Mefloquine induces oxidative stress and neurodegeneration in primary rat cortical neurons.
Mefloquine is an effective antimalarial that can cause adverse neurological events including headache, nausea, fatigue, insomnia, anxiety and depression. In this study, we examined the oxidative stress response in primary rat cortical neurons treated with mefloquine by quantifying oxidative stress markers glutathione (GSH) and F(2)-isoprostanes (F(2)-isoPs). Furthermore, we examined whether mefloquine induces synaptodendritic degeneration of primary rat cortical neurons. GSH was quantified in cortical neurons after 24-h treatment with mefloquine (0, 1, 5, 10 microM) using monochlorobimane. F(2)-isoPs were quantified in cortical neurons after 24-h treatment with mefloquine (0, 1, 5, 10 microM) using a stable isotope dilution method with detection by gas chromatography/mass spectrometry and selective ion monitoring. The concentration dependent decrease in GSH and the concomitant increase of F(2)-isoPs indicates the presence of oxidative stress in primary rat cortical neurons treated with mefloquine. Following a 24-h treatment with mefloquine, primary rat cortical neurons (0, 5, 10 microM) were fixed with 4% paraformaldehyde. Images from eight optical sections covering a distance of 2.88 microm on the z-axis were acquired using a confocal laser scanning unit. Traced images were analyzed with NeuroExplorer, a neurophysiological data analysis package. Mefloquine induces a concentration dependent decrease in the number of spines per neuron and the spine density, suggesting that mefloquine induced oxidative stress may be associated with the synaptodendritic degeneration. Together with previous work, there is strong evidence that a relationship exists between calcium homeostasis disruption, ER stress response, the oxidative stress response, and neurodegeneration. Understanding how oxidative stress alters the morphology of cortical neurons treated with mefloquine will provide further insight into the mechanism(s) related to clinically observed adverse neurological events.


Management of upper cervical spine fractures in elderly patients: current trends and outcomes.
Upper cervical spine fractures in the elderly represent serious injuries. Their frequency is on the rise. Their early accurate diagnosis might be compromised by the existence of extensive degenerative changes and deformities. Adequate stabilisation allowing fracture healing is of paramount importance. However, the debate is ongoing as to the best protocol that can be applied taking into consideration the presence of comorbidities and the increase risk of mortality in this frail patient population. A literature review, based on PubMed, related to protocols reporting on fracture fixation of the upper cervical spine, fractures (C1-C2) was carried out. Papers including information about type of fracture, treatment carried out, complication rates, mortality and morbidities were eligible to be included in this study. Fourteen papers met the inclusion criteria. Six reported on all types of injuries of the upper cervical spine, and eight only odontoid fractures (C2). Overall mortality rate ranged between 0 to 31.4%. Overall morbidity rate was from 10.3 to 90.9%. No significant difference was identified between three types of treatment (rigid collar cuff without fracture reduction, halo cast with reduction of fracture displacement, and surgical treatment). Halo-cast got the highest rate of complications. Surgical treatment got a mortality rate from 0 to 40.0%, and a morbidity rate from 10.3 to 62.5%. Non-union rate ranged between 8.9 to 62.5%. Elderly patients with upper cervical spine fractures must be notified that these injuries are associated with high incidence of non-union, morbidity and mortality.


Cisplatin and Vinorelbine -Mediated Electrochemotherapeutic Approach Against Multidrug Resistant Small Cell Lung Cancer (H69AR) In Vitro.
Small cell lung cancer (SCLC) originates from neuroendocrine branchial cells (15-20%). It is regarded as distinct from other lung cancers due to its biological and clinical features. In most cases of SCLC, surgery or radiotherapy alone is not an effective cure. The aim of our study was to examine the cytotoxic effects of chemotherapy supported by electroporation (EP) on a resistant SCLC model, in vitro. The multidrug resistant small lung cell line H69AR was used to evaluate the cytotoxic effects of cisplatin (CPPD) and vinorelbine (Navirel®; NAV) at lower doses when used with EP. Cells were treated with different concentrations of CPPD and NAV, alone or in combination with the following EP parameters: 400-1200 V/cm, 8 pulses of 100 μs duration, at 1Hz. The cell viability was estimated by MTT assay after 24 and 48 h. Apoptotic cells were detected by neutral comet assay and immunofluorescence assay with PARP-6. CPPD and NAV alone showed a dose-dependent effect on cell viability. Cytostatic drugs combined with EP revealed increased anticancer activity. Lower doses of CPPD or NAV delivered by EP were as effective as higher doses of these drugs without EP. The electrochemotherapeutic protocols increased the number of apoptotic cells and increased immunoreactivity of PARP-6. Our results indicated higher sensitivity of H69AR cells to NAV supported by EP. In SCLC cells, an increased anticancer activity was potentiated by exposure of cells to high intensity electric pulses and low drug doses. It is suggested that this method could be effectively applied in the treatment of lung cancer.


Quantitative and qualitative processes of change during staff-coaching sessions: an exploratory study.
Staff training is one of the interventions that managers can embed in their organizations to help staff improve their professional competences related to challenging behaviour of clients with intellectual disabilities. Individual coaching adds learning opportunities that are feasible but difficult to achieve in an in-service setting. In the present study, we have followed the coaching process of three staff members. Based on differences in the Linell balance of power across sessions, we explored the question: do different coaching processes have similar patterns in the development of dominance and coherence in interactions between coach and staff? Additionally, a qualitative approach was conducted to illustrate and enrich the meaning of quantitative outcomes. Processes were different regarding the balance of power at the start of the coaching, probably due to differences in resistance and insecurity. As a consequence of different starting points and differences in learning styles, each coaching process had its unique development over time. At the end, all dyads were comparable in the sense that all dyads were highly satisfied about the outcomes and process of coaching. This is in line with similar levels of power at the end of the coaching sessions suggesting equal contributions and leadership. The present findings suggest some relevant competencies of coaches within health-care services. Due to the small number of participants, the results have to be interpreted with caution. The present study provides suggestions for future research and clinical practice.


An improved HPLC-fluorescence stereoselective method for analysis of (+)-S- and (-)-R-sotalol enantiomers in plasma sample.
A simplified high performance chromatographic method (HPLC) was performed for sotalol enantiomers in plasma samples for purposes of investigation of the kinetic disposition of racemic sotalol in cardiac arrhythmic patients under multiple dose and multidrug therapy regimens. After addition of NaCl:Na2CO3 (4:1) and plasma protein precipitation by acetonitrile:methanol mixture (1:1) the supernatant was evaporated. The residue containing sotalol racemate was submitted to derivatization reaction with (-)-menthylcloroformate to R(-)- and S(+)-sotalol diastereoisomers. The diastereoisomers were resolved in HPLC, by a C18 column with fluorescent detection under lexcitation = 235 nm and lemission = 310 nm. The retention times for R- and S-sotalol were 20 and 22 minutes while that of internal standard S(-)-atenolol, was 17 minutes. The detection limit for each enantiomer was 12.5 ng/mL and intra-day/inter-day coefficients of variation were less than 10% for each enantiomer within a concentration range of 200 and 2000 ng/mL. The method was appropriate for the objective proposed.


Acremonium strictum fungaemia in a paediatric patient with acute leukaemia.
A 7-y-old boy with relapsed acute lymphatic leukaemia developed fungaemia due to Acremonium strictum, a fungus belonging to the group of the hyaline hyphomycetes. Initially, the fungus was misdiagnosed as Candida sp. due to the presence of abundant adventitious forms. At the time of diagnosis the patient was neutropenic and had a central venous catheter (CVC) in situ. The formation of an occlusive thrombotic mass in the v. subclavia dextra complicated the infection. Treatment consisted of amphotericin B, fluconazole, granulocyte colony-stimulating factor (G-CSF) and removal of the CVC. However the patient responded clinically only after the intravascular thrombus had been removed surgically. Amphotericin B, voriconazole and terbinafine showed high activity in vitro against the Acremonium isolate. A literature review revealed 5 other immunocompromised paediatric patients with a systemic or localized infection due to Acremonium spp.


Isolation and characterization of the acid and base degradation products of andrographolide.
Andrographolide was subjected to degradation under acidic and basic conditions. Three degradation products including two novel compounds, 8,9-didehydroandrographolide (AG-A) and 15-seco-andrographolide (AG-B2), and a known product, 14-deoxy-11,12-didehydroandrographolide (AG-B1), were isolated by chromatography and identified on the basis of their NMR and MS data. The degradation product, AG-A, may result from the isomerization of andrographolide under acidic conditions whereas the base degradation products, AG-B1 and AG-B2, were formed most likely due to the dehydration of allyl alcohol and the hydrolysis of andrographolide at the lactone ring, respectively.


Automatic droplet transportation on a plastic microfluidic device having wettability gradient surface.
This paper presents a microfluidic device that can automatically transport a droplet on a plastic plate. This device consists of a Cyclo Olefin Polymer (COP) plate and a SiO2 membrane and has wettability gradient surface. Lithographic patterns of hydrophilic SiO2 permitted wettability modification of a hydrophobic COP surface. A series of alternate hydrophobic and hydrophilic wedge-shaped patterns generated a required gradient in wettability. When we dropped a droplet on the wettability gradient surface, it moved along the wettability gradient due to an imbalance between surface tension forces acting on the opposite sides of the droplet edge. The droplet transportation test was carried out using water of 5 μl. As a result, we succeeded in automatically transporting the droplet on the SiO2/COP wettability gradient pattern. We also carried out droplet transportation in an enclosed microchannel for preventing droplet evaporation using DI (Deionized) water of 5 μl. In this case, the droplet was automatically transported by forming the wettability gradient pattern at the top and bottom in an enclosed microchannel without evaporation.


Application of trace metal analysis to basic problems in neurobiology studies of patients with Reye's syndrome.
Reye's syndrome (Rs) is an acute illness in children manifested by encephalopathy and fatty degeneration of the liver. The syndrome may be secondary to injury of mitochondria following a toxic insult in a susceptible individual with a viral illness. Since the response to infection often involves a change in trace metals, we investigated the metal status of patients with Rs. Decreased levels of serum and liver selenium (Se) and copper (Cu) were demonstrated via PIXE analysis, in addition to an increase in serum iron (Fe) and zinc (Zn). In a subsequent study using a rat animal model of Rs, the hepatotoxin 4-pentenoic acid (4-PA) produced similar changes in serum and liver trace metals. Serum and liver Se levels were also significantly depleted in rats exposed to another toxin, valproic acid (VPA). Aspirin, known to complex metals, may also be associated with Rs. Rats chronically exposed to aspirin had decreased serum Se, Fe, and Zn compared to controls. Selenium was also decreased in liver, as was Cu. Atomic absorption spectrophotometric analysis of serum and liver Cu for mice exposed to aspirin and influenza A virus were also studied. In liver, Cu was significantly decreased in mice on Cu-deficient diets but, not in control mice exposed to virus, or aspirin and virus. For the Se-deficient animals, liver Cu was not different from controls, but there was an increase in tissue Cu for Se-sufficient mice exposed to virus and aspirin; Cu levels were decreased in sera of this latter group. Serum Cu was increased in Cu-sufficient mice exposed to virus and aspirin. The above data are of biologic and toxicologic interest because of metalloenzyme localization in the mitochondrial matrix, the cellular compartment showing the greatest degree of pathologic change in Rs. In particular, Se-dependent gluthathione peroxidase is a major deterent of peroxidative damage of lipid membranes. The accumulated evidence suggests that alteration of trace metals, e.g., decrease in Se, may promote peroxidation of mitochondrial membranes in patients with Rs.


Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer.
Adhesion of inflammatory cells to vascular endothelium is mediated by specific cell adhesion receptors on both leukocytes and endothelial cells. One of the adhesion molecules on the endothelium is P-selectin. Decreased vascular P-selectin expression has been associated with tumor progression in melanoma patients. We now report on the expression of endothelial P-selectin in colorectal cancer (CRC). We studied a colorectal tissue specimen series ranging from normal colorectal tissue via unmetastasized primary tumors to tumors with the same depth of invasion at the primary site but with liver metastases. Moreover, P-selectin expression levels in liver metastases were determined. The number of P-selectin positive vessels as a fraction of the total number of vessels, both intra- and peritumorally, was determined by staining for CD62P and CD34, respectively. Furthermore, by immunostaining for leukocytes (CD45) and macrophages (CD68), it was evaluated whether levels of P-selectin expression influenced infiltrate density and composition. The results showed that levels of peritumoral P-selectin expression were reciprocal to the degree of progression in CRC. This relation was even more pronounced intratumorally: in metastasized primary tumors and in the metastatic lesions, P-selectin expression was virtually absent. This distribution pattern was reflected in the numbers of leukocytes that accumulated in the various tissues, since in the primary tumors with metastases, and in the metastatic lesions, hardly any infiltrating cells were observed. In these lesions, leukocytes were present in the peritumoral zone, but seemed unable to enter the tumor tissue. In primary tumors without metastasis, the intratumoral leukocyte infiltration density was significantly higher. Recruitment levels of macrophages remained constant throughout the different tissues. We suggest that downregulation of endothelial P-selectin expression is a mechanism by which CRC lesions evade inflammatory regression and, thereby, progress to a more advanced stage of malignancy.


Early childhood caries and candida albicans.
Data sourcesSeven electronic databases including PubMed, Web of Science, Scopus, Embase, Cochrane Library, LILACS and ClinicalTrials.gov and grey literature were searched. There was no information regarding the restriction of language or publication date.Study selectionFour reviewers included both epidemiological and experimental clinical studies that investigated the presence of oral C. albicans in children (age < 6 years), with or without ECC. Studies including children with severe systematic diseases were excluded.Data extraction and synthesisData were abstracted independently by four reviewers. Risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Meta-analysis was performed. The overall odds ratio of associations between the presence of C. albicans and ECC was calculated. Subgroup analysis on the different sample collection sites (plaque, swab and saliva) was performed.ResultsFifteen cross-sectional studies were included for the qualitative assessment and nine studies for meta-analysis. Regarding the quality assessment, all included studies were rated as 'fair' or 'good'. Children with the presence of oral C. albicans had 6.51 times as likely, to have ECC experience, compared to those without C. albicans (95% CI: 4.948.57, p<0.01). The odds of experiencing ECC in children with C. albicans versus those without C. albicans were 6.69 for plaque, 6.3 for oral swab, and 5.26 for salivary samples.ConclusionsChildren with oral C. albicans have higher odds of experiencing ECC, compared to children without C. albicans.


Determination of the Critical Micelle Concentration of Neutral and Ionic Surfactants with Fluorometry, Conductometry, and Surface Tension-A Method Comparison.
Micelles are of increasing importance as versatile carriers for hydrophobic substances and nanoprobes for a wide range of pharmaceutical, diagnostic, medical, and therapeutic applications. A key parameter indicating the formation and stability of micelles is the critical micelle concentration (CMC). In this respect, we determined the CMC of common anionic, cationic, and non-ionic surfactants fluorometrically using different fluorescent probes and fluorescence parameters for signal detection and compared the results with conductometric and surface tension measurements. Based upon these results, requirements, advantages, and pitfalls of each method are discussed. Our study underlines the versatility of fluorometric methods that do not impose specific requirements on surfactants and are especially suited for the quantification of very low CMC values. Conductivity and surface tension measurements yield smaller uncertainties particularly for high CMC values, yet are more time- and substance consuming and not suitable for every surfactant.


[Comparison of 2 in vitro methods of titration of antibodies neutralizing the classic swine plague virus].
Swine fever virus neutralization have been studied by the following method: variable plaque forming units numbers are mixed with a predetermined serum dilution. Infectivity is measured before (VO) and after (Vr) neutralization reaction. Neutralization index (N.I. = logVo/V) represent the difference between the two titers. It had been demonstrated that mass law is a good approximation to describe swine fever virus neutralization. So the most useful form in which to express the relation between N.I. and dilution logarithm (log D) is NI = NIo--K log D (I) where K is the constante corresponding to the slope of neutralization curve. A sligh K variation is observed according to immunoglobulin classes sharing antibody activity. Average K value is equal to 3. NIO is the NI obtained when extrapolating the curve to log D = o. These results have permitted to compare the two seroneutralization methods commonly used: "constant serum" method and "variable serum" method (determination of serum dilution inhibiting 50% of infectivity: D50). From formula (I) the following relation can be obtained: see formular. Theoretical and experimental log D50 values were appromaximatively the same (difference inferior or equal to 0.3). So D50 can be calculated by both methods.


Reliability of the Zurich Neuromotor Assessment.
Reliability of measurements of timed performance and ratings of associated movements (AMs) for tasks of the Zurich Neuromotor Assessment is investigated and methods to improve it are proposed. Better results were found for timed performance than for AMs. On average, intra-rater, inter-rater, and test-retest reliability (measured via intraclass correlation) were around 0.95, 0.9, and 0.65 for timed performance, and around 0.8, 0.7, and 0.45 for AMs. Reliability can be dramatically improved by considering neuromotor components (i.e., summary measures of individual measurements obtained at different tasks) instead of single tasks, which is significant for clinical work and research.


Activation of the adenosine A2A receptor attenuates experimental autoimmune encephalomyelitis and is associated with increased intracellular calcium levels.
Multiple sclerosis (MS) is a common autoimmune disease that inevitably causes inflammatory nerve demyelination. However, an effective approach to prevent its course is still lacking and urgently needed. Recently, the adenosine A2A receptor (A2AR) has emerged as a novel inflammation regulator. Manipulation of A2AR activity may suppress the MS process and protect against nerve damage. To test this hypothesis, we treated murine experimental autoimmune encephalomyelitis (EAE), a model for MS, with the selective A2AR agonist, CGS21680 (CGS). We evaluated the effects of CGS on the pathological features of EAE progression, including CNS cellular infiltration, inflammatory cytokine expression, lymphocyte proliferation, and cell surface markers. Treatment with CGS significantly suppressed specific lymphocyte proliferation, reduced infiltration of CD4(+) T lymphocytes, and attenuated the expression of inflammatory cytokines, which in turn inhibited the EAE progression. For the first time, we demonstrate that CGS can increase the intracellular calcium concentration ([Ca(2+)]i) in murine lymphocytes, which may be the mechanism underlying the suppressive effects of CGS-induced A2AR activation on EAE progression. Our findings strongly suggest that A2AR is a potential therapeutic target for MS and provide insight into the mechanism of action of A2AR agonists, which may offer a therapeutic option for this disease.


Determination of the superconductor-insulator phase diagram for one-dimensional wires.
We establish the superconductor-insulator phase diagram for quasi-one-dimensional wires by measuring a large set of MoGe nanowires. This diagram is roughly consistent with the Chakravarty-Schmid-Bulgadaev phase boundary, namely, with the critical resistance being equal to RQ=h/4e2. Deviations from this boundary for a small fraction of the samples prompt us to suggest an alternative phase diagram, which matches the data exactly. Transport properties of wires in the superconducting phase are dominated by phase slips, whereas insulating nanowires exhibit a weak Coulomb blockade behavior.


In vivo modulation of the number of muscarinic receptors in rat brain by cholinergic ligands.
Administration of the muscarinic agonist oxotremorine led to a decrease in the number of muscarinic receptors, as determined by specific binding of [3H]quinuclidinyl benzilate ([3H]QNB), in several rat brain regions both during development and at maturity. In contrast, administration of the muscarinic antagonist scopolamine led to an increase in the number of [3H]QNB-binding sites in various brain regions. Scopolamine also prevented the decrease in the number of [3H]QNB-binding sites induced by administration of an organophosphorus drug. The results are compatible with the hypothesis that the number of brain muscarinic receptors, or at least of a sub-class of them, is regulated by their transmitter.


Exosomes-based biomarker discovery for diagnosis and prognosis of prostate cancer.
African American men in the United States have higher incidence and mortality rates due to prostate cancer (PCa) compared to other races. In 2016 alone, nearly 30,000 cases of PCa in African American men were diagnosed and 4,450 men died from PCa. The underlying reasons for this health disparity in PCa are complex and include social, economic, and biologic determinants. To reduce or eliminate this health disparity, we must better understand the biology of the disease in African Americans and then develop novel diagnostic and prognostic biomarkers useful for timely and effective treatment decisions. Recently, there has been remarkable progress in understanding the role of exosomes (vesicles of 30-150 nm diameter) in cancer development and progression. Exosomes are loaded with unique cargo, including proteins, nucleic acids, lipids, and metabolites, that could predict the cells of their origin. Therefore, circulating exosomes in cancer patients are being used as a type of biopsy to identify novel biomarkers for early diagnosis, prognosis, and therapeutics. In this review, we discuss the promising use of exosomes to (a) identify race-related unique biological features of PCa, and (b) discover novel biomarkers for better diagnosis and prognosis of PCa, with the goal of reducing cancer health disparities.


[Identification of new genes that affect [PSI^(+)] prion toxicity in Saccharomyces cerevisiae yeast].
Translation termination is an important step in gene expression. Its correct processing is governed by eRF1 (Sup45) and eRF3 (Sup35) proteins. In Saccharomyces cerevisiae, mutations in the corresponding genes, as well as Sup35 aggregation in [PSI^(+)] cells that propagate the prion form of Sup35 lead to inaccurate stop codon recognition and, consequently, nonsense suppression. The presence of stronger prion variants results in the more efficient suppression of nonsense mutations. Previously, we proposed a synthetic lethality test that enables the identification of genes that may influence either translation termination factors or [PSI^(+)] manifestation. This is based on the fact that the combination of sup45 mutations with the strong [PSI^(+)] prion variant in diploids is lethal. In this work, a set of genes that were previously shown to enhance nonsense suppression was analyzed. It was found that ABF1, FKH2, and REB1 overexpression decreased the growth of strains in a prion-dependent manner and, thus, might influence [PSI^(+)] prion toxicity. It was also shown that the synthetic lethality of [PSI^(+)] and sup45 mutations increased with the overexpression of GLN3 and MOT3 that encode Q/N-rich transcription factors. An analysis of the effects of their expression on the transcription of the release factors genes revealed an increase in SUP35 transcription in both cases. Since SUP35 overexpression is known to be toxic in [PSI^(+)] strains, these genes apparently enhance [PSI^(+)] toxicity via the regulation of SUP35 transcription.


Combined use of autologous transfusion techniques to avoid allogeneic transfusion in spinal fusion surgery with instrumentation.
This study conducted a retrospective review of the medical records of 321 patients to delineate the efficacy of the combined use of autologous transfusion (AT) techniques. Transfusion profiles between an AT and homologous transfusion (HT) group were compared. A much lower proportion of patients were exposed to allogeneic blood in the AT group (13%) than in the HT group (98%, p<0.001). In the AT group, a significantly smaller proportion of patients were exposed to allogeneic blood in patients transfused with three or four AT techniques (8%) than those with one or two techniques (29%, p<0.05). A febrile reaction (11% of patients) after a reinfusion of post-operatively shed blood was the only side effect associated with an AT. In conclusion, an AT is effective for preventing the exposure of allogeneic blood in spinal fusion surgery. The combined use of multiple AT techniques may further improve its efficacy.


Observation of 4 nm pitch stripe domains formed by exposing graphene to ambient air.
We study epitaxial graphene on the 6H-SiC(0001) surface under ambient conditions using frequency-modulation atomic force microscopy. We observe large terraces with a self-assembled stripe structure within a highly adsorbate covered surface on top of the graphene. To identify the origin of the structure, we compare the experimental data on graphene with calculations and experiments on graphite that predict the formation of a solid-gas monolayer in the solid-liquid interface of hydrophobic surfaces.


Emergence of CD8+ T cells expressing NK cell receptors in influenza A virus-infected mice.
Both innate and adaptive immune responses play an important role in the recovery of the host from viral infections. In the present report, a subset of cells coexpressing CD8 and NKR-P1C (NK1.1) was found in the lungs of mice infected with influenza A virus. These cells were detected at low numbers in the lungs of uninfected mice, but represented up to 10% of the total CD8(+) T cell population at day 10 postinfection. Almost all of the CD8(+)NK1.1(+) cells were CD8alphabeta(+)CD3(+)TCRalphabeta(+) and a proportion of these cells also expressed the NK cell-associated Ly49 receptors. Interestingly, up to 30% of these cells were virus-specific T cells as determined by MHC class I tetramer staining and by intracellular staining of IFN-gamma after viral peptide stimulation. Moreover, these cells were distinct from conventional NKT cells as they were also found at increased numbers in influenza-infected CD1(-/-) mice. These results demonstrate that a significant proportion of CD8(+) T cells acquire NK1.1 and other NK cell-associated molecules, and suggests that these receptors may possibly regulate CD8(+) T cell effector functions during viral infection.


[Benign prostate hypertrophy and sexual health].
This article is centered on the possible impact of benign prostate hypertrophy on the male sexual life. Not only concerning the symptomatology of this affection but also concerning the side-effects of medication as well as, if necessary, a surgical intervention. A particular attention is given to the possibility of using new associations between medication, for instance between alpha-blockers and inhibitors of 5-phosphodiesterases.


Electrical coating method of graphene oxide.
In this work, we use the electrical method to coat graphene oxide (GO) on ITO (Indium Tin Oxide) glass. The coated GO was characterized by Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The coated surface was monitored by scanning electron microscope (SEM) and atomic force microscope (AFM). Based on this coating method, we can control the thickness of GO film by changing the applied voltage. Result of thickness control was analyzed by AFM and transmittance measurement. Also this method can selectively deposition of GO film is possible on patterned ITO. This result was confirmed by Raman spectroscopic mapping.


Prevention of chronic urinary retention in orthotopic bladder replacement in the female.
Chronic urinary retention is a frequent complication after orthotopic bladder replacement. Herein a new technical modification to avoid voiding dysfunction is described. Between January 1995 and January 2004, 62 women had orthotopic bladder replacement after radical cystectomy. From November 1998 on, 35 patients were operated using a new technical modification, consisting in the fixation of a large and thick flap of peritoneal and extraperitoneal tissue deriving from the posterior wall of the vagina to the edges of endopelvic fascia to create a resistant hammock under the reservoir. 25 women have a follow-up longer than 12 months, range 12-56, and are considered in this study. Only one, out of 25 patients, still has occasionally stress incontinence but she did not need to use pads. Two patients are incontinent at night. None of 25 patients has a residual urine volume greater than 100 ml or needed intermittent catheterization. Median bladder capacity is 350 ml, range 280-430 ml. Median creatinine level is 1.1 mg/dl, range 0.7-1.2 mg/dl. The creation of a posterior support to the neobladder, by harvesting a thick flap, has, in our series, completely avoided the occurrence of chronic urinary retention, which is the most common long-term complication of bladder replacement in the female. Our series is sufficiently large to exclude serendipity and to be compared with other series in the literature.


Nitrosylhemoglobin Wood: effects of inositol hexaphosphate on thiol reactivity and electron paramagnetic resonance spectrum.
Properties of Hb Wood (beta-97(FG4)His leads to Leu), a high oxygen affinity hemoglobin with reduced hemeheme interaction, were examined in its nitric oxide liganded form. The reactivity of the beta-93 thiol groups and the electron paramagnetic resonance (EPR) spectrum were examined to determine what effect the amino acid substitution, which occurs at the alpha1beta2 interface, would have on inositol hexaphosphate induced transition of this form of the tetramer. Binding of inositol hexaphosphate (IHP) in a 1:1 stoichiometry was demonstrated. In spite of apparently normal interaction with IHP, there was little or no change in the reactivity of the beta-93 thiol groups and in the electron paramagnetic resonance (EPR) spectrum as contrasted with the marked changes characteristic of normal hemoglobin (HbA). In contrast with NO-HbA, there was also no development of the EPR hyperfine structure in NO-Hb Wood with increased protonation of the protein at pH below 7.0. Taken together with the observations of Henry and Banerjee ((1973), J. Mol. Biol. 73, 469) on the development of NO-Hb EPR hyperfine structure and of Perutz et al. (1974a), Biochemistry 13, 2174) on changes in thiol reactivity with the R leads to T transition, the results suggest that IHP or H+ cannot switch NO-Hb Wood to the T conformation. Since the atomic structures of met- and deoxyhemoglobin offer no indication that His-97 plays any special part in the allosteric mechanism (M. E. Perutz, personal communication), it appears that the replacement of His-97 by Leu reduces the stability of the T structure relative to that of R.


Radiation doses in common X-ray examinations carried out in two dedicated paediatric hospitals.
In this study, the entrance surface dose (ESD) and the respective effective dose (E) were determined for paediatric patients undergoing various common radiological examinations in two dedicated paediatric hospitals. Measurements of ESD were carried out in 289 examinations using thermoluminescent dosemeters. The patients were categorised according to their age and the mean ESD and E values were determined for each examination and age category. These ESD values were compared with the existing diagnostic reference levels (DRLs). In both hospitals there were cases where the DRLs were exceeded but in one of them this was rather the general rule, since additionally to the routine use of grid and low tube potential settings, occasional use of fluoroscopy for positioning check was also observed. While the remedial actions required to appropriately reduce the doses were clearly identified, this cannot be achieved without the cooperation of medical physicists with operators and radiologists.


Outpatient clinics. Down the line.
A hospital with a 157-week wait for orthopaedic outpatient appointments has introduced a telephone booking system which has reduced waiting by 53 weeks. The system, introduced with a 23,000 Pounds grant from the local health group, has cut non-attendance from 17 to 5 per cent and is estimated to have saved the orthopaedics department 216,000 Pounds. Two part-time clerical workers staff the initiative. Telephone booking is now being rolled out to include outpatient clinics of other specialties and orthopaedic day case lists.


[Effects of chorionic gonadotropin on the hematopoietic stem cells].
It was shown on the exogenic colony-forming unit (CFU) assay that the chorionic gonadotropin (CG) administration to female mice CBA in doses correlating with its concentration in different stages of woman pregnancy stimulated (depending upon the doses) the CFU formation of bone marrow, but not spleen origin. Injections of CG to the ovariectomized mice has the opposite (inhibited) effect on the CFU contents in bone marrow and spleen. CG-administration in the dose of 40 U1 to the ovariectomized and non-castrated irradiated recipients bone marrow cells stimulates (statistically significant) colonies formation. As for 200 U1 dose hormone has the similar effect only on the non-castrated animals.


Outbreak of Serogroup C Meningococcal Disease Primarily Affecting Men Who Have Sex with Men - Southern California, 2016.
During March 4-August 11, 2016, 25 outbreak-associated cases of meningococcal disease, including two deaths (8% case-fatality ratio), were reported in Southern California. Twenty-four of the cases were caused by serogroup C Neisseria meningitidis (NmC) and one by N. meningitidis with an undetermined serogroup (Figure). On June 24, 2016, in response to this increase in NmC cases, primarily among men who have sex with men (MSM) in Los Angeles County, the city of Long Beach, and Orange County, the California Department of Public Health (CDPH) issued a press release and health advisory, declaring an outbreak of NmC in Southern California (1).


Tryptophan metabolism in pregnant sheep: increased fetal kynurenine production in response to maternal tryptophan loading.
The effects of a tryptophan load on the plasma concentration of kynurenine, the precursor for the production in the brain of the neuroactive products kynurenic acid and quinolinic acid, were determined in pregnant sheep at midgestation and late gestation and in nonpregnant sheep. Pregnant ewes were given an intravenous infusion of 100 mg/kg L-tryptophan during 2 hours at 95 to 98 days' gestation (n = 4) or 135 to 138 days' gestation (n = 10). Nonpregnant ewes (n = 6) were studied in late estrus. Arterial blood samples taken from 2 hours before to 48 hours after the start of the infusion were used for analysis of plasma tryptophan, kynurenine, and cortisol concentrations. Tryptophan loading at both gestational ages resulted in significantly greater increases in kynurenine concentrations in fetal plasma (at 95-98 days' gestation, from 5.7 +/- 1.2 micromol/L [baseline] to 247.9 +/- 86.7 micromol/L (peak); at 135-138 days' gestation, from 9.0 +/- 2.3 micromol/L [baseline] to 289.0 +/- 194.0 micromol/L [peak]) than in maternal plasma [at 95-98 days' gestation, from 4.6 +/- 0.8 micromol/L [baseline] to 118.0 +/- 79.7 micromol/L [peak]; at 135-138 days' gestation, from 4.8 +/- 2.9 micromol/L [baseline] to 98.3 +/- 67.8 micromol/L [peak]). It took longer for kynurenine concentrations to return to basal values in the fetus (24-30 hours) than in the ewe (8-12 hours). The kynurenine responses in pregnant and nonpregnant ewes were not different from each other. The production of kynurenine from tryptophan is significantly greater in the fetal lamb than in the pregnant or nonpregnant adult ewe.


Predictive value of admission platelet volume indices for in-hospital major adverse cardiovascular events in acute ST-segment elevation myocardial infarction.
Although mean platelet volume (MPV) is an independent correlate of impaired angiographic reperfusion and 6-month mortality in ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), there is less data regarding the association between platelet distribution width (PDW) and in-hospital major adverse cardiovascular events (MACEs). A total of 306 patients with STEMI pPCI were evaluated. No reflow was defined as a post-PCI thrombolysis in myocardial infarction (TIMI) flow grade of 0, 1, or 2 (group 1). Angiographic success was defined as TIMI flow grade 3 (group 2). The values of MPV and PDW were higher among patients with no reflow. In-stent thrombosis, nonfatal myocardial infarction, in-hospital mortality, and MACEs were significantly more frequent among patients with no reflow. In multivariate analysis, PDW, MPV, high-sensitivity C-reactive protein, and glucose on admission were independent correlates of in-hospital MACEs. Admission PDW and MPV are independent correlates of no reflow and in-hospital MACEs among patients with STEMI undergoing pPCI.


Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.
The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.


Genetic association between mannose-binding lectin polymorphisms and viral hepatitis: a meta-analysis.
Some previous genetic association studies tried to investigate potential associations between mannose-binding lectin (MBL) polymorphisms and viral hepatitis. However, the results of these studies were not consistent. Therefore, we performed the present meta-analysis to explore associations between MBL polymorphisms and viral hepatitis in a larger pooled population. Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible studies for pooled analyses. We used Review Manager Version 5.3.3 to conduct statistical analyses. Totally 27 studies were included for analyses (4,840 cases and 5,729 controls). The pooled analyses showed that MBL promoter (-211C/G, dominant model: P = 0.0002, I2 = 40%; over-dominant model: P = 0.0001, I2 = 22%) and exon 1 (codon 52, 54 and 57, dominant model: P = 0.04, I2 = 49%; allele model: P = 0.01, I2 = 48%) polymorphisms were both significantly associated with viral hepatitis in overall population. Further subgroup analyses revealed similar significant findings for MBL promoter polymorphism in HBV and HCV, but no any positive results were detected in subgroup analyses for MBL exon 1 polymorphism. These results suggested that MBL promoter and exon 1 polymorphisms could be used to identify individuals at higher susceptibility to HBV and HCV.


A study of former patients placed in private proprietary homes.
The authors report on a study of 1999 residents of 26 private proprietary homes for adults in the metropolitan New York City area; 76 per cent of the residents were former psychiatric inpatients. The former patients were compared with the other residents in areas of physical and psychiatric functioning and social performance; the former patients showed more dysfunction due to psychological problems than the other residents, who tended to be older and suffer from physical problems. The former patients were also categorized into three groups according to whether their needs were considered greater than, less than, or consistent with the level of services provided in the homes; the results suggest that a substantial proportion of former patients may be more appropriately placed in other facilities.


Do angle and anatomy influence outcomes in bifurcation stenting?
Coronary bifurcation lesions are regarded as complex and their treatment is still the subject of substantial debate. Important elements to consider before approaching a bifurcation include angle and anatomy, in particular the take off angle (proximal angle, A) that is between the proximal MB and SB and the carina angle (distal angle, B) that is between distal main branch (MB) and side branch (SB) and also the extent and distribution of disease on the side branch and its size. Many techniques have been used to treat coronary bifurcation lesions such as provisional stenting or double stenting but no consensus technique has been accepted primarily due to variation of disease severity, angle and anatomy. Angle B is the unique statistically significant independent predictor factor influencing outcomes. Bifurcation angle and anatomy are important predictors of short and long-term outcomes after bifurcation treatment. Moreover we should evaluate it after wiring MB and SB so as after pre-dilatation because of side branch access and carina area angle anatomy variation and plaque shift. Should be investigated if the developing of new dedicated devices for bifurcation lesions could mix the advantages of one and two-stent techniques.


Mass-analyzed ion kinetic energy (MIKE) spectrometry and the direct analysis of coca.
The technique of mass-analyzed ion kinetic energy (MIKE) spectrometry is briefly reviewed. The direct analysis, without need of prior extraction or chromatographic purification, of cocaine and cinnamoylcocaine in coca plant tissues has been accomplished with this new technique. Detection limits of below 1 ng, with a quantitative accuracy of +/- 30% at the nanogram level, have been demonstrated.


Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis.
To determine whether fever control with antipyretic therapy effects the mortality of febrile critically ill adults. Systematic review using MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials, CINAHL, Google Scholar, and 2 clinical trial registries from inception to April 2012. Randomized clinical trials comparing treatment of fever with no treatment or comparing different thresholds for fever control in adults without acute neurological injury admitted to intensive care units (ICUs) were selected for review. The effect of fever control on all-cause ICU-mortality was determined using a random effects meta-analysis. Five randomized clinical trials in 399 patients were included. The temperature threshold for treatment in the intervention group was commonly 38.3°C to 38.5°C, whereas it was typically 40.0°C for controls. Four studies used physical measures and 3 used pharmacologic measures for temperature control. There was no significant heterogeneity among the included studies (I(2) = 12.5%, P = .3). Fever control did not significantly effect ICU mortality with a pooled risk ratio of 0.98 (95% confidence interval 0.58-1.63, P = .9). This meta-analysis found no evidence that fever treatment influences mortality in critically ill adults without acute neurological injury. However, studies were underpowered to detect clinically important differences.


Length of optic nerve double inversion recovery hypersignal is associated with retinal axonal loss.
To assess the association between optic nerve double inversion recovery (DIR) hypersignal length and retinal axonal loss in neuroinflammatory diseases affecting optic nerves. We recruited patients previously affected (> 6 months) by a clinical episode of optic neuritis (ON). We had 25 multiple sclerosis (MS) patients, eight neuromyelitis optica spectrum disorder (NMOSD) patients and two patients suffering from idiopathic caused ON undergo brain magnetic resonance imaging (MRI); including a 3-dimensional (3D) DIR sequence, optical coherence tomography (OCT) examination and visual disability evaluation. Evaluation criteria were retinal thickness/volume, optic nerve DIR hypersignal length and high/low contrast vision acuity. In the whole cohort, we found good associations (< 0.0001) between optic nerve DIR hypersignal length, peripapillary retinal nerve fiber layer thickness, inner macular layers volumes, and visual disability. We found subclinical radiological optic nerve involvement in 38.5% of non-ON MS eyes. Optic nerve DIR hypersignal length may be a biomarker for retinal axonal loss, easily applicable in routine and research on new anti-inflammatory or neuroprotective drug evaluation. Detection of subclinical ON with 3D-DIR in a non-negligible proportion of MS patients argues in favor of optic nerve imaging in future OCT MS studies, in order to achieve a better understanding of retinal axonal loss in non-ON eyes.


Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors.
Follicular lymphoma (FL) is the second most frequent type of non-Hodgkin's lymphoma in adults. The disease is characterized by an indolent course with frequent relapses. Ultimately, resistance to chemotherapy or transformation to a more aggressive phase of the disease in the form of diffuse large B-cell lymphoma develops, and patients die as a result of their disease. Median survival is 8 to 10 years. The range is very wide, however, with patients surviving for more than 15 years and 10% to 15% of the patients who run a rapidly fatal course and die within 3 years after diagnosis. The translocation t(14;18) is the basic molecular defect in FL and results in protection from apoptosis by aberrant overexpression of bcl-2 protein. Accumulation of genomic alterations and clonal selection account for subsequent progression and transformation. Recently, the role of the immunologic microenvironment of FL in determining clinical behavior and prognosis has been substantiated. Combined genetic and immunologic data may now support a model for the development of FL as a disease of functional B cells in which specific molecular alterations infer intrinsic growth properties of the tumor cells as well as dictate a specific functional cross talk with the immunologic regulatory network resulting in extrinsic growth support. These insights may lead to improvement of risk stratification, but most importantly will provide tools for developing new targets and strategies for treatment.


Evaluation of filtering techniques to extract movement intention information from low-frequency EEG activity.
Low-frequency electroencephalographic (EEG) activity provides relevant information for decoding movement commands in healthy subjects and paralyzed patients. Brainmachine interfaces (BMI) exploiting these signals have been developed to provide closed-loop feedback and induce neuroplasticity. Several offline and online studies have already demonstrated that discriminable information related to movement can be decoded from low-frequency EEG activity. However, there is still not a well-established procedure to guarantee that this activity is optimally filtered from the background noise. This work compares different configurations of non-causal (i.e., offline) and causal (i.e., online) filters to classify movement-related cortical potentials (MRCP) with six healthy subjects during reaching movements. Our results reveal important differences in MRCP decoding accuracy dependent on the selected frequency band for both offline and online approaches. In summary, this paper underlines the importance of optimally choosing filter parameters, since their variable response has an impact on the classification of low EEG frequencies for BMI.


[Physiological and pathological autoimmunity in neurological disease].
Over the last years, the functions of the immune system have radically been revised. It has been illustrated how the different responses of the innate defense and the adaptative system were intimately intricated. Innate immunity is an elaborate strategy, switched on by an invariant receptor-based response that is able to develop a specific defense against some pathogens. Moreover, this innate immunity governs T- and B-cell-dependent adaptive immune response, mediated via dendritic cells whose maturation is controlled by immune specificity. The concepts of autoreactivity have also strongly progressed and the functions of the physiological autoimmune response have been highlighted. The notion of T- and B-cell self-antigens not only shapes the immune repertoire, but also the self-recognition process which is a tool for the control of the immune response itself. New concepts of the pathophysiology of autoimmune diseases have emerged from a better understanding of the immune response, balancing between an intrinsic deregulation of the immune system and system deficiency to mount an effective response against an initial injury. Of course, therapeutic strategies are challenged by these data. We should expect that control of several autoimmune processes will be achieved in a few years, e.g. in rheumatoid arthritis or Crohn's disease controlled with biotherapies.


Induction of Parkinson disease-related proteins in motor neurons after transient spinal cord ischemia in rabbits.
The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. However, the mechanisms of such vulnerability are not fully understood. We investigated a possible mechanism of neuronal death by immunohistochemical analysis for DJ-1, PINK1, and alpha-Synuclein. We used a 15-min rabbit spinal cord ischemia model, with use of a balloon catheter. Western blot analysis for DJ-1, PINK1, and alpha-Synuclein; temporal profiles of DJ-1, PINK1, and alpha-Synuclein immunoreactivity; and double-label fluorescence immunocytochemical studies were performed. Western blot analysis revealed scarce immunoreactivity for DJ-1, PINK1, and alpha-Synuclein in the sham-operated spinal cords. However, they became apparent at 8 h after transient ischemia, which returned to the baseline level at 1 day. Double-label fluorescence immunocytochemical study revealed that both DJ-1 and PINK1, and DJ-1 and alpha-Synuclein were positive at 8 h of reperfusion in the same motor neurons, which eventually die. The induction of DJ-1 and PINK1 proteins in the motor neurons at the early stage of reperfusion may indicate oxidative stress, and the induction of alpha-Synuclein may be implicated in the programmed cell death change after transient spinal cord ischemia.


Immunodeficiency diseases with rheumatic manifestations.
Most clinicians associate primary immunodeficiency disorders (PIDDs) with susceptibility to frequent or severe infections. It is less commonly recognized, however, that PIDDs are frequently associated with autoimmune or rheumatologic manifestations. This review provides a synopsis of the rheumatic manifestations associated with immunodeficiencies in each of the major compartments of the immune system.


Physician exposure to ionizing radiation during trauma resuscitation: a prospective clinical study.
A prospective study of emergency physician whole body and extremity exposure to ionizing radiation during trauma resuscitation over a three-month period was conducted. Radiation film badges and thermoluminescent dosimeter finger rings were permanently attached to leaded aprons worn by emergency medicine residents during all trauma resuscitations. One set of apron and finger ring dosimeters was designated for the resident who managed the airway and stabilized the neck, when necessary, during cervical spine radiography (A-CS resident). A separate set of dosimeters was designated for the resident supervising the resuscitation. During the study period, 150 major trauma patients requiring 481 radiographic studies were treated. The mean monthly cumulative whole body exposures were 136.7 +/- 85.0 and 103.3 +/- 60.3 mrem for A-CS and supervising residents, respectively. The mean weekly cumulative extremity exposures were 523.3 +/- 611.0 and 46.7 +/- 18.6 mrem for A-CS and supervising residents, respectively. Calculated whole body exposures per patient were 2.7 mrem for the A-CS resident and 2.1 mrem for the supervising resident. Calculated extremity exposures per patient were 41.9 +/- 48.9 and 3.7 +/- 1.5 mrem, respectively. To exceed the annual whole body exposure limit established by the National Council of Radiologic Protection, the A-CS resident, working 200 shifts per year, would have to treat 9.2 trauma patients per shift. To exceed the annual extremity exposure limit, the A-CS resident would have to treat 5.9 trauma patients per shift. Of note, European exposure limits are 10% of current US limits. We conclude that significant exposures may occur to physicians working in trauma centers and that the use of shielding devices is indicated.


Calretinin immunohistochemistry versus acetylcholinesterase histochemistry in the evaluation of suction rectal biopsies for Hirschsprung Disease.
Diagnosis of Hirschsprung disease (HSCR) relies on histologic and/or histochemical staining of sections from suction rectal biopsies. Acetylcholinesterase histochemistry (AChE) facilitates diagnosis but is not universally employed, in part because it requires special tissue handling. Calretinin immunohistochemistry (IHC) may be a useful alternative, because loss of calretinin immunoreactive nerves reportedly correlates spatially with aganglionosis. We investigated the patterns of calretinin IHC in suction rectal biopsies from HSCR and non-HSCR patients and compared the diagnostic value of calretinin IHC with a widely used rapid AChE method. In suction rectal biopsies that contain ganglion cells, small nerves in the lamina propria, muscularis mucosae, and superficial submucosa contain granular aggregates of calretinin immunoreactivity. Immunolabeling of these nerves is completely absent in the aganglionic biopsies of HSCR patients. Multiple observers independently reviewed calretinin IHC and AChE sections of suction rectal biopsies from 14 HSCR patients and 17 non-HSCR controls. Five observers, blinded to the correct diagnosis, scored each patient's calretinin IHC and AChE slides as HSCR, not HSCR, or equivocal. The frequencies of major and minor discrepant diagnoses were compared. Calretinin IHC yielded no misdiagnoses or major discrepancies between observers. In contrast, 2 misdiagnoses and significantly more interobserver disagreement resulted from the AChE-stained sections. Calretinin IHC appears to be a reasonable, and potentially superior, alternative to AChE as an adjunctive diagnostic method for evaluating suction rectal biopsies for HSCR.


Structural features of force-generating cross-bridges. A 2D-X-ray diffraction study.
In several concepts of muscle contraction it was proposed that during force generation cross-bridges assume a rigor-like conformation. However, so far 2D-X-ray diffraction patterns recorded during isometric contraction did not reveal structural features of rigor-like cross-bridges. It was therefore supposed that the number of force generating cross-bridges in isometric steady state contraction is too low to be detected in 2D-X-ray diffraction patterns. To test this concept we studied the features of 2D-X-ray diffraction patterns of different fractions of rigor-like cross-bridges by varying the concentration of the nucleotide analog ATP gamma S at high [Ca++]. Although we had a fully activated system, i.e., that weak binding cross-bridges were attached to the activated thin filament, none of the patterns was like the active pattern. Analysis of the intensity change of the actin layer lines at 1/370 A-1 and at 1/59 A-1 in diffraction patterns recorded during isometric contraction vs. relaxed and rigor conditions as well as mechanical experiments revealed that the fraction of force generating cross-bridges apparently is as high as 55-70%. Yet, in agreement with previous studies, in spite of this large fraction of force generating cross-bridges, no rigor-like features were detected in diffraction patterns recorded during isometric contraction. Moreover, the intensity distribution along the actin layer lines was clearly different in rigor compared to isometric contraction. Taken together these results provide evidence that in contrast to the above mentioned models the majority of the force generating cross-bridges seems to be in a conformation which is different from rigor.


[The "pro" and "con" of the hypothesis of interimpulse intervalic information coding in the nervous system].
The present views are outlined on the principles of information code in the nervous system. It is shown that the frequency modulation of the rhythmical neuronal activity alone is unable to provide the processing and coding of the information necessary for cognitive activity. The fluctuation of the between-impulse intervals which has been revealed by many authors is a treated as novel acquisition in the process of progressive evolution. The intervals and their various combinations as code signals can ensure the information processes simultaneously in a great number of neurons and synapses. The present state of neurophysiology and information theory don't enable an alternative hypothesis to be advanced.


Antiviral activities of hypericin.
Hypericin, a photodynamic plant quinone, readily inactivated murine cytomegalovirus (MCMV), Sindbis virus, and human immunodeficiency virus type 1 (HIV-1), especially on exposure to fluorescent light. Sindbis virus was significantly more sensitive than MCMV. The inactivated MCMV, when used to infect cells, was incapable of synthesizing early or late viral antigens. In addition to this direct virucidal effect, when hypericin was added to cells infected with viable MCMV, inhibition was also observed, particularly when the compound was added in the first two hours of infection. Again the antiviral effect was augmented by visible light. At effective antiviral concentrations, there were no discernible adverse effects on cultured cells. Thus hypericin appears to have two modes of antiviral activity: one directed at the virions, possibly on membrane components (although other virion targets cannot be ruled out), and the other directed at virus-infected cells. Both activities are substantially enhanced by light. Other recent studies on the antiviral activities of hypericin have not considered the role of light, and it is conceivable that apparent discrepancies between their results may have reflected different conditions of light exposure.


Association between intrapartum fetal heart rate patterns and neonatal abstinence syndrome in methadone exposed neonates.
Determine whether infants exposed to chronic maternal methadone with abnormal intrapartum fetal heart rate (FHR) patterns are more likely to require treatment for neonatal abstinence syndrome (NAS). Intrapartum FHR tracings analyzed in 104 pregnancies at ≥ 34 weeks gestation for FHR variability, accelerations, and decelerations. FHR patterns compared between neonates based on treatment with methadone for NAS. Secondary analysis included relation between maternal methadone dose and intrapartum FHR patterns, initiation of methadone, age at methadone initiation, and total neonatal methadone dose. Study powered to detect 30% increase in NAS incidence in neonates with abnormal FHR tracings. Seventy-six (73%) of 104 neonates required methadone treatment for NAS. Neonates who required methadone had higher average baseline FHR (131 vs. 126 bpm; p < 0.04) in active labor and less likely to have FHR tracings without accelerations (1.7% vs. 20.3%; p = 0.007) in latent labor. No significant associations between neonate's need for methadone and intrapartum FHR variability or FHR decelerations. No association between maternal methadone dose (range 30-280 mg) and treatment for NAS. The need for an infant to require methadone treatment for NAS was not reliably predicted by the intrapartum FHR patterns or the maternal methadone dose.


[Application of ARIMA model in prediction of mortality rate of suicide in Hainan province].
Objective: To analyze the trend of suicide mortality in residents of Hainan province, and explore the application of time sequence model in the prediction of the mortality of suicide. Methods: The mortality data of suicide in residents of Hainan province between January, 2014 and December, 2016 were collected and analyzed with time sequence model and the mortality rate of suicide during January-June, 2017 in Hainan was predicted with the model. Results: During January, 2014 to June 2017, a total of 576 suicide cases were reported in Hainan, the mortality rate was 1.5/100 000. The established ARIMA model had good fitting for the suicide mortality in previous times and the prediction result was quite similar to the actual mortality, the predicted mortality rate was within the 95% confidence interval of the actual rate. Conclusion: The time sequence model for the prediction of suicide mortality in Hainan was "ARIMA (0, 1, 0) (0, 0, 0) (12)" , and the prediction effect of the model was better, which can be used to predict the suicide mortality in Hainan.


Urine vascular endothelial growth factor-A is not a useful marker for endometriosis.
To determine whether urine VEGF is elevated in women with endometriosis. Prospective observational study. Tertiary care government and private hospitals. During laparoscopy for pelvic pain or infertility, urine was collected and possible endometriosis lesions were excised. Of 62 women, 40 had histology-proven endometriosis and 22 had no histological proof of the disease. None. Urine VEGF-A(121, 165) was measured and compared in women with and without biopsy-proven endometriosis. Urine VEGF levels corrected for creatinine excretion were similar in women with (83.6 +/- 11.3 pg/mg Cr) and without (88.5 +/- 10.4 pg/mg Cr) endometriosis (P =.77). The frequency distribution of urine VEGF measurements for women with and without endometriosis was similar. No significant difference was noted in urine VEGF levels when comparing endometriosis stages or in those with endometriomas compared to controls. Urine VEGF did not vary significantly over the menstrual cycle or between groups by cycle phase. No cutoff point discriminated individuals with and without the condition. It is unlikely that urine VEGF-A(121, 165), as measured in this study, will be a useful non-invasive marker for endometriosis.


Percutaneous cystolithotomy of large urinary-diversion calculi using a combination of laparoscopic and endourologic techniques.
Patients with urinary diversions are at higher risk for bladder urolithiasis. Often, the stone burden is large, necessitating open stone removal. We describe our technique for removing such stones using a combination of laparoscopic and endourologic instrumentation. With the patient in the dorsal lithotomy position or supine, cystoscopy is performed via the native urethra or catheterizable stoma, respectively. With the urinary reservoir distended with normal saline, percutaneous access is obtained under direct vision with a 10-mm trocar introduced through the scar of the previous suprapubic cystostomy. A laparoscopic entrapment bag is introduced through the trocar, into which the calculi are manipulated. The bag is delivered percutaneously through the trocar site with subsequent removal of the trocar. A 30F Amplatz renal dilator sheath (Cook Urological, Spencer, IN) is introduced directly into the bag. An ultrasonic lithotrite passed through a nephroscope is utilized to fragment and evacuate the calculi. Closure of the neocystotomy is not performed. A drainage catheter is left in for 7 days. This procedure has been successful in eight consecutive patients, six with bladder augmentations, one with a bladder reconstruction with appendicovesicostomy, and one with an Indiana pouch. All calculi were radiopaque, having a mean linear size of 4.1 cm (range 1.5-7.0) cm. Several patients had multiple stones. The mean operating room time was 123 minutes (range 48-228 minutes). Two patients had concomitant ureteroscopy with laser lithotripsy for ureteral calculi. All were rendered stone free with one procedure and were discharged within 23 hours after surgery. There were no immediate or delayed complications. Our technique of percutaneous cystolithotomy utilizing laparoscopic and endourologic instrumentation is safe and effective for the removal of large calculi from urinary diversions. It is well tolerated, allows complete stone removal in a single sitting, and obviates an open procedure.


Moderate intensity treadmill exercise alters food preference via dopaminergic plasticity of ventral tegmental area-nucleus accumbens in obese mice.
Obesity has been associated with the excessive intake of palatable food as well as physical inactivity. To investigate the neurobiological mechanism underlying the exercised-induced prevention and treatment of obesity, the present study examined the effect of treadmill exercise on the preference for palatable food in mice. Levels of tyrosine hydroxylase (TH) in the ventral tegmental area-nucleus accumbens system were also analysed, as well as levels of dopamine, dopamine transporter, and D2 receptors in the nucleus accumbens. Forty C57BL/6J mice were randomly divided into a control group (CG, n=10) and a high-fat diet group (HG, N=30). Mice of the HG group were fed a high-fat diet for 12 weeks in order to induce a model of obesity, following which the obese mice were randomly divided into an obese control group (OG, n=11) and an obese+exercise group (OEG, n=12). OEG mice received 8 weeks of treadmill exercise intervention. Our results indicate that, relative to animals in the OG group, OEG mice exhibited significant decreases in the preference for high-fat diets and insulin resistance, along with increases in the preference for sucrose and milk, TH and D2 receptor expression, and levels of dopamine in the ventral tegmental area-nucleus accumbens system. These results suggest that moderate-intensity treadmill exercise can alter food preference in obese mice, which may be mediated by dopaminergic plasticity of the ventral tegmental area-nucleus accumbens and enhanced insulin sensitivity.


Perceptual responses in free vs. constant pace exercise.
The purpose of the present investigation was to study the influence of free versus constant pace on perceived exertion (RPE) and estimated time Limit (ETL). Ten athletes performed a graded test aimed to determine maximal oxygen uptake (VO2max) and the velocity associated with VO2max (vVO2max), a constant run to exhaustion at 90 % vVO2max to determine the time and distance to exhaustion at this relative velocity, a free paced run over the distance to exhaustion set by the time to exhaustion at 90 % vVO2max. Oxygen uptake and velocity during constant pace and free pace runs were both averaged throughout the entire period of exercise and without the last lap. The results did not show any significant effect of free versus constant pace on RPE and ETL. Averaged oxygen uptake between free and constant pace runs was not significantly different, whereas averaged vVO2max, % vVO2max and time to exhaustion was significantly higher for free pace runs only for the entire exercise. Consequently, compared to the constant pace run, the free pace one only allowed athletes to finish the run by a sprint which was effective in increasing performance, but not to perceive the free pacing run as being less strenuous than the constant pace one.


Expression patterns of developmental genes reveal segment and parasegment organization of D. melanogaster genital discs.
We have used the expression patterns of genes known to be important during early Drosophila development to determine the segment-parasegment organization of the genital discs and to localize the three primordia in the male and female genital discs, engrailed (en) and hedgehog (hh) were used to locate posterior compartments in A8-A10, while cubitus interrupts (ci) localized the anterior compartments for each segment, decapentaplegic (dpp) identified the anterior cells that abut en and hh at the anterior-posterior border. abdominal-A (abd-A) identified the anterior compartment for abdominal segment 8 (aA8) in females but was not detected in the repressed female primordium in male discs. Abdominal-B (Abd-B) was expressed throughout the discs except for a small area along the edge of the posterior lobes, leaving open the possibility that A11 may contribute to the genital discs, caudal (cad) was expressed segmentally in the anal primordium of A10, extending through the Abd-B unstained region, wingless (wg) and gooseberry (gsb) may have assumed an added role in the discs perhaps providing proximal-distal cues. Models are presented to show how the segments and parasegments may fuse together during embryogenesis to form the mature male and female genital discs.


Progesterone diminishes the sensitivity of gonadotropin-releasing hormone-stimulated luteinizing hormone (LH) release and protects an LH pool from desensitization: actions opposed by cholera toxin.
In the present study we used characterized perifusion model for the development of homologous desensitization to GnRH in the pituitary gonadotrope. This system relies on immobilized primary pituitary cultures that are perifused with various pulse patterns and concentrations of GnRH; these patterns and concentrations are selected to maintain, inhibit, restore, circumvent the desensitization process. The data indicate that progesterone (P) inhibits LH release in response to pulsatile administration of GnRH; this effect is blocked by the P antagonist, RU486, and is opposed by cholera toxin, an agent that provokes the formation of cAMP. In multiple and rapid pulse administration of 5 nM GnRH, which is usually associated with desensitization, the area under the LH release curve is progressively diminished when cells are preincubated with medium only or with medium containing cholera toxin. In contrast, cells pretreated with P are less responsiveness to GnRH, but maintain a relatively constant level of LH release (area under the curve). These data suggest a modulatory role for P in the development of the desensitized state and indicate that P can functionally protect a pool of LH from the onset of desensitization.


[Club drugs: old medicines as new party drugs].
During the last few years the term club drugs has been used for defining an heterogeneous group of chemical substances in permanent evolution, that are consumed for recreational purposes. These substances have been extensively used, firstly by the Rave culture and later by the so called Club culture. These movements are characterized by the search of amplified sensations, by means of the combination of electronic music, marathon dancing and substance abuse. After years with a predominating consumption of designer amphetamines in these groups, it seems that the use of another type of substances is increasing, fundamentally drugs with hallucinogenic effects. This review focus in four of these substances; ketamine, dextromethorphan, nitrous oxide and gamma-hydroxybutyric acid (GHB, liquid ecstasy), and includes a discussion of their pharmacology, recreational use, adverse effects and patient management. These drugs are, at he same time, drugs of abuse and medicines with concrete indications in therapeutics, with an important increase of their consumption in the last few years. The Rave and Club cultures are also described.


[Epidemioclinical aspects of dermatomyositis in the region of Tunis].
Dermatomyositis (DM) is a rare but serious disease. The aim was to evaluate the epidemiology, presenting clinical manifestations, therapeutic features and outcome of patients with DM. From January 1986 to December 2003, we collected retrospectively cases of DM identified at the dermatology department of Habib Thameur hospital. We included only patients with definitive diagnosis of DM. We included 13 patients, mean aged 32.85 years: 9 adults and 4 children. We identified 9 cases of adult DM among them 2 cases of wiihich were of paraneoplastic DM and 4 cases of juvenile DM among them 1 case of amyopathic DM and 1 case of DM associated with connective tissue disease. The evolution of DM followed the course of the neoplasm for the 2 patients with paraneoplastic DM. All patients received corticotherapy initially. Patients were followed-up for an average of 3 years (2 months to 10 years). We found no serious repercussions on the growth of children with juvenile DM. DM is rare in Tunisia. In our study, its frequency is about 0.72 patients per year. Age of onset of DM is markedly smaller than the one reported in the relevant litterature. Our 2 cases of DM associated with cancer are considered like really paraneoplastic. Juvenile DM seems to have a relatively good prognosis.


Adaptive alterations of elastic fibers in the bilaminar zone of rabbit temporomandibular joint following disc displacement.
To study the adaptive alterations of elastic fibers in the bilaminar zone (BZ) of rabbit temporomandibular joint (TMJ) following disc displacement. Twenty-eight Japanese white rabbits were used in this study. The right temporomandibular joints of 20 of 28 rabbits were subjected to the surgical procedure of anterior disc displacement (ADD). Four rabbits in the surgical group were sacrificed at 2, 4, 6, 8 and 12 weeks after operation. Their temporomandibular joints were studied histochemically. Elastic fibers were reduced in number and ran irregularly in the superior lamina of BZ from ADD rabbits. The jungly elastic fibers (EFs) could still be seen at 2 weeks after operation. At 4 weeks, the number of EFs decreased significantly; EFs lost their jungly arrangement and were shaped like rough dots, of which the arrangement and the lengths were different. Six weeks after operation, many EFs were replaced by distorted, uneven, non-oriented fine EFs, distributed unevenly and some thick or fine EFs that ran irregularly. The number of EFs decreased further and their arrangement was more deranged at 8 weeks. At 10 and 12 weeks, EFs in the superior lamina of BZ were similar to those at 8 weeks. Our results show that EFs lost their function as well as their distribution and arrangement after disc displacement.


Theory of Primary Photoexcitations in Donor-Acceptor Copolymers.
We present a generic theory of primary photoexcitations in low band gap donor-acceptor conjugated copolymers. Because of the combined effects of strong electron correlations and broken symmetry, there is considerable mixing between a charge-transfer exciton and an energetically proximate triplet-triplet state with an overall spin singlet. The triplet-triplet state, optically forbidden in homopolymers, is allowed in donor-acceptor copolymers. For an intermediate difference in electron affinities of the donor and the acceptor, the triplet-triplet state can have a stronger oscillator strength than the charge-transfer exciton. We discuss the possibility of intramolecular singlet fission from the triplet-triplet state, and how such fission can be detected experimentally.


[Production of non-volatile amines by strains of enterococci].
During the last few years there has been great interest concerning the problems related with the presence of pressor amines in different kinds of cheese, specially since the "cheese syndrome" was made evident. Since the capacity of the bacterial groups involved in cheese manufacture to produce these amines has not yet been clarified, it was decided to study the production capacity of tyramine, tryptamine and histamine of enterococci strains probably used in the starter cultures. Forty-one enterococci strains were analysed cultivating them in milk and in milk with the addition of the corresponding aminoacids. It was determined that only low percentages of Streptococcus faecalis subsp. liquefaciens and Streptococcus durans strains (34% and 11% respectively) produced traces of tyramine and tryptamine in milk. But when cultivated in the presence of the corresponding aminoacids, a large percentage of strains of all the species produced tyramine in high concentrations and different percentages of them produced tryptamine in concentrations no higher than 200 ppm. All strains analysed proved to be unable to produce histamine. It can be concluded that there exists a strong probability for enterococci to produce tyramine and tryptamine in different concentrations specially when developed in the presence of the corresponding aminoacids.


Novel interferon-based pre-transplantation conditioning in the treatment of a congenital metabolic disorder.
Hematopoietic stem cell (HSC) gene therapy is a potentially curative treatment modality for monogenic hematological diseases and storage disorders. It is necessary, however, to establish pre-bone marrow (BM) transplant conditioning regimens that minimize DNA damage and toxicity. Type I interferon (IFN) signaling activates quiescent HSCs and enables them to be sensitive to 5-fluorouracil (FU)-mediated cytotoxicity, thus implying a molecular basis for improving HSC transplant outcomes. Here we show that type I IFN preconditioning, without irradiation or DNA alkylating agents, significantly enhanced the HSC engraftment efficiency in wild-type (WT) recipient mice. The importance of active type I IFN signaling in HSC recipients was further demonstrated using mice lacking IFN regulatory factor 2 (IRF2), a transcriptional suppressor of type I IFN signaling. In both WT and Irf2(-/-) recipients, active type I IFN signaling greatly enhanced the sensitivity to 5-FU or low-dose irradiation of HSCs. Importantly, IFN-based pre-BM transplant conditioning was also applicable to the treatment of Sly syndrome, a congenital storage disorder with β-glucuronidase deficiency, in which it restored enzyme expression at the HSC level and reciprocally reduced pathological glycosaminoglycan storage. Our findings suggest type I IFN-based preconditioning, combined with HSC transplantation, as a novel nongenotoxic treatment of some congenital diseases.


Sexual activity and chronic heart failure.
Little has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity.


Time-dependent oxidative stress and histopathological changes in Cyprinus carpio L. exposed to microcystin-LR.
Microcystins (MCs) are produced by cyanobacteria in aquatic environments and are a potential risk to aquatic organisms. Increasing evidence suggests that oxidative stress may play an important role in the toxicity mechanism of MCs on fish, but most studies were based on relatively high concentrations. In this study, the effect of time-dependent oxidative stress in livers of Cyprinus carpio L. (C. carpio) exposed to 10 μg l(-1) of microcystin-LR (MC-LR) for 0-14 days was investigated. MC-LR induced histopathological changes in liver and gills were also assessed after 14 days exposure. Electron paramagnetic resonance (EPR) spectrum was used to directly investigate the reactive oxygen species (ROS) in fish liver and results showed that hydroxyl radical ((∙)OH) was significantly induced at 0.5 day and then tended to decline with an increase of exposure period. As a response of antioxidant, catalase (CAT) activity increased slightly at first and then decreased with exposure period. A pronounced promotion of glutathione-S-transferase (GST) indicated that the conjugation reaction of MC-LR and GSH occurred. A time-dependent decrease of reduced glutathione (GSH) with an increase of oxidized glutathione (GSSG) level suggested GSH was involved in detoxification of MC-LR in the liver. Oxidative damage was evidenced by the significant increase of malondialdehyde (MDA) level at 2-6 days. After 14 days exposure, a series of pathological changes, like partially dissolved parenchymal architecture, vacuolar degeneration, necrosis, hemorrhage and slight inflammatory cells infiltration in fish liver tissues could be observed. Scanning electron microscopic (SEM) studies showed that dissolved MC-LR could also result in pathological changes like partial broken epithelial cells, deformed taste buds and loose gill filament and lamella in gill tissues. These results suggest that although a restoring response occurred, C. carpio could still be adversely affected by MC-LR at 10 μg l(-1).


Butyrylcholinesterase-positive innervation of the spleen in rats.
Innervation of the spleen in rats was studied. Butyrylcholinesterase-(BuChE)-positive nerve components of the organ were visualized by the direct thiocholine method. BuChE-positive nerve components enter the spleen in a common bundle with arteries. In the organ they form characteristic periarterial and periarteriolar plexiform arrangements, which are especially conspicuous around the aa. centrales running through the white pulp. Then, nerve fibres extend away from these plexuses into adjacent layers of trabeculae further into marginal layers of periarterial lymphatic sheath (PALS) as well as into the mantle zone of follicles. Several scattered periarteriolar and solitary nerve fibres can be seen in the marginal sinuses and cords of the red pulp. In the fibrous capsula BuChE-positive nerve fibres can also be seen which have an evident connection with trabecular and parenchymal nerves of the organ. Microscopic findings support the notion that BuChE-positive nerve profiles supply not only the vasculature, but also the parenchymal components of the spleen, and they may participate, to a great extent, in the regulation of the immune processes in this organ.


Recently discovered EZH2 and EHMT2 (G9a) inhibitors.
Methyltransferase enzymes are promising epigenetic oncotargets. Recent efforts toward the development of inhibitors of two methyltransferases, EZH2 and G9a, as potential anticancer therapies are reviewed with a focus on the structure-activity relationships of compounds published from 2012. Benzamide-substituted 2-pyridones are still by far the most popular selective EZH2 inhibitor class but alternative classes are now being reported. There are now three EZH2 inhibitors in clinical development with the first responses in lymphoma patients with tazemetostat. Potent inhibitors of G9a are also published but no examples have yet reached the clinic. Dual blockage of EZH2-G9a is exemplified by one series of compounds. We conclude this review by presenting the three clinical stage compounds with the first clinical response data.


Immunohistochemical demonstration of prostaglandins E2, F2 alpha, and 6-keto-prostaglandin F1 alpha in rat dental pulp with experimentally induced inflammation.
Using formalin-fixed and EDTA-decalcified cryostat sections, the immunohistochemical localization of prostaglandin (PG) E2, PGF2 alpha, and 6-keto-PGF1 alpha (a stable metabolite of PGI2) was examined in normal rat and inflamed dental pulp. Inflammation was induced by opening the pulp chamber. There was no immunoreactivity for prostaglandins in normal dental pulp, whereas positivities for PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were demonstrated in the cytoplasm of macrophages and endothelial cells in the inflamed dental pulp. In addition to these cells, numerous pulp cells and odontoblasts existing in the inflamed pulp and its apical noninflamed area also were intensely stained for PGF2 alpha. Such an area with positive cells gradually extended in an apical direction with the progression of inflammation. These findings suggested that PG production from these host cells is involved in development of inflammation of rat dental pulp.


Directed dihydroxylation of cyclic allylic alcohols and trichloroacetamides using OsO4/TMEDA.
The oxidation of a range of cyclic allylic alcohols and amides with OsO4/TMEDA is presented. Under these conditions, hydrogen bonding control leads to the (contrasteric) formation of the syn isomer in almost every example that was examined. Evidence for the bidentate binding of TMEDA to OsO4 is presented and a plausible mechanism described.


Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene.
We have isolated and sequenced the mouse preprodynorphin gene (Pdyn). The Pdyn gene can encode for six biologically active dynorphin peptides. The predicted mouse preprodynorphin has 90%, 67%, and 66% identity with the predicted rat, porcine, and human preprodynorphins, respectively. Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney.


Essential oils of three taxa of the Nepeta argolica aggregate from Greece.
The essential-oil composition of three not previously studied taxa belonging to the Nepeta argolica aggregate was examined. The oils of N. argolica ssp. malacotrichos and N. argolica ssp. vourinensis (both Greek endemics) are rich in 1,8-cineole (30.9-55.6% of the total oil composition), while those of the Balkan endemic N. spruneri are rich in either sesquiterpenes (mainly caryophyllene oxide, 14.6-19.8%) or in 4aα,7α,7aβ- and 4aα,7α,7aα-nepetalactones (total content 17.5-40.5%), accompanied by caryophyllene oxide (11.5-11.7%) and 1,8-cineole (up to 16.5%). The comparison of our results with published information concerning the related taxa of the N. argolica aggregate showed that while oils with as main components nepetalactones or 1,8-cineole are common, sesquiterpene-rich oils are reported for the first time within the aggregate.


Genetic control by cis-acting regulatory RNAs in Bacillus subtilis: general principles and prospects for discovery.
In recent years, Bacillus subtilis, the model organism for gram-positive bacteria, has been a focal point for study of posttranscriptional regulation. In this bacterium, more than 70 regulatory RNAs have been discovered that respond to intracellular proteins, tRNAs, and small-molecule metabolites. In total, these RNA elements are responsible for genetic control of more than 4.1% of the genome-coding capacity. This pool of RNA-based regulatory elements is now large enough that it has become a worthwhile endeavor to examine their general features and to extrapolate these simple observations to the remaining genome in an effort to predict how many more may remain unidentified. Furthermore, both metabolite- and tRNA-sensing regulatory RNAs are remarkably widespread throughout eubacteria, and it is therefore becoming increasingly clear that some of the observations for B. subtilis gene regulation will be generally applicable to many different species.


Bright molecules with sense, logic, numeracy and utility.
Using cartoons as an organizational aid, we illustrate how the 'fluorophore-spacer-receptor' format of fluorescent PET (photoinduced electron transfer) sensors and switches can be logically extended in many different directions. These include emissive sensors for various chemical species and properties, and exploit various kinds of emission. Common sensing issues such as dynamic range, internal referencing, selectivity, mapping and space resolution are addressed. The sensory output function is also developed into more complex forms, molecular logic/computation being one such example. Molecular logic leads to molecular arithmetic. Real-life applications to physiological monitoring, medical diagnostics and molecular computational identification of small objects are included.


Energy barriers for the addition of H, *CH3, and *C2H5 to *CH2=CHX [X = H, CH3, OH] and for H-atom addition to RCH=O [R = H, CH3, *C2H5, n-C3H7]: implications for the gas-phase chemistry of enols.
Although enols have been identified in alcohol and other flames and in interstellar space and have been implicated in the formation of carboxylic acids in the urban troposphere in the past few years, the reactions that give rise to them are virtually unknown. To address this data deficit, particularly with regard to biobutanol combustion, we have carried out a number of ab initio calculations with the multilevel methods CBS-QB3 and CBS-APNO to determine the activation enthalpies for methyl addition to the CH(2) group of CH(2)=CHX where X = H, OH, and CH(3). These average at 26.3 +/- 1.0 kJ mol(-1) and are not influenced by the nature of X; addition to the CHX end is energetically costlier and does show the influence of group X = OH and CH(3). Replacing the attacking methyl radical by ethyl makes very little difference to addition at CH(2) and follows the same trend of a higher barrier for addition to the CH(OH) end. In the case of H-addition it is more problematic to draw general conclusions since the DFT-based methodology, CBS-QB3, struggles to locate transition states for some reactions. However, the increase in barrier heights in reaction at the CHX end in comparison to addition at the methylene end is evident. For hydrogen atom reaction with the carbonyl group in the compounds methanal, ethanal, propanal, and butanal we see that for addition at the O-center the barrier heights of ca. 38 kJ mol(-1) are not influenced by the nature of the alkyl group whereas addition at the C-center is different on going from H --> alkyl but seems to be invariant at 20 kJ mol(-1) once alkylated. Rate constants for H-atom elimination from 1-hydroxyethyl, 1-hydroxypropyl, and 1-hydroxybutyl radicals, valid over the range 800-2000 K, are reported. These demonstrate that enols are more prevalent than previously suspected and that 1-buten-1-ol should be almost as abundant as its isomeric aldehyde 1-butanal during the combustion of 1-butanol and that this will also be the case for other alcohols provided that the appropriate structural features are present. Since the toxicity of enols is not known experiments and further theoretical studies are clearly desirable before the large-scale usage of alcohol biofuels commences. An enthalpy of formation for butanal of Delta(f)H(298.15 K) = -204.4 +/- 1.4 kJ mol(-1) [Buckley, E.; Cox, J. D. Trans. Faraday Soc. 1967, 63 , 895 901] is recommended, the uncertainty surrounding that for the 2-hydroxypropyl radical has been markedly reduced, and new values for 1-buten-1-ol, 1-propen-1-ol, and 2-propen-2-ol of -171.8 +/- 1.6, -151.8 +/- 1.7, and -169.9 +/- 1.5 kJ mol(-1), respectively, are proposed.


Hypoglycemia induced by interaction between clarithromycin and disopyramide.
A 59-year-old man receiving hemodialysis was hospitalized due to severe hypoglycemic attack. The patient had been treated with disopyramide (50 mg/day) because of paroxysmal atrial fibrillation. Hypoglycemia occurred after taking clarithromycin (CAM, 600 mg/day), a macrolide antibiotic. The serum disopyramide concentration reached 8.0 micrograms/ml (23.6 microM) in the presence of CAM, while it was 1.5 micrograms/ml before the addition of CAM. A 75 g oral glucose tolerance test and daily profiles of blood glucose value showed that blood glucose levels were significantly lower in the presence of CAM and disopyramide compared to that in the absence of these drugs. The Turner index in the presence of CAM and disopyramide was significantly higher than that in the absence of these drugs, suggesting that a toxic concentration of disopyramide enhanced insulin secretion, resulting in the induction of hypoglycemic attacks, in which the inhibitory effects of CAM on the hepatic chytochrome P-450 might be involved. QT and QTc intervals were prolonged in the presence of CAM and disopyramide, but torsades de points were not observed in this patient receiving nicorandil (15 mg/day). Thus, it should be taken into account that life-threatening hypoglycemia may result from the interaction between clarithromycin and disopyramide.


Characterisation of the rare cadmium chromate pigment in a 19th century tube colour by Raman, FTIR, X-ray and EPR.
In an investigation of the artists' materials used by P. S. Krøyer the contents of the tube colours found in Krøyer's painting cabinet were examined. In most cases, the results of the pigment analyses were as expected based on our knowledge of artists' colours used in the late 1800s and early 1900s. However, in one of the tube colours labelled "Jaune de Cadmium Citron" (cadmium lemon yellow) an extremely rare cadmium chromate pigment was found. The pigment was analysed and characterised by Raman microscopy (MRS), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffraction (PXRD), single-crystal X-ray crystallography, and electron paramagnetic resonance (EPR) spectroscopy. Cadmium chromate was synthesised by precipitation from an aqueous solution of cadmium nitrate and potassium chromate, and the resulting yellow crystals proved identical to the pigment found in the tube colour "Jaune de Cadmium Citron". The structure determined by single-crystal X-ray diffraction identified the pigment as 2CdCrO4·KOH·H2O or more accurately as KCd2(CrO4)2(H3O2) illustrating the μ-H3O2- species. The yellow colour of the paint sample taken from the tube had a greenish hue, which became even more prominent upon storage and drying. EPR analysis of the sample showed the presence of paramagnetic degradation products containing Cr(III) and Cr(V).