Irritable bowel syndrome is underdiagnosed and ineffectively managed among endurance athletes.
Lower gastrointestinal (GI) symptoms are common among endurance athletes and can impair performance. Symptom characteristics are similar to irritable bowel syndrome (IBS). No previous research has examined IBS diagnosis (medically or by diagnostic criteria) within this population. The objectives of this study were to determine the prevalence of IBS among endurance athletes and examine their GI symptom management strategies. A previously validated, online questionnaire assessed IBS diagnosis, the meeting of IBS diagnostic criteria (Rome III or Manning), general GI symptoms, and symptom mitigation strategies of endurance athletes. The questionnaire was distributed to United States athletes completing a marathon, ultra-marathon, half-distance triathlon, or full-distance triathlon. Medically diagnosed IBS was reported by 2.8% of endurance athletes. The total prevalence of IBS (n = 430) was 9.8% (medical diagnosis and Rome III). Athletes with IBS experienced more frequent symptoms during exercise as well as at rest; however, only 47.6% had consulted a medical professional. Over 56% of athletes experienced at least 1 symptom sometimes, often, or always during training and competition and 18.6% had symptoms that sometimes or often interrupted/prevented training. Almost half (45.8%) of athletes and 80.0% of athletes with IBS reported trying nutritional modifications to help ease symptoms while 20.6% and 52.4% used over-the-counter medications, respectively. Novelty Most endurance athletes who suffer from IBS are undiagnosed, while even more experience GI symptoms but do not fit diagnostic criteria. Despite using various symptom management methods, endurance athletes are still experiencing symptoms and could potentially benefit from current IBS-mitigating strategies.


Determination of insulin-like growth factor 1 in dogs using a commercially available immunoradiometric assay1).
The objective of the present study was to characterize a commercially available immunoradiometric assay (IRMA) intended for the determination of human insulin-like growth factor 1 (IGF-1) when used to determine IGF-1 in canine plasma samples. The assay was evaluated by assessment of the precision, accuracy, and detection limit, and by comparing the IGF-1 values observed in healthy dogs and in dogs with acromegaly and hereditary pituitary dwarfism to values reported in the literature. Since extraction of IGF-1 from its binding proteins is essential for reliable test results, the efficiency of the extraction method used in the assay was also examined. The main conclusions can be summarized as follows: The commercially available IRMA method offers a precise determination of the IGF-1 concentration in canine plasma samples with IGF-1 values directly comparable to those obtained by others. The assay accuracy was confirmed for normal dogs by parallelity between IGF-1 concentrations and plasma dilutions, whereas plasma from acromegalic dogs could not fullful parallelity. The detection limit was below the IGF-1 concentrations observed in dogs with hereditary pituitary dwarfism. In plasma samples with low or normal IGF-1 levels, the assay's extraction efficiency was comparable to that found using other extraction methods. In samples with IGF-1 concentrations above usual physiological levels, the extraction efficiency decreased unexplainably. However, this decrease in extraction efficiency seems to be of only minor importance when the measurements are used in the diagnosis of canine acromegaly.


Autoimmune diagnostics in diabetes mellitus.
Type 1 diabetes results from a specific destruction of the insulin-producing beta-cells of the pancreas. The disease is characterized by the appearance of specific autoantibodies against islet cell antigens. Autoantibodies to insulin, glutamic acid decarboxylase, tyrosine phosphatase IA-2 and cytoplasmic islet cell antibodies are useful markers for the differential diagnosis of type 1 diabetes when clinical and metabolic criteria alone do not allow definite classification. Autoimmune diagnostics is of particular importance in adults to discriminate between type 1 and type 2 diabetes and to assess the diagnosis of latent autoimmune diabetes in adults.


Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.
Synthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only ∼20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.


Blinding in Physical Therapy Trials and Its Association with Treatment Effects: A Meta-epidemiological Study.
The aim of this study was to examine whether blinding of participants, assessors, health providers, and statisticians have an effect on treatment effect estimates in physical therapy (PT) trials. This was a meta-epidemiological study. Randomized controlled trials in PT were identified by searching the Cochrane Database of Systematic Reviews for meta-analyses of PT interventions. Assessments of blinding in PT trials were conducted independently following established guidelines. Three hundred ninety-three trials and 43 meta-analyses that included 44,622 patients contributed to this study. Only a quarter of the trials were adequately blinded (n = 80; 20%). Most individual components of blinding as well as what they were blinded to were also poorly reported. Although trials with inappropriate blinding of assessors and participants tended to underestimate treatment effects when compared with trials with appropriate blinding of assessors and participants, the difference was not statistically significant (effect size, -0.07; 95% confidence interval, -0.22 to 0.08; effect size, -0.12; 95% confidence interval, -0.30 to 0.06, respectively). The lack of statistical significance between blinding and effect sizes should not be interpreted as meaning that an impact of blinding on effect size is not present in PT. More empirical evidence in a larger sample is needed to determine which biases are likely to influence reported effect sizes of PT trials and under which conditions.


Profile of leukocyte-endothelial cell interactions induced in venules and arterioles by nucleoside reverse-transcriptase inhibitors in vivo.
There is controversy regarding cardiovascular (CV) toxicity of the nucleoside reverse-transcriptase inhibitors used to treat human immunodeficiency virus infection. We evaluated the effects of nucleoside reverse-transcriptase inhibitors on leukocyte-endothelium interactions, a hallmark of CV diseases, in rat mesenteric vessels using intravital microscopy and in human arterial cells using a flow chamber system. Abacavir and didanosine increased rolling, adhesion and emigration in rat vessels. These effects were reversed with antibodies against Macrophage-1 antigen (Mac-1) or intercellular adhesion molecule 1 and were reproduced in human cells. Lamivudine, zidovudine, emtricitabine, and tenofovir had no effects. Our results support the association of abacavir and didanosine with CV diseases.


[Allergic aspects of juvenile asthma].
In children, wheezing is not necessarily related to allergy. Without being asthmatic, a child may suffer from asthmatiform dyspnea, especially in cases of respiratory infection. It may be difficult to decide whether the patient has benign "wheezy bronchitis" or is exhibiting the first symptoms of asthma. It appears that viral infections may play a significant role in the development of respiratory allergy in atopic subjects.


Acylation of the alanine149 N-terminal of alpha-chymotrypsin and its effect on catalytic function.
A novel, active derivative of alpha-chymotrypsin was prepared from alanine-neochymotrypsinogen in which the epsilon-amino groups and the alpha-amino group of N-terminal Ala149 were acetylated. The catalytic properties at neutral and alkaline pH of this enzyme derivative were compared with those of a control alpha-chymotrypsin derivative in which only the epsilon-amino groups were acetylated. While the Km (app) of the two derivatives were the same at pH 7 to 8, at more alkaline pH the derivative having the masked Ala149 had much lower Km (app) values than the control. It is concluded that the inactivation of alpha-chymotrypsin at high pH is linked, at least in part, to the ionization state of its N-terminal Ala149 group.


Identifying robustness in the regulation of collective foraging of ant colonies using an interaction-based model with backward bifurcation.
Collective behaviors in social insect societies often emerge from simple local rules. However, little is known about how these behaviors are dynamically regulated in response to environmental changes. Here, we use a compartmental modeling approach to identify factors that allow harvester ant colonies to regulate collective foraging activity in response to their environment. We propose a set of differential equations describing the dynamics of: (1) available foragers inside the nest, (2) active foragers outside the nest, and (3) successful returning foragers, to understand how colony-specific parameters, such as baseline number of foragers, interactions among foragers, food discovery rates, successful forager return rates, and foraging duration might influence collective foraging dynamics, while maintaining functional robustness to perturbations. Our analysis indicates that the model can undergo a forward (transcritical) bifurcation or a backward bifurcation depending on colony-specific parameters. In the former case, foraging activity persists when the average number of recruits per successful returning forager is larger than one. In the latter case, the backward bifurcation creates a region of bistability in which the size and fate of foraging activity depends on the distribution of the foraging workforce among the model's compartments. We validate the model with experimental data from harvester ants (Pogonomyrmex barbatus) and perform sensitivity analysis. Our model provides insights on how simple, local interactions can achieve an emergent and robust regulatory system of collective foraging activity in ant colonies.


Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK1/2 Inhibitor for Treatment of Triple-Negative Breast Cancer with a Compromised G1-S Checkpoint.
Historically, phenotypic-based drug discovery has yielded a high percentage of novel drugs while uncovering new tumor biology. CC-671 was discovered using a phenotypic screen for compounds that preferentially induced apoptosis in triple-negative breast cancer cell lines while sparing luminal breast cancer cell lines. Detailed in vitro kinase profiling shows CC-671 potently and selectively inhibits two kinases-TTK and CLK2. Cellular mechanism of action studies demonstrate that CC-671 potently inhibits the phosphorylation of KNL1 and SRp75, direct TTK and CLK2 substrates, respectively. Furthermore, CC-671 causes mitotic acceleration and modification of pre-mRNA splicing leading to apoptosis, consistent with cellular TTK and CLK inhibition. Correlative analysis of genomic and potency data against a large panel of breast cancer cell lines identifies breast cancer cells with a dysfunctional G1-S checkpoint as more sensitive to CC-671, suggesting synthetic lethality between G1-S checkpoint and TTK/CLK2 inhibition. Furthermore, significant in vivo CC-671 efficacy was demonstrated in two cell line-derived and one patient tumor-derived xenograft models of triple-negative breast cancer (TNBC) following weekly dosing. These findings are the first to demonstrate the unique inhibitory combination activity of a dual TTK/CLK2 inhibitor that preferably kills TNBC cells and shows synthetic lethality with a compromised G1-S checkpoint in breast cancer cell lines. On the basis of these data, CC-671 was moved forward for clinical development as a potent and selective TTK/CLK2 inhibitor in a subset of patients with TNBC. Mol Cancer Ther; 17(8); 1727-38. ©2018 AACR.


[Development of Silk Fibroin Composite Films for Corneal Repair].
It is important to design a long-period transparent bioactive material for corneal repair in the process of corneal tissue renovation. This article discusses the silk fibroin and formamide blend membranes as a corneal stroma repair material. Silk fibroin solution was mixed with formamide in different proportions to obtain insoluble transparent silk fibroin film by casting method. The blending membranes had excellent mechanical properties, cell compatibility and long-term transparent properties. Rabbit corneal stromal cells were seeded on the sterilized composite films. The rate of cell surface adhesion was over 90% after cells were placed on it for 5 hours. When cells were seeded on blend membranes from one day to seven days, Alma Blue was added to complete medium. Compared with the cell culture plate, there was no significant difference in cell proliferation on formamide/silk films. The results indicated that formamide/silk films might be used as a corneal stroma repair material and worth of further investigatinn


Sensitive and rapid diagnosis of potato spindle tuber viroid disease by nucleic Acid hybridization.
A sensitive and reliable new method for the detection of potato spindle tuber viroid in potato tubers has been developed. The method is based on hybridization of highly radioactive recombinant DNA to viroid RNA that has been attached to a solid support. The method can be automated and permits the rapid testing of large numbers of tubers.


[Dentato-rubro-pallido-luysium atrophy in an infant].
After an uneventful pregnancy and labour one hour post partum a tonic-clonic seizure occurred in a female infant. In the following time a muscular hypertonicity developed and the statomotor development ceased. No clue for a neurometabolic disease was found and the child died of an aspiration pneumonia at 5 months of age. Neuropathological examination disclosed a Dentato-Rubro-Pallido-Luysium-Atrophy (DRPLA). Apart from two healthy siblings an older sister had died six months old after an almost identical clinical course. No autopsy was done in this first case. DRPLA is a rare systemic degeneration and begins to our knowledge always in adolescence or adult age. The nosological classification of this unusual case is discussed and the literature is reviewed.


3,4-Diaminopyridine induced stimulus-bound repetitive firing in frog sympathetic ganglion: no changes in postsynaptic membrane excitability.
It has been shown previously that 3,4-diaminopyridine (3,4-DAP) facilitates synaptic transmission in the frog sympathetic ganglion inducing so-called stimulus-bound repetition (SBR), i.e. a brief burst of repetitive postganglionic discharges after a single orthodromic stimulus. In the present study we analyzed one of the possible mechanisms of the 3,4-DAP-induced SBR, namely changes in postsynaptic membrane excitability. We found that 3,4-DAP in concentration optimal for inducing SBR (2 X 10(-4) mol.l-1) had no direct effect on the excitability of the postsynaptic membrane of frog sympathetic neurones. The excitability was expressed as the threshold for action potentials elicited orthodromically, antidromically and directly, as well as the spike activity evoked by constant depolarizing current pulses. We also indirectly excluded the involvement of two other possible mechanisms of neuronal membrane excitability modulation in the 3,4-DAP-induced SBR, i.e. the M-current suppression by analyzing the participation of muscarinic receptor activation in the SBR, and inhibition of the Ca(2+)-activated K+ currents by measuring the duration of afterhyperpolarization of antidromic action potential. Our findings indicate that no remarkable changes in the properties of the postsynaptic membrane contribute to the generation of 3,4-DAP-induced SBR in the frog sympathetic ganglion. This strongly supports the hypothesis that the mechanism underlying SBR evoked by this drug is presynaptic.


Effects of selenium and cadmium on changes in the gene expression of immune cytokines in chicken splenic lymphocytes.
Cadmium (Cd) is an environmental pollutant that is considered to be a potent toxin to organisms. Selenium (Se) has been known for its concomitant biological effects and characteristics with Cd. Due to the lack of the research regarding how the duality of Cd/Se affects immune cytokines in poultry, this paper aims to partly tackle this question. Chicken splenic lymphocytes with Cd (10(-6) mol/L CdCl2), Se (10(-7) mol/L Na2SeO3), Cd + Se (10(-7) mol/L Na2SeO3 and 10(-6) mol/L CdCl2), and a control group were incubated for 12, 24, 36, 48, and 60 h, respectively. At each time point, the cells were collected and the messenger RNA (mRNA) expression levels of interleukin (IL)-1β, IL-2, IL-4, IL-10, IL-17, and interferon-γ (IFN-γ) were also examined. Compared with the control group and the Se-alone-treated group, the mRNA expression levels of IL-2, IL-4, IL-10, IL-17, and IFN-γ decreased significantly in the Cd-alone-treated group. By contrast, the mRNA expression level of IL-1β markedly increased. Levels of IL-2, IL-4, IL-10, IL-17, and IFN-γ in Cd + Se-treated groups were significantly higher than those in Cd-alone-treated groups; however, the levels were not as high as the Se-alone-treated groups and the control group. The mRNA expression level of IL-1β in the Cd + Se-treated group was lower than in the Cd-alone-treated group. The relationships with IL-2, IL-4, and IL-10 were found to be closer in the PC 1 matrix and 3D plot of the principal component analysis (PCA) loadings. IL-17 and IFN-γ were closer in the matrix of PC 2. However, IL-1β gene expression appeared to be isolated in the matrix of PC 3. In addition, the results of cytokine cluster analysis showed that IL-2, IL-4, IL-10, IL-17, and IFN-γ were in the first group and that IL-1β was in the second group. Therefore, Se partly attenuate immune toxicity induced by Cd in chicken splenic lymphocytes.


Structure of BaO on hierarchical macro-meso-microporous alumina and its effect of interaction with Pt nanoparticle on NO2 desorption.
Recently, the lean NOx trap technology using supported Pt catalyst on alumina was devised to store NOx under lean condition and to reduce into N2 and water under rich condition in lean burn engine. In this work, the effect of the Pt nanoparticle supported on hierarchical macro-meso-microporous BaO-Al2O3 on NO2 desorption has been investigated with NO2 temperature programmed desorption, TEM, SEM, TGA and hydrogen chemisorption. Crystalline BaO phase of 20-30 nm thickness were obtained on the hierarchical macro-meso-microporous Al2O3 with a simple impregnation of Ba(NO3)2 and Ba(ClO4)2. The interaction of Pt and BaO was resulted in the formation of atomically dispersed Pt nanoparticles and also decreased the desorption temperature of NO2 adsorbed on BaO at much lower temperature than that from the BaO-Al2O3 support only. This synergistic lowering of NO2 desorption temperature may be originated from the interaction between Pt and BaO.


Comparison of the possible risk factors of bone mineral density in subjects with ulcerative colitis and healthy subjects.
Inflammatory bowel disease (IBD) is a gastrointestinal system disorder with a variety of causes. The prevalence of reduced bone mineral density (BMD) is greater in people with IBD as compared with healthy individuals. In this study, we aimed to investigate the possible risk factors for low BMD in subjects with ulcerative colitis (UC) and in healthy control subjects. A total of 40 subjects with UC and 29 healthy subjects were enrolled in the study. Age; sex; body mass index; location and duration of disease; current corticosteroid, azathioprine, or other immunosuppressive medications; smoking; consumption of alcohol, milk, and milk products; menstrual pattern in women; and use of vitamin D, calcium, folic acid, multivitamins, and iron preparations were recorded. BMD was measured by dual-energy x-ray absorptiometry at L2-L4 of the spine and the femoral neck. The BMD of patients was found to be lower than that in the control group. The T and z scores of the lumbar vertebra and femoral neck were normal in 21 subjects (52.5%). A total of 17 (42.5%) subjects had osteopenia, and 2 (5%) subjects had osteoporosis. Parathyroid hormone, 1,25(OH)2 vitamin D3, osteocalcin, and urinary markers were found to be similar in both groups. There were no significant differences between subjects with UC and subjects in the control group according to age, sex, and conventional risk factors. The BMD of subjects with UC was found to be lower than that in subjects of similar age and sex in the control group. Our findings suggest that that the disease itself is the most important pathogenic factor contributing to low BMD.


Re'COG'nition at the Golgi.
The conserved oligomeric Golgi (COG) complex co-ordinates retrograde vesicle transport within the Golgi. These vesicles maintain the distribution of glycosylation enzymes between the Golgi's cisternae, and therefore COG is intimately involved in glycosylation homeostasis. Recent years have greatly enhanced our knowledge of COG's composition, protein interactions, cellular function and most recently also its structure. The emergence of COG-dependent human glycosylation disorders gives particular relevance to these advances. The structural data have firmly placed COG in the family of multi-subunit tethering complexes that it shares with the exocyst, Dsl1 and Golgi-associated retrograde protein (GARP) complexes. Here, we review our knowledge of COG's involvement in vesicle tethering at the Golgi. In particular, we consider what this knowledge may add to our molecular understanding of vesicle tethering and how it impacts on the fine tuning of Golgi function, most notably glycosylation.


Guided bone growth in sheep: a model for tissue-engineered bone flaps.
The emerging field of tissue engineering is yielding a variety of new strategies for bone replacement. In vivo assessment of candidate bone substitutes to demonstrate biocompatibility, degradability, and the ability to produce meaningful quantities of bone is essential prior to clinical use. We present results of a large animal model using formed plastic chambers implanted adjacent to the rib periosteum in sheep to fabricate vascularized bone flaps of different shapes. Chambers packed with morcellized corticocancellous bone graft, representing the most favorable natural circumstances for bone formation, were compared to empty chambers, representing the least favorable. Implants containing bone chips yielded formed blocks of vascularized bone after 6 weeks with evidence of remodeling after 13 weeks. Histomorphometric analysis demonstrated that there was full bone penetration into shallow (5 mm) chambers and 8.8 mm (+/-0.6) penetration into deep (10 mm) implants after 6 weeks. Molded bone segments failed to grow in empty chambers. This model presents a quantifiable range of bone forming potential to which different bone substitutes may be compared for usefulness in creating tissue engineered bone flaps for reconstructive surgery.


Giant left ventricular pseudo-false aneurysm following myocardial infarction.
We report a successful surgical case of giant left ventricular pseudo-false aneurysm in a 63-year-old man. The abnormality of the inferior wall of the left ventricle was discovered incidentally by abdominal ultrasonography for health examination at another hospital. Transthoracic echocardiography and left ventriculography revealed a giant false aneurysm (74x75x40 mm) in the inferior wall of the left ventricle with a large orifice (70x58 mm). Repair of the aneurysm was performed under arrested heart, closing the large orifice with a Hemashield patch. Postoperative pathological examination proved that the wall of the aneurysm had myocardial tissue. The microscopic results strongly suggested that this aneurysm was a pseudo-false aneurysm.


The antidepressants venlafaxine ("Effexor") and fluoxetine ("Prozac") produce different effects on locomotion in two species of marine snail, the oyster drill (Urosalpinx cinerea) and the starsnail (Lithopoma americanum).
Human antidepressants have been previously shown to induce foot detachment from the substrate in aquatic snails. Prior to foot detachment, antidepressants also affect snail crawling speed. We tested two commonly prescribed antidepressants, venlafaxine ("Effexor") and fluoxetine ("Prozac") on crawling speed and time to reach the air-water interface in two species of marine snail, the oyster drill Urosalpinx cinerea and the American starsnail Lithopoma americanum. Exposure to venlafaxine increased crawling speed in both species, while fluoxetine slowed them down. Our lowest LOEC (lowest observed effect concentration) was 31.3 μg/L venlafaxine in Urosalpinx. Similarly, snails (L. americanum) exposed to venlafaxine tended to move faster and more often to the air-water interface, but exposure to fluoxetine slowed them down. Our lowest LOEC was 345 μg/L fluoxetine in Lithopoma. These results indicate that venlafaxine boosts locomotion, while fluoxetine reduces it, and both behaviors are preludes to foot detachment. The different effects of these two antidepressants on snail locomotion suggest differing physiological mechanisms of action in marine snails as well as possible ecological consequences.


Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants.
Growth-promoting macroglia (aldynoglia) with growth properties and immunological markers similar to Schwann cells, are found in loci of the mammalian CNS where axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus-hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle freely with astrocytes and can migrate in brain and spinal cord. Transplantation of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal cord after multiple central rhizotomy, promoted sensory and central axon growth and partial functional restoration, judging by anatomical, electrophysiological and behavioural criteria. OEC transplants suppressed astrocyte reactivity, thus generally favouring axon growth after a lesion. However, the functional repair promoted by OEC transplants was partial in the best cases, depending on lesion type and location. Cyst formation after photochemical cord lesion was partially prevented but neither the corticospinal tract, interrupted by a mild contusion, nor the sectioned medial longitudinal fascicle, did regrow after OEC transplantation in the injured area.


Actin cytoskeleton polymerization in Dbl-transformed NIH3T3 fibroblasts is dependent on cell adhesion to specific extracellular matrix proteins.
The Dbl oncogene is the putative exchange factor for two small GTP-binding proteins, RhoA and CDC42 which are involved in the polymerization of actin to produce stress fibers and filopodia, respectively. We report here that Dbl oncogene-transformed NIH3T3 cells show actin stress fibers only when cells are plated on fibronectin. Plating of cells on collagen I and IV as well as on poly-D-lysine and gelatin induces polymerization of actin to form filopodia, lamellipodia and membrane ruffles but not stress fibers. The putative collagen receptors, alpha1/beta1 and alpha2/beta1 integrins are expressed at reduced level in Dbl-transformed cells compared to untransformed NIH3T3 fibroblasts. Nevertheless, adhesion to collagens is not altered. Inhibitory monoclonal antibody to mouse integrin beta1 subunit blocked adhesion of both Dbl-transformed and untransformed NIH3T3 cells, demonstrating that adhesion to collagen I and IV is mediated by the beta1 family of integrins. Dbl product rapidly induces the depolymerization of actin stress fibers, rounding up of the cells, and formation of filopodia and lamellipodia when microinjected in NIH3T3 cells plated on gelatin. Thus, Dbl may exert its effect on actin cytoskeleton organization in response to extracellular proteins by altering integrin-mediated signalling pathways.


Inhibition of 3 beta-hydroxysteroid-dehydrogenase: an approach for prostate cancer treatment?
Over 80% of clinically manifested prostate cancers respond to androgen withdrawal. Several alternatives to castration have been explored. Since a growth promoting role for androstenedione has been suggested, we investigated the effect of inhibition of 3 beta-hydroxy-steroid-dehydrogenase (3 beta-HSD), a key enzyme involved in the biosynthesis of practically all steroids. In a previous study a reduced proliferation rate of androgen responsive R3327-H tumor was demonstrated after in vivo treatment with 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4MA) - a putative 5 alpha-reductase inhibitor. In the present investigation 3 beta-HSD enzyme activity derived from human placenta, testis and ovarian cancer cell line and from rat testis was determined using radiolabeled dehydroepiandrosterone (DHEA) or pregnenolone. Among different synthetic compounds known to interfere with steroidogenesis, only 4MA was shown to potently inhibit in vitro 3 beta-HSD activity from all tissue sources. 4MA was administered to male Copenhagen rats bearing R3327-H androgen dependent prostate tumors and levels of different androgens in serum and prostate tumor were measured using reversed phase HPLC and radioimmunoassay. The decreased content of androstenedione in serum and tumor tissue with DHEA accumulation in prostate tumor tissue showed an effective 3 beta-HSD inhibition by 4MA occurring in vivo as well. These observations unequivocally demonstrate a 3 beta-HSD inhibiting effect of 4MA in vitro as well as in vivo and point to a role for androstenedione in the promotion of cell proliferation in androgen sensitive tumors. 3 beta-HSD dependent androstenedione production could thus constitute a proper target -eventually combined with other endocrine treatment - for the treatment of hormone dependent prostate cancer.


Effects of long-term running stress on the ultrastructure of the aging mouse heart.
Apical regions of the left ventricular myocardium of female C57BL/6J mice, aged between 6 and 27 months, that had been subjected to endurance running for 2, 10 or 15 months, were examined by light and electron microscopy. Focal degenerative changes were found in myocytes of these experimental mice, including loss of myofibrils, erosion of myocytes and changes in nuclei, lipofuscin content and mitochondria. The interstitial connective tissue showed an increase in collagen in aged myocardia. Endurance-trained runners frequently showed signs of platelet aggregation or microthrombi in small capillaries associated with myocytes. These were most common in endurance-trained middle-aged and very elderly mice, but were not found in sedentary age-matched controls. Our experiments indicate that running stress may be damaging to cardiac tissue in aged animals. Our findings may be of significance in helping the understanding of the development and the etiology of stress-induced cardiovascular damage in the elderly.


Identification of sustainable flux in the process of using flat-sheet membrane for simultaneous thickening and digestion of waste activated sludge.
The influences of mixed liquor properties on critical flux were investigated in the membrane for simultaneous thickening and digestion of activated sludge (MSTD) process, and the sustainable operation of the MSTD process was examined by employing sub-critical operation. The critical flux significantly decreased with the increase of operation time due to the variations of sludge properties in the MSTD process. Test results showed that mixed liquor suspended solids (MLSS), capillary suction time (CST), soluble microbial products (SMP) and chemical oxygen demand concentrations of colloids (COD(c)) were found to have significant influences on critical flux while the extracellular polymeric substances (EPS) had mild impacts. MLSS was then chosen as an indicated parameter, and an empirical relationship was established to predict the variation of critical flux in the MSTD process. The variable sub-critical flux operation was proposed to realize the sustainable operation according to the changing law of the critical flux during the MSTD process. The result showed that the membrane fouling potential in the MSTD process could be controlled at an operationally accepted condition by the variable sub-critical flux operation.


Simultaneous determination of aliskiren and hydrochlorothiazide from their pharmaceutical preparations using a validated stability-indicating MEKC method.
A stability-indicating MEKC method was developed and validated for the simultaneous determination of aliskiren (ALI) and hydrochlorothiazide (HCTZ) in pharmaceutical formulations using ranitidine as an internal standard (IS). Optimal conditions for the separation of ALI, HCTZ and its major impurity chlorothiazide (CTZ), IS and degradation products were investigated. The method employed 47 mM Tris buffer and 47 mM anionic detergent SDS solution at pH 10.2 as the background electrolyte. MEKC method was performed on a fused-silica capillary (40 cm) at 28°C. Applied voltage was 26 kV (positive polarity) and photodiode array (PDA) detector was set at 217 nm. The method was validated in accordance with the ICH requirements. The method was linear over the concentration range of 5-100 and 60-1200 μg/mL for HCTZ and ALI, respectively (r(2) >0.9997). The stability-indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using the PDA detection. Precision and accuracy evaluated by RSD were lower than 2%. The method proved to be robust by a fractional factorial design evaluation. The proposed MEKC method was successfully applied for the quantitative analysis of ALI and HCTZ both individually and in a combined dosage tablet formulation to support the quality control.


Anesthesia considerations and post-operative pain management in pregnant women with chronic opioid use.
The prevalence of opioid use disorder in pregnancy has escalated markedly in recent years. Chronic opioid use during pregnancy poses several challenges for providing adequate analgesia and anesthesia in the peripartum period. These challenges include the potential for withdrawal, opioid tolerance and opioid-induced hyperalgesia. Here we discuss alterations in analgesic pharmacokinetics and pharmacodynamics that are associated with chronic opioid use. In addition, when treating pain in patients with opioid use disorder it is important to distinguish between different subgroups. In this review, we will discuss practical management strategies for parturients with (1) untreated opioid use disorder, (2) parturients on medication-assisted treatment (methadone, buprenorphine) and (3) patients recovering from opioid use disorder that are currently abstinent. Finally, we offer an overview of non-opioid strategies that may be utilized as part of a multimodal approach to providing optimal analgesia in this patient population.


Individual dietary intake methodology: a 50-year review of progress.
This article provides an overview of five decades (1936 through 1987) of publications on individual dietary assessment methodology, such as dietary histories, estimated and weighed food records, food frequency questionnaires, and 24-hour recalls. Representative studies were selected to characterize data collection and analyses methods of each decade. During the 1930s and 1940s, dietary intake methodology was in its initial stages; popular methods were the dietary history technique and lengthy food records. The 1950s were characterized by extensive comparisons of methodologies, which now often included shorter-term food records and 24-hour recalls. The 1960s ushered in large scale epidemiological studies, the food frequency technique, and use of computer technology for computation; the 24-hour recall was still widely used in that decade and the next. Advances of the 1970s and 1980s include expansion of nutrient databases, sophisticated statistical techniques for analysis, and refinement of data collection methodologies for analysis, and refinement of data collection methodologies. The chronological approach used in this review not only highlights progress of each decade but also identifies the repetitive efforts of some studies. The need for creative approaches is emphasized as current research needs are identified.


[Chromatographic separation of racemic thalidomide and teratogenic activity of its enantiomers (author's transl)].
Racemic thalidomide is chromatographically separated on optically active polyamide giving both enantiomers. After i.p. administration only the S-(-)-enantiomer is teratogenic on SWS mice and Natal rats.


Vasopressin increases GABAergic inhibition of rat hypothalamic paraventricular nucleus neurons in vitro.
This investigation used an in vitro hypothalamic brain slice preparation and whole cell and perforated-patch recording to examine the response of magnocellular neurons in hypothalamic paraventricular nucleus (PVN) to bath applications of vasopressin (VP; 100-500 nM). In 22/38 cells, responses were characterized by an increase in the frequency of bicuculline-sensitive inhibitory postsynaptic potentials or currents with no detectable influence on excitatory postsynaptic events. Perforated-patch recordings confirmed that VP did not have an effect on intrinsic membrane properties of magnocellular PVN neurons (n = 17). Analysis of intrinsic membrane properties obtained with perforated-patch recording (n = 23) demonstrated that all of nine VP-sensitive neurons showed a rebound depolarization after transient membrane hyperpolarization from rest. By contrast, 12/14 nonresponding neurons displayed a delayed return to resting membrane potentials. Recordings of reversed inhibitory postsynaptic currents with chloride-loaded electrodes showed that responses to VP persisted in media containing glutamate receptor antagonists but were abolished in the presence of tetrodotoxin. In addition, responses were mimicked by vasotocin [Phe(2), Orn(8)], a selective V(1a) receptor agonist, and blocked by [beta-Mercapto-beta, beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2), Arg(8)]-VP (Manning compound), a V(1a)/OT receptor antagonist. Neither [deamino-Cys(1),Val(4),D-Arg(8)]-VP, a selective V(2) receptor agonist, nor oxytocin were effective. Collectively, the results imply that VP acts at V(1a) receptors to excite GABAergic neurons that are presynaptic to a population of magnocellular PVN neurons the identity of which features a unique rebound depolarization. Endogenous sources of VP may be VP-synthesizing neurons in suprachiasmatic nucleus, known to project toward the perinuclear regions of PVN, and/or the magnocellular neurons within PVN.


Exploring selection and recruitment processes for newly qualified nurses: a sequential-explanatory mixed-method study.
To map current selection and recruitment processes for newly qualified nurses and to explore the advantages and limitations of current selection and recruitment processes. The need to improve current selection and recruitment practices for newly qualified nurses is highlighted in health policy internationally. A cross-sectional, sequential-explanatory mixed-method design with 4 components: (1) Literature review of selection and recruitment of newly qualified nurses; and (2) Literature review of a public sector professions' selection and recruitment processes; (3) Survey mapping existing selection and recruitment processes for newly qualified nurses; and (4) Qualitative study about recruiters' selection and recruitment processes. Literature searches on the selection and recruitment of newly qualified candidates in teaching and nursing (2005-2013) were conducted. Cross-sectional, mixed-method data were collected from thirty-one (n = 31) individuals in health providers in London who had responsibility for the selection and recruitment of newly qualified nurses using a survey instrument. Of these providers who took part, six (n = 6) purposively selected to be interviewed qualitatively. Issues of supply and demand in the workforce, rather than selection and recruitment tools, predominated in the literature reviews. Examples of tools to measure values, attitudes and skills were found in the nursing literature. The mapping exercise found that providers used many selection and recruitment tools, some providers combined tools to streamline process and assure quality of candidates. Most providers had processes which addressed the issue of quality in the selection and recruitment of newly qualified nurses. The 'assessment centre model', which providers were adopting, allowed for multiple levels of assessment and streamlined recruitment. There is a need to validate the efficacy of the selection tools.


A coupled NAD+-peroxidase spectrophotometric assay for cholesterol.
We describe a modified enzymic reagent for determination of cholesterol and cholesterol ester in serum and in high-density lipoprotein. In this new procedure, the hydrogen peroxide produced by the action of cholesterol oxidase is used as a substrate for NAD+ peroxidase. Spectrophotometric determination of the NADH consumed in this coupled reaction provides a direct and absolute measure of the cholesterol originally present in free form and that liberated by the action of cholesterol ester hydrolase.


[Advances in gastrointestinal disorders associated with non-steroidal antiinflammatory agents and aspirin].
Patients with gastrointestinal (GI) risk factors who require non-steroidal antiinflammatory drugs (NSAIDs) or aspirin must receive gastropreventive therapies. According to some recent surveys, the low prescription rates of these therapies reported some years ago are progressively improving in several European countries, which should be accompanied by a subsequent decrease in the frequency of hospitalizations due to complications of the upper GI tract, but not of those located in the lower GI tract. The most recent data confirm that celecoxib has a better GI safety profile both in the upper and lower GI tract than traditional NSAIDs. The NSAID most frequently involved in admissions for GI complications is aspirin and consequently at-risk patients receiving this drug should also receive antisecretory agents. Cotherapy consisting of proton pump inhibitors with double antiplatelet therapy is highly frequent in Spain, which has been associated with a low incidence of upper GI bleeding, and a growing incidence of patients with lower GI bleeding usually due to pre-existing vascular lesions. Another therapeutic tool that has been proposed to reduce the occurrence of upper GI bleeding in patients taking aspirin is Helicobacter pylori eradication therapy. The most recent data show that eradication of H. pylori infection in patients with a previous peptic ulcer bleeding episode who continue to take aspirin reduces the recurrence rate of this complication to levels observed in patients without a history of ulcer bleeding history who take aspirin for cardiovascular disease.


Antioxidant activity of Citrus paradisi seeds glyceric extract.
The antioxidant activity of Citrus paradisi (grapefruit) seeds glyceric extract dissolved in ethanol and in aqueous media was evaluated using three different methods: evaluation by DPPH assay, by 5-lipoxygenase assay and by luminol/xanthine/xanthine oxidase chemiluminescence assay. The total phenolic content was determined by the Prussian Blue method opportunely modified. The grapefruit seeds glyceric extract utilized as aqueous solutions demonstrated antioxidant properties better than those displayed by alcoholic solutions.


Estrogen receptor beta genetic variants and combined oral contraceptive use as relates to the risk of hypertension in Chinese women.
Estrogen receptor beta (ESR2) plays an important role in cardiovascular physiology and blood pressure regulation, whereas estrogens may influence gene expression, growth, and cellular differentiation in target tissues by activating estrogen receptors. This study aims to investigate the association between common genetic variants of ESR2 gene and the risk of hypertension and to explore the combined effected of ESR2 variants and combined oral contraceptive (COC) use for hypertension risk. A population-based case-control study was conducted in 621 female hypertensive patients and 621 female normotensive controls. ESR2 G1082A heterozygote genotype (GA) was in significant relationship with hypertension (crude odds ratio [OR] = 1.38, 95% CI: 1.09-1.76; adjusted odds ratio [OR] = 1.38, 95% CI: 1.09-1.76). No association was observed for ESR2 G1730A polymorphism. Furthermore, the joint effects of the heterozygote of G1082A polymorphism (heterozygote model: GG/AA vs. GA) and cumulative COC use time ≥15 years significantly increased the risk of hypertension [adjusted odds ratio (OR) = 2.19, 95% CI: 1.49-3.24], and the interaction effects between those two risk factors were significant (p = 0.0001). The heterozygote GA genotype of ESR2 gene G1082A polymorphism may be a risk genotype for hypertension in Chinese women, and the GA genotype (heterozygote model: GG/AA vs. GA) of G1082A locus together with COC use simultaneously contributed to hypertension development.


Distinct regions of the cadherin cytoplasmic domain are essential for functional interaction with Galpha 12 and beta-catenin.
Heterotrimeric G proteins of the G(12) subfamily mediate cellular signals leading to events such as cytoskeletal rearrangements, cell proliferation, and oncogenic transformation. Several recent studies have revealed direct effector proteins through which G(12) subfamily members may transmit signals leading to various cellular responses. Our laboratory recently demonstrated that Galpha(12) and Galpha(13) specifically interact with the cytoplasmic domains of several members of the cadherin family of cell adhesion molecules (Meigs, T. E., Fields, T. A., McKee, D. D., and Casey, P. J. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 519-524). This interaction causes beta-catenin to release from cadherin and relocalize to the cytoplasm and nucleus, where it participates in transcriptional activation. Here we report that two distinct regions of the epithelial cadherin (E-cadherin) tail are required for interaction with beta-catenin and Galpha(12), respectively. Deletion of an acidic, 19-amino acid region of E-cadherin abolishes its ability to bind beta-catenin in vitro, to inhibit beta-catenin-mediated transactivation, or to stabilize beta-catenin; causes subcellular mislocalization of beta-catenin; and disrupts cadherin-mediated cell adhesion. On the other hand, deletion of a distinct 11-amino acid region of E-cadherin dramatically attenuates interaction with Galpha(12); furthermore, Galpha(12) is ineffective in stimulating beta-catenin release from an E-cadherin cytoplasmic domain lacking this putative Galpha(12)-binding region. These findings indicate that Galpha(12) and beta-catenin do not compete for the same binding site on cadherin and provide molecular targets for selectively disrupting the interaction of these proteins with cadherin.


Beliefs about menopause of general practitioners and mid-aged women.
Recent general population studies suggest that experience of the normal menopause transition is relatively unremarkable for the majority of women, but negative stereotyped beliefs about menopause remain pervasive. This study explored GPs' beliefs and opinions about menopause in general, and compared the GPs' beliefs with those of their mid-aged female patients. All GPs at five general practices (n = 24) and 101 45-year-old women registered at the same practices took part. Large proportions of both groups believed that most women experience somatic and psychological difficulties during menopause. GPs expressed more negative beliefs than patients but were also more likely to express positive/neutral beliefs. Some causal attributions of menopausal problems were shared by the two groups, but they differed on others. When both GPs and patients hold negative social stereotypes about menopause, problems of mid-aged women may be misattributed to menopause. Health information on menopause may be biased towards negative images of menopause and of aging women.


Increased fertilization and pregnancy rate in polypronuclear fertilization cycles in in vitro fertilization-embryo transfer.
To compare fertilization and pregnancy rates between cycles with polypronuclear fertilizations and cycles with normal fertilizations. In vitro fertilization-embryo transfer (IVF-ET) cycles in which oocytes were retrieved were divided into two groups according to the nature of fertilization. All patients were participants of our IVF-ET program. A significantly higher fertilization rate was found in the polypronuclear fertilization cycles (61% versus 36.6%) and also an improved pregnancy rate (47.5% versus 19.6%) and per embryo transfers (53% versus 28.8%). The vast majority of polypronuclear fertilizations occurred in mature oocytes. We believe that the increased receptability of the oocytes improves fertilization and conception rates. The polypronuclear fertilization is an extreme expression of such improved receptibility and should be considered as an encouraging sign for conception.


[Value of prolactin determination in oligozoospermia].
Serum levels of prolactin were determined in 181 patients with idiopathic oligozoospermia, in order to find out a possible interference of hyperprolactinemia and disturbed spermatogenesis. In 4 cases hyperprolactinemia was found. Suppression of prolactin levels by bromocriptine in those cases did not result in an increase of spermatogenetic activity. From these data it can be concluded that hyperprolactinemia plays no significant role in idiopathic oligozoospermia. The value of determination of serum levels of prolactin remains questionable.


A flow cytometric assay of CD34-positive cell populations in the bone marrow.
CD34+ BM cells form a heterogenous population of primitive stem cells and more mature progenitors committed to different lineages of differentiation. By combining CD45 expression with SSC, it is possible to separate immature cells from more differentiated BM cells, and, by three-colour flow cytometry, analyse the antigens expressed in various subsets of cells. In this paper we show that in the normal BM at least four distinct CD34+ cell populations can be identified by their different patterns of CD45 expression and SSC. The most immature CD34+ cell population (0.1% of the BM cellularity) lacked all signs of lineage commitment and was CD45RA negative and only weakly CD45 positive. With increasing expression of the CD45 antigens, a second CD34+ population (0.2% of the BM cellularity) was formed expressing mainly primitive lymphatic antigens. However, 30% of the cells co-expressed B-cell line antigens and myeloid antigens. Cells committed to the myeloid cell line lost B-cell line antigens, gained CD45 antigen expression and SSC and formed two CD34+ cell populations (0.2% and 0.1% of the BM cellularity, respectively) differing only with respect to the pattern of myeloid antigen expression and SSC characteristics. Similarly, differentiation along the lymphatic pathway implicated down-regulation of myeloid antigens, loss of the stem cell antigen and immature lymphatic antigens and gain of CD45 expression and mature lymphatic antigens.


Looking within the household: gender roles and responses to malaria in Ghana.
Studies of factors affecting treatment-seeking behaviour for malaria have rarely considered the influence of gender roles and relations within the household. This study supported district-level government workers in the Volta Region of Ghana in conducting a situational analysis of gender inequities in relation to the malaria burden and access to healthcare services for malaria in one community in their district. Qualitative and participatory methods, such as focus group discussions, in-depth individual interviews and ranking exercises, were used. The study found that women who lacked either short- or long-term economic support from male relatives, or disagreed with their husbands or family elders about appropriate treatment-seeking, faced difficulties in accessing health care for children with malaria. This illustrates the significant influence of women's access to resources and decision-making power on treatment-seeking behaviour for children with febrile illnesses, and the importance of approaching malaria management in the community or household from a gender perspective.


Vaccines for other neonatal infections: neonatal BCG vaccination against tuberculosis.
This section focuses on current progress in the use of vaccines against a range of other infectious agents, both bacterial (pertussis, pneumococcus and group B streptococcus) and mycobacterial (bacille Calmette-Guérin) to prevent neonatal infection.


FGF-2 stimulation affects calvarial osteoblast biology: quantitative analysis of nine genes important for cranial suture biology by real-time reverse transcription polymerase chain reaction.
Appropriately timed closure of the cranial sutures is a critical factor in normal postnatal morphogenesis of the cranial vault. Suture patency is necessary to permit rapid neonatal expansion of the cerebral hemispheres, and later ossification is important for bony protection of the cerebrum. Premature suture ossification (craniosynostosis) leads to myriad adverse functional and developmental consequences. Several murine studies have implicated dura-derived fibroblast growth factor-2 (FGF-2) paracrine signaling as a critical factor promoting physiologic posterior frontal suture fusion. In this study, the authors used real-time reverse transcription polymerase chain reaction (RT-PCR) to study an in vitro system that models the in vivo stimulation of suture calvarial osteoblasts by dura-derived FGF-2. The authors advocate real-time RT-PCR as a powerful and rapid technique that offers advantages in the highly sensitive, specific, and reproducible analyses of nine genes known to be important in cranial suture biology. The genes studied were growth factors [FGF-2, transforming growth factor (TGF)-beta 1, TGF-beta 2, and TGF-beta 3], growth factor receptors (FGF-R1, FGF-R2, TGF-beta RI, and TGF-beta RII), and a marker of osteoblast differentiation (Co1-I alpha I). These analyses provide a "snapshot" of several important genes involved in suture fusion that is more inclusive and quantitative than that which has been previously reported.


HealthMarts, HIPCs (health insurance purchasing cooperatives), MEWAs (multiple employee welfare arrangements), and AHPs (association health plans): a guide for the perplexed.
This paper considers how pending proposals to authorize new forms of group purchasing arrangements for health insurance would fit and function within the existing, highly complex market and regulatory landscape and whether these proposals are likely to meet their stated objectives and avoid unintended consequences. Cost savings are more likely to result from increased risk segmentation than through true market efficiencies. Thus, these proposals could erode previous market reforms whose goal is increased risk pooling. On the other hand, these proposals contain important enhancements, clarifications, and simplification of state and federal regulatory oversight of group purchasing vehicles. Also, they address some of the problems that have hampered the performance of purchasing cooperatives. On balance, although these proposals should receive cautious and careful consideration, they are not likely to produce a significant overall reduction in premiums or increase in coverage.


Sequence diversity of the haemagglutinin open reading frame of recent highly pathogenic avian influenza H5N1 isolates from Egypt.
The sequences encoding the haemagglutinin (HA) of twelve H5N1 isolates obtained in 2006 and 2007 from different avian species in backyard holdings and poultry farms in Egypt revealed amino acid variations across the polypeptide and also in the polybasic cleavage motif of three of the isolates from backyard poultry with one, so far, unique mutation in an isolate from a chicken. The HAs of two isolates (A/goose/Egypt/R4/2007, A/chicken/Egypt/R3/2007) collected on the same day in the same village from two neighbouring houses were found to differ from each other. Five out of the seven nucleotide exchanges in these two isolates were translationally silent, and two resulted in amino acid substitutions: one in the polybasic cleavage motif and the other in the signal peptide. Circulation of different H5N1 strains possessing considerable variations in backyard poultry, particularly domestic waterfowl, draws attention to the evolution of H5N1 subtypes in Egypt.


Problem-solving skills training for mothers of children recently diagnosed with autism spectrum disorder: A pilot feasibility study.
Problem-solving skills training is an intervention designed to teach coping skills that has shown to decrease negative affectivity (depressive symptoms, negative mood, and post-traumatic stress symptoms) in mothers of children with cancer. The objective of this study was to see whether mothers of children recently diagnosed with autism spectrum disorder would be receptive to receiving problem-solving skills training (feasibility trial). Participants were recruited from a local outpatient developmental clinic that is part of a university department of pediatrics. Participants were to receive eight 1-h sessions of problem-solving skills training and were asked to complete assessments prior to beginning problem-solving skills training (T1), immediately after intervention (T2), and 3 months after T2 (T3). Outcome measures assessed problem-solving skills and negative affectivity (i.e. distress). In total, 30 mothers were approached and 24 agreed to participate (80.0%). Of them, 17 mothers completed problem-solving skills training (retention rate: 70.8%). Mothers of children with autism spectrum disorder who completed problem-solving skills training had significant decreases in negative affectivity and increases in problem-solving skills. A comparison to mothers of children with cancer shows that mothers of children with autism spectrum disorder displayed similar levels of depressive symptoms but less negative mood and fewer symptoms of post-traumatic stress. Data suggest that problem-solving skills training may be an effective way to alleviate distress in mothers of children recently diagnosed with autism spectrum disorder. Data also suggest that mothers of children with autism spectrum disorder were moderately receptive to receiving problem-solving skills training. Implications are that problem-solving skills training may be beneficial to parents of children with autism spectrum disorder; modifications to improve retention rates are suggested.


The interaction between the effects of insulin and ouabain on the activity of Na transport system in frog skeletal muscle.
The effects of insulin and ouabain on 22Na efflux and net Na loss were examined in frog sartorius muscles. After removal of ouabain, 22Na efflux which had been inhibited by ouabain remained at the inhibited level for more than 2 hr. In ouabain-free solution, insulin stimulated the Na efflux from ouabain-preincubated muscles. The stimulating effect of insulin on 22Na efflux was completely blocked by the presence of ouabain. Insulin shifted the Na efflux vs. intracellular Na concentration relationship toward the region of lower Na concentrations, and made the slope of log (Na efflux) vs. log [Na]1 relationship less step. On the other hand, ouabain shifted the Na efflux vs. intracellular Na concentration relationship toward the region of higher Na concentration, and made the slope of the log (Na efflux) vs. log [Na]1 relationship steeper. The relationship between insulin-stimulated Na efflux and intracellular Na concentration obtained from ouabain-preincubated muscle was located in the region of higher Na concentrations than that obtained from control muscle. These findings suggest that insulin increases an apparent affinity of binding sites for Na ions, and the possibility that insulin increases the Vmax of Na transport system may be excluded. In contrast with the effect of insulin, ouabain may be considered to decrease the apparent affinity of binding site for Na ions.


Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis.
Multiple signalling pathways are involved in the mechanism by which insulin stimulates hepatic glycogen synthesis. In this study we used selective inhibitors of glycogen synthase kinase-3 (GSK-3) and an allosteric inhibitor of phosphorylase (CP-91149) that causes dephosphorylation of phosphorylase a, to determine the relative contributions of inactivation of GSK-3 and dephosphorylation of phosphorylase a as alternative pathways in the stimulation of glycogen synthesis by insulin in hepatocytes. GSK-3 inhibitors (SB-216763 and Li+) caused a greater activation of glycogen synthase than insulin (90% vs. 40%) but a smaller stimulation of glycogen synthesis (30% vs. 150%). The contribution of GSK-3 inactivation to insulin stimulation of glycogen synthesis was estimated to be less than 20%. Dephosphorylation of phosphorylase a with CP-91149 caused activation of glycogen synthase and translocation of the protein from a soluble to a particulate fraction and mimicked the stimulation of glycogen synthesis by insulin. The stimulation of glycogen synthesis by phosphorylase inactivation cannot be explained by either inhibition of glycogen degradation or activation of glycogen synthase alone and suggests an additional role for translocation of synthase. Titrations with the phosphorylase inactivator showed that stimulation of glycogen synthesis by insulin can be largely accounted for by inactivation of phosphorylase over a wide range of activities of phosphorylase a. We conclude that a signalling pathway involving dephosphorylation of phosphorylase a leading to both activation and translocation of glycogen synthase is a critical component of the mechanism by which insulin stimulates hepatic glycogen synthesis. Selective inactivation of phosphorylase can mimic insulin stimulation of hepatic glycogen synthesis.


The relationship between attachment, personality and antisocial tendencies in a prison sample: a pilot study.
This study examined the role of adult attachment and personality in relation to antisocial tendencies (i.e. convictions for violence and interpersonal problems in romantic relationships) in Norwegian prison inmates (N=92). Attachment styles and personality were measured using self-report questionnaires (RSQ; Griffin & Bartholomew, 1994; and NEO-FFI, Costa & McCrae, 1992a). The prison inmates scored higher on avoidant than on anxious attachment style. While age and agreeableness (negatively associated) emerged as significant predictors of violence, anxious attachment explained most of the variances in aggression in intimate relationships. The study suggests that different types of antisocial tendencies could have different attachment and general personality correlates.


Different mechanisms in the attachment of cells to native and denatured collagen.
The attachment of cells to collagen has been reported previously to require the presence of serum and the particular serum protein involved in this process, variously known as CIG, CAP or fibronectin, has been isolated. This conclusion that cell attachment to collagen requires serum (or more precisely, fibronectin) is based on experiments measuring the kinetics of cell attachment to films of collagen. We have measured the kinetics of attachment of HeLa and attachment to films of collagen-containing substrata under a variety of experimental conditions and present evidence that the serum-dependent mechanism of cell attachment described by others is actually only the case for films of denatured collagen, while cell attachment to native collagen fibres occurs by a different, serum-independent, mechanism. The possible relevance of these findings to cell-matrix interactions in vivo is discussed.


Antibiotic misuse in medium-sized Swiss hospitals.
Antibiotics account for a substantial proportion of hospital drug expenditures and tend to be misused or overused, generating unnecessary costs and causing the emergence of resistant bacteria. Antibiotic use was evaluated in a one-day prevalence study performed on the surgical and medical wards of eight Swiss non-university hospitals. 173 of the 695 inpatients present (25%) were on antibiotics and 163 could be evaluated. 35 prescriptions were secondary to an infectious disease consultation. 60 of the remaining 128 (47%) were considered inappropriate, of which 17 (28%) lacked any indication for antibiotic use. The rates of misuse were higher in surgery than in medicine (58 vs. 34%; OR = 2.5 [95% CI: 1.1-5.9]), and higher for prophylaxis than for treatment (72 vs. 41%; OR = 4.1 [95% CI: 1.3-15.5]). Savings of 545 euros (95% CI: from -116 to 1,206 euros) on the study day and 6,256 euros (95% CI: from -2,221 to 14,732 euros) for the total treatments or prophylaxis administered would have resulted from infectious disease consultations.


"Peak tracking chip" for label-free optical detection of bio-molecular interaction and bulk sensing.
A novel imaging method for bulk refractive index sensing or label-free bio-molecular interaction sensing is presented. This method is based on specially designed "Peak tracking chip" (PTC) involving "tracks" of adjacent resonant waveguide gratings (RWG) "micropads" with slowly evolving resonance position. Using a simple camera the spatial information robustly retrieves the diffraction efficiency, which in turn transduces either the refractive index of the liquids on the tracks or the effective thickness of an immobilized biological layer. Our intrinsically multiplex chip combines tunability and versatility advantages of dielectric guided wave biochips without the need of costly hyperspectral instrumentation. The current success of surface plasmon imaging techniques suggests that our chip proposal could leverage an untapped potential to routinely extend such techniques in a convenient and sturdy optical configuration toward, for instance for large analytes detection. PTC design and fabrication are discussed with challenging process to control micropads properties by varying their period (step of 2 nm) or their duty cycle through the groove width (steps of 4 nm). Through monochromatic imaging of our PTC, we present experimental demonstration of bulk index sensing on the range [1.33-1.47] and of surface biomolecule detection of molecular weight 30 kDa in aqueous solution using different surface densities. A sensitivity of the order of 10(-5) RIU for bulk detection and a sensitivity of the order of ∼10 pg mm(-2) for label-free surface detection are expected, therefore opening a large range of application of our chip based imaging technique. Exploiting and chip design, we expect as well our chip to open new direction for multispectral studies through imaging.


Parental involvement and mental well-being of Indian adolescents.
This study examined the association between parental involvement and mental well being among the 6721 school going adolescents aged 13 to 15 years who participated in Indias nationally representative Global School based Student Health Survey (GSHS) in 2007. Parental involvement (homework checking, parental understanding of their childrens problems, and parental knowledge of their childrens freetime activities) was reported by students to decrease with age, while poor mental health (loneliness, insomnia due to anxiety, and sadness and hopelessness) increased with age. Age adjusted Logistic regression models showed that high levels of reported parental involvement were significantly associated with a decreased likelihood of poor mental health.


Expression of mRNA encoding basic fibroblast growth factor (bFGF) in bovine corpora lutea and cultured luteal cells.
A radiolabelled cRNA was synthesized using a 1.4 kb cDNA complementary to mRNA encoding bovine basic fibroblast growth factor (bFGF) as a template, and used as a probe to investigate the expression of mRNA encoding bFGF in bovine ovarian tissue, and luteal cells in primary culture. Northern analysis of poly(A +)RNA prepared from follicles and corpora lutea of various stages revealed a major mRNA species of 7 kb in corpora lutea of all stages, the amount of which was higher late in the luteal phase. No hybridizable message was detectable in follicles of any size. When luteal cells were established in primary culture, expression of the 7 kb mRNA species was maintained. This expression was increased markedly when cells were treated with LH/hCG or Bt2cAMP. Prostaglandin F-2 alpha treatment caused a marked decrease in the basal content of this 7 kb mRNA, and also severely impaired the ability of LH to stimulate this expression.


Japan's Support of Hemodialysis in Southeast Asia.
With continuing economic development in the developing countries of Southeast Asia, the numbers of dialysis facilities and patients are increasing every year. However, dialysis-related devices tend to be provided with financial support from developed countries and/or donations from nonprofit organizations, and some donated devices are disposed of, without attempts at repair, when they break down. Device management and dialysate quality can also be problematic. To help address these issues, Japan started to provide technical guidance and support for dialysate purification in these countries. As a result, dialysate quality improved and local medical staff can now perform dialysis therapy using purified dialysate. At the same time, education was provided to staff, and their improved knowledge and skills have contributed to appropriate device maintenance, ensuring the dialysate used is of sufficient quality. Currently, approaches for human resource development are being actively provided in these countries through cooperation with local academic societies or other organizations in the field. Key Messages: A review of the current status of management of dialysis-related devices and dialysate quality in developing countries reveals that financial support and donations for medical devices alone are insufficient and the development of local human resources is crucial. Nurturing and training of clinical engineers, who directly operate today's advanced medical devices for patients, as well as device maintenance and management are urgent issues to address.


Association of preexisting medical conditions with in-hospital mortality in multiple-trauma patients.
Mortality after trauma has been shown to be influenced by host factors, such as age and preexisting medical conditions (PMCs). The independent predictive value of specific PMCs for in-hospital mortality after adjustment for injury severity, injury pattern, age, and presence of other PMCs has not been fully elucidated. Records of 11,142 trauma patients (18 years of age or older, Injury Severity Score > or = 16, years 2002 to 2007) documented in the Trauma Registry of the German Society for Trauma Surgery were analyzed to assess the association of PMCs with in-hospital mortality. Multiple logistic regression models were used for this analysis. PMCs were affirmed for 3,836 of the 11,142 patients studied (34.4%). An independent statistical association with increased in-hospital mortality was found for 6 of 14 analyzed PMCs after adjustment for age and the Revised Injury Severity Classification score, respectively, ie, heart disease, obesity, hepatitis/liver cirrhosis, malignancies, coagulation disorder, and peripheral arterial occlusive disease stage IV. The association with mortality varied with different injury patterns. Specific PMCs were associated with increased mortality after trauma independent from injury severity and age. Knowledge of the identified relevant PMCs could help the medical team to be able to assess the mortality risk profile of trauma patients in a more detailed and quantifiable way.


Neonatal tuberculosis.
Tuberculosis remains a prevalent disease worldwide, with approximately 9 million cases diagnosed annually. The emergence of multidrug-resistant tuberculosis has proven to be a challenging international public health issue. In the United States, however, the incidence of tuberculosis has been decreasing since 1992. There were just over 9,500 reported cases in 2013, and almost 500 of those were in children younger than age 15 years. Foreign-born persons are a high-risk group and account for 65% of new cases annually. Other high-risk groups include ethnic minorities, HIV-infected patients, and people living in low-socioeconomic urban areas.


A strategic dosing scheme for the control of fasciolosis in cattle and sheep in Ireland.
This study examined the effectiveness of a strategic dosing scheme in lowering the incidence of fasciolosis on a mixed dry-stock farm and in maintaining the reduced incidence following a reduction in dosing intensity. Two neighbouring farms with a history of chronic fluke disease were selected, the strategic dosing scheme being implemented on one (the trial farm) while the other (the control farm) continued to treat according to its normal practice. The strategic dosing scheme was designed to suppress the faecal egg output of Fasciola hepatica at critical times of the year in order to limit infection of the intermediate host snail population and thus reduce the subsequent contamination of the pasture with metacercariae. On the trial farm cattle and sheep were treated three times per year for the first 2 years at approximately 8 week intervals, starting in March of each year. A fourth treatment was given when the cattle were housed and out-wintered sheep received an additional treatment in January. In Years 3 and 4 the dosing intensity was reduced. By the end of Year 2, data from faecal egg counts, tracer-sheep fluke burdens and snail infection levels indicated that the treatment strategy had succeeded in suppressing the fluke population and eliminating the occurrence of clinical fasciolosis. The decrease in dosing intensity in Years 3 and 4 maintained both stock and snail infections at low levels and there was no re-emergence of the disease.


Decreased expression of RPS15A suppresses proliferation of lung cancer cells.
Lung cancer is the leading cause of cancer-related death in the world. Previous report has identified ribosomal protein s15a (RPS15A) as a TGF-β-responsible gene in the lung adenocarcinoma cell line A549. In this study, we used specific si-RNA to downregulate RPS15A expression in A549 cells and found that decreased RPS15A expression significantly inhibited cell proliferation and survival, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Moreover, A549 cells were obviously accumulated in the G0/G1 phase in response to RPS15A knockdown, suggesting that RPS15A inhibition could induce a diminution of proliferation through cell cycle arrest. In addition, immunohistochemistry analysis further revealed that RPS15A was overexpressed in surgically resected lung cancer tissues. In conclusion, we identify RPS15A as a novel potential oncogenic gene involved in lung carcinogenesis. This study may provide a preliminary experimental basis for a gene therapy approach for treating lung cancer.


Phacoemulsification--why?
When a new operation replaces an old, it must be better, not just equally good. The Kelman method of cataract extraction has given impressive results in patients under the age of 30 years. However, for senile cataracts it is not better, the hospital stay is not shortened, and the recovery time is directly proportional to the age of the patient and to the preoperative condition of the eye, not to the type of extraction. Phacoemulsification is a cataract extraction and, therefore, should receive exactly the same monetary reward. No comparative series of cases done by the same surgeon or surgeons of equal skill has demonstrated that the Kelman phacoemulsification procedure is accompanied by fewer retinal detachments, Irvine-Gass syndromes, or other postoperative complications. The Kelman phacoemulsification method should be an adjunct to, and not a replacement for, the current intracapsular cataract extraction.


Continuous ambulatory peritoneal dialysis and clinical outcomes in patients with refractory congestive heart failure.
Peritoneal dialysis has been proposed as a therapeutic alternative for patients with refractory congestive heart failure. The objective of this study was to assess its effect on long-term clinical outcomes in patients with advanced heart failure and renal dysfunction. A total of 62 patients with advanced heart failure (class III/IV), renal dysfunction (glomerular filtration<60 mL/min/1.73 m(2)), persistent fluid congestion despite loop diuretic treatment and at least 2 previous hospitalizations for heart failure were invited to participate in a continuous ambulatory peritoneal dialysis program. Of these, 34 patients were excluded and adjudicated as controls. The most important reasons for exclusion were refusal to participate, inability to perform the technique and abdominal wall defects. The primary endpoint was all-cause mortality and the composite of death/readmission for heart failure. To account for baseline imbalance, a propensity score was estimated and used as a weight in all analyses. The peritoneal dialysis (n=28) and control groups (n=34) were alike in all baseline covariates. During a median follow-up of 16 months, 39 (62.9%) died, 21 (33.9%) patients were rehospitalization for heart failure, and 42 (67.8%) experienced the composite endpoint. In the propensity score-adjusted models, peritoneal dialysis (vs control group) was associated with a substantial reduction in the risk of mortality using complete follow-up (hazard ratio=0.40; 95% confidence interval, 0.21-0.75; P=.005), mortality using days alive and out of hospital (hazard ratio=0.39; 95% confidence interval, 0.21-0.74; P=.004) and the composite endpoint (hazard ratio=0.32; 95% confidence interval, 0.17-0.61; P=.001). In refractory congestive heart failure with concomitant renal dysfunction, peritoneal dialysis was associated with long-term improvement in clinical outcomes. Full English text available from:www.revespcardiol.org.


IgG avidity to distinguish secondary from primary measles vaccination failures: prospects for a more effective global measles elimination strategy.
The nearly 40-year long debate on the relevance of secondary measles vaccination failure has been inconclusive because a feasible method for the assessment of the duration of immunity has been lacking. Even if a two-dose measles vaccination policy is now universally endorsed, WHO still officially adheres to the view that a single successful measles vaccination, without natural boosters, induces a lifelong immunity and deems secondary failures epidemiologically irrelevant - in the belief that the latter are rare and do not participate in the transmission chain. A recently published study on measles-IgG avidity, which allows for separation of secondary from primary vaccination failures, tentatively showed that the official view does not necessarily hold true. The results may have wide implications on global measles eradication efforts. The potential of IgG avidity measurement in complex postvaccination measles epidemiology is discussed.


Hypercalcemia following renal transplantation in a cat.
An 11-year-old 3.0-kg (6.6-lb) neutered male Persian was referred for renal transplantation. Serum total calcium concentration was slightly high prior to surgery, but the week after surgery, total and ionized calcium concentrations were extremely high, and a small mass was palpable on the right side of the trachea at the level of the thyroid and parathyroid glands. Exploratory surgery of the ventral aspect of the neck was performed, and a right external parathyroid mass was removed. One hour after surgery, the serum ionized calcium concentration was within reference limits, and the serum calcium concentration remained normal for the next 14 months without any specific treatment. The gross and histologic appearance of the mass, combined with the rapid decrease in serum calcium concentration following its removal, confirmed that the mass was a functional parathyroid adenoma. Although a common postoperative complication in people, hypercalcemia following renal transplantation appears to be a rare complication in cats. Surgery should be considered if the condition is a result of a parathyroid adenoma.


The molecular defect leading to Fabry disease: structure of human alpha-galactosidase.
Fabry disease is an X-linked lysosomal storage disease afflicting 1 in 40,000 males with chronic pain, vascular degeneration, cardiac impairment, and other symptoms. Deficiency in the lysosomal enzyme alpha-galactosidase (alpha-GAL) causes an accumulation of its substrate, which ultimately leads to Fabry disease symptoms. Here, we present the structure of the human alpha-GAL glycoprotein determined by X-ray crystallography. The structure is a homodimer with each monomer containing a (beta/alpha)8 domain with the active site and an antiparallel beta domain. N-linked carbohydrate appears at six sites in the glycoprotein dimer, revealing the basis for lysosomal transport via the mannose-6-phosphate receptor. To understand how the enzyme cleaves galactose from glycoproteins and glycolipids, we also determined the structure of the complex of alpha-GAL with its catalytic product. The catalytic mechanism of the enzyme is revealed by the location of two aspartic acid residues (D170 and D231), which act as a nucleophile and an acid/base, respectively. As a point mutation in alpha-GAL can lead to Fabry disease, we have catalogued and plotted the locations of 245 missense and nonsense mutations in the three-dimensional structure. The structure of human alpha-GAL brings Fabry disease into the realm of molecular diseases, where insights into the structural basis of the disease phenotypes might help guide the clinical treatment of patients.


Incorporation and metabolism of punicic acid in healthy young humans.
The objective of this study was to investigate the incorporation and metabolism of punicic acid (PA, cis9,trans11,cis13-18:3) in healthy young humans. The study was a randomized controlled trial. After 7 days adaptation with sunflower seed kernels supplementation, 30 subjects were then divided into the control and test group (n = 15). The test group was supplemented with Trichosanthes kirilowii (TK) seed kernels containing 3 g of PA per day in the form of triacylglycerols for 28 days. The control group was provided with sunflower seed kernels. After consumption of TK seeds containing 3 g PA per day for 28 days, the proportion of PA was increased from 0.00 to 0.47% in plasma and 0.00 to 0.37% in red blood cell membranes (RBCM), respectively. The proportion of cis9,trans11-18:2 was increased from 0.05 to 0.23% in plasma and 0.03 to 0.17% in RBCM after 28 days of intervention, respectively. Our results suggest that PA can be effectively incorporated into human plasma and RBCM, and is also associated with the increasing proportion of cis9,trans11-18:2 in humans, presumably as a result of metabolism by a saturation reaction. Edible TK seeds could be a potential dietary source of conjugated linoleic acids.


Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression.
Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.


Expression of neurotransmitters and neurotrophins in human adenoid tissue.
Mucosae-associated lymphoid tissues are richly innervated and the mucosae contain peptidergic nerve endings associated with different types of cells and macrophages. The lymphatic tissue is known to interact with the nervous system and several organs, implicated in the host response to a wide range of stressors, and is also richly innervated. We focussed our attention on the immune organs with particular regard to the human adenoid lymphatic tissues in order to investigate the neuroimmune links and the possible existence of relationships among different neurotransmitters and lymphocytes, macrophages, epithelial cells and nerve fibers by testing the expression of certain neurotransmitters and neurotrophins (NTs) with their own receptors.


Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trial.
Curcuma longa L. (CL), an Indian herb, has been used to treat many disorders because of its wide spectrum of pharmacological activities. It has been shown to exhibit anti-oxidant and anti-inflammatory properties, and is being used as herbal remedy since ancient times. Osteoarthritis of knee (KOA) is a chronic painful disorder in which prolong use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids may result into many serious side effects; hence, there is a need to develop herbal drugs, having good analgesia without side effects. Therefore, we planned to evaluate the efficacy of CL in KOA. The study was designed as a randomized, double-blind, placebo-controlled trial in patients of KOA. After obtaining ethical clearance and written informed consent, a total of 160 patients of KOA were randomly enrolled into two groups to receive either CL extract or placebo along with the standard drug regimen. The patients were assessed on day 0, day 60, and day 120. On the days of their visit, the clinical prognosis was assessed by visual analog scale (VAS) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index. On these days, the radiographs were also taken for Kellgren and Lawrence grading and blood samples were collected for assessing the changes in levels of IL-1β and biomarkers of oxidative stress, such as reactive oxygen species and malondialdehyde (MDA). Over all significant improvement was observed in the patients of CL extract group as compared to placebo group. Clinically, the VAS and WOMAC scores became better, and simultaneously, the levels of biomarkers, viz., IL-1β, ROS, and MDA, were also significantly (p < 0.05) improved. It may be concluded that on chronic administration, CL suppresses inflammation and brings clinical improvement in patients of KOA, which may be observed by decreased level of IL-1β and VAS/WOMAC scores, respectively. At the same time, CL decreases the oxidative stress also.


Laparoscopic cholecystectomy: early Mayo Clinic experience.
Prospective data and follow-up information were collected on the initial 200 patients who underwent laparoscopic cholecystectomy at the Mayo Clinic. The operation was completed laparoscopically in all but five patients, who required conversion to laparotomy because of dense scarring or stones in the common bile duct. The median surgical time was 85 minutes. The major postoperative complications were retained stones in the common bile duct (in seven patients), intraperitoneal hemorrhage that necessitated transfusion (in two patients), and intra-abdominal abscess and pulmonary infection (in one patient each). The median hospital stay was 1 day (range, 0 to 8 days), and the median times to full activity and normal employment were 8 days and 12 days, respectively. Laparoscopic cholecystectomy is associated with a low frequency of complications in most patients with symptomatic gallstones and allows a rapid return to normal activity. Currently, laparoscopic cholecystectomy is the treatment of choice for most patients with symptomatic cholelithiasis.


Cannabinoid type 1 receptor gene polymorphism and macronutrient intake.
Cannabinoid type 1 receptor (CB1-R) is a key mediator in the control of food intake and is linked to obesity. To evaluate the relationship between CB1-R gene polymorphism and dietary macronutrient intake in elderly subjects. This study included 118 subjects (60 males, 58 females) from a population survey carried out in southern Italy in 1992-1993 who were older than 65 years and previously characterized for CB1-R polymorphism (75 with GG wild-type genotype, 41 with heterozygous polymorphic allele AG, and 2 with genotype AA). All subjects completed a validated semi-quantitative food frequency questionnaire. Statistical methods included multiple logistic regression to model macronutrient intake to genotype, controlling for potential confounders. When controlled for age, gender, and body mass index, the intake of dietary cholesterol and saturated fats corrected for calories was inversely associated with the CB1-R 1359 G/A polymorphism, while the intake of starchy carbohydrates was directly associated with this polymorphism. In our unselected elderly population, the 1359 G/A polymorphism is linked with a specific macronutrient intake. This could be explained by the role of the cannabinoid system as a determinant of food intake and eating behavior.


Cells regulate the activities of cytokines by glycosylation.
Cytokines, including the interferons, interleukins, colony stimulating factors, and chemokines, are first-line, hormone-like defense molecules that orchestrate immune functions in a nonspecific, i.e., antigen-independent, way. The multiplicity of cytokines has a genetic basis, but oligomerization and especially glycosylation add to the heterogeneity and signaling functions of the cytokines. It is theorized that the cell uses glycosylation of cytokines to alter its functions. This is achieved by changing the specific biological activities, by altering diffusability, tissue distribution, and pharmacokinetics, and by targeting different populations of responsive cells. One interesting possibility is that multiple glycosylation forms compete for receptor binding resulting in a natural selection process or possibly antagonistic effects. Cytokines as ligands often are multimers and cytokine receptors are almost without exception heterodimers, which within receptor families share common subunits. Hence, carbohydrate-lectin interactions might contribute to ligand dimerization and receptor recognition through multivalent bindings.


Structure and stability of beta-pleated sheets.
Beside alpha-helices, beta-sheets are the most common secondary structure elements of proteins. In this article, the question of structure and stability of parallel and antiparallel sheets of various lengths is addressed. All data obtained are compared to a selected set of protein structures. In antiparallel beta-sheets, one of the two possible H-bonded structures (containing 14 atoms in the H-bonded pseudoring) is energetically more favored and also more abundant in proteins than the other one (with 10 atoms involved in the pseudoring). Parallel beta-sheets and their subunits are energetically less stable and indeed found to occur more rarely in proteins. Antiparallel hairpins are disfavored compared to beta-sheets formed by sequentially separated strands. Agreement between theory and experimental data indicates that characterization of structural building blocks at an appropriately accurate level of theory is a useful tool to get insight into fundamentals of protein structure.


Isolated mitral replacement with stent-mounted antibiotic-treated aortic allograft valves.
The results of valve replacement with a stent-mounted antibiotic-treated aortic allograft valve are reported in 129 patients with isolated mitral valve disease. Of these patients, 70 per cent were in N.Y.H.A. Class IV. The hospital mortality rate was 3.9 percent. The cumulative complication-free rate at 5 years was only 37 percent as 21 percent died late, a further 15 percent were alive following reoperation, 4 percent had an embolic episode, 4 percent were alive with important incompetence, and 20 percent had unimportant incompetence. Proved valve failure was due mainly to detachment of the aortic wall remnant of the valve from the pillar of the rigid metal stent (16 percent incidence at 5 years) and methods for preventing this complication are discussed. Because of these complications the use of this device in the mitral position has been discontinued.


The steroid receptor antagonists RU40555 and RU486 activate glucocorticoid receptor translocation and are not excreted by the steroid hormones transporter in L929 cells.
RU40555 is a recently available glucocorticoid receptor (GR) antagonist that differs from RU486 by a methyl radical. We have used the mouse fibroblast cell line L929 to study the in vitro effects of RU40555 on GR translocation and function and on the membrane steroid hormones transporter. The results showed that: 1) RU40555 competed for the binding of labelled dexamethasone (Dex) with a K(i) of 2.4 nM; 2) both RU40555 and RU486 were equally potent inhibitors of Dex-induced GR-mediated gene transcription; 3) maximum GR translocation induced by micromolar concentrations of Dex and the GR antagonists was approximately 30-55% loss in the cytoplasmic GR and approximately 40-90% increase in the nuclear GR (assessed by GR immunostaining in cytoplasm and nucleus and western blots of immunoprecipitated GR protein in cytosolic and nuclear fractions) and was similar for the two antagonists; 4) at nanomolar concentrations, RU40555 and RU486 induced more GR translocation than Dex (assessed by [(3)H]Dex binding and western blot of immunoreactive GR in the same cytosolic homogenates); 5) blocking the steroids membrane transporter with verapamil (100 microM) in the presence of Dex (10 nM) increased GR translocation to levels similar to those induced by RU40555 (10 nM) and RU486 (10 nM) alone; 6) verapamil did not affect GR translocation in the presence of RU40555 or RU486. These data demonstrate similar quantitative effects on GR translocation by RU486 and the new GR antagonist, RU40555. Moreover, RU40555, like RU486, is an effective GR antagonist. Finally, there is no evidence that the intracellular concentrations of RU40555 or RU486 are regulated by the steroids membrane transporter in L929 cells.


Frequent additional tachyarrhythmias in patients with inappropriate sinus tachycardia undergoing sinus node modification: an important cause of symptom recurrence.
Symptom recurrence following sinus node modification (SNM) for inappropriate sinus tachycardia (IST) remains significant despite achieving acute procedural success. The impact of non-IST tachyarrhythmias on symptom recurrence remains poorly characterized. The objective was to determine the prevalence and nature of additional tachyarrhythmias preceding and following SNM for IST. Consecutive patients with IST undergoing SNM at the University of Pennsylvania were studied. SNM was initially performed using an anatomic approach targeting the superolateral crista terminalis under intracardiac echocardiographic guidance and later using an electrophysiologic approach, targeting the site of the earliest right atrial activation during maximum heart rate (HR) with isoproterenol infusion. An effort was made to shift the site more caudally until a decrease of >25% in resting HR was achieved, with a blunted response to isoproterenol and flattening of the P-wave axis in leads III and aVF. Patients were followed for arrhythmia recurrence. Tachyarrhythmias were documented with electrocardiographic monitoring and then characterized during EP study. Thirty-three patients underwent SNM and were followed for a mean of 2.0 ± 1.5 years. During follow-up, 27% developed a non-IST tachyarrhythmia and 18% developed recurrent IST. Additionally, 42% of patients had a non-IST tachyarrhythmia prior to SNM. Non-IST tachyarrhythmias are common in patients with IST before and after SNM. A major reason for symptom recurrence following SNM is development of a non-IST tachyarrhythmia. These tachyarrhythmias should be detected and treated to optimize patient outcomes.