Fine-scale movements and habitat use of juvenile southern flounder Paralichthys lethostigma in an estuarine seascape.
Habitat use of juvenile southern flounder Paralichthys lethostigma was examined within a shallow estuarine seascape during June and July 2011 using acoustic telemetry. Fine-scale movement and habitat use of P. lethostigma was investigated with an acoustic positioning system placed in a seascape that varied in habitat type, physicochemical conditions and bathymetry. The use of different habitat types was examined with Euclidean distance-based analyses, and generalized additive models were used to determine the relative importance of habitat type relative to physicochemical conditions and bathymetry. Tracks of P. lethostigma ranged in distance between 1477 and 8582 m and speed was 4·2 ± 1·1 m min⁻¹ (mean ± s.e.) for all P. lethostigma combined. Depth, slope and habitat type had the most influence on P. lethostigma occurrence and deep sandy areas with shallow slopes were used most frequently. In addition, depth use by P. lethostigma was influenced by tidal cycles, indicating habitat use varies temporally and is dynamic. Finally, temperatures <30·5° C were used more than warmer waters within the study area. The results successfully identify movements by juvenile P. lethostigma, and indicate that definitions of essential habitats need to account for dynamics in habitat use.


Total Synthesis and Biological Assessment of Mandelalide A.
A new convergent total synthesis of the marine macrolide mandelalide A (1) has been developed that is based on macrocyclic ring closure by a Shiina-type macrolactonization and the construction of the requisite precursor seco acid by a highly efficient Sonogashira cross-coupling reaction between two fragments of comparable complexity. Key steps in the elaboration of the acid building block were the enantioselective, catalytic addition of a protected acetylene to crotonaldehyde and the construction of the tetrahydropyran unit that is embedded in the macrocycle by means of an acid-catalyzed Prins reaction. The synthesis of the alcohol fragment features the formation of the trisubstituted tetrahydrofuran ring through an acetal cleavage/epoxide opening cascade reaction and a rarely used radical alkynylation of a primary alkyl iodide. Intriguingly, the dihydroxylation of a terminal double bond as part of the synthesis of this building block gave the same major product for both the α- and β-AD-mix reagents, albeit with moderate or low selectivity. Synthetic mandelalide A (1) was a potent proliferation inhibitor of A549, HT460, and H1299 human lung cancer cells in vitro, but not of SK-N-SH neuroblastoma cells. However, in no case did we observe complete cell kill even at the highest compound concentration tested (5 μm).


Surface and depth profiling investigation of a drug-loaded copolymer utilized to coat taxus express2 stents.
The surface of a styrene-b-isobutylene-b-styrene triblock copolymer, containing a solid-phase drug, was studied by time-of-flight secondary ion mass spectrometry employing 15-keV Ga+ and 20-keV C60+ ion sources. This polymer/drug system has direct application in the cardiac stent arena, where it has been used to treat restenosis or renarrowing of arterial walls after stent or angioplasty procedures. Overall, the results illustrate the successful use of a cluster ion beam for greatly enhancing the high-mass fragment ion and molecular ion intensities from the surface and bulk of the polymer system. The use of C60+ also established the ability to remove common overlayers like poly(dimethylsiloxane), which was not possible using a Ga+ ion source. Furthermore, the use of C60+ allowed depth profiles to be obtained using primary ion dose densities in excess of 6 x 1014 C60+/cm2. Resultant sputter craters reached depths of approximately 2 microm and possessed relatively flat bottoms without the need for sample rotation. AFM and profilometry studies support the relatively gentile removal of surface species via phase contrast and topographic imaging. In addition, the findings suggest that relatively high ion doses do not significantly alter the phase distribution or surface topography of the polymer surface; however, a slight increase in surface roughness was detected.


Antireflective silica thin films with super water repellence via a solgel process.
A solgel process was developed, through which silica films possessing both high antireflection and super water repellence were obtained. In this process, methyl-modified SiO2 sols synthesized by colloidal suspension of SiO2 particles and hexamethyldisilazane (HMDS) were used to deposit spinning-coating films on optical glass substrates. On the resultant films the contact angle for water increased with the increasing amount of HMDS in the reaction mixture. The biggest contact angle was 165 degrees, and the lowest reflectivity on one-sided film reached 0.03%. The antireflections were high all the while. One advantage of this process is that neither a roughened surface nor fluoroalkyltrialkoxylsilane (FAS) is needed to obtained super water repellence.


Serum proline and blood lactate levels in alcoholic patients without hepatic failure: relationship with alcohol ingestion and histological activity.
It has not yet been established whether serum proline and blood lactate levels are increased in alcoholic liver disease. We measured serum proline and blood lactate in controls and in patients with different stages of alcoholic liver disease in the absence of hepatic failure. Samplings were done in both abstinent and drinking alcoholics. Compared to controls, there was a striking increase in serum proline levels in 52 abstinent alcoholics with little or no hepatic fibrosis by histological assessment (0.10 +/- 0.01 vs. 0.155 +/- 0.008; p less than 0.005). Blood lactate levels were within the normal range and did not correlate with serum proline levels. On the other hand, serum proline and blood lactate levels were independent of hepatic necrosis and inflammation scores. In addition, in 10 patients with blood alcohol concentrations between 0.3 mg/ml and 7.8 mg/ml, serum lactate and proline were significantly elevated (2.42 +/- 0.29 mg/ml and 0.275 +/- 0.0026 mg/ml, respectively; p less than 0.005). These results show that there is an association between serum proline levels and the abstinence period in alcoholic patients. They further suggest that in alcoholic patients neither serum proline nor blood lactate concentrations are reliable markers for liver histological activity (necrosis and inflammation) or fibrosis.


The ovalbumin gene is associated with the nuclear matrix of chicken oviduct cells.
The DNA in a eucaryotic nucleus is arranged into a series of supercoiled loops that are anchored at their bases to the nuclear matrix. Using nuclease digestion, one can progressively cleave DNA from the loops, thereby isolating residual DNA that is progressively closer to the nuclear matrix anchorage sites. We have determined that the ovalbumin gene is preferentially associated with the nuclear matrix of chicken oviduct cells, but is not preferentially associated with the nuclear matrix of chicken liver cells. As a control, the beta-globin gene, which is not transcribed in oviduct cells, was found not to be preferentially associated with the oviduct nuclear matrix. The observation that the transcriptionally active ovalbumin gene is preferentially associated with the nuclear matrix may have significant implications for gene expression and the organization of nuclear DNA into supercoiled-loop domains.


Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer.
Although multidrug resistance (MDR) is known to develop through a variety of molecular mechanisms within the tumor cell, many tend to converge toward the alteration of apoptotic signaling. The enzyme glucosylceramide synthase (GCS), responsible for bioactivation of the proapoptotic mediator ceramide to a nonfunctional moiety glucosylceramide, is overexpressed in many MDR tumor types and has been implicated in cell survival in the presence of chemotherapy. The purpose of this study was to investigate the therapeutic strategy of coadministering ceramide with paclitaxel, a commonly used chemotherapeutic agent, in an attempt to restore apoptotic signaling and overcome MDR in the human ovarian cancer cell line SKOV3. Poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were used to encapsulate and deliver the therapeutic agents for enhanced efficacy. Results show that indeed the cotherapy eradicates the complete population of MDR cancer cells when they are treated at their IC(50) dose of paclitaxel. More interestingly, when the cotherapy was combined with the properties of nanoparticle drug delivery, the MDR cells can be resensitized to a dose of paclitaxel near the IC(50) of non-MDR (drug sensitive) cells, indicating a 100-fold increase in chemosensitization via this approach. Molecular analysis of activity verified the hypothesis that the efficacy of this therapeutic approach is indeed due to a restoration in apoptotic signaling, although the beneficial properties of PEO-PCL nanoparticle delivery seemed to enhance the therapeutic success even further, showing the promising potential for the clinical use of this therapeutic strategy to overcome MDR.


Stars versus warnings: Comparison of the Australasian Health Star Rating nutrition labelling system with Chilean Warning Labels.
The Health Star Rating (HSR) is a voluntary front-of-pack nutrition labelling system that rates products from ½ to 5 stars (five being healthiest). The Chilean Warning Label system displays warnings on foods high in sugar, saturated fat, sodium, or energy. We aimed to evaluate alignment between the systems. New Zealand packaged products (n=13,868) were classified according to the two systems. Alignment was assessed by cross-checking the number of products meeting the criteria for warnings against star ratings. Products with no warnings but an HSR <2, or with >1 warning but an HSR of ≥3.5 were considered outliers. Two-thirds of products met the criteria for at least one warning. There was a significant positive relationship between the number of warnings and mean HSR: 0 warnings = HSR 3.77±.0166 (p<0.001), 1 warning = HSR 2.70±.0206 (p<0.001) and >1 warning = HSR 2.00±.0160 (p<0.001). The systems were non-aligned for 1,117 products (8%). HSR and the Chilean Warning Label systems are broadly aligned. Non-alignment is due to the Chilean system restricting warnings to foods containing added ingredients and HSR awarding points for positive components. Implications for public health: These results could be helpful in informing improvements to the HSR system.


[The physiological characteristics of the antioxidant properties of Lipin in bronchial asthma in children].
In children of 4-7 years old with bronchial asthma (BA) has been studied the values of lipid peroxidation, antioxidant status and some others in blood plasma and erythrocytes without and with the use of new drug Lipin. It was shown that in children with BA the malondialdehyde concentration increased, the superoxydedismutase activity decreased, the NAD concentration increased, and the ratio of superoxidedismutase/malondialdehyde greatly decreased in comparison with normal children. The use of Lipin led to diminuation of lipid peroxidation, to marked increase of superoxidedismutase activity, to decrease of NAD concentration, and to significant increase of superoxidedismutase/malondialdehyde ratio. These results were indicated on the expressed antioxidant properties of Lipin in children's with BA.


Measured infrared optical cross sections for a variety of chemical and biological aerosol simulants.
We conducted a series of spectral extinction measurements on a variety of aerosolized chemical and biological simulants over the spectral range 3-13 microm using conventional Fourier-transform IR (FTIR) aerosol spectroscopy. Samples consist of both aerosolized particulates and atomized liquids. Materials considered include Bacillus subtilis endospores, lyophilized ovalbumin, polyethylene glycol, dimethicone (SF-96), and three common background materials: kaolin clay (hydrated aluminum silicate), Arizona road dust (primarily SiO2), and diesel soot. Aerosol size distributions and mass density were measured simultaneously with the FTIR spectra. As a result, all optical parameters presented here are mass normalized, i.e., in square meters per gram. In an effort to establish the utility of using Mie theory to predict such parameters, we conducted a series of calculations. For materials in which the complex indices of refraction are known, e.g., silicone oil (SF-96) and kaolin, measured size distributions were convolved with Mie theory and the resultant spectral extinction calculated. Where there was good agreement between measured and calculated extinction spectra, absorption, total scattering, and backscatter were also calculated.


[Effect of hypervolemic hemodilution on C-reactive protein level in patients receiving spinal surgery].
To investigate the changes in high-sensitivity C-reactive protein (hs-CRP) levels following acute hypervolemic hemodilution (AHH) in patients undergoing spinal surgery and assess the safety of AHH in terms of postoperative infection. Forty patients undergoing spinal operation were randomly assigned into observation group and control group (n=20). Each patient was infused 4 ml/kg/h lactated Ringers solution for maintenance of the total blood volume, and in the observation group, the patients received additional infusion of 4% gelofusine solution at the rate of 20 ml/kg/h 30 min before the operation. Venous blood samples were collected to monitor the hematocrit (Hct), prothrombin time (PT), activated partial thromboplastin time (APTT) and hs-CRP before anesthesia (T0), 2 h after the beginning of the operation (T1), at the end of the operation (T2), and 24 h after the operation (T3). After AHH, Hct decreased significantly at T1 as compared with that at T0 (P<0.05) and that of the control group (P<0.01), but showed no significant difference between the two groups at T2. PT and APTT showed significant changes at T1 compared with T0 (P<0.05) but within the normal range, and were similar between the two groups at T3. hs-CRP increased significantly in the two groups at T3 compared with that at T0 (P<0.05), and a significant difference was noted between the two groups (P<0.01). AHH does not affect the hemodynamics and blood coagulation of the patients undergoing spinal surgery but causes a significant elevation of hs-CRP, suggesting an increased risk of postoperative infection.


Oxygenated Fatty Acids with Anti-rice Blast Fungus Activity in Rice Plants.
Expecting that the different characteristics of rice plants against rice blast fungus, that is, susceptibility of the weaker cultivar, Sasanishiki and resistance of the stronger cultivars, Fukuyuki and Fukunishiki, may be due to the absence or presence of anti-fungus compounds in the rice plants, the anti-rice blast fungus substances in these three kinds of rice plants were explored. We found five epoxides and five allyl alcohols as anti-rice blast fungus compounds. The epoxides were 12,13-epoxy- and 9,10-epoxylinoleic acids, and 15,16-epoxy-, 12,13-epoxy-, and 9,10-epoxylinolenic acids. The allyl alcohols are 13-hydroxy and 9-hydroxy linoleic acids, and 16-hydroxy, 13-hydroxy, and 9-hydroxy linolenic acids. In inoculated Sasanishiki, the activity is due to the formation of the allyl alcohols.


Complex intrapatient sequence variation in the V1 and V2 hypervariable regions of the HIV-1 gp 120 envelope sequence.
Human immunodeficiency virus (HIV) quasi-species fluctuate both in time and in space. In general intrapatient variation is less extensive than interpatient variation. The V1 and V2 hypervariable regions of the envelope gene were analyzed for patient samples harboring highly divergent genomes in other loci. Proviral sequences were amplified by PCR, cloned, and sequenced. It was concluded that intrapatient variation may exceed interpatient variation but the presence of two clearly distinct populations was not confirmed. The env hypervariable regions appeared to be evolving independently of one another, cautioning against extrapolation of data, particularly from the V3 region. Virus typing and the assessment of HIV superinfection by genetic methods will prove difficult and experimental approaches will have to be carefully designed.


Different distribution of daunomycin in plasma membranes from drug-sensitive and drug-resistant P388 leukemia cells.
When the anthracycline daunomycin (DNM) is incorporated into isolated plasma membranes from P388 murine leukemia cells, the drug partitions between 'deep' and 'surface' membrane domains. Such domains have been characterized on the basis of: (1) fluorescence resonance energy transfer between 1,6-diphenylhexa-1,3,5-triene or 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene as energy donors, which are well known in their positioning within the membrane, and daunomycin as the energy acceptor, and (2) quenching of the fluorescence of the membrane-associated drug by the water-soluble quencher iodide. The distribution of DNM between the two plasma membrane domains is different depending on the cellular phenotype. Thus, in membranes from drug-sensitive cells, DNM is preferentially confined to 'surface' domains, while in membranes from drug-resistant cells, the drug distributes more homogeneously between 'surface' and 'deep' domains. Experiments using artificial lipid vesicles suggest that differences in the relative levels of certain lipids in the plasma membranes from drug-sensitive and drug-resistant cells, namely phosphatidylserine and cholesterol, are partly responsible for the observed differences in the distribution of DNM. Since drug-membrane interactions are important in anthracycline cytotoxicity, it is possible that our observations on a different membrane distribution of daunomycin, may be related to the different sensitivity to the drug exhibited by these cells.


Implementation of a computerized psychiatric assessment tool at a DUI treatment facility: a case example.
Psychiatric comorbidity is common among patients in a variety of treatment settings, yet treatment providers seldom use standardized mental health assessments to identify these problems. Using standardized assessment tools gives practitioners and clients the opportunity to tailor treatment and aftercare efforts to a potential problem, and trains practitioners to provide valid and reliable measurements of mental health. Despite the benefits, there are barriers to implementing formal assessment tools. This paper discusses the barriers the authors encountered and the strategies they used to implement a standardized mental health assessment at a state-licensed Driving Under the Influence (DUI) offender treatment program.


[Malignant testicular non-Hodgkin's lymphoma in a young subject].
The authors report a rare case of testicular non-Hodgkin's malignant lymphoma (NHML) in a 21-year-old man with a fatal outcome. In the light of the literature, they analyse the clinical features, clinical course and treatment of this lymphoma.


Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress.
Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.


Therapeutic potential of naringin: an overview.
Naringin is a natural flavanone glycoside that is found in the Chinese herbal medicines and citrus fruits. Studies have demonstrated that naringin possesses numerous biological and pharmacological properties, but few reviews of these studies have been performed. The present review gathers the fragmented information available in the literature describing the extraction of naringin, its pharmacology and its controlled release formulations. Current research progress and the therapeutic potential of naringin are also discussed. A literature survey for relevant information regarding the biological and pharmacological properties of naringin was conducted using Pubmed, Sciencedirect, MEDLINE, Springerlink and Google Scholar electronic databases from the year 2007-2015. Naringin modulates signalling pathways and interacts with signalling molecules and thus has a wide range of pharmacological activities, including anti-inflammatory, anti-cancer activities, as well as effects on bone regeneration, metabolic syndrome, oxidative stress, genetic damage and central nervous system (CNS) diseases. Information was gathered that showed the extraction of naringin can be improved using several modifications. There has been some progress in the development of controlled release formulations of naringin. Naringin is a promising candidate for further in vivo studies and clinical use. More detailed studies regarding its mechanism of action are required.


Correction of esthetic and biomechanical outcomes after maxillary anterior single dental implant fracture: a case report.
Rehabilitation of the single anterior tooth in the esthetic region after a dental implant fracture requires management of contributing biomechanical and/or biological etiologic factors. The multidisciplinary treatment of a fractured maxillary anterior single dental implant with a staged, combined surgical and prosthetic approach is discussed. Alleviation of several, but not all, risk factors eliminated the need for replacement of gingiva with pink porcelain and maintained a stable post implant host complex.


Obstructive hypertrophic cardiomyopathy: echocardiography, pathophysiology, and the continuing evolution of surgery for obstruction.
Our understanding of the pathophysiology of obstruction in hypertrophic cardiomyopathy has evolved since initial descriptions in the late 1950s. This review addresses the cause of obstruction, from early ideas that a muscular outflow tract sphincter was the cause, through the discovery of systolic anterior motion (SAM) of the mitral valve, to current understanding that flow drag, the pushing force of flow, is the dominant hydrodynamic mechanism for SAM. The continuing redesign and modification of surgical procedures to relieve outflow obstruction have corresponded to ideas about the cause of this condition. In this review we discuss the evolution of surgical procedures to relieve obstruction and review modern surgical approaches. Medical and nonsurgical methods for reducing obstruction are reviewed, as well as efforts to prevent sudden arrhythmic cardiac death. Echocardiography has become central to understanding this complex phenomenon, and for clinical diagnosis, operative planning and intraoperative management.


Binary nucleation rates for ethanol/water mixtures in supersonic Laval nozzles.
Although the conditions corresponding to the onset of condensation of aqueous-alcohol mixtures have been measured in supersonic nozzles [B. E. Wyslouzil et al., J. Chem. Phys. 113, 7317 (2000)], the true nucleation rates have not. Here, we propose a new analytical method to estimate the temperature, the concentrations of condensable species in both the vapor and the liquid phases, and the amount of the condensate using only the measured static pressure profiles in the nozzle. We applied the method to ethanol/water (CH(3)CH(2)OH/D(2)O or CH(3)CH(2)OD/D(2)O) mixtures and confirmed that the aerosol volume fractions derived from pressure measurements and small angle neutron scattering measurements are in very good agreement when this method is used. Combining the results from the pressure measurements with the number densities of the condensed droplets, measured either by small angle neutron or small angle x-ray scattering, we determined the first quantitative ethanol/water binary nucleation rates in the supersonic nozzle at a temperature of 229±1 K.


Identification and expression regulation of symbiotically activated legume genes.
Legume plants are able to enter two different endosymbioses with soil prokaryotes and soil fungi, leading to nitrogen-fixing root nodules and to arbuscular mycorrhiza (AM), respectively. We applied in silico and microarray-based transcriptome profiling approaches to uncover the transcriptome of developing root nodules and AM roots of the model legume Medicago truncatula. Several hundred genes were found to be activated in different stages of either symbiosis, with almost 100 genes being co-induced during nodulation and in arbuscular mycorrhiza. These co-induced genes can be associated with different cellular functions required for symbiotic efficiency, such as the facilitation of transport processes across the perisymbiotic membranes that surround the endosymbiotic bacteroids in root nodules and the arbuscules in AM roots. To specify promoter elements required for gene expression in arbuscule-containing cells, reporter gene fusions of the promoter of the Vicia faba leghemoglobin gene VfLb29 were studied by loss-of-function and gain-of-function approaches in transgenic hairy roots. These analyses specified a 85-bp fragment that was necessary for gene expression in arbuscule-containing cells but was dispensible for gene activation in root nodules. In contrast to promoters mediating gene expression in the infected cells of root nodules, the activation of genes in AM appears to be governed by more complex regulatory systems requiring different promoter modules.


Halogenated Meroditerpenoids from a South Pacific Collection of the Red Alga Callophycus serratus.
A detailed examination of the red alga Callophycus serratus collected in Tonga led to the isolation of six new halogenated meroditerpenoids: callophycol C (1), callophycoic acid I (2), iodocallophycols E (3) and F (4), iodocallophycoic acid B (5), and callophycoic acid J (6). Of these, compounds 3-5 are new iodinated additions to the growing family of Callophycus meroditerpenoids. The relative configurations of compounds 1-6 were deduced by analyses of 1D NOE data and 1H-1H scalar coupling constants, and 3-6 are proposed to differ from the closely related compounds reported in the literature, iodocallophycoic acid A and iodocallophycols A-D. Iodocallophycol E (3) exhibited moderate cytotoxicity against the promyelocytic leukemia cell line HL-60 with an IC50 value of 6.0 μM.


Childhood trauma and dissociation in women with pseudoseizure-type conversion disorder.
Conversion disorder is thought to be associated with psychological factors because of the presence of conflict and other stressors prior to the condition. The aim of this study is to compare adult patients with pseudoseizure-type conversion disorder with healthy control group in terms of childhood trauma, dissociative disorder and family history of psychiatric disorders. 56 female patients were admitted to the general psychiatry hospital outpatient clinic between January and July 2005. All patients had a negative experience about their families just before having the conversion. Diagnosis was made according to the DSM-IV criteria. A control group consisting of similar patient demographics of the disease group has been selected. Socio-demographic information forms, the Childhood Trauma Questionnaire (CTQ) and Dissociation Questionnaire (DIS-Q), were completed on the patients. CTQ total (t=12.12, P<0.001) and subscales, emotional abuse and emotional neglect (EA-EN) (t=12.74, P<0.001), physical abuse (PA) (t=10.05, P<0.001), and sexual abuse (SA) (t=7.69, P<0.001) were significantly high in the conversion group. DIS-Q mean points were statistically higher in the conversion group (t=11.05, P<0.001). The findings suggest that pseudoseizures (conversion disorder) should be included within dissociative disorders in DSM system as in ICD. It is usually uncommon for the patient to tell about childhood trauma without being specially questioned about this issue. Thus, it would be helpful to uncover these experiences by using related scales in conversion disorder patients.


Adenocarcinoma of the upper aerodigestive tract.
Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low-grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed.


Fully automated nipple detection in digital breast tomosynthesis.
We propose a nipple detection algorithm for use with digital breast tomosynthesis (DBT) images. DBT images have been developed to overcome the weaknesses of 2D mammograms for denser breasts by providing 3D breast images. The nipple location acts as an invaluable landmark in DBT images for aligning the right and left breasts and describing the relative location of any existing lesions. Nipples may be visible or invisible in a breast image, and therefore a nipple detection method must be able to detect the nipples for both cases. The detection method for visible nipples based on their shape is simple and highly efficient. However, it is difficult to detect invisible nipples because they do not have a prominent shape. Fibroglandular tissue in a breast is anatomically connected with the nipple. Thus, the nipple location can be detected by analyzing the location of such tissue. In this paper, we propose a method for detecting the location of both visible and invisible nipples using fibroglandular tissue and changes in the breast area. Our algorithm was applied to 138 DBT images, and its nipple detection accuracy was evaluated based on the mean Euclidean distance. The results indicate that our proposed method achieves a mean Euclidean distance of 3.10±2.58mm. The nipple location can be a very important piece of information in the process of a DBT image registration. This paper presents a method for the automatic nipple detection in a DBT image. The extracted nipple location plays an essential role in classifying any existing lesions and comparing both the right and left breasts. Thus, the proposed method can help with computer-aided detection for a more efficient DBT image analysis.


You be the examiner!: "Model answers" that require critical thinking.
"You be the examiner!" is an online approach to providing students with immediate, readily accessible, and nonthreatening feedback on their understanding of key biochemical concepts. The feedback aims to affirm correct understanding and, where further study appears necessary, direct the student to the relevant sections of their textbook and/or lecturer-provided study notes. Rather than providing model answers to previous examination questions, "You be the examiner" asks the students to evaluate typical "student" answers to such questions. Instead of a single "correct" answer, students encounter a range of answers that they must assess for accuracy and appropriateness.


Ultra- and microstructure of the female reproductive system of Matsucoccus matsumurae.
The ultra- and microstructure of the female reproductive system of Matsucoccus matsumurae was studied using light microscopy, scanning and transmission electron microscopy. The results revealed that the female reproductive system of M. matsumurae is composed of a pair of ovaries, a common oviduct, a pair of lateral oviducts, a spermatheca and two pairs of accessory glands. Each ovary is composed of approximately 50 telotrophic ovarioles that are devoid of terminal filaments. Each ovariole is subdivided into an apical tropharium, a vitellarium and a short pedicel connected to a lateral oviduct. The tropharium contains 8-10 trophocytes and two early previtellogenic oocytes termed arrested oocytes. The trophocytes degenerate after egg maturation, and the arrested oocytes are capable of further development. The vitellarium contains 3-6 oocytes of different developmental stages: previtellogenesis, vitellogenesis and choriogenesis. The surface of the vitellarium is rough and composed of a pattern of polygonal reticular formations with a center protuberance. The oocyte possesses numerous yolk spheres and lipid droplets, and is surrounded by a mono-layered follicular epithelium that becomes binucleate at the beginning of vitellogenesis. Accessory nuclei are observed in the peripheral ooplasm during vitellogenesis.


Understanding the patient experience of pain and discomfort during cardiac catheterization.
Patient centeredness is an essential component of high-quality care, yet little is known regarding the patient experience during procedures performed in the cardiac catheterization lab. Available literature focuses on the safe delivery of sedation, but does not address patient-reported satisfaction or comfort. Further delineation of how procedural factors impact the patient experience is needed. We conducted a retrospective, exploratory analysis of adult cardiac catheterization outpatients (n = 375) receiving physician ordered, nurse administered procedural sedation (benzodiazepine and/or opioids) between April and June, 2017. Data were abstracted from the procedural database, Electronic Health Record, and Press Ganey© surveys. The mean age was 63 (SD 12.2), a majority were male (n = 226; 60%), white (n = 271; 73%), and overweight (mean body mass index = 29, SD 6.8). Patient-reported satisfaction with pain control and perceived staff concern for comfort were >75th percentile (Press Ganey© survey), with no difference in preprocedure and postprocedure pain scores (p = .596). Intraprocedural medication dose range and mean frequency were highly variable: midazolam (0.25-5.5 mg; 1.48); fentanyl (12.5-200 mcg; 1.63); and hydromorphone (0.5-2.5 mg; 1.33). Median time interval between administration of initial sedation and local anesthetic was 6 min. Patients with longer intervals had less frequent dosing (p < .001) and less total procedural sedation (p < .001). Sensitivity analysis revealed that trainee/fellow involvement (p = .001), younger age (p = .002), and shorter time intervals (p < .001) were associated with increased frequency and larger total dose. Waiting to gain vascular access following administration of procedural was associated with less frequent subsequent dosing, lower overall administration, and similar patient satisfaction. Optimizing processes for administering periprocedural sedation may allow for less medication without impacting patient experience.


Effects of N6-cyclohexyl adenosine (CHA) on isolation-induced aggression in male mice.
Several studies have suggested adenosine receptor involvement in the modulation of aggressive behavior; however, the influence of adenosine A1 agonists on aggression is scarcely known. In this study, we examined the effect of N6-cyclohexyl adenosine (CHA; 0.025-0.4 i.p.), a selective adenosine A1 receptor agonist, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic standard opponents 60 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. CHA exhibited an ethopharmacological profile characterized by a selective decrease of offensive behaviors (threat and attack) at the intermediate dose (0.1 mg/kg), without impairment of motor activity. In contrast, the antiaggressive action of the highest doses used (0.2 and 0.4 mg/kg) was accompanied by a marked increase of immobility. It is concluded that the behavioral effects observed in this study could be related to an adenosine modulatory action on other neurotransmitter systems (dopamine/serotonin).


Versatile Rhodococcus equi-Escherichia coli shuttle vectors.
Rhodococcus equi is an intracellular pathogen of macrophages, causing disease in young foals, humans, and sporadically other animals. Although R. equi is easy to grow and manipulate, the analysis of virulence is hampered by a lack of molecular tools. This paper describes the development of a number of versatile plasmids for use in R. equi. Plasmids pREV2 and pREV5 use origins of replication derived from the Mycobacterium fortuitum plasmids pAL5000 and pMF1. These plasmids and their derivatives are compatible in R. equi, allowing their use for analysis of gene function in trans. The stability of these plasmids in R. equi in the absence of selection for the plasmid borne antibiotic resistance markers, and their integrity following passage through Escherichia coli and R. equi was determined.


Correlation of antenatal ultrasonography and pathological examinations in 153 malformed fetuses.
Findings in 153 abnormal fetuses diagnosed by antenatal ultrasound and subsequently examined by a pediatric pathologist were reviewed. The primary diagnoses in the 153 cases were 67 nervous system anomalies, 19 gastrointestinal system anomalies, 18 genitourinary system anomalies, 13 chromosomal abnormalities, 10 skeletal system anomalies, and 26 other abnormalities. Forty-six percent of the total number had multiple abnormalities. In 67 cases (44%), autopsy showed further anomalies or altered the ultrasonographic diagnosis. However, in only 36 (25%) were there autopsy findings that altered management. Errors in ultrasound diagnosis were most commonly associated with the presence of multiple anomalies and oligohydramnios. Expert pathological examination remains an essential tool in the management of fetal anomaly.


Therapeutic Progression in Abused Women Following a Drug-Addiction Treatment Program.
This study explored the prevalence of victims of abuse and the therapeutic progression among women who sought treatment for drug addiction. A sample of 180 addicted Spanish women was assessed. Information was collected on the patients' lifetime history of abuse (psychological, physical, and/or sexual), socio-demographic factors, consumption variables, and psychological symptoms. Of the total sample, 74.4% ( n = 134) of the addicted women had been victims of abuse. Psychological abuse affected 66.1% ( n = 119) of the patients, followed by physical abuse (51.7%; n = 93) and sexual abuse (31.7%; n = 57). Compared with patients who had not been abused, the addicted women with histories of victimization scored significantly higher on several European version of the Addiction Severity Index (EuropASI) and psychological variables. Specifically, physical abuse and sexual abuse were related to higher levels of severity of addiction. Regarding therapeutic progression, the highest rate of dropout was observed among victims of sexual abuse (63.5%; n = 33), followed by victims of physical abuse (48.9%; n = 23). Multivariate analysis showed that medical and family areas of the EuropASI, as well as violence problems and suicide ideation, were the main variables related to physical and/or sexual abuse. Moreover, women without abuse and with fewer family problems presented the higher probability of treatment completion. The implications of these results for further research and clinical practice are discussed.


S-glutathiolation by peroxynitrite of p21ras at cysteine-118 mediates its direct activation and downstream signaling in endothelial cells.
The highly reactive species, peroxynitrite, is produced in endothelial cells in pathological states in which the production of superoxide anion and NO is increased. Here, we show that peroxynitrite added exogenously or generated endogenously in response to exposure to an NO donor or oxidized low-density lipoproteins (oxLDL) increases p21ras activity in bovine aortic endothelial cells. The activation is not dependent on upstream elements but rather is due to direct targeting of p21ras by reversible S-glutathiolation of cysteine thiols as demonstrated by biotin-labeling techniques. The time course of p21ras S-glutathiolation following peroxynitrite corresponds to the increase in its Raf-1 binding activity and translocation to the membrane. Moreover, p21ras S-glutathiolation and activation can be reversed by dithiothreitol, confirming the importance of a disulfide bond. S-glutathiolation also promoted guanine nucleotide exchange of recombinant p21ras. In addition, the oxidant-induced activation of Mek/Erk and PI3 kinase/Akt was abrogated by dominant-negative and Cys-118 p21ras mutants, and the latter also prevented S-glutathiolation of p21ras. These results indicate that peroxynitrite arising from NO donors or pathological stimuli such as oxLDL triggers direct S-glutathiolation of p21ras Cys-118, which increases p21ras activity and mediates downstream signaling.


[Microbiological aspects of suppurative-inflammatory complications (pericultitis) after hysterectomy].
Bacteriologic findings in 101 patients before and after hysterectomy for benign tumors, inflammations, uterine prolapse are presented. Changes in aerobic and anaerobic vaginal and endocervical microflora species were demonstrated with respect to the phase of the cycle and the age of the patient. Pre- and postoperative genital mifroflora is represented by aerobic and anaerobic opportunity organisms, such as enterococcus, epidermal staphylococcus, E. coli, lactobacilli, eubacteria, and bacteroides. Postoperative complications are caused by associations of aerobic and anaerobic bacteria, with anaerobic organisms as the leading causative agent. Categories of risk with respect to infectious postoperative complications have been identified on the basis of microbiologic parameters.


Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.
Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.


[Adults with sickle cell anemia in Senegal. Clinical study of 40 homozygote subjects].
While the well-documented life expectancy of patients with homozygous sickle cell anemia (SS) is 40 years in industrialized countries, this question remains unanswered in black Africa. The purpose of this prospective study was to establish the clinical phenotype for Senegal. A severity score based on 12 clinical, laboratory, radiological, and prognostic findings was calculated and correlated with age and hemoglobin F level. A total of 40 SS homozygotes over 15 years of age (mean age: 25 years) were hospitalized between January 1996 and January 1998 at the Principal Hospital in Dakar. The most common events requiring hospitalization were vasoocclusive phenomena (n = 26) but the incidence of these complications declined significantly with age (p < 0.05). The mean hemoglobin level was 4.4 mmol/l and the mean hemoglobin F level was 6.2 p. 100. The incidence of visceral involvement was low (lithiasic vesicules in 17 cases, necrosis of the head of the femur in 7, and abnormal cardiac ultrasound findings in 10). Only one patient died during the study. No correlation was found between severity score and either age or hemoglobin F level. These findings confirm that the phenotype is less severe in Senegal. However they also show that organ damage is common by the time that patients reach adulthood and thus underline the need for prevention and education to improve survival of SS homozygotes in Senegal.


Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity.
Mammary analog secretory carcinoma (MASC) is a recently described tumor predominantly arising in the parotid gland. These tumors represent locally invasive malignancies with microcystic architecture, low-grade nuclei, and granular pink vacuolated cytoplasm. They display strong vimentin and S100 positivity and harbor an identical t(12;15)(p13;q25) to their breast counterpart, leading to a ETV6-NTRK3 fusion oncogene. These features help exclude the most important differential diagnostic considerations, namely, acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, not otherwise specified. Here we present a series of 7 recent examples of MASC, which showed features not previously described. These 7 cases were observed in patients ranging in age from 14 to 77 years (mean, 40 y), occurred almost exclusively in male patients (6:1), and showed >50% (4 of 7 cases) involvement of the oral cavity, with only 2 arising in the parotid. The remaining case is the first reported in the submandibular gland. The tumors showed a variety of patterns including single macrocysts, combined macrocystic and microcystic spaces, and solid architecture. They showed prominent hobnailing in the cystic areas. Secretions within the cysts and tubular areas tended to be positive for periodic acid schiff, periodic acid schiff diastage and mucicarmine, the latter also showing occasional intracytoplasmic mucin droplets, a feature not previously recognized. One case showed prominent mucinous differentiation, which, coupled with high-molecular-weight keratins (HMWK) positivity, mimicked mucoepidermoid carcinoma (MEC). The tumors were generally positive for HMWK (6 of 7), S100 (5 of 7), vimentin, CK19, and other epithelial markers. The finding of duct involvement, proven with an incomplete p63-positive basal layer surrounding a minority of tumor cell nests and cysts, raised the possibility of a ductal epithelial origin for MASC. Alternatively, this could represent secondary ductal involvement by tumor. All cases showed rearrangement of the ETV6 gene by fluorescence in situ hybridization, confirming the diagnosis of MASC. These findings reinforce MASC as a unique low-grade salivary gland tumor entity with morphologic overlap with AciCC, MEC, and cystadenocarcinoma.


Campylobacter jejuni isolated from poultry meat in Brazil: in silico analysis and genomic features of two strains with different phenotypes of antimicrobial susceptibility.
Campylobacter jejuni is the most common bacterial cause of foodborne diarrheal disease worldwide and is among the antimicrobial resistant "priority pathogens" that pose greatest threat to public health. The genomes of two C. jejuni isolated from poultry meat sold on the retail market in Southern Brazil phenotypically characterized as multidrug-resistant (CJ100) and susceptible (CJ104) were sequenced and analyzed by bioinformatic tools. The isolates CJ100 and CJ104 showed distinct multilocus sequence types (MLST). Comparative genomic analysis revealed a large number of single nucleotide polymorphisms, rearrangements, and inversions in both genomes, in addition to virulence factors, genomic islands, prophage sequences, and insertion sequences. A circular 103-kilobase megaplasmid carrying virulence factors was identified in the genome of CJ100, in addition to resistance mechanisms to aminoglycosides, beta-lactams, macrolides, quinolones, and tetracyclines. The molecular characterization of distinct phenotypes of foodborne C. jejuni and the discovery of a novel virulence megaplasmid provide useful data for pan-genome and large-scale studies to monitor the virulent C. jejuni in poultry meat is warranted.


Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
To examine first trimester safety of angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensin-receptor-blockers (ARBs). Prospective observational cohort regarding pregnancy ACEI/ARBs-exposure including contacts to two Teratology Information Services in Israel (1994-2007) and Italy (1990-2008), with two comparison groups: (1) exposed to other antihypertensives (OAH) (2) after non-teratogenic exposure (NTE) in similar time frames. 252 ACEI/ARBs-exposed, 256 OAH-exposed and 495 NTE-exposed pregnancies were followed-up. The rate of major congenital anomalies was comparable between the groups (8/190, 4.2%, ACEI/ARB; 9/212, 4.2%, OAH; 18/471, 3.8% NTE; p = 0.954) among first trimester exposed pregnancies. The median gestational age at delivery was two weeks earlier, rate of preterm deliveries more than 2-fold higher, and median birth weight more than 200 g lower in the ACEI/ARB and OAH groups compared to the NTE group. The present study suggests that ACEI/ARBs are not major teratogens when used in the first trimester, and can reassure women with similar exposures.


[Management of patients with benign prostatic hyperplasia by urologists: the DUO study].
The DUO study intended to define the factors determining diagnostic and treatment strategies for benign prostatic hyperplasia (BPH) management. This longitudinal, observational study was conducted in France (June 2004 to March 2005), with a representative sample of private and hospital urologists. 1027 BPH patients were included by 202 urologists and 856 were followed-up 6 months later. Mean I-PSS was 14.9 (+/- 6.7) at inclusion and 10.5 (+/- 6.7) at the follow up visit. At inclusion, pharmacologic treatment was prescribed to 84% of the patients, surgery to 13% and no treatment to 3%. Factors in favour of surgery (versus drugs) were BPH severity (OR = 2.5 if IPSS = 20), patients' choice (OR = 2.5), quality of life improvement (OR = 2.2), post-void residual (OR = 2.1) and dribbling (OR = 1.6). Patients' age and prostatic volume have no impact on this choice. Factors in favour of a combination of an alpha-blocker plus an 5alpha-reductase inhibitor (versus an alpha-blocker) were prostate volume (OR = 7.8), patient's age (OR-3.0 if age = 74) and post-void residual (OR = 2.3) and those in favour of a 5alpha reductase inhibitor (versus an alpha-blocker) were prostate volume (OR = 7.6), PSA results (OR = 5.8), patients' age (OR = 5.4 if > 74 years, OR = 2.1 if > 68 years). Medical or surgical treatment of BPH results in IPSS improvement at 6 months. Patients' age and prostatic volume favour 5alpha-reductase inhibitor initiation and have no impact on surgical treatment decision. Surgery is performed in severe BPH or when patients expecting a quality of life improvement do that choice.


High susceptibility to ADP-induced thrombus formation in mast cell-deficient W/Wv mice.
We used mast cell-deficient W/Wv mice to clarify whether mast cell-derived heparin may play a role in inhibiting thrombus formation in the living organism. Small veins in the mesentery of W/Wv or congenic +/+ mice were stretched over an inverted microscope; a micropipette filled with varying concentrations of ADP was set close to the outside of a vein by using a micromanipulator. Thrombus formation was directly examined under the microscope. The concentration of ADP necessary for thrombus formation was significantly lower in the W/Wv mice than in the congenic +/+ mice. Furthermore, the concentration of ADP necessary for aggregation of platelets in platelet-rich plasma (PRP) was significantly lower in W/Wv mice than in +/+ mice. The higher sensitivity of PRP of W/Wv mice is not attributed to the platelets, but to the plasma, since platelets of +/+ mice suspended in platelet-poor plasma (PPP) of W/Wv mice were more sensitive to ADP than platelets of W/Wv mice suspended in PPP of +/+ mice. The present results suggest that plasma of W/Wv mice may lack any inhibitory factor(s) or contain promoting factor(s) for platelet aggregation.


Editorial: 'People get ready': Are mental disorder diagnostics ripe for a Kuhnian revolution?
How is practical progress possible in child psychology and psychiatry? How does science advance to promote therapeutic innovation? The importance of the exciting stuff - new insights and ideas, studied using cutting edge and innovative technologies - is self-evident. However, the philosophy of science has shown us that less obvious and more mundane elements are also essential. This is because scientific progress is only possible where attempts to break new ground are solidly anchored in a stable shared framework of assumptions - a metatheory - about the general nature of the phenomenon being studied. This framework defines what questions are considered 'scientific' - questions that it 'makes sense' to ask from a scientific point of view and those that are considered out of bounds (scientists with less subtle minds even considering such to be nonquestions rather than different sorts of questions). Kuhn called this framework a paradigm and the research activity that originates from it, normal science (Kuhn, 1962, The Structure of Scientific Revolutions; Princeton, NJ: Princeton University Press). These frameworks also serve a vital regulatory function because they contain common concepts that embody shared points of reference that allow scientists to communicate with each other to share their ideas, hypotheses and findings (Habermas, 1979, Communication and the evolution of society; Boston: Beacon Press).


Missed opportunities for diagnosing primary HIV infection.
To investigate the extent to which primary HIV infection (PHI) presents to healthcare providers and the degree to which it is unrecognised. All individuals diagnosed with having recent HIV infection between 2003 and 2005 were identified (based on the following criteria: an evolving antibody response, negative HIV test within 18 months or a serological testing algorithm for recent HIV seroconversion). Symptoms of PHI and previous presentation to other healthcare providers were ascertained from HIV clinic notes and laboratory records (a single laboratory performing all of the HIV tests in the area). Of the 108 subjects, 103 (95%) were male and 93 (86%) were men who had sex with men. A total of 76 of the 108 individuals (70%) reported symptoms of seroconversion. Of these, 40 (53%) presented to a healthcare provider during the symptomatic period. Of these, 21 (52%) were diagnosed with having PHI at first presentation. In the 19 patients (48%) in which a diagnosis of having PHI was not made at first presentation, 15 were seen in primary care, 3 in accident and emergency, and 1 in genitourinary medicine (GUM). The diagnosis of PHI is often missed. Individuals in high-risk groups need to be informed to access healthcare when they experience symptoms of seroconversion. Non-HIV/GUM healthcare providers (especially primary care) may benefit from training in case recognition to improve rates of diagnosis.


A new Vietnamese species of Euconnus (Napochus) with modified antennal club (Coleoptera: Staphylinidae: Scydmaeninae).
Napochus Thomson, 1859 is the largest subgenus of Euconnus Thomson, 1859, currently comprising over 300 nominal species (Newton Franz 1998; Jałoszyński 2015, 2016, 2017a, b). The subgenus was recently redefined and its adult morphological structures were illustrated and described in detail (Jałoszyński 2015). Moreover, the subgenera Neonapochus Machulka, 1929, Paranapochus Franz, 1986, Smicrophus Casey, 1897, Cephaloconnus Franz, 1998 and Cerviconnus Franz, 1962, and a genus Protoscydmus Franz, 1992 were placed as junior synonyms of Napochus (Jałoszyński 2015, 2016, 2017a, b). Currently Napochus is defined mainly by the subtrapezoidal pronotum, which is always broadest behind middle (typically at base or shortly in front of base) and strongly narrowed anterad, so that its anterior margin is much shorter than the posterior margin; and by the tetramerous antennal club. The latter, however, may be indistinctly tetramerous in some species, with the antennomere VIII only slightly larger than VII; antennae in such beetles may appear gradually broadened or even trimerous. The problem of antennal variability within Napochus requires further studies, and it is possible that the number of antennomeres forming the club should be excluded from the diagnosis, as too variable. Until recently, species of Euconnus similar to the type species of Napochus and with unmodified antennomeres were placed in Napochus, and one species, in which males have the antennal club modified, in a subgenus Neonapochus. Also beetles resembling Napochus but showing a sexual dimorphism in the head capsule (with cavities, impressions or unusual concavities in males) were placed not in Napochus, but in Cephaloconnus. Jałoszyński (2016, 2017b) demonstrated that beetles showing such modifications do not differ from Napochus in any important characters, and synonymized Neonapochus and Cephaloconnus with Napochus.


A hydrogen-bonded heterodimer of 1-(4-hexyloxyphenyl)pyridin-4(1H)-one with 4-cyanobenzoic acid.
The two components of the title heterodimer, C17H21NO2.C8H5NO2, are linked end-to-end via O-H...O(=C) and C-H...O(=C) hydrogen-bond interactions. Additional lateral C-H...O interactions link the dimers in a side-by-side fashion to produce wide infinite molecular ribbons. Adjacent ribbons are interconnected via pi-pi stacking and C-H...pi(arene) interactions. This structure represents the first evidence of robust hydrogen-bond formation between the moieties of pyridin-4(1H)-one and benzoic acid.


Investigation of Blended Fibre Filtering Materials.
Five variants of mixtures of different synthetic fibres at different area ratios were manufactured into needled nonwovens intended to be used as a filtering material for respiratory protection. Two variants were produced according to an earlier patent, and the contents of the other three was completely new. Samples of the nonwovens were tested for sodium chloride particles penetration and for breathing resistance. The results showed that one variant of a nonwoven, designated PP/PPFM, had very valuable filtering properties and that those properties were stable in time.


Seasonal variation of antibacterial activities in the green alga Ulva pertusa Kjellman.
The present study was performed to screen out the extracts of algae and assess the seasonal variation in antimicrobial activity of Ulva pertusa against Gardnerella vaginalis. Seasonal variation in antibacterial activity was observed, with the extracts showing no activity during summer and autumn, and showing antibacterial activity from early winter (December) to middle spring (April). The maximum value of antimicrobial activity (6.5 mm inhibition zone at 5 mg disk(-1)) of U. pertusa against G. vaginalis was observed in April. Otherwise, for both chlorophyll a and b, the highest content (2.87 mg g(-1) and 1.37 mg g(-1)) was observed in March 2009. These results may reflect variation in cellular chemical compositions such as secondary metabolite(s) rather than chlorophyll and biological activities according to season.


Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity.
Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis.


Cellular response to rare earth mixtures (La and Gd) as components of degradable Mg alloys for medical applications.
Rare earth (RE) elements have been proposed to improve the corrosion resistance of degradable Mg alloys for medical applications. However, good biocompatibility of the elements released by Mg alloys during degradation is essential for their use in implants. Most studies are focused on material science and engineering aspects, but the effects of ions released at the biological interface are not frequently addressed. The aim of this study was to contribute to the knowledge of in vitro toxicological effects of two RE Mg-alloying elements, La and Gd, as individual ions and in mixtures with and without Mg ions. Different combinations (Mg+Gd, Mg+La, and Mg+Gd+La) were used to evaluate their possible synergistic effects on CHO-K1 cells. Two sets of experiments were designed to assess (1) the cyto-genotoxic effect of La and Gd ions by neutral red (NR) technique, Reduction of tetrazolium salt (MTT), Viability with Acridine Orange staining, Clonogenic test, and Comet assay; and, (2) the possible synergistic toxicological effect of La and Gd ions in mixtures, and the influence of osmolarity increase on cellular response. Cytotoxic effects of RE were found at concentrations ≥200 μM RE while DNA damage was detected for doses ≥1500 μM and ≥1600 μM for La and Gd, respectively. When mixtures of ions were evaluated, neither synergistic cytotoxic effects nor biological damage related to osmolarity increase were detected.


Pulmonary arterial changes in patients with ventricular septal defects and severe pulmonary hypertension.
In 25 patients, aged eight months to 31 years, with ventricular septal defect (VSD; isolated in 15, the others with atrial septal defect, PDA, coarctation or patent ductus arteriosus + coarctation), each with severe pulmonary artery hypertension (pulmonary artery systolic pressure [Ppa] at least 75% of systemic and an elevated pulmonary vascular resistance), we related morphologic and morphometric data from open-lung biopsy to hemodynamic measurements obtained at cardiac catheterization during the same hospital admission. Of the hemodynamic features measured, only the ratios of pulmonary-to-systemic flow and pulmonary-to-systemic resistance correlated significantly with structure. Neither pulmonary artery pressure (Ppa) nor pulmonary vascular resistance correlated significantly with any structural feature studied. The increased external diameter of respiratory bronchiolar arteries in those with the more advanced Heath-Edwards grades reflects dilatation and suggests that it is in the small arteries of the distal arterial bed that the changes of pulmonary hypertension are most significant. Neither age nor body weight correlated significantly with the degree of structural or hemodynamic abnormality. In the ten patients who underwent VSD closure, Ppa was measured postoperatively. The Heath-Edwards grade (no more than one grade-III lesion) and arterial density (at least one-half that normal for age) were the best correlates of the difference between preoperative Ppa and Ppa immediately after corrective surgery. The presurgical catheterization data, including pulmonary resistance and the resistance ratio, did not correlate significantly with change in Ppa following VSD closure.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular epidemiology of the attachment glycoprotein (G) gene in respiratory syncytial virus in children with acute respiratory infection in Japan in 2009/2010.
This study performed a detailed genetic analysis of the glycoprotein (G) gene of respiratory syncytial virus (RSV) detected in 50 Japanese children with acute respiratory infection (ARI) in the 2009/2010 season. A phylogenetic tree constructed by the neighbour-joining method showed that 34 and 16 of the RSV strains could be classified into subgroups A and B, respectively. Strains belonging to subgroups A and B were further subdivided into GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%). The deduced amino acid sequences implied that a relatively high frequency of amino acid substitutions occurred in the C-terminal 3rd hypervariable region of the G protein in these strains. In addition, some positively selected sites were estimated. The results suggest that RSV with genotypes GA2 and BA was associated with ARI in Japanese children in 2009/2010.


Clear cell odontogenic carcinoma: A rare case report with emphasis on differential diagnosis.
Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignancy with a female predilection, typically presenting as swelling in anterior region of mandible. CCOC was classified as a malignant neoplasm of odontogenic origin by the WHO in 2005 as it exhibits an aggressive growth pattern, local recurrence, and tendency of distant metastasis. Histologically, CCOC is characterized by sheets and islands of vacuolated/clear cells. Since clear cells are present in few odontogenic tumors, salivary gland neoplasms, and metastatic tumors to the jaws; presence of clear cells in a lesion of head and neck area poses a diagnostic challenge. Knowledge about the clinical course, histopathologic pattern, and immunoprofile of CCOC aids in differentiating it from other clear cell tumors. Herein, we present a case of CCOC in anterior mandibular region of 60-year-old female patient with an emphasis on its differential diagnosis from other clear cell lesions of the jaws.


[Cerebral embolism due to lone atrial septal aneurysm].
A 71-year-old man was admitted to our hospital because of headache and left hemiparesis. Brain CT scan showed hemorrhagic infarction of the right frontal lobe. Intravenous digital subtraction angiography revealed no occlusion of cerebral arteries. No arrhythmias were observed by the holter ECG. Transthoracic echocardiography showed no abnormalities. Anticoagulation therapy (heparin and warfarin) was started under the diagnosis of cerebral embolism without definite embolic source and there was no recurrence during following four years. Transesophageal echocardiography showed an atrial septal aneurysm (ASA) without patent foramen ovale. A potential cause of cerebral embolism due to atrial septal aneurysm is paradoxical embolization through an interatrial shunt (patent foramen ovale). It was speculated that ASA was a direct source of thrombus formation in this case (lone ASA). Transesophageal echocardiography should be performed to find atrial septal aneurysm in patients with cryptogenic stroke, especially embolic stroke without definite embolic sources.


Plain bupivacaine: an unpredictable spinal anaesthetic agent.
Plain bupivacaine 0.5% or 0.75% was injected intrathecally in four groups of 10 patients. Group A received 0.75% bupivacaine 2.7 ml at L3/4, group B 0.5% bupivacaine 4 ml at L3/4, group C 0.75% bupivacaine 2.7 ml at L2/3 and group D 0.75% bupivacaine 2 ml at L3/4. A very wide range of height of block was found in each group and because of this there were few statistically significant differences between the groups. The mean height of anaesthetic blockade was significantly higher when 20 mg (group C) was injected compared with 15 mg (group D). Decreasing the volume of injection from 4 ml (group B) to 2.7 ml (group A) did not decrease this variability. By injecting at L2/3 spinal space (group C) the mean maximum level of anaesthesia (T7) was four segments higher than group A (T11) injected at L3/4, and this was reflected in a greater incidence of arterial hypotension.


[Comparative study on identification of Clematidis Radix et Rhizoma from different origins based on microstructure and NIRS method].
Microscopic identification and NIRS methods were applied to identify Clematidis Radix et Rhizoma of two different origins. The results showed that both methods could identify the samples. NIRS could identify the two samples nondestructively, and provides a basis for establishment of a standard herbs radix clematidis NIRS fingerprint in the future.


More than an imitation game: Top-down modulation of the human mirror system.
All interpersonal interactions are underpinned by action: perceiving and understanding the actions of others, and responding by planning and performing self-made actions. Perception of action, both self-made and observed, informs ongoing motor responses by iterative feedback within a perception-action loop. This fundamental phenomenon occurs within single-cells of the macaque brain which demonstrate sensory and motor response properties. These 'mirror' neurons have led to a swathe of research leading to the broadly accepted idea of a human mirror system. The current review examines the putative human mirror system literature to highlight several inconsistencies in comparison to the seminal macaque data, and ongoing controversies within human focused research (including mirror neuron origin and function). In particular, we will address the often-neglected other side to the 'mirror': complementary and opposing actions. We propose that engagement of the mirror system in meeting changing task-demands is dynamically modulated via frontal control networks.


Effect of concurrent infection with Ostertagia circumcincta and Trichostrongylus vitrinus on the performance of lambs.
The interaction between Ostertagia circumcincta and Trichostrongylus vitrinus was investigated in lambs continuously infected over 12 weeks. Four groups of seven lambs were given either zero, 1000 T vitrinus larvae per day, 2500 O circumcincta larvae per day or infected concurrently. Overall liveweight gain was reduced by 17, 20 and 30 per cent in T vitrinus, O circumcincta and concurrent infection, respectively. T vitrinus infection significantly lowered serum phosphorus concentrations by week 4. In the concurrent infection the decline in phosphorus concentration was more gradual and only differed significantly from the controls during the final four weeks of the trial. There were no significant differences between the total numbers of T vitrinus or O circumcincta recovered from single or combined infections. The lack of an additive effect on performance may be due to a delayed establishment of T vitrinus in the presence of O circumcincta.


Albumin is a necessary stabilizer of TBE-vaccine to avoid fever in children after vaccination.
A thiomersal-free and also an albumin-free tick-borne encephalitis-vaccine (TBE-vaccine) was developed. This vaccine was approved by the Austrian health authorities in the year 2000. Contrary to previous experience, 779 cases of fever attacks occurred following the first vaccination of children under 15 years of age. The induction of the immune system by different TBE virus (TBEV) vaccines (FSME-Immun [1999], Ticovac [2000] and FSME-Immun [2001] all from Baxter Hyland Immuno, Vienna) was compared in an in vitro immune stimulation test in order to find an explanation for the unexpected fever attacks. It was shown that only Ticovac, which contains no albumin as a stabilizer, can induce relative high amounts of TNF-alpha (P < or = 0.0001) and lower amounts of IL-1 beta (P < or = 0.05). Increase of both cytokines is first observed following an incubation of 4 h. The maximum is reached after 15 h. After 26 h, it has reverted to the original value. The course of concentration of both cytokines corresponds to the time of observed febrile phases. Albumin or immunoglobulin prevents a rise of cytokines so that it is recommended to add the albumin again to the vaccine.


DNA analysis in the case of Kaspar Hauser.
In 1828 a mysterious young man appeared in Nürnberg, Germany, who was barely able to speak or walk but could write down his name, Kaspar Hauser. He quickly became the centre of social interest but also the victim of intrigue. His appearance, his origin and assassination in 1833 were, and still are, the source of much debate. The most widely accepted theory postulates that Kaspar Hauser was the son of Grand Duke Carl von Baden and his wife Stephanie de Beauharnais, an adopted daughter of Napoleon Bonaparte. To check this theory, DNA analysis was performed on the clothes most likely worn by Kaspar Hauser when he was stabbed on December 14th, 1833. A suitable bloodstain from the underpants was divided and analysed independently by the Institute of Legal Medicine, University of Munich (ILM) and the Forensic Science Service Laboratory, Birmingham (FSS). Mitochondrial DNA (mtDNA) was sequenced from the bloodstain and from blood samples obtained from two living maternal relatives of Stephanie de Beauharnais. The sequence from the bloodstained clothing differed from the sequence found in both reference blood samples at seven confirmed positions. This proves that the bloodstain does not originate from a son of Stephanie de Beauharnais. Thus, it is becoming clear that Kaspar Hauser was not the Prince of Baden.


Reduced corticosteroid-binding globulin cleavage in active rheumatoid arthritis.
Corticosteroid-binding globulin (CBG), the cortisol transport protein, is cleaved from high-affinity (haCBG) to low-affinity (laCBG) CBG at sites of inflammation releasing bioavailable, anti-inflammatory cortisol. Rheumatoid arthritis (RA) is a glucocorticoid-responsive disorder, with paradoxically normal cortisol levels despite elevated inflammatory mediators. Our objective was to determine whether CBG cleavage relates to RA disease activity. We hypothesized that impaired CBG cleavage may limit delivery of free cortisol to inflamed joints in RA. Prospective, cross-sectional observational study. Fifty-three patients with RA recruited from a Rheumatology outpatient clinic at a tertiary referral centre in Adelaide, Australia, and 73 healthy controls. Total CBG, haCBG and laCBG, total, free and salivary cortisol, inflammatory markers including interleukin-6 soluble receptor (IL-6sR) and macrophage migration inhibitory factor and clinical measures of disease activity. Among patients with RA, a wide range of disease activity scores was observed (DAS28: range 1·2-6·4). laCBG was lower in patients with RA (mean ± SEM); 153 ± 9, compared with healthy controls; 191 ± 8 nmol/l, P = 0·003. Levels of total and haCBG were higher in patients with more severe RA disease activity. Free and total cortisol, free cortisol:IL-6sR ratio and total cortisol:IL-6sR ratio correlated negatively with disease activity. These results suggest that patients with RA have reduced CBG cleavage compared to healthy controls and that cleavage is reduced further with higher RA disease activity. Hence, impaired CBG-mediated delivery of endogenous cortisol may perpetuate chronic inflammation in RA.


Measurement of fatigue in knee flexor and extensor muscles.
In order to examine fatigue of the knee flexor and extensor muscles and to investigate the characteristics of muscular fatigue in different sports, a Cybex machine was used to measure muscle fatigue and recovery during isokinetic knee flexion and extension. Eighteen baseball players, 12 soccer players and 13 marathon runners were studied. Each subject was tested in the sitting position and made to perform 50 consecutive right knee bends and stretches at maximum strength. This was done 3 times with an interval of 10 min between each series. The peak torque to body weight ratio and the fatigue rate were determined in each case. In all subjects, the peak torque to body weight ratio was higher for extensors than flexors. Over the 3 trials, the fatigue rate of extensors showed little change, while that of flexors had a tendency to increase. In each subject, knee extensors showed a high fatigue rate but a quick recovery, while knee flexors showed a low fatigue rate but a slow recovery. As the marathon runners had the smallest fatigue rates for both flexors and extensors, we concluded that marathon runners had more stamina than baseball players and soccer players.


Synthesis and antimicrobial activity of some N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles.
Several N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles (4) were synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 4 were also tested for antifungal activity against Saccharomyces cerevisiae. The findings clearly showed that all the compounds 4 were devoid of antifungal activity, whereas the compounds 4i-m,o-r were effective against the bacterial strains used. Compounds 4k,m,p,q proved to be the most active antibacterial agents showing in some cases minimum inhibitory concentrations (MIC) lower than chloramphenicol and gentamicin, used as reference compounds. In the case of two representative bacterial strains (Gram-positive and Gram-negative, respectively), a parabolic relationship was found between the antibacterial activity of compounds 4i-m,o-r expressed as log1/MIC and the molecular lipophilicity measured as RM values.


Evaluation of several flow cytometric assays for the analysis of T-cell responses in goats.
Flow cytometry (FCM) provides an alternative to radioactive methods for the analysis of T-cell responses. However, a comparative study of common FCM assays in an outbred ruminant model is lacking, which motivated this work. Goats immunized with the obligate intracellular bacterium Cowdria ruminantium, inactivated and emulsified in oil-based adjuvants, were used as a model to study T-cell recall responses in vitro. FCM-based methods to measure Cowdria-induced lymphoblastogenesis, DNA synthesis, and interleukin-2 receptor (IL-2R) expression by T-cell subsets were compared. IL-2R expression was the most sensitive and reliable method provided that the number of molecules per cell was analyzed and not simply the percentage of positive cells of a given phenotype. Despite high background due to adjuvant and low proliferation, this method could detect antigen-specific activation of immune CD4(+) and CD8(+) T cells. FCM-based measurement of lymphoblastogenesis and DNA synthesis are not the most appropriate methods to analyze T-lymphocyte activation during vaccination of outbred animals. On several occasions, analysis of IL-2R expression was the only assay capable of discriminating between vaccinated and naive animals in this model.


EYEWORMS (OXYSPIRURA PETROWI) IN NORTHERN BOBWHITES (COLINUS VIRGINIANUS) FROM THE ROLLING PLAINS ECOREGION OF TEXAS AND OKLAHOMA, 2011-13.
The Northern Bobwhite ( Colinus virginianus ) has been steadily declining throughout much of its historic range for decades. The Rolling Plains ecoregion of Texas and western Oklahoma, historically rich with wild Northern Bobwhites and one of the last remaining quail strongholds, also has a declining population. During August and October in 2011-13, 348 Northern Bobwhites from the Rolling Plains were examined for eyeworms (Oxyspirura petrowi). Of these 348 Northern Bobwhites, 144 (41.4%) were infected with 1,018 total eyeworms. Eyeworm abundance (mean±SE) was 2.9±0.4 (range 0-64), with an intensity (mean±SE) of 7.1±0.6. Eyeworm prevalence was significantly higher in adult Northern Bobwhites (58.7%) than in juveniles (35.4%). Recent research suggests that eyeworms have the potential to cause cellular tissue damage to the eye, but it is unknown how these worms affect host survivability. This study further expands the regional distribution of O. petrowi in Northern Bobwhites in the Rolling Plains ecoregion and assesses the prevalence and abundance of infection across host age, host sex, and year. Further research is warranted on the life history of O. petrowi and assessing the impacts of eyeworms on their definitive host at individual and population levels.


[Permanent cosmetics and magnetic resonance imaging].
We report a case illustrating the possible relation between permanent cosmetics (tattoos) and magnetic resonance imaging (MRI). A 24-year-old woman underwent a permanent cosmetic tattoo (eyeliner) on the four eyelids 5 months before an MRI was performed for headache. After 1 min, the patient reported a burning sensation associated with an eyelid erythema. The MRI examination was interrupted. The burning sensation resolved by the end of the examination and erythema 2 h later. Cosmetic tattoo technicians, patients, and MR technologists should be informed of the minor risk associated with the site of the permanent cosmetic tattoo (eyelid, eyebrow).


Combination cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy for extensive non-small cell carcinomas of the lung.
Fifty consecutive patients with extensive non-small cell carcinoma of the lung were randomized to one of two chemotherapeutic regimens. Twenty-three patients (group 1) received cyclophosphamide (600 mg/mg(2)), doxorubicin (40 mg/m(2)), and cisplatin (50 mg/m(2)) every 3 weeks; 27 patients (group 2) received cyclophosphamide (600 mg/m(2)), doxorubicin (40 mg/m(2)), and cisplatin (100 mg/m(2)) every 3 weeks. The objective response rates were 4% and 7% in groups 1 and 2, respectively. Median survival duration was 15.2 weeks (group 1) and 21.7 weeks (group 2; P greater than or equal to 0.3). Hematologic toxicity was minimal in group 1 and moderate in group 2. Renal toxicity was moderate in group 2 only. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin as used in this study is not superior to previous studies in this institution using cyclophosphamide as a single agent.


Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol.
To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.


Deconstructing the energy landscape: constraint-based algorithms for folding heteropolymers.
We apply the computational methodology of phase retrieval to the problem of folding heteropolymers. The ground state fold of the polymer is defined by the intersection of two sets in the configuration space of its constituent monomers: a geometrical chain constraint and a threshold constraint on the contact energy. A dynamical system is then defined in terms of the projections to these constraint sets, such that its fixed points solve the set intersection problem. We present results for two off-lattice hydrophobic-polar models: one with only rotameric degrees of freedom, and one proposed by Stillinger [Phys. Rev. E 48, 1469 (1993)] with flexible bond angles. Our phase retrieval inspired algorithm is competitive with more established algorithms and even finds lower-energy folds for one of the longer polymer chains.


Assessing the role of the biomaterial Aquavene in patient reactions to Landmark midline catheters.
Landmark midline catheters (Menlo Care, Inc., Palo Alto, CA) provide peripheral venous access for the infusion of medications or fluids. They are constructed of an inner layer of polyurethane and an outer layer of the biomaterial Aquavene, a blend of polyurethane and polyethylene oxide to which butylated hyroxyanisole (BHA), butylated hydroxytoluene (BHT), and triallyl-s-triazine trione (TTT) are added. Once inside the vein, the Aquavene material becomes hydrated and the catheter swells resulting in minimal trauma to the vein. It is well recognized that some patients experience reactions to catheterization. Recent reports of hypersensitivity-like reactions in some patients catheterized with Landmark catheters have prompted the manufacturer to reexamine biocompatibility data and clinical data to assess whether Aquavene was the source of the patient responses. None of the biocompatibility studies provided by Menlo Care in support of U.S. registration and marketing of Aquavene-based catheters demonstrated any tendency for Aquavene or material extracted from Aquavene to invoke an immunological or toxicological response. Examination of potential catheter residuals revealed that significant amounts of BHA and BHT were unlikely to be released from the catheters during expected use. The amounts of polyethylene oxide and TTT expected to be released during the first few minutes after catheter insertion (when most of the patient reactions were reported) are almost 92,500 and 270,000 times lower, respectively, than nontoxic animal exposures. These analyses do not support chemically mediated toxicity as an explanation for the adverse events experienced by some patients. A review of the postmarket surveillance data on Aquavene-based catheters revealed that the reported events were not consistent with a hypersensitivity (immunogenic) response to the biomaterial. The rare reported adverse events tend to occur quickly, most often after flushing of the catheter, and resolve quickly, even when the catheter remains in place. Determining the frequency and severity of adverse events reported in association with the use of Landmark catheters will ultimately require a controlled prospective study, preferably one with a concurrent control group using alternative products.


Diabetes and periodontal disease. Review of the literature.
Diabetes mellitus (DM) is a metabolic disease characterized by an increased blood glucose level, while periodontal disease is mainly characterized by the destruction of tooth support tissues. Detailed investigation is warranted to consider these highly prevalent chronic diseases together and analyze their mutual influence. Over the years, various biologically plausible mechanisms have been established for a common inflammatory etiopathogenesis of these diseases. Numerous epidemiological studies have found a high degree of association between DM and periodontal disease, and periodontal disease has even been proposed as a sixth complication of DM. It has also been demonstrated that this relationship is bidirectional, with periodontitis exerting an effect on DM. These findings have diagnostic and therapeutic implications. Thus, the high prevalence of periodontal disease in DM indicates the need to evaluate glucose levels in periodontal patients. Conversely, intervention studies have demonstrated that the treatment of periodontal disease improves the glycemic control of DM patients.


Effect of nonpayment for preventable infections in U.S. hospitals.
In October 2008, the Centers for Medicare and Medicaid Services (CMS) discontinued additional payments for certain hospital-acquired conditions that were deemed preventable. The effect of this policy on rates of health care-associated infections is unknown. Using a quasi-experimental design with interrupted time series with comparison series, we examined changes in trends of two health care-associated infections that were targeted by the CMS policy (central catheter-associated bloodstream infections and catheter-associated urinary tract infections) as compared with an outcome that was not targeted by the policy (ventilator-associated pneumonia). Hospitals participating in the National Healthcare Safety Network and reporting data on at least one health care-associated infection before the onset of the policy were eligible to participate. Data from January 2006 through March 2011 were included. We used regression models to measure the effect of the policy on changes in infection rates, adjusting for baseline trends. A total of 398 hospitals or health systems contributed 14,817 to 28,339 hospital unit-months, depending on the type of infection. We observed decreasing secular trends for both targeted and nontargeted infections long before the policy was implemented. There were no significant changes in quarterly rates of central catheter-associated bloodstream infections (incidence-rate ratio in the postimplementation vs. preimplementation period, 1.00; P=0.97), catheter-associated urinary tract infections (incidence-rate ratio, 1.03; P=0.08), or ventilator-associated pneumonia (incidence-rate ratio, 0.99; P=0.52) after the policy implementation. Our findings did not differ for hospitals in states without mandatory reporting, nor did it differ according to the quartile of percentage of Medicare admissions or hospital size, type of ownership, or teaching status. We found no evidence that the 2008 CMS policy to reduce payments for central catheter-associated bloodstream infections and catheter-associated urinary tract infections had any measurable effect on infection rates in U.S. hospitals. (Funded by the Agency for Healthcare Research and Quality.).


Activation of the capsaicin-receptor TRPV1 by the acetaminophen metabolite N-arachidonoylaminophenol results in cytotoxicity.
The anandamide reuptake inhibitor N-arachidonoylaminophenol (AM404) and the reactive substance N-acetyl-p-benzoquinone imine (NAPQI) are both metabolites of acetaminophen and may contribute to acetaminophen-induced analgesia by acting at TRPV1 expressed in the peripheral or central nervous system. While NAPQI slowly sensitizes and activates TRPV1 by interacting with distinct intracellular cysteine residues, detailed properties of AM404 as an agonist of TRPV1 have not yet been reported on. We explored the effects of AM404 on recombinant human TRPV1 and in rodent dorsal root ganglion (DRG) neurons. HEK 293 cells expressing different isoforms of recombinant TRPV1 and rodent DRG neurons were employed for patch clamp and calcium imaging experiments. Cytotoxicity was assessed by propidium iodide and Annexin V staining on TRPV1-HEK 293 cells and with trypan blue staining on DRG neurons. AM404 activates hTRPV1 at concentrations >1μM and in a concentration-dependent manner. AM404 also potentiates TRPV1-mediated currents evoked by heat and anandamide. Moreover, AM404-evoked currents are potentiated by NAPQI. While the partly capsaicin-insensitive rabbit (o) TRPV1 fails to respond to AM404, AM404-sensitivity is restored by insertion of the capsaicin binding-domain of rat TRPV1 into oTRPV1. In DRG neurons, AM404-evoked calcium influx as well as cell death is mediated by TRPV1. AM404 gates TRPV1 by interacting with the vanilloid-binding site, and TRPV1 is the main receptor for AM404 in DRG neurons. While direct activation of TRPV1 requires high concentrations of AM404, it is possible that synergistic effects of AM404 with further TRPV1-agonists may occur at clinically relevant concentrations.


[Risk factors for delirium tremens: a literature review].
Delirium tremens (DT) is the most severe complication from alcohol withdrawal. Risk factors for DT (before the withdrawal begins) and early predictive factors for the development of the withdrawal syndrome towards DT (once withdrawal has started) are not clearly established. We reviewed the literature from PubMed/Medline database to identify risk factors for DT. Twenty-one studies were been selected. Three only were prospective. The most commonly identified risk factors included personal history of DT, seizures, presence of acute somatic comorbidity especially infectious, presence of early withdrawal symptoms, and genetic predisposition. Most of these risk factors are still debated and prospective studies might appear useful considering the DT prevalence and the absence of consensual both diagnostic and therapeutic protocols.


Evaluation antimicrobial and antiadhesive properties of the biosurfactant Lunasan produced by Candida sphaerica UCP 0995.
Different groups of biosurfactants exhibit diverse properties and display a variety of physiological functions in producer microorganisms; these include enhancing the solubility of hydrophobic/water-insoluble compound, heave metal binding, bacterial pathogenesis, cell adhesion and aggregation, quorum sensing and biofilm formation. Candida sphaerica was grown in a low cost medium, consisting of distilled water supplemented with 9% refinery residue of soybean oil and 9% corn steep liquor, for 144 h at 28°C and 150 rpm. The cell-free supernatant obtained at the end of the experiments was submitted to extraction, and afterward the biosurfactant was isolated using methanol with a yield of 9 g l(-1). The critical micelle concentration of the biosurfactant was found to be 0.25 mg ml(-1) with a surface tension of 25 mN m(-1). Several concentrations of the biosurfactant (0.625-10 mg ml(-1)) were used to evaluate its antimicrobial and antiadhesive activities against a variety of microorganisms. The biosurfactant showed antimicrobial activity against Streptococcus oralis (68%), Candida albicans (57%), and Staphylococcus epidermidis(57.6%) for the highest concentration tested. Furthermore, the biosurfactant at a concentration of 10 mg ml(-1) inhibited the adhesion between 80 and 92% of Pseudomonas aeruginosa, Streptococcus agalactiae, Streptococcus sanguis12. Inhibition of adhesion with percentages near 100% occurred for the higher concentrations of biosurfactant used. Results gathered in this study point to a potential use of the biosurfactant in biomedical applications.


Nanoparticle-mediated drug delivery to high-grade gliomas.
High grade gliomas (HGGs) are fatal brain tumors due to their infiltration capacity and the presence of resistant cell populations. Further, the brain is naturally protected from many exogenous molecules by the brain blood barrier (BBB), which limits or cancels passage of cytotoxic drugs to the tumor sites. In order to cope with the latter problem, nanoparticle (NP)-based carriers are intensively investigated, due to multiple possibilities to drive them across the BBB to the tumor sites and drop cytotoxic molecules there. The current status of research on NP for drug delivery to HGGs has been analyzed. The results indicate gold, lipids and proteins as three main materials featuring NP formulations for HGG treatment. Albeit specific drug targeting to HGG cells may have not been so far significantly improved, NP may help drugs crossing the BBB and enter the brain thus potentially fixing at least one part of the problem. High grade gliomas (HGG) are very aggressive tumours and current therapy remains unsatisfactory. The advance in nanomedicine has allowed the development of novel treatment modalities. In this review article, the authors outlined the current status in using nanoparticle (NP)-based carriers for drug delivery to HGG. This should help readers to understand and develop ideas for further drug carrier designs.