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We have studied the relative pre- and postjunctional neuromuscular blocking effects of Org 9426 in the isolated rat hemidiaphragm muscle using twitch tension and electrophysiological recording techniques. Postjunctional effects were assessed from decreases in twitch height and from end-plate current amplitude and time constant of decay. Prejunctional effects were assessed from the fade of tetanic twitch tension and end-plate current amplitude rundown. There were no significant differences between the relative pre- and postjunctional effects of Org 9426 and those of previously studied steroidal neuromuscular blocking compounds. It is concluded, therefore, that the rapid onset and short duration of Org 9426 seen in vivo is not a consequence of a strong prejunctional, relative to postjunctional, blocking effect of the compound.

Many procedures have been described for the treatment of rectal internal mucosal prolapse (RMP), but the therapeutic effect is questionable. This work is to evaluate clinical and functional outcome of a modified Delorme’s operation—trans-anal purse-string sutures for rectal mucosa and submucosa (TAS) for the treatment of RMP. The clinical data of 58 patients with rectal mucosal prolapse treated with rectal mucosa and submucosal tissue (TAS) between June 2004 and June 2008 were analyzed retrospectively. No patient died. Satisfaction with surgery was high in 48 cases (82.8%), moderate in seven (12.1%), and low in three (5.17%). Prolapse relapse rate was 5.17%. Anal tenesmus and urge to defecate resolved in 52 (89.7%) patients. Constipation improved in 25 of 28 (89.3%) previously constipated patients. No surgery-associated constipation occurred. The mean operative time was 31 (range 22–46) min. Mean hospital stay was 3 days (range 2–6). Mean patient follow-up was 32 months (range 12–60). From our data, TAS for the treatment of RMP showed encouraging results with little complications and an acceptable relapse rate. This economical procedure induces only mild trauma and is easy to perform, making it worthy of further practice and investigation.

Security issues which exist while sequences produced by Logistic chaotic map used in encryption is analyzed. Moreover, an improved algorithm to the problem is proposed. The algorithm solves the some common problems of Logistic chaotic map such as “stable windows”, blank windows and uneven distribution of sequences etc. by increasing bifurcation parameters. It overcomes the defects of sequences crossing over the bounds by the modular operation which breaks through the limits that the bifurcation control parameters can not be bigger than 4. The experiment results show that the sequences generated by the improved algorithm have better pseudo-randomness, lower computational complexity and much bigger key space. Therefore, it is very suitable for the data encryption, especially for multimedia data.

Large conductance calcium- and voltage- gated potassium (BK) channels are important regulators of physiological homeostasis and their function is potently modulated by protein kinase A (PKA) phosphorylation. PKA regulates the channel through phosphorylation of residues within the intracellular C-terminus of the pore-forming α-subunits. However, how PKA phosphorylation of the α-subunit effects changes in channel activity are unknown. The STREX variant of BK channels is inhibited by PKA as a result of phosphorylation of a serine residue within the evolutionary conserved STREX insert. As this inhibition is dependent upon phosphorylation of only a single α-subunit in the channel tetramer we hypothesised that phosphorylation results in major conformational rearrangements of the C-terminus. Using a combined imaging, biochemical and electrophysiological strategy we have defined the mechanism of PKA-inhibition of BK channels. We demonstrate that the cytosolic C-terminus of the STREX BK channel uniquely interacts with the plasma membrane via palmitoylation of evolutionary conserved cysteine residues. PKA-phosphorylation of STREX dissociates the C-terminus from the plasma membrane resulting in channel inhibition. Abolition of channel palmitoylation by site-directed mutagenesis or pharmacological inhibition of palmitoyl-transferases prevents PKA-mediated inhibition. Thus PKA inhibition of BK channels is conditional upon the palmitoylation status of the channel. Palmitoylation and phosphorylation are both dynamically regulated thus cross-talk between these two major post-translational signalling cascades provides a novel mechanism for conditional regulation of BK channels. Interplay of these distinct signalling cascades has important implications for the dynamic regulation of BK channels and the control of physiological homeostasis.

Large conductance calcium- and voltage-gated potassium (BK) channels are important regulators of physiological homeostasis and their function is potently modulated by protein kinase A (PKA) phosphorylation. PKA regulates the channel through phosphorylation of residues within the intracellular C terminus of the pore-forming α-subunits. However, the molecular mechanism(s) by which phosphorylation of the α-subunit effects changes in channel activity are unknown. Inhibition of BK channels by PKA depends on phosphorylation of only a single α-subunit in the channel tetramer containing an alternatively spliced insert (STREX) suggesting that phosphorylation results in major conformational rearrangements of the C terminus. Here, we define the mechanism of PKA inhibition of BK channels and demonstrate that this regulation is conditional on the palmitoylation status of the channel. We show that the cytosolic C terminus of the STREX BK channel uniquely interacts with the plasma membrane via palmitoylation of evolutionarily conserved cysteine residues in the STREX insert. PKA phosphorylation of the serine residue immediately upstream of the conserved palmitoylated cysteine residues within STREX dissociates the C terminus from the plasma membrane, inhibiting STREX channel activity. Abolition of STREX palmitoylation by site-directed mutagenesis or pharmacological inhibition of palmitoyl transferases prevents PKA-mediated inhibition of BK channels. Thus, palmitoylation gates BK channel regulation by PKA phosphorylation. Palmitoylation and phosphorylation are both dynamically regulated; thus, cross-talk between these 2 major posttranslational signaling cascades provides a mechanism for conditional regulation of BK channels. Interplay of these distinct signaling cascades has important implications for the dynamic regulation of BK channels and physiological homeostasis.

Aims: To evaluate the clinical and functional outcome of transanal purse-string sutures for rectal mucosa and submucosa plus perianal suture (TAS-PAS) for the management of full-thickness rectal prolapse. Methods: The clinical data of 62 patients with full-thickness rectal prolapse treated with TAS-PAS between March 2000 and March 2008 were analyzed retrospectively. Results: No patient died. Satisfaction with surgery was high in 50 cases (80.6%), moderate in 9 cases (14.5%), and low in 3 cases (4.84%). Prolapse relapse rate was 4.84%. Anal continence improved in 82.6% of pa tients, constipation improved in 69.2%, and anal tenesmus in 86.7%. No surgery-associated constipation occurred. The mean operative time was 52 min (range 40–80). Mean hospital stay was 4 days (range 3–7). Mean patient follow-up was 17 months (range 4–36). Conclusions: From our data, TAS-PAS for the management of full-thickness rectal prolapse showed encouraging results with little complications and an acceptable relapse rate. This procedure induces only mild trauma and is easy to perform making it worthy of further practice and investigation.

Calcium-activated potassium (BK) channels play a central role in regulating multiple physiological processes, from the control of blood flow to neuronal excitability. Coordinated regulation of BK channel activity by changes in actin cytoskeleton dynamics has been implicated in several of these processes and related disease states such as epilepsy and stroke. However, how BK channels interact with the actin cytoskeleton is essentially unknown. Here we demonstrate noncanonical Src homology domain 3 (SH3) binding site motifs in the intracellular C terminus of the BK channel pore-forming alpha-subunit that are conserved from fish to humans. These noncanonical motifs target multiple SH3 domain cellular signaling proteins to BK channels, including the SH3 adapter protein cortactin (EMS1). We demonstrate that cortactin provides a molecular bridge between BK channels and the cortical actin cytoskeleton in cells. Disruption of the SH3-mediated interaction prevents the regulation of BK channel activity controlled by changes in actin cytoskeletal dynamics. Targeting of cortactin to BK channels via a novel, noncanonical SH3 domain binding motif has important implications for the coordination of BK channel function in normal physiology and disease.

In this paper multilevel fast multipole algorithm (MLFMA) based on an improved electric field integral equation (IEFIE) is developed to achieve fast solution of electromagnetic scattering from 3D open structures. The present method attains much faster convergence than traditional EFIE. And, a reasonable accuracy is also achieved in a few iterations. Numerical results demonstrate the validity and efficiency of the present method.

The pore-forming alpha-subunits of large conductance calcium- and voltage-activated potassium (BK) channels are encoded by a single gene that undergoes extensive alternative pre-mRNA splicing. However, the extent to which differential exon usage at a single site of splicing may confer functionally distinct properties on BK channels is largely unknown. Here we demonstrated that alternative splicing at site of splicing C2 in the mouse BK channel C terminus generates five distinct splice variants: ZERO, e20, e21(STREX), e22, and a novel variant deltae23. Splice variants display distinct patterns of tissue distribution with e21(STREX) expressed at the highest levels in adult endocrine tissues and e22 at embryonic stages of mouse development. deltae23 is not functionally expressed at the cell surface and acts as a dominant negative of cell surface expression by trapping other BK channel splice variant alpha-subunits in the endoplasmic reticulum and perinuclear compartments. Splice variants display a range of biophysical properties. e21(STREX) and e22 variants display a significant left shift (>20 mV at 1 microM [Ca2+]i) in half-maximal voltage of activation compared with ZERO and e20 as well as considerably slower rates of deactivation. Splice variants are differentially sensitive to phosphorylation by endogenous cAMP-dependent protein kinase; ZERO, e20, and e22 variants are all activated, whereas e21 (STREX) is the only variant that is inhibited. Thus alternative pre-mRNA splicing from a single site of splicing provides a mechanism to generate a physiologically diverse complement of BK channel alpha-subunits that differ dramatically in their tissue distribution, trafficking, and regulation.

To study and compare bone-forming mechanism after compound of autologous periosteum-wrapped tendon with spongiosa homogenate and other implants in articular cavity, and to explore the possibility of the compound as a substitute for the lunate in Kienbock's disease.Forty-five New Zealand white rabbits were randomly divided into three groups: periosteum group (group A, n=15), composite group (group B, n=15), and control group (group C, n=15). The three sorts of implants were placed into articular cavity of the knee respectively. The changes of bone formation and bone morphogenetic protein (BMP) distribution of the implants were examined under optical microscope with HE and immunohistochemical staining and measured by CT 3, 6 and 9 weeks after operation.The result of BMP staining was negative after 3 weeks and positive in new cartilage cells after 9 weeks in group A. The positive BMP staining was observed in group B after 3 weeks and 9 weeks, which mainly distributed in new bone cells and cartilage cells. And negative BMP staining was observed every stage in group C. The quantitative CT bone mineral density (BMD) values of 3 implants were analyzed, the difference was significant between the groups (P0.01), except that between groups A and C in the 3rd week (P0.05).The above results demonstrated that the compound of autologous periosteum-wrapped tendon and spongiosa homogenate can produce bone and cartilage massively under the induction of periosteum and bone-forming factors such as BMP in spongiosa homogenate and the compound can be used as a substitute for the lunate.

Describes a local dynamic electrocardiogram (EGG) monitoring network. It connects the ambulatory ECG monitors to a central processing unit (hospital or ambulance centre) by common telephone network. An ambulatory ECG monitor transfers the digitized ECG waveforms and analyzing data to central processing unit by the common telephone network. It monitors dynamically the heart disease patient's ECG during their day to day activities for a long time and far away.

1. Large-conductance Ca(2+)- and voltage-activated potassium (BK) channels are important regulators of cellular excitability. Here, we present a patch-clamp electrophysiological analysis of splice-variant-specific regulation by the synthetic glucocorticoid dexamethasone (DEX) of BK channels consisting of cloned STREX or ZERO alpha-subunit variants expressed in human embryonic kidney (HEK 293) cells. 2. STREX channels in isolated membrane patches were inhibited by protein kinase A (PKA) and this was blocked on pre-treatment of intact cells with DEX (100 nM) for 2 h. 3. The effect of DEX required the synthesis of new mRNA and protein. Furthermore, it required protein phosphatase 2A (PP2A)-like activity intimately associated with the channels, as it was blocked by 10 nM okadaic acid but not by the specific protein phosphatase-1 inhibitor peptide PPI-2. 4. ZERO variant channels that lack the STREX insert were activated by PKA but were not influenced by DEX. ZERO channels containing a mutant STREX domain (S4(STREX)A) were also activated by PKA. Importantly, DEX blocked PKA activation of S4(STREX)A channels in a PP2A-dependent manner. 5. Taken together, the STREX domain is crucial for glucocorticoid regulation of BK channels through a PP2A-type enzyme. Moreover, glucocorticoids appear to induce a generic set of proteins in different types of cells, the actions of which depend on the expression of cell-specific targets.

The properties of the hyperpolarization-activated inward cation current (Ih) in mouse anterior pituitary, AtT20 D16:16 corticotropes was characterized by whole cell patch clamp recording. In response to hyperpolarizing steps a large, slowly activating, voltage-dependent inward current was activated with a half maximal activation voltage (V0.5) of -96.2+/-3.1 mV with a time constant of 168+/-13 msec determined at -140 mV at room temperature. Ih had a reversal potential of -35.5+/-1.0 mV and -23.3+/-1.4 mV using 5 mM and 25 mM extracellular K+, respectively, with a relative permeability ratio for Na+ and K+ of 0.24. The current was completely blocked by 2 mM extracellular CsCl and partially blocked by ZD7288 (100 microM) but was unaffected by TEA (10 mM) or Ba2+ (1 mM). RT-PCR analysis revealed robust expression of HCN1, but not HCN2 or HCN3, subunits of hyperpolarization-activated cation channels. The endogenous Ih current was weakly activated by cAMP but robustly inhibited by the cAMP antagonist, Rp-8-CPT-cAMPS. Activation or suppression of protein kinase C activity had no significant effect on the Ih current. The data suggest that in AtT20 D16:16 corticotropes Ih is tonically regulated by the cAMP-signaling cascade and may serve to limit excessive hyperpolarization.

The regulation of large conductance calcium- and voltage-activated potassium (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior pituitary corticotroph cells. Maximal activation of PKC using the phorbol esters, 4β-phorbol 12-myristate, 13-acetate (PMA), phorbol 12, 13 dibutyrate (PDBu) and 12-deoxyphorbol 13-phenylacetate (dPPA) elicited a rapid, and sustained, inhibition of the outward steady-state voltage- and calcium- dependent potassium current predominantly carried through BK channels. The effect of PMA was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and chelerythrine chloride (CHE; 25 μM) and was not mimicked by the inactive phorbol ester analogue 4α-PMA. PMA had no significant effect on the 1 mM tetraethylammonium (TEA)-insensitive outward current or pharmacologically isolated, high voltage-activated calcium current. PMA had no significant effect on steady-state outward current in cells pre-treated for 2 h with 1 μM of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant effect on steady-state outward current amplitude or sensitivity to 1 mM TEA and did not block PMA-induced translocation of the phorbol ester-sensitive PKC isoforms, PKCα and PKCe, to membrane fractions. Taken together these data suggest that in AtT20 D16:16 corticotroph cells BK channels are important targets for PKC action and that glucocorticoids inhibit PKC signalling downstream of PKC activation. In many neuroendocrine cells of the anterior pituitary gland, activation of the protein kinase C (PKC) intracellular signalling pathway leads to sustained cellular excitability and neurosecretion although the cellular mechanisms and targets for PKC are poorly understood (Ozawa & Sand, 1986; Mason et al. 1988). In anterior pituitary corticotrophs PKC mediates the sustained phase of adrenocorticotrophin (ACTH) secretion stimulated by activation of the phospholipase C pathway by the hypothalamic secretagogue vasopressin (Carvallo & Aguilera, 1989; Oki et al. 1990). Vasopressin elicits a biphasic elevation of intracellular free calcium (Corcuff et al. 1993; Tse & Lee, 1998) and during the sustained phase of calcium influx stimulates PKC translocation and enhances PKC activity at the plasma membrane, an effect that is mimicked by the cell-permeant PKC-activating phorbol esters (Carvallo & Aguilera, 1989). In AtT20 mouse corticotroph cells phorbol-ester-mediated activation of PKC has been proposed to exert effects both distal and proximal to voltage-dependent calcium influx, which may result from activation of different PKC isoforms (McFerran et al. 1995) to elicit ACTH release (Phillips & Tashjian, 1982; Woods et al. 1992; Clark & Kempainen, 1994; McFerran et al. 1995). Intracellular free calcium measurements in AtT20 cells suggest that PKC-induced calcium influx results, at least in part, from inhibition of TEA-sensitive potassium conductances. This inhibition results in membrane depolarization and subsequent, indirect, enhancement of voltage-gated calcium influx (Reisine & Guild, 1987; Reisine, 1989). However, ionic conductances regulated by PKC activation in corticotrophs have not been identified. In rat GH4C1 pituitary cells activation of PKC results in inhibition of the TEA-sensitive large conductance calcium- and voltage-activated potassium (BK) channels (Shipston & Armstrong, 1996), which act as immediate negative feedback regulators of voltage-dependent calcium influx in several systems (Robitaille et al. 1993; Yazejian et al. 1997). Furthermore, BK channels are an important target for cellular regulation by two distinct, physiologically relevant, intracellular signalling pathways in AtT20 corticotrophs. Activation of the cAMP-dependent protein kinase pathway results in inhibition of BK channels leading to a robust secretory response. Protein kinase A (PKA)-mediated inhibition of BK channel function is blocked by activation of a protein-synthesis-dependent signalling cascade activated by glucocorticoid hormones. The cross-talk between these two pathways at the level of BK channels is an important determinant of the secretory response in this system (Shipston et al. 1996; Lim et al. 1998; Tian et al. 1998). As TEA-sensitive BK channels act as immediate negative feedback regulators of voltage-dependent calcium influx in several systems (Robitaille et al. 1993; Yazejian et al. 1997) and PKC-mediated calcium influx is dependent upon inhibition of a TEA-sensitive conductance in AtT20 cells (Reisine & Guild, 1987; Reisine, 1989), we have addressed whether BK channels are an important cellular target for PKC action in this system. Furthermore, as glucocorticoids block PKC-stimulated ACTH release (Phillips & Tashjian, 1982; Woods et al. 1992; Clark & Kempainen, 1994; McFerran et al. 1995) and antagonize PKA-mediated inhibition of BK channels in this system (Shipston et al. 1996; Tian et al. 1998) we have addressed the question as to whether glucocorticoids also block PKC-mediated regulation of BK channels in AtT20 D16:16 corticotroph cells.

Adrenal glucocorticoid hormones rapidly exert powerful effects on neurons, immune and neuroendocrine cells through induction of de novo protein synthesis. In this study, we investigated, using mouse clonal anterior pituitary AtT20 D16:16 corticotrophs, whether (i) glucocorticoids rapidly inhibit glucose transport and (ii) whether this inhibition of glucose transport is directly correlated with early inhibition of ACTH secretion. Glucose uptake in AtT20 D16:16 cells was Na+-independent because the Na+-independent glucose transport inhibitor phloretin (100 microM) completely inhibited specific 14C-deoxygluose (DoG) uptake and replacement of extracellular Na+ with N-methyl D-glucamine+ had no effect. Furthermore, the Na+-independent glucose transporters, GLUTs 1 and 3 were expressed in AtT20 D16:16 cells. The synthetic type II glucocorticoid receptor agonist dexamethasone, rapidly, within 2 h, inhibited DoG uptake into AtT20 D16:16 cells through a mechanism that was dependent on de novo mRNA synthesis. Glucocorticoid inhibition of glucose transport was not correlated with early inhibition of ACTH secretion because removal of glucose from the external medium had no effect on CRF-stimulated ACTH secretion or the efficacy of early glucocorticoid inhibition of ACTH release. Although the Na+-independent glucose transport inhibitor phloretin significantly inhibited CRF-stimulated ACTH release, this effect of phloretin was a result of its potent activation of large conductance calcium-activated potassium (BK) channels. These data suggest that different molecular pathways and/or glucocorticoid induced proteins underlie the mechanism(s) of early glucocorticoid inhibition of glucose uptake and ACTH release, respectively.

The vesicular hypothesis of quantal acetylcholine release describes the process by which discrete packages (or quanta) of the transmitter are released from nerve terminals through the exocytosis of the content of synaptic vesicles. However, cholinergic synaptic vesicles can no longer be vaguely regarded as simple membrane bound ‘sacks’ of the transmitter. Modern molecular, biochemical, morphological and electrophysiological research has revealed them to be complex cellular structures with a heterogeneous mixture of functions. Thus, not all synaptic vesicle populations are formed under the same circumstances and there are variations in the releasability of synaptic vesicle populations. This review briefly outlines some of the experimental research that has lead to our current thinking on the heterogeneity of vesicular acetylcholine storage in cholinergic nerve terminals. In addition, a model for vesicular acetylcholine storage and release is presented that attempts to accommodate many of the modern ideas concerning cholinergic synaptic vesicle function and interaction.

1. 1. Nicotinic antagonists such as tubocurarine affect acetylcholine release from motor nerve terminals at the neuromuscular junction. 2. 2. Electrophysiological studies comparing the prejunctional actions of tubocurarine to those of vesamicol and vecuronium have been used to provide an insight into the mechanisms involved in the prejunctional effects of tubocurarine-like compounds. 3. 3. The observed prejunctional actions of tubocurarine can be accounted for by a model in which the compound has two separately identifiable effects on the nerve terminal. At low frequencies of nerve stimulation tubocurarine augments acetylcholine release while at high frequencies of nerve stimulation tubocurarine depresses acetylcholine release. 4. 4. Both of the effects of tubocurarine on acetylcholine release area consequence of a change in the number of quanta within the nerve terminal immediately available for release upon nerve stimulation. 5. 5. On the basis of our experimental observations, we suggest that the two prejunctional effects of tubocurarine are mediated through two pharmacologically distinct prejunctional nAChRs.

The major action of non-depolarizing neuromuscular blocking agents is that they are competitive antagonists at the skeletal muscle postjunctional nicotinic receptor. In addition, they also block acetylcholine receptors in the autonomic nervous system, including muscarinic receptors at the sino-atrial node, and nicotinic receptors at ganglia. As well as blocking the muscle postjunctional nicotinic receptors, large concentrations can produce non-competitive block by occluding the endplate channel itself. The well-known phenomena of tetanic fade and train-of-four fade have been ascribed to a prejunctional action of the compounds. This is controversial. It has been argued that the prime prejunctional effect of, for example, tubocurarine, is to reduce transmitter mobilization. Others have argued that the prime effect is to increase release. This paper describes how different elements of our research effort over the years have led to a hypothesis that attempts to unify some of these apparently contradictory views.

1. The frequency (0.5-150 Hz) and calcium dependence (0.5-2.0 mM) of the effects of the nicotinic antagonist tubocurarine (0.2 microM) on acetylcholine (ACh) liberation from motor nerve terminals has been examined using binomial analysis of quantal transmitter release. 2. At an extracellular calcium ion concentration ([Ca2+]o) of 2.0 mM, tubocurarine produced a decrease in the endplate current (EPC) quantal content of approximately 30% at high frequencies of motor nerve stimulation (50-150 Hz). In contrast, at low frequencies of stimulation (0.5-1.0 Hz), tubocurarine enhanced the EPC quantal content by approximately 20%. 3. The enhancement of EPC quantal content produced by tubocurarine at low frequencies of motor nerve stimulation was [Ca2+]o dependent, being abolished when [Ca2+]o was lowered from 2.0 to 0.5 mM. In contrast, the decrease in quantal content produced by tubocurarine at high frequencies of motor nerve stimulation was independent of [Ca2+]o, being approximately 30% at all calcium ion concentrations studied. 4. In direct contrast to tubocurarine, the nicotinic antagonist vecuronium (1.0 microM) produced no increase in EPC quantal content at low frequencies of nerve stimulation. However, at high frequencies of nerve stimulation it decreased EPC quantal content to a similar extent to 0.2 microM tubocurarine. The frequency-dependent decrease in EPC quantal content produced by 1.0 microM vecuronium in 2.0 mM [Ca2+]o was very similar to that seen with 0.2 microM tubocurarine in 0.5 mM [Ca2+]o. 5. Binomial analysis revealed that all the changes in EPC quantal content associated with both nicotinic antagonists were due to changes in the size of the pool of quanta in the nerve terminal available for immediate release with no effect on the probability of release of an individual quantum. 6. The results are interpreted in terms of two separately identifiable prejunctional actions of the nicotinic antagonists, both involving an action at nicotinic ACh receptors situated on the motor nerve terminal. Thus, at high frequencies of motor nerve stimulation tubocurarine and vecuronium produce a [Ca2+]o-independent decrease in ACh release, probably through an inhibitory action on a positive-feedback prejunctional nicotinic autoreceptor closely related to the muscle-type nicotinic ACh autoreceptor. However, at low frequencies of motor nerve stimulation we suggest that tubocurarine, but not vecuronium, produces a [Ca2+]o-dependent increase in ACh release through an action at a negative-feedback prejunctional neuronal-type nicotinic ACh autoreceptor.

Complexity of the graph isomorphism algorithms mainly depends on matching time which is directly related to efficiency of their partition methods. This paper proposed a partition method by sorted sequences of length-L path numbers, and divided cells of partition into 3 categories: not similar; completely similar; similar but not completely. The method was tested on several types of graphs with different order, each type with the same order 100 graphs. The results indicate that not similar cells can be refined by adding path length to other types or trivial cells if the vertex is not similar with all other vertices. For almost all asymmetric graphs, the path length is a small value, e.g., for 6-regular graphs with 100∼1000 vertices the average path length is 4 to get all cells to trivial ones.

Background Although Klebsiella pneumoniae bloodstream infections (KP-BSIs) have recently attracted attention due to an alarming raise in morbidity and mortality, there have been few reports on the epidemiology of KP-BSIs in mainland China. We sought to describe the epidemiological, microbiological, and clinical characteristics of KP-BSIs, focusing on the risk factors of carbapenem resistance and patient mortality. Methods A retrospective analysis of WHONET data of KP-BSI patients admitted to a teaching hospital in Shanghai, China, between January 1, 2011 and December 31, 2015 was performed, and the annual percentage of patients with carbapenem-resistant K. pneumoniae (CRKP) was determined. Risk factors related to the carbapenem resistance and patient mortality were analyzed using binary logistic regression model. The genetic relatedness of CRKP strains isolated from intensive care unit (ICU) patients was determined by pulsed-field gel electrophoresis (PFGE). Results A total of 293 incidences of KP-BSIs were identified in a 5-year period, 22.18% of these (65/293) were CRKP strains, and the proportion of CRKP-BSI in ICU was 59.62% (31/52), equaling the levels observed in the epidemic regions. A number of KP-BSIs (114), obtained from January 1, 2014, to December 31, 2015, were further investigated. Skin and soft tissue infection source (odds ratio [OR] 26.63, 95% confidence interval [CI] 4.8–146.8) and ICU-acquired infection (OR 5.82, 95% CI 2.0–17.2) was shown to be powerful risk factors leading to the development of CRKP-BSI. The crude 28-day mortality rates of KP-BSI and CRKP-BSI patients were 22.8% and 33.3%, respectively. Lung as the probable source of infection (OR 4.23, 95% CI 1.0–17.3), and high Sequential Organ Failure Assessment (SOFA) score (OR 1.40, 95% CI 1.2–1.6) were strong prognostic factors determining crude 28-day KP-BSI mortality rates. PFGE analysis demonstrated that 10/11 random CRKP isolates in ICU belonged to the same clonal type. Conclusions During the study period, we observed a significant increase in the occurrence of CRKP infections among the identified KP-BSIs in our hospital and especially in ICU, and we demonstrated that carbapenem resistance is associated with the increased mortality of KP-BSI patients.