Inhibition of Biofilm and Virulence Factors of Candida albicans by Partially Purified Secondary Metabolites of Streptomyces chrestomyceticus Strain ADP4.
Despite several advancements in antifungal drug discovery, fungal diseases like Invasive Candidiasis (IC) still remain associated with high rates of morbidity and mortality worldwide. Thus there is an enormous need for anti-Candida drugs. The main objectives of the work included: 1. To investigate therapeutically significant classes of secondary metabolites produced by S. chrestomyceticus strain ADP4. 2. To investigate and analyze inhibition of significant virulence attributes of C. albicans, such as, biofilm and secretory hydrolytic enzymes by ADP4 secondary metabolites. 3. Mechanistic analysis of probable compounds for their site of action on Secretary Aspartyl Proteinase 3 (Sap3). Metabolite extract-SDB (MESDB) of S. chrestomyceticus strain ADP4 was fractionated on silica gel column chromatography. Fractions were analyzed for anti-Candida activity by disc diffusion assay. Active fractions were further purified by differential solvent treatment. MIC90 values were determined by broth dilution method. MFC was based on counting viable cells. Inhibition of yeast to hyphae transition and that of production of hydrolytic enzymes were estimated by plate assays. GC-MS of MESDB and Partially Purified Metabolite preparations (PPMs) was done. GRIP docking studies with Sap 3 of C. albicans was done using VLife MDS 4.6 software. Chemical profiling showed that ADP4 secondary metabolites contained alkaloids, flavonoids, polyphenols, terpenoids and triterpenes. The MESDB and the PPMs showed low or no cytotoxicity but were able to effectively contain virulence attributes of Candida pathogen. Docking studies revealed that some of the probable compounds have affinity for aspartic acid residue in Sap3 enzyme of C. albicans. Secondary metabolite of strain ADP4 included important classes of therapeutically important compounds. Their anti-Candida activity was mediated by inhibition of critical virulence factors of the pathogen.


Effect of octanoate injection on rat blood-brain barrier.
Serum concentrations of short and medium chain fatty acids, including octanoate, are elevated in hepatic encephalopathy and Reye syndrome. Injection of octanoate into animals produces features reminiscent of Reye syndrome, but the mechanisms are unknown. To evaluate the effect of octanoate on blood-brain barrier permeability, three techniques were used. Entry of horseradish peroxidase and trypan blue into brain was not observed after octanoate injection. Brain uptake of tryptamine, tyrosine and methionine was increased significantly by octanoate, while uptake of insulin was unchanged. This study suggests that octanoate may produce central nervous system alterations by facilitating entry of certain low molecular weight compounds into brain. This may represent one mechanism for the development of encephalopathy in liver disease and Reye syndrome.


Obstacles to Adolescent Care in General Practice.
The physician who provides care for the adolescent must integrate a number of issues outside the usual framework of medical practice. The adolescent alternates between the child and young adult, and so creates a series of challenges for his or her physician relative to the young person's autonomy and the continued legal role of the family. This article outlines several problems inherent in work with adolescents. ADOLESC MED 2:389-396, 1991


Alteration of the extracellular matrix of cultured human keratinocytes by transformation and during differentiation.
We have investigated the production of 3 extracellular matrix proteins (fibronectin, laminin and entactin) and glycosaminoglycans (GAGs) by keratinocytes derived from human squamous-cell carcinomas (SCCs). All the SCC lines retained the ability to synthesize fibronectin, laminin and entactin, and to incorporate them into an extracellular matrix. In some of the SCC lines fibronectin production was higher than in normal keratinocytes, and in most lines laminin production was equal to or higher than that seen in normal keratinocyte strains. All the tumorigenic SCC lines produced less entactin than normal keratinocytes. Five out of 7 SCC lines showed a shift in GAG production compared with normal keratinocytes, so that in these lines heparan sulphate was the major GAG as opposed to hyaluronic acid in the normal keratinocytes. As these changes could have been a consequence of the reduced differentiation found in the SCC lines, we fractionated normal keratinocytes into 4 size classes corresponding to different stages of differentiation, using Percoll gradient centrifugation. It was found that the ability to produce these extracellular matrix glycoproteins and GAGs was lost as keratinocytes terminally differentiated. However, this did not explain the matrix changes seen in the SCC lines, since the undifferentiated normal keratinocytes produced a normal pattern of extracellular matrix components. Nonetheless, the loss of extracellular matrix production may well explain the reduction in substratum adhesiveness which occurs as keratinocytes terminally differentiate.


Parvovirus B19 infection infrequently involved in children and adults with myelodysplastic syndrome.
Parvovirus B19 infection has occasionally been reported to mimic myelodysplastic syndrome (MDS) or to cause worsening of anemia in MDS. We examined the presence of parvovirus DNA in a series of children (n=19) and adults (n=39) with a diagnosis of MDS. The series of adults included only refractory anemia (RA) and RA with ring sideroblasts (RARS). Investigation for parvovirus B19 DNA in bone marrow cells was performed employing the nested form of the polymerase chain reaction (PCR). Only a 51-year-old male with RA tested positive for parvovirus DNA. Serial examinations demonstrated the disappearance of parvovirus DNA from the bone marrow. We conclude that parvovirus infection may only rarely mimic MDS or be a superimposed infection in childhood MDS or in RA and RARS in adults.


Cerebrospinal Fluid Monoamine Metabolite Analysis in Pediatric Movement Disorders.
Abnormal concentrations of dopamine and serotonin metabolites in the cerebrospinal fluid is the diagnostic hallmark of a group of treatable conditions known as the monoamine neurotransmitter disorders. We assessed cerebrospinal fluid dopamine and serotonin metabolite concentrations in a series of 69 patients affected by movement disorders of unknown etiology. Abnormal results were disclosed in 13/69 subjects (19%). Both primary and secondary monoamine neurotransmitter disorders were observed. The clinical presentation of both forms was hypokinetic-rigid syndrome or dystonia. L-Dopa treatment resulted in significant improvement of the clinical picture in the majority of primary neurotransmitter disorders. Eight patients presented a secondary neurotransmitter disorder. One suffered from a GM2 gangliosidosis and one from infantile bilateral striatal necrosis. Etiologic diagnoses were not established in the others. L-Dopa was started in four patients, leading to a significant improvement of hypokinesia in the patient suffering from GM2 gangliosidosis and a slight improvement in 3 unclassified patients.


DNA triple helix stabilization by bisguanidinyl analogues of biogenic polyamines.
The polycationic nature of biogenic polyamines such as spermine (SPM, 1) and spermidine (SPD, 2) plays an important role in selective binding to polyanionic nucleic acids. These interactions are mediated by electrostatic and hydrogen bonding forces which led to stabilization of DNA duplexes and triplexes. Transformation of primary amino groups in these molecules into corresponding guanidinium functions is expected to amplify the electrostatic component resulting in improved binding. An easy chemical transformation route as described here gives rise to bisguanidinated derivatives of spermine (SPMG, 3) and spermidine (SPDG, 4). Both enhances DNA duplex stability over the parent polyamines whereas SPMG is more selective for stabilization of DNA triplexes even at pH 7.0. The results have implication for designing of new DNA binding ligands.


Transcriptome profiling of the developing postnatal mouse testis using next-generation sequencing.
Mammalian testis development is a complex and highly sophisticated process. To study the dynamic change of normal testis development at the transcriptional level, we investigated mouse testes at three postnatal ages: 6 days postnatal, 4 weeks old, and 10 weeks old, representing infant (PN1), juvenile (PN2), and adult (PN3) stages, respectively. Using ultra high-throughput RNA sequencing (RNA-seq) technology, we obtained 211 million reads with a length of 35 bp. We identified 18837 genes that were expressed in mouse testes, and found that genes expressed at the highest level were involved in spermatogenesis. The gene expression pattern in PN1 was distinct from that in PN2 and PN3, which indicates that spermatogenesis has commenced in PN2. We analyzed a large number of genes related to spermatogenesis and somatic development of the testis, which play important roles at different developmental stages. We also found that the MAPK, Hedgehog, and Wnt signaling pathways were significantly involved at different developmental stages. These findings further our understanding of the molecular mechanisms that regulate testis development. Our study also demonstrates significant advantages of RNA-seq technology for studying transcriptome during development.


Biochar facilitated bioprocessing and biorefinery for productions of biofuel and chemicals: A review.
Biochar is traditionally used to improve soil properties in arable land and as adsorbent or precursor of activated carbon in wastewater treatment. Recent advances have shown biochar potentials in enhancing productions of biofuels and chemicals such as bio-ethanol, butanol, methane, hydrogen, bio-diesel, hydrocarbons and carboxylic acids. The properties of biochar such as high levels of porosity, functional groups, cation exchange capacity, pH buffering capacity, electron conductivity, and macro-/micro- nutrients (Na, K, Ca, Mg, P, S, Fe, etc.) provide appropriate conditions to relieve physicochemical stresses on microorganisms through pH buffering, detoxification, nutrients supply, serving as electron carrier and supportive microbial habitats. This paper critically reviewed biochar production and characteristics, biochar utilization in anaerobic digestion, composting, microbial fermentation, hydrolysate detoxification, catalysis in biomass refinery and biodiesel synthesis. This review provides novel vision of biochar application, which could guide future research towards cleaner and more economic production of renewable fuels and bio-based chemicals.


Rapid effects of 17beta-estradiol on epithelial TRPV6 Ca2+ channel in human T84 colonic cells.
The control of calcium homeostasis is essential for cell survival and is of crucial importance for several physiological functions. The discovery of the epithelial calcium channel Transient Receptor Potential Vaniloid (TRPV6) in intestine has uncovered important Ca(2+) absorptive pathways involved in the regulation of whole body Ca(2+) homeostasis. The role of steroid hormone 17beta-estradiol (E(2)), in [Ca(2+)](i) regulation involving TRPV6 has been only limited at the protein expression levels in over-expressing heterologous systems. In the present study, using a combination of calcium-imaging, whole-cell patch-clamp techniques and siRNA technology to specifically knockdown TRPV6 protein expression, we were able to (i) show that TRPV6 is natively, rather than exogenously, expressed at mRNA and protein levels in human T84 colonic cells, (ii) characterize functional TRPV6 channels and (iii) demonstrate, for the first time, the rapid effects of E(2) in [Ca(2+)](i) regulation involving directly TRPV6 channels in T84 cells. Treatment with E(2) rapidly (<5 min) enhanced [Ca(2+)](i) and this increase was partially but significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV6 protein expression. These results indicate that when cells are stimulated by E(2), Ca(2+) enters the cell through TRPV6 channels. TRPV6 channels in T84 cells contribute to the Ca(2+) entry/signalling pathway that is sensitive to 17beta-estradiol.


Two Doses of Intravitreal Ziv-Aflibercept versus Bevacizumab in Treatment of Diabetic Macular Edema: A Three-Armed, Double-Blind Randomized Trial.
To compare the efficacy of 2 doses of intravitreal ziv-aflibercept (IVZ) with intravitreal bevacizumab (IVB) in the treatment of center-involved diabetic macular edema (DME) at 12 weeks. Three-armed, double-blind, randomized clinical trial. Eyes with center-involved DME. In this trial, 123 eyes with DME were randomly assigned to 3 injections of 1.25 mg IVZ, 2.5 mg IVZ, and 1.25 mg IVB every 4 weeks. Complete ophthalmologic examination and central macular thickness (CMT) measurement by optical coherence tomography were performed every 4 weeks up to 12 weeks. Change in best-corrected visual acuity (BCVA) at 12 weeks. Although no significant difference was evident between the 2 ziv-aflibercept groups at 12 weeks, the BCVA change was significantly better in the ziv-aflibercept 1.25 mg group than in the IVB group at the 12-week visit (P = 0.021). In regard to CMT changes, there was no significant difference between the 2 ziv-aflibercept groups; however, a significantly greater reduction in CMT was observed in the ziv-aflibercept 2.5 mg group compared with the IVB group at 12 weeks (P = 0.037). Subgroup analysis disclosed no difference in BCVA outcomes at 12 weeks among the groups in the eyes with baseline BCVA ≥20/50. In the eyes with baseline BCVA <20/50, the improvement was significantly better at 12 weeks in the ziv-aflibercept 1.25 mg group compared with the IVB group (P = 0.011). The 12-week results of this trial disclosed that both 1.25 mg and 2.5 mg doses of IVZ and IVB demonstrated BCVA improvement over baseline in the treatment of center-involved DME. However, a stronger effect of IVZ compared with IVB in terms of both visual acuity improvement and macular thickness reduction was detected in the eyes with initial BCVA <20/50. Longer-term efficacy and safety data will be needed to understand the role for this drug in practice.


Enrichment-toy trauma in a New Zealand White rabbit.
An injury was caused by an enrichment toy (a whiffle ball, which is a perforated hollow ball made of hard plastic) that led to its removal from the rabbit enrichment program. Manipulata and food treats form the basis of the Yale rabbit enrichment program. All singly housed rabbits are given toys such as balls, chains, wood blocks, PVC tubing, Nylabones, and corrugated plastic tunnels. Before they are used, all potential enrichment devices are reviewed for safety and potential veterinary problems. The whiffle ball had been considered safe because it was made of hard non-toxic plastic, had no sharp edges, was too large to be swallowed or inhaled, and was judged too sturdy to be broken by the rabbits. However, the ball became lodged in the incisors of an adult female New Zealand White rabbit, preventing her from eating or drinking for 12 h and causing marked trauma to her gums. Removal of the ball necessitated anesthetizing the rabbit and using bone cutters to cut away the ball. Ideally, environmental enrichment should increase species-specific normal behavior and minimize stereotypies and self- and conspecific-directed abusive behavior. This case illustrates that safety assessments for an enrichment device must include both the inherent properties of the device and the risks if the toy is misused or damaged. Considerations for safety assessment are discussed.


Vipassana: the Buddha's tool to probe mind and body.
The chapter reviews certain practical aspects related to Vipassana , a first-person method taught by the Buddha, to probe one's stream of conscious experience, its contents and related material events. Although references to Vipassana are found scattered throughout the Pali literature the most comprehensive and detailed account with regard to its practice is contained in the Satipatthana Sutta. This chapter summarizes some salient features of Vipassana practice as found in the Sutta. It could be possible that formal first-person methods will be found necessary to track the succession of internal subjective states even in the scientific study of consciousness. A review of classical methods could provide directions for further studies.


Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys.
The large majority of mitochondrial DNA (mtDNA) deletions analyzed from mitochondrial myopathies and aging humans have been found to be flanked by direct repeats, a finding which has led to the slip-replication hypothesis of deletion formation. In this study, we have characterized 13 mtDNA deletion breakpoints from skeletal muscle harvested from 9- to 27-year-old rhesus monkeys. Seven of the deletions, five of which were unique to a particular animal, did not have direct repeats at the deletion breakpoints. In contrast, two of the three deletions common to several animals had direct repeats flanking the breakpoints. It appears, therefore, that at least two different mechanisms exist by which mtDNA deletions are formed during aging, one requiring and one independent of flanking direct repeats. Furthermore, the species in which mtDNA deletions are detected may determine which mechanism predominates.


How do we sequence urgent cases?
Because the medical deadline is determined in hours, there is a precise mathematical definition for OR efficiency, and the impact on patient delays can be estimated. The priorities described above will give a single answer to a sequence of urgent cases.


Fluorometric determination of the activity of inorganic pyrophosphatase and its inhibitors by exploiting the peroxidase mimicking properties of a two-dimensional metal organic framework.
A copper(II)-based two-dimensional metal-organic framework with nanosheet structure (CuBDC NS) that possesses peroxidase (POx) mimicking activity was prepared. In the presence of hydrogen peroxide, the system catalyses the oxidation of terephthalic acid to a blue-fluorescent product (excitation = 315 nm; emission = 425 nm). Pyrophosphate has a very strong affinity for Cu2+ ion and blocks the POx-mimicking activity of the CuBDC NS. If, however, inorganic pyrophosphatase is present, the POx mimicking activity is gradually restored because pyrophosphate is hydrolyzed. The findings were used to design a method for the determination of the activity of inorganic pyrophosphatase by fluorometry. Fluorescence increases linearly in the 1-50 mU·mL-1 inorganic pyrophosphatase activity range. The limit of detection is 0.6 mU·mL-1 (S/N = 3). Graphical abstract A copper(II)-based two-dimensional metal-organic framework (CuBDC NS) is described that possesses POx-mimicking activity. Inorganic pyrophosphate (PPi) was hydrolyzed to phosphate in the presence of inorganic pyrophosphatase (PPase). Hence, it cannot coordinate with Cu2+ in CuBDC NS, its structure was well-conserved to catalyses the oxidation of terephthalic acid (H2BDC) to produce a blue fluorescent product (oxBDC) in the presence of hydrogen peroxide (H2O2).


Low-voltage SnO₂ nanowire transistors gated by solution-processed chitosan-based proton conductors.
Recently, a bioprotonic field-effect transistor with chitosan nanowire channel was demonstrated [Nat. Commun., 2011, 2, 476]. Here, it is interesting to find that solution-processed chitosan films with a large electric-double-layer (EDL) specific capacitance can also be used as the gate dielectrics for low-voltage individual SnO(2) nanowire transistors. The field-effect electron mobility, current on/off ratio and sub-threshold slope of such a hybrid SnO(2) nanowire device is estimated to be 128 cm(2) V(-1) s(-1), 2.3 × 10(4) and 90 mV per decade, respectively. Such low-voltage nanowire EDL transistors gated by chitosan-based proton conductors are promising for nanosensors and bioelectronics.


Intercellular adhesion molecule-1 (ICAM-1) expression is necessary for monocyte adhesion to the placental bed endothelium and is increased in type 1 diabetic human pregnancy.
That adhesion molecule expression is upregulated in endothelial cells of the placental bed in pregnancies complicated by type 1 diabetes mellitus, and that this is associated with increased adherence of peripheral blood monocytes, which can be reversed by reduction in activity or expression of relevant adhesion molecules. Specific aims were to compare the adherence of monocytes from normal pregnancies to decidual endothelial cells from both normal and diabetic pregnancies, and to examine the involvement of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in regulation of such adhesion. We examined adhesion of peripheral blood monocytes (isolated by density gradient centrifugation) of normal third trimester pregnant women, to cultured endothelial cells (isolated from decidual biopsies collected at elective caesarean section) from both normal women and those with type 1 diabetes. Adhesion molecule expression was determined by flow cytometry. The role of ICAM-1 was further investigated by monoclonal antibody-blocking experiments and gene-silencing methodology. There was a significant increase in monocyte adhesion to decidual endothelial cells from diabetic pregnancies, associated with increased endothelial cell expression of ICAM-1, but not VCAM-1. ICAM-1 expression in normal decidual endothelial cells was stimulated by pro-atherogenic and pro-inflammatory stimuli. Following ICAM-1 antibody blockade, monocyte adhesion was decreased by > 70%. ICAM-1 silencing by small interfering RNAs also inhibited monocyte adhesion and ICAM-1 expression. These findings implicate upregulation of ICAM-1 in decidual endothelial cells in the development of placental bed vascular pathology in diabetic pregnancy.


Electronic structure contributions to electron-transfer reactivity in iron-sulfur active sites: 2. Reduction potentials.
This study utilizes photoelectron spectroscopy (PES) combined with theoretical methods to determine the electronic structure contributions to the large reduction potential difference between [FeCl(4)](2)(-)(,1)(-) and [Fe(SR)(4)](2)(-)(,1)(-) (DeltaE(0) approximately 1 V). Valence PES data confirm that this effect results from electronic structure differences because there is a similarly large shift in the onset of valence ionization between the two reduced species (DeltaI(vert) = 1.4 +/- 0.3 eV). Specific electronic contributions to DeltaI(vert) have been investigated and defined. Ligand field effects, which are often considered to be of great importance, contribute very little to DeltaI(vert) (DeltaE(LF) < -0.05 eV). By contrast, electronic relaxation, a factor that is often neglected in the analysis of chemical reactivity, strongly affects the valence ionization energies of both species. The larger electronic relaxation in the tetrathiolate allows it to more effectively stabilize the oxidized state and lowers its I(vert) relative to that of the chloride (DeltaE(rlx) = 0.2 eV). The largest contribution to the difference in redox potentials is the much lower effective charge () of the tetrathiolate in the reduced state, which results in a large difference in the energy of the Fe 3d manifold between the two redox couples (DeltaE(Fe)( )(3d) = 1.2 eV). This difference derives from the significantly higher covalency of the iron-thiolate bond, which decreases and significantly lowers its redox potential.


Improved outcome and cost effectiveness in ablation of persistent atrial fibrillation under general anaesthetic.
Outcome of persistent atrial fibrillation (AF) ablation remains suboptimal. Techniques employed to reduce arrhythmia recurrence rate are more likely to be embraced if cost-effectiveness can be demonstrated. A single-centre observational study assessed whether use of general anaesthesia (GA) in persistent AF ablation improved outcome and was cost-effective. Two hundred and ninety two patients undergoing first ablation procedures for persistent AF under conscious sedation or GA were followed. End points were freedom from listing for repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at 1 year. Freedom from atrial arrhythmia was higher in patients who underwent ablation under GA rather than sedation (63.9% vs. 42.3%, hazard ratio (HR) 1.87, 95% confidence interval (CI): 1.23-2.86, P = 0.002). Significantly fewer GA patients were listed for repeat procedures (29.2% vs. 42.7%, HR 1.62, 95% CI: 1.01-2.60, P = 0.044). Despite GA procedures costing slightly more, a saving of £177 can be made per patient in our centre for a maximum of two procedures if all persistent AF ablations are performed under GA. In patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.


Is newer always better? A comparative study of 3 lithotriptor generations.
At a single center we compared the efficacy of 3 generations of lithotriptors using identical protocol inclusion and followup criteria but with different modes of anesthesia. We compared stone disintegration and dilatation of the pyelocaliceal system achieved in a prospective, randomized trial comparing the original HM3 (Dornier Medtech, Kennesaw, Georgia) and Lithostar Plus (LSP) lithotriptors, and a matched, consecutive series of 107 treatments with the Modulith SLX. Stone disintegration and dilatation of the pyelocaliceal system were evaluated by abdominal plain x-ray and renal ultrasonography 1 day and 3 months after treatment. A total of 82 treatments with the HM3, 75 with the LSP and 107 with the SLX were analyzed, matched for stone burden and location within the pyelocaliceal system. On postoperative day 1, 91%, 65% and 48% patients treated with the HM3, LSP and SLX, respectively, were stone-free or had fragments that were 2 mm or less (HM3 vs LSP p <0.001, HM3 vs SLX p <0.001 and LSP vs SLX p = 0.015). Three to 5 mm fragments were found in 7%, 21% and 35% of patients (p = 0.006, <0.001 and 0.06), and fragments 6 mm or greater were found in 1%, 14% and 15% (p = 0.002, <0.001 and 0.1, respectively). The re-treatment rate was 4% in the HM3 group, 13% in the LSP group and 38% in the SLX group (HM3 vs LSP p = 0.05, HM3 vs SLX p <0.001 and LSP vs SLX p <0.001). Obstructive pyelonephritis occurred in 1% of the HM3 group, 8% of the LSP group and 5% of the SLX group (HM3 vs LSP p = 0.02, HM3 vs SLX p = 0.12 and LSP vs SLX p = 0.4). All re-treatments except those in 5 patients were performed with the HM3. Therefore, the 3-month stone-free rate was comparable in all 3 groups (HM3 87%, LSP 80% and SLX 81%). This study indicates that the HM3 lithotriptor disintegrates caliceal and renal pelvic stones better than the LSP and SLX machines, resulting in fewer complications and re-treatments. Disintegration with the LSP machine was also superior to that of the SLX with a need for fewer re-treatments.


Measuring the primary care experiences of low-income and minority patients.
This article describes a community-based survey of patients' experiences in community and migrant health centers that was designed to (1) develop a method to measure patients' experiences and (2) create a national database of patient experiences. The project succeeded in surveying the most difficult-to-reach poor and minority populations (mainly Medicaid and uninsured populations) in medically underserved areas, although more than 10% lack ready access to a telephone, another 22% do not speak English well enough to be interviewed in English, and many have limited literacy. We analyzed the responses from 3 perspectives: (1) demographics and health status, (2) dimensions of care, and (3) patient progress through the community and migrant health center system.


The effect of palmitoylation on the conformation and physical stability of a model peptide hormone.
Peptides are ideal drug candidates due to their potency and specificity, but suffer from a short half-life and low membrane permeability. Acylation can overcome these limitations but the consequences to stability under different formulation conditions and stresses are largely unreported. Using synchrotron radiation circular dichroism (SRCD), we show that palmitoylation of a 28 amino acid peptide hormone (pI 9.82) induced a structural transition from 310-helix to α-helix, irrespective of buffer type and pH investigated (5.5-8.0) when compared to the non acylated analogues. These conformational preferences were retained in the presence of non-ionic micelles but not anionic micelles, which induced an α-helical structure for all peptides. Palmitoylation promoted an irreversible peptide denaturation under thermal stress at pH ≥ 6.5 and increased the propensity for loss of helical structure under high photon flux (here used as a novel accelerated photostability test). The presence of either ionic or non-ionic micelles did not recover these conformational changes over the same irradiation period. These results demonstrate that acylation can change peptide conformation and decrease thermal-/photo-stability, with important consequences for drug-development strategies.


Cytological effects of culture media conditioned by B16 melanoma cells and 3T3 fibroblasts.
Culture media conditioned (CM) by mixed populations of mouse B16 melanoma cells and 3T3 fibroblasts cultivated as monolayers exert cytological effects on B16 or 3T3 cells when treated separately in culture. By ultrafiltration of these CM, we show that a stimulatory activity on B16 melanoma cells proliferation is present in fractions with M.W. greater than 10,000 daltons. A strong cytotoxic activity for B16 melanoma cells and, to a lower degree, for 3T3 fibroblasts is detected in fractions with M.W. less than 1,000 daltons. The ultrastructural analysis of cells (B16 or 3T3) treated with cytotoxic fractions reveals in them mitochondrial swelling, blebs, broken membranes and dead cells.


Communication: κ-dynamics--an exact method for accelerating rare event classical molecular dynamics.
κ-dynamics is an accelerated molecular dynamics method for systems with slow transitions between stable states. Short trajectories are integrated from a transition state separating a reactant state from products. The first trajectory found that leads directly to a product without recrossing the transition state and starts in the reactant state is followed. The transition time is drawn from a distribution given by the transition state theory rate and the number of attempted trajectories. Repeating this procedure from each state visited gives a statistically exact state-to-state trajectory.


Effects of pimozide and domperidone administration on prolactin levels in neonatally estrogenized female rats.
The effects of two dopaminergic blockers, pimozide and domperidone, on the prolactin secretion were investigated in adult female rats treated neonatally with estrogens (100 micrograms of estradiol benzoate s.c. on day 1). These rats showed hyperprolactinemia (556 micrograms/l vs 57.7 in oil-injected) and treatment with pimozide or domperidone failed to increase prolactin levels in the adult age. These results suggest that the hyperprolactinemia in neonatally estrogenized female rats is produced by loss of the dopaminergic inhibition on prolactin secretion, so that the pharmacological blockade of dopaminergic receptors is uneffective. The dopamine levels in hypothalamus were similar in control and estrogenized females suggesting that failure in dopaminergic inhibition is due to a decrease in dopamine secretion to portal vessels.


Borreliacidal activity of saliva of the tick Amblyomma americanum.
Amblyomma americanum (Linneaus) (Acari: Ixodidae), an important tick vector of human and animal disease, is not a competent vector of the bacterial agent of Lyme disease, Borrelia burgdorferi, although its range overlaps the geographical distribution of Lyme disease within the United States. A possible mechanism that could prevent acquisition of B. burgdorferi spirochetes from infected hosts is the toxic effect of A. americanum saliva on B. burgdorferi. The data presented here indicate that after 24 and 48 h of exposure to A. americanum saliva, significantly fewer B. burgdorferi were alive compared to treatment controls as assessed by spirochete motility under dark-field microscopy and resistance to the dead stain, propidium iodide. After 48 h, fewer than 13% of saliva-exposed B. burgdorferi were alive. In contrast, significantly more B. burgdorferi exposed to Ixodes scapularis (Acari: Ixodidae) saliva survived after 24 or 48 h compared to A. americanum saliva or treatment controls.


Epidemiological characteristics of brucellosis in sheep and goats in Bulgaria: 2005-2008.
To analyse and present the epidemiological and epizootological situation of brucellosis in humans, sheep and goats caused by Brucella melitensis. The veterinary health services analyzsd epidemiological reports, as well as other official documents, in relation to the epidemiology and the measures undertaken for control of brucellosis in Bulgaria, 2005-08. In Bulgaria animal infections caused by Brucella melitensis have been eradicated since 1941. In 2005 several Bulgarian citizens with Brucella infection were diagnosed in the National Reference Laboratory. All the cases were imported, mostly by employees on sheep and goat farms in Greece. For a period of four years, the number of infected humans was 120 and distributed in 12 districts. Epidemiological investigations suggested that 45 persons (37.5%) were infected in Greece and 4 in Cyprus, Turkey, Italy and Tanzania respectively. All other patients were considered to be infected in Bulgaria. They were owners of infected sheep and goats or consumers of contaminated dairy products with Brucella melitensis. In June 2006, the first outbreaks of brucellosis in sheep and goat farms were recorded in the Smolyan district. By the end of 2008, the infection was registered in 16 villages of 4 districts. The average prevalence rate in the infected herds was 12.2% in goats and 1.8% in sheep. In order to achieve eradication 496 goats and 117 sheep were slaughtered. A farm where goats from Greece were introduced illegally in 2005 was identified as the primary source of the infection. the negative epidemiological aspects of free movement of goods and persons in the European Union are considered.


Surface visualization at CT colonography simulated colonoscopy: effect of varying field of view and retrograde view.
Colonoscopy is the gold standard for diagnosis of mucosal disease, but has a recognized "miss rate" for polyps probably because some lesions lie in areas of the colonic surface that do not enter the field of view. Using CT colonography (CTC) simulation this pilot study aimed to determine how much colonic surface is visualized with a standard, modern optical colonoscope (field of view 140 degrees ) with or without the addition of a retrograde viewing auxiliary imaging device (RVAID; 135 degrees ) and of a wide-angle (170 degrees ) colonoscope. Supine CTC datasets for 20 patients were reviewed with customized CTC software that calculated the percentage of colonic surface seen and number and area of nonvisualized "missed" areas at a unidirectional three-dimensional (3D) endoluminal flythrough, approximating the view obtained at optical colonoscopy. The field of view could be varied from 0-180 degrees . The combination of a colonoscope with RVAID was simulated by an additional flythrough facing the rectum. Mean colonic surface area was 2,743 +/- 759 cm2. Percentage colonic surface visualized at simulated optical colonoscopy with a 90 degrees , 140 degrees , and 170 degrees field of view was 68.0 +/- 5.2%, 86.6 +/- 3.3%, and 92.2 +/- 3.3%, respectively, P < 0.001. Simulation of a 140 degrees colonoscope with an RVAID resulted in almost complete surface visualization, 98.7 +/- 0.5%, with total missed area reduced 10-fold compared with a 170 degrees colonoscope, P < 0.001. CTC simulated 140 degrees optical colonoscopy visualizes over 85% of the colonic surface. 170 degrees colonoscopy provides a modest reduction in missed surface and the simulated addition of RVAIDs appears beneficial.


A generic approach for examining the effectiveness of traffic control devices in school zones.
The effectiveness and performance of traffic control devices in school zones have been impacted significantly by many factors, such as driver behavioral attributes, roadway geometric features, environmental characteristics, weather and visibility conditions, region-wide traffic regulations and policies, control modes, etc. When deploying traffic control devices in school zones, efforts are needed to clarify: (1) whether traffic control device installation is warranted; and (2) whether other device effectively complements this traffic control device and strengthens its effectiveness. In this study, a generic approach is developed to examine and evaluate the effectiveness of various traffic control devices deployed in school zones through driving simulator-based experiments. A Traffic Control Device Selection Model (TCDSM) is developed and two representative school zones are selected as the testbed in Beijing for driving simulation implementation to enhance its applicability. Statistical analyses are conducted to extract the knowledge from test data recorded by a driving simulator. Multiple measures of effectiveness (MOEs) are developed and adopted including average speed, relative speed difference, and standard deviation of acceleration for traffic control device performance quantification. The experimental tests and analysis results reveal that the appropriateness of the installation of certain traffic control devices can be statistically verified by TCDSM. The proposed approach provides a generic framework to assess traffic control device performance in school zones including experiment design, statistical formulation, data analysis, simulation model implementation, data interpretation, and recommendation development.


Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial.
Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis; however, there is conflicting evidence regarding the efficacy of Ginkgo biloba use. We performed a randomized, placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis. We randomized unacclimatized adults to receive acetazolamide, Ginkgo biloba, or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours. We graded AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System (LLS) and compared the incidence of AMS (defined as LLS score > or =3 and headache). Fifty-seven subjects completed the trial (20 received acetazolamide; 17, Ginkgo biloba, and 20, placebo). The LLS scores were significantly different between groups; the median score of the acetazolamide group was significantly lower than that of the placebo group (P=.01; effect size, 2; and 95% confidence interval [CI], 0 to 3), unlike that of the Ginkgo biloba group (P=.89; effect size, 0; and 95% CI, -2 to 2). Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group (effect size, 30%; 95% CI, 61% to -15%), and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group (effect size, -5%; 95% CI, -37% to 28%). In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba.


Nine year experience with the clinical use of total artificial hearts as cardiac support devices.
One hundred sixteen total artificial hearts (TAH) were implanted in 113 patients by 29 centers between April 4, 1969 and March 1, 1988. Five were permanent and 111 were temporary implants (3 patients received second implants). Eight different types of TAHs have been used. The ages ranged from 15 to 62 (mean age: permanent 57, temporary 42). Sixty-seven percent (72/108) of patients receiving the TAH for temporary support were transplanted; 6 patients were waiting for a transplant. Forty-seven percent (34/72) were alive after transplantation. Of the 92 patients receiving the Jarvik TAH (the most frequently used device) as a temporary device, 67% (62/92) were transplanted (6 currently supported) and 55% were alive after transplantation; 85% were back to work, with a normal life-style. The thromboembolic rate for patients who received the device as a temporary support was 10%, with 3 patients having residual sequellae. No deaths resulted from mechanical failure. Experience to date suggests that the use of the TAH as a temporary device can be beneficial if patients are carefully selected.


Enhancing effect of bile and bile acid on stomach tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The carcinogenic or cocarcinogenic effects of bile or bile acid on stomach carcinogenesis were investigated in inbred W rats. Bile or bile acid was introduced into the stomach by choledochogastrostomy or with food after the administration of N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] in drinking water. The animals that received MNNG and bile or sodium taurocholate (CAS: 145-42-6; N-choloyltaurine sodium salt) had a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the relevant MNNG-treated controls. The result suggested an enhancing effect of bile and sodium taurocholate in stomach tumorigenesis.


Specific alterations of cerebral hemodynamics during a planning task: a transcranial Doppler sonography study.
Planning plays an important role in daily activities, and several experimental paradigms have been investigated with brain imaging methods showing activity in putative brain regions such as dorsolateral prefrontal cortex and other frontal and non-frontal regions. The Stockings of Cambridge (SOC), a related procedure to the Tower of London task, was introduced to 21 healthy subjects while they underwent bilateral transcranial Doppler sonography (TCD) of the middle (MCA) and anterior (ACA) cerebral arteries. Different levels of difficulty were applied during continuous registration of peak mean cerebral blood flow velocity (CBFV). A specific test procedure allowed separating the actual planning from the execution phase. There was also a similar control task, which did not involve planning. CBFV differed among the planning, execution, and control conditions (MCA: P < 0.01; ACA: P < 0.001), but did not show a significant difference between the MCA and ACA (P > 0.1). Easy tasks yielded a more rapid increase of CBFV in the MCA compared to difficult problems during planning (P < 0.05). In conclusion, our findings of specific CBFV patterns support the idea of different cognitive challenges for planning and control and between easy and difficult conditions.


Effects of 2 mg.kg⁻¹ of intravenous lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to orotracheal intubation.
Lidocaine potentiates the effects of neuromuscular blockers and attenuates the hemodynamic response to orotracheal intubation. The objective of the present study was to test the effects of lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to intubation. Eighty patients were distributed in 4 groups: Groups 1 and 2 received 0.6 mg.kg(-1) of rocuronium; patients in Group 2 also received 2 mg.kg(-1) of lidocaine before intubation. Patients in Groups 3 and 4 received 1.2 mg.kg(-1) of rocuronium; patients in Group 4 received additional 2 mg.kg(-1) of lidocaine. The latency of the neuromuscular blockade was measured by acceleromyography. Hemodynamic evaluation was performed at baseline, immediately before, and 1 minute after orotracheal intubation (OI). Statistically significant differences were not observed between the latency from 0.6 mg.kg(-1) and 1.2 mg.kg(-1) of rocuronium in patients who received lidocaine before induction and those who did not. The latency in patients who received 0.6 mg.kg(-1) of rocuronium with lidocaine was statistically similar to that of those who received 1.2 mg.kg(-1) rocuronium independently of whether lidocaine was administered or not. Patients who did not receive lidocaine before induction showed the same increases in systolic, diastolic, and mean arterial pressure and heart rate after OI, which was not observed in those patients who received lidocaine. Intravenous lidocaine before anesthetic induction was capable of attenuating the hemodynamic response associated to OI maneuvers, but it did not reduce the latency of the neuromuscular blockade produced by two different doses of rocuronium.


Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients.
The purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. New-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD. Patient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11). A total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR pint = 0.059; ST pint = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (pint = 0.042). New-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.


Separation of steroid isomers by ion mobility mass spectrometry.
Ion mobility mass spectrometry performed in a compact traveling wave cell (TWIM-MS) is shown to provide a reliable, fast and repeatable method to separate derivatized steroid isomers. Three steroid isomer pairs were analyzed in their native form and as their p-toluenesulfonyl isocyanate derivatives. The native steroids were separated from each other, but no separation could be attained for the isomers. The derivatized steroid isomers were, however, properly separated by TWIM-MS with peak-to-peak resolutions close to or as high as baseline resolution (Rp-p=0.77-1.08).


Prognostic significance of hepatic arterial collaterals in liver transplant recipients with biliary strictures.
The aim of this study was to determine the prevalence of hepatic artery stenosis (HAS) and the prognostic implications of hepatic arterial collaterals in liver transplant (LT) recipients with biliary strictures. The 105 LT recipients transplanted between 2004 and 2015 at our center had documented biliary strictures. HAS and collaterals were assessed in high-quality imaging of the hepatic artery available from 66 recipients. Clinical, demographic, and biochemical recipient and donor data were retrospectively analyzed and tested for their association with biliary or arterial complications after LT. The prevalence of HAS was 68% (45 of 66) in LT recipients with biliary strictures. Seventy-six percent (37 of 49) of patients with nonanastomotic biliary strictures had HAS. This was significantly higher than in patients with anastomotic stricture, where 47% (8 of 17) of patients had a pathological hepatic arteriogram (P=.039). The location of bile duct strictures was not predictive for outcome. In contrast, arterial collaterals were associated with significantly better patient and graft survival. Impaired hepatic arterial perfusion is frequently associated with nonanastomotic strictures, but less closely correlated with anastomotic strictures. On survival analysis, hepatic arterial collaterals have a protective effect.


Port access video-assisted proximal anastomosis with the symmetry aortic connector in MIDCABG procedure.
We present an alternative way to create a video-assisted port access proximal anastomosis in the ascending aorta with the Symmetry Bypass System Aortic Connector (St. Jude Medical ATG, St. Paul, MN). This technique was successfully used in a patient undergoing urgent minimally invasive direct coronary artery bypass grafting (MIDCABG), in whom the left internal mammary artery was not harvested owing to subtotal occlusion of the left subclavian artery. Port access use of mechanical anastomotic devices may increase the indications for minimally invasive coronary artery surgery.


[Misuse of psychotropic medications in a population of subjects held for custody in the city of Paris].
Identify which psychotropic medications are misused and peddled in a population of subjects held for custody in the city of Paris. Subjects held for custody in the Medico-Legal Emergency Unit of the Paris Hôtel-Dieu hospital were examined and interrogated between March 2006 and March 2007 in order to assess their consumption of psychotropic medications. Sixty one of the 659 subjects (9.2%) interrogated were included in the study. Their main source of psychotropic medications was street dealers. The most frequently misused psychotropic agent was clonazepam (42.6%), followed by buprenorphine (30.65%) and methadone (21.3%). Clonazepam appears to have replaced flunitrazepam which now only comes in fifth position (11.4%). The finding that methadone is the third most misused drug should lead us to query this medication's dispensing method. Practitioners should remain vigilant regarding the potential misuse of psychotropic medications, particularly since they may induce severe undesirable events (addiction, neurological disorders, possibly lethal overdosage).


K-Fold: a tool for the prediction of the protein folding kinetic order and rate.
K-Fold is a tool for the automatic prediction of the protein folding kinetic order and rate. The tool is based on a support vector machine (SVM) that was trained on a data set of 63 proteins, whose 3D structure and folding mechanism are known from experiments already described in the literature. The method predicts whether a protein of known atomic structure folds according to a two-state or a multi-state kinetics and correctly classifies 81% of the folding mechanisms when tested over the training set of the 63 proteins. It also predicts as a further option the logarithm of the folding rate. To the best of our knowledge, the tool discriminates for the first time whether a protein is characterized by a two state or a multiple state kinetics, during the folding process, and concomitantly estimates also the value of the constant rate of the process. When used to predict the logarithm of the folding rate, K-Fold scores with a correlation value to the experimental data of 0.74 (with a SE of 1.2). http://gpcr.biocomp.unibo.it/cgi/predictors/K-Fold/K-Fold.cgi. http://gpcr.biocomp.unibo.it/~emidio/K-Fold/K-Fold_help.html.


Childhood emotional abuse and dissociation in patients with conversion symptoms.
The aim of the present study was to evaluate the relationship between reported childhood trauma and dissociation in patients who have a conversion symptom. Thirty-two outpatients with a conversion symptom were evaluated using Dissociative Experiences Scale, Somatoform Dissociation Questionnaire, Childhood Trauma Questionnaire, Spielberger Trait Anxiety Inventory, Clinician-Administered Dissociative State Scale, and Dissociative Disorders Interview Schedule. A DSM-IV dissociative disorder was diagnosed in 46.9% of the patients. Conversion patients with a dissociative disorder had borderline personality disorder more frequently than those without a dissociative disorder. Among childhood trauma types, emotional abuse was the only significant predictor of dissociation in regression analysis. None of the childhood trauma types predicted borderline personality disorder criteria. Borderline personality disorder, dissociation and reports of childhood emotional abuse refer to a subgroup among patients with conversion symptom. Dissociation seems to be a mediator between childhood trauma and borderline phenomena among these patients.


Retinoblastoma gene family expression in lymphoid tissues.
It appears more and more clear that retinoblastoma (RB) family of proteins represents key molecules in tumour suppression. This family consists of pRb/p105, p107 and pRb2/p130, which participate in a gene regulatory network that governs the cellular response to antimitogenic signals, and whose deregulation constitutes one of the hallmarks of cancer. Irrespective of their structural and biochemical similarities, RB proteins carry out different functional tasks. The expression of RB gene family in the reactive lymphoid tissues again confirms the different role of each member in cell cycle control and differentiation of normal cells. These different functional properties appear to be maintained in tumours lymphoid tissues, where alterations of the RB/p105 gene appear to be relatively rare. In this review, we will summarize the current knowledge about the role of the RB proteins in reactive and neoplastic lymphoid tissue.


The protective effect of fluoride treatments against enamel erosion in vitro.
Fluoride is known to reduce enamel solubility during the caries process. The aim of this investigation was to determine whether fluoride preparations affect erosion attributed to citric acid and citric acid-based soft drinks. Flat enamel specimens embedded in epoxy resin were prepared from caries free, human third molar teeth extracted from patients aged 18-35 years. Specimens were polished to have a profile within a tolerance of +/-0.3 microm measured on a profilometer. Specimens were taped to leave a 2 mm window of exposed enamel. Groups of specimens were exposed to citric acid and soft drinks with and without the addition of sodium fluoride or exposed to the same solutions after pre-treatment with fluoride products. Enamel loss was measured by profilometer after 10, 20 and 30 min of acid exposure. The different acidic solutions varied significantly in the amount of erosion produced both with and without the addition of fluoride. In addition, the different fluoride products differed significantly in the protective effect afforded. Both fluoride application methods reduced in mean terms, enamel erosion at all time points and by all acidic solutions. The majority of differences were <25% and as the study was powered to show differences as significant at or above this level few reached statistical significance. Fluoride applied to enamel either in acidic solutions or as a pre-treatment, reduces enamel erosion; however, the actual clinical benefit appears low. More studies are required, including investigations in situ.


Somatotopic representation of tactile duration: evidence from tactile duration aftereffect.
Accurate perception of sub-second tactile duration is critical for successful human-machine interaction and human daily life. However, it remains debated where the cortical processing of tactile duration takes place. Previous studies have shown that prolonged adaptation to a relatively long or short auditory or visual stimulus leads to a repulsive duration aftereffect such that the durations of subsequent test stimuli within a certain range appear to be contracted or expanded. Here, we demonstrated a robust repulsive tactile duration aftereffect with the method of single stimuli, where participants determined whether the duration of the test stimulus was shorter or longer than the internal mean formed before the adaptation (Experiment 1A). The tactile duration aftereffect was also observed when participants reproduced the duration of the test stimulus by holding down a button press (Experiment 1B). Importantly, the observed tactile duration aftereffect was tuned around the adapting duration (Experiment 1C). Moreover, the effect was confined in the adapted sensory modality (Experiment 2) and the enacted fingers within a somatotopic framework (Experiment 3). These findings suggest the early somatosensory areas with the topographic organization of hands play an essential role in sub-second tactile duration perception.


Unusual Wenckebach upper rate response of an atrial-based DDD pacemaker.
We describe in this report an unusual form of Wenckebach upper rate response produced by a DDD pulse generator with atrial-based lower rate timing. The pacemaker maintained the programmed upper and lower rate intervals at the expense of a prolonged atrial paced-ventricular paced AV interval. This form of upper rate behavior eliminated the longer cycle (containing the unsensed P wave) that occurs at the end of the pacemaker Wenckebach sequence during traditional DDD pacing with ventricular-based lower rate timing.


Nucleotide sequence of 5 S ribosomal ribonucleic acid of Iguana iguana.
Cell cultures of the reptile Iguana iguana have been labeled with 32PO4(3-) and the resulting radioactive 5 S rRNA isolated. Enzymatic digests of the radioactive RNA were fractionated by standard procedures, and the products of the digestions sequenced. From the sequences of the oligonucleotides produced by enzymatic digestion of the Iguana 5 S rRNA it is possible to propose a primary sequence for this RNA which differs in only two positions (2 and 25) from the sequence known for mammalian 5 S rRNAs. This sequence is closer to that of mammals than is that of any other nonmammalian species yet examined.


Immunohistochemical demonstration of neuropeptides in the articular disk of the human temporomandibular joint.
The distribution of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) was examined in the human temporomandibular articular disk using an indirect immunofluorescent method. All examined neuropeptides were observed in nerve fibers in the disk. These fibers were mostly located in the loose fibrous tissue of the posterior part (posterior attachment) and in the lateral region of the anterior part (anterolateral loose fibrous tissue) of the disk. The posterior attachment and anterolateral loose fibrous tissue occasionally contained isolated nerve fibers which usually showed immunoreactivity (IR) for CGRP or SP. In this tissue, perivascular fibers contained VIP or NPY, whereas isolated fibers and free nerve endings showed the IR for CGRP or SP. These neuropeptides may be involved in the regulation of blood flow and/or pain sensation in the human articular disk of the temporomandibular joint.


Rotigotine may control drooling in patients with Parkinson's Disease: Preliminary findings.
To evaluate the efficacy of rotigotine in controlling the drooling of Parkinson's Disease (PD) patients. We assessed 7 PD patients (Hoehn and Yahr scale >2.5) with three different clinical scores (Drooling Severity and Frequency Scale - DSFS, Drooling Rating Scale - DRS and Sialorrhea Clinical Scale for PD - SCS) before and after 4 weeks of therapy. Statistical differences were analyzed with Wilcoxon signed-rank test. We observed that rotigotine significantly improves drooling as measured by the lowering of the three scores (p<0.05). Among non-motor symptoms of PD, drooling is one of the most embarrassing and disabling for patients. Current treatments are unsatisfactory and novel approaches are thus desirable. In this open-label pilot study we demonstrated on a small sample of patients that up to 4mg/24h of rotigotine, a non-ergolinic dopamine agonist with continuous transdermal delivery, may be helpful in the management of drooling in advanced PD.


Evaluation of the feeding value of Dichrostachys cinerea pods for fattening pigs in Cuba.
Dichrostachys cinerea (L.) Wight & Arn. is a tropical leguminous shrub widely regarded as an invasive species in Cuba, after having invaded a significant proportion of its arable land during the past decades. Concurrently, smallholder pig producers are highly constrained by the scarcity of protein feeds. This study aimed to assess the feeding value of D. cinerea pod meal (DCPM) as an alternative protein supplement for pigs in Cuban smallholder production systems. An on-farm feeding trial was carried out with three groups (N = 10) of growing-fattening pigs over 60 days, where DCPM replaced 0, 15, and 30% in DM of a dietary commercial concentrate. Then, in an in vivo digestibility trial with eight growing pigs, apparent digestibilities of DCPM were determined for dry matter (DM), organic matter (OM) and crude protein (CP). Finally, in vitro digestibilities for OM (fecal and ileal) and CP (ileal) were determined. In the feeding trial, pig body weight gains were not affected by increased dietary substitution levels of concentrate for DCPM. Blood parameters, with a few exceptions, did not show significant differences among groups. Values for in vivo OM and CP digestibilities were 40.81 and 50.26%, and substantially higher than in vitro values. In conclusion, our results showed that at least 30% of DM in commercial concentrate could be substituted by DCPM without affecting pig growth performances under Cuban smallholder conditions. The low digestibility of DCPM is, however, not acceptable for intensive pig production systems. In vitro enzyme digestibility methods developed for commercial pig feeds are not suitable for DCPM without further calibration.


Do Co-ethnic concentrated neighborhoods protect children with undocumented parents? Focusing on child behavioral functioning.
Undocumented immigrants concentrate in ethnic enclaves, but little is known about the implications of living in such neighborhoods for children of undocumented immigrants. Using data on Mexican-origin children from the Los Angeles Family and Neighborhood Survey and the decennial census, this paper examines the influence of co-ethnic concentrated neighborhoods on children's behavioral functioning, and the extent to which parental nativity and documentation status moderate the neighborhood effects. Multilevel linear regression models show that the proportion of co-ethnics in the neighborhood apparently has no influence on Mexican-origin children. However, cross-level interactions reveal that the neighborhood context has differential effects by parental documentation status. The higher the percentage of co-ethnics in the neighborhood, the lower (better) the externalizing scores for children of undocumented immigrants, a pattern not observed for children of US-born or documented parents. The mechanism through which co-ethnic enclaves benefit children of undocumented Mexican immigrants deserves future research.


[Treatment of myeloma in the elderly].
The treatment of elderly patients with multiple myeloma was based for the last forty years on the combination of alkeran plus prednisone. The survival was short. Three new molecules, thalidomide, bortezomib and revlimid are completely changing the way we treat myeloma as well as the prognosis. These new molecules are tested either alone or in combination. The addition of thalidomide to alkeran plus prednisone has increased overall survival of two years. For the first time, major therapeutic improvements are emerging giving rise to better prognosis.


Observations on the characteristics of stimulated defaecation in severe idiopathic constipation.
A combined manometric and radioisotope study is described which was designed to investigate the motility characteristics of induced defaecation in the colon, rectum and anal canal, in patients with severe constipation. Five women with severe idiopathic constipation, aged 30-45 years, were studied. A multiple channel water-perfused manometric tube was placed colonoscopically into either the whole colon or left colon to monitor pressure activity. In two whole-colon studies, 5.5 MBq 111In DTPA and later 9 MBq 99mTc DTPA were instilled into the colon to monitor the transit of colonic contents in response to two separate stimuli. Motor activity was initiated on both occasions by intraluminal instillation of 5.5 mg bisacodyl. In the whole-colonic studies a right colonic stimulus initiated multiple high-pressure peristaltic waves which traversed the entire length of the colon. The bowel was then refractory to a second stimulus at the splenic flexure. In the five left colonic studies, a stimulus at the splenic flexure produced high-pressure peristaltic waves which proceeded distally, and which included a rise in rectal pressure. The anal canal relaxed simultaneously with the onset of peristalsis high in the left colon, and remained relaxed until the pressure wave reached the anus and bowel content had been expelled. In both types of study high-pressure waves corresponded to the effective transport of radioisotope. The constipated patients showed a coordinated motor response to the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cost-effectiveness evaluation on comprehensive control measures carrying out in schistosomiasis endemic areas with regard to different layers of administrative villages stratified by infection situation of human and domestic animals. I. Cost-effectiveness study in inner embankment of marshland and lake regions from 2006 to 2010].
To evaluate the cost-effectiveness of the comprehensive control measures carrying out in schistosomiasis endemic inner embankment of marshland and lake regions from 2006 to 2010, so as to provide the reference for further rational allocation of limited health resources and ultimately speeding up the procedure of schistosomiasis elimination. With reference to the requirements of the national schistosomiasis transmission control and phase goals for schistosomiasis control in Hubei Province, Jiangling County, one schistosomiasis control pilot of Hubei Province combined with the National Health and Family Planning Commission and Ministry of Agriculture, was selected for the study. A definition of the infection rates of human and domestic animals was used for endemic villages stratified by different layers (i.e., the village with the infection rates of human and domestic animals ≥ 3% belonged to the first layer, ≥ 1% belonged to the second layer; < 1% belonged to the third layer). By using the stratification method and cost-effectiveness analysis, the endemic villages stratified with the different layers were investigated and all the data of schistosomiasis endemic situation, cost and effectiveness of schistosomiasis control were collected and comprehensively analyzed from 2006 to 2010. In the effectiveness of schistosomiasis control, by the end of 2010, there were no first layer villages, there were 114 second layer villages, and there were 18 third layer villages in Jiangling County. In the former first layer villages, the schistosomiasis patients decreased year by year ultimately to 0; but in the second and third layer villages, the schistosomiasis patients increased. In the fecal treatment and management, the coverage rates of harm less sanitary latrines were 27.45% in 2009 and 48.74% in 2010 respectively in the second layer villages, whereas there were no harmless sanitary latrines in the first and third layer villages. In the 5 years, the input of comprehensive control measures was 10 266 3900 Yuan, much higher than the human and buffalo examinations and treatments, Oncomelania hupensis snail investigation and elimination (4 183 000 Yuan) and other labor inputs (2 239 500 Yuan). In the ratio of cost-effectiveness, the annual ratio of unit cost (1% reduction of human and buffalo infection and 1 hm2 reduction of snail areas) increased yearly. In addition, the semi-logarithmic stability trend analysis of health inputs and cost showed that there was a stable balance between inputs and cost in the different layers (logarithmic values of any two layers of pair-wise comparison were < 1, and in the third layer villages, the annual average logarithmic values of 5 years were < 1). Whereas, in the first and second layer villages, the annual average cost was fluctuated (the costs was higher than the inputs). The schistosomiasis situation is reduced year by year in Jiangling County from 2006 to 2010. Whereas, the main infection source (buffaloes) still exists and the present control measures including fecal management should be further strengthened. In the resource allocation, in the field of health, the annual distribution of key inputs and unit-cost control also has a further space of adjustment.


Malignant schwannoma with rhabdomyosarcoma features in a patient with neurofibromatosis.
We have described a case of rhabdomyosarcoma arising in a patient with neurofibromatosis. Local surgery, chemotherapy, and radiation therapy all seemed to play an essential role in treating this highly malignant tumor.


Gynaecological neoplasms in postmenopausal women of Himachal Pradesh.
A controlled prospective study was conducted on 300 postmenopausal women attending the Kamla Nehru Hospital from November, 1990 to August, 1992. The incidence of gynaecological neoplasms was 31.3% in both the study group (300 postmenopausal women) and the control group (300 premenopausal women). The incidence of malignant neoplasms was 24.6% in study group and 8.6% in control group. This difference was highly significant (p < 0.001). Carcinoma cervix (16%) was the commonest gynaecological malignancy followed by ovarian cancer (6%). The incidence of benign neoplasms was lower in the study group (6.6%) as compared to the control (22.6%).


Modeling generic aspects of ideal fibril formation.
Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term "critical concentration" is used for different things, involved in either nucleation or elongation.


Impact of preoperative breast MRI on surgical decision making and clinical outcomes: a systematic review.
Preoperative magnetic resonance imaging (MRI) is increasingly used in the workup of breast cancer patients and could lead to changes in surgical management. It is unclear how the information gained from MRI studies affects surgical decision making and influences clinical outcomes. These issues are addressed in this review. PubMed database searches were performed to retrieve and analyze respective original research and review articles on preoperative MRI in the evaluation of breast cancer patients. Preoperative MRI is a highly sensitive but nonspecific method that leads to changes in surgical management with increased numbers of more extended surgical interventions. It appears that a relatively large proportion of MRI-driven changes in surgical management result in overtreatment without conclusively proven beneficial effects on such clinical outcomes as decrease in reoperation rates or improved patient survival. Thus, routine use of supplementary preoperative breast MRI should be discouraged until compelling evidence of its effectiveness is available.


Anganwadi worker's participation in rural newborn care.
Anganwadi worker was involved in rural newborn care as a link between a dai and a health worker. She was trained to ensure that, (i) borderline LBW/preterm baby was kept warm at home and (ii) a very small baby was referred to hospital. The training was conducted during routine monthly meetings and cost of equipping each anganwadi worked out to be Rs 110. Newborn survival, infant survivals and overall MCH performance improved. Thus, newborn care formed an ideal entry point into MCH activities.


Symphysiotomy for the trapped aftercoming parts of the breech: a review of the literature and a plea for its use.
The most dreaded complication of vaginal breech delivery is entrapment of the aftercoming head. When this is due to disproportion, persistent attempts at vaginal extraction are likely to result in a dead or damaged baby. A largely unknown solution in this desperate predicament is to surgically enlarge the pelvis by means of a symphysiotomy. A review of the literature shows that symphysiotomy performed to free the trapped aftercoming head will save at least 80% of babies if the procedure is performed without delay. Every obstetrician should be prepared to perform a symphysiotomy if the aftercoming head is trapped.


The predictive value of cardiotocography.
Continuous fetal heart rate (FHR) recordings from 200 parturients in first stage of labour were evaluated according to conventional systems and compared with the Apgar scores at one minute. The results were disappointing, but they indicate that an improvement could be achieved by taking into consideration the periodical total uterine impulse (TUI) in the first stage of labour.


Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. I. Producing organism, fermentation, isolation and biological activities.
Several chlorinated metabolites with nematicidal, antimicrobial, and cytotoxic activities were isolated from submerged cultures of the ascomycete Lachnum papyraceum. Three compounds were identified as (+)-mycorrhizin A (3), (+)-chloromycorrhizin A (4) and (+)-dechloromycorrhizin A (5). The occurrence of 5 as a natural product is new. Two compounds, lachnumon (1) and lachnumol A (2), were found to be new fungal metabolites with cytotoxic, nematicidal and antimicrobial activities.


Current understanding of severe preeclampsia, pregnancy-associated hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, hemolysis, elevated liver enzymes, and low platelet syndrome, and postpartum acute renal failure: different clinical syndromes or just different names?
Endothelial cell injury, with subsequent vasospasm, platelet activation, unbalanced prostacyclin-thromboxane ratio, and decreased release of endothelium-derived relaxing factor, play a central role in the pathogenesis of several disorders such as preeclampsia, hemolysis, elevated liver enzymes, and low platelet syndrome, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute fatty liver of pregnancy, and acute renal failure. It is possible that all these diseases are part of a spectrum of the same illness. Although the cause remains unknown, the pathophysiology of these diseases is important for an early diagnosis. Differential diagnosis is often difficult due to the overlap of these syndromes. The purpose of this review is to clarify the differences and similarities among these pregnancy-related complications.


Brain uptake and utilization of fatty acids: applications to peroxisomal biogenesis diseases.
The brain is rich in diverse fatty acids saturated, monounsaturated and polyunsaturated fatty acids with chain lengths ranging from less than 16 to more than 24 carbons that make up the complex lipids present in this organ. While some fatty acids are derived from endogenous synthesis, others must come from exogenous sources. The mechanism(s) by which fatty acids enter cells has been the subject of much debate. While some investigators argue for a protein-mediated process, others suggest that simple diffusion is sufficient. In the brain, uptake is further complicated by the presence of the blood-brain barrier. Brain fatty acid homeostasis is disturbed in many human disorders, as typified by the peroxisomal biogenesis diseases. A workshop designed to bring together researchers from varied backgrounds to discuss these issues in an open forum was held in March, 2000. In addition to assessing the current state of knowledge, areas requiring additional investigation were identified and recommendations for future research were made. A brief overview of the invited talks is presented here.


Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments?
TomoDirect (TD) can only operate in free-breathing. The purpose of this study is to compare TD with breath-hold 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) techniques for left breast treatments, and to determine if the lack of respiratory gating is a handicap for cardiac sparing. 15 patients treated for left breast had two computed tomography simulation, in free breathing (FB) and in deep-inspiration breath-hold (DIBH). Four treatments were planned: TD-FB, 3DCRT-FB, 3DCRT-DIBH and IMRT-DIBH. Dose to PTV, heart, lungs, right breast and patient were compared. A slightly lower cardiac mean dose is found for 3DCRT-DIBH than for TD-FB group (1.99Gy Vs 2.89Gy, p=0.0462), while no statistical difference is found for heart V20. TD-FB plans show the best PTV dose homogeneity (0.053, p<0.001) and the lowest left lung mean dose (5.16Gy, p<0.001). No major differences are found for the other organs. TomoDirect and breath-hold 3DCRT are complementary techniques for left breast treatments: for a minority of patients, respiratory gating is mandatory to lower cardiac dose; for the remaining majority of patients, TomoDirect achieves better PTV homogeneity and reduced left lung dose, with cardiac dose equivalent to 3DCRT-DIBH.


Passive versus active recovery during high-intensity intermittent exercises.
To compare the effects of passive versus active recovery on muscle oxygenation and on the time to exhaustion for high-intensity intermittent exercises. Twelve male subjects performed a graded test and two intermittent exercises to exhaustion. The intermittent exercises (15 s) were alternated with recovery periods (15 s), which were either passive or active recovery at 40% of .VO2max. Oxyhemoglobin was evaluated by near-infrared spectroscopy during the two intermittent exercises. Time to exhaustion for intermittent exercise alternated with passive recovery (962 +/- 314 s) was significantly longer (P < 0.001) than with active recovery (427 +/- 118 s). The mean metabolic power during intermittent exercise alternated with passive recovery (48.9 +/- 4.9 mL.kg-1.min-1) was significantly lower (P < 0.001) than during intermittent exercise alternated with active recovery (52.6 +/- 4.6 mL.kg-1.min-1). The mean rate of decrease in oxyhemoglobin during intermittent exercises alternated with passive recovery (2.9 +/- 2.4%.s-1) was significantly slower (P < 0.001) than during intermittent exercises alternated with active recovery (7.8 +/- 3.4%.s-1), and both were negatively correlated with the times to exhaustion (r = 0.67, P < 0.05 and r = 0.81, P < 0.05, respectively). The longer time to exhaustion for intermittent exercise alternated with passive recovery could be linked to lower metabolic power. As intermittent exercise alternated with passive recovery is characterized by a slower decline in oxyhemoglobin than during intermittent exercise alternated with active recovery at 40% of .VO2max, it may also allow a higher reoxygenation of myoglobin and a higher phosphorylcreatine resynthesis, and thus contribute to a longer time to exhaustion.


Mortality and herpesvirus infections of the Pacific oyster Crassostrea gigas in Tomales Bay, California, USA.
Seed losses of Pacific oysters Crassostrea gigas have been associated with an ostreid herpesvirus-1 (OsHV-1) in Europe, and in 2002, a similar OsHV was detected in Tomales Bay, California, USA. In May of 2003, 5 stocks of seed Pacific oysters were planted at 2 sites (Inner Bay and Outer Bay) in Tomales Bay and monitored for mortality, presence/prevalence of OsHV (using polymerase chain reaction [PCR] and histology), and growth. Temperature (degrees C) and salinity data were collected every half an hour at each site. OsHV was detected at both the Inner and Outer Bay sites on the same sample date and mean temperature predicted OsHV presence (p < 0.005). High levels of mortality occurred 2 wk (Inner Bay site) and 4 wk (Outer Bay site) after OsHV detection. OsHV presence predicted mortality (p = 0.01). Temperature maximums and overall temperature exposure were greater at the Inner Bay site and may explain why mortality affected these oysters sooner than oysters planted at the Outer Bay site. Differences in cumulative mortality were significant among stocks (p < 0.0001), but not between sites (p > 0.05). OsHV prevalence was similar among stocks (p > 0.05) and between sites (p > 0.05). No evidence of herpesvirus-induced Cowdry type A nuclear inclusions or other pathogens were observed. Changes in tissue and cellular architecture including dilation of the digestive tubules and nuclear chromatin margination and pycnosis were observed in OsHV-infected oysters, consistent with previously observed OsHV infections. Stocks with smaller oysters had higher mortality rates than those with larger oysters; growth rate did not correlate with mortalities (p > 0.05). Taken together, these data suggest that the OsHV may cause or act in synergy with temperature to kill Pacific oyster seed in Tomales Bay, but further investigation of OsHV etiology in seed oysters is needed.


A multifrequency high-field electron paramagnetic resonance study of Co(II)S(4) coordination.
Advanced electron paramagnetic resonance (EPR) methods have been employed in the study of two high-spin cobalt(II) complexes, Co[(SPPh(2))(2)N](2) (Co(Ph,Ph)L(2)) and Co[(SPPh(2))(SP(i)Pr(2))N](2) (Co(iPr,Ph)L(2)), in which the bidentate disulfidoimidodiphosphinato ligands make up for a pseudotetrahedral sulfur coordination of the transition metal. The CoS(4) core in the two complexes has slightly different structure, owing to the different peripheral groups (phenyl or isopropyl) bound to the phosphorus atoms. To determine the zero-field splitting, notoriously difficult for high-spin cobalt(II), the two complexes required different approaches. For Co(Ph,Ph)L(2), the study of the X-band EPR spectrum of a single crystal as a function of temperature revealed a nearly axial character of the zero-field splitting (ZFS; E/D approximately -0.05). For Co(iPr,Ph)L(2), the combination of the EPR spectra at 9, 95, and 275 GHz revealed a rhombic character of the ZFS (E/D approximately -0.33). The energy difference between the Kramers doublets in Co(Ph,Ph)L(2) and Co(iPr,Ph)L(2) amounts to 24 cm(-1) and 30 cm(-1), respectively. From the X-band EPR spectra of diamagnetically diluted single crystals at fields up to 2.5 T for Co(Ph,Ph)L(2) and 0.5 T for Co(iPr,Ph)L(2), the effective g tensors and cobalt hyperfine tensors have been determined, including the direction of the principal axes in the cobalt sites. The values of the EPR observables are discussed in relation to the structural characteristics of the first (CoS(4)) and second coordination sphere in the complexes.


High-level expression and characterization of a thermophilic β-mannanase from Aspergillus niger in Pichia pastoris.
A novel, high-level expression, thermostable mannan endo-1,4-beta-mannosidase is urgently needed for industrial applications. The mannan endo-1,4-β-mannosidase gene (MAN) from Aspergillus niger CBS 513.88 was optimized based on the codon usage bias in Pichia pastoris and synthesized by overlapping PCR to produce MAN-P. It was expressed in P. pastoris GS115 from a constitutive expression vector pHBM-905 M. MAN-P reached 594 mg/l in shake-flasks after 192 h induction. On production in a 5 l fermenter, the yield of MAN-P reached ~3.5 mg/ml and the enzyme activity was 1612 U/ml. The enzyme exhibited a maximum activity of 3049 U/ml at 80 °C and retained 60% enzyme activity at 80 °C for 2 h. The pH optimum was 4.5 and the enzyme was stable over the pH range 1.5-11. The thermostability of MAN-P is higher than other known fungal mannanases and the expression and thermophilic properties make MAN-P useful for industrial applications.


Current opinion of aromatase inhibitor-induced arthralgia in breast cancer in the UK.
Aromatase inhibitors are now a standard of care in the management of hormone-responsive early breast cancer in postmenopausal women. The troublesome side-effect of arthralgia remains a distinct clinical problem, with limited data on its aetiology and management. The aim of this questionnaire study was to evaluate the opinion of UK breast cancer clinicians on the importance of this treatment side effect. In 2009, a questionnaire was sent to 772 breast surgeons and oncologists who manage breast cancer within the UK. The questionnaire evaluated the importance, investigation, management and the need for guidelines for aromatase inhibitor-induced arthralgia (AIA). Four hundred and sixteen (54%) returned questionnaires were suitable for analysis. By specialty, 234 (56%) were completed by breast surgeons, 134 (32%) by clinical oncologists, 45 (11%) by medical oncologists and one by a general surgeon. Three hundred and eighty-three (92%) specialists graded the importance of AIA as either very important or important; 211 (51%) did not know the aetiology of AIA; 280 (68%) did not perform bloods; 254 (61%) did not request radiology and 251 (60%) felt management was the responsibility of the oncologists. Three hundred and forty-nine (84%) considered that their practice would benefit from national guidelines. This questionnaire has highlighted that AIA is a major patient concern. Further research, educational initiatives and guidance are needed to improve the management of this treatment complication.


Differential effects of bifrontal tDCS on arousal and sleep duration in insomnia patients and healthy controls.
Arousal and sleep represent basic domains of behavior, and alterations are of high clinical importance. The aim of this study was to further elucidate the neurobiology of insomnia disorder (ID) and the potential for new treatment developments, based on the modulation of cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS). Specifically, we tested the hypotheses that bi-frontal anodal tDCS shortens and cathodal tDCS prolongs total sleep time in patients with ID, compared to sham stimulation. Furthermore, we tested for differences in indices of arousal between ID patients and healthy controls and explored their potential impact on tDCS effects. Nineteen ID patients underwent a within-subject repeated-measures sleep laboratory study with adaptation, baseline and three experimental nights. Bifrontal anodal, cathodal and sham tDCS was delivered in a counterbalanced order immediately prior to sleep. Wake EEG was recorded prior to and after tDCS as well as on the following morning. Subsequently, we compared patients with ID to a healthy control group from an earlier dataset. Against our hypothesis, we did not observe any tDCS effects on sleep continuity or sleep architecture in patients with ID. Further analyses of nights without stimulation demonstrated significantly increased levels of arousal in ID patients compared to healthy controls, as indexed by subjective reports, reduced total sleep time, increased wake after sleep onset and increased high frequency EEG power during wakefulness and NREM sleep. Of note, indices of increased arousal predicted the lack of effect of tDCS in ID patients. Our study characterizes for the first time differential effects of tDCS on sleep in patients with ID and healthy controls, presumably related to persistent hyperarousal in ID. These findings suggest that adapted tDCS protocols need to be developed to modulate arousal and sleep dependent on baseline arousal levels.


[Pseudomonas aeruginosa unilateral endogenous endophthalmitis in a preterm infant: a case report].
Endogenous endophthalmitis is a rare eye disease, affecting vulnerable subjects (such as preterm or older elderly subjects), with reserved visual and sometimes vital prognosis. We present a preterm boy, born at 35 weeks and 2 days gestation, who developed a right eye Pseudomonas aeruginosa endogenous endophthalmitis secondary to a left-foot peripherical catheter-infection-associated bacteremia. He had a first intravenous antibiotic therapy associating third-generation cephalosporin and fluoroquinolone, then Ceftazidime® by intravitreous injection and a subconjunctival injection of betamethasone. Because of the development of vitreoretinal retraction, phacophagia and vitrectomy were performed. We point and discuss the severity of this disease, associated with poor visual and vital prognosis, and the importance of prompt biological diagnosis so that the appropriate intravenous antibiotic therapy is chosen. Treatment is also discussed, especially the interest value of antibiotic intravitreous injection in preterm infants.


Epidemiological and Microbiological Investigation of an Outbreak of Severe Disease from Shiga Toxin-Producing Escherichia coli O157 Infection Associated with Consumption of a Slaw Garnish.
Investigating outbreaks of Shiga toxin-producing Escherichia coli (STEC) in England is a priority due to the potential severity of disease. However, there are often challenges in investigating outbreaks due to the small numbers of cases, poor patient recall, and low levels of bacteria that are challenging to detect in food samples using traditional laboratory culture techniques, and frequently a source is not identified. In September 2014, we investigated an STEC O157 outbreak associated with consuming a slaw garnish, and we report our findings here. Twenty confirmed cases were identified. Outbreak cases were interviewed, and menus reviewed to identify dishes consumed outside the home. Cases shared a history of eating meals at different chain restaurants. Analysis of menu items indicated shared consumption of slaw garnishes by 85.6% cases, although just 35.7% reported consuming them during interviews. Whole-genome sequencing linked cases where interpretation of the multilocus variable number tandem repeat analysis profile was obscured and indicated that the strain originated from a domestic (i.e., United Kingdom) source. Traceback identified that carrots and cabbages grown in the United Kingdom were the likely source of infection. Samples of products were examined, but STEC was not recovered. Epidemiological investigations linked the outbreak to consumption of a slaw garnish, which was poorly recalled by cases, and likely comprised of domestically produced raw vegetables. The causative organism was not isolated from food samples, and we conclude that future investigations should include sampling of animals and wildlife in the vicinity of farms where implicated produce is grown.


Malarial anemia leads to adequately increased erythropoiesis in asymptomatic Kenyan children.
Malarial anemia is associated with a shift in iron distribution from functional to storage compartments. This suggests a relative deficit in erythropoietin production or action similar to that observed in other infections. Our study in Kenyan children with asymptomatic malaria aimed at investigating whether malaria causes increased erythropoiesis, and whether the erythropoietic response appeared appropriate for the degree of resulting anemia. Longitudinal and baseline data were used from a trial with a 2 x 2 factorial design, in which 328 anemic Kenyan children were randomly assigned to receive either iron or placebo, and sulfadoxine-pyrimethamine or placebo. Erythropoiesis was evaluated by serum concentrations of erythropoietin and soluble transferrin receptor. Prospectively collected data showed that malarial infection resulted in decreased hemoglobin concentrations, and increased serum concentrations of erythropoietin and transferrin receptor. Conversely, disappearance of malarial antigenemia resulted in increased hemoglobin concentrations, and decreased concentrations of these serum indicators. Additionally, our baseline data showed that current or recent malarial infection is associated with increased serum concentrations of erythropoietin and transferrin receptor, and that these were as high as or perhaps even higher than values of children without malarial infection and without inflammation. Our findings indicate that in asymptomatic malaria, the erythropoietic response is adequate for the degree of anemia, and that inflammation probably plays no or only a minor role in the pathogenesis of the resulting anemia. Further research is needed to demonstrate the role of deficient erythropoietin production or action in the pathogenesis of the anemia of symptomatic malaria.


Off-tarp emissions, distribution, and efficacy of carbonated fumigants in a low permeability film tarped field.
Carbonated fumigants have been shown to distribute quickly and uniformly in sandy soils and improve pest control efficacy for annual crops. Low permeability films, such as VaporSafe® (TIF), could further improve fumigant dispersion by effectively retaining the fumigant in soil; however, there is a concern that the TIF can lead to higher off-tarp edge emissions. An orchard field trial was conducted to determine the off-tarp emissions, distribution, efficacy, and fate of carbonated Telone® C35 [63.4% 1,3-dichloropropene (1,3-D), 34.7% chloropicrin (CP)] that was shank-injected at 46cm soil depth. Treatments included carbonated fumigants at full- or 2/3 rates and a full rate of regular (nitrogen-pressurized) fumigants covered with standard polyethylene (PE) film, TIF, or no surface seal. Fumigant emissions at the regular tarp edge (25cm from the shank line) peaked at 3.98μgm-2s-1 for 1,3-D and 0.05μgm-2s-1 for CP. The addition of a TIF tarp extension (to 85cm from the shank line) reduce peak off-tarp emissions to <1 and <0.03μgm-2s-1 for 1,3-D and CP, respectively. Fumigant concentration under TIF was usually at least twice that under PE regardless of carbonation. Carbonation at 345KPa with 1.5% of dissolved CO2 did not significantly improve fumigant dispersion in soil profile compared to the conventional nitrogen pressurization. In a citrus nematode bioassay, only the 2/3 rate of carbonated fumigation treatment sealed with PE failed to control nematodes at 25cm away from shank line. This research indicates that a 60-cm TIF extension can effectively reduce off-tarp edge emissions in strip fumigation treatments. While the adaptability of carbonation of fumigants is still questionable, further research efforts are needed in finding effective solutions to control plant parasitic nematodes, which remain a challenge in orchard fumigation.


Chondrocytes inhibit endothelial sprout formation in vitro: evidence for involvement of a transforming growth factor-beta.
Using a quantitative in vitro model of spontaneous endothelial sprout formation, we have attempted to define physiological inhibitors of angiogenesis from hyaline cartilage, a tissue whose antiangiogenic properties have been well described. The model consists of embedding bovine microvascular endothelial cell aggregates into fibrin or collagen gels, which results in the formation of radially growing sprouts. When chondrocytes derived from the permanent cartilagenous region of the chick embryo sternum are cocultured with the endothelial cell aggregates, sprout formation is markedly inhibited. Addition of anti-TGF-beta antibodies to the cocultures significantly reduced the inhibitory effect of chondrocytes on sprout formation. Chondrocyte-conditioned medium or exogenously added TGF-beta 1 have a similar albeit transient inhibitory effect. Depletion of TGF-beta from chondrocyte conditioned medium with anti-TGF-beta antibodies and solid-phase protein-A significantly decreases the inhibition of sprout formation. These results demonstrate that a chondrocyte-derived TGF-beta-like molecule inhibits capillary sprout formation in vitro and suggest that the antiangiogenic properties of cartilage may at least in part, be mediated by TGF-beta.