the calibration curve was linear over the range 0.1-50 μg mL(-1) and the square of correlation coefficient (R(2)) was 0.9992 for sorbic acid and 0.9994 for benzoic acid. Relative standard deviation (RSD %) was 6.1% and 3.1% (n = 5) for sorbic and benzoic acids, respectively. Limits of detection were 150 ng g(-1) for sorbic acid and 140 ng g(-1) for benzoic acid and recoveries were 88% and 103.7% respectively. Good reproducibility (RSD %), short extraction time and no matrix interference were advantages of the proposed method which was successfully applied to the determination of sorbic and benzoic acids in milk products.


A research facility for habitation questions to be built at the German Aerospace Center in Cologne: future challenges of Space medicine.
For long term habitation in space and for living on Moon and Mars, many questions still need to be resolved. Such habitation questions include prevention of and rehabilitation from negative effects of weightlessness that are, in many instances, comparable to problems of aging people on Earth as well as of patients during and recovery from long term stays in bed. Therefore the DLR Institute of Aerospace Medicine has designed a concept for a research facility that will make it possible to join space research directly with terrestrial applications. From a strategic point of view, one major emphasis of :envihab is to form a closely interrelated network of scientists and the industry and the public. The project has been in the planning phase for several years. After an international architectural contest, the winning concept was selected in 2007 by a Jury with ESA participation.


Codon reassignment in Candida species: an evolutionary conundrum.
A number of Candida species translate the standard leucine CUG codon as serine rather than as leucine. Such codon reassignment in nuclear-encoded mRNAs is unusual and raises a number of important questions about the origin of the genetic code and its continuing evolution. In particular we must establish how a codon can come to be reassigned without extinction of the species and what, if any, selective pressure drives such potentially catastrophic changes. Recent studies on the structure and identity of the novel CUG-decoding tRNA(Ser) from several different Candida species have begun to shed light on possible evolutionary mechanisms which could have facilitated such changes to the genetic code. These findings are reviewed here and a possible molecular mechanism proposed for how the standard leucine CUG codon could have become reassigned as a serine codon.


[Construction and clinical application of lentivirus-AQP4 expressing vector].
To construct the human aquaporin-4 (AQP4) expressing vector and detect anti-AQP4 antibody in serum of patients with neuromyelitis optica (NMO). RNA was extracted from human glioblastoma and AQP4 cDNA obtained through RT-PCR.The fragment was cloned into the lentiviral expressing vector (iDUET101) and transformed into competent strain Hb101 for later amplification; plasmids were extracted from the amplified positive-bacteria-colony, sequenced and transfected into HEK-293T cells. Expression of AQP4 was identified by RT-PCR, Western blot and immunofluorescence assay. And anti-AQP4 antibody in human serum was tested. The sequence of target fragment matched with that of human AQP4 fragment sequences (NM_001650) completely. The constructed AQP4 fragment transfected in HEK-293T cell was tested by immunofluorescent examination and it exhibited obvious fluorescence located in cell membrane. Western blot test was positive. And the fragment was about 34 KD. Cellular immunofluorescence examination showed 11 examples of 12 NMO patient serums (91.7%) were positive, 4 in 34 multiple sclerosis (11.8%) positive and negative in all 50 serum samples of healthy controls. The HEK-293T cell transfected with lentivirus-AQP4 vector can express stably. And the expressed fragment may be applied in clinical examination.


Guest induced morphological transformation from nanospheres to nanowires by hydrogen bond self-assembly.
Phosphorescent nanospheres of a carboxyl-functionalized iridium complex ([Ir(ppy)2(Hdcbpy)], ppy: 2-phenylpyridine; Hdcbpy: 4-carboxy-2,2'-bipyridyl-4'-carboxylate) were prepared by a conventional precipitation method. Driven by hydrogen bond interaction between carboxylic groups of the complex and the guest molecule tris(imidazoline), these nanospheres can be transformed into 1-dimensional nanowires in the presence of tris(imidazoline) at the concentration of the iridium complex higher than 4.8 mM, while nanowires change back to nanospheres with the diameter obviously smaller than that of the sole complex of [Ir(ppy)2(Hdcbpy)]. The interaction between carboxylic groups and tris(imidazoline) molecules was confirmed by FT-IR spectra. The structures of the nanowires and nanospheres were further studied by XRD diffraction analysis. With the morphological transformation from nanospheres to nanowires, the phosphorescence of nanostructures was blue shifted from 590 to 564 nm.


Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya.
HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear.


Propafenone disposition kinetics in cardiac arrhythmia.
Propafenone disposition kinetics were studied after intravenous and oral doses in patients with ventricular arrhythmias. Plasma concentration-time data were fit to a two-compartment model for all but one patient, whose data required fitting to a three-compartment model. The model-independent calculated values of clearance, steady-state volume of distribution, and terminal t1/2 were 11.2 +/- 4.8 ml/min/kg, 3.6 +/- 2.1 l/kg, and 5.0 +/- 3.6 hr. After 5 days on oral propafenone, elimination t1/2 was 6.2 +/- 3.3 hr. The longer t1/2s and the estimates of steady-state bioavailability above 100% suggests that clearance decreases during chronic oral dosing. Considerable intersubject variability was noted in all disposition parameters.


Effects of captopril in patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension.
Ten patients with chronic obstructive pulmonary disease (COPD) with normal left ventricular function were given a single dose of captopril (0.25 mg/kg). Mean systemic arterial pressure, heart rate and coronary flow to the right ventricle were reduced significantly after captopril. In contrast captopril did not cause a significant fall in pulmonary arterial pressure or pulmonary vascular resistance. We conclude that captopril fails to produce haemodynamic benefits in such hypoxic patients and that angiotensin II is not playing a significant role in maintaining pulmonary vasoconstriction.


Treatment of bone disease in patients on chronic hemodialysis with dihydrotachysterol.
Nine out of 24 patients on chronic hemodialysis were found to have biochemical, radiologic and bone biopsy evidence of moderate to severe bone disease. Two patients had bone pain and muscle weakness, 2 had pseudofractures, and one patient had a pathologic fracture of the neck of the femur. Eight patients were treated with dihydrotachysterol (D.H.T.), 0.25 to 0.37 mg/day initially. Four patients required doses between 0.5 and 1.0 mg daily. The alkaline phosphatase decreased in all patients, returning to normal in 6 patients. The symptoms of bone pain and muscle weakness resolved, and the pseudofractures healed. Repeat bone biopsies were performed in 6 patients 12 mos or more after treatment with D.H.T. The osteoid area fell from 29.6 +/- 22.8 to 11.5 +/- 7.5% (p less than 0.025). Resorptive surface decreased in all patients. D.H.T., in doses of up to 1.0 mg/day, is effective in the treatment of both the osteitis fibrosa and the osteomalacic component of bone disease in patients on hemodialysis.


Protein Kinase CK2 Regulates Leukocyte-Endothelial Cell Interactions during Ischemia and Reperfusion in Striated Skin Muscle.
Ischemia and reperfusion (I/R) causes tissue injury by inflammatory processes. This involves the upregulation of endothelial surface proteins by phospho-regulated signaling pathways, resulting in enhanced interactions of leukocytes with endothelial cells. Recently, we found that protein kinase CK2 is a crucial regulator of leukocyte-mediated inflammation. Therefore, in this study we investigated the involvement of CK2 in leukocyte-endothelial cell interactions during I/R injury. We first analyzed the inhibitory action of (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA) and CX-4945 on CK2 kinase activity and the viability of human dermal microvascular endothelial cells (HDMEC). To mimic I/R conditions in vitro, HDMEC were exposed to hypoxia and reoxygenation and the expression of adhesion molecules was analyzed by flow cytometry. Moreover, we analyzed in vivo the effect of CK2 inhibition on leukocyte-endothelial cell interactions in the dorsal skinfold chamber model of I/R injury by means of repetitive intravital fluorescence microscopy and immunohistochemistry. We found that TBCA and CX-4945 suppressed the activity of CK2 in HDMEC without affecting cell viability. This was associated with a significant downregulation of E-selectin and intercellular adhesion molecule (ICAM)-1 after in vitro hypoxia and reoxygenation. In vivo, CX-4945 treatment significantly decreased the numbers of adherent and transmigrated leukocytes in striated muscle tissue exposed to I/R. Our findings indicate that CK2 is involved in the regulation of leukocyte-endothelial cell interactions during I/R by mediating the expression of E-selectin and ICAM-1.


Psychometric evaluation of the Iranian version of brief fear of negative evaluation scale-straightforward item (BFNE-S): A validation study.
Background: The Brief Fear of Negative Evaluation Scale-Straightforward Item (BFNE-S) is an internationally recognized tool for measuring fear of negative evaluation. The current investigation was designed to assess the reliability and validity of the Persian version of BFNE-S in a non-clinical sample in Iran. Methods: A cross-sectional study was conducted on a sample of university students. They completed the Iranian version of the BFNE-S and the Social Phobia Inventory (SPIN). Internal consistency was assessed using the Cronbach's alpha coefficient. Validity was examined using known groups comparison to test how well the questionnaire differentiates between subgroups of the study sample that differed in gender. In addition convergent validity was performed to examine the correlation between the BFNE-S and scores derived from the SPIN. Furthermore, the structural validity of the questionnaire was examined by performing confirmatory factor analysis using the LISREL 8.8 software. Results: A total of 150 university students participated in the study. The results obtained from reliability analysis indicated that the Iranian version of the BFNE-S had desirable internal consistency. The Cronbach's alpha coefficient was 0.89. Satisfactory discriminant and convergent validity of the questionnaire also were established. The BFNE-S score was significantly higher in female respondents compared to male respondents as hypothesized (P = 0.008). The BFNE-S was correlated to the Iranian version of the Social Phobia Inventory (SPIN) in the expected direction (r = 0.58, P <0.001). The confirmatory factor analysis indicated a good fit to data lending support to its original one-dimensional structure. Conclusion: The findings indicated that the Iranian version of the BFNE-S was a valid measure of fear of negative evaluation. Since the scale showed a unitary factor structure, the theoretical basis for the BFNE-S is confirmed.


Rapid method for analysis of chloroacetanilide and chloronitrophenoxyaniline herbicides by gas chromatography.
The herbicides Alachlor and Alclonifen are recently used in France for pre-emergent weed control in corn, essentially in association. For this reason, an improved method has been developed by gas chromatography for simultaneously characterising and quantifying the two herbicides. The best conditions were obtained by using a gas chromatograph equipped with an ion trap detector, and a 30 m x 0.25 mm DB-1701 fused silica capillary column. Retention times of Alachlor and Aclonifen were 12.8 and 23.2 min respectively. The limit of detection was of 2.0 ppb for each herbicide.


Apigenin's anticancer properties and molecular mechanisms of action: Recent advances and future prospectives.
Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties. This review is intended to summarize the most recent advances in the anti-proliferative and chemo-preventive effects of apigenin in different cancer models. Analysis of the data from the studied cancer models has revealed that apigenin exerts its anti-proliferative effects through multiple and complex pathways. This guided us to discover some controversial results about the exact role of certain molecular pathways such as autophagy in the anticancer effects of apigenin. Further, there were cumulative positive evidences supporting the involvement of certain pathways such as apoptosis, ROS and DNA damage and repair. Apigenin possesses a high potential to be used as a chemosensitizing agent through the up-regulation of DR5 pathway. According to these preclinical findings we recommend that further robust unbiased studies should consider the possible interactions between different molecular pathways.


Management of Hyperactive Delirium in the Pediatric Intensive Care Unit: Case Series of Three Young Children.
Children in the intensive care unit (ICU) are at high risk of developing delirium, given their underlying disease processes, the adverse effects of treatments and medications, and the stressful, abnormal environment. If prevention and nonpharmacologic measures to treat delirium are unsuccessful, atypical antipsychotics are considered, although they are not approved by Food and Drug Administration for the treatment of pediatric delirium and could have significant adverse side effects. This case report presents three pediatric patients with hyperactive ICU delirium that risked life-threating complications who were successfully treated with short courses of atypical antipsychotic medications.


Insights into the organization of plumatellid larvae (lophotrochozoa, Bryozoa) by means of 3D-imaging and confocal microscopy.
Within the Lophotrochozoa, the Bryozoa or Ectoprocta remain one of the phyla whose phylogenetic relation to other lophotrochozoans is still controversely discussed. To complement existing data and to gain more insight into bryozoan character evolution, we analyzed the morphology of the larva of the phylactolaemate Plumatella sp. The larva of Plumatella spp. consists of an outer ciliated mantle that covers two differentiated polypides. The muscular and serotonergic nervous system of the polypides correspond to previous studies. The two polypides and their corresponding buds differ in size, which, together with a comparison among bryozoans, indicates that a single polypide is the basal condition. The whole larval mantle and mantle fold are supplied with circular and longitudinal muscles, the former being more pronounced in the mantle fold. The apical plate on the anterior side contains a diffuse mesh of crossing fibers and thus differs from previous descriptions, which recognized a regular muscular grid. The serotonergic nervous system in the mantle and mantle fold consists of a diffuse basiepidermal nerve net with its highest concentration at the apical plate. Serotonin immunoreactivity so far has not been detected in the mantle fold. However, the presence of other neurotransmitters in the mantle fold shown by previous studies indicates that this nerve net is a common feature of phylactolaemate larvae. The main difference between currently analyzed phylactolaemate larvae seems to be the complexity of the larval mantle musculature, which most likely plays an important role during metamorphosis. This study confirms previous interpretations that the apical plate pole does not correspond to the apical pole of gymnolaemate larvae but to their oral side. Accelerated asexual development on the aboral pole leads to the suggestion that an apical organ is never formed and the apical plate compensates for its absence in the free-swimming period.


Coherent dual-comb interferometry with quasi-integer-ratio repetition rates.
We demonstrate a generalized method for dual-comb interferometry that involves the use of two frequency combs with quasi-integer-ratio repetition rates. We use a 16.67 MHz comb to probe an 80-cm-long ring cavity and a 100 MHz comb to asynchronously sample its impulse response. The resulting signal can be seen as six time-multiplexed independent interferograms. We perform a deconvolution of the photodetector's impulse response to prevent any crosstalk between these multiplexed data sets. The measurement is then demultiplexed and corrected with referencing signals. We obtain a measurement with a spectral point spacing of 16.67 MHz and a spectral SNR of 55 dB by averaging 15,000 interferograms, corresponding to a measurement time of 500 s. Compared to conventional dual-comb spectroscopy, this generalized technique allows to either reduce the spectral point spacing or the acquisition time by changing the repetition rate of only one of the combs.


[Studies on restraint ulcers in rats in conditions of acute copper deficiency].
In the present experiment, we have investigated the impact of the acute copper deficiency on the pathogenesis of stress ulcers' formation in rats during cold-restraint stress. A powdered milk diet, lasting for 5 days, causes a significantly decrease of stomach copper content in rat, comparing to content in rats receiving standard laboratory diet. The severity of mucosal disturbances, expressed as total number and area of stress ulcers, is most prominent in animals receiving hypocupric diet. Their treatment with Ranitidine extends the morphological disturbances in the stomach mucosa and produces highest level of lipid peroxidation and lowest activity of superoxide dismutase in the stomach compared to the other groups. In conclusion, the appropriate copper balance plays an essential role for the natural resistance of the stomach mucosa and Ranitidine, in conditions of acute copper deficiency, makes deeper the disturbances produced by stress.


Influence of atrial fibrillation in trans-catheter aortic valve replacement.
In high-risk patients with severe aortic stenosis transcatheter aortic valve replacement (TAVR) procedures have been found to be beneficial. Up to now TAVR has been preferably performed on elderly patients, who cannot undergo conventional aortic valve replacement (AVR). Usually, due to their advanced age, these patients suffer from atrial fibrillation (AF) and are also more predisposed to present left ventricular dysfunction. Both conditions influence short and long-term prognosis in conventional AVR surgery. We do not really know how this translates in new procedures such as TAVR. The purpose of the present paper was to review how AF could affect TAVR procedures.


Differences in management of atrial fibrillation between cardiologists and non-cardiologists in Greece.
We aimed to assess trends in the management of atrial fibrillation (AF) at various levels of medical care in Greece and to compare the treatment practices of cardiologists to those of non-cardiologists. From January to May 2007, 500 questionnaires were mailed to cardiologists, internists and general practitioners, randomly selected from regional medical associations. Questions assessed management practices for paroxysmal, persistent and permanent AF. A total of 309 physicians (194 cardiologists and 115 non-cardiologists) responded. Cardiologists showed no preference regarding the site of cardioversion of paroxysmal AF, whereas non-cardiologists tend to cardiovert paroxysmal AF in the emergency department. Intravenous amiodarone is the most frequently used antiarrhythmic agent for cardioversion by both groups (63% vs. 71%, p=NS). Cardiologists utilise propafenone or ibutilide more frequently than non-cardiologists (24% vs. 11%, p<0.05 and 10% vs. 2%, p<0.01 respectively), while 12% of non-cardiologists would use digitalis for cardioversion (vs. 0.5% of cardiologists, p<0.001). Cardiologists prescribe commonly, but less frequently than non-cardiologists (42% vs. 59%, p<0.01) an antiarrhythmic drug after the first episode of paroxysmal AF, propafenone being the most popular among cardiologists (66%) and amiodarone (33%) or digitalis (23%) among general practitioners/internists. Beta-blockers are considered as first choice agents for rate control among cardiologists, while non-cardiologists would prescribe mainly digitalis. Antiplatelet agents were suggested by most physicians after cardioversion of the first episode of AF in low-risk patients. Cardiologists prefer aspirin, while non-cardiologists would prescribe clopidogrel as first choice antiplatelet agent. Both groups would recommend anticoagulants in high risk patients; nevertheless, in elderly patients without other risk factors, anticoagulants are more often prescribed by cardiologists (79% vs. 50%, p<0.001). Important differences exist in the management of AF between cardiologists and general practitioners/internists in Greece. Non-cardiologists overuse digitalis, underuse beta-blockers, prefer clopidogrel to aspirin and are reluctant to prescribe anticoagulants in the elderly.


Removal of ammonia by OH radical in aqueous phase.
Many advanced oxidation technologies have been developed to remove ammonia in wastewater. All these technologies have one common characteristic, that is, the removal processes involve OH radical (*OH). In this research work, H2O2 was selected as *OH precursor. The removal of ammonia under 253.7 nm irradiation from low-pressure mercury lamp in the presence of H2O2 was studied to investigate the ammonia removal efficiency by *OH. Results show that the *OH, generated by H2O2 photolysis, could oxidize NH3 to NO2- and further to NO3-. Removal efficiencies of ammonia were low and were affected by initial pH value and ammonia concentration. Laser flash photolysis technique with transient absorption spectra of nanosecond was used to investigate the oxidation pathway and kinetics of ammonia oxidation by *OH. Results illustrate that *OH could oxidize NH3 to form *NH2 with a second-order rate constant of (1.0 +/- 0.1) x 10(8) M(-1) s(-1) (20 degrees C). *NH2, the main product of *OH with NH3, would further react with H2O2 to yield *NHOH. Since *NHOH could not stay stable in solution, it would rapidly convert to NH2O2- and consequently NO2- and NO3-. The rate constants for these elementary reactions were also given. The low removal efficiency of ammonia by *OH was mainly due to the slow reaction rate constant


High Frequency of Homologous Recombination in the Genome of Modified Vaccinia Virus Ankara Strain (MVA).
MVA is a genetically modified vaccinia virus strain, which is replication defective and extremely safe for research and clinical use. To further improve the safety of MVA and achieve more efficient selection of recombinant constructs, a transient selection marker system has been developed, which contains vaccinia virus k1l gene flanked by two identical fragments. In this report, four recombinant MVAs were constructed with this system, and homologous recombination of recombinant MVAs was studied during the construction procedure. The results showed that the recombination frequency of these rMVAs was significantly high, though lower than that observed in other vaccinia virus strains. The k1l free rMVAs could be conveniently obtained after 3 or 4 blind passages. Our data indicated that recombinant MVA with a transient selection marker system was safe for use as live vaccine and gene therapy vector for human. In addition, blind passages could enhance the efficiency in isolation of k1l free recombinants


Two new coumarins from Talaromyces flavus.
Two new coumarins, talacoumarins A (1) and B (2), were isolated from the ethyl acetate extract of the wetland soil-derived fungus Talaromyces flavus BYD07-13. Their structures were elucidated by spectroscopic data (NMR, MS) analyses. The absolute configuration of C-12 in 1 was assigned using the modified Mosher's method, whereas that of C-12 in 2 was deduced via the circular dichroism data of its corresponding [Rh2(OCOCF3)4] complex. Compounds 1 and 2 were evaluated for their anti-Aβ42 aggregation, cytotoxic, and antimicrobial activities. The results showed that the two compounds had moderate anti-Aβ42 aggregation activity, and this is the first report on the Aβ42 inhibitory aggregation activity of coumarins.


Influence of Different Techniques of Laboratory Construction on the Fracture Resistance of Fiber-Reinforced Composite (FRC) Bridges.
The aim of the current investigation is to evaluate optimal pontic and retainer fiber positions for Polyethylene fiber-reinforced composite (FRC) restorations. In series I notch disc specimens were used to mimic loading cuspal regions of pontics. Four groups (n=15/group; codes A to D) were prepared from Artglass composite. Groups A to C were reinforced with polyethylene fibers, and group D was an unreinforced control. Fibers were positioned either around (A), beneath the notch (B), or at the disc base (C). Specimens were stored in distilled water at 37 degrees C for 24 h before testing to failure (CHS=1mm/min) in a universal testing machine. Mean torque to failure values ranked [P< 0.05; one-way analysis of variance (ANOVA)] as follows A = B > C = D. In series II five groups of three unit bridges (n =5/group; codes A to E) were prepared from Artglass dental composite without (group A) or with (groups B to E) different Connect fiber reinforcement locations/techniques. Bridges were cemented using 2 bond resin cement to a standardized substructure. After storage, as per series I, bridges were loaded mid-pontic region to failure. One-way ANOVA showed no significant (P=0.08) difference between test groups. The research hypothesis was that notched disc and 3 unit bridge test techniques would discriminate equally between fiber-reinforced specimens and an unreinforced composite control was rejected.


How Much Volume Should Healthcare Ethics Consult Services Have?
No standard method exists to assess how many consults a healthcare ethics consultation (HCEC) service should perform. To address this, we developed a method to estimate the volume of HCEC services based on a mixed-methods approach that included a systematic review and survey data on the volume of consult services requested. Our investigation included a systematic review of studies that reported the volume of HCEC services that were requested from 2000 to 2017, institutional surveys, and statistical analyses that estimated the volume of HCEC services that were adjusted to the size of the hospitals in the survey and to population acuity. We contacted the authors of 19 studies that met our inclusion criteria; 17 authors responded to the institutional survey and five provided annualized data points. We found that standard methods of reporting the volume of HCEC services led to inaccuracies in estimating the growth of HCEC services over time. To rectify this, we proposed two means to estimate volume based on either the service goals of HCEC services or hospital size and acuity. The statistical limitations of our study highlight the need to standardize the sharing and reporting of data in clinical ethics. Future work should further standardize methods of HCEC quality assessment using measures similar to those we describe.


U2@ I h(7)-C80: Crystallographic Characterization of a Long-Sought Dimetallic Actinide Endohedral Fullerene.
The nature of actinide-actinide bonds has attracted considerable attention for a long time, especially since recent theoretical studies suggest that triple and up to quintuple bonds should be possible, but little is known experimentally. Actinide-actinide bonds inside fullerene cages have also been proposed, but their existence has been debated intensively by theoreticians. Despite all the theoretical arguments, critical experimental data for a dimetallic actinide endohedral fullerene have never been obtained. Herein, we report the synthesis and isolation of a dimetallic actinide endohedral metallofullerene (EMF), U2@C80. This compound was fully characterized by mass spectrometry, single crystal X-ray crystallography, UV-vis-NIR spectroscopy, Raman spectroscopy, cyclic voltammetry, and X-ray absorption spectroscopy (XAS). The single crystal X-ray crystallographic analysis unambiguously assigned the molecular structure to U2@ I h(7)-C80. In particular, the crystallographic data revealed that the U-U distance is within the range of 3.46-3.79 Å, which is shorter than the 3.9 Å previously predicted for an elongated weak U-U bond inside the C80 cage. The XAS results reveal that the formal charge of the U atoms trapped inside the fullerene cage is +3, which agrees with the computational and crystallographic studies that assign a hexaanionic carbon cage, ( I h-C80)6-. Theoretical studies confirm the presence of a U-U bonding interaction and suggest that the weak U-U bond in U2@ I h(7)-C80 is strengthened upon reduction and weakened upon oxidation. The comprehensive characterization of U2@ I h(7)-C80 and the overall agreement between the experimental data and theoretical investigations provide experimental proof and deeper understanding for actinide metal-metal bonding interactions inside a fullerene cage.


Circum-pacific late cenozoic structural rejuvenation: implications for sea floor spreading.
The hypothesis of sea floor spreading and lithosphere plates seems to unify the origins of both oceanic ridges and volcanic arc-trench systems; therefore knowledge of well-known land areas should shed light upon sea floor tectonics. Impressive evidence of a major mid-Cenozoic discontinuity in the tectonic history of circum-Pacific land areas suggests a roughly synchronous change in sea floor development, more evidence for which may be anticipated in the future.


The development of end-state comfort planning in preschool children.
We investigated the development of the end-state comfort effect in young children. Fifty-one children from three age-groups (3, 4, and 5 years old) participated in the study. They performed the dowel placing task, which required them to reach for a horizontal dowel and to insert one of its ends into a target disk. Depending on which end was instructed, end-state comfort could be reached by picking up the dowel either with an overhand or with an underhand grip. All children reached for the dowel with an overhand grasp when this resulted in a comfortable end-state (i.e., thumb-up posture). A different pattern emerged when an underhand grip had to be selected. Here, 18% of the 3-year-olds, 45% of the 4-year-olds, and 67% of the 5-year-olds used an underhand grip and finished the action comfortably. For the first time, these results show a distinct pattern of gradual improvement in children's sensitivity to reach end-state comfort across three age-groups.


Child custody mediation: an interdisciplinary synthesis.
The high divorce rate and increasing number of children affected by divorce have paralleled major changes both in divorce law and in the ways in which social conflicts are resolved. Principles of contemporary law and conflict resolution are joined with the findings of research on child development in families of divorce in a conceptual synthesis relevant to the practice of child custody mediation.


An exploration of attitudes towards female genital mutilation (FGM) in men and women accessing FGM clinical services in London: a pilot study.
This pilot study researched the attitudes towards and the knowledge of female genital mutilation (FGM) in adult women with FGM and their partners. The participant population consisted of English-speaking women and men over 18 years old attending specialist FGM clinics in two London hospitals. The participants completed a questionnaire on the attitudes and the knowledge of FGM, which were adapted with permission from the United Nations Children's Fund and the United States Agency for International Development household surveys. 54 participants (51 women, 3 men) took part in the surveys. 89% of participants thought that FGM should be stopped (95%CI: 0.81-0.97) and 72% said they knew FGM is illegal in the United Kingdom (UK). 15% reported that FGM caused no danger, or were unaware of any danger to women's health. This study demonstrates the opposition to FGM by participants, but some lack of knowledge regarding the legal and health implications. The exploration of attitudes in diaspora community groups is often cited as key to safeguarding girls from FGM. This is one of the first UK studies of individuals from FGM-practising communities, and we recommend use of the study questionnaires for a multicentre, cross-community study. Impact statement What is already known about this subject? Women and children are affected by female genital mutilation (FGM) globally and in the United Kingdom (UK). The majority of knowledge on practices and the attitudes towards FGM comes from UNICEF and USAID research in Africa and there is scant data on FGM practices in diaspora communities in the UK. What do the results of this study add? This study provides an appropriate questionnaire and protocol for use in community-based national research to improve healthcare for women by collecting up-to-date data on the attitudes towards FGM among the members of FGM-practising communities in the UK. What are the implications of these findings for clinical practice and further research? The implications of the results of this study are that health professionals need to understand that patients do not always know the law on FGM, even after a consultation. Health and social care professionals are placed in a unique position to work with community members to educate men and women to end FGM.


[Retropharyngeal abscess in an adult and an elderly woman].
Retropharyngeal abscess is reported to be decreasing in frequency in recent years. We report two cases of retropharyngeal abscess that were diagnosed within four years in Department of Otorhinolaryngology, Gifu University Hospital. Case 1 was a 36-year-old male who was suggested to have an abscess as primary infection and case 2 was a 71-year-old female whose abscess seemed to be a secondary infection following unknown primary infection. Endoscopic or open neck drainage as well as antibacterial chemotherapy mainly with combinations of flomoxef and clindamycin in the case 1 and piperacillin and clindamycin in the case 2 was successfully carried out. They were discharged an 15-day and 24-day after operation in the cases 1 and 2, respectively. A 30 min. culture after sample collection on operation demonstrated aerobe-anaerobe mixed infection in both cases; three aerobes and four anaerobes in the case 1 and three aerobes and two anaerobes in the case 2. These results suggest that retropharyngeal abscess may be a complicated infection involving more bacterial species than has been commonly believed. Measuring susceptibility of isolates to antimicrobial agents, a strain of Capnocytophaga sp. and a strain of anaerobic gram-negative rod were highly resistant to piperacillin, cefroxine and ofloxacin. It is important for adequate antibacterial chemotherapy to grasp the bacteriology of retropharyngeal abscess and analyze susceptibility of antimicrobial agents.


Application of predictive biosimulation within pharmaceutical clinical development: examples of significance for translational medicine and clinical trial design.
The challenge of accurately predicting human clinical outcome based on preclinical data has led to a high failure rate of compounds in human clinical trials. A series of methods are described by which biosimulation can address these challenges and guide the design and evaluation of experimental and clinical protocols. Early compound development often proceeds on the basis of preclinical data from animal models. The systematic evaluation possible in a simulation can assist in the critical step of translating the preclinical outcomes to human physiology. Later in the process, clinical trials definitively establish a therapy's beneficial effects, as well as any adverse side effects. Biosimulation allows for the optimal design of clinical trials to ensure that key issues are addressed effectively and efficiently, and in doing so, improves the success rate of the trials.


Specific sites in the cytoplasmic N terminus modulate conformational transitions of the Na,K-ATPase.
The cytoplasmic N terminus of the Na,K-ATPase is a highly charged and flexible structure that comprises three predicted helical regions including H1 spanning residues 27 to 33 and H2 spanning residues 42 to 50. Previous deletion mutagenesis experiments showed that deletion of residues up to and including most of H2 shifts the E(1)/E(2) conformational equilibrium toward E(1). The present study describes a clustered charge-to-alanine mutagenesis approach designed to delineate specific sites within the N terminus that modulate the steady-state E(1) <--> E(2) and E(1)P <--> E(2)P poise. Criteria to assess shifts in poise include (i) sensitivity to inhibition by inorganic orthovanadate to assess overall poise; (ii) K(+)-sensitivity of Na-ATPase measured at micromolar ATP to assess changes in the E(2)(K) + ATP --> E(1) x ATP + K(+) rate; (iii) K'(ATP) for low-affinity ATP binding at the latter step; (iv) overall catalytic turnover, and (v) the E(1)P --> E(2)P transition. The results of alanine replacements in H1 (31KKE) suggest that this site stabilizes E(2)P and to a lesser extent E(2). In H2, residues within 47HRK have a role in stabilizing E(2) but not E(2)P as revealed with double mutants 31KKE --> AAA/47H --> A and 31KKE --> AAA/47HRK --> AAA. Taken together, these observations suggest that sites 31KKE in H1 and 47HRK in H2 have distinct roles in modulating the enzyme's conformational transitions during the catalytic cycle of the enzyme.


Poncet's disease. A case report.
A patient with tuberculosis and polyarthritis is described. The investigations and rapid resolution of the arthritis in response to therapy suggested the diagnosis of Poncet 's disease. The distinction between Poncet 's disease and tuberculous arthritis is prognostically important.


Comprehensive analysis of differential expression profiles of mRNAs and lncRNAs and identification of a 14-lncRNA prognostic signature for patients with colon adenocarcinoma.
The objective of this study was to identify potentially significant genes and long non-coding RNAs (lncRNAs) in colon cancer for a panel of lncRNA signatures that could be used as prognostic markers for colon adenocarcinoma (COAD) based on the data from The Cancer Genome Atlas (TCGA). RNA-seq V2 exon data of COAD were downloaded from the TCGA data portal for 285 tumor samples and 41 normal tissue samples adjacent to tumors. Differentially expressed mRNAs and lncRNAs were identified. A functional enrichment analysis of differentially expressed mRNAs was performed, followed by protein-protein interaction (PPI) network construction and significant module selection. Additionally, the regulatory relationships in differentially expressed mRNAs and lncRNAs were assessed, and an lncRNA-lncRNA co-regulation and functional synergistic analysis were performed. Furthermore, the risk score model and Cox regression analysis based on the expression levels of lncRNAs were used to develop a prognostic lncRNA signature. A total of 976 differentially expressed mRNAs and 169 differentially expressed lncRNAs were identified. MDFI and MEOX2 were the PPI network hubs. We found these lncRNAs to be mainly involved in vascular smooth muscle contraction and the cGMP-PKG signaling pathway. Several lncRNA-lncRNA pairs had co-regulatory relationships or functional synergistic effects, including BVES-AS1/MYLK-AS1, ADAMTS9-AS1/MYLK-AS1 and FENDRR/MYLK-AS1. The differential expression profile analysis of four candidate lncRNAs (MYLK-AS1, BVES-AS1, ADAMTS9-AS1, and FENDRR) in COAD tumors were confirmed by reverse transcription-quantitative PCR. Moreover, this study identified a 14-lncRNA signature that could predict the survival for COAD patients.


Comparison of noncross-linked and cross-linked hyaluronic acid with regard to efficacy of the proliferative activity of cutaneous fibroblasts and keratinocytes in vitro.
Intradermal application of hyaluronic acid (HA) in varying chain length and cross-linking density is used routinely for hydrodynamic volume replacement of the extracellular matrix to reduce the clinical effects of aging. In vitro data show that via receptors of the hyaladherin group hyaluronic acid has additionally direct or indirect effects on cells. In the case of native noncross-linked HA, it has been proved that the proliferative and metabolic activity of cutaneous fibroblasts can be increased. The aim of this study was to investigate whether these effects can be proved also for cross-linked HA and how these effects can be quantified for different preparations. The effect on proliferative activity in cultures of native cutaneous fibroblasts and keratinocytes was investigated for noncross-linked HA, for noncross-linked HA with added glycerol, for HA that was stabilized in the carboxyl and hydroxyl groups per inner esterification, and for HA that was chemically cross-linked by 1,4-butanediol-diglycidylether, mixed in small particles in a biphasic compound with native HA, each in different concentrations (0.1, 1.0 and 10.0 mg/mL). HA that was stabilized in the carboxyl and hydroxyl groups per inner esterification induces the strongest proliferative effect on both cell types. Native noncross-linked HA and chemically cross-linked HA show a rather modest proliferative effect and on fibroblasts only, whereas noncross-linked HA with added glycerol in high concentrations provokes a rather antiproliferative effect. The data show that HA does induce direct effects on cells depending on type and density of the cross-linkage. The practical relevance in terms of a metabolic filler effect needs to be verified in clinical studies.


Exploring the potential of gametic reconstruction of parental genotypes by F1 hybrids as a bridge for rapid introgression.
Interspecific hybridization and genetic introgression are commonly observed in natural populations of many species, especially trees. Among oaks, gene flow between closely related species has been well documented. And yet, hybridization does not lead to a "melting pot", i.e., the homogenization of phenotypic traits. Here, we explore how the combination of several common reproductive and genomic traits could create an avenue for interspecific gene flow that partially explains this apparent paradox. During meiosis, F1 hybrids will produce approximately (½)n "reconstructed" parental gametes, where n equals the number of chromosomes. Crossing over would introduce a small amount of introgressive material. The resulting parental-type gametophytes would probably possess a similar fertilization advantage as conspecific pollen. The resulting "backcross" would actually be the genetic equivalent of a conspecific out-cross, with a small amount of heterospecific DNA captured through crossing over. Even with detailed genomic analysis, the resulting offspring would not appear to be a backcross. This avenue for rapid introgression between species through the F1 hybrid will be viable for organisms that meet certain conditions: low base chromosome number, conserved genomic structure and size, production of billions of gametes/gametophytes during each reproductive event, and conspecific fertilization advantage.