Elastic, Conductive, and Mechanically Strong Hydrogels from Dual-Cross-Linked Aramid Nanofiber Composites.
Recent research on conductive hydrogels has revealed their potential for building advanced soft bioelectronic devices. Their mechanical flexibility, water content, and porosity approach those of biological tissues, providing a compliant interface between the human body and electronic hardware. Conductive hydrogels could be utilized in many soft tools such as neural electrodes, tactile interfaces, soft actuators, and other electroactive devices. However, most of the available conductive hydrogels exhibit weak mechanical properties, which hinders their application in durable biointegrated systems. Here, we report aramid nanofiber-based hydrogels providing a combination of high elasticity, strength, and electrical conductivity. Highly branched aramid nanofibers (ANFs) provide a robust three-dimensional (3D) framework resembling those in load-bearing soft tissues. When interlaced with poly(vinyl alcohol) (PVA) and cross-linked with both noncovalent and covalent interactions, the nanofiber composites exhibit a high water content of ∼76.4 wt %, strength of ∼7.5 MPa, ductility of ∼407%, and shape recovery of ∼99.5% under cyclic tensile stress of 0.3 MPa. Mobile ions impart a conductivity of ∼2 S/m to the hydrogels, enabling large-strain sensors with stable operation. In addition, the embedded silver nanoparticles afford broad-spectrum antimicrobial activities, which is favorable for medical devices. The versatility of aramid nanofiber-based composites suggests their further possibilities for functionalization and scalable fabrication toward sophisticated bioelectronic systems.


Guidelines for experimental design protocol and validation procedure for the measurement of heat resistance of microorganisms in milk.
Studies on the heat resistance of dairy pathogens are a vital part of assessing the safety of dairy products. However, harmonized methodology for the study of heat resistance of food pathogens is lacking, even though there is a need for such harmonized experimental design protocols and for harmonized validation procedures for heat treatment studies. Such an approach is of particular importance to allow international agreement on appropriate risk management of emerging potential hazards for human and animal health. This paper is working toward establishment of a harmonized protocol for the study of the heat resistance of pathogens, identifying critical issues for establishment of internationally agreed protocols, including a harmonized framework for reporting and interpretation of heat inactivation studies of potentially pathogenic microorganisms.


Technique of robotic assisted minimally invasive esophagectomy (RAMIE).
Minimally invasive esophagectomy (MIE) has gained popularity over the last two decades as an oncologically sound alternative to open esophagectomy. Robotic assisted minimally invasive esophagectomy (RAMIE) has been developed at few highly-specialized centers, and overall experience with this technique remains limited. Herein, we describe our overall approach to this operation and specific technical issues.


FUN AND GAMES: DESIGNING A GAMIFIED CENTRAL VENOUS CATHETERIZATION TRAINING SIMULATOR.
Gamification, or adding elements of games to training systems, has the potential to increase learner engagement and information retention. However, the use of gamification has yet to be explored in Central Venous Catheterization (CVC) trainers which teach a commonly performed medical procedure with high incidence rates. In order to combat these errors, a Dynamic Haptic Robotic Trainer (DHRT) was developed, which focuses on vessel identification and access. A DHRT+ system is currently under development that focuses on whole procedure training (e.g. sterilization and catheter insertion), including a gamified Graphical User Interface. The goal of this paper was to (1) develop a game-like, patient-centered interface to foster personalized learning and (2) understand the perceived utility of gamification for CVC skill development with expert doctors. This paper outlines some of the potential benefits and deficits of the use of gamification in medical trainers that can be used to drive simulation design.


Chemical Composition of Aromas and Lipophilic Extracts from Black Morel (Morchella importuna) Grown in China.
Morels (Morchella spp.) are valuable medicinal and edible mushrooms. In this study, chemical profiles of aromas and lipophilic extracts of black morel (Morchella importuna) grown in China were analyzed by gas chromatography/mass spectroscopy, along with the evaluation of antioxidant and antimicrobial activities for the lipophilic extracts. Sixty-five compounds in total were identified from the aromas, and 1-octen-3-ol was the main component for aromas of fresh (34.40%) and freeze-dried (68.61%) black morels, while the most abundant compound for the aroma of the oven-dried sample was 2(5H)-furanone (13.95%). From the lipophilic extracts, 29 compounds were identified with linoleic acid as the main compound for fresh (77.37%) and freeze-dried (56.46%) black morels and steroids (92.41%) as the main constituent for an oven-dried sample. All three lipophilic extracts showed moderate antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) with the IC50 values ranging 7.56 ∼ 17.52 mg/mL and 5.75 ∼ 9.73 mg/mL, respectively, and no obvious antimicrobial activity was observed for lipophilic extracts. The drying methods affect the chemical profile of black morel, and freeze-drying was favorable for retaining nutrients and morel smell. This is the first report on the aroma and lipophilic extracts of M. importuna grown in China.


Interface structures of gold nanoparticles on TiO2 (110).
Scanning transmission electron microscopy and density functional theory are used to characterize atomic structures of nanoscale heterointerfaces between gold nanoparticles and a TiO2 (110) surface. It is found that when the gold nanoparticle size is smaller than a few nanometers, gold atoms preferentially attach to specific sites on the TiO2 surface and thus form an epitaxial and coherent heterointerface. Conversely, as the gold size becomes larger, the gold-TiO2 interface loses lattice coherency in order to accommodate the large lattice mismatch between the two dissimilar crystals.


Susac syndrome: challenges in the diagnosis and treatment.
Susac syndrome is a disorder thought to be mediated by an autoimmune response towards endothelial cells, leading to a characteristic clinical triad of encephalopathy, visual disturbances due to branch arterial occlusions and sensorineural hearing impairment. Although it is a rare disease, three reasons make it important. First, given its variable presentation, Susac syndrome is underdiagnosed. Second, it is considered an important differential diagnosis in different neurological, psychiatric, ophthalmological and hearing disorders, and consequently is frequently misdiagnosed. Third, in many cases, Susac syndrome is diagnosed and treated late, with significant irreversible sequelae including dementia, blindness and hearing loss. Neuropathology findings derived from both Susac syndrome patient tissue and novel transgenic mouse models indicate cytotoxic CD8+ T cells adhere to microvessels, inducing endothelial cell swelling, vascular narrowing and occlusion, causing microinfarcts. Anti-endothelial cell antibodies are present in serum in 25% of Susac syndrome patients, but it is unclear whether they are aetiologically related to the disease, or an epiphenomenon. The clinical triad comprising encephalopathy, branch arterial occlusions, and sensorineural hearing impairment is considered pathognomonic, although great variability is found in presentation and natural course of disease. At first evaluation, only 13-30% of patients exhibit the full clinical triad, making diagnosis difficult. Retinal fluorescein angiography, optic coherence tomography, MRI and tonal audiometry are helpful methods for diagnosing and monitoring disease activity during treatment. By contrast, there are no reliable objective immune markers to monitor disease activity. Immunosuppression is the current treatment, with high-dose corticosteroid therapy as the mainstay, but additional therapies such as intravenous immunoglobulins, cyclophosphamide, rituximab and mycophenolate mofetil are often necessary, because the disease can be devastating, causing irreversible organ damage. Unfortunately, low rates of disease, variability in presentation and paucity of objective biomarkers make prospective controlled clinical trials for Susac syndrome treatment difficult. Current immunosuppressive treatments are therefore based on empirical evidence, mainly from retrospective case series and expert opinion. In this review, we draw attention to the need to take consider Susac syndrome in the differential diagnosis of different neurological, psychiatric, ophthalmological and hearing disorders. Furthermore, we summarize our current knowledge of this syndrome, in reference to its pathophysiology, diagnosis and management, emphasizing the need for prospective and controlled studies that allow a better therapeutic approach.


High efficiency platinum acetylide nonlinear absorption chromophores covalently linked to poly(methyl methacrylate).
We report three platinum acetylide acrylate monomers containing known two-photon absorption (TPA) chromophores and their covalent incorporation into polymers via free radical polymerization with methyl methacrylate. The photophysical properties of the platinum acetylide monomers and resulting poly(methyl methacrylate) (PMMA) copolymers were investigated to determine if the one- and two-photon photophysical properties of the chromophores were maintained in the copolymers. The photophysical properties of the series of copolymers were studied in solution and solid state with minimum shifts exhibited in the ground state absorption, photoluminescence, and triplet-triplet transient absorption spectra. The polymer films displayed markedly stronger phosphorescence and longer triplet excited state lifetimes than the polymers in solution or the monomers. The incorporation of the platinum acetylide chromophores into the PMMA copolymers allows the materials to be cast as thin films or into free-standing monoliths. Films with ~3.6 μm in thickness and monoliths with 1 mm path length were fabricated and examined. The nonlinear absorption responses of the polymers in solution were measured via the nanosecond z-scan method, and the solid state polymer monoliths were measured via nonlinear transmittance. Both measurements indicate that the polymers exhibited strong transmittance attenuation at input pulse energies exceeding 100 μJ.


Transmission of lungworms of harbour porpoises and harbour seals: molecular tools determine potential vertebrate intermediate hosts.
Harbour porpoises (Phocoena phocoena) and harbour seals (Phoca vitulina) from German waters are infected by six species of lungworms (Metastrongyloidea). These nematodes parasitise the respiratory tract, are pathogenic and often cause secondary bacterial infections. In spite of their clinical and epidemiological significance, the life cycle and biology of lungworms in the marine environment is still largely unknown. Regions of ribosomal DNA (ITS-2) of all lungworms parasitising harbour porpoises and harbour seals in German waters were sequenced to characterise and compare the different species. The phylogenetic relationship among the lungworm species was analysed by means of their ITS-2 nucleotide sequences and the species-specific traits of the ITS-2 were used to screen wild fish as possible intermediate hosts for larval lungworms. Molecular markers were developed to identify larval nematodes via in-situ hybridisation of tissues of harbour porpoise and harbour seal prey fish. Potential wild intermediate fish hosts from the North Sea were dissected and found to harbour larval nematodes. Histological examination and in-situ hybridisation of tissue samples from these fish showed lungworm larvae within the intestinal wall. Based on larval ITS-2 nucleotide sequences, larval nematodes were identified as Pseudalius inflexus and Parafilaroides gymnurus. Turbot (Psetta maxima) bred and raised in captivity were experimentally infected with live L1s of Otostrongylus circumlitus and ensheathed larvae were recovered from the gastrointestinal tract of turbot and identified using molecular tools. Our results show that fish intermediate hosts play a role in the transmission of metastrongyloid nematodes of harbour porpoises and harbour seals.


Follow the carrot: a route through the difficult esophagus or duodenum.
The side-viewing optics of the duodenoscope present a challenge during esophageal and duodenal intubation. Strictures and diverticula can make this challenge even greater. Techniques including intubation over a wire or through an overtube have been reported to allow passage of the duodenoscope in such cases. We have encountered 5 cases in which intubation was not possible despite using these techniques. The cases displayed a variety of endoscopic challenges and we devised a novel solution that allowed endoscopic retrograde cholangiopancreatography to be successfully completed in all. With this method all procedures could be effectively performed with no complications and no greater risk to the patient than conventional endoscopic retrograde cholangiopancreatography. This simple, low-cost technique could be adopted by any biliary endoscopist when standard techniques fail.


A consecutive, prospective analysis of the Rotoglide 1st metatarsophalangeal joint replacement.
Following 1st metatarsophalangeal joint replacement, there is a normalisation of foot pressure distribution as demonstrated by peak pressures of the 1st and 5th metatarsal heads and their ratio as measured by pedobarographs. This compares favourably with the unaffected foot. Functional dorsiflexion range of motion is maintained and there is a significant improvement in the reported patient outcome measure.


Impairment of prednisolone metabolism by cyclosporine treatment in renal graft recipients.
Pharmacokinetics of prednisolone were studied in 64 randomly chosen renal transplant patients treated with azathioprine and prednisolone (Aza-Po) or cyclosporine and prednisolone (CsA-Po). Intrinsic clearance for prednisolone was calculated after an oral test dose of 0.5 mg prednisolone/kg bodyweight. In 38 patients on Aza-Po treatment the mean clearance for prednisolone was 0.17 +/- 0.04 1/kg/hr (range 0.11-0.27) and in 39 patients on CsA-Po the mean prednisolone clearance was 0.12 +/- 0.02 (0.07-0.17) (P less than 0.001). Eight patients on CsA-Po were tested on three occasions; prednisolone clearance at 2-4 weeks was 0.13 +/- 0.02 (range 0.11-0.17), at 3-6 months 0.11 +/- 0.01 (0.10-0.12) and at 2-5 years 0.11 +/- 0.02 (0.09-0.14). In 11 patients the treatment was changed from Aza-Po to CsA-Po. The prednisolone clearance then decreased from 0.18 +/- 0.05 1/kg/hr (range 0.13-0.27) to 0.12 +/- 0.03 (0.10-0.16) (P less than 0.001). When the treatment was changed from CsA-Po to Aza-Po in 2 patients the prednisolone clearance increased from 0.12 and 0.10 to 0.17 and 0.12 1/kg/hr, respectively. These data show not only that the prednisolone metabolism is slower in cyclosporine-treated patients but also that this metabolism is retarded when azathioprine is replaced by cyclosporine, and that it is accelerated when cyclosporine is replaced by azathioprine. In the CsA-Po treated patients the prednisolone clearance was also found to be lower after 3-6 months than after less than one month (P less than 0.05) but there has been no further decrease in the prednisolone metabolism after up to more than 4 years of cyclosporine treatment.


Adherence to treatment in a behavioral intervention curriculum for parents of children with autism spectrum disorder.
Parents (N = 21) of children with autism spectrum disorders responded to a survey on adherence to skills instruction and problem behavior management strategies they had previously been observed to master in a standardized training curriculum based on the principles of applied behavior analysis. Survey items were guided by existing models of and research in treatment adherence. Parents reported adherence below observed mastery criteria in five of six skill areas. Three independent variables indexing caregiver perception were significantly correlated with reported adherence: perceived effectiveness as a behavior change agent, confidence in the intervention to produce meaningful change, and acceptance of child in family and community. Perceived confidence significantly predicted adherence in a regression model (p < .05). Implications of caregiver perception in explanatory frameworks for adherence are discussed, and next steps in the measurement and study of treatment adherence in behavior analysis are proposed.


Enzymatic reconstruction of a hybrid glycosaminoglycan containing 6-sulfated, 4-sulfated, and unsulfated N-acetylgalactosamine.
Using the transglycosylation reaction of testicular hyaluronidase, reconstructions of hybrid glycosaminoglycans (GAGs) containing 6-sulfated (GalNAc6S), 4-sulfated (GalNAcS) and unsulfated N-acetylgalactosamine (GalNAc) were investigated. First, chondroitin 4-sulfate (Ch4S) as a donor containing GalNAc4S and the pyridylaminated (PA) chondroitin 6-sulfate (Ch6S) hexasaccharide as an acceptor containing GalNAc6S were subjected to transglycosylation reaction. Second, when the resulting PA-Ch6S(hexa-)-Ch4S(di-)octasaccharide and chondroitin (Ch) were used as an acceptor and as a donor containing GalNAc, respectively, a new decasaccharide having a hybrid structure composed of disaccharide units derived from Ch6S, Ch4S and Ch was reconstructed. Using a systematic combination of each donor and acceptor molecule, it was possible to reconstruct various types of hybrid GAGs.


Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model.
Extracorporeal circulation induces ischemia/reperfusion injury in the small intestinal wall. One reason for this damage is a perfusion shift from the muscular toward the mucosal layer. This study investigated the effect of this perfusion shift on the small-intestinal apoptosis and proliferation. Twenty-eight pigs were randomly assigned to the following cohorts and underwent a thoracolaparotomy and a 1 hour main procedure: cohort I: control; cohort II: thoracic aortic cross-clamping (TAC) without perfusion; cohort III: TAC and distal aortic perfusion (DAP); cohort IV: TAC, DAP, and selective visceral perfusion. The main procedure was followed by 2 hours of reperfusion in all cohorts. Tissue samples were taken during the experiment, stained, and analyzed for apoptosis and proliferation (caspase-3, annexin-V, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling, and proliferating cell nuclear antigen). Six animals died unexpectedly during the experiment and were excluded from the analysis. Extensive tissue damage and necrosis was only found in cohort II after the main procedure. In the mucosa, the proliferation was increased in cohort III at the end of the experiment (P = .0157 cohort I vs II). In contrast, the annexin-V/proliferating cell nuclear antigen ratio was significantly higher in cohorts II and IV than in cohorts I and II at the end of the experiment (P = .0034). Furthermore, the caspase-3/annexin-V ratio was increased in all cohorts at the end of the experiment (P = .0015). Mucosal proliferation is the early repair mechanism of the limited small intestinal ischemia/reperfusion injury after DAP. Furthermore, the extensive surgical trauma shifted the mucosal apoptosis into an advanced state.


Unmet diagnostic needs in contact oral mucosal allergies.
The oral mucosa including the lips is constantly exposed to several noxious stimuli, irritants and allergens. However, oral contact pathologies are not frequently seen because of the relative resistance of the oral mucosa to irritant agents and allergens due to anatomical and physiological factors. The spectrum of signs and symptoms of oral contact allergies (OCA) is broad and a large number of condition can be the clinical expression of OCA such as allergic contact stomatitis, allergic contact cheilitis, geographic tongue, oral lichenoid reactions, burning mouth syndrome. The main etiological factors causing OCA are dental materials, food and oral hygiene products, as they contain flavouring agents and preservatives. The personal medical history of the patient is helpful to perform a diagnosis, as a positive history for recent dental procedures. Sometimes histology is mandatory. When it cannot identify a direct cause of a substance, in both acute and chronic OCA, patch tests can play a pivotal role in the diagnosis. However, patch tests might have several pitfalls. Indeed, the presence of metal ions as haptens and specifically the differences in their concentrations in oral mucosa and in standard preparation for patch testing and in the differences in pH of the medium might result in either false positive/negative reactions or non-specific irritative reactions. Another limitation of patch test results is the difficulty to assess the clinical relevance of haptens contained in dental materials and only the removal of dental materials or the avoidance of other contactant and consequent improvement of the disease may demonstrate the haptens' responsibility. In conclusion, the wide spectrum of clinical presentations, the broad range of materials and allergens which can cause it, the difficult interpretation of patch-test results, the clinical relevance assessment of haptens found positive at patch test are the main factors that make sometimes difficult the diagnosis and the management of OCA that requires an interdisciplinary approach to the patient.


[Arthroscopic technique using crossed K-wires for avulsion fractures of intercondylar eminence in children].
Avulsion fractures of the intercondylar eminence (ICE) of the tibia have become increasingly frequent in older school age. Due to recent advances in arthroscopic techniques, it is now possible to treat them by minimally invasive methods. This retrospective study presents evaluation of clinical outcomes of an arthroscopic technique using crossed K-wires. Thirty-five patients with ICE avulsion fracture, 17 girls and 18 boys at an average age of 13 years (7-18), were included in this study. All were indicated for surgical treatment on the basis of radiographic evidence of McKeever type II and III fractures. The technique of arthroscopic reduction and fixation with crossed K-wires was used. The clinical evaluation of knee stability (anterior drawer test and Lachmann s-test) was made by one clinician. The modified Tegner-Lysholm score was assessed. RESULTS Of the 35 patients, 26 (74%) had minimal knee instability (anterior drawer up to 5 mm), two patients were primarily converted to open reduction with good results, and three (8.5%) experienced temporary knee instability (anterior drawer of 5-10 mm) that resolved spontaneously within 24 months of surgery. Four patients (11.5%) had symptoms of persistent residual instability (anterior drawer more than 10 mm) and were indicated for anterior cruciate ligament reconstruction at a later stage. The average Tegner-Lysholm scores were 86.3/100 and 98.6/100 at 6 and 24 months, respectively. DISCUSSION At the present time at our department, McKeever type II and III avulsion fractures of the intercondylar eminence are indicated for minimally invasive surgical treatment. By exact reduction it is possible to decrease the risk of post-operative knee instability. The current trend is the use of arthroscopy-assisted minimally invasive techniques such as the method of K-wire fixation described here. Arthroscopic surgery for ICE avulsion fractures shows good results, is associated with low post-operative risks, is minimally invasive and easy to reproduce. It can be recommended as the method of choice for treating ICE avulsion injury in children.


Novel design of (PEG-ylated)PAMAM-based nanoparticles for sustained delivery of BDNF to neurotoxin-injured differentiated neuroblastoma cells.
Brain-derived neurotrophic factor (BDNF) is essential for the development and function of human neurons, therefore it is a promising target for neurodegenerative disorders treatment. Here, we studied BDNF-based electrostatic complex with dendrimer nanoparticles encapsulated in polyethylene glycol (PEG) in neurotoxin-treated, differentiated neuroblastoma SH-SY5Y cells, a model of neurodegenerative mechanisms. PEG layer was adsorbed at dendrimer-protein core nanoparticles to decrease their cellular uptake and to reduce BDNF-other proteins interactions for a prolonged time. Cytotoxicity and confocal microscopy analysis revealed PEG-ylated BDNF-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery to the neurotoxin-treated cells over 24 h without toxic effect. We offer a reliable electrostatic route for efficient encapsulation and controlled transport of fragile therapeutic proteins without any covalent cross-linker; this could be considered as a safe drug delivery system. Understanding the polyvalent BDNF interactions with dendrimer core nanoparticles offers new possibilities for design of well-ordered protein drug delivery systems.


Immunopotentiation and tumor inhibition with levamisole.
The immunopotentiating drug, levamisole, was found to augment human lymphocyte responses to vegetable mitogens in vitro. However, the effect was dose-dependent and at high concentrations suppression rather than augmentation of the immune response was observed. In view of the potential widespread use of the drug in the treatment of human cancer, a study was undertaken in rats bearing breast cancer to determine whether a similar dose-response effect would be observed in terms of tumor growth. Tumor inhibition was found to be dose-dependent, and at high doses tumor inhibition did not occur while at lower doses the growth of the cancer was inhibited. The rate of tumor growth correlated well with the responses of splenic lymphocytes to vegetable mitogens. In a later study, it was not possible to show that levamisole had any effect in boosting immune responses of patients undergoing surgery. It is concluded that levamisole is capable of increasing immune responses in man in vitro, and that the drug is able to inhibit the growth of breast cancer in the rat. However, these effects are dose-dependent, and clinical trials of the use of levamisole in patients with cancer should include careful immune monitoring to be sure that augmentation rather than suppression of the immune response is being achieved.


Simpson-Golabi-Behmel syndrome: an X-linked encephalo-tropho-schisis syndrome. 1988.
The following paper by Professor GiovanniNeri and colleagues was originally published in 1988, American Journal of Medical Genetics 30:287–299. This paper represented a seminal work at the time of publication as it not only reported a new family with a disorder that had been called the "gigantism-dysplasia syndrome", but also suggested naming the condition the Simpson-Golabi-Behmel syndrome. This eponym has clearly stood "the test of time", and that designation is now widely accepted. This paper is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We report on another family with the so-called "gigantism-dysplasia syndrome", an X-linked condition characterized by pre-and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi-Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al. in 1975 and by Behmel et al. in 1984. Therefore, we suggest that this entity be designated the Simpson-Golabi-Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X-linked encephalo-tropho-schisis syndrome.


Efficacy of calcium- and fluoride-containing materials for the remineralization of primary teeth with early enamel lesion.
The aim of the study was to determine the efficacy of different products containing fluoride, calcium and phosphate for enamel remineralization in eroded primary teeth. A total of 90 sound primary canine teeth were randomly divided into 5 groups of 18 teeth each: 1) control (polished enamel), 2) 5% DuraShield sodium fluoride varnish, 3) 500 ppm fluoridated toothpaste, 4) casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream, and 5) Clinpro White varnish containing functionalized tri-calcium phosphate (fTCP). Enamel microhardness (EMH) was measured in all samples before and after demineralization and after 28 days of remineralization. Also 8 samples in groups 2 to 5 and four samples of sound and demineralized enamel were examined with atomic force microscopy (AFM). All data were analyzed with one-way ANOVA (p<0.05). Mean microhardness of demineralized enamel was significantly lower than in enamel at baseline (p<0.001). Remineralization significantly increased microharness in groups 2 to 5 compared to the control group (p<0.001). Percent EMH after remineralization with CPP-ACP was significantly higher than after fTCP (p=0.029), toothpaste (p< 0.001) or fluoride varnish (p<0.001); however, there was no significant difference between toothpaste and fluoride varnish (p=0.062). Microhardness increased more after fTCP treatment than after treatment with sodium fluoride varnish (p<0.001) or fluoridated toothpaste (p=0.045). AFM images showed that enamel roughness decreased most after treatment with fTCP, followed by CPP-ACP, toothpaste and fluoride varnish. The efficacy of CPP-ACP cream for remineralizing eroded enamel was greater than fluoride toothpaste, fluoride varnish or fTCP varnish.


In-hospital mortality in patients with acute limb ischemia over a 12-year period in the Brazilian public health-care system.
Arterial diseases represent a severe public health problem in the 21st century. Although men have a higher overall prevalence, reports have suggested that women may exhibit atypical manifestations, be asymptomatic, and have hormonal peculiarities, resulting in worse outcomes and severe emergencies, such as acute limb ischemia (ALI). To analyze the morbidity and mortality profile of ALI emergencies in Brazil between 2008 and 2019. An ecological study was carried out with secondary data from SIH/SUS, using ICD-10 code I.74 The proportions of emergency hospital admissions and in-hospital mortality rates (HMR) by gender, ethnicity, and age were extracted from the overall figures. P<0.05 was considered significant. From 2008 to 2019, there were 195,567 urgent hospitalizations due to ALI in Brazil, 111,145 (56.8%) of which were of men. Women had a higher HMR (112:1,000 hospitalizations) than men (85:1,000 hospitalizations) (p<0.05), and a higher chance of death (OR=1.36; p<0.05). Furthermore, mean survival was significantly higher among men (8,483/year versus 6,254/year; p<0.05). Stratified by ethnicity, women who self-identified as white (OR=1.44; p<0.05), black (OR=1.33; p<0.05), and brown (RR=1.25; p <0.05) had greater chances of death than men in the same ethnicity categories. Moreover, women over the age of 50 years had a higher chance of death, with a progressive increment in risk as age increased. There was a trend to worse prognosis in ALI emergencies associated with women, especially in older groups. The literature shows that the reasons for these differences are still poorly investigated and more robust studies of this relevant disease in the area of vascular surgery are encouraged.


Coexistence curve near the tricritical point in ternary polymer solutions.
Two-phase coexistence curves were measured for ternary solutions of bimodal polystyrene in methylcyclohexane with the molecular weight ratio near the tricritical value 23. Coexistence curves were determined by the refractive index method on a diagram of temperature versus volume fraction of total polystyrene. The diameter was strongly curved near the top. The double logarithmic plots of volume fraction difference between two coexisting phases versus reduced temperature yielded the critical exponent beta=0.250+/-0.005 for the tricritical solution and, 0.412+/-0.005 and 0.383+/-0.016 for solutions not far from the tricritical one. The former value could be compared with the classical tricritical exponent beta=1 / 4 and the latter values near 0.40 could be explained by a crossover between the ordinary critical exponent 0.32 or the tricritical exponents 1 / 4 and the classical exponent 1 / 2.


First identification of Nocardia seriolae GapA adhesion function and its three B-cell epitopes with cell-binding activity.
Fish nocardiosis mainly caused by Nocardia seriolae (N. seriolae) is a serious threat to aquaculture. Bacterial adhesion to host cells mediated by adhesin is an initial step of pathogenesis. But it is not clear whether glyceraldehyde-3-phosphate dehydrogenase (GapA) is an adhesin of N. seriolae. Here, recombinant GapA protein (rGapA) was prokaryotic expressed, and its role in the bacterial adhesion to Ctenopharyngodon idella kidney cells was investigated by indirect immunofluorescence, protein-binding assay and adhesion inhibition assay. The results showed that an obvious green fluorescence was observed on the surface of the cells co-incubated with rGapA protein; the cytomembrane proteins of the cells pretreated with rGapA could react with anti-rGapA antibody; and the antibody significantly inhibited the adhesion ability of the bacteria. Subsequently, B-cell linear epitopes of GapA protein were identified by using a immunoinformatics approach combined with peptide ELISA and Western blot for the first time. It was found that four predicted epitopes (Ep58-69 , Ep139-150 , Ep186-197 , Ep318-329 ) could all react with anti-rGapA antibody and obviously inhibit the immunoreactivity between rGapA and anti-rGapA antibody, and they were confirmed as indeed B-cell linear epitopes of the protein. Furthermore, flow cytometry analysis found the percentage of positive cells co-incubated with FITC-labelled epitope peptides (Ep139-150 , Ep186-197 , Ep318-329 ) was significantly higher than those in the FITC-labelled Ep58-69 , unrelated control peptide and cell control. Collectively, GapA is an adhesin of N. seriolae, and epitope peptides (Ep139-150 , Ep186-197 , Ep318-329 ) possess cell-binding activity, which are potential candidates for developing a multiple epitopes-based adhesin vaccine against fish nocardiosis.


Hospice volunteer training: making the experience more meaningful.
Each volunteer coordinator continues to make changes and adjustments in the hospice training classes--some changes arise from circumstances such as staff availability, and some are conscious choices to try new ways of structuring the learning environment. As we shape and refine the experience that we provide for our new volunteers, let us make a special effort to create one that offers not only a comprehensive overview of hospice goals, philosophy, and end-of-life issues, but also a personally challenging and enriching team interaction.


Imaging in clear ocean water.
A parametric analysis is given of imaging in backscattered light in clear ocean water characterized by temperature and salinity inhomogeneities whose scale length is large compared to the diameter of the light beam. An expression for the beam pattern of a finite underwater laser beam is derived where the effects of source coherence on the imaging properties of backscattered light are discussed. On the basis of the model assumed here, it is concluded that the resolution cannot be significantly improved by reduction of the camera threshold. This limitation results from the rapid decrease of the modulation transfer function for increasing spatial frequencies, which indicates that image modulation below 2% falls another 10 dB at only negligibly higher spatial frequencies. Thus, a 10-dB improvement in the limiting resolution of the camera will not result in significantly better image quality through ocean water.


Neuritogenic activities of 1-alkyloxygenipins.
We designed 1-alkyloxygenipins with the aim of improving the stability of genipins based on the structural and electronic properties of genipins, and prepared 1-alkyloxygenipins and examined their neuritogenic activities in PC12h cells. All genipin-derivatives exhibited electronic properties similar to those of genipin and induced significant neurite outgrowth. These compounds will be classified as nitric oxide synthase (NOS) activators (neuritogenic active compounds) since their lowest unoccupied molecular orbital (LUMO)-energies are similar to that of tetrahydrobiopterin (H4B). (1R)-isoPropyloxygenipin showed activity comparable to that of genipin, and unlike the parent compound genipin, it was found to be physiologically stable in rat liver homogenate.


Clinimetrics corner: a closer look at the minimal clinically important difference (MCID).
Minimal clinically important difference (MCID) scores are commonly used by clinicians when determining patient response to treatment and to guide clinical decision-making during the course of treatment. For research purposes, the MCID score is often used in sample size calculations for adequate powering of a study to minimize the false-positives (type 1 errors) and the false-negatives (type 2 errors). For clinicians and researchers alike, it is critical that the MCID score is a valid and stable measure. A low MCID value may result in overestimating the positive effects of treatment, whereas a high MCID value may incorrectly classify patients as failing to respond to treatment when in fact the treatment was beneficial. The wide range of methodologies for calculating the MCID score results in varied outcomes, which leads to difficulties with interpretation and application. This clinimetrics corner outlines key factors influencing MCID estimates and discusses limitations with the use of the MCID in both clinical and research practice settings.


Prevalence of physical inactivity and its relation to social class in U.S. adults: results from the Third National Health and Nutrition Examination Survey, 1988-1994.
This study examines the prevalence of physical inactivity during leisure time in a national representative sample of U.S. adults. Data were obtained from the Third National Health and Nutrition Examination Survey, conducted between 1988 and 1994. A total of 18,825 adults aged 20 yr and older participated in a home interview where information about physical activity, education, income, occupation, employment, and labor force participation was obtained. The prevalence of physical inactivity among U.S. adults was 23%, with more women (28%) than men (17%) reporting being inactive during their leisure time. Additionally, inactivity is more common among in social class such as persons who are less educated, living below the poverty line, living in households with income below 20,000 dollars, and who are retired. In every category of social class, women experienced a higher prevalence of physical inactivity than men. We conclude that social class is associated with physical inactivity and that more research is needed to better understand the effect that other social and environmental factors have on sedentary behaviors in our society.


Association between ureteric stent dwell time and urinary tract infection.
Ureteric stone obstruction commonly presents to the emergency department, with definitive management often involving ureteroscopy and laser lithotripsy. Insertion of a ureteric stent prior to staged lithotripsy is commonly performed in the public healthcare system. Foreign bodies in the urinary tract are also known to increase urinary tract infection (UTI) risk. This study aims to evaluate the association between stent dwell time and UTI prior to lithotripsy. The medical records of all patients who were treated for ureteric stones with initial stent insertion and staged lithotripsy, from 1 January 2018 to 30 June 2019 at a single tertiary centre, by eight urologists were retrospectively reviewed. Demographic features, disease factors and urine culture data were collected and analysed. Of the 172 patients (median age 56.7 years) identified, one-third had a positive pre-stent urine culture. Twenty-three percent had a positive pre-lithotripsy urine culture with 38% of females compared with 15% of males having a positive culture (P = 0.001). Only 4.3% of patients had a pre-lithotripsy UTI when the stent dwell time was less than 1 month compared with 26.2% when ureteric stents were in situ for longer than 1 month (P = 0.021). The correlation between ureteric stent dwell time and pre-lithotripsy UTI was not linear. Patient comorbidities, stone size, burden and location were not statistically correlated to pre-lithotripsy UTI. In delayed two-staged surgical management of acute urolithiasis, optimal ureteric stent dwell time is less than 1 month to reduce pre-lithotripsy UTI. Female gender is an independent risk factor for pre-lithotripsy UTI.


Is Brain MRI Needed in Diagnostic Evaluation of Mild Intellectual Disability?
The purpose of our study was to suggest an imaging strategy and guidelines for the selection of the children with mild intellectual disability (ID) for magnetic resonance imaging (MRI), to avoid unnecessary imaging. The brain MRIs and patient reports of 471 children were reviewed for the imaging findings and ID severity. The correlation between the clinical and brain MRI findings was analyzed in the 305 children with mild ID. Thirty-eight (12.5%) of the children with mild ID had significant abnormal brain MRI findings. Thirty-five of these had other neurological symptoms or diseases in addition to ID, which were an indication for brain MRI. In the logistic regression analysis, seizures (in patients without an epilepsy diagnosis), epilepsy, movement disorders, dysmorphia, encephalitis, traumatic brain injury, and abnormal head size were statistically significant symptoms or comorbidities associated with abnormal MRI findings. Only three children (1.0%) with mild ID had a significant MRI finding without any other clinical symptoms or disease. Routine MRI in children with mild ID without specific neurological symptoms, dysmorphic features, or related diseases is not suggested for revealing an etiology of mild ID. Since children with ID usually need to be sedated for MRI, routine imaging in the diagnostic evaluation of mild ID should be carefully considered. Clinical examination, other symptoms, and related diseases should be carefully assessed to decide the need for MRI.


A natural killer cell granule protein that induces DNA fragmentation and apoptosis.
We report the purification from a rat natural killer (RNK) large granular lymphocyte leukemia of a 32-kD granule protein that induces rapid DNA fragmentation and apoptosis. The protein, which we have called "fragmentin," was capable of causing DNA from intact YAC-1 cells to be cleaved into oligonucleosomal-sized fragments and producing severe chromatin condensation within 1 h. Amino acid sequence of tryptic peptides indicated that fragmentin was highly homologous to the NK and T cell granule serine proteases RNK protease 1 and mouse cytotoxic T cell protease I (CCPI)/granzyme B. Preincubation with the serine esterase inhibitor 3,4-dichloroisocoumarin blocked fragmentin-induced DNA damage, but had no effect on cytolysin. Fragmentin activity against four lymphoma target cells was completely dependent on the presence of cytolysin. Fragmentin produced rapid membrane damage as well as DNA fragmentation at nonlytic cytolysin doses, suggesting that fragmentin activity was not limited to its effects on the nucleus. Fragmentin and cytolysin activity were completely inhibited by EGTA, indicating the process was Ca2+ dependent. A role for cytolysin in endocytosis of fragmentin was suggested by the observation that treatment of YAC-1 with cytochalasin B or sodium azide and 2-deoxyglucose blocked DNA fragmentation but not cytolysin activity. A 30-kD N alpha-CBZ-L-lysine thiobenzyl esterase, which copurified with fragmentin, was inactive on its own but was able to synergistically amplify the DNA damage induced by fragmentin in the presence of cytolysin. Fragmentin activity was not dependent on protein synthesis, as cycloheximide treatment of YAC-1 cells did not prevent DNA damage. We postulate that fragmentin is the molecular mediator of NK cell-mediated DNA fragmentation and apoptosis.


Real-time parallel optical logic operation using photorefractive two-wave mixing and fringe-shifting techniques.
The coupling effect between phase and intensity in photorefractive two-wave mixing in a Bi(12)SiO(20) crystal is demonstrated. By using interference fringe-shifting techniques that are executed by a Mach-Zehnder interferometer, an optical parallel logic operation system that is based on the coupling effect is implemented.


Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.
Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment.


Ultrasonography with color Doppler and power Doppler in the diagnosis of periapical lesions.
To evaluate the efficacy of ultrasonography (USG) with color Doppler and power Doppler applications over conventional radiography in the diagnosis of periapical lesions. Thirty patients having inflammatory periapical lesions of the maxillary or mandibular anterior teeth and requiring endodontic surgery were selected for inclusion in this study. All patients consented to participate in the study. We used conventional periapical radiographs as well as USG with color Doppler and power Doppler for the diagnosis of these lesions. Their diagnostic performances were compared against histopathologic examination. All data were compared and statistically analyzed. USG examination with color Doppler and power Doppler identified 29 (19 cysts and 10 granulomas) of 30 periapical lesions accurately, with a sensitivity of 100% for cysts and 90.91% for granulomas and a specificity of 90.91% for cysts and 100% for granulomas. In comparison, conventional intraoral radiography identified only 21 lesions (sensitivity of 78.9% for cysts and 45.4% for granulomas and specificity of 45.4% for cysts and 78.9% for granulomas). There was definite correlation between the echotexture of the lesions and the histopathological features except in one case. USG imaging with color Doppler and power Doppler is superior to conventional intraoral radiographic methods for diagnosing the nature of periapical lesions in the anterior jaws. This study reveals the potential of USG examination in the study of other jaw lesions.


Tuning anisotropic electronic transport properties of phosphorene via substitutional doping.
Using first-principles calculations, we studied the anisotropic electronic transport properties of pristine and X-doped phosphorene (X = B, Al, Ga, C, Si, Ge, N, As, O, S, and Se atoms). The results show that doping different elements can induce obviously different electronic transport characteristics. Moreover, isovalent doping maintains semiconducting characteristics and anisotropic transport properties, while group IV and VI atoms doping can induce metal properties. Meanwhile, Al and Ga substituting P decrease the anisotropic behaviors of transport, and other atom doping still preserves anisotropic characteristics. Interestingly, obvious negative differential resistance behaviors can be observed in C, Si, Ge, O, S, and Se-doped phosphorene.


Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin.
Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.


The kallikrein-kinin and renin-angiotensin systems in the kidney of an African lungfish, Protopterus annectens.
Renin-like activity (RLA), angiotensin I converting enzyme-like (ACELA), and kallikrein-like activity (KLA), activities of the key enzymes of renin-angiotensin and kallikrein-kinin systems, were sought in the kidney of the African lungfish Protopterus annectens during the aquatic phase. RLA, examined by RIA (using porcine angiotensinogen as substrate), was 0.38 +/- 0.05 ng angiotensin I/mg protein/hr. ACELA and KLA were investigated in assays spectrophotometrically. ACELA, measured at 37 and at 20 degrees , was, respectively, 1.55 +/- 0.55 and 0.61 +/- 0.23 nmol hippurate/min/mg protein. KLA was 7.34 +/- 0.93 mU/mg protein in the crude kidney extract and 31.05 +/- 7.50 mU/mg protein after electrophoretic purification. Renal kininogenase activity was inhibited by 100% by D-Phe-Phe-Arg-chloromethyl ketone (10 microM), 98% by phenylmethylsulfonyl fluoride (2 nM), and 91% by aprotinin (1000 kIU). The apparent molecular weight of the renal kininogenase on SDS-PAGE was 27,000 Da. Both the renal enzyme and the purified glandular kallikrein, used as a control, have the same mobility on polyacrylamide gel electrophoresis. Immunoreactivities toward angiotensin II and bradykinin were localized by double immunostaining in the same cells of the proximal tubules. Putative angiotensin II receptors were demonstrated immunohistochemically, in the supranuclear region of proximal tubular cells, using an antibody to the sequence between amino acids 225 and 237 of the mammalian AT1 receptor.


[Pulmonary disease due to Mycobacterium xenopi].
A 54-year old man with pulmonary disease due to Mycobacterium xenopi is described. He had a history of pulmonary tuberculosis at 8 years of age. He was admitted to our hospital in October 1992, complaining of productive cough and fever. A chest X-ray on October 20 showed an infiltrative shadow with a cavity, although chest X-ray picture on October 2 showed only inactive shadow, in the right upper lobe. Acid-fast organisms were seen in his sputum specimens and M. xenopi was identified by culture. The isolates were confirmed to be M. xenopi by the DNA-DNA hybridization method. He was treated with isoniazid, rifampicin and streptomycin. The fever decreased within a week. After two months of therapy, sputum cultures became negative and chest X-ray findings improved. It was concluded that this is a case of rapidly progressed pulmonary disease caused by M. xenopi in the normal host. This patient's condition responded to antituberculosis drugs.


Glial precursor cell transplantation therapy for neurotrauma and multiple sclerosis.
Traumatic injury to the brain or spinal cord and multiple sclerosis (MS) share a common pathophysiology with regard to axonal demyelination. Despite advances in central nervous system (CNS) repair in experimental animal models, adequate functional recovery has yet to be achieved in patients in response to any of the current strategies. Functional recovery is dependent, in large part, upon remyelination of spared or regenerating axons. The mammalian CNS maintains an endogenous reservoir of glial precursor cells (GPCs), capable of generating new oligodendrocytes and astrocytes. These GPCs are upregulated following traumatic or demyelinating lesions, followed by their differentiation into oligodendrocytes. However, this innate response does not adequately promote remyelination. As a result, researchers have been focusing their efforts on harvesting, culturing, characterizing, and transplanting GPCs into injured regions of the adult mammalian CNS in a variety of animal models of CNS trauma or demyelinating disease. The technical and logistic considerations for transplanting GPCs are extensive and crucial for optimizing and maintaining cell survival before and after transplantation, promoting myelination, and tracking the fate of transplanted cells. This is especially true in trials of GPC transplantation in combination with other strategies such as neutralization of inhibitors to axonal regeneration or remyelination. Overall, such studies improve our understanding and approach to developing clinically relevant therapies for axonal remyelination following traumatic brain injury (TBI) or spinal cord injury (SCI) and demyelinating diseases such as MS.


Clinical and electroencephalographic characteristics of benign occipital epilepsy of childhood in two tertiary Brazilian hospitals.
This study intended to investigate the clinical and electroencephalographic benign occipital epilepsy of childhood (BOEC) characteristics in a population sample of patients from two tertiary Brazilian hospitals. We analyzed retrospectively 4912 electroencephalograms (EEGs) records, and the included patients were submitted to a new clinical and EEG evaluation. Were included 12 (0.92%) patients; 4 (33.3%) with criteria for early BOEC; 6 (50%) for late form and 2 (16.7%) with superimposed early and late onset forms. After new investigation, 2 (16.7%) had normal EEG; 4 (33.3%) had paroxysms over the occipital region; 3 (25%) over the temporal posterior regions and 3 (25%) over the posterior regions. Sharp waves were the predominant change, occurring in 8 (66.6%); spike and slow wave complexes in 1 (8.3%) and sharp and slow wave complexes in 1 (8.3%). Vomiting, headache and visual hallucinations were the most common ictal manifestations, presented in 100% of patients with superimposed forms. Vomiting were absent in the late form and headache was present in all forms of BOEC.


An immunohistochemical survey of pS2 expression in human epithelial cancers.
The oestrogen-inducible pS2 protein isolated from human breast-cancer cells appears to have prognostic significance in breast-cancer patients. Using both monoclonal and polyclonal pS2 anti-sera, we have carried out an immunocytochemical survey of 9 epithelial cancers. Some degree of specific tumour staining was observed in 4 tissues, the extent varying greatly between specimens. Most (11/13) of the colorectal cancers showed immunoreactivity, as did 4/5 pancreatic carcinomas. In some of these cases, patchy staining was also observed in adjacent non-tumour cells. Two bronchio-alveolar carcinomas showed positivity, but 5 poorly differentiated adenocarcinomas of the lung did not. In the ovary, staining was observed in 3/3 mucinous cystadenocarcinomas but only in 1/8 of the serous type. No reactivity was seen in specimens of salivary gland, kidney, liver, prostate or uterus. This pilot study indicates that pS2 may be a useful marker of adenocarcinomas in human neoplasms apart from those in the breast, and suggests that more extensive surveys might be worthwhile.


Schizophrenia-like behavior is not altered by melatonin supplementation in rodents.
An emerging area in schizophrenia research focuses on the impact of immunomodulatory drugs such as melatonin, which have played important roles in many biological systems and functions, and appears to be promising. The objective was to evaluate the effect of melatonin on behavioral parameters in an animal model of schizophrenia. For this, Wistar rats were divided and used in two different protocols. In the prevention protocol, the animals received 1 or 10mg/kg of melatonin or water for 14 days, and between the 8th and 14th day they received ketamine or saline. In the reversal protocol, the opposite occurred. On the 14th day, the animals underwent behavioral tests: locomotor activity and prepulse inhibition task. In both protocols, the results revealed that ketamine had effects on locomotor activity and prepulse inhibition, confirming the validity of ketamine construction as a good animal model of schizophrenia. However, at least at the doses used, melatonin was not able to reverse/prevent ketamine damage. More studies are necessary to evaluate the role of melatonin as an adjuvant treatment in psychiatric disorders.


Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions.
Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX(3)C chemokine fractalkine (CX(3)CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription-polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.


Accomplishments in 2008 in the management of hepatobiliary cancers.
HEPATOCELLULAR CARCINOMA: EpidemiologyManagement of HCC-Standard Approaches and Reports During the Past Year SurgeryLocoregional Treatment Local AblationChemoembolizationOther Local Treatment ModalitiesSystemic TreatmentClinical Trial DesignBasic Science and Biomarkers Basic and Translational SciencePrognostic and Predictive Markers Prognostic MarkersPredictive MarkersAccomplishments and Future DirectionsApplication of the AccomplishmentsFuture Directions BILIARY TRACT CANCERS: Overview of the DiseaseManagement of Biliary Tract Cancers-Current Approaches and Reports During the Past Year Surgical Resection and Adjuvant TherapySystemic Therapy for Unresectable or Metastatic Biliary Tract Cancer Cytotoxic ChemotherapyCytotoxic Chemotherapy in Combination With Targeted AgentSingle-Agent Targeted TherapyCombination of Targeted AgentsBiologyFuture Directions.


Apolipoprotein(a) phenotype and lipoprotein(a) level predict peritoneal dialysis patient mortality.
To examine the associations between lipoprotein(a) [Lp(a)] level, apolipoprotein(a) [apo(a)] phenotype, and patient mortality in peritoneal dialysis (PD) patients. Observational prospective study of prevalent PD patients. Tertiary-care health sciences center. 54 prevalent PD patients were followed prospectively for 24 months. The exposures were Lp(a) level and apo(a) phenotype, designated by the apo(a) isoform size (number of kringle 4 repeats). Outcome was death from any cause. There were 24 deaths in 77.9 patient-years' follow-up. The independent predictors of death in the multivariate survival analysis were age [relative risk (RR) = 1.03, p = 0.23], diabetes (RR = 3.00, p = 0.03), diastolic blood pressure < or = 70 mmHg (RR = 2.94, p = 0.03), serum albumin (RR = 0.87, p < 0.01), and Lp(a) level (RR = 1.004, p < 0.01). There was strong inverse correlation of Lp(a) with apo(a) isoform size (r = -0.62, p < 0.01). With Lp(a) removed from the model, apo(a) isoform size was a significant predictor of death (RR = 0.91, p = 0.0497). Lipoprotein(a) level and apo(a) phenotype are associated with PD patient mortality. Measurement of Lp(a) level and apo(a) phenotype may be useful in clinical practice to identify patients at high risk for cardiovascular disease. Large prospective studies are needed to determine if a reversal of the increase in Lp(a) level associated with renal disease and dialysis is feasible and beneficial in reducing the risk of cardiovascular disease and mortality.


Identification of a previously undetected source of systematic error in capillary viscometry measurements.
A new analysis of the factors affecting the driving head within a capillary viscometer has identified a previously undetected source of error due to surface tension. In contrast to the well-known capillary rise correction to the effective driving head, this additional effect requires that a correction be made to the apparent head of liquid. Calculations show that this source of error may be responsible for deviations in experimental results as large as 1%. A new calibration equation which compensates for both surface tension effects is recommended.


Impaired sensitivity to visual contrast in children treated early and continuously for phenylketonuria.
Contrast sensitivity was assessed in 47 children aged 5.4-9.8 years: 12 with phenylketonuria (PKU), six unaffected siblings and 29 children from the general population. Children with PKU, despite early and continuous treatment and despite phenylalanine (Phe) levels within accepted limits, were impaired across the range of spatial frequencies [1.5-18.0 cycles per degree of visual angle (c.p.d.)]. They were most impaired at the next to the highest spatial frequency, where "group' accounted for 70% of the variance in sensitivity to contrast, controlling for acuity, sex, age and test site. Never, at any spatial frequency, was the contrast sensitivity of any PKU subject better than that of his or her sibling. All subjects were tested under conditions of 20/20 vision, with correction if needed. The mean IQ of PKU subjects was 99; IQ was not significantly related to contrast sensitivity performance. We interpret these findings as support for Diamond's hypothesis that moderately elevated plasma Phe levels (3-5 x normal), combined with reduced plasma tyrosine (Tyr), moderately reduce the levels of Tyr reaching the eye and brain, which adversely affects those dopamine neurons that fire and turn over dopamine most rapidly (the dopamine neurons in the retina and those projecting to prefrontal cortex). This would lead to the deficit in contrast sensitivity found here and to the selective deficit in prefrontal cortex cognitive functions previously reported in PKU children under moderately good dietary control.


Duration of symptoms and spread of colorectal cancer: a short history does not mean early disease.
The 5-year survival rates for colorectal cancer are generally lower in the UK than other European countries. In an attempt to improve prognosis, central government has stipulated that patients with suspicious symptoms ought to be seen within 2 weeks of referral from a primary care physician. In order to evaluate whether symptom duration affects stage at presentation of colorectal cancer, a retrospective analysis of all patients presenting over a 2-year period to a large district general hospital was performed. There was no significant difference (P = 0.885) in Dukes' staging in patients with symptoms lasting less or more than 6 months. Though seeing patients with symptoms suspicious of colorectal cancer in specialist out-patient clinics within 2 weeks of presentation to the primary care physician would probably reduce the number of patients presenting as an emergency, it is unlikely to improve prognosis. Thus funds diverted towards the 2-week wait are probably best utilised for other procedures such as colonoscopy and for improving care once the diagnosis of cancer has been made. Diagnosis of colorectal cancer at an earlier stage is best achieved by screening of the population.


Current uses of total parenteral nutrition.
Total parenteral nutrition has become a well-established intervention for the following indications: to sustain life in patients with short-bowel syndrome; for perioperative use in nutritionally deprived patients; to improve quality of life for patients with inflammatory bowel diseases; to assist the healing of enterocutaneous and pancreatic fistulas; for supportive care in patients with acute pancreatitis; as an adjunct to therapy in patients with acute renal or hepatic failure; for hypermetabolic states such as sepsis, trauma, burns and acquired immunodeficiency syndrome; in neonatal and pediatric patients; in transplantation recipients, including bone marrow, renal, cardiac and liver transplants; for precoronary artery bypass graft myocardial glycogen loading; in the field of obstetrics; to enhance survival in patients with closed head injuries; to treat life-threatening anorexia nervosa; in patients with cystic fibrosis and for nutritional support in home use.


Chamiside A, a Cytochalasan with a Tricyclic Core Skeleton from the Endophytic Fungus Chaetomium nigricolor F5.
Chamiside A (1), a novel cytochalasan with a new 6/6/5-fused tricyclic core skeleton, was isolated from an endophytic fungus, Chaetomium nigricolor F5, harbored in the medicinal plant Mahonia fortunei. Its structure was unambiguously determined by extensive spectroscopic analyses, measurement of single-crystal X-ray diffraction, and electronic circular dichroism calculation. A biosynthetic pathway for the unique ring system in 1 was proposed. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus.


Thyroperoxidase microsatellite polymorphism in thyroid diseases.
Autoimmune thyroid diseases (AITD) cluster in families, although the nature of this phenomenon is still poorly understood. One possible approach to the identification of genetic factors contributing to the pathogenesis of AITD is the study of association between polymorphic markers and AITD themselves. In the present study we have analyzed the allelic distribution of sRA-1, a TPO tetranucleotide repeat, among patients with AITD, in comparison with patients with nonautoimmune thyroid diseases and the general population. The polymorphic marker was analyzed by PCR followed by electrophoresis on polyacrylamide denaturant gel. Our data show that no association exists between AITD and any of sRA-1 alleles, despite the important role that TPO plays as a thyroid autoantigen.


Effects of early-stage aging on locomotor dynamics and hindlimb muscle force production in the rat.
Attenuation of locomotor function is common in many species of animals as they age. Dysfunctions may emerge from a constellation of age-related impairments, including increased joint stiffness, reduced ability to repair muscle tissue, and decreasing fine motor control capabilities. Any or all of these factors may contribute to gait abnormalities and substantially limit an animal's speed and mobility. In this study we examined the effects of aging on whole-animal locomotor performance and hindlimb muscle mechanics in young adult rats aged 6-8 months and 'early aged' 24-month-old rats (Rattus norvegicus, Fischer 344 × Brown Norway crosses). Analyses of gaits and kinematics demonstrated that aged rats moved significantly more slowly, sustained longer hindlimb support durations, moved with a greater proportion of asymmetrical gaits, were more plantigrade, and moved with a more kyphotic spinal posture than the young rats. Additionally, the external mechanical energy profiles of the aged animals were variable across trials, whereas the younger rats moved predominantly with bouncing mechanics. In situ analyses of the ankle extensor/plantar flexor muscle group (soleus, plantaris, and medial and lateral gastrocnemii) revealed reduced maximum force generation with aging, despite minimal changes in muscle mass. The weakened muscles were implicated in the degradation of hindfoot posture, as well as variability in center-of-mass mechanics. These results demonstrate that the early stages of aging have consequences for whole-body performance, even before age-related loss of muscle mass begins.


Prostatein or steroid binding protein (PSBP) induces experimental autoimmune prostatitis (EAP) in NOD mice.
In a previous study, we showed that nonobese diabetic (NOD) mice, a strain that present an inherited predisposition to develop both spontaneous and induced autoimmune lesions, are susceptible to the induction of experimental autoimmune prostatitis (EAP), developing a severe inflammatory reaction in the prostate, accompanied by humoral and T-cell-mediated responses. In this study we asked whether the protein steroid binding protein (PSBP) or prostatein (a major autoantigen in the rat model of EAP) is a potential autoantigen in the NOD mouse model and examined the ability of purified PSBP to induce EAP in this strain. Our results indicate clearly that NOD male mice react immunologically to PSBP by developing lymphocytic inflammatory lesions in prostatic tissue and producing both a cellular- and humoral-specific autoimmune response. But our results suggest also the existence of other prostatic autoantigens present only in total prostate extract. Such additional antigens could enhance the autoimmune response and result in more severe forms of inflammation. We also analyzed the respective contributions of MHC antigens and CD4/CD8 T-cell subsets in NOD mice lacking expression of beta 2-microglobulin (NOD.beta2m degrees/degrees) or MHC class II beta chain (NOD.Abeta degrees/degrees) and demonstrate an essential role for CD4(+) T cells in the development of EAP in the NOD model. In conclusion, we demonstrate that PSBP is an autoantigen recognized by the NOD immune system, capable of generating humoral and cellular autoimmune responses and of inducing EAP. Moreover, using selected knock-out NOD mice we demonstrate an essential role for CD4(+) T cells in the development of EAP.


Modulating Interfacial Energy Dissipation via Potential-Controlled Ion Trapping.
As a metal (gold) surface at a given, but variable potential slides past a dielectric (mica) surface at a fixed charge, across aqueous salt solutions, two distinct dissipation regimes may be identified. In regime I, when the gold potential is such that counterions are expelled from between the surfaces, which then come to adhesive contact, the frictional dissipation is high, with coefficient of friction μ ≈ 0.8-0.9. In regime II, when hydrated counterions are trapped between the compressed surfaces, hydration lubrication is active and friction is much lower, μ = 0.05 ± 0.03. Moreover, the dissipation regime as the surfaces contact is largely retained even when the metal potential changes to the other regime, attributed to the slow kinetics of counterion expulsion from or penetration into the subnanometer intersurface gap. Our results indicate how frictional dissipation between such a conducting/nonconducting couple may be modulated by the potential applied to the metal.


Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages.
Bisphosphonates are widely used in the treatment of diseases involving excessive bone resorption, such as osteoporosis, cancer-associated bone disease, and Paget's disease of bone. They target to the skeleton due to their calcium-chelating properties, where they primarily act by inhibiting osteoclast-mediated bone resorption. The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. In recent years, these concepts have been refined, with an increased understanding of the exact mode of inhibition of FPP synthase and the consequences of inhibiting this enzyme. Recent studies further suggest that the R2 side chain, as well as determining the potency for inhibiting the target enzyme FPP synthase, also influences bone mineral binding, which may influence distribution within bone and duration of action. While bisphosphonates primarily affect the function of resorbing osteoclasts, it is becoming increasingly clear that bisphosphonates may also target the osteocyte network and prevent osteocyte apoptosis, which could contribute to their anti-fracture effects. Furthermore, increasing evidence implicates monocytes and macrophages as direct targets of bisphosphonate action, which may explain the acute phase response and the anti-tumour activity in certain animal models. Bone mineral affinity is likely to influence the extent of any such effects of these agents on non-osteoclast cells. While alternative anti-resorptive therapeutics are becoming available for clinical use, bisphosphonates currently remain the principle drugs used to treat excessive bone resorption.


Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage.
Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.


Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells.
The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis. In the present work, we demonstrate that expression of Sox2 in Clara cells is required for the differentiation of ciliated, Clara, and goblet cells that line the bronchioles of the postnatal lung. The gene was selectively deleted in Clara cells utilizing Scgb1a1-Cre, causing the progressive loss of Sox2 in the bronchioles during perinatal and postnatal development. The rate of bronchiolar cell proliferation was decreased and associated with the formation of an undifferentiated, cuboidal-squamous epithelium lacking the expression of markers of Clara cells (Scgb1a1), ciliated cells (FoxJ1 and alpha-tubulin), and goblet cells (Spdef and Muc5AC). By adulthood, bronchiolar cell numbers were decreased and Sox2 was absent in extensive regions of the bronchiolar epithelium, at which time residual Sox2 expression was primarily restricted to selective niches of CGRP staining neuroepithelial cells. Allergen-induced goblet cell differentiation and mucus production was absent in the respiratory epithelium lacking Sox2. In vitro, Sox2 activated promoter-luciferase reporter constructs for differentiation markers characteristic of Clara, ciliated, and goblet cells, Scgb1a1, FoxJ1, and Agr2, respectively. Sox2 physically interacted with Smad3 and inhibited TGF-beta1/Smad3-mediated transcriptional activity in vitro, a pathway that negatively regulates proliferation. Sox2 is required for proliferation and differentiation of Clara cells that serve as the progenitor cells from which Clara, ciliated, and goblet cells are derived.


Purification and activation properties of UreD-UreF-urease apoprotein complexes.
In vivo assembly of the Klebsiella aerogenes urease nickel metallocenter requires the presence of UreD, UreF, and UreG accessory proteins and is further facilitated by UreE. Prior studies had shown that urease apoprotein exists in an uncomplexed form as well as in a series of UreD-urease (I.-S. Park, M.B. Carr, and R.P. Hausinger, Proc. Natl. Acad. Sci. USA 91:3233-3237, 1994) and UreD-UreF-UreG-urease (I.-S. Park and R.P. Hausinger, J. Bacteriol. 177:1947-1951, 1995) apoprotein complexes. This study demonstrates the existence of a distinct series of complexes consisting of UreD, UreF, and urease apoprotein. These novel complexes exhibited activation properties that were distinct from urease and UreD-urease apoprotein complexes. Unlike the previously described species, the UreD-UreF-urease apoprotein complexes were resistant to inactivation by NiCl2. The bicarbonate concentration dependence for UreD-UreF-urease apoenzyme activation was significantly decreased compared with that of the urease and UreD-urease apoproteins. Western blot (immunoblot) analyses with polyclonal anti-urease and anti-UreD antibodies indicated that UreD is masked in the UreD-UreF-urease complexes, presumably by UreF. We propose that the binding of UreF modulates the UreD-urease apoprotein activation properties by excluding nickel ions from binding to the active site until after formation of the carbamylated lysine metallocenter ligand.


[Assessment of sapheno-femoral junction continence in 42 patients with primary varicocele].
Varicose veins present a major health problem, causing chronic leg symptoms and disability to a large segment of population. The prevalence rate in adults shows great geographical variations and increases with age. Several authors reported that most cases of primary varicose veins are due to valvular incompetence of saphenofemoral junctions. On the base of close physiopathologic and hemodynamic relationships between primary varicose veins and primary varicocele we decided to evaluate the continence of saphenofemoral junctions in a selected group of young men affected by primary varicocele. MATERIALS AND METHODS. 42 patients were included in the study. The age ranged from 13 to 55 years; the mean age was 28 years. In all cases a clinical and instrumental (ultranosography. Doppler flowmetry) diagnosis of primary varicocele was performed. Bidirectional Doppler flowmetry was used to evaluate the continence of 84 saphenofemoral junctions. RESULTS. Among the group of studied 36 (85.7%) showed a monolateral or bilateral valvular incompetence of saphenofemoral junctions; in the remaining 6 patients (14.3%) there was no evidence of valvular insufficiency. In 84 saphenofemoral junctions studied 52 (61.9%) were found incompetent, 32 to the left side and 20 to the right side. Moreover 2 patients had clinically detectable varicose veins of the lower limbs and symptoms related to chronic venous insufficiency. DISCUSSION. Varicose veins are one of the most prevalent chronic conditions in industrialized countries and places a considerable demand on the health services. Since this pathology is potentially preventable it seems very important to select within populations asymptomatic groups in which there is an increasing risk of chronic venous insufficiency and to perform a clinical and instrumental assessment, based on non invasive techniques. In the past varicose veins were related to other diseases and among them some authors suggested primary varicocele, that is due to venous spermatic reflux and/or valvular incompetence; furthermore varicocele and varicose veins are often familiar. In our 42 patients affected by varicocele only 6 (14.3%) had no Doppler flowmetry evidence of incompetence of saphenofemoral junctions and more than half (61.9%) of the junctions were found incompetent. CONCLUSIONS. In our experience we found a considerable relationship between primary varicocele and venous incompetence of saphenofemoral junctions. Perhaps these patients must be considered a group with an increasing risk to develop primary varicose veins. So we suggest that clinical examination and instrumental assessment should be performed in young men affected by varicocele, in order to obtain a prevention of chronic venous insufficiency of the lower limbs. Nevertheless this retrospective study has to be further confirmed by longterm prospective studies.


Atomic-scale viscoplasticity mechanisms revealed in high ductility metallic glass films.
The fundamental plasticity mechanisms in thin freestanding Zr65Ni35 metallic glass films are investigated in order to unravel the origin of an outstanding strength/ductility balance. The deformation process is homogenous until fracture with no evidence of catastrophic shear banding. The creep/relaxation behaviour of the films was characterized by on-chip tensile testing, revealing an activation volume in the range 100-200 Å3. Advanced high-resolution transmission electron microscopy imaging and spectroscopy exhibit a very fine glassy nanostructure with well-defined dense Ni-rich clusters embedded in Zr-rich clusters of lower atomic density and a ~2-3 nm characteristic length scale. Nanobeam electron diffraction analysis reveals that the accumulation of plastic deformation at room-temperature correlates with monotonously increasing disruption of the local atomic order. These results provide experimental evidences of the dynamics of shear transformation zones activation in metallic glasses. The impact of the nanoscale structural heterogeneities on the mechanical properties including the rate dependent behaviour is discussed, shedding new light on the governing plasticity mechanisms in metallic glasses with initially heterogeneous atomic arrangement.


Research utilization among clinical nurse specialists.
The purpose of this descriptive study was to explore utilization behavior of clinical nurse specialists (CNSs) relative to research-based information as distinguished from nonresearch-based information. A nontraditional conceptualization of knowledge utilization as encompassing both cognitive and instrumental application was employed. Twenty-four CNSs were interviewed in a field survey. Results indicated that subjects most frequently use findings conceptually; while on occasion, as illustrated in case examples, they reported using research both conceptually and instrumentally. Only half of the subjects, however, could list explicit criteria for evaluation of the applicability of findings to practice. What is most striking in this study's findings is its congruence with results from other research conducted on various, nonnursing populations.


Comparison of inspiratory effort in sniff-like aspiration reflex, gasping and normal breathing in cats.
The changes in airway occlusion pressure and airflow, occurring during two spasmodic breathing patterns, were studied and compared with normal breathing pattern in 12 anaesthetized cats. The inspiratory effort developed during the sniff-like aspiration reflex elicited by mechanical stimulation of the nasopharynx under control conditions proved to be very similar in character and intensity to the activity observed during gasping which occurred on resuscitation, of the same cats, from hypoxic apnoea. The starting (P50) and maximum (Pmax) airway occlusion pressure developed in these two spasmodic breathing patterns were very high. Extremely rapid rates of contraction and relaxation were detected by computer-assisted measurements of dynamic changes in both the pressure values and the slopes of pressure curves. The results suggest common effector mechanisms, reflecting similar forceful inspiratory drives, for the aspiration reflex and gasping. These two spasmodic processes differ substantially from normal breathing. Nevertheless, the aspiration reflex differs from gasping in that it can be elicited by activation of upper airway afferents during eupnea. Moreover, as yet, there is no definitive evidence that the brainstem mechanisms responsible for generating the aspiration reflex are the same as those of the gasp. The main benefits of this reflex are its rather easy elicitability under various conditions and its capability to induce important cardiorespiratory effects (e.g.) reversal of central apnoea) owing to its powerful activity.


Polio outbreak among nomads in Chad: outbreak response and lessons learned.
In response to the 2011 and 2012 polio epidemic in Chad, Chad's Ministry of Public Health, with support from Global Polio Eradication Initiative partners, took steps to increase vaccination coverage of nomadic children with targeted polio campaigns. This article describes the strategies we used to vaccinate nomads in 3 districts of Chad. Our targeted interventions involved using mobile vaccination teams, recruiting local nomads to identify settlements, using social mobilization, and offering vaccinations to children, women, and animals. Vaccination coverage of nomadic children 0-59 months of age increased, particularly among those never before vaccinated against polio. These increases occurred mostly in the intervention districts of Dourbali, from 2956 to 8164 vaccinated children, and Kyabe, from 7319 to 15 868. The number of first-time vaccinated nomadic children also increased the most in these districts, from 60 to 131 in Dourbali and from 1302 to 2973 in Kyabe. Coverage in the Massaguet district was only 37.7%. Our success was probably due to (1) appointment of staff to oversee implementation, (2) engagement of the national government and its partners, (3) participation of nomadic community leaders, (4) intersectoral collaboration between human and animal health services, and (5) flexibility and capacity of vaccinators to vaccinate when and where nomads were available.


Therapeutic Success in Swiss COPD Patients Receiving Dual Bronchodilation Therapy as COPD Maintenance Treatment.
Health-related quality of life (HRQoL) in patients with moderate to severe chronic obstructive pulmonary disease (COPD) is often reduced by high symptom burden and frequent exacerbations. So far, data on therapeutic success in Swiss COPD patients receiving dual bronchodilation therapy as COPD maintenance treatment are limited. Data from a recently published, non-interventional study on clinical benefit after the start of combined tiotropium-olodaterol treatment were analyzed focusing on Swiss patients compared to the overall cohort including patients from various European countries. Demographic data on the changes in Clinical COPD Questionnaire (CCQ) for the assessment of HRQoL in correlation to symptoms and the number of exacerbations, as well as physician's global assessment (PGE), were evaluated 6 weeks after treatment start. In Switzerland (n = 61), significantly more patients had comorbidities and exacerbations but showed less symptoms compared to the overall cohort (n = 4639). HRQoL improved in both cohorts, with a negative correlation to symptom burden and number of exacerbations in the overall cohort. PGE scores improved after 6 weeks with a better general condition at baseline in Swiss patients (PGE score 4/5: 68.9% [Swiss cohort] vs. 49.0% [overall cohort]. Despite significant differences regarding the presence of symptoms and exacerbations, therapeutic success was similar in both patient groups. Highly symptomatic patients benefited mostly from tiotropium-olodaterol treatment.


A monoclonal antibody reactive with human eosinophils.
EO-1, an IgGl murine monoclonal antibody raised against human eosinophilic leukemia cells, reacts with eosinophils, basophils, platelets, and a few (2%) mononuclear cells but not with neutrophils. In the bone marrow, mature and immature eosinophils and basophils express the EO-1 antigen, whereas immature myeloid cells do not. The distribution of EO-1 antigen on leukemic cells is concordant with this finding, ie, typical myeloid lines (HL-60, KG-1, and ML-1) and fresh acute myelogenous leukemia cells are all unreactive with EO-1. Immunoprecipitation of an extract from surface-131I-labeled platelets with EO-1 and sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing or nonreducing conditions, yielded a specific band of molecular weight 23,000. Previously described monoclonal antibodies reacting with eosinophils also recognize neutrophils. EO-1 is a unique antibody with specificity restricted to eosinophils, basophils, and platelets and might therefore be a valuable reagent for the study of their function and differentiation.


Colour, polarity, disparity, and texture contributions to motion segregation.
We measured how different cues are combined in motion-segregation processes by using motion stimuli where randomly distributed target dots were organised in global revolving motion while the remaining noise dots performed random motion. Target dots were cued with a different colour, polarity, disparity depth, or texture orientation than the noise dots, or they were the same as the noise dots. The stimuli were presented with a prolonged static cue preview which provided position cues to target dots or, briefly with static pre-target and post-target noise frames, which provided false position cues (no preview). All cues efficiently facilitated global motion segregation in cued-preview conditions. Colour completely failed to facilitate global motion segregation in no-preview conditions. Polarity and disparity facilitated segregation in no-preview conditions, although sensitivities were lower than in the preview conditions. Remarkably, texture orientation largely facilitated motion segregation by the same amount in both cued-preview and no-preview conditions. So, colour provides only position cues to the motion-segregation task whereas texture orientation, disparity, and to a lesser extent polarity are integrated with the segregation process.


Developing A Rapid Transfer from Opioid Full Agonist to Buprenorphine: "Ultrarapid Micro-Dosing" Proof of Concept.
Buprenorphine/naloxone has been shown to be effective for treating opioid use disorder (OUD). However, the traditional method of induction requires a patient to be in moderate-to-severe withdrawal, which is challenging, time-consuming, and a common reason for leaving against medical advice. Induction strategies that minimize the severity and duration of patient discomfort while enabling patients to reach therapeutic doses during short hospital admissions can mitigate difficulties when inducing a patient on buprenorphine/naloxone. This case-series illustrates two patients with OUD using illicit fentanyl, who were successfully started on buprenorphine/naloxone using 24-hour and 6-hour micro-dosing induction protocol. During induction, the patients were up-titrated to a therapeutic dose through ultrarapid micro-dosing with ongoing use of short-acting opioids. Both patients reached therapeutic doses experiencing minimal levels of withdrawal. This case-series is a proof of concept for the use of a buprenorphine/naloxone ultrarapid micro-induction protocol for inpatients with OUD. By reducing the length of induction and precluding the need for withdrawal, this method offers several advantages over previously published inductions protocols and can improve the accessibility of buprenorphine/naloxone to patients with OUD.


Neurocognitive, functional, and health outcomes at 5 years of age for children after complex cardiac surgery at 6 weeks of age or younger.
This work provides neurocognitive, functional, and health outcomes for 5-year survivors of early infant complex cardiac surgery, including those with chromosomal abnormalities. Of 85 children (22.4% mortality), 61 received multidisciplinary, individual evaluation and parental questionnaires at 5 years. Full-scale, verbal, and performance IQ scores were compared by using analysis of variance among children who received different surgeries (arterial switch, 20; Norwood for hypoplastic left heart syndrome, 14; simple total anomalous pulmonary venous connection, 6; miscellaneous, 21; and chromosomal abnormalities, 8). Predictions from mental scores at 2 years for IQ scores at 5 years were determined. Children with chromosomal abnormalities had lower full-scale and verbal IQs at 5 years than other survivors, with no differences found among the remaining groups. For children post-Norwood, performance IQ scores remained lower than for children after the arterial-switch operation. Prediction of full-scale IQ (<70) from 2-year mental scores for all 61 children were as follows: sensitivity, 87.5%; specificity, 88.1%; positive predictive value, 53.8%; and negative predictive value, 97.9%. For full-scale IQ of <85, predictions were 90.0%, 87.8%, 78.3%, and 94.7%, respectively. For those 53 without chromosomal abnormalities, full-scale IQ <70, respective predictions were 86.7%, 90.0%, 28.6%, and 97.8%, and for full-scale IQ <85, respective predictions were 85.7%, 89.7%, 75.0%, and 94.6%. Parental report indicated good health in 80% and adequate function in 67% to 88% of the children, although health-utilization numbers suggest that these reports are optimistic. Five-year full-scale and verbal IQs were similar among groups, excluding those with chromosomal abnormalities. Children with chromosomal abnormalities had the lowest scores. Excluding those with chromosomal abnormalities, the mean mental scores for the children as a group tended to increase from 2 to 5 years of age, with an overall high percentage of correct classifications at 2 years.


Risk factors for radiographic articular destruction of hands and wrists in rheumatoid arthritis.
To carry out a cross sectional case-control study of the risk factors for articular destruction in a large sample of patients with a long history of rheumatoid arthritis (RA), presupposing that the variables we measured were unrelated to the duration of disease. Each inpatient with RA admitted to our department from January 1, 1985, to December 31, 1995, underwent standard examination, laboratory tests, and hand roentgenograms. We carried out a radiographic cross sectional study on 287 of them. Radiographic evaluation was performed by the same observer (correlation coefficient 0.97) using the modified Sharp method. To investigate an association between articular destruction and prognostic variables, a matched analysis of the case-control data and calculation of the odds ratio (OR) with 95% confidence intervals (CI) were carried out. For each patient with severe articular destruction, patients hospitalized during the study period with the same disease duration but without severe articular destruction were included as controls. The sample size was chosen to show an OR > 2 (1-alpha = 95%; 1-beta = 80%). The risk of articular joint destruction was higher in women than in men (OR 2.72, CI 1.17-7.9, p<0.023), whereas age at onset or the presence of HLA-DR4, antiperinuclear factor, or antikeratin antibodies was not sufficiently strongly associated with the process of articular destruction to be considered relevant prognostic markers. We conclude that female sex is significantly associated with a higher risk of articular destruction.