Non-projectiveness of X-ray Pendellösung-fringed diffraction images.
It has been experimentally found that X-ray moiré fringes are not exactly given as a projected figure from the specimen crystal as predicted by the standard theory of X-ray dynamical diffraction, but show a kind of spatial oscillation along the beam path out of the crystal. This paper reports that a similar spatial oscillation has been found for Pendellösung fringes in a similar experiment recording plane-wave X-ray topographs of a silicon wedge crystal onto a set of multi-stacked films. The oscillation of the Pendellösung fringes was easily found among the simultaneous topographs on the multi-stacked films by examining the fringe profiles, and was also found in topographic images by somewhat careful inspection. It is noteworthy that a simple reciprocal correspondence was observed between the amplitude of fringe oscillation and the fringe contrast. This finding of non-projectiveness, i.e. the fringe oscillation noted above, in Pendellösung fringes as well as in moiré fringes suggests that the non-projectiveness occurs as a very basic property of X-ray interference fringes produced by crystal diffraction.


Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2'-deoxycytidine.
Epigenetic modifications of cytosine residues in DNA and the amino termini of histone proteins have emerged as key mechanisms in chromatin remodeling, impacting both the transcriptional regulation and the establishment of chromosomal domains. Using the chromatin immunoprecipitation (ChIP) assay, we demonstrate that aberrantly silenced genes in cancer cells exhibit a heterochromatic structure that is characterized by histone H3 lysine 9 (H3-K9) hypermethylation and histone H3 lysine 4 (H3-K4) hypomethylation. This aberrant heterochromatin is incompatible with transcriptional initiation but does not inhibit elongation by RNA polymerase II. H3-K9 methylation may, therefore, play a role in the silencing of tumor-suppressor genes in cancer. Treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR), previously known for its ability to inhibit cytosine methylation, induced a rapid and substantial remodeling of the heterochromatic domains of the p14ARF/p16INK4a locus in T24 bladder cancer cells, reducing levels of dimethylated H3-K9 and increasing levels of dimethylated H3-K4 at this locus. In addition, 5-Aza-CdR increased acetylation and H3-K4 methylation at the unmethylated p14 promoter, suggesting it can induce chromatin remodeling independently of its effects on cytosine methylation.


[Development of the adrenal medulla in rats subjected to treatment inducing the Sipple syndrome].
The human Sipple syndrome associates a thyroid-C-cell tumor and a pheochromocytoma. A treatment with the antithyroid drug thiamazole allows obtaining experimentally a similar syndrome in rat. Present paper seeks to analyse changes which happened in the medullary zone of adrenal glands before and during the development of the tumors. During the treatment by thiamazole both adrenal cortex and medulla were atrophied. After the treatment was stopped, the weight of the gland increased, as compared with its previous state, and this was chiefly due to the hyperplasia of medullary cells, from which pheochromocytomas originate. The initial atrophy of adrenal gland depends on the thiamazole-induced hyperthyroidism, but the mechanism of the medullary hyperplasia subsequent to the treatment ending is unknown. It results probably from a secondary hyperthyroidism.


Acute increases in arterial blood pressure produced by occlusion of the abdominal aorta induces antinociception: peripheral and central substrates.
Occlusion of the abdominal aorta proximal to the renal arteries results in an increase in arterial blood pressure, inhibition of forepaw and hindpaw withdrawal to a noxious mechanical stimulus, and inhibition of the tail-flick reflex to noxious heat. Occlusion of the abdominal aorta distal to the renal arteries does not elevate arterial blood pressure and produces no antinociceptive effects. Occlusion of the vena cava lowers arterial blood pressure and produces no antinociception. The inhibitory effects of occlusion of the abdominal aorta depend upon activation of high pressure baroreceptors since bilateral sinoaortic denervation, but not bilateral vagotomy, eliminates the inhibition with respect to all behavioral measures. The inhibitory effects with respect to the tail-flick reflex also depend upon activation of a descending inhibitory system since reversible cold block of the spinal cord at the level of the second thoracic vertebra eliminates the antinociception. This antinociception is also eliminated following intrathecal administration of the noradrenergic receptor antagonist phentolamine, but not by intrathecal administration of either methysergide or naloxone. These data support the view that activation of high pressure baroreceptors by increases in arterial blood pressure produces antinociception via activation of a spinopetal noradrenergic system.


[Transient retinal detachment and hyposphagma in a patient with non-Hodgkin lymphoma of the T cell type (author's transl)].
A 21-year-old male patient with non-Hodgkin lymphoma of the "convoluted' T cell type and marked involvement of skin and central nervous system presented in the early stages of the disease with subconjunctival bleeding of the eyeballs and massive serious retinal detachment near the optic disc in both eyes. In addition, there was a severe disseminated intravascular coagulation (DIC) caused by the lymphoma. It appears that the non-haemorrhagic retinal detachment on both sides is due to a neoplastic lymphocellular infiltration with high affinity of this malignant lymphoma to the central nervous system. Treatment of the underlying disease and of DIC with rapid onset of total remission lead to resorption of the conjunctival haemorrhages and fast reduction of the retinal detachment.


Nurse shortage prompts interim care home closure.
A shortage of nurses in the Isle of Man has led to the temporary closure of a care home for older, mentally ill patients.


Study of aldose reductase inhibition in intact lenses by 13C nuclear magnetic resonance spectroscopy.
Carbon-13 nuclear magnetic resonance spectroscopy has been used in the study of glucose metabolism, specifically aldose reductase inhibition, in intact rabbit lenses maintained in organ culture. This technique provides an effective method of screening potential inhibitors of aldose reductase under conditions that more closely approximate in vivo conditions than do earlier methods. The aspirin substitutes acetaminophen and ibuprofen were studied as aldose reductase inhibitors and were found to be effective in reducing sorbitol accumulation in lenses exposed to high glucose stress. Results of this work with various inhibitors of aldose reductase are discussed in terms of lens metabolism and implications regarding diabetic complications such as cataract formation.


Abdominal abscess: late complication after gastroepiploic coronary artery bypass grafting.
The gastroepiploic artery is widely used an arterial conduit during coronary artery revascularisation surgery. We report an unusual complication of a 56-year-old man who developed a late intra-abdominal abscess extending into the mediastinum adjacent to the right ventricle more than 2 years after surgery. This was managed with percutaneous drainage and the patient made a full recovery. The case illustrates the potential problems associated with harvesting of this artery and the need for careful haemostasis.


Prognostic significance of disease-free interval in head and neck cutaneous squamous cell carcinoma with nodal metastases.
The purpose of this study was to determine whether the disease-free interval (DFI) between treatment of primary head and neck cutaneous squamous cell carcinoma (SCC) and the development of regional metastases is an independent prognostic factor. A retrospective analysis of 229 patients with metastatic nodal head and neck cutaneous SCC, treated with curative intent by surgery ± adjuvant radiotherapy was conducted. After adjusting for the effect of nodal staging, extracapsular spread, involved margins, adjuvant radiotherapy, and immunosuppression, a short DFI (≤9 months vs >9 months) was a significant predictor of disease-related mortality (hazard ratio [HR], 3.0; 95% confidence interval [CI], 1.4-6.5; p = .004) and locoregional relapse (HR, 2.0; 95% CI, 1.1-4.0; p = .044). The DFI is a potentially powerful independent prognostic factor in patients with regional metastases secondary to head and neck cutaneous SCC. It provides information before definitive treatment that may ultimately assist clinicians in applying a risk-adapted management paradigm.


B 96, a seventh allele at the rabbit kappa chain b locus.
A previously undetected allotypic specificity, A96, was observed in the wild rabbit population of Zembra (Tunisia). The A96 allotype is inherited as a b allotype, and its antigenic determinants are located on the kappa light chains of immunoglobulins. Although cross-reacting with b6, the A96 allotype carries its own allotypic determinants, and is therefore distinct form the known allotypes of the b series (b4, b5, b6, b9, b4var and b95). The data indicate that A96 is encoded by an allele at the b locus, tentatively designated b 96.


Spigelian hernia long considered as diverticulitis: CT scan diagnosis and laparoscopic treatment. Computed tomography.
Spigelian hernia (SH) develops in the spigelian aponeurosis. In some cases, its clinical symptoms may mimic those infrequently the diagnosis of sigmoid diverticulitis. Herein we report the case of a patient who for 12 years experienced a pain and a mass in the left lower quadrant that appeared after straining and then disappeared again after rest. A diagnosis of sigmoid diverticulitis was made. She was admitted to hospital for the acute onset of an intense abdominal pain in the left lower quadrant associated with fever. Physical exam showed a 10 x 15 cm mass in the left lower quadrant. Computed tomography (CT) scan showed a left-sided SH containing a small bowel loop and a sigmoid loop. The SH was reduced easily with bed rest and external pressure. Under laparoscopy, a Gore-Tex mesh was stapled on the posterior side of the anterolateral abdominal wall so that it widely covered the abdominal wall defect. The reducible SH, the incarcerated SH, and the strangulated SH represent the majority of the clinical aspects of SH. Although many differential diagnoses are proposed, but the diagnosis of sigmoid diverticulitis is an infrequent one. Ultrasound (US) scan or a CT scan that shows the defect in the abdominal wall, the hernial sac, and its contents is an easy means of confirming the diagnosis of SH. SH can be treated through a direct approach or through a midline laparotomy. Laparoscopy is advisable for a tension-free treatment with an intraperitoneal mesh. It is important to make the diagnosis of SH before its strangulation. For that reason, CT scan and US scan are highly recommended. Laparoscopic treatment, which is effective and safe, is advisable in such cases.


Cystic meningiomas in infancy.
A convexity meningioma associated with a large peritumoral cyst in a 5-month-old girl is reported. Although meningiomas histologically confirmed within the first year of life are quite rare, a review of the cases sporadically appearing in the literature revealed the existence of a group of meningiomas in infants that have unique features in common. The case presented here is a typical example. The clinical characteristics of such a group of meningiomas are discussed.


On the taxonomic state of water mite taxa (Acari: Hydrachnidia) described from the Palaearctic, part 3, Hygrobatoidea and Arrenuroidea with new faunistic data.
Following revision of material from museum collections and recent field work, new taxonomic and faunistic data are given for several representatives of the water mite superfamilies Hygrobatoidea and Arrenuroidea.


Phenytoin, tetrodotoxin, and acetylcholine release.
To determine if phenytoin reduces depolarization-linked acetylcholine release from synaptosomes solely by interacting with Na+, the effect of phenytoin (100 to 200 microM) and/or tetrodotoxin (1 microM) on ACh release was assayed in synaptosomes depolarized with either KCl 56 mM or veratridine 10 microM. Phenytoin reduced release in both depolarizing solutions. In KCl the effect of phenytoin was greater at 200 microM than 100 microM but with veratridine, phenytoin 200 microM was not more effective than 100 microM. Tetrodotoxin failed to affect release induced by KCl but the effect of tetrodotoxin and phenytoin on veratridine-stimulated release was much greater than that with phenytoin alone 100 microM. In conclusion, the inhibition of acetylcholine release by phenytoin must be independent of any effect of the drug on Na conductance.


Public health campaign to promote hand hygiene before meals in a college of veterinary medicine.
Veterinary students can be exposed to environmental infectious agents in school that may include zoonotic pathogens. Encouraging effective hand hygiene can minimize the spread of zoonoses and promote public health and the One Health concept among veterinary students. The purpose of this study was to determine if a campaign could improve hand hygiene among veterinary students at extracurricular meetings serving meals. Nine Kansas State University College of Veterinary Medicine (KSU-CVM) extracurricular organizations participated in the study, sanitizer was provided at each meeting, and baseline hand-hygiene data were observed. A hand-hygiene opportunity was defined as any student observed to approach the buffet food line. Sanitizer use (yes/no) and gender (male/female) were recorded. Campaign interventions included a 3.5-minute educational video and a novel motivational poster. The video was presented to all first-year, second-year, and third-year veterinary students. Posters encouraging hand sanitization were displayed on doors and tables alongside sanitizers at each meeting. Observational hand-hygiene data were collected immediately after introduction of interventions and again 3 months later. Environmental sampling for presence of bacteria in and around meeting locations was also performed. Observed hand hygiene was lowest during baseline (11.0% ± 1.7), improved significantly post-intervention (48.8% ± 3.2), and remained improved at 3-month follow-up (33.5% ± 4.0). Females had higher probability of hand sanitizing (35.9% ± 2.2) than males (21.4% ± 2.4) (p<.01). Clostridium perfringens was isolated from 2/42 samples, and Salmonella spp. were isolated from 4/42 samples. A short-term public health campaign targeting veterinary students successfully improved hand hygiene before meals.


Stereochemistry of aromatic phenytoin hydroxylation in various drug hydroxylation phenotypes in humans.
Phenytoin pharmacokinetics exhibit large intersubject differences and coinheritance of phenytoin metabolism with known drug hydroxylation polymorphisms was therefore suspected. To study the inherited enzymatic mechanisms underlying phenytoin disposition in humans, we have investigated the rate and the stereochemical course of aromatic phenytoin hydroxylation in subjects with and without genetic drug hydroxylation deficiencies for mephenytoin or debrisoquine. For the separate analysis of S- and R-enantiomers of 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH; the major phenytoin metabolite), a chiral ligand exchange chromatography system was used. The S-enantiomer of HPPH was the major urinary phenytoin metabolite irrespective of the various drug hydroxylation phenotypes studied. By contrast, the formation of the HPPH R-enantiomer was significantly decreased in poor metabolizer phenotypes of mephenytoin leading to a bimodal distribution of the urinary HPPH S/R-ratio in humans which was correlated closely with the mephenytoin hydroxylation index. Thus, HPPH S/R-values greater than 40 are likely to occur in S-mephenytoin hydroxylation-deficient phenotypes. Analysis of HPPH S/R-ratios in urine samples in a population of 122 randomly selected epileptic patients under chronic phenytoin treatment showed that product-stereoselective aromatic phenytoin hydroxylation is preserved after chronic drug administration. In subjects with and without genetic S-mephenytoin hydroxylation deficiency, extensive HPPH formation was confirmed by a pronounced NIH-shift of the tritium isotope during the product-stereoselective hydroxylation of the pro-S phenyl ring of phenytoin. Substrate-stereoselective glucuronidation of R- and S-HPPH (and related enantiomeric hydantoin metabolites) could be excluded based on identical urinary excretion of p.o. administered pure metabolite enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of 4-hydroxyandrostenedione on 19-hydroxylation of deoxycorticosterone in the golden Syrian hamster.
4-Hydroxyandrostenedione, a known inhibitor of ovarian and peripheral aromatization of androgen (testosterone and androstenedione) to form estrogen, was studied for its inhibitory effect on the 19-hydroxylating enzyme system of the adrenal for the conversion of deoxycorticosterone to 19-hydroxydeoxycorticosterone. In vitro incubation of Golden Syrian hamster adrenal homogenates with tritiated deoxycorticosterone demonstrated (80-85%) reduction in label incorporated into 19-hydroxydeoxycorticosterone in the presence of 4-hydroxyandrostenedione.


Altruism, spite, and greenbeards.
Hamilton's theory of inclusive fitness showed how natural selection could lead to behaviors that decrease the relative fitness of the actor and also either benefit (altruism) or harm (spite) other individuals. However, several fundamental issues in the evolution of altruism and spite have remained contentious. Here, we show how recent work has resolved three key debates, helping clarify how Hamilton's theoretical overview links to real-world examples, in organisms ranging from bacteria to humans: Is the evolution of extreme altruism, represented by the sterile workers of social insects, driven by genetics or ecology? Does spite really exist in nature? And, can altruism be favored between individuals who are not close kin but share a "greenbeard" gene for altruism?


Pregnancy in the diabetic patient: timing and mode of delivery.
The clinical outcome of 141 consecutive diabetic pregnancies managed in the National Maternity Hospital between January 1, 1979, and October 31, 1982, is described. Patients with gestational diabetes were excluded. There were 12 spontaneous abortions, and the perinatal mortality in 129 viable pregnancies was 31/1000. The malformation rate was 6.4%. Significant perinatal morbidity occurred in 20% of infants. The incidence of cesarean section was 20%. Spontaneous labor after 38 weeks occurred in 30% because there was a deliberate policy to allow all uncomplicated pregnancies to continue to term. This policy had benefits for the infant as well as the mother because there was a notable reduction in neonatal morbidity. Possible explanations of high cesarean section rates in other centers are discussed.


Game changer: the topology of creativity.
This article examines the sociological factors that explain why some creative teams are able to produce game changers--cultural products that stand out as distinctive while also being critically recognized as outstanding. The authors build on work pointing to structural folding--the network property of a cohesive group whose membership overlaps with that of another cohesive group. They hypothesize that the effects of structural folding on game changing success are especially strong when overlapping groups are cognitively distant. Measuring social distance separately from cognitive distance and distinctiveness independently from critical acclaim, the authors test their hypothesis about structural folding and cognitive diversity by analyzing team reassembly for 12,422 video games and the career histories of 139,727 video game developers. When combined with cognitive distance, structural folding channels and mobilizes a productive tension of rules, roles, and codes that promotes successful innovation. In addition to serving as pipes and prisms, network ties are also the source of tools and tensions.


Southern genes. Genetics and its institutions in the Italian South, 1930s-1970s.
The paper examines the historical vicissitudes of Genetics and Medical Genetics in the "Mezzogiorno", focussing on the emergence of local traditions and their mingling with international trends. The development of these disciplines took place in a peculiar mix of politics and science that lead to a rapid growth in the '50s and the '60s, followed by an harsh crisis. Though important and enduring results were attained, Italian genetics community failed to maintain the status reached in the two preceding decades, and quickly moved to the periphery of international networks.


Immunolocalisation of the glutathione S-transferases, GST-26 and GST-28, within adult Schistosoma japonicum.
This paper describes the first ultrastructural immunolocalisation study of the 26-kDa and 28-kDa glutathione S-transferases within adult Schistosoma japonicum (GST-26 and GST-28). Polyclonal antibodies raised against GST-28 (in mice) and against GST-26 (in rabbits) were used to examine the distribution of the proteins within adult parasites. Both proteins were localised within the parenchymal region of the male parasite. Additionally, both proteins were present within parenchymal cells located between the vitelline glands of female parasites. There were no detectable levels of GST-26 or GST-28 on the surface or within the tegument matrix of either the male or female worms. Possible functions for GST-26 and GST-28 within S. japonicum and their significance as vaccine target molecules are addressed.


Dissolvable layered double hydroxide as a sorbent in dispersive micro-solid phase extraction for the determination of acidic quinolones in honey by HPLC.
This study presents a simple and green dispersive micro-solid phase extraction method for preconcentration of acidic quinolones from honey prior to high performance liquid chromatography determination. A two-dimensional nanostructured zinc-aluminum layered double hydroxide was synthesized and used as the sorbent for dispersive micro-solid phase extraction. Its different characteristics from conventional sorbents is that it is dissolvable in acidic solution (pH < 4). After the extraction, the analyte elution step was omitted and thus the use of organic solvents was avoided. The key parameters influencing the extraction efficiency such as the amount of sorbent, pH of sample solution, vortex time, type and volume of acidic solution were investigated and optimized. The method exhibited low limits of detection (3.0-5.0 ng/g), good linearity (10-2000 ng/g) with coefficients of determinations higher than 0.9991, acceptable precision (RSD<9.1%) and accuracy (RE<5.8%). The proposed method is fast, efficient, eco-friendly, and suitable for the determination of acidic quinolones in honey samples.


Anatomical Medial Patellofemoral Ligament Reconstruction for Recurrent Patella Dislocation: Two-Strand Grafts versus Four-Strand Grafts.
The purpose of this study was to describe two anatomical medial patellofemoral ligament (MPFL) reconstruction methods: reconstruction with two-strand grafts and reconstruction with four-strand grafts and to evaluate the clinical and radiological results. From January 2010 to January 2013, patients who sustained recurrent patella dislocation and met inclusion criteria were included in the study and divided into two groups randomly to undergo MPFL reconstruction either by two-strand grafts (T group) or four-strand grafts (F group). Patients were followed up 1 month, 1 year, 2 years, and 3 years postoperatively. The apprehension test was applied to test patella stability. The Kujala score, Lysholm score, and Crosby-Insall grading were used to evaluate the function of the affected knee. The patellar congruence and patellar tilt angle were used to measure the morphology of the patellofemoral joint. In addition, patients' subjective assessments and complications were recorded. Thirty-eight patients in T group and 38 patients in F group were followed for at least 36 months. The apprehension test was positive in all patients preoperatively but was negative at follow-up. The Kujala score, Lysholm score, patellar congruence angle, and the patellar tilt angle of patients in both groups improved significantly at 36-month follow-up when compared with those assessed preoperatively. However, patients in the F group achieved better clinical results in terms of Kujala score, patellar congruence angle, patellar tilt angle, and Crosby-Insall grading when compared with those in the T group 3 years after the operation. Most patients (92% of patients in the T group and 97% of patients in the F group) were satisfied with the surgery. The anatomical MPFL reconstruction with two-strand grafts or four-strand grafts were both safe techniques for recurrent patella dislocation with satisfactory clinical outcomes. The anatomical fixation with four-strand grafts achieved better clinical and radiographic results in the follow-up, which may be a better reconstruction method.


Hemodialysis catheter: induced giant right atrial thrombus.
Transient central venous hemodialysis catheters are used commonly while waiting for arteriovenous fistulas to mature. Thrombosis is a possible complication of indwelling central venous catheters utilized for hemodialysis. However, a giant right atrial thrombus is relatively rare. In this report, we present a case of right atrial thrombus related to transient indwelling hemodialysis catheter, which had been in situ for 45 days.


Non-specific immunological determinations in Meniere's disease: any role in clinical practice?
Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.


High-performance liquid chromatographic separation of inositol phosphate isomers employing a reversed-phase column and a micellar mobile phase.
Surfactants have been employed in high-performance liquid chromatography (HPLC) for the separation of ionic and non-ionic compounds. We have developed a method employing a reversed-phase column and a mobile phase containing a surfactant, hexadecyltrimethylammonium hydroxide (HDTMA+OH-), for the separation of several inositol phosphate positional isomers. Various parameters were studied for their effect on the chromatographic capacity factor (k'). They included the concentration of HDTMA+OH-, the pH of the bulk micellar suspension and the addition of inorganic salts to the mobile phase. Resolution of the inositol monophosphates was controlled by a mixed mechanism, where the predominant elements were electrostatic forces and the formation of micelles. The elution of the inositol polyphosphate isomers was obtained by increasing the amount of a non-polar solvent, in agreement with an ion-pairing process. This method represents an alternative to ion-exchange HPLC. If offers a practical advantage when detection of radiolabeled samples by in-line radioactive flow detectors is required, because low-quenching solvents with good miscibility with scintillant fluids are employed. The analysis of various chromatographic conditions, the system reproducibility and its application to the analysis of biological samples are described.


Thermal stability of polyethylene terephthalate food contact materials: formation of volatiles from retain samples and implications for recycling.
PET packaging materials have been tested for volatile content after exposure to high temperatures. Samples included laminates, bottles, and roasting bags, and were heated at 120 degrees C, 150 degrees C and 230 degrees C for 50 min, according to sample type. Volatiles released from the material were trapped on Tenax, identified by GC-MS and assessed against a 10 micrograms/kg migration threshold limit. Few volatiles were found for samples composed only of PET. Volatiles from laminates varied according to the sample structure, but the main substances identified were not related to PET, but probably came from printing inks and adhesives. It is concluded that the migration potential of PET in high temperature applications is very low and that the formation of volatiles during use is unlikely to cause any special problems in polymer recovery in recycling schemes, provided that other packaging residues are removed effectively.


NMR analysis of the Fischer-Tropsch wastewater: Combination of 1D selective gradient TOCSY, 2D DOSY and qNMR.
The Fischer-Tropsch (FT) process is a practical approach to convert synthesis gas (CO and H2) into hydrocarbons and oxygenates, and these product mixtures are usually well-characterized. However, the analysis of Fischer-Tropsch waste water (FTW) is still somewhat underdeveloped and the exact composition of FTW remains unclear. Herein, various qualitative NMR techniques, especially diffusion-ordered spectroscopy (DOSY) and one dimension (1D) selective gradient total correlation spectroscopy (SelTOCSY) were strategically applied in the analysis of FTW. The NMR results show that the DOSY technique can pseudo-separate most of components in complex mixtures over the diffusion dimension. The SelTOCSY technique is used as a supporting method in the cases where the DOSY technique cannot clearly distinguish overlapped signals. Moreover, the quantitative 1H NMR (qNMR) was further used to quantify the components of the sample. These routine and advanced qualitative and quantitative NMR technique utilized here provide a fast, effective and feasible method for the identification of complex mixtures in FTW, which might be a powerful and fast alternative to gas chromatography or high performance liquid chromatography for FTW research.


Epidemiological methods to study the interaction between HIV infection and other sexually transmitted diseases.
Numerous studies performed over the past 5 years have indicated an association between HIV infection and other sexually transmitted diseases (STDs), particularly those involving genital ulceration. Such an association may be causal, indicating that STDs increase susceptibility to, or infectivity of, HIV infection or may result, in whole or in part, from the mutual dependence of HIV and STDs on patterns of sexual activity, or from an effect of HIV infection on the clinical course of STDs. In this paper we discuss the issues arising in the design and analysis of studies conducted to investigate this association. A numerical illustration is used to demonstrate non-causal associations that may arise in observational studies due to confounding and misclassification. Published cross-sectional and longitudinal studies are reviewed, and recommendations made for future studies. Special emphasis is given to the use of randomized intervention trials to overcome many of the biases associated with observational studies, and to provide information on the efficacy of intensive STD treatment programmes in reducing the transmission of HIV.


Telemetric ICP monitoring after surgery for posterior fossa and third ventricular tumors. Technical note.
After surgery for posterior fossa or third ventricular tumors, hydrocephalus may persist or evolve. Proper management of this complication requires timely detection. Temporary external ventricular drainage has been suggested by some authors as an adjunct to clinical observations and radiographic studies for unshunted patients. As an alternative, the authors have used a telemetric method of pressure monitoring in association with a ventricular catheter and subcutaneous reservoir. This has been found useful in eight patients without the disadvantages inherent in other methods of management.


Local endostatin treatment of gliomas administered by microencapsulated producer cells.
We describe a technique for the treatment of malignant brain tumors based on local delivery of the anti-angiogenic protein endostatin from genetically engineered cells encapsulated in ultrapure sodium alginate. Alginate consists of L-guluronic and D-mannuronic acid, which in the presence of divalent cations forms an extended gel network, in which cells reside and remain immunoisolated, when implanted into the rat brain. Here, we show that endostatin-transfected cells encapsulated in alginate maintain endostatin secretion for at least four months after intracerebral implantation in rats. During the implantation period 70% of the encapsulated cells remained viable, as opposed to 85% in in vitro-cultured capsules. Rats that received transplants of BT4C glioma cells, together with endostatin-producing capsules (0.2 microg/ml per capsule), survived 84% longer than the controls. The endostatin released from the capsules led to an induction of apoptosis, hypoxia, and large necrotic avascular areas within 77% of the treated tumors, whereas all the controls were negative. The encapsulation technique may be used for many different cell lines engineered to potentially interfere with the complex microenvironment in which tumor and normal cells reside. The present work may thus provide the basis for new therapeutic approaches toward brain tumors.


Anticandidal agent for multiple targets: the next paradigm in the discovery of proficient therapeutics/overcoming drug resistance.
Candida albicans is a prominent human fungal pathogen. Current treatments are suffering a massive gap due to emerging resistance against available antifungals. Therefore, there is an ardent need for novel antifungal candidates that essentially have more than one target, as most antifungal repertoires are single-target drugs. Exploration of multiple-drug targeting in antifungal therapeutics is still pending. An extensive literature survey was performed to categorize and comprehend relevant studies and the current therapeutic scenario that led researchers to preferentially consider multitarget drug-based Candida infection therapy. With this article, we identified and compiled a few potent antifungal compounds that are directed toward multiple virulent targets in C. albicans. Such compound(s) provide an optimistic platform of multiple targeting and could leave a substantial impact on the development of effective antifungals.


The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling.
The Spemann organizer plays a central role in neural induction, patterning of the neuroectoderm and mesoderm, and morphogenetic movements during early embryogenesis. By seeking genes whose expression is activated by the organizer-specific LIM homeobox gene Xlim-1 in Xenopus animal caps, we isolated the receptor tyrosine kinase Xror2. Xror2 is expressed initially in the dorsal marginal zone, then in the notochord and the neuroectoderm posterior to the midbrain-hindbrain boundary. mRNA injection experiments revealed that overexpression of Xror2 inhibits convergent extension of the dorsal mesoderm and neuroectoderm in whole embryos, as well as the elongation of animal caps treated with activin, whereas it does not appear to affect cell differentiation of neural tissue and notochord. Interestingly, mutant constructs in which the kinase domain was point-mutated or deleted (named Xror2-TM) also inhibited convergent extension, and did not counteract the wild-type, suggesting that the ectodomain of Xror2 per se has activities that may be modulated by the intracellular domain. In relation to Wnt signaling for planar cell polarity, we observed: (1) the Frizzled-like domain in the ectodomain is required for the activity of wild-type Xror2 and Xror2-TM; (2) co-expression of Xror2 with Xwnt11, Xfz7, or both, synergistically inhibits convergent extension in embryos; (3) inhibition of elongation by Xror2 in activin-treated animal caps is reversed by co-expression of a dominant negative form of Cdc42 that has been suggested to mediate the planar cell polarity pathway of Wnt; and (4) the ectodomain of Xror2 interacts with Xwnts in co-immunoprecipitation experiments. These results suggest that Xror2 cooperates with Wnts to regulate convergent extension of the axial mesoderm and neuroectoderm by modulating the planar cell polarity pathway of Wnt.


Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction.
Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon plays a role in intrauterine growth restriction. Therefore, we investigated microvascular endothelial function in women with intrauterine growth restriction. Laser Doppler fluxmetry was used combined with iontophoresis of acetylcholine and sodium nitroprusside, namely, endothelium-dependent and endothelium-independent vasodilators. We studied 12 women with intrauterine growth restriction and 16 controls in the third trimester of pregnancy. All women had prepregnancy body mass indexes < 26. Acetylcholine-mediated vasodilatation was significantly increased in women with intrauterine growth restriction compared with controls (743% +/- 120% vs 390% +/- 67%, P = .01); sodium nitroprusside-mediated vasodilatation was not different (360% +/- 55% vs 363% +/- 65%, P > .99). Nonobese women with normotensive intrauterine growth restriction show abnormal endothelium-dependent microvascular vasodilatation, suggesting endothelial dysfunction as in preeclampsia. Obviously, for the clinical manifestation of preeclampsia additional factors are required, and a role of metabolic syndrome and obesity has been suggested.


Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2 Diabetes in Chinese Han Population.
This study was to investigate the relationship between SLC22A1 and SLC22A4 gene polymorphisms and genetic susceptibility to type 2 diabetes in Chinese Han population. The research group comprised 110 Chinese Han patients with type 2 diabetes, and the control group included 110 healthy volunteers. The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs2073838 and rs272893 loci were detected in the two groups. Statistically significant differences were identified in the genotype distributions of SLC22A1 gene rs628031 and rs2282143 loci between the two groups (p < 0.05). The A allele frequency of SLC22A1 gene rs628031 locus and the T allele frequency of rs2282143 locus were higher in the research group than in the control group (p < 0.05). The genotype distributions of rs272893 locus showed a significant difference between the two groups (p < 0.05), but not SLC22A4 gene rs2073838 locus (p > 0.05). The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs272893 locus of patients with type 2 diabetes indicated a significant difference between the two groups, suggesting that these genetic locus mutations increase the risk of type 2 diabetes in Chinese Han patients.


Recombinant adenovirus-mediated vascular endothelial growth factor gene transfer attenuates hypoxia-induced apoptosis of neural stem cells in vitro.
To study the effects of vascular endothelial growth factor (VEGF) gene transfer on hypoxia-induced apoptosis of neural stem cells in vitro. C17.2 neural stem cells cultured in vitro were infected by recombinant adenovirus containing VEGF gene and cultured under hypoxic condition. VEGF expression in these cells was detected by Western blotting, and the apoptotic index was calculated from results of triphosphate-biotin nick end-labeling (TUNEL) assay. Flow cytometry was employed to examine the changes in the cell apoptotic rate after VEGF gene transfer, and the apoptotic bodies were observed under fluorescence microscope with Hoechst33342 staining. The expression of VEGF was significantly increased in pAdCMV VEGF(165)-infected cells, resulting in inhibition of the apoptosis of C17.2 neural stem cells induced by hypoxia manifested by a significantly lower apoptotic rate of the stem cells transfected by pAdCMV VEGF(165) than that of the untransfected cells (10.38%;+/-0.48%; vs 19.98 %;+/-0.55%;, P<0.01) and of the cells transfected with pAdCMV VEGF(165) along with VEGF anti-sense oligodeoxynucleotide (19.07%;+/-0.64%;, <0.01) after hypoxia. Recombinant adenovirus can efficiently mediate VEGF gene transfer into C17.2 neural stem cells, resulting in high expression of the exogenous VEGF in vitro, which effectively reduces C17.2 neural stem cell apoptosis induced by hypoxia.


Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage.
Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 +/- 2.1 microns (MMAD +/- delta g). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of > or = 300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM > or = 40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures > or = 10 mg/m3. Lung instillations at 250, 500, and 1000 micrograms of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6x control). However, rats gavaged with VDM had serum enzyme levels 10-100x control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.


First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis.
To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. Prospective randomized trials were included. p-score was used to rank treatment effects. A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.


[The Happiness of Being a Psychotherapist].
Professional work enables people to become conscious of their self-efficiency, to develop self-confidence and to have feelings of belongingness. How far does psychotherapy as a profession satisfy these desiderata? Psychotherapists are able to make others happier than they would otherwise be, but this does not seem to be sufficient for them to find satisfaction in their work. On average, psychotherapists seem to be fairly satisfied with their job. There are, however, great individual differences partly correlated with therapy efficacy. Dissatisfied psychotherapists should make an effort to overcome their difficulties by supervision and continued training, both in their own and in their patients' interest.


Co-existence of spontaneous splenic rupture and tuberculosis of the spleen.
A rare case of splenic tuberculosis complicated by splenic rupture is reported. A 73-year-old man, hospitalized for peptic ulcer bleeding, presented in oligemic shock, was transferred to the operating room. Hemoperitoneum, due to rupture of an enlarged spleen was detected. The pathology revealed splenic tuberculosis. He had an uneventful recovery. Postoperatively, he received a combination of anti-tuberculous therapy for 6 months.


Effect of Botulinum toxin A application in neuro-ophtalmologic indications on Schirmers test and tears osmolarity.
Botulinum toxin type A (BT-A) is used in the treatment of neuro-ophthalmologic disorders such as essential blepharospasm and facial hemispasm for more than 20 years. Although the long-term effect of repeated application of the BT-A was confirmed, the BT-A effect on tears production and retention is not clear. In our work we investigated whether applied BT-A in patients with blepharospasm and hemifacial spasm affect tears production. Tears quality was measured with Schirmers and tear osmolarity test during neuro-ophthalmologic diseases treatment, which was evaluated before and 14 days after application of BT-A (Botox inj, Allergan, Irvine, USA) into the orbicularis oculi muscle. BT-A doses of 16-18 U with unilateral and 32 to 36 U bilateral applications were used. The mean tear production in Schirmers test before BT-A application was 8.38 ± 0.63 mm, and 2 weeks after BT-A application was 7.12 ± 0,6 mm (n = 50). Tear osmolarity was 305.4 ± 9.2 mOsm before BT-A application, and 2 weeks after BT-A application it was 305.2 ± 8,6 mOsm (n = 13). We found significant difference between two groups in tear quantity (p < 0.012), but not quality (p > 0.05). Application of the BT-A reduced the amount of tears measured by Schirmers test. These results confirm rational basis of the empirical clinical experience where an artificial tears substitution is recommended for patients with neuro-ophthalmologic disorders treated by BT-A.


Diethyldithiocarbamate (DEDC) impairs neuronal recovery following sciatic nerve injury in rats.
Purpose: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. Methods: Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. Results: Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves. Conclusions: Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress.


Validation of Christianella Guiart, 1931 (Cestoda: Trypanorhyncha) and its taxonomic relationship with Grillotia Guiart, 1927.
Christianella Guiart, 1931 (Cestoda: Trypanorhyncha) is redefined as a subgenus of Grillotia Guiart, 1927 based on the type-species, G. (C.) minuta (van Beneden, 1849), from the elasmobranch Squatina squatina (Linnaeus). Grillotia smarisgora (Wagener, 1854) is treated as a synonym of G. (C.) minuta, as are G. angeli Dollfus, 1969 and G. bothridiopunctata Dollfus, 1969. Other species included in the subgenus are G. (C.) carvajalregorum Menoret & Ivanov, 2009 (formerly Progrillotia dollfusi Carvajal & Rego, 1983), G. (C.) australis Beveridge & Campbell, 2001, G. (C.) longispinis (Linton, 1890) n. comb. (formerly Rhynchobothrium longispine Linton, 1890) and G. (C.) yuniariae Palm, 2004. The subgenus is similar to Grillotia Guiart, 1927 (sensu stricto), having two bothria and an atypical heteroacanthous armature, but differs in having a single row of intercalary hooks, fewer, elongate segments with testes often in longitudinal columns, a distinctive basal armature, an internal seminal vesicle which extends beyond the cirrus or hermaphroditic sac and no uterine pore. The adults of three species are known, all parasitising members of Squatina Duméril.


Continuous cell lines from embryonic tissues of ticks (Acari: Ixodidae).
Six new cell lines were established in continuous culture from embryonic tissues of ixodid ticks. Four were from Dermacentor variabilis and two from D. parumapertus. The cells are mostly fibroblastic and diploid. Mosquito-borne viruses (Chikungunya, O'nyong, yellow fever, and St. Louis encephalitis) as well as tick-borne ones (Langat, Powassan, Colorado tick fever, Kemerovo, and Sawgrass) replicated in certain of these cell lines, but a nonvector-borne flavivirus, Modoc, did not. An underscribed virus from D. occidentalis ticks, which could not be isolated in Vero cells or newborn mice, was readily isolated in the D. variabilis cell line.


[Research progress on regulation effect of Panax notoginseng saponins on mitochondria].
Mitochondria is the key energy source of cells and plays an important role in energy synthesis and release, and maintenance of cellular functions. As the most important active ingredients in Chinese medicine pseudo-ginseng, Panax notoginseng saponins(PNS) have pharmacological effects on protecting against thrombosis, dilating blood vessels, lowering the blood pressure, anti-inflammation, and antioxidant, etc. Domestic and foreign studies have shown that PNS participates in regulating mitochondrial energy metabolism, oxidative stress, biosynthesis, apoptosis, mitophagy and the status of membrane channels. Therefore, the mitochondria is one of the important targets of PNS. In this paper, the regulation effects of P. notoginseng saponins on mitochondria were reviewed.


Cichlid-catfish mutualistic defense of young in Lake Malawi, Africa.
Bagrid catfish and cichlid parents engage in a mutualistic defense of their young from predators. Over 50% of the catfish broods observed contained cichlid young, primarily of three species: Crytocara pleurostigmoides, C. pictus and Rhamphocromis sp. Three catfish broods, monitored for over 50 days, had a survivorship rate 6 times greater during periods when cichlids were present than when cichlids were absent. During two and a half h of observations of catfish broods without cichlids, I observed 23 strikes by predators on catfish young. However, when cichlids were present no foraging attacks were observed upon the catfish, but 32 occurred against cichlids in two and a half hours of observations. When the catfish parents were experimently removed the cichlid young were consumed first then the catfish young. When cichlids were present the catfish young survived over 80% longer than those in broods without cichlids. It is concluded that the parental catfish increase the survival of their own young be allowing cichlids into the brood. Because of an asymmetry of costs between the two species, cichlid mothers are more likely to abandon these interspecific broods than are the catfish.


Block copolymers containing organic semiconductor segments by RAFT polymerization.
Approaches to the synthesis of block copolymers containing organic semiconductor segments (polythiophene, perylene diimide) by RAFT polymerization have been explored. A method involving transformation of a vinyl derivative to a macro-RAFT agent provides for the synthesis of block copolymers which are joined by a short non-hydrolysable linkage.


Assembly of microtubules at the tip of growing axons.
The growth of axons in the developing nervous system depends on the elongation of the microtubules that form their principal longitudinal structural element. It is not known whether individual microtubules in the axon elongate at their proximal ends, close to the cell body, and then move forward into the lengthening axon, or whether tubulin subunits are transported to the tip of the axon and assembled there onto the free ends of microtubules. The former possibility is supported by studies of slow axonal transport in mature nerves from which it has been deduced that microtubule assembly occurs principally at the neuronal cell body. By contrast, the polarity of microtubules in axons, which have their 'plus' or 'fast-growing' ends distal to the cell body, suggests that assembly occurs at the growing tip, or growth cone, of the axon. We have addressed this question by topically applying Colcemid (N-desacetyl-N-methylcolchicine), and other drugs which alter microtubule stability, to different regions of isolated nerve cells growing in tissue culture. We find that the sensitivity to these drugs is greatest at the growth cone by at least two orders of magnitude, suggesting that this is a major site of microtubule assembly during axonal growth.


[Disruptive behavior in adolescence and its relationship with temperament and coping styles].
Employing the DSM-IV TR classification, which classifies both antisocial behavior disorder and oppositional defiant disorder under the label of disruptive behavior disorder, a study was conducted with two aims: a) to determine the symptomatological differences of disruptive behavior disorder in adolescence depending on gender, age and school location, and b) to analyse the relationships between temperament, coping and the psychopathological dimensions of antisocial and oppositional defiant behavior. The YI-4, EATQ-R and ACS were administered to a sample of 1,240 adolescents between 11 and 17 years of age. The results show that boys display a greater number of antisocial behaviors than girls. No differences in school location were observed. In the oppositional defiant symptoms, there were differences according to age group, with 13 to 14 years being an age when there is a greater symptomatology. The data indicate a positive correlation with psychopathological dimensions of both surgency and non-productive coping and a negative correlation with effortful control and productive coping.


Malignant parotid tumors. Diagnostic considerations and therapeutic suggestions.
This paper presents our experience of the problem of diagnosis and surgical treatment of malignant parotid tumors, based on a retrospective evaluation of a series of 478 parotid tumors, of which 100 were malignant. Out of 75 primaris malignant tumors of epithelial origin, 35 belonged to the "epidermoid" group (adenocarcinomas, undifferentiated carcinomas, malignant mixed tumors, squamous cell carcinoma), 20 were mucoepidermoid carcinomas, 15 adenoid cystic carcinomas and 5 were acinic cell carcinoma. Altogether, 58.7% of the treated patients do not at the moment present evidence of disease; 33.3% are dead from the disease or are alive with active disease; 5.3% are dead from other causes and 2.7% are lost to follow-up. Underlining the importance of histologic examination of the swelling by intraoperative biopsy, the authors propose a diagnostic and therapeutic protocol.


Clinical features and short-term outcome of presumptive intracranial complications associated with otitis media/interna: a multi-center retrospective study of 19 cats (2009-2017).
The aim of this study was to compile an overview of the clinical features of intracranial complication of otitis media/interna (OMI) in cats managed across five veterinary referral hospitals. Of additional interest were culture results that could inform empirical antibiotic selection, as well as outcome with both medical and surgical management. A retrospective medical record review was conducted at five veterinary referral practices to identify cats with a diagnosis of intracranial complication secondary to OMI between 2009 and 2017. Clinical features, diagnostic findings, treatment and outcome were recorded. At total of 19 cats were identified. Sixty-three percent had no previous history of ear infection. Otoscopic examination was normal in 47% of cases. The most common bacterial isolate was Pasteurella multocida, which was identified in 24% of cases. Outcome was successful for 83% of cats managed with ventral bulla osteotomy (VBO) and in 66% of cats managed without surgical intervention. Clinical suspicion of intracranial complications of OMI should remain high in cats with central vestibular disease even if otoscopic examination is normal. Antibiotic selection should be based on a culture and sensitivity; however, initial antibiotic therapy should include broad-spectrum coverage with special consideration for P multocida. Cats with intracranial complications of OMI can have a good outcome with either surgical or medical management and prospective studies are needed to assess the role of VBO in enhancing recovery.


Binding of a Hoechst dye to d(CGCGATATCGCG) and its influence on the conformation of the DNA fragment.
Hoechst dye 33258 is a planar drug molecule that binds to the minor groove of DNA, especially where there are a number of A.T base pairs. We have solved the structure of the Hoechst dye bound to the DNA dodecamer d(CGCGATATCGCG) at 2.3 A. This structure is compared to that of the same dodecamer with the minor-groove-binding drug netropsin bound to it, as well as to structures that have been solved for this Hoechst dye bound to a DNA dodecamer containing the central four base pairs with the sequence AATT. We find that the position of the Hoechst drug in this dodecamer is quite different from that found in the other dodecamer since it has an opposite orientation compared to the other two structures. The drug covers three of the four A.T base pairs and extends its piperazine ring to the first G.C base pair adjacent to the alternating AT segment. Furthermore, the drug binding has modified the structure of the DNA dodecamer. Other DNA dodecamers with alternating AT sequences show an alternation in the size of the helical twist between the ApT step (small twist) and the TpA step (large twist). In this structure the alternation is reversed with larger twists in the ApT steps than in the TpA step. In addition, there is a rotation of one of the thymine bases in the DNA dodecamer that is associated with hydrogen bonding to the Hoechst drug. This structure illustrates the considerable plasticity found in the DNA molecule when it binds to different planar molecules inserted into the minor groove.


[Genetic diversity of reaction of common wheat (Triticum aestivum L.) cultivars to light intensity].
The effect of low light intensity (LI) on the period from sprouting to earing was studied in 12 cultivars of the spring common wheat under controlled conditions. Differences between cultivars with respect to their responses to LI (RLIs) were found both for those that were photoperiod-sensitive and those that were almost photoperiod-neutral. Specifically, a prolonged photoperiod and a low LI differently increased the period from sprouting to earling in different cultivars. Genetic analysis of the RLI demonstrated, for the first time, that the weak response was incompletely dominant in F1. The results of genetic analysis agree with the hypothesis that the cultivars Pitic 62 and Novosibirskaya 22 differ in alleles of two loci controlling the RLI in wheat.


Timed-release polymer nanoparticles.
Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.


LIM-homeodomain genes in mammalian development and human disease.
The human and mouse genomes each contain at least 12 genes encoding LIM homeodomain (LIM-HD) transcription factors. These gene regulatory proteins feature two LIM domains in their amino termini and a characteristic DNA binding homeodomain. Studies of mouse models and human patients have established that the LIM-HD factors are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. In this article, we review the roles of the LIM-HD proteins in mammalian development and their involvement in human diseases.


Long-term Exposure to Fine Particulate Matter and Breast Cancer Incidence in the Danish Nurse Cohort Study.
Background: An association between air pollution and breast cancer risk has been suggested, but evidence is sparse and inconclusive.Methods: We included 22,877 female nurses from the Danish Nurse Cohort who were recruited in 1993 or 1999 and followed them for incidence of breast cancer (N = 1,145) until 2013 in the Danish Cancer Register. We estimated annual mean concentrations of particulate matter with diameter <2.5 μg/m3 (PM2.5) and <10 μg/m3 (PM10), and nitrogen dioxide (NO2) at nurses' residences since 1990 using an atmospheric chemistry transport model. We examined the association between the 3-year running mean of each pollutant and breast cancer incidence using a time-varying Cox regression.Results: We found no association between breast cancer and PM2.5 (HR, 0.99; 95% confidence interval, 0.94-1.10 per interquartile range of 3.3 μg/m3), PM10 (1.02; 0.94-1.10 per 2.9 μg/m3), or NO2 (0.99; 0.93-1.05 per 7.4 μg/m3).Conclusions: Air pollution is not associated with breast cancer risk.Impact: Exposure to air pollution in adulthood does not increase the risk of breast cancer, but more data on the effects of early exposure, before first birth, are needed. Cancer Epidemiol Biomarkers Prev; 26(3); 428-30. ©2016 AACR.


The uncoupling of autophagy and zinc homeostasis in airway epithelial cells as a fundamental contributor to COPD.
The proper regulation of zinc (Zn) trafficking proteins and the cellular distribution of Zn are critical for the maintenance of autophagic processes. However, there have been no studies that have examined Zn dyshomeostasis and the disease-related modulation of autophagy observed in the airways afflicted with chronic obstructive pulmonary disease (COPD). We hypothesized that dysregulated autophagy in airway epithelial cells (AECs) is related to Zn dysregulation in cigarette smoke (CS)-induced COPD. We applied a human ex vivo air-liquid interface model, a murine model of smoke exposure, and human lung tissues and investigated Zn, ZIP1, and ZIP2 Zn-influx proteins, autophagy [microtubule-associated 1A/1B-light chain-3 (LC3), Beclin-1], autophagic flux (Sequestosome), apoptosis [Bcl2; X-linked inhibitor of apoptosis (XIAP), poly (ADP)-ribose polymerase (PARP)], and inflammation [thymic stromal lymphopoietin (TSLP), regulated on activation, normal T cell expressed and secreted (RANTES), and IL-1β]. Lung tissues from CS-exposed mice exhibit reduced free-Zn in AECs, with elevated ZIP1 and diminished ZIP2 expression. Interestingly, increased LC3 colocalized with ZIP1, suggesting an autophagic requirement for free-Zn to support its catabolic function. In human AECs, autophagy was initiated but was unable to efficiently degrade cellular debris, as evidenced by stable Beclin-1 and increased LC3-II, but with a concomitant elevation in Sequestosome. Autophagic dysfunction due to CS exposure coupled with Zn depletion also induced apoptosis, with the reduction of antiapoptotic and antiautophagic proteins Bcl2 and XIAP and PARP cleavage. This was accompanied by an increase in RANTES and TSLP, an activator of adaptive immunity. We conclude that the uncoupling of Zn trafficking and autophagy in AECs constitutes a fundamental disease-related mechanism for COPD pathogenesis and could provide a new therapeutic target.


Ultrasound-assisted extraction of polysaccharides from mulberry leaves.
Ultrasound-assisted extraction (UAE) of polysaccharides from mulberry leaves was studied. The effects of four factors on the yield of polysaccharides were investigated. The results showed that optimum conditions were extraction power of 60W, extraction temperature of 60°C, extraction time of 20min and ratio of water to raw material of 15:1 (ml/g). The three different methods (UAE, MAE and CSE) were compared for extracting polysaccharides from the mulberry leaves by SEM images. Totally, UAE had the largest yield of polysaccharides. The crude polysaccharides obtained from UAE were purified and two components (MPS-1 and MPS-2) were obtained. Their structure was analysed with chemical methods. From FT-IR, they were polysaccharides. MPS-1 had more functional groups than MPS-2. From HP GPC analysis, molecular weights of MPS-1 and MPS-2 were 24898D and 61131D, respectively. From GC analysis, MPS-1 was composed of Sor, Ara, Xyl and Glc, and MPS-2 was composed of Rha, Ara, Xyl, Glc, Gal and Man.


Navigation-guided en bloc resection and defect reconstruction of craniomaxillary bony tumours.
The aim of this study was to evaluate the validity of navigation-guided en bloc tumour resection and defect reconstruction in the treatment of craniomaxillary bony tumours. Three patients with ossifying fibroma and two patients with fibrous dysplasia were enrolled in this study. After preoperative planning and three-dimensional simulation, the osteotomy lines for resection were delineated and the normal anatomic structures for defect reconstruction were ascertained. With the guidance of an Accu-Navi navigation system, an en bloc tumour resection and simultaneous defect rehabilitation were performed. The system provided continuously updated information on the position and movement of surgical instruments in the operating field in relation to the preoperative imaging data set. The system error measured by the computer did not exceed 1mm. The osteotomy lines and reconstruction contour were checked by postoperative computed tomography, and good matching with the preoperative planning was achieved. Patients showed no signs of tumour recurrence or prosthesis infection during follow-up (range 12-35 months). Image-guided navigation makes radical bone tumour resection more reliable by implementing preoperative planning, showing the determined safety margins, preserving vital structures and guiding reconstruction.


TI2BioP: Topological Indices to BioPolymers. Its practical use to unravel cryptic bacteriocin-like domains.
Bacteriocins are proteinaceous toxins produced and exported by both gram-negative and gram-positive bacteria as a defense mechanism. The bacteriocin protein family is highly diverse, which complicates the identification of bacteriocin-like sequences using alignment approaches. The use of topological indices (TIs) irrespective of sequence similarity can be a promising alternative to predict proteinaceous bacteriocins. Thus, we present Topological Indices to BioPolymers (TI2BioP) as an alignment-free approach inspired in both the Topological Substructural Molecular Design (TOPS-MODE) and Markov Chain Invariants for Network Selection and Design (MARCH-INSIDE) methodology. TI2BioP allows the calculation of the spectral moments as simple TIs to seek quantitative sequence-function relationships (QSFR) models. Since hydrophobicity and basicity are major criteria for the bactericide activity of bacteriocins, the spectral moments ((HP)μ(k)) were derived for the first time from protein artificial secondary structures based on amino acid clustering into a Cartesian system of hydrophobicity and polarity. Several orders of (HP)μ(k) characterized numerically 196 bacteriocin-like sequences and a control group made up of 200 representative CATH domains. Subsequently, they were used to develop an alignment-free QSFR model allowing a 76.92% discrimination of bacteriocin proteins from other domains, a relevant result considering the high sequence diversity among the members of both groups. The model showed a prediction overall performance of 72.16%, detecting specifically 66.7% of proteinaceous bacteriocins whereas the InterProScan retrieved just 60.2%. As a practical validation, the model also predicted successfully the cryptic bactericide function of the Cry 1Ab C-terminal domain from Bacillus thuringiensis's endotoxin, which has not been detected by classical alignment methods.


Patient adherence to osteoporosis medications: problems, consequences and management strategies.
Adherence to osteoporosis medications is relatively poor. Approximately 20-30% of patients taking daily or weekly treatments may suspend their treatment within 6 to 12 months of initiating therapy. Patients with poor adherence increase their risk of osteoporotic fractures and hospitalisation. The majority of patients who discontinue therapy appear to do so because of drug-induced adverse effects. Fear of adverse effects or other health risks is another commonly cited reason for discontinuing therapy. Factors associated with medication adherence include fractures, regular exercise, female sex, fewer non-osteoporosis medications and co-morbidities, early menopause, willingness to take medications, awareness of osteoporosis status based on a diagnostic test, anti-inflammatory therapy and corticosteroid therapy. Factors associated with non-adherence include adverse effects, pain and being unsure about bone mineral density (BMD) test results. Bisphosphonates, a common class of drugs for treating osteoporosis, have specific administration requirements (e.g. fasting, remaining upright and not ingesting other medications concomitantly). Patient surveys indicate that 12-18% of patients report non-compliance with at least one administration rule. Strategies to increase adherence include reducing administration frequency to weekly or monthly, monitoring patients with bone markers and BMD testing, providing adequate instructions, practitioner feedback and support, and educational materials and sessions. Future studies are needed regarding strategies to increase adherence to osteoporosis medications.


Risk of pulmonary embolism and deep venous thrombosis in patients with asthma: a nationwide case-control study from Sweden.
Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma.We conducted this nationwide case-control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sex- and education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders.Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37-1.50), for DVT of 1.56 (95% CI 1.47-1.65) and for combined PE and DVT of 1.60 (95% CI 1.32-1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT.Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE.


Chlorobenzilate-induced effects on enzyme-altered foci in rat liver and intercellular communication in rat liver WB-F344 epithelial cells.
The mouse liver carcinogen chlorobenzilate (CB), a DDT-related pesticide, was investigated for enhancement of enzyme altered foci incidence in partially hepatectomized, diethyl-nitrosamine-initiated rats. In this in vivo experiment, CB administered per os (25 or 100 mg/kg per day for 10 weeks) enhanced foci incidence at the high dose level. In order to study potential mechanisms involved, CB was investigated for inhibition of gap-junctional intercellular communication in rat liver epithelial WB-F344 cells and Chinese hamster V79 cells in vitro. CB abolished dye transfer in WB-F344 cells and inhibited metabolic cooperation in V79 cells. Two CB metabolites were unable to induce such tumor promotion related effects. The results of this investigation provide support for the involvement of an epigenetic, tumor promoting mechanism in CB-induced liver tumors in laboratory animals.


Altitudinal and climatic associations of seed dormancy and flowering traits evidence adaptation of annual life cycle timing in Arabidopsis thaliana.
The temporal control or timing of the life cycle of annual plants is presumed to provide adaptive strategies to escape harsh environments for survival and reproduction. This is mainly determined by the timing of germination, which is controlled by the level of seed dormancy, and of flowering initiation. However, the environmental factors driving the evolution of plant life cycles remain largely unknown. To address this question we have analysed nine quantitative life history traits, in a native regional collection of 300 wild accessions of Arabidopsis thaliana. Seed dormancy and flowering time were negatively correlated, indicating that these traits have coevolved. In addition, environmental-phenotypic analyses detected strong altitudinal and climatic clines for most life history traits. Overall, accessions showing life cycles with early flowering, small seeds, high seed dormancy and slow germination rate were associated with locations exposed to high temperature, low summer precipitation and high radiation. Furthermore, we analysed the expression level of the positive regulator of seed dormancy DELAY OF GERMINATION 1 (DOG1), finding similar but weaker altitudinal and climatic patterns than seed dormancy. Therefore, DOG1 regulatory mutations are likely to provide a quantitative molecular mechanism for the adaptation of A. thaliana life cycle to altitude and climate.


A decision theory approach to fitness for purpose in analytical measurement.
The choice of an analytical procedure and the determination of an appropriate sampling strategy are here treated as a decision theory problem in which sampling and analytical costs are balanced against possible end-user losses due to measurement error. Measurement error is taken here to include both sampling and analytical variances, but systematic errors are not considered. The theory is developed in detail for the case exemplified by a simple accept or reject decision following an analytical measurement on a batch of material, and useful approximate formulae are given for this case. Two worked examples are given, one involving a batch production process and the other a land reclamation site.


Mediterranean diet of Crete: foods and nutrient content.
To describe the traditional diet of Crete and evaluate the nutrient composition of 3 types of diet common in Crete by means of chemical analyses of composite food samples. To compare results with dietary analyses from a nutrient database developed at the University of Crete, Greece. Three composite diet samples were obtained based on 7-day weighed food records representing the traditional Cretan Mediterranean diet (diet A), typical diet of present-day Greek adolescents (diet B), and fasting diet of the Eastern Orthodox church (diet C). Analyses were performed chemically and using a nutrient database. Chemical analyses provided a definitive measure, for the first time, of the nutrient composition of the complete Greek diet as it was in the early 1960s. In comparing chemical analyses with nutrient database analyses, differences greater than 15% of the analyzed value were found in all 3 diets for cholesterol and some vitamins. The differences between analyzed and calculated values in total fat and saturated fat content were less than 15% in all diets. The present study provides 2 practical examples of the Mediterranean diet, which although widely publicized has rarely been analyzed chemically. Diet A has been shown to be related to the lowest rates for coronary heart disease and cancer mortality compared with the diets of the other populations of the Seven Countries study. As such, it could be recommended for health promotion and prevention of disease. Diet C contains even lower amounts of saturated fatty acids and would be excellent for patients with hypercholesterolemia. The high antioxidants in diet C probably maintain very low levels of low-density lipoprotein cholesterol. Dietary analyses of the Greek diet could be based on an operational database such as ours if further chemical analyses are performed on specific foods. These would result in improved precision of the database and possible extension into national food composition tables and a national dietary database.


[Well differentiated localized prostate carcinoma: prognostic relevance of tertiary Gleason pattern 4 and tumor volume].
Early introduction of adjuvant radiation or hormone therapy after radical prostatectomy has been advocated in recent literature aiming to improve survival rates in high risk prostate cancer. Traditional prognostic parameters such as serum PSA, Gleason score and clinical stage have been used to identify these cases however accuracy is far from ideal. Recently, tumor volume and presence and percentage of a tertiary less differentiated Gleason pattern have been considered better indicators of prostate cancer behavior. The purpose of this study was to evaluate the importance of presence and percentage of a Gleason pattern 4 and of tumor volume in the outcome of patients treated for well-differentiated prostate adenocarcinoma. Seventy seven patients submitted to radical prostatectomy for well-differentiated prostate carcinoma, Gleason score 6 or less, and followed up for at least 5 years were selected. Thirty seven experienced biochemical recurrence while 40 did not. The percentage of Gleason pattern 4, the percentage of the gland involvement (considered as "tumor volume"), capsular invasion and extraprostatic extension were submitted to univariate and multivariate analyses for the evaluation of possible associations with biochemical recurrence. Tumor volume was the most important parameter to predict biochemical recurrence by univariate and multivariate analysis. The median of tumor volume was 25.0% for patients who suffered recurrence, and 11.5% for those with no recurrence (p=0.003). The percentage of Gleason pattern 4 was predictive of recurrence in univariate analysis only. The median percentage of Gleason pattern 4 was 7.5% for patients without recurrence and 19.0% for those who presented recurrence (p=0.046). Tumor volume is very objective, easy to evaluate and the most important parameter to predict biochemical recurrence in well-differentiated adenocarcinoma of the prostate. On the other hand, presence and percentage of a tertiary less differentiated Gleason pattern correlated with systemic relapse. Both parameters should be included in future studies to evaluate the role of adjuvant therapy in high risk prostate cancer.


Emotional states and sleep disorders in adolescent and young adult cystic fibrosis patients.
The aim of the study was to evaluate level of anxiety, depression and aggression and the sleep quality among Polish adolescent and young adult suffering from cystic fibrosis including the evaluation of their FEV1. The study involved 70 patients both male and female aged between 14 and 25 and suffering from cystic fibrosis. Anxiety, depression and aggression were evaluated by means of Hospital Anxiety and Depression Scale and the quality of sleep was examined following Athens Insomnia Scale another aspect taken into consideration was patients' FEV1. The data analysis was carried out by means of Chi2, Kolmogorov-Smirnov test, Student's t-test, Fisher-Snedecor test, Pearson correlation coeficient. The level of statistical significance was set at p <0.05. Anxiety was observed in 27 (38.6%) cases, depression in 17 (24.3%) and aggression in 46 (65.7%) cases. Anxiety (p = 0.017) and aggression (p = 0.004) were significantly higher among women than among men. 37 (52.8%) patients reported sleep disorders. The findings proved that there is a connection between the quality of sleep and anxiety (r = 0.631; p = 0.000), depression (r = 0.621; p = 0.000) and aggression (r = 0.293; p = 0.014). No significant relationship was found between the quality of sleep and patients' expiratory volume. Emotional disorders such as anxiety, depression and aggression as well as sleep disorders are commonly reported in patients suffering from cystic fibrosis.


Cardiovascular risk factors contribute to disparities in graft outcomes in African American renal transplant recipients: a retrospective analysis.
Data examining cardiovascular (CV) risk factors in renal transplant recipients (RTRs) and their contribution to the disparity in graft survival between African American (AA) patients and non-AAs is limited. A single-center, retrospective analysis of 1003 adult RTRs from January 1, 2000 to May 1, 2008 to inspect the impact of race on post-transplant CV events, treatment of CV risk factors and their independent influence on graft outcomes was performed. AAs experienced a higher incidence of late graft loss, with 1- and 5-year graft survival rates of 93% and 76% vs 95% and 84% in the non-AA group, respectively. AA patients had a higher prevalence of hypertension (HTN) and diabetes mellitus (DM) and demonstrated reduced control of DM post-transplant (AA 74% vs non-AA 82%, p = 0.053). Multivariate analysis for graft survival indicated acute rejection, delayed graft function (DGF) and incidence of CV events were significant risk factors for graft failure, while the use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were protective. In conclusion, after controlling for CV risk factors and events, race did not have an independent effect on outcomes, suggesting CV risk factors and events contribute to this disparity. Clinical summary. AAs experienced a higher rate of graft failure and CV events; after adjusting for multiple immunological and CV risk factors, race no longer remained an independent risk factor for post-transplant CV events or graft failure; although disparities in post-transplant outcomes remain, race alone does not account for the disparity; the racial disparity is due to the higher incidence of DGF and acute rejection, as well as traditional CV risk factors, including HTN and DM.


Sub-syndromes of tardive dyskinesia and some clinical correlates.
Syndromes of dyskinetic movements in subjects (N = 70) with chronic schizophrenia were investigated, using principal components analysis of AIMS ratings. Consonant with previous research, three discrete groupings were found, namely dyskinetic movements of lips-jaw-tongue, limb-truncal and facial movements. These were then related to demographic, psychological and movement disorder variables. The limb-truncal, but neither the lips-jaw-tongue nor facial movements components, were associated with negative symptoms and cognitive impairment.


Influence of the age and sex of human hosts on the distribution of Escherichia coli ECOR groups and virulence traits.
Escherichia coli were isolated from the faeces of 266 individuals living in the Canberra region of Australia. The isolates were characterized for their ECOR group membership (A, B1, B2 or D) and for the presence of 29 virulence-associated traits. Overall, 19.5 % of the strains were members of group A, 12.4 % B1, 45.1 % B2 and 22.9 % D. The frequency with which strains belonging to the four ECOR groups were observed varied with the age and sex of the hosts from which they were isolated. In males, the probability of isolating A or D strains increased with host age, whilst the probability of detecting a group B2 strain declined. In females, the probability of recovering A or B2 strains increased with increasing host age and there was a concomitant decline in the likelihood of isolating B1 or D strains. Of the 29 virulence-associated traits examined, 24 were detected in more than one strain. The likelihood of detecting most traits varied with a strain's ECOR membership, with the exception of afa/draBC, astA, cvaC, eaeA, iss and iutA, for which there was no statistically significant evidence of an association with ECOR group. The frequency with which fimH, iha, eaeA, iroN, hlyD, iss, ompT and K1 were detected in a strain depended on the age or sex of the host from which the strain was isolated. In group B2 strains many of the virulence traits were non-randomly associated, with some co-occurring in a strain less often than expected by chance, whilst others were co-associated. In 17 cases, the extent to which two virulence traits were co-associated was found to depend on host sex and age. The results of this study suggest that the morphological, physiological and dietary differences that occur among human individuals of different sex or age may influence the distribution of E. coli genotypes.


Inhibition of the expression of inducible nitric oxide synthase and cyclooxygenase-2 in macrophages by 7HQ derivatives: involvement of IkappaB-alpha stabilization.
Nitric oxide is an important biological mediator associated with multiple pathophysiological phenomena, such as platelet aggregation, vasodilation, septic shock, and autoimmune diseases. Prostaglandins, derived from cyclooxygenases, play prominent roles in homeostasis and inflammation. In this study, we characterized the effects of 7HQ derivatives (7-[(4-methylene-5-oxo-2-R-2-tetrahydrofuranyl) methoxy]-3,4-dihydrocarbostyril, where R is methyl, phenyl, p-fluorophenyl and p-phenylphenyl; 7HQ-1,-2,-3 and-4, respectively) in murine RAW 264.7 cells, a macrophage-like cell line. Lipopolysaccharide, the active component of endotoxin, significantly induced the expression of inducible nitric oxide synthase and cyclooxygenase-2, leading to the accumulation of nitrite and prostaglandin E(2), respectively. These actions of lipopolysaccharide were inhibited by 7HQ derivatives; additionally, the inhibition of the expression, rather than the activity, of inducible nitric oxide synthase correlated well with that of nitric oxide formation. Western blotting and electrophoretic mobility shift assay results demonstrated that the 7HQ derivatives could effectively inhibit IkappaB-alpha degradation and nuclear factor kappaB (NF-kappaB) translocation. At higher concentrations, 7HQ derivatives also inhibited cyclooxygenase-2 enzyme activity. These results suggest that 7HQ derivatives exhibit inhibitory effects on lipopolysaccharide-induced nitric oxide production and expression of inducible nitric oxide synthase and cyclooxygenase-2 through inhibition of IkappaB-alpha degradation and NF-kappaB activation.


Drug abuse screening with immunoassays: unexpected cross-reactivities and other pitfalls.
Immunoassays are the only practical means of coping with the increasing demand for drug abuse screening because of their simplicity and ease of automation. However, it is essential that the analyst understands the strengths and weaknesses of such assays to enable correct interpretation of results. This is especially important with the increasing popularity of near-patient testing where assays are liable to be carried out by inexperienced and untrained staff. False-positive and false-negative results, unexpected cross-reactivities and other pitfalls are discussed, together with an attempt to explain the reasons for these problems.


Response of four broiler strains to dietary phosphorus above and below the requirement when brooded at two temperatures.
Four strains of broilers (1,200 birds) were fed diets containing .14, .51, and .88% available phosphorus. The birds were raised for 3 wk at two brooding temperatures, 29.4 C and 35 C, with each being reduced 2.8 degrees per week. Feed consumption, feed conversion, body weight, bone weight (tibia), strength and percentage ash, and mortality were measured in order to assess broiler response. An increase or improvement in each measurement was observed from feeding diets containing .51% rather than .14% available phosphorus, but no further increase or improvement was observed in measurements by feeding diets containing .88% rather than .51% available phosphorus. The values for feed consumption, weight gain, and bone weight were significantly lower at the higher temperatures than at the lower temperatures. There were interactions of broiler strain-by-phosphorus with feed consumption, BW gain, and bone weight and strength; also, of temperature-by-phosphorus with bone strength, bone ash, and mortality. These interactions indicate that the bird's response to phosphorus is influenced by strain and environmental temperature.


Reconstitution of the D-glucose transporter of bovine thymocyte plasma membrane: partial purification of transport activity by chromatography on agarose lentil lectin and agarose ethanethiol.
The D-glucose transporter of bovine-thymocyte plasma membrane was partially purified using several procedures in sequence. Dimethylmaleic anhydride extraction removed extrinsic membrane proteins (approximately 50% of the total membrane protein) after which sodium cholate solubilized 40% of the residual protein. Reconstitution of solubilized proteins into phospholipid liposomes indicated a 2.5-fold increase in sugar transport specific activity relative to membrane solubilized without dimethylmaleic anhydride extraction. Detergent removal by gel filtration on G-50 Sephadex resulted in reaggregation of intrinsic membrane proteins. Ultracentrifugation of the reaggregated proteins generated a particulate fraction (pellet 1) which contained about 50% of the total D-glucose transport activity of the preparation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of pellet 1 demonstrated removal of a major band at 68,000 daltons and two minor bands not removed by dimethylmaleic anhydride. The 68,000-dalton protein was not removed by any other method tested. Chromatography of resolubilized pellet 1 on a tandem-bed column of agarose ethanethiol and agarose lentil lectin resulted in a 6-fold increase in transport specific activity of nonabsorbed proteins relative to pellet 1. Approximately 15% of the protein (80-90% of the transport activity) applied to the tandem-bed column was recovered in the nonabsorbed fraction. Sodium dodecyl sulfate-gel electrophoresis of proteins in the nonabsorbed fraction showed apparent enrichment of a diffuse zone at 52,000-45,000 daltons. The overall increase in specific activity of the partially purified preparation was about 12-fold relative to unpurified solubilized proteins.


Impaired muscle regeneration and myoblast differentiation in mice with a muscle-specific KO of IGF-IR.
IGF-I and its receptor IGF-IR are seen as critical effectors of muscle hypertrophy, a notion recently questioned. Using MKR transgenic mice that express a dominant negative IGF-IR only in skeletal muscle, we have examined the role of the IGF-IR signaling in differentiation and repair of muscle fibers after damage-induced muscle regeneration. This process is impaired in MKR muscle, with incomplete regeneration, persistence of infiltrating cells and sustained expression of differentiation markers. Analysis of MKR and WT muscle-derived progenitor stem cells and myoblasts showed twice as many such cells in MKR muscle and an incomplete in vitro differentiation, that is, despite similar levels of myogenin expression, the level of fusion of MKR myoblasts was significantly reduced in comparison to WT myoblasts. These data show IGF-IR signaling is not only required at early hyperplasia stages of muscle differentiation, but also for late stages of myofiber maturation and hypertrophy.


How and when should we monitor chimerism after allogeneic stem cell transplantation?
Chimerism analysis has become an important tool for the peri-transplant surveillance of engraftment. It offers the possibility to realize impending graft rejection and can serve as an indicator for the recurrence of the underlying malignant or nonmalignant disease. Most recently, these investigations have become the basis for treatment intervention, for example, to avoid graft rejection, to maintain engraftment and to treat imminent relapse by pre-emptive immunotherapy. This invited review focuses on the clinical implications of characterization of hematopoietic chimerism in stem cell transplantation.


CT colonography training for radiographers--a formal evaluation.
To evaluate the efficacy of a new intensive "hands-on" course designed to train small teams of radiographers in computed tomography colonography (CTC) technique and initial interpretation for patient triage. The course comprised small-group lectures, active participation in the daily CTC service with practical technique and image interpretation training by experienced radiologists and radiographers. Evaluation was by assessment of knowledge using randomized sets of multiple choice questions (MCQ; pre/post-course), practical technique using checklists and expert global scores, and interpretation performance outcomes using randomized pre/post-course test datasets (five validated CTC examinations each). Paired t-tests were used to investigate change in performance for MCQ score and interpretation accuracy. Thirteen courses with 49 participants were evaluated over 2 years. Practical skills were high, with mean (SD) checklist scores of 14/15 (0.85) and global scores of 26/30 (2.3). MCQ scores increased significantly from a mean of 59% pre-course to 69% post-course, p<0.001. Correct classification of CTC examination improved significantly from a mean of 55% pre-course to 71% post-course, p<0.001. Cancer and large polyp (>10mm) detection rates also improved significantly from 49% to 60%, p=0.002. Structured training in CTC can significantly improve knowledge and interpretation skills of radiographers, while assessing safe procedural performance. Implementation of similar programmes nationally may help reduce performance gaps between centres.