[Successful use of allogeneic stem cell transplantation for treatment-refractory mycosis fungoides].
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.


Lysosomal Proteolysis Is Associated With Exercise-Induced Improvement of Mitochondrial Quality Control in Aged Hippocampus.
Exercise improves cognitive function in older adults, but the underlying mechanism is largely unknown. Both lysosomal degradation and mitochondrial quality control decline with age. We hypothesized that exercise ameliorates age-related cognitive decline through the improvement of mitochondrial quality control in aged hippocampus, and this effect is associated with lysosomal proteolysis. Sixteen to eighteen-month old male Sprague Dawley rats underwent swim exercise training for 10 weeks. The exercise regimen prevented cognitive decline in aged rats, reduced oxidative stress, and rejuvenated mitochondria in the aged hippocampus. Exercise training promoted mitochondrial biogenesis, increased mitochondrial fusion and fission, and activated autophagy/mitophagy in aged hippocampal neurons. Lysosomal inhibitor chloroquine partly blocked beneficial effects of exercise on cognitive function, oxidative stress, autophagy/mitophagy, and mitochondrial quality control in aged rats. These results suggest that preservation of cognitive function by long-term exercise is associated with improvement of mitochondrial quality control in aged hippocampus and that lysosomal degradation is required for this process. Our findings suggest that exercise training or pharmacological regulation of mitochondrial quality control and lysosomal degradation may be effective strategies for slowing down age-related cognitive decline.


Interspecific nuclear-cytoplasmic compatibility controlled by genes on group 1 chromosomes in durum wheat.
Triticum longissimum cytoplasm is incompatible with the T. turgidum nuclear genome. Two nuclear genes, scs and Vi, derived from the nuclear genome of T. timopheevii and by a spontaneous mutation, respectively, restore nuclear-cytoplasmic compatibility, normal plant vigor, and male fertility in these alloplasmic genotypes. The objectives of this study were (i) to determine the chromosomal locations of scs and Vi; (ii) to identify DNA markers for scs and Vi; and (iii) to determine the interactions involving the dosage of scs and Vi. Two populations segregating for scs and Vi were produced and scored for seedling vigor (indicating presence of scs) and degree of self-fertility (indicating presence of Vi). Four RFLP markers were mapped near scs. Aneuploid analysis revealed that these markers, and hence the scs gene, are located on the long arm of chromosome 1A. Four RFLP markers were mapped near Vi on 1BS. Results indicated that other factors may be inhibiting the expression of Vi. We determined the dosage of scs and Vi in both populations with the aid of the linked RFLP markers. Individuals with two versus one dose of scs had reduced self-fertility, while individuals with two versus one dose of Vi had similar self-fertility.


Clinical teaching in physician's assistant training programs.
This is a report on the clinical component of physician's assistant (PA) training programs. Given the significant role physicians played in establishing the new profession, it is not surprising many PA programs are built on the traditional model of medical education, with clinical training occurring after didactic and laboratory-based courses in the basic sciences. It is also not unexpected that programs rely heavily on physicians as clinical instructors. This situation, however, is changing. An increasing number of PA graduates are serving as role models and as instructors in patient care settings. These graduates are also assuming positions of leadership in PA programs. Like their counterparts in medical schools, the PA faculty members surveyed in this project are not adequately prepared for their work as teachers, but they do demonstrate an eagerness to enhance their skills and to continue to upgrade the quality of teaching in their programs. Two areas in which PA faculty would particularly like help are evaluation and faculty development.


[Strategies on perianal abscess and fistula-in-ano: interpretation of the guidelines from USA and German].
The Practice Parameters for the Management of Perianal Abscess and Fistula-in-ano from USA(2011) and German guidelines for anal abscess (2012) are based on the evidence and specialists consensus from colorectal field. Standardization of the anal abscess management may simplify the anal fistula treatment. This review is to concepts from other countries and guide the treatment in China.


Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects.
Many markers of airway inflammation and oxidative stress can be measured non-invasively in exhaled breath condensate (EBC). However, no attempt has been made to directly detect free radicals using electron paramagnetic resonance (EPR) spectroscopy. Condensate was collected in 14 children with cystic fibrosis (CF) and seven healthy subjects. Free radicals were trapped by 5,5-dimethyl-1-pyrroline-N-oxide. EPR spectra were recorded using a Bruker EMX spectrometer. Secondly, to study the source of oxygen centered radical formation, catalase or hydrogen peroxide was added to the condensate. Radicals were detected in 18 out of 21 condensate samples. Analysis of spectra indicated that both oxygen and carbon centered radicals were trapped. Within-subject reproducibility was good in all but one subject. Quantitatively, there was a trend towards higher maximal peak heights of both oxygen and carbon centered radicals in the children with CF. Catalase completely suppressed the signals in condensate. Addition of hydrogen peroxide resulted in increased radical signal intensity. Detection of free radicals in EBC of children with CF and healthy subjects is feasible using EPR spectroscopy.


Optimization of functional nanoparticles formation in associative mixture of water-soluble portion of Farsi gum and beta-lactoglobulin.
Electrostatic interaction between beta-lactoglobulin (β-Lg) and water-soluble fraction of Farsi gum (WSFPG) was studied under the influence of pH, β-Lg:WSFPG mixing ratio (MR) and total concentration (TC) through performing various experiments such as turbidity, particle size and zeta potential measurements. Changes in the relative viscosity during in-situ acidification were studied at various ionic strengths. Lower amounts of absorbance and sedimentation were observed by decreasing the MR. An increase in the TC increased the absorbance of complexed samples. The smallest particle sizes, obtained at a same MR (1:3), were 108 and 188nm at TCs of 0.1 and 0.3wt%, respectively. The decreased relative viscosity upon acidification was a proof for the wrapping phenomenon in the biopolymer mixture. A further decrease in the relative viscosity was observed at higher ionic strength. The results of this study may facilitate the rational design of functional nanoparticles in associative mixtures of β-Lg and WSFPG.


Extragonadal germ cell tumors: Not just a matter of location. A review about clinical, molecular and pathological features.
Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms, which arise in anatomical locations other than gonads. The pathogenesis of these neoplasms is still poorly understood and it is a matter of debate if they really represent extragondal primary neoplasms or rather extragondal metastasis from occult gonadal neoplasms. The actual observations suggest that EGGCTs represent a unique entity, so their biology and behavior are substantially different from gonadal counterparts. The diagnosis of EGGCTs is often challenging, and differential diagnosis is particularly wide. Nevertheless, a correct diagnosis is essential for the correct management of the patient. We summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.


Isotherm-Based Thermodynamic Models for Solute Activities of Organic Acids with Consideration of Partial Dissociation.
Organic acids make up a significant fraction of the organic mass in atmospheric aerosol particles. The calculation of gas-liquid-solid equilibrium partitioning of the organic acid is therefore critical for accurate determination of atmospheric aerosol physicochemical properties and processes such as new particle formation and activation to cloud condensation nuclei. Previously, an adsorption isotherm-based statistical thermodynamic model was developed for capturing solute concentration-activity relationships for multicomponent aqueous solutions over the entire concentration range (Dutcher et al. J. Phys. Chem. C/A 2011, 2012, 2013), with model parameters for energies of adsorption successfully related to dipole-dipole electrostatic forces in solute-solvent and solvent-solvent interactions for both electrolytes and organics (Ohm et al. J. Phys. Chem. A 2015). However, careful attention is needed for weakly dissociating semivolatile organic acids. Dicarboxylic acids, such as malonic acid and glutaric acid are treated here as a mixture of nondissociated organic solute (HA) and dissociated solute (H(+) + A(-)). It was found that the apparent dissociation was greater than that predicted by known dissociation constants alone, emphasizing the effect of dissociation on osmotic and activity coefficient predictions. To avoid additional parametrization from the mixture approach, an expression was used to relate the Debye-Hückel hard-core collision diameter to the adjustable solute-solvent intermolecular distance. An improved reference state treatment for electrolyte-organic aqueous mixtures, such as that observed here with partial dissociation, has also been proposed. This work results in predictive correlations for estimation of organic acid and water activities for which there is little or no activity data.


Production of polyclonal antibodies to Batrachochytrium dendrobatidis and their use in an immunoperoxidase test for chytridiomycosis in amphibians.
Polyclonal antibodies were produced for diagnosing chytridiomycosis in amphibians. Two sheep and 4 rabbits were inoculated with homogenized whole culture of Batrachochytrium dendrobatidis in Freund's complete adjuvant or triple adjuvant. Antisera from all animals reacted strongly with all stages of B. dendrobatidis and stained the walls, cytoplasm, rhizoids and zoospores in an indirect immunoperoxidase test. Significant cross-reactivity occurred only with some fungi in the Chytridiomycota, and there are no members of this phylum besides B. dendrobatidis that infect frogs. The immunoperoxidase stain is a useful screening test when combined with recognition of the morphology and infection site of B. dendrobatidis.


Weekly Cisplatin-Based Concurrent Chemoradiotherapy for Treatment of Locally Advanced Head and Neck Cancer: a Single Institution Study.
The organ preservation approach of choice for the treatment of locally advanced head and neck cancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacious treatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaks and increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy of concurrent chemoradiation using 40 mg/m2 weekly cisplatin. This is a single institutional retrospective study including the data of 266 locally advanced head and neck cancer patients who were treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-value of < 0.05 was taken to be significant statistically for all purposes in the study. The mean age of the study patients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatment time was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors, 3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of the study patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles of weekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional control and disease free survival. Concurrent chemoradiotherapy with moderate dose weekly cisplatin is an efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which can be used in developing countries with limited resources.


Cognitive impairment in patients with rheumatoid arthritis.
Neurological manifestations of Rheumatoid Arthritis (RA) are usually uncommon. However, a number of recent studies have reported that the burden of cognitive impairment in RA could be significant. We sought to explore the prevalence and clinical predictors of cognitive impairment in persons with RA. This is a cross-sectional case-control study with patients with RA. Different trained and blinded interviewers registered clinical-epidemiological data and applied a standardized neurological assessment for each subject of the study. At baseline, functional limitations were characterized using the Health Assessment Questionnaire (HAQ). Cognitive impairment was evaluated with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) while neuropsychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS). Using a proper statistical analysis, we compared the neurological outcomes between case and controls and we determined the clinical predictors of cognitive decline. A total of 210 patients with RA and 70 healthy controls were included in our study. More than two thirds of our patients were classified as cognitively impaired. The mean MMSE and MoCA scores were significantly lower in RA subjects compared to the control group (p < 0.001). Neuropshychiatric impairment was more prevalent in RA patients (59.5%) than in controls (17.1%) as well (p < 0.001). Greater functional limitations were correlated with worse MMSE, MoCA and HADS scores (p < 0.001). The findings of this study suggest that there is evidence of cognitive impairment in adults with RA.


Changes in mucosal and humoral atopic-related markers and immunoglobulins in elite cyclists participating in the Vuelta a España.
Atopic-related factors, humoral and mucosal immunoglobulins (Ig), and cortisol were measured in 17 professional cyclists competing in the 2003 Vuelta a España (a three-week multi-stage race). Venous blood and saliva samples were obtained the morning before the start of the race (T0), on the first rest day after 10 days of racing (T1), and before the start of the last stage after 21 days of racing (T2). Atopic-related factors, IgE, eosinophil cationic protein (ECP), and eosinophils, were significantly altered during the race. Serum IgE (T1: + 10 %) and ECP (salivary, T1: 113 % and serum, T2: 155 %) were significantly increased, while eosinophils (T1: - 32 %, T2: - 55 %) were significantly lower, than pre-race levels. Salivary sIgA secretion rate was significantly decreased at T2 (- 36 %). Pearson product-moment correlations revealed a modest correlation between salivary sIgA and salivary ECP (T1: r = 0.30; T2: r = 0.48; p < 0.01). Serum IgM, total IgG, IgG1, IgG2, IgA levels, at T1 and T2, and cortisol at T2, were significantly lower than pre-race levels. In conclusion, the elevation in IgE and ECP suggests an up-regulation of atopic-related factors in professional cyclists participating in the Vuelta a España. The correlation between salivary sIgA and salivary ECP indicates a role for sIgA in mediating mucosal inflammation. The alterations in Ig levels may indicate Ig isotype switching. An increasing state of hormonal fatigue may have influenced the observed immune alterations.


[Data analysis of the objective observation parameters of benign prostatic hyperplasia patients accepting different treatment regimens].
To observe different objective observation parameters of the benign prostatic hyperplasia (BPH) patients accepting different treatment strategies, and to further analyze the relationship of these factors with the treatment option. Three hundred and twenty-nine BPH patients, aged 50-80, were assigned into 3 groups jointly decided by the physicians and patients based on the individual conditions and the patients' willingness: watchful waiting group (n=61), aged (63 +/- 8), drug treatment group (n=179), aged (68 +/- 7), and operation group (n=89), aged (71 +/- 6). The data of prostate volume, prostate specific antigen (PSA), maximum flow rate (Qmax), average flow rate, urinating volume, and residual urine volume before treatment were recorded. The prostate volume of the watchful waiting group was 33.0 ml, significantly smaller then those of the drug treatment and operation groups (40.1 and 65.5 ml respectively, both P < 0.01); the Qmax of the watchful waiting group was 17.1 ml/s, significantly higher than those of the drug treatment and operation groups (12.4 and 9.1 ml/s respectively, both P < 0.01), and the urinating volume of the watchful waiting group was 332 ml, significantly more than those of the drug treatment and operation groups (247 and 188 ml respectively, both P < 0.01). The serum PSA of the operation group was 5.44 ng/ml, significantly higher than those of the watchful waiting and drug treatment groups (1.53 and 1.99 ng/ml respectively, both P < 0.01); and the residual urine volume of the operation group was 208 ml, significantly higher than those of the watchful waiting and drug treatment groups (21 and 45 ml respectively, both P < 0.01). There were no significant differences in the serum PSA and residual urine volume between the drug treatment and watchful waiting groups. Prostate volume, PSA, Qmax, average flow rate, urinating volume, and residual urine volume are important influential factors influencing the treatment option of BPH. Data analysis of the objective observation parameters will be helpful in clinical decision making.


First in line or first in time? Effects of settlement order and arrival date on reproduction in a group-living beetle Dendroctonus ponderosae.
1. In group-living organisms, individuals that initiate aggregations, termed pioneers, may suffer higher mortality costs than individuals that join established aggregations. Here we examine the hypothesis that aggregation initiators achieve higher reproductive success in the early phases of colonization, potentially through lower competition and increased access to the resource (finder's advantage), and that this benefit is sufficient to outweigh the costs of pioneering. 2. We also examine the role of arrival date (irrespective of order within the aggregation) on reproductive success, because individuals in seasonal environments may gain an advantage by arriving early. We test these hypotheses using mountain pine beetles, Dendroctonus ponderosae (Coleoptera: Curculionidae, Scolytinae), an obligately aggregating insect wherein pioneers suffer high mortality due to tree defences. We measured reproductive success at the start of winter when most components of final offspring number were likely to be determined. 3. Surviving pioneers that successfully recruited conspecifics had smaller broods than individuals that joined aggregations, refuting our hypothesis. The later that a beetle settled within an aggregation, the higher its reproductive success. However, beetles that settled early in the season produced more offspring than those that settled later in the season, and this effect was generally stronger than settlement order within an aggregation. Our study highlights the importance of examining the effects of both settlement order and arrival date on the costs and benefits of pioneering aggregations.


Formation of immature and mature genomic RNA dimers in wild-type and protease-inactive HIV-1: differential roles of the Gag polyprotein, nucleocapsid proteins NCp15, NCp9, NCp7, and the dimerization initiation site.
Formation of immature genomic RNA (gRNA) dimers is exquisitely nucleocapsid (NC)-dependent in protease-inactive (PR-in) HIV-1. This establishes that Pr55gag/Pr160gag-pol has NC-dependent chaperone activity within intact HIV-1. Mutations in the proximal zinc finger and the linker of the NC sequence of Pr55gag/Pr160gag-pol abolish gRNA dimerization in PR-in HIV-1. In wild type, where the NC of Pr55gag is processed into progressively smaller proteins termed NCp15 (NCp7-p1-p6), NCp9 (NCp7-p1) and NCp7, formation of immature dimers is much swifter than in PR-in HIV-1. NCp7 and NCp15 direct this rapid accumulation. NCp9 is sluggish in this process, but it stimulates the transition from immature to mature gRNA dimer as well as NCp7 and much better than NCp15. The amino-terminus, proximal zinc finger, linker, and distal zinc finger of NCp7 contribute to this maturation event in intact HIV-1. The DIS is a dimerization initiation site for all immature gRNA dimers, irrespective of their mechanism of formation.


Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.
This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. Retrospective noncomparative, interventional case series. Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We propose cyclodiode as an effective treatment for many patients in the management of refractory glaucoma after penetrating keratoplasty.


Double reading of current chest CT examinations: Clinical importance of changes to radiology reports.
Misinterpretation of radiological examinations is an important contributing factor to diagnostic errors. Double reading reduces interpretation errors and increases sensitivity. Consultant radiologists in Norwegian hospitals submit 39% of computed tomography (CT) reports for quality assurance by double reading. Our objective was to estimate the proportion of radiology reports that were changed during double reading and to assess the potential clinical impact of these changes. In this retrospective cross-sectional study we acquired preliminary and final reports from 1023 consecutive double read chest CT examinations conducted at five public hospitals. The preliminary and final reports were compared for changes in content. Three experienced pulmonologists independently rated the clinical importance of these changes. The severity of the radiological findings in clinically important changes was classified as increased, unchanged, or decreased. Changes were classified as clinically important in 91 (9%) of 1023 reports. Of these: 3 were critical (demanding immediate action), 15 were major (implying a change in treatment) and 73 were intermediate (affecting subsequent investigations). More clinically important changes were made to urgent examinations and less to female first readers. Chest radiologist made more clinically important changes than other second readers. The severity of the radiological findings was increased in 73 (80%) of the clinically important changes. A 9% rate of clinically important changes made during double reading may justify quality assurance of radiological interpretation. Using expert second readers and targeting a selection of urgent cases prospectively may increase the yield of discrepant cases and reduce harm to patients.


Perinatal factors affecting thyroid hormone status in extreme preterm infants.
Pragmatic criteria are required for defining transient hypothyroxinemia and to permit entry to clinical trials of thyroxine substitution of only those extreme preterm infants who are hypothyroxinemic. The purpose of this article is to suggest that transient hypothyroxinemia is defined by postnatal serum T(4) levels, which are cord levels corrected to an equivalent gestational age had the fetuses remained in utero, and that those levels are adjusted for the significant prenatal and intrapartum factors. Lowered serum FT(4) levels are not a consistent pathognomonic feature of transient hypothyroxinemia as postnatal FT(4) levels in this large series of preterm infants are within or above the cord values of equivalent gestational age, irrespective of severity of illness. Although serum T(3) and thyroid-stimulating hormone levels do not contribute to the diagnosis of transient hypothyroxinemia, measurement of their levels is nevertheless required for trial monitoring involving thyroxine substitution to avoid inadvertent suppression of the developing hypothalamic-pituitary-thyroid axis by excess T(4) substitution.


Structure-activity relationships of 3-O-β-chacotriosyl oleanane-type triterpenoids as potential H5N1 entry inhibitors.
A series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 1 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 1 indicated that the subtle modification of oleanolic acid as an aglycon has key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of OA or alteration of the C-3 configuration of OA from 3β-to 3α-forms can significantly improve the selective index while maintaining their antiviral activities in vitro. Compound 8 was selected for further mechanistic study because of its distinguished inhibition activity and good selective index. Molecular simulation study and surface plasmon resonance analysis confirmed that compound 8 stabilized HA2 subunit of hemagglutinin (HA) by binding with amino acid residues LYS-26, ASN-53, ASN-27 and ASN-50, therefore may prevent HA from conformational rearranging, which is a critical step for viral entry.


Tandem Transformations via Friedel-Crafts Acylation Followed by a Ring-Expansion, Ring-Opening, and Cycloisomerization Sequence.
A tandem synthetic route to a diverse array of cyclic compounds has been developed from Friedel-Crafts acylation of alkynes followed by the microwave irradiation of β-chlorovinyl ketone intermediates. The stereoisomeric β-chlorovinyl ketone intermediates smoothly underwent a thermal α-vinyl enolization and ring expansion to vinyl and carbocyclic furans as well as cyclopetene derivatives in good to excellent yields without the need for any catalysts.


No iconic memory without attention.
The experiments reported extend the findings of our earlier paper, (Mack, Erol, & Clarke, 2015) and allow us to reject Bachmann and Aru's critique of our conclusion (2015) that IM requires attention. They suggested our manipulations, which diverted attention from a letter reporting task in a dual task procedure where the task-cue occurred after the array disappeared, might only have affected access to IM and not the "existence of the phenomenal experience". By further decreasing the probability of reporting letters to only 10% and adding a final trial in which the letter matrix was either completely absent or distorted, we found more than half our subjects were unaware of its absence, or distortion i.e., were inattentionally blind. We take this as powerful evidence against the existence of any phenomenal experience component of iconic memory and consistent with the view that iconic memory demands attention and that conscious perception does as well.


Nail disorders in children.
The spectrum of nail abnormalities that may be seen in the pediatric population is discussed in this article. Developmental abnormalities, both hereditary and congenital, are discussed. Acquired nail abnormalities that may be similar to those seen in adults are also described.


Chromium speciation in river sediment pore water contaminated by tannery effluent.
Cr(VI) is far more soluble and toxic than Cr(III). Sediment pore water was investigated in a river adjacent to the property of a large former tannery, into which Cr-contaminated effluent was discharged over a 55-year period, and where extremely high Cr concentrations have been found in the sediments. Dialysis cells, or peepers, were used to generate depth profiles of Cr concentration in sediment pore water. Samples were analyzed for total Cr using inductively coupled plasma-mass spectrometry (ICP-MS) and for Cr species using high performance liquid chromatography (HPLC)-ICP-MS. The results show an absence of Cr(VI) in all samples. Furthermore, incomplete recovery of Cr(VI) added to the samples collected at the locations with highest sediment Cr concentrations indicate strong reducing conditions at those locations, which are not conducive to the presence of Cr(VI).


The effect of natural and synthetic D-fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinases.
The effect of natural "activation factor" and synthetic fructose-2,6-P2 on the allosteric kinetic properties of liver and muscle phosphofructokinases was investigated. Both synthetic and natural fructose-2,6-P2 show identical effects on the allosteric kinetic properties of both enzymes. Fructose-2,6-P2 counteracts inhibition by ATP and citrate and decreases the Km for fructose-6-P. This fructose ester also acts synergistically with AMP in releasing ATP inhibition. The Km values of liver and muscle phosphofructokinase for fructose-2,6-P2 in the presence of 1.25 mM ATP are 12 milliunits/ml (or 24 nM) and 5 milliunits/ml (or 10 nM), respectively. At near physiological concentrations of ATP (3 mM) and fructose-6-P (0.2 mM), however, the Km values for fructose-2,6-P2 are increased to 12 microM and 0.8 microM for liver and muscle enzymes, respectively. Thus, fructose-2,6-P2 is the most potent activator of the enzyme compared to other known activators such as fructose-1,6-P2. The rates of the reaction catalyzed by the enzymes under the above conditions are nonlinear: the rates decelerate in the absence or in the presence of lower concentrations of fructose-2,6-P2, but the rates become linear in the presence of higher concentrations of fructose-2,6-P2. Fructose-2,6-P2 also protects phosphofructokinase against inactivation by heat. Fructose-2,6-P2, therefore, may be the most important allosteric effector in regulation of phosphofructokinase in liver as well as in other tissues.


Cavernous artery intima-media thickness: a new parameter in the diagnosis of vascular erectile dysfunction.
A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Delta-cavernous calliper]). Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. An increased cavernous IMT (>or=0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.


Programs and policies to assist high school dropouts in the transition to adulthood.
Dan Bloom of MDRC examines policies and programs designed to help high school dropouts improve their educational attainment and labor market outcomes. So called "second-chance" programs, he says, have long provided some combination of education, training, employment, counseling, and social services. But the research record on their effectiveness is fairly thin, he says, and the results are mixed. Bloom describes eleven employment- or education-focused programs serving high school dropouts that have been rigorously evaluated over the past thirty years. Some relied heavily on paid work experience, while others focused more on job training or education. Some programs, especially those that offered paid work opportunities, generated significant increases in employment or earnings in the short term, but none of the studies that followed participants for more than a couple of years found lasting improvements in economic outcomes. Nevertheless, the findings provide an important foundation on which to build. Because of the high individual and social costs of ignoring high school dropouts, the argument for investing more public funds in services, systems, and research for these young people is strong. The paucity of conclusive evidence, however, makes it hard to know how to direct resources and magnifies the importance of ensuring that all new initiatives provide for rigorous evaluation of their impacts. Bloom concludes with recommendations for policy and research aimed at building on current efforts to expand and improve effective programs for dropouts while simultaneously developing and testing new approaches that might be more effective and strengthening local systems to support vulnerable young people. He stresses the importance of identifying and disseminating strategies to engage young people who are more seriously disconnected and unlikely to join programs. A recurring theme is that providing young people with opportunities for paid work may be useful both as an engagement tool and as a strategy for improving long-term labor market outcomes.


Vasculitis-like Syndromes.
Vasculitis often presents a diagnostic challenge as the disease processes may have varied presentations. This article reviews some vasculitis-like "mimics," particularly emphasizing viral and bacterial infections, drug-related disorders, various malignancies, and other autoimmune disorders, all of which may have a similar clinical presentation. This article also highlights recent advances and the importance of accurate diagnosis and therapy.


State of provincial regulations and guidelines to promote low impact development (LID) alternatives across Canada: Content analysis and comparative assessment.
The use of Low Impact Development (LID) alternatives requires the establishment of appropriate regulations and guidelines on acceptable practices and developing consensus among stakeholders, thus assuring the rights of all water-users and for conflict resolution. This content analysis aims to examine whether stormwater regulations and guidelines have addressed the use of LID alternatives in urban settings and compares the current state of regulations in the context of Canadian provinces and territories., A list of eight core criteria relevant to the implementation of LID has been identified and an ordinal scale ranging from 1 to 6 is proposed to track the progress towards LID-friendly regulations in each province. Furthermore, based on comparative assessment, Canadian provinces are categorized into three groups: 'highly, moderately, and slightly LID-friendly' to project a broad view of the current state of regulations required to promote LID alternatives. . Results show that LID has become the mainstream technology for stormwater management in Alberta, British Columbia, Ontario, and Quebec, which are categorized as 'highly LID-friendly' provinces. The provinces where LID alternatives have gained considerable acceptance are categorized as 'moderately LID-friendly', which include Manitoba, Newfoundland and Labrador, Nova Scotia, Prince Edward Island, and Saskatchewan. Lastly, the province of New Brunswick is categorized as 'slightly LID-friendly', because of very limited use of LID alternatives in the stormwater management regulations. These findings of this content analysis can be of significant value to strengthen provincial/territorial regulations and extend the benefits of LID in stormwater quality management and sustainable water management.


Vitamin D receptors in breast cancer cells.
1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.


Estimation-identification problem for diffusive transport in porous materials based on single reservoir test: results for silica hydrogel.
In this paper the problems of selection of an appropriate model of diffusive transport in silica hydrogel and estimation of model parameters are considered. The analytical solutions and simulations of diffusive transport in a single reservoir test with equilibrium model of sorption are developed. The mathematical models refer to transport of solute from a porous material to water or in reverse direction assuming arbitrary initial concentrations and Dirichlet or mixed type of boundary conditions. In order to quantify the relative importance of the model parameters, logarithmic sensitivity analysis of solute concentration with respect to estimated parameters describing diffusion, sorption, and interfacial effects is performed. The application of the discussed models for estimation of transport parameters is discussed using experimental results for diffusion of sodium chloride in silica hydrogel.


Targeting Histone Acetylation: Readers and Writers in Leukemia and Cancer.
Chromatin packaging of DNA provides a framework for transcriptional regulation. Modifications to DNA and histone proteins in nucleosomes lead to conformational changes, alterations in the recruitment of transcriptional complexes, and ultimately modulation of gene expression. We provide a focused review of control mechanisms that help modulate the activation and deactivation of gene transcription specifically through histone acetylation writers and readers in cancer. The chemistry of these modifications is subject to clinically actionable targeting, including state-of-the-art strategies to inhibit basic oncogenic mechanisms related to histone acetylation. Although discussed in the context of acute leukemia, the concepts of acetylation writers and readers are not cell-type-specific and are generalizable to other cancers. We review the challenges and resistance mechanisms encountered to date in the development of such therapeutics and postulate how such challenges may be overcome. Because these fundamental cellular mechanisms are dysregulated in cancer biology, continued research and in-depth understanding of histone acetylation reading and writing are desired to further define optimal therapeutic strategies to affect gene activity to target cancer effectively.


Rapid diagnosis and discrimination of bacterial meningitis in children using gram probe real-time polymerase chain reaction.
In this study, we developed a method of simultaneous detection and discrimination of bacteria in cerebrospinal fluid (CSF) with gram probe real-time polymerase chain reaction (PCR). Our results showed 25 clinical strains representing 13 gram-positive and 12 gram-negative bacterial species. They were identified correctly with the corresponding gram probe. The standard curve showed that the amplification efficiency of templates with different concentrations of bacteria was almost the same with a potential detection limit of 10 colony-forming units/mL. A total of 482 children who were clinically suspected of bacterial meningitis were included in this study. A total of 1.0 mL of CSF was collected from every child and was subjected to gram probe-based PCR (GP-PCR), CSF culture, and CSF routine analysis. The positive rate of the GP-PCR array was (32/482, 6.64%) significantly higher than that of CSF culture (23/482, 4.77%). GP-PCR was proved to be an excellent technique for rapid and accurate diagnosis and discrimination of bacterial meningitis, and hence its use as a diagnostic tool in future seems very promising.


Rehabilitation nursing: the state of the art.
Little has appeared in South African Nursing literature on rehabilitation and the role of the nurse in the rehabilitative process. This article sets out to convey some of the developments which have occurred in this discipline as it has become established as a specialist area of practice. Against this background the role of the nurse in rehabilitation has been identified. Recommendations have been made regarding the development of this specialisation in the South African health care setting.


A 17-Month Review of the Care Model, Service Structure, and Design of THRIVE, a Community Mental Health Initiative in Northern Singapore.
Effective delivery of psychiatric care requires the development of a range of services. The existing Singapore health care system provides a comprehensive range of psychiatric services based in restructured hospitals. The Ministry of Health Community Mental Health Masterplan (2012-2017) aims to build novel services for the community. This Masterplan envisions the development of ASCATs (Assessment Shared Care Teams) and COMITs (Community Intervention Teams) to build the capacity and capability for psychiatric care to be delivered outside the hospital in the community. A community mental health plan comprising a fast access clinic, internet-delivered self-help and building a community network of providers was devised for the North of Singapore through the THRIVE (Total Health Rich In Vitality and Energy) programme. This article provides an introduction to the care model, service structure and design of the THRIVE, and reviews its milestones and achievements from its inception in August 2012 until December 2013.


Development of hypertension in adolescents with pre-hypertension.
To evaluate the risk for developing incident hypertension (HTN) in adolescents with pre-hypertension. A secondary analysis of students participating in multiple school-based blood pressure (BP) screens from 2000 to 2007 was completed. At each screen, height, weight, and 2 to 4 BPs were measured on as many as 3 occasions when BP remained ≥ 95th percentile. Students with confirmed HTN at their initial screen were excluded, and incident HTN was defined as having a BP ≥ 95th percentile at all 3 visits of a later screen. Incidence rates (IR) and hazard ratios (HR) were calculated by using Cox Proportional models. Of 1006 students, HTN developed in 11 (IR 0.5%/year) in a mean of 2.1 years of observation. IRs were higher in "at-risk" students (pre-hypertensive or hypertensive with follow-up BP <95th percentile), 1.4%/year (HR, 4.89; 1.48-16.19) and students with a BP ≥ 90th percentile at 3 baseline visits, 6.6%/year HR 24.33 (5.68-104.29)]. Although not significant, students with pre-hypertension by the 2004 Task Force definition also had an increased IR of 1.1%/year (HR, 2.98; 0.77-11.56)]. Elevated BP increases the risk for the development of HTN during adolescence. Effective strategies for preventing HTN in at-risk adolescents are needed.


Terazosin in benign prostatic hyperplasia: effects on blood pressure in normotensive and hypertensive men.
To determine the effects of terazosin on blood pressure and on antihypertensive therapy when used in managing benign prostatic hyperplasia (BPH). Safety data from a large, multinational study were analysed retrospectively. Normotensive and hypertensive patients received escalating dosages of terazosin for 10 weeks and were maintained on 5 or 10 mg daily doses for 16 weeks (single-blind period). After the initial treatment period, only men having sufficient improvements in International Prostate Symptom Score (> or = 30%) and in peak flow rate (> or = 10%) were randomly assigned to continue terazosin or to receive placebo for 24 weeks (double-blind period). In hypertensive patients, terazosin reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the single-blind period; these clinically significant reductions were maintained in patients receiving terazosin during the double-blind period. However, in normotensive and controlled hypertensive patients terazosin produced no clinically significant mean changes in SBP or DBP during either study period. Terazosin did not adversely affect patients receiving concomitant antihypertensive medication. Terazosin is a safe treatment for BPH in normotensive and hypertensive men, including men who are already taking additional antihypertensive drugs.


Management of the pregnant, insulin-dependent diabetic woman.
An intensive care program was offered to all insulin-dependent, pregnant diabetic women who presented to The New York Hospital Obstetrical Clinic in their eighth week or less of gestation. The patients were hospitalized for 1 wk to normalize their blood glucose and to teach the technique of self-monitored glucose determination, diet and exchange lists, and the method to titrate insulin according to the blood glucose determination. The mean blood glucose for the first 10 patients accepted to the program was 169 mg/dl at the start of the program with a mean hemoglobin A1c of 9.4% for the group (normal < 5.5%) and glucosuria up to 50 g/24 h. After discharge, mean glucose was 91 mg/dl, and urinary glucose excretion was 1.4 g/24 h. HbA1c fell into the normal range 5 wk after normoglycemia was achieved (3.4%) (nl < 5.5%). Normoglycemia was maintained as outpatients until 3 wk before delivery when the patients were readmitted for tests of fetal well-being. Mean weight gain for the mothers was 12.2 kg. Mean glucose at delivery was 87 mg/dl and HbA1c was 3%. Hormonal profiles (hCG, hPRL, estrogens, progesterone, hPL) normalized after normoglycemia was achieved and remained normal until delivery. Mean gestational age at time of delivery was 38.8 wk with a mean infant birth weight of 2988 g. No infant manifested hypoglycemia, hypocalcemia, erythremia, or respiratory disease. The use of self-monitored blood glucose allows for optimal care of the insulin-dependent, pregnant diabetic woman while she remains at home with her family.


Novel insights into the role of hypoxia‑inducible factor‑1 in the pathogenesis of human post‑intubation tracheal stenosis.
Hypoxia is an important mechanism involved in dermal scar formation. Post-intubation tracheal stenosis (PTS) has similar pathological characteristics and formation mechanisms to skin hypertrophic scars. Hypoxia-inducible factor‑1α (HIF‑1α) is a nuclear transcription factor that facilitates the adaptation of human cells to compromised oxygen tension under hypoxic conditions. The aim of this study was to investigate whether hypoxia and HIF-1α were involved in PTS. In the first part of our study, we observed the effects of tracheal mucosal pressure exerted by the endotracheal tube cuff and duration of intubation on tracheal stenosis using prospective methods. In the second part of our study, 24 patients were divided into three groups, according to the characteristics observed using bronchoscopy: granulation phase group, proliferative phase group and mature phase group. Tissues showing dysplasia were obtained using bronchoscopy forceps, and western blotting was performed to detect the protein expression of HIF-1α and its target genes, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β. In experiment one, we observed that the tracheal mucosal pressure exerted by the endotracheal tube cuff in the PTS group was significantly higher compared with that in the group without PTS, and the duration of intubation was longer compared with that in the group without PTS (P<0.05). In experiment two, we observed that the expression of HIF-1α was highest in the granulation phase, showed a decrease in the proliferative phase and in the mature phase was significantly reduced compared with the other two phases. The results were similar for VEGF and bFGF. TGF‑β protein expression was highest in the proliferative phase, significantly reduced in the mature phase and the same trends were observed for collagen type Ⅰ and III, and α-smooth muscle actin. HIF-1α is involved in the pathogenesis of PTS and may be a potential key regulator in the initiation and facilitation of this process.


Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes.
A directing-group-free palladium-catalyzed direct arylation of simple polyfluoroarenes with arylboronic acids through selective C-F bond activation is described. The combination of Pd(OAc)2 with BrettPhos was identified as an efficient catalytic system to promote the reaction with high regioselectivity and broad substrate scope. Preliminary mechanistic studies reveal that the oxidative addition of Pd to the C-F bond is involved in the catalytic cycle.


Adrenomedullin promotes lung angiogenesis, alveolar development, and repair.
Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and alveolar development. Accordingly, we report that lung mRNA expression of AM increases during normal alveolar development. In vivo, intranasal administration of the AM antagonist, AM22-52 decreases lung capillary density (12.4 +/- 1.5 versus 18 +/- 1.5 in control animals; P < 0.05) and impairs alveolar development (mean linear intercept, 52.3 +/- 1.5 versus 43.8 +/- 1.8 [P < 0.05] and septal counts 62.0 +/- 2.7 versus 90.4 +/- 3.5 [P < 0.05]) in neonatal rats, resulting in larger and fewer alveoli, reminiscent of BPD. This was associated with decreased lung endothelial nitric oxide synthase and vascular endothelial growth factor-A mRNA expression. In experimental oxygen-induced BPD, a model of arrested lung vascular and alveolar growth, AM attenuates arrested lung angiogenesis (vessel density, 6.9 +/- 1.1 versus 16.2 +/- 1.3, P < 0.05) and alveolar development (mean linear intercept, 51.9 +/- 3.2 versus 44.4 +/- 0.7, septal counts 47.6 +/- 3.4 versus 67.7 +/- 4.0, P < 0.05), an effect in part mediated by inhibition of apoptosis. AM also prevents pulmonary hypertension in this model, as assessed by decreased right ventricular hypertrophy and pulmonary artery medial wall thickness. Our findings suggest a role for AM during normal alveolar development. AM may have therapeutic potential in diseases associated with alveolar injury.


[Mechanism of granulocyte colony-stimulating factor for promoting cell viability of bone marrow mesenchymal stem cells.].
The present study was aimed to investigate the mechanism of the granulocyte colony-stimulating factor (G-CSF) on the viability of the bone marrow mesenchymal stem cells (MSCs). MSCs were cultured by classical whole bone marrow adhering method, and the MSCs were analyzed for the cell surface differentiation markers CD34, CD133, CD90 and CD105 by flow cytometry (FCM). The ability of the MSCs to differentiate into osteocytes and adipocytes was tested in osteogenic and adipogenic mediums, separately. The effect of G-CSF (20 mug/mL) on the passage 3 MSCs viability was evaluated by MTT method, and the molecular mechanism of the G-CSF mediated effects was assayed through the pretreatment of the signal pathway inhibitors including 50 nmol/L wortmannin (phosphatidylinoesitol 3 kinase inhibitor), 50 mumol/L PD98059 [extracellular signal-regulated-kinase1/2 (ERK1/2) inhibitor], 30 mumol/L SB203580 (p38 mitogen-activated protein kinase inhibitor), 10 mumol/L H89 (protein kinase A inhibitor), 20 mumol/L Y27632 (Rho kinase inhibitor), 1 mumol/L rapamycin [mammalian target of rapamycin (mTOR) inhibitor], 10 mmol/L straurosporine [protein kinase C (PKC) inhibitor], 6 nmol/L G0697 (PKCalpha inhibitor) and 50 mumol/L Pseudo Z (PKCzeta inhibitor). Cultured passage 3 MSCs expressed CD90 and CD105 strongly, and showed the ability of multi-differentiation into osteocytes and adipocytes. G-CSF promoted the viability of MSCs, and the promotion was completely inhibited by PKC inhibitor straurosporine and partially inhibited by wortmannin, rapamycin, PD98059, SB203580 or G0697. However, its effect was not inhibited by H89, Y27632 and Pseudo Z. It is thus suggested that the promoting effect of G-CSF on MSCs viability was closely related to AKT-mTOR-PKC signal pathway, and PKC maybe the central role in the signal pathway.


Quantitative imaging of basic functions in renal (patho)physiology.
Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased approximately 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times ( approximately 45 s) to glomerular filtration, with a delay of approximately 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.


Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation.
Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases, some of which are proven to be associated with aggressive clinical behavior such as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is recently described as a rare and aggressive variant of PTC. Herein, we are reporting a case of HVPTC in a patient who presented with hemoptysis and an intratracheal blood clot that was aspirated and submitted for cytopathological examination. Cytomorphology displayed neoplastic cells with profound micropapillary architecture, elongated nuclei, and prominent hobnail configuration. Nuclear features of PTC such as pseudoinclusions, nuclear overlapping, crowding, and grooves were readily identified. Subsequent total thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC is a rare locally aggressive subtype, which may present with metastasis from an occult thyroid primary. HVPTC needs to be included in the differential diagnosis of metastatic carcinoma with micropapillary architecture on fine needle aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754-756. © 2017 Wiley Periodicals, Inc.


Bow, range, and sequential effects in absolute identification: a response-time analysis.
Accuracy and response time (RT) measures were obtained in the absolute identification of line length. Different groups of subjects performed the task under different experimental conditions where range and relative spacing were the main independent variables. For comparison purposes, another group of subjects performed a digit-identification task. Results were analyzed for bow, range, and sequential effects using both accuracy and RT data. A preliminary analysis of RT distributions was also performed. Several phenomena previously documented using accuracy are reproduced, while new observations are reported for RT. The results show a dissociation between RT and accuracy in that the experimental manipulations sometimes affected accuracy but not necessarily RT.


Susceptibility of helicobacter pylori to metronidazole and its bioactive derivatives.
The hydroxy derivative of metronidazole can exhibit equal or greater activity to the parent drug against several bacteria. The susceptibility status of 22 H. pylori strains to these breakdown compounds was determined in order to determine their possible role in the therapy of H. pylori associated peptic ulcer disease. The susceptibility was determined using the agar dilution method and substantial activity (MIC90 = 0.33 .tg/ml) for the hydroxy metabolite of metronidazole versus H. pylori was observed. The findings define a role for the hydroxy derivative of metronidazole in peptic ulcer disease and support the limited data on the possibility of cooperative interactions between the parent compound, its main derivatives and related companion drugs in this condition.


Peroxide-metabolizing systems of the crystalline lens.
The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.


Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in multiple sclerosis.
Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population.


Effects of trolox, locally applied on round windows, on cisplatin-induced ototoxicity in guinea pigs.
Cisplatin (CDDP), an antitumor agent widely used in the treatment of pediatric solid tumors, has dose-limiting side effects such as ototoxicity and nephrotoxicity. Recently, evidence has been accumulated to demonstrate that these side effects are closely related to oxidative stress. In the present study, we attempted to suppress CDDP-induced ototoxicity in guinea pigs by administering trolox, a water-soluble analogue of alpha-tocopherol which is a natural lipid-soluble antioxidant, locally on round windows. Hartley albino guinea pigs (250-300 g) were treated with CDDP (0.3 mg/ml) in the presence or absence of a combined treatment of trolox (5 mM). Both drugs were administered locally on round windows. The combined treatment of trolox distinctly improved the ototoxic side effects induced by CDDP. These were: elevation of auditory brain stem response threshold at 4, 8 and 16 kHz and substantial losses of outer hair cells with the base-to-apex gradient. Trolox, locally applied on round windows, showed a suppression on CDDP-ototoxicity. The results obtained in the present study suggest that a local application of trolox in the tympanic cavity can be a promising candidate to prevent the CDDP-ototoxicity in the future.


Arteriovenous malformation of the spinal cord and cauda equina fed by branches of the internal iliac artery and associated with vertebral hemangiomas.
A rare case of an arteriovenous malformation (AVM) of the spinal cord is presented. The patient was a 35-year-old man who experienced progressive paraparesis and rectovesical disturbances. In this patient a spinal AVM was fed by branches of the left internal iliac artery and was associated with a sacral hemangioma. An additional hemangioma of the third lumbar vertebral body was also found. On reviewing the literature, only 4 cases, including ours, of spinal AVM with feeding vessels originating from the internal iliac artery were found. One of these patients had an associated vertebral hemangioma.


Formation of methylurea from methylamine and carbamyl phosphate: a possible environmental hazard.
Methylurea, a precursor of carcinogenic nitroso compound, was formed by incubating methylamine and carbamyl phosphate in neutral buffer. The formation was checked on a radiochromatogram, as well as by color reaction. The presence of methylamine and carbamyl phosphate in preserved, fermented foods provided a suitable condition for the formation of methylurea.


Presence of the fire ant Solenopsis invicta (Westwood) (Hymenoptera: Formicidae) stimulates burrowing behavior by larvae of the sandfly Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae).
The sandfly Lutzomyia longipalpis (Lutz & Neiva) vectors leishmaniasis in the neotropics. Although much is known about the biology of adult flies, little is known about interactions with its natural enemies. Here, we examined behavior of larvae of L4 L.longipalpis on a soil substrate when exposed to the fire ant Solenopsis invicata (Westwood). When ants were absent, most larvae tended to remain at or close to the soil surface, but when ants were present the larvae burrowed into the soil. Sandflies seek refuges in the presence of generalist predators, thus rendering them immune to attack from many potential enemies.


GPs' perceptions of the gender-related barriers to discussing sexual health in consultations--a qualitative study.
This paper explores the barriers related to gender that general practitioners (GPs) face when discussing sexual health matters in primary care consultations. Qualitative study. In-depth interviews were conducted with 22 GPs recruited from different practice types and locations across Sheffield, UK. Transcripts were analysed thematically, assisted by NUD*IST qualitative data analysis programme. GPs were virtually unanimous in believing that patients preferred to see same-sex GPs regarding sexual health, and some felt that as a consequence they became "de-skilled" in dealing with sexual matters of opposite sex patients. Discussion of sexual issues was also perceived to be hindered if the patient was male; for women, reproductive health issues provided an appropriate context to asking about sexual health. Barriers that prevent discussion of sexual matters in consultations can not only impinge upon potential treatment for the patient, but also have an indirect affect on the patient's life, health and intimate relationships. Solutions to overcoming such barriers relate largely to the provision of training for medical students and qualified GPs.


Community care: costs and benefits for a chronic patient.
The authors analyzed the costs and benefits of community care for a middle-aged chronic woman patient who was receiving care from a neighborhood health center after a total of eight years of hospitalization. Cost comparisons over a three-year period were made between the neighborhood center and a state hospital, the center and a day program of a community mental health center, and the center and the inpatient unit of a community mental health center. Cost of care in the neighborhood center fell from $2110 in the first year to $640 in the third, while costs in the alternative settings increased substantially. The patient's clinical status was rated "much improved" in the community.


Metastatic liver tumour segmentation from discriminant Grassmannian manifolds.
The early detection, diagnosis and monitoring of liver cancer progression can be achieved with the precise delineation of metastatic tumours. However, accurate automated segmentation remains challenging due to the presence of noise, inhomogeneity and the high appearance variability of malignant tissue. In this paper, we propose an unsupervised metastatic liver tumour segmentation framework using a machine learning approach based on discriminant Grassmannian manifolds which learns the appearance of tumours with respect to normal tissue. First, the framework learns within-class and between-class similarity distributions from a training set of images to discover the optimal manifold discrimination between normal and pathological tissue in the liver. Second, a conditional optimisation scheme computes non-local pairwise as well as pattern-based clique potentials from the manifold subspace to recognise regions with similar labelings and to incorporate global consistency in the segmentation process. The proposed framework was validated on a clinical database of 43 CT images from patients with metastatic liver cancer. Compared to state-of-the-art methods, our method achieves a better performance on two separate datasets of metastatic liver tumours from different clinical sites, yielding an overall mean Dice similarity coefficient of [Formula: see text] in over 50 tumours with an average volume of 27.3 mm(3).


Subsocial behaviour and brood adoption in mixed-species colonies of two theridiid spiders.
Cooperation and group living often evolves through kin selection. However, associations between unrelated organisms, such as different species, can evolve if both parties benefit from the interaction. Group living is rare in spiders, but occurs in cooperative, permanently social spiders, as well as in territorial, colonial spiders. Mixed species spider colonies, involving closely related species, have rarely been documented. We examined social interactions in newly discovered mixed-species colonies of theridiid spiders on Bali, Indonesia. Our aim was to test the degree of intra- and interspecific tolerance, aggression and cooperation through behavioural experiments and examine the potential for adoption of foreign brood. Morphological and genetic analyses confirmed that colonies consisted of two related species Chikunia nigra (O.P. Cambridge, 1880) new combination (previously Chrysso nigra) and a yet undescribed Chikunia sp. Females defended territories and did not engage in cooperative prey capture, but interestingly, both species seemed to provide extended maternal care of young and indiscriminate care for foreign brood. Future studies may reveal whether these species adopt only intra-specific young, or also inter-specifically. We classify both Chikunia species subsocial and intra- and interspecifically colonial, and discuss the evolutionary significance of a system where one or both species may potentially benefit from mutual tolerance and brood adoption.


Pathophysiology of cyanoginosin-LR: in vivo and in vitro studies.
Cyanoginosin-LR, one of the group of virulent cyclic heptapeptide toxins (cyanoginosins) isolated from some strains of the cyanobacterium, Microcystis aeruginosa, kills mice within 1-2 hr after iv or ip injection. Although the liver is a target organ of the toxin, the rapidity of lethality is incompatible with metabolic death from failure of hepatocellular function. However, disintegration of sinusoidal endothelium causes massive intrahepatic hemorrhage. The loss of the structural integrity of hepatic sinusoids provides a previously undescribed mechanism for embolization of disintegrating cells from the liver to the lung. No injury to either cultured bovine pulmonary artery endothelial cells or mouse peritoneal macrophages was observed following prolonged incubation with high concentrations of the toxin, and there was no increase in vascular permeability to 125I-labeled albumin detected before intrahepatic hemorrhage. However, plasma fibronectin increased transiently after toxin injection. Acute, severe thrombocytopenia, a characteristic of cyanoginosin-LR toxicity, remains unexplained since platelets did not concentrate in the lungs, liver, or spleen. There are similarities between the effects of cyanoginosin-LR and of the lipopolysaccharide endotoxins, such as elevations of plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha.


p53 phosphorylation and association with murine double minute 2, c-Jun NH2-terminal kinase, p14ARF, and p300/CBP during the cell cycle and after exposure to ultraviolet irradiation.
p53 phosphorylation and association with proteins is implicated in its stability and activity. We have compared the association of DNA-bound and overall pools of p53 with murine double minute 2 (Mdm2), c-Jun NH2-terminal kinase (JNK), p300/CBP, and p14ARF during cell cycle progression. Whereas DNA-bound p53 associates with JNK at G0-G1 and with Mdm2 and p300 during S and G2-M phases, the general pool of p53 was found in complex with JNK and Mdm2 almost throughout the cell cycle. Phosphorylation of p53 at serines 9, 15, and 20 is at the highest levels at G1 and at serines 37 and 392 during G2-M phase. Whereas a high dose of UV irradiation was required for phosphorylation of serines 15 and 392 between 8 and 24 h after treatment, a low dose caused immediate phosphorylation on serines 9, 20, and 372. These dynamic changes in the phosphorylation of p53 are expected to play a pivotal role in p53 association, stability, and function.


A classification of developmental activities of academic family medicine supported by federal grants.
Substantial funds have been awarded to academic departments of family medicine through the federal Establishment of Departments of Family Medicine grants program, initiated in 1980 under the Public Health Service Act. In 1989 the authors analyzed the successful grant applications in a sample of 61 institutions variously funded or re-funded for the grant cycles from 1980 through 1986 in order to classify the supported developmental activities. Three dimensions for explicating this activity emerged: (1) the functional area of the activity (e.g., curricular development); (2) the objectives of the activity (e.g., improving relevance of instruction); and (3) the strategies to be used to attain the objectives (e.g., addition of specialized faculty). This classification scheme provides a tentative but useful framework for characterizing departmental development.


Morbidity after flap reconstruction of hypopharyngeal defects.
Laryngopharyngeal reconstruction continues to challenge in terms of operative morbidity and optimal functional results. The primary aim of this study is to determine whether complications can be predicted on the basis of reconstruction in patients undergoing pharyngectomy for tumors involving the hypopharynx. In addition, we detail a reconstructive algorithm for management of partial and total laryngopharyngectomy defects. A retrospective review was performed of 153 patients undergoing flap reconstruction for 85 partial and 68 circumferential pharyngectomies at a single institution over a 10-year period. There were 118 males and 35 females, the median age was 62 years, and mean follow up was 3.1 years. Pharyngectomy was performed for recurrence after radiotherapy in 80 patients and as primary surgery in 73. Free flap reconstruction was used in 42%, with 30 jejunal, 15 radial forearm, 11 anterolateral thigh, five rectus abdominis, and three gastro-omental flaps. Gastric transposition and pectoralis major pedicle flap was used in 14% and 44% of patients, respectively. Morbidity was analyzed according to extent of defect, regional versus free flap, enteric versus fasciocutaneous free flap reconstruction, and the effect of laparotomy. The total operative morbidity and mortality rate was 71% and 3%, respectively. The most common complications were hypocalcemia in 45%, pharyngocutaneous fistula in 33%, and wound complications in 25%. The late complication and stricture rate was 26% and 15%, respectively. On univariate analysis, circumferential defects were associated with increased total (P=.046) and flap-related morbidity (P=.037), hypocalcemia (P<.001), late complications (P=.003), and stricture (P=.009). Gastric transposition had increased total (P=.007), flap-related (P=.035), late complications (P=.034), and hypocalcemia (P=.001). Pharyngocutaneous fistula was increased in patients undergoing salvage pharyngectomy for radiation failure (P=.048) compared with primary surgery. On multivariate analysis, gastric transposition independently predicted for wound complications (P=.014) and fistula (P=.012). Circumferential defects predicted for flap-related morbidity (P=.030), hypocalcemia (P=.017), and late complications (P=.042). Tracheoesophageal speech was the method of voice restoration in 44% of patients. Oral diet was achieved in 93% of patients; however, 16% required gastrostomy tube feeds for either total or supplemental nutrition. The operative morbidity associated with pharyngeal reconstruction is substantial in terms of early and late complications. We were able to predict morbidity by defect extent and reconstruction type and initial treatment modality. Swallowing function is acceptable; however, less than half of the patients undergoing pharyngectomy had tracheoesophageal puncture voice restoration.


Benzimidazole derivatives endowed with potent antileishmanial activity.
Two sets of benzimidazole derivatives were synthesised and tested in vitro for activity against promastigotes of Leishmania tropica and L. infantum. Most of the tested compounds resulted active against both Leishmania species, with IC50 values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound 8 resulted about 100-/200-fold more potent than miltefosine, even if the selectivity index (SI) versus HMEC-1 cells was only moderately improved. In the set of 2-benzyl and 2-phenyl benzimidazoles, bearing a basic side chain in position 1, compound 28 (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds 8 and 28 represent interesting hit compounds, susceptible of structural modification to improve their safety profiles.


[Isolation and degradation characteristics of dichloromethane-degradation bacterial strain by Methylobacterium rhodesianum H13].
A dichloromethane-degrading bacterium Methylobacterium rhodesianum H13 which utilized the DCM as the sole carbon and energy source was isolated. According to the research, M. rhodesianum H13 could completely degrade 5 mmol x L(-1) DCM in 23 h with the initial cell concentration of 0.82 mg x L(-1), pH 7.0, 30 degrees C, and the cell yield rate was about 0.136 g x g(-1) DCM. With the degradation of DCM, Cl- concentration gradually raised (the release of Cl- concentration was about 2 times higher as the DCM), pH value dropped to 6.75, and the solution was weakly acidic. Temperature, pH, DCM concentration, Cl- concentration and other factors were investigated through the shake flask experiments, and the optimal conditions for DCM degradation were: temperature 30 degrees C, pH 7.0. The study also indicated that 5 mmol x L(-1) of DCM was the optimum concentration for M. rhodesianum H13 and high levels of DCM could inhibit the degradation. The research has an important application value for the DCM environmental pollution.


Integrative graph regularized matrix factorization for drug-pathway associations analysis.
Pathway-based drug discovery can give full consideration to the efficacy of compounds in the systemic physiological environment. The recently emerged drug-pathway association identification approaches gain popularity due to its potential to decipher the mechanism of action and the targets of compounds. In this study, we propose a novel drug-pathway association identification method: Integrative Graph regularized Matrix Factorization (IGMF). It employs graph regularization to encode data geometrical information and prevent possible overfitting in prediction. Furthermore, it achieves parts-based and sparse data representation by imposing L1-norm regularization on the objective function. Empirical studies demonstrate that IGMF has strong advantages in identifying more new drug-pathway associations compared to its peer methods. It further shows a good capability to unveil the intrinsic structures of data. As an effective drug-pathway discovery method, it will inspire new analytics methods in this subfield.


Oral side effects of isotretinoin chronic intake.
Isotretinoin (13-cis-retinoic acid) is a retinoid that has been used for the past 20 years to treat a variety of dermatologic conditions. It is beneficial in many skin conditions, although its side effects and toxicity require careful monitoring by physicians and other health professionals, among them, dentists, who should be prepared to manage an adverse occurrence. In this paper, the oral side effects of isotretinoin are described; and some of them are illustrated.


Pulmonary embolism: surgery in a hyperbaric chamber.
A 20-year-old man with a known history of thrombophlebitis experienced massive pulmonary embolism with hypoxia and shock. Embolectomy was performed with hyperbaric oxygenation for cardiopulmonary support. Ligation of the inferior vena cava was required postoperatively to prevent further embolism. Hyperbaric oxygenation is an effective method of cardiopulmonary support for pulmonary embolectomy.


Synthesis in Escherichia coli and immunological characterization of a polypeptide containing the cleavage sites associated with trypsin enhancement of rotavirus SA11 infectivity.
About 45% of the rotavirus SA11 VP3 gene was inserted into a thermoinducible expression plasmid under the control of phage lambda PL promoter. The primary translation product predicted on the basis of the plasmid construction was a hybrid protein in which the 98 amino-terminal amino acids of phage MS2 polymerase were followed by amino acids 42 to 387 of the VP3 protein, which included the region containing the cleavage sites associated with trypsin enhancement of infectivity. On induction, a polypeptide that had the expected mol. wt. and contained VP3-related amino acid sequences as judged by immunological criteria, was synthesized to a level representing about 15% of the total bacterial protein. When a bacterial lysate enriched for the fusion polypeptide was injected into mice, it induced antibodies which inhibited haemagglutination and neutralized SA11 rotavirus infectivity.


Shear distortion and failure of capillary bridges. Wetting information beyond contact angle analysis.
Water capillary bridges are prepared that span hydrophilic pinning features on parallel opposing smooth, flat, and hydrophobic surfaces. These bridges are distorted by shearing the parallel plates at a low rate. The capillary bridges lengthen and distort to balance Laplace pressure (equilibrate mean curvature) as the features are separated and eventually rupture at a distance that is a function of the liquid volume, the advancing and receding contact angles of the surfaces, the separation between the parallel surfaces, and in particular, the shape and orientation of the hydrophilic pinning features. Two modes of capillary bridge failure are observed: (1) tensile, in which the capillary bridge breaks to form sessile drops on both the upper and lower surfaces, and (2) sessile, in which sessile capillary bridge rupture occurs on one surface to form a puddle (contact-line-distorted sessile drop) on the feature and a retained capillary bridge spanning the hydrophobic surface and the hydrophilic feature on the opposing surface. The shape and orientation of the features control the mode of capillary bridge failure as well as the distribution of water between the two separate sessile drops or the retained capillary bridge and the puddle.


Flow Diversion and Outcomes of Vertebral Fusiform Aneurysms After Stent-Only Treatment: A Hemodynamic Study.
The aim of this study was to determine the effectiveness of treating vertebral fusiform aneurysms (VFAs) only with stents. Using computational fluid dynamics, we evaluated the hemodynamic patterns of VFAs after stent-only treatment (SOT) and monitored hemodynamic changes in the side branches. Between September 2014 and December 2015, we enrolled 10 consecutive patients with VFAs who underwent SOT. Successful aneurysm reconstruction is defined as perfect reconstruction of the parent artery and complete or nearly complete occlusion of the aneurysm. Otherwise, the reconstruction was considered unsuccessful. After SOT, we used computational fluid dynamics to assess hemodynamic changes in aneurysmal velocity, wall shear stress, and relative residual time (RRT) as well as velocity in side branches. Ten patients were studied. At follow-up after initial treatment, 7 of the 10 reconstructions were successful. Compared with the 3 unsuccessful reconstructions, successful reconstructions showed a significantly greater increase in the mean RRT (1185.1% vs. 204.8%; P = 0.030) and a greater reduction in mean velocity (44.5% vs. 34.7%; P = 0.053) and wall shear stress (49.2% vs. 27.9%; P = 0.087). The average velocity in the branches decreased by 10.0% after SOT. There was also a significant difference between the mean reduction in the rate of flow velocity in the aneurysm and the side branches (42.1% vs. 10.0%; P < 0.001). We found a significant increase in RRT of successful reconstruction of aneurysms. There may be less effect on the flow in branches arising from VFAs after SOT, whether the aneurysms showed complete occlusion or not.


Clinical predictors of successful implantable cardioverter defibrillator implantation.
Successful implantation of an implantable cardioverter defibrillation system is critically dependent on demonstration that the lead system to be implanted can defibrillate reliably. Defibrillation efficacy in turn is dependent on several sets of factors that include: (1) defibrillation technique and the lead system being tested; (2) defibrillation testing protocol and criteria for implantation; and (3) clinical variables that may be intrinsic to the patient or extrinsic factors to which the patient is being exposed. Existing clinical data are limited but suggest that poor left ventricular function is the clinical variable most consistently associated with poor defibrillation efficacy and a failure to meet implant criteria of the epicardial lead systems. Antiarrhythmic drugs may elevate the defibrillation threshold, but evidence that this has important clinical ramifications on implantation success rates is very limited and incomplete.


Biochemical Characterization and Low-Resolution SAXS Molecular Envelope of GH1 β-Glycosidase from Saccharophagus degradans.
The marine bacteria Saccharophagus degradans (also known as Microbulbifer degradans), are rod-shaped and gram-negative motile γ-proteobacteria, capable of both degrading a variety of complex polysaccharides and fermenting monosaccharides into ethanol. In order to obtain insights into structure-function relationships of the enzymes, involved in these biochemical processes, we characterized a S. degradans β-glycosidase from glycoside hydrolase family 1 (SdBgl1B). SdBgl1B has the optimum pH of 6.0 and a melting temperature T m of approximately 50 °C. The enzyme has high specificity toward short D-glucose saccharides with β-linkages with the following preferences β-1,3 > β-1,4 ≫ β-1,6. The enzyme kinetic parameters, obtained using artificial substrates p-β-NPGlu and p-β-NPFuc and also the disaccharides cellobiose, gentiobiose and laminaribiose, revealed SdBgl1B preference for p-β-NPGlu and laminaribiose, which indicates its affinity for glucose and also preference for β-1,3 linkages. To better understand structural basis of the enzyme activity its 3D model was built and analysed. The 3D model fits well into the experimentally retrieved low-resolution SAXS-based envelope of the enzyme, confirming monomeric state of SdBgl1B in solution.


Contingent associations and the double-function, verbal-discrimination task.
Three experiments examined the role of contingent associations in learning double-function, verbal-discrimination lists. Some 15-pair lists of category instances were constructed in such a way that the learning of three contingent associations based on category names would mediate correct performance for all 15 pairs. The first experiment gave no evidence that the three contingencies aided learning. The second experiment showed that subjects could be taught the three contingent associations in isolation and that they could then apply them successfully to the double-function list. To make the contingencies more apparent to the subjects, the category names were used during feedback in the third experiment. The learning was not facilitated by such feedback. It was concluded that the learning observed for the usual double-function list does not involve contingent associations.


[Freeze fracturing and thin-section study of intercellular junctions between odontoblasts and the rat incisor. Changes induced by vinblastine].
The study of thin sections and replicas obtained after freeze-fracture showed that the intercellular junctions of the young secretory odontoblasts of the rat incisor were of two types. Zonula adherens (desmosomes) united the cellular bodies at the predentinal border. Ahead of these structures gap junctions were observed. An injection of vinblastine sulfate induced 4h, a) an enlargement of intermembranous spaces between the gap junctions, b) a reduction of the contact surfaces in the desmosomes and c) a thickening of the intracytoplasmic dense material made of microfilaments, associated with the junctional complex. These modifications favoured the observation of these structures after freeze-fracture. The desmosome junctions could play a mechanical function (partitioning of the predentinal compartment) whereas the gap junction allowed the electrotonic coupling of the odontoblasts. They allowed however an intercellular diffusion route for ionic components (calcium) and matrix components of serum origin.


[Surgical treatment of obstructive sleep apnea by modifying the facial skeleton with reference to cephalometric parameters].
Cephalometry: Morphologic alterations can be found in a great deal of patients with OSAS, predisposing to the rise of sleep apnea. In addition to preexisting investigations we developed a cephalometric analysis to judge these alterations in patients with OSAS. Comparing 160 patients to healthy people pharyngeal obstructions could be found in more than one third of the patients, usually combined with a retrognathic dolichofacial morphology. As successful treatment of our own patients shows, curing of obstructive sleep apnea is possible in respect of these cephalometric alterations. The basis of surgical treatment consists of surgical advancement of the mandible by sagittal split osteotomy and advancement of the maxilla by Le Fort I-osteotomy. Advancement surgery must be done in consideration of the morphologic alterations mentioned above. Additionally secondary procedures can be taken into account as genioplasty, soft-tissue-corrections or corrections of the upper airways.


Oestrogen and transplant vascular disease.
1. The aetiology of chronic rejection is clearly multifactorial and relates to both immunological and non-immunological factors. 2. Our studies suggest that the insulin-like growth factor (IGF)-I ligand and receptor genes are rate limiting in smooth muscle proliferation in the development of transplant arteriosclerosis. 3. Suppressing growth factor ligand or receptor expression could be effective strategies for the prevention or treatment of transplant arteriosclerosis. 4. We consistently find chronic oestradiol treatment of transplant recipients inhibits arteriosclerosis by attenuating both IGF-I expression and the immune response, particularly major histocompatibility complex class II expression. 5. Thus, a cell- or tissue-specific oestrogen with minimal feminizing properties may be an ideal drug for prevention of one of the major causes of loss of transplant function.


Control of a human tumour (Ewing sarcoma) in mice by a single lethal dose of dimethyl-myleran and bone marrow.
A Ewing sarcoma grown in immunosuppressed mice was eradicated with a single lethal dose of dimethylmyleran (DMM) followed by autologous or syngeneic bone marrow. Sarcomas treated 2 weeks after grafting in a phase of rapid proliferation disappeared and large sarcomas treated after 6 or 10 weeks were reduced to necrotic tissue. A human osteosarcoma also regressed distinctly after this therapy while a human colon carcinoma responded poorly. Sub-lethal DMM treatment induced complete remissions in only 62% of the mice. Tumours which display sensitivity in this model may be treated clinically with lethal doses of DMM and autologous marrow transplantations.


ARF binds the C-terminal region of the Escherichia coli heat-labile toxin (LTA1) and competes for the binding of LTA2.
Cholera toxin (CT) and the heat-labile enterotoxin (LT) from Escherichia coli are highly related in terms of structure and biochemical activities and are the causative agents of cholera and traveler's diarrhea, respectively. The pathophysiological action of these toxins requires their activity as ADP-ribosyltransferases, transferring the ADP-ribose moiety from NAD onto the stimulatory, regulatory component of adenylyl cyclase, Gs. This reaction is highly dependent on the protein cofactor, termed ADP-ribosylation factor (ARF), that is itself a 20 kDa regulatory GTPase. In this study, we define sites of interaction between LTA and human ARF3. The residues identified as important to ARF binding include several of those previously shown to bind to the A2 subunit of the toxin and those important to the organization of two flexible loops, previously implicated as regulators of substrate entry. A model for how ARF acts to enhance the catalytic activity is proposed. A critical portion of the overlap between ARF and LTA(2) in binding LTA(1) includes a short region of sequence homology between LTA(2) and the switch II region of ARF. LTA(2) also interacted with ARF effectors in two-hybrid assays, and thus, we discuss the possibility that the LTA(2) subunit may function in cells as a partial ARF mimetic to compete for the binding of ARF to LTA(1) or regulate aspects of the toxin's transport from the cell surface to the ER.


Global scientific productivity in the field of PET: a 10-year survey of research activities.
The objective of this study was to assess global research output in the field of PET and to provide a general picture of PET research. Publications on PET from 2007 to 2016 were identified using the Web of Science. The total number of papers, the number of papers adjusted by gross domestic product (GDP)/population size, total citations, and average citations were investigated. A total of 40 670 papers were identified in the field of PET between 2007 and 2016. The number of papers published per year were significantly increased during this period (P=0.000). High-income countries published the maximum papers (89.95%), followed by middle-income countries (10.05%), whereas no papers were published by authors from low-income countries. The USA published the largest number of papers (11 936), followed by Japan (3667), Germany (3424), China (2508), and the UK (2424), and the USA had the highest total number of citations (361 498). The UK had the highest average citations (31.81). Positive correlations were found between the total number of papers and GDP (P=0.000, r=0.909)/population (P=0.000, r=0.772). When normalized by GDP, Denmark ranked the first (23.56), followed by The Netherlands (17.18) and Belgium (15.32). When adjusted for population, Denmark ranked the first (111.55), followed by The Netherlands (87.91) and Switzerland (86.93). Global scientific production represents a rapid increase in the PET field in recent years. The majority of PET papers are from high-income countries. The USA is the most prolific country, whereas some smaller European countries may be more prolific relative to their GDP/population.