The impact of socioeconomic and clinical factors on purchase of prescribed analgesics before and after hysterectomy on benign indication.
Pelvic pain is a primary symptom of women referred for hysterectomy. This study identified risk factors for purchase of prescribed analgesics before and after hysterectomy and examined purchase changes after hysterectomy, specifically focusing on socioeconomic effects. Nearly all Danish women (n=13,420) with a hysterectomy on benign indication between 2004 and 2006 were included in a registry-based follow-up study. Information on prescription analgesic purchase was from the Danish National Prescription Registry. Factors associated with a purchase and associations between socioeconomic factors and changes in analgesic purchase were assessed. Analgesic purchase after hysterectomy was independently predicted by age below 35 or above 65 years, body mass index >29.9, high American Society of Anesthesiologists (ASA) score, uterus weight <300 g, comorbidity, and less than high school education. In this study, 15% of women initiated or increased analgesic purchase after hysterectomy, whereas 50% with a purchase before hysterectomy ceased buying afterward. Women with low socioeconomic status (SES) (assessed by education, employment, and income) were more likely to increase purchase of analgesics than women with high SES (odds ratio for less than high school vs. more than high school=1.58; 95% confidence interval, 1.31-1.91) and less likely to cease use than women with high SES (odds ratio=0.67; confidence interval, 0.52-0.86 for low vs. high education). These results suggest that purchase of analgesics after hysterectomy is related to preoperative factors. Compared with women with high SES, women with low SES had less favorable changes in analgesic purchase after hysterectomy.


Biophysics of cadherin adhesion.
Since the identification of cadherins and the publication of the first crystal structures, the mechanism of cadherin adhesion, and the underlying structural basis have been studied with a number of different experimental techniques, different classical cadherin subtypes, and cadherin fragments. Earlier studies based on biophysical measurements and structure determinations resulted in seemingly contradictory findings regarding cadherin adhesion. However, recent experimental data increasingly reveal parallels between structures, solution binding data, and adhesion-based biophysical measurements that are beginning to both reconcile apparent differences and generate a more comprehensive model of cadherin-mediated cell adhesion. This chapter summarizes the functional, structural, and biophysical findings relevant to cadherin junction assembly and adhesion. We emphasize emerging parallels between findings obtained with different experimental approaches. Although none of the current models accounts for all of the available experimental and structural data, this chapter discusses possible origins of apparent discrepancies, highlights remaining gaps in current knowledge, and proposes challenges for further study.


Clinical Analysis of the Renal Protective Effect of GLP-1 on Diabetic Patients Based on Edge Detection.
With the rapid development of IoT technology, it is a new trend to combine edge computing with smart medicine in order to better develop modern medicine, avoid the crisis of information "sibling," and meet the requirements of timeliness and computational performance of the massive data generated by edge devices. However, edge computing is somewhat open and prone to security risks, so the security and privacy protection of edge computing systems for smart healthcare is receiving increasing attention. The two groups were compared before and after treatment for blood glucose, blood lipids, blood pressure, renal function, serum advanced glycosylation end products (AGEs) and cyclic adenosine monophosphate (cAMP), serum oxidative stress indicators, and levels of cAMP/PKA signalling pathway-related proteins in peripheral blood mononuclear cells. The results of this study show that the reduction of AGEs, the improvement of oxidative stress, and the regulation of the cAMP/PKA signalling pathway may be associated with a protective effect against early DKD. By introducing the edge computing system and its architecture for smart healthcare, we describe the security risks encountered by smart healthcare in edge computing, introduce the solutions proposed by some scholars to address the security risks, and finally summarize the security protection framework and discuss the specific solutions for security and privacy protection under this framework, which will provide some help for the credible research of smart healthcare edge computing.


Pancreas transplantation in streptozotocin-diabetic juvenile pigs. Evaluation of function among duct-ligated, duct-occluded, and nonligated allografts.
This study examined pancreatic allograft function in transplanted diabetic juvenile pigs. The grafts were transplanted with ligated, occluded (Ethibloc) or open ducts. No immunosuppression was used. Irreversible and permanent diabetes was induced by streptozotocin. Graft function was assessed by measuring glucose tolerance and insulin production during an i.v. glucose tolerance test. The fractional growth rate of the transplanted host was used to evaluate the long-term consequence of transplantation. Normal glucose tolerance was achieved in 50%, and a slight impairment in 10% of the animals. In 35%, no detectable graft function was observed. Duct-ligated and Ethibloc-occluded grafts had a significantly lower function rate within the first week compared with grafts with open ducts. The fractional growth rate was significantly decreased in animals receiving grafts with occluded ducts. This was probably not due to different insulin production. No graft failures were observed within the first week in open-duct graft transplantations. Graft failures were associated with elevated serum alpha-amylase and were probably due to vascular impairment. Normal glucose tolerance in transplanted pigs was associated with elevated levels of normal insulin and C-peptide in peripheral blood, concomitant with low levels of proinsulin. Our results show that a pancreatic graft should be transplanted with open ducts. Obstructed ducts lead to an increased frequency of graft failure, while the transplanted hosts with such functioning grafts show retarded growth due to unidentified factors.


Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes.
Introduction: In ventricular myocytes, spontaneous release of calcium (Ca2+) from the sarcoplasmic reticulum via ryanodine receptors ("Ca2+ sparks") is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of ischemic tissue, along with an increase in Ca2+ spark rate and ROS production, each of which has been implicated in arrhythmogenesis. Yet, whether there is an impact of ischemia on the stretch-induced increase in Ca2+ sparks and ROS has not been investigated. We hypothesized that ischemia would enhance the increase of Ca2+ sparks and ROS that occurs with stretch. Methods: Isolated ventricular myocytes from mice (male, C57BL/6J) were loaded with fluorescent dye to detect Ca2+ sparks (4.6 μM Fluo-4, 10 min) or ROS (1 μM DCF, 20 min), exposed to normal Tyrode (NT) or simulated ischemia (SI) solution (hyperkalemia [15 mM potassium], acidosis [6.5 pH], and metabolic inhibition [1 mM sodium cyanide, 20 mM 2-deoxyglucose]), and subjected to sustained stretch by the carbon fiber technique (~10% increase in sarcomere length, 15 s). Ca2+ spark rate and rate of ROS production were measured by confocal microscopy. Results: Baseline Ca2+ spark rate was greater in SI (2.54 ± 0.11 sparks·s-1·100 μm-2; n = 103 cells, N = 10 mice) than NT (0.29 ± 0.05 sparks·s-1·100 μm-2; n = 33 cells, N = 9 mice; p < 0.0001). Stretch resulted in an acute increase in Ca2+ spark rate in both SI (3.03 ± 0.13 sparks·s-1·100 μm-2; p < 0.0001) and NT (0.49 ± 0.07 sparks·s-1·100 μm-2; p < 0.0001), with the increase in SI being greater than NT (+0.49 ± 0.04 vs. +0.20 ± 0.04 sparks·s-1·100 μm-2; p < 0.0001). Baseline rate of ROS production was also greater in SI (1.01 ± 0.01 normalized slope; n = 11, N = 8 mice) than NT (0.98 ± 0.01 normalized slope; n = 12, N = 4 mice; p < 0.05), but there was an acute increase with stretch only in SI (+12.5 ± 2.6%; p < 0.001). Conclusion: Ischemia enhances the stretch-induced increase of Ca2+ sparks in ventricular myocytes, with an associated enhancement of stretch-induced ROS production. This effect may be important for premature excitation and/or in the development of an arrhythmogenic substrate in acute regional ischemia.


P3 amylase isoenzyme in the diagnosis of pancreatitis.
P3 amylase isoenzyme was found to be present in the plasma of 43 out of 140 patients with suspected pancreatitis. Of 43 patients with the P3 isoenzyme, pancreatitis was definitely confirmed in 21 by laparotomy. Of the remainder, 19 had probable pancreatitis based on a combination of clinical, biochemical, endoscopic (ERCP), ultrasonic and computerised tomographic evidence, while 3 had possible pancreatitis based on clinical evidence alone. Of 97 patients without the P3 isoenzyme 1 patient had evidence of probable pancreatitis and 1 had evidence of possible pancreatitis. Statistical analysis (excluding the 4 cases of possible pancreatitis) showed that the P3 amylase isoenzyme had a sensitivity of 98%, a specificity of 100% and an efficiency of 99%. The predictive values of a positive and negative test were 100% and 99% respectively. Hyperamylasemia was not a pre-requisite to the presence of the P3 isoenzyme, since 11 out of 13 patients, with normal total amylase levels, were found to have the P3 band and confirmation of their pancreatitis. It is concluded that the P3 amylase isoenzyme is a specific and sensitive test for pancreatitis, and appears also to be superior to the total plasma amylase.


Renal failure after open heart surgery.
One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis.


Eight histidine residues are catalytically essential in a membrane-associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase.
The eukaryotic fatty acid desaturases are iron-containing enzymes that catalyze the NAD-(P)H- and O2-dependent introduction of double bonds into methylene-interrupted fatty acyl chains. Examination of deduced amino acid sequences for the membrane desaturases from mammals, fungi, insects, higher plants, and cyanobacteria has revealed three regions of conserved primary sequence containing HX(3 or 4)H,HX(2 or 3)HH, and HX(2 or 3)HH. This motif is also present in the bacterial membrane enzymes alkane hydroxylase (omega-hydroxylase) and xylene monooxygenase. Hydropathy analyses indicate that these enzymes contain up to three long hydrophobic domains which would be long enough to span the membrane bilayer twice. The conserved His-containing regions have a consistent positioning with respect to these potential membrane spanning domains. Taken together, these observations suggest that the membrane fatty acid desaturases and hydrocarbon hydroxylases have a related protein fold, possibly arising from a common ancestral origin. In order to examine the functional role of these conserved His residues, we have made use of the ability of the rat delta 9 desaturase gene to complement a yeast strain deficient in the delta 9 desaturase gene function (ole1). By site-directed mutagenesis, eight conserved His residues in the rat delta 9 desaturase were individually converted to Ala. Each His-->Ala mutation failed to complement the yeast ole1 mutant. In contrast, mutation of three nonconserved flanking His residues or a partially conserved Arg residue within the conserved motif to Ala allowed for complementation of the ole1 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)


Heterogeneous ATP patterns in microvascular networks.
ATP is not only an energy carrier but also serves as an important signalling molecule in many physiological processes. Abnormal ATP level in blood vessel is known to be related to several pathologies, such as inflammation, hypoxia and atherosclerosis. Using advanced numerical methods, we analysed ATP released by red blood cells (RBCs) and its degradation by endothelial cells (ECs) in a cat mesentery-inspired vascular network, accounting for RBC mutual interaction and interactions with vascular walls. Our analysis revealed a heterogeneous ATP distribution in the network, with higher concentrations in the cell-free layer, concentration peaks around bifurcations and heterogeneity among vessels of the same level. These patterns arise from the spatio-temporal organization of RBCs induced by the network geometry. It is further shown that an alteration of hematocrit and flow strength significantly affects ATP level as well as heterogeneity in the network. These findings constitute a first building block to elucidate the intricate nature of ATP patterns in vascular networks and the far reaching consequences for other biochemical signalling, such as calcium, by ECs.


Cytotaxonomic characteristics of the genus Glyptotendipes Kieffer (Chironomidae, Diptera) from fish and retention ponds (Silesia, southern Poland).
The cytotaxonomic characteristics of species of the genus Glyptotendipes (Chironomidae): G. glaucus Meigen, G. paripes Edwards, and G. barbipes (Staeger) are described. The studied material was collected from a fish pond at Gołysz and a sewage retention pond at Chybie in Silesia. All the studied species have the chromosome set 2n = 8, but with many specific structural and functional changes. The cytogenetic data of G. glaucus showed that the studied specimens of this species have been produced by the introgressive hybridization of two sibling species: G. glaucus x G. pallens, and subsequent crossing-over in the hybrid chromosome CD. Owing to this process, the band pattern of chromosome arm D coincided with those of G. pallens. New aberrations (homo- and heterozygous deletions in arm G as well as heterozygous inversions in chromosome arm B) were detected in G. glaucus. Specific band sequences were discovered in chromosomes of G. paripes. The band patterns established in chromosomes AB and G of this species were identical with those of Siberian populations. The banding patterns of the polytene chromosomes of G. barbipes do not differ from the standard. However, high frequency of pericentric inversion of chromosome AB was established. Many new puffs were found in the polytene chromosomes of all the studied species. Their nucleolar organizer was very sensitive to environmental changes. In G. glaucus it appeared in three different states: very active, slightly active, and heterozygous state. The organic pollution existing in the sewage retention pond may contribute to possible mutations and chromosomal damage in Glypotendipes species. Structural and functional rearrangements of the polytene chromosomes of these species mobilized their genomes and provide for survival under polluted conditions.


Surgical treatment of middle cerebral artery aneurysms.
The authors report their experience with the surgical therapy of middle cerebral artery (MCA) aneurysms in 413 cases, and describe their technique. After the M1 portion of the MCA is identified, the Sylvian fissure is opened. During the administration of 20% mannitol, temporary occluding clips are applied to the feeding and draining vessels of the aneurysm. The aneurysm is freed from all surrounding tissue, and the aneurysm neck is treated by ligation, clipping, or wrapping. Analysis of surgical results in 91 cases operated on after the surgical approach had become standardized indicates that more than 94% of patients have returned to useful social lives by the time of follow-up evaluation. Twenty-four percent of these patients were operated on within 48 hours after subarachnoid hemorrhage.


Patterns and trends in facial fractures in New Zealand between 1999 and 2009.
To describe patterns and trends in facial fractures in New Zealand over a decade. A secondary analysis of Ministry of Health data on facial fractures occurring between 30 June 1999 and 1 July 2009. Patient demographic characteristics and the details of injury were analysed and described. Over the study period, the incidence of injury was constant. A total of 26,637 facial fractures were recorded. Most (79%) occurred in males, giving a male-to-female ratio of 4:1. Peak injury rates for both males and females, coincide with the legal alcohol purchasing age. Interpersonal violence (IPV) was the leading cause of facial fractures, accounting for 38%; it increased steadily each year. The number of fractures attributed to sports/other, and road traffic accidents (RTA) had fallen. Māori still continue to experience a disproportionate rate of facial fractures, twice that of the NZ European population. Interpersonal violence is an increasing problem in NZ and contributes to a greater number of facial fractures each year. More measures are required to reduce the number of IPV-related injuries. Perhaps the most effective would be to return the legal alcohol purchasing age to 20 years. More is also required to reduce facial fractures in the high-risk injury groups of young adults, males, and Māori.


The effect of the speaker gender on speech intelligibility in normal-hearing subjects with simulated high frequency hearing loss.
To determine whether speaker gender affects speech discrimination scores, in normal hearing and simulated high frequency hearing loss situations. Listeners were twenty normal volunteers. The speech stimuli were eight phonetically balanced monosyllabic word lists, uttered by a male and a female speakers. These lists were low-pass filtered at 1500, 2500 and 3500 Hz's to represent high frequency hearing loss. To obtain speech discrimination scores, the subjects listened to each of the eight lists in a different filtering and talker conditions in a randomized order. For statistical analysis, Mann-Whitney U test was used. In normal hearing situation, the scores obtained by male and female speeches, were similar (p=0.60). On the contrary, statistically significant differences were observed in all of the three high frequency hearing loss situations (p<0.01). Female speech is significantly more difficult to discriminate than male speech in normal-hearing subjects with simulated high frequency hearing loss and probably in patients with high frequency hearing loss.


Large-scale study of phosphoproteins involved in long-term potentiation in the rat dentate gyrus in vivo.
The mechanisms underlying the induction of synaptic plasticity and the formation of long-term memory involve activation of cell-signalling cascades and protein modifications such as phosphorylation and dephosphorylation. Based on a protein candidate strategy, studies have identified several protein kinases and their substrates, which show an altered phosphorylation state during the early phases of long-term potentiation (LTP), yet only a limited number of synaptic phosphoproteins are known to be implicated in LTP. To identify new phosphoproteins associated with LTP, we have undertaken a proteomic study of phosphoproteins at different time points following the induction of LTP in the dentate gyrus in vivo (0, 15 and 90 min). For each time point, proteins from the dentate gyrus were separated by two-dimensional gel electrophoresis and stained with Pro-Q Diamond, a fluorescent stain specific for phosphoproteins. Fourteen proteins whose phosphorylation state varied significantly following LTP were identified using matrix-assisted laser desorption ionization/time of flight mass spectrometry and electrospray ionization-Orbitrap tandem mass spectrometry (MS/MS). They are involved in various cellular functions implicated in synaptic plasticity, such as intracellular signalling, axonal growth, exocytosis, protein synthesis and metabolism. Our results highlight new proteins whose phosphorylation or dephosphorylation is associated with LTP induction or maintenance. Further studies focusing on the regulation of specific phosphorylation sites will lead to greater understanding of the individual implications of these proteins in LTP as well as of their molecular interactions.


Age-dependent growth inhibition of estrogen-sensitive rat mammary tumors. Probable role of alpha-fetoprotein.
The growth patterns of estrogen (E)-sensitive mammary tumors (SNMU) and autonomous mammary tumors (ANMU) were compared in normal host F344 and BUF rats of different ages. Both SNMU and ANMU tumors have comparable amounts of E receptors of similar physicochemical properties. The E sensitivity was apparent in SNMU tumors regardless of the age of inoculation. The latency period before tumors became palpable was considerably lengthened when the SNMU tumors were inoculated into newborn hosts. The growth pattern of the ANMU tumor was not affected by the age or sex of the host. Comparable results previously obtained with two hypophyseal cell lines suggest that this growth pattern could now be extended to other E-sensitive autonomous systems and become a generalized principle. These results suggest that: 1) the presence of 17 beta-estradiol (E2) receptors is not sufficient to qualify cells to be considered E-sensitive, 2) E-sensitive cells may be delayed in expressing their malignant growth properties if inoculated during the perinatal period, and 3) alpha-fetoprotein may be the substance responsible for the inhibition of the growth of E-sensitive tumor cells during the perinatal stage.


A comparison of the FREDDY and holmium lasers during ureteroscopic lithotripsy.
Two laser devices that are used today in endoscopic treatment of renal and ureteral calculi are the frequency-doubled double-pulse neodynium:YAG (FREDDY) and Holmium:YAG lasers. The mechanism of action of these lasers differs, thus conferring potentially different safety and efficacy profiles. The in vitro efficacy of these lasers in treating urinary stones has been explored, but to our knowledge no study compares the in vivo efficacy. The purpose of this study is to compare the stone-free and complication rates of the FREDDY and holmium lasers. Subjects were included in the study (from January 2004 to September 2006) if they had adequate documentation of stone size and location, postoperative stone burden, and perioperative complications. Stone-free status was determined based on intraoperative findings and postoperative imaging. Complications included bleeding, ureteral perforation, any intraoperative event necessitating termination of the procedure, ureteral stricture, hydronephrosis, and admission to the hospital with a diagnosis related to the procedure. Sixty patients with adequate follow-up were identified. Thirty patients were treated with FREDDY and 30 patients with Holmium laser. Fisher's exact test was employed for statistical analysis. There was no significant difference in the average stone size between the FREDDY and Holmium groups, which were 6.7 mm and 6.1 mm, respectively. Stone-free rates in the FREDDY and Holmium groups were 76.7% and 93.3%, respectively, P = 0.149. The complication rates were 17.4% in the FREDDY group and 10% in the Holmium group, P = 0.667. The complication and stone-free rates did not significantly differ between the FREDDY and Holmium lasers, though there was a trend toward a higher stone-free rate and lower complication rate with the holmium laser. Holmium laser may be more effective than the FREDDY laser in fragmenting calcium oxalate monohydrate stones. The device and laser fiber costs were comparable.


Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES.
Chemokines MCP-1 and RANTES are induced when authentic bone resorbing human osteoclasts differentiate from monocyte precursors in vitro. In addition, MCP-1 and RANTES can stimulate the differentiation of cells with the visual appearance of osteoclasts, being multinuclear and positive for tartrate resistance acid phosphatase (TRAP +). We show here that MIP1alpha is also potently induced by RANKL during human osteoclast differentiation and that this chemokine also induces the formation of TRAP + multinucleated cells in the absence of RANKL. MIP1alpha was able to overcome the potent inhibition of GM-CSF on osteoclast differentiation, permitting the cells to pass through to TRAP + multinuclear cells, however these were unable to form resorption pits. Chemokine receptors CCR2b and CCR4 were potently induced by RANKL (12.6- and 49-fold, P = 4.0 x 10(-7) and 4.0 x 10(-8), respectively), while CCR1 and CCR5 were not regulated. Chemokine treatment in the absence of RANKL also induced MCP-1, RANTES and MIP1alpha. Unexpectedly, treatment with MCP-1 in the absence of RANKL resulted in 458-fold induction of CCR4 (P = 1.0 x 10(-10)), while RANTES treatment resulted in twofold repression (P = 1.0 x 10(-4)). Since CCR2b and CCR4 are MCP-1 receptors, these data support the existence of an MCP-1 autocrine loop in human osteoclasts differentiated using RANKL.


Retrospective study of the relationship of Torque teno sus virus 1a and Torque teno sus virus 1b with porcine circovirus associated disease.
Genus Iotatorquevirus consists of 2 species, Torque teno sus virus 1a and Torque teno sus virus 1b, which are ubiquitous in swine populations, and are widely reported in association with porcine circovirus associated disease (PCVAD). To evaluate the relationship with PCVAD, 100 formalin-fixed paraffin-embedded tissue samples were used to detect both Iotatorquevirus species by nested PCR and sequencing. Sixty-eight PCVAD cases were selected as well as 32 porcine circovirus type 2 (PCV2) non-affected cases. Overall, 33 of the 100 cases were positive for Torque teno sus virus 1a and 8 of 100 were positive for Torque teno sus virus 1b. Only 24 of 68 (35%) PCVAD cases were positive for Torque teno sus virus 1a; 39% (9/23) of post-weaning multisystemic wasting syndrome, and 33% (15/45) of PCV2-associated reproductive failure cases. Among PCV2 non-affected cases, 28% were positive for Torque teno sus virus 1a and 6% were positive for Torque teno sus virus 1b. Torque teno sus virus 1b was not detected in PCV2-associated reproductive failure cases. Regardless of the PCV2-status, a lower frequency of both Iotatorquevirus species was found than depicted in other reports and there was no statistical relationship with PCVAD (χ 2 < 0.01). Given the worldwide genomic variability of Iotatorquevirus species, it is feasible that species prevalent in Mexico share a lower nucleotide sequence identity, leading to different pathogenic potential.


Toxicity of antioxidative extract collected from Styela clava tunics in ICR mice.
Some polymers and bioactive compounds derived from Styela clava tunic (SCT) have been reported as traditional medicine for the treatment of inflammation, oxidative stress and surgical wounds although there is little scientific evidence of their liver and kidney toxicity. To investigate the toxicity of ethanol extracts of SCT (EtSCT) in the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed following oral administration of 50 and 100 mg/kg body weight/day of EtSCT for 14 days. EtSCT showed a high level of free radical scavenging activity for DPPH (93.1%) and NO (16.2%) as well as the presence of 14.8 mg/mL of flavonoids and 36.2 mg/mL of phenolics, while EtSCT treated groups did not show any significant alterations in the body and organ weight, clinical phenotypes, urine parameters or mice mortality when compared with the vehicle treated group. In addition, constant levels of serum biochemical markers including alanine phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (CRE) were maintained. Moreover, no specific histopathological features induced by most toxic compounds were observed in liver and kidney sections stained with hematoxilin and eosin. Therefore, the present results indicate that EtSCT with strong antioxidant activity cannot induce any specific toxicity in liver and kidney organs of ICR at doses of 100 mg/kg body weight/day.


Time Trend of Outcomes for Severe Acute Pancreatitis After Publication of Japanese Guidelines Based on a National Administrative Database.
This study aimed to investigate the recent time trend of outcomes for severe acute pancreatitis after publication of Japanese guidelines based on a national administrative database. A total of 10,400 patients with severe acute pancreatitis were referred to 1021 hospitals between 2010 and 2012 in Japan. We collected patients' data from the administrative database to compare in-hospital mortality (within 28 days and overall), length of stay (LOS), and medical costs during hospitalization. The study periods were categorized into 3 groups according to fiscal year: 2010 (n = 2698), 2011 (n = 3842), and 2012 (n = 3860). In-hospital mortality within 28 days and overall in-hospital mortality were significantly decreased according to fiscal year (6.3% [2010] vs 5.7% [2011] vs 4.5% [2012], P = 0.005; 7.6% vs 7.1% vs 5.6%, P = 0.002, respectively). However, mean LOS and medical costs were not different between fiscal years (27.0 vs 27.1 vs 26.9 days, P = 0.218; 13,998.0 vs 14,156.4 vs 14,319.2 USD, P = 0.232, respectively). This study shows that mortality of severe acute pancreatitis was reduced according to the time course, whereas LOS or medical costs were stable after publication of the Japanese guidelines.


[Features of the neurocognitive profile of patients with protracted and chronic endogenous manic and manic-delusional states].
To study the neurocognitive profile of patients with protracted and chronic endogenous manic and manic-delusional states (EMDS). Thirty-two female patients, aged 18 to 55 years (mean age 36.2±10.2 years), with protracted and chronic EMDS were studied. Based on the clinical typology of EMDS, patients were divided into 4 groups of 8 patients each: group 1 - «acute» subtype, group 2 - «chronified» subtype, group 3 - «developing» subtype and group 4 - subtype «double mania». Neuropsychological, clinical-psychopathological and statistical methods were used. Disturbances of regulatory and executive functions and a decrease in neurodynamic indicators of mental activity in patients with EMDS are significantly more pronounced compared with the control group (p<0.05). The values of the index of severity of disturbances of regulatory and executive functions in patients with EMDS range from 0.95 points (group 1) to 1.14 points (group 4), without statistically significant differences between the groups. The highest severity of neurodynamic disorders is observed in group 1 (1.88 points), while in other groups the index values range from 0.88 points in group 2 to 1.09 in group 4 (p<0.05). Patients of group 1 have greater severity and wider spectrum of neurodynamic symptoms compared with group 2 (U=45.00; p<0.0021), group 3 (U=30.00; p<0.04), and group 4 (U=45.00; p<0.001). It should be noted that the cognitive impairments identified in patients with EMDS did not reach the level of dementia. The most characteristic of EMBS are cognitive impairments associated with a decrease in the parameters of the neurodynamics of mental activity related to the first functional block, as well as with deficiency of executive functions, impaired planning and organization of cognitive activity, due to the weakness of the structures of the third functional block.


Amine-Imine Nickel Catalysts with Pendant O-Donor Groups for Ethylene (Co)Polymerization.
The introduction of a secondary interaction is an efficient strategy to modulate transition-metal-catalyzed ethylene (co)polymerization. In this contribution, O-donor groups were suspended on amine-imine ligands to synthesize a series of nickel complexes. By adjusting the interaction between the nickel metal center and the O-donor group on the ligands, these nickel complexes exhibited high activities for ethylene polymerization (up to 3.48 × 106 gPE·molNi-1·h-1) with high molecular weight up to 5.59 × 105 g·mol-1 and produced good polyethylene elastomers (strain recovery (SR) = 69-81%). In addition, these nickel complexes can catalyze the copolymerization of ethylene with vinyl acetic acid, 6-chloro-1-hexene, 10-undecylenic, 10-undecenoic acid, and 10-undecylenic alcohol to prepare the functionalized polyolefins.


Oxaza adamantyl cannabinoids. A new class of cannabinoid receptor probes.
The preparation of C3 oxaza adamantyl cannabinoids has been described starting from phloroglucinol. Straightforward manipulations of the aromatic ring lead to a bromononaflate that is a benzyne precursor and that serves as a common intermediate for the synthesis of diverse C3-substituted tricyclic cannabinoids. Generation of the benzyne in the presence of an oxaza adamantyl amide anion results in efficient and regiospecific addition to C3 of the aromatic ring. This represents an attractive strategy for the synthesis of classical tricyclic cannabinoids that bear a modified aromatic appendage. The oxaza adamantyl cannabinoids that have been prepared represent a new class of ligands for the CB1 and CB2 receptors.


The Viable Violinist.
In the aftermath of the Kermit Gosnell trial and Giubilini and Minerva's article 'After-birth abortion', abortion-rights advocates have been pressured to provide an account of the moral difference between abortion, particularly late-term abortion, and infanticide. In response, some scholars have defended a moral distinction by appealing to an argument developed by Judith Jarvis Thomson in A defense of abortion. However, once Thomson's analogy is refined to account for the morally relevant features of late-term pregnancy, rather than distinguishing between late-term abortion and infanticide, it reinforces their moral similarity. This is because late-term abortion requires more than detachment - it requires an act of feticide to ensure the death of the viable fetus. As such, a Thomsonian account cannot be deployed successfully as a response to Giubilini and Minerva. Those wishing to defend late-term abortion while rejecting the permissibility of infanticide will need to provide an alternative account of the difference, or else accept Giubilini and Minerva's conclusion.


Comparing the Genetic Diversity and Antimicrobial Resistance Profiles of Campylobacter jejuni Recovered from Cattle and Humans.
Campylobacter jejuni, a leading cause of gastroenteritis in humans, is a foodborne pathogen that can reside in chickens, pigs, and cattle. Because resistance to fluoroquinolones and macrolides, which are commonly used to treat human infections, has emerged in C. jejuni, it is imperative to continously monitor resistance patterns and examine the genetic variation in strains from human infections and animal reservoirs. Our previous study of C. jejuni from human campylobacteriosis cases showed a significantly higher rate of tetracycline resistance compared to national trends, and identified multilocus sequence type (ST)-982 and a history of cattle contact to be associated with tetracycline resistance. To further investigate these associations, we conducted a cross-sectional study to determine the frequency of antimicrobial resistance and examine the genetic diversity of C. jejuni recovered from 214 cattle at three Michigan herds. Overall, the prevalence of C. jejuni was 69.2% (range: 58.6-83.8%) for the three farms, and 83.7% (n = 113) of isolates were resistant to one or more antimicrobials. Resistance to only tetracycline predominated among the cattle isolates (n = 89; 65.9%) with most resistant strains belonging to ST-459 (96.5%) or ST-982 (86.4%). Among the 22 STs identified, STs 459 and 982 were more prevalent in one feedlot, which reported the use of chlortetracycline in feed upon arrival of a new herd. PCR-based fingerprinting demonstrated that the ST-982 isolates from cattle and humans had identical banding patterns, suggesting the possibility of interspecies transmission. Resistance to macrolides (1.5%) and ciprofloxacin (16.3%) was also observed; 14 of the 22 ciprofloxacin resistant isolates represented ST-1244. Together, these findings demonstrate a high prevalence of antimicrobial resistant C. jejuni in cattle and identify associations with specific genotypes. Continuous monitoring and identification of risk factors for resistance emergence are imperative to develop novel methods aimed at decreasing pathogen persistence in food animal reservoirs and the frequency of resistant infections in humans.


Cognitive Constraints and Island Effects.
Competence-based theories of island effects play a central role in generative grammar, yet the graded nature of many syntactic islands has never been properly accounted for. Categorical syntactic accounts of island effects have persisted in spite of a wealth of data suggesting that island effects are not categorical in nature and that non-structural manipulations that leave island structures intact can radically alter judgments of island violations. We argue here, building on work by Deane, Kluender, and others, that processing factors have the potential to account for this otherwise unexplained variation in acceptability judgments.We report the results of self-paced reading experiments and controlled acceptability studies which explore the relationship between processing costs and judgments of acceptability. In each of the three self-paced reading studies, the data indicate that the processing cost of different types of island violations can be significantly reduced to a degree comparable to that of non-island filler-gap constructions by manipulating a single non-structural factor. Moreover, this reduction in processing cost is accompanied by significant improvements in acceptability. This evidence favors the hypothesis that island-violating constructions involve numerous processing pressures that aggregate to drive processing difficulty above a threshold so that a perception of unacceptability ensues. We examine the implications of these findings for the grammar of filler-gap dependencies.


Charge transport through graphene junctions with wetting metal leads.
Graphene is believed to be an excellent candidate material for next-generation electronic devices. However, one needs to take into account the nontrivial effect of metal contacts in order to precisely control the charge injection and extraction processes. We have performed transport calculations for graphene junctions with wetting metal leads (metal leads that bind covalently to graphene) using nonequilibrium Green's functions and density functional theory. Quantitative information is provided on the increased resistance with respect to ideal contacts and on the statistics of current fluctuations. We find that charge transport through the studied two-terminal graphene junction with Ti contacts is pseudo-diffusive up to surprisingly high energies.


Effect of surgical timing on recovery and associated injuries after anterior cruciate ligament reconstruction.
This study was undertaken to determine the optimal time after injury for arthroscopically assisted anterior cruciate ligament reconstruction using a double semitendinosus graft. We analyzed 87 patients. Time from injury to surgery was established as acute, subacute, or chronic; the three groups were matched. Meniscal damage and treatment were categorized. Chondral lesions were graded, postoperative parameters of motion, strength recovery, and stability were tabulated at 3, 6, 12, and 18 months. Complications were compared. Six percent of the patients with chronic knee injuries had two normal menisci at surgery, compared with 29% of the acute and subacute groups. Reparable tears were found in 37.8% of the knees. Chondral lesions were found in the tibiofemoral joint in 17% of acute, 7% of subacute, and 44% of the chronic knees. Postoperative motion recovery was significantly less at all time intervals for the acute group. Quadriceps strength recovery was slower in the acute knees. Stability was similar in all groups. Arthrofibrosis was found in 22% of acute, 0 subacute, and 12.5% of the chronic knees. Patellofemoral pain was noted in 17% of the acute, 0 of the subacute, and 9.3% of the chronic knees. This study showed that surgery done within 6 months of injury does not jeopardize the knee. Recovery after acute anterior cruciate ligament reconstruction is significantly slower than after subacute or chronic reconstruction.


12-O-tetradecanoyl-phorbol-13-acetate decreases influx of extracellular Ca2+ induced by depolarization in GH4C1 cells: effects of pretreatment with 1,25-dihydroxycholecalciferol.
In GH4C1 rat pituitary cells, 1,25-dihydroxycholecalciferol (1,25(OH)2D3) causes amplification of both the TRH-induced spike phase in cytosolic free calcium [( Ca2+]i) and the increase in [Ca2+]i induced by depolarization with K+. In the present study we investigated the actions of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on Ca2(+)-homeostasis in GH4C1 cells pretreated with 1,25(OH)2D3 for 24 h. In control and 1,25(OH)2D3-pretreated cells, incubation with TPA (0.1-300 nM) for 15 min in the presence of 45Ca2+ did not affect the basal uptake of 45Ca2+. However, if the cells were treated with 50 mM K+, TPA induced a time- and concentration-dependent decrease in depolarization-induced net 45Ca2+ uptake. A maximal decrease of 30-50% was observed with 100-300 nM TPA, 1,25(OH)2D3 pretreated cells being more responsive to the action of TPA than control cells. sn-1-Oleoyl-2-acetyl-glycerol, which mimics the action of TPA on protein kinase C (PKC), did not alter depolarization-induced uptake of 45Ca2+. Two agents which inhibit PKC activity, polymyxin B and K252A, did not prevent the effect of TPA on depolarization-induced uptake of 45Ca2+, whereas staurosporin totally inhibited the action of TPA. In Fura-2 loaded cells pretreated with 1,25(OH)2D3, incubation with 200 nM TPA for 9 min decreased the depolarization-induced spike and plateau phases of change in [Ca2+]i; only the spike phase was decreased in control cells. TPA did not affect basal [Ca2+]i in either group. Treatment with TPA for only 3 min decreased the TRH-induced spike in [Ca2+]i only in 1,25(OH)2D3 pretreated cells; however, after a 5-min treatment with TPA, the TRH-induced spike in [Ca2+]i was decreased in both control and 1,25(OH)2D3 pretreated cells. TPA did not affect the spike in [Ca2+] induced by 50 nM ionomycin. Na+/Ca2+ exchange was not altered by TPA, nor did TPA enhance efflux of 45Ca2+ from cells preloaded with 45Ca2+ for 2.5 h. We conclude that, in GH4C1 cells, TPA modulates plasma membrane calcium flux, probably via an inhibitory action on voltage-operated Ca2+ channels. This inhibitory action may be independent of activation of PKC, and 1,25(OH)2D3 pretreated cells are more responsive to the actions of TPA than are control cells. These results are consistent with our previous findings that 1,25(OH)2D3 enhances voltage-dependent Ca2+ channel activity in GH4C1 cells.


Retrospective Comparison of 27-Gauge and 25-Gauge Microincision Vitrectomy Surgery with Silicone Oil for the Treatment of Primary Rhegmatogenous Retinal Detachment.
To retrospectively compare the safety and effectiveness of 27-gauge (27G) microincision vitrectomy surgery (MIVS) with 25-guage (25G) MIVS for the treatment of primary rhegmatogenous retinal detachment (RRD) with silicone oil tamponade. Ninety-two patients with RRD who underwent MIVS from May 1, 2015, to June 30, 2017, were included in this study. Fifty-eight eyes underwent 25G MIVS and 34 eyes underwent 27G MIVS. We analyzed the characteristics of the patients, surgical time, main clinical outcomes, and rate of complications. The mean surgical time was 56.7 ± 35.9 min for the 25G MIVS and 55.7 ± 36.1 min for the 27G MIVS, and there was no significant difference (P=0.894) between the two groups. The primary anatomical success rate after a single operation was 94.8% for 25G MIVS and 91.2% for 27G MIVS (P=0.666). Baseline and final visit best-corrected visual acuity (BCVA) were 1.9 ± 1.1 and 1.0 ± 0.8 in the 25G group, and 1.7 ± 1.0 and 1.1 ± 0.8 in the 27G group. Last visit BCVA increased significantly in both groups (P < 0.001). However, there were no significant differences in terms of visual improvement ratio (>0.2 logMAR) between the two groups (P=0.173). No severe intraoperative complication was observed. Iatrogenic retinal breaks occurred in 2 eyes (3.4%) in the 25G group and 1 eye (2.9%) in the 27G group during the peripheral vitreous base shaving. The transient ocular hypertension (>25 mmHg) within postoperative week 1 was 25.9% in the 25G group and 11.8% in the 27G group (P=0.120). This study found no significant anatomical or functional difference between 27G and 25G MIVS in the treatment of primary RRD. Therefore, 27G vitrectomy appears to be a safe and effective surgery for the treatment of primary RRD.


Two color DNA barcode detection in photoluminescence suppressed silicon nitride nanopores.
Optical sensing of solid-state nanopores is a relatively new approach that can enable high-throughput, multicolor readout from a collection of nanopores. It is therefore highly attractive for applications such as nanopore-based DNA sequencing and genotyping using DNA barcodes. However, to date optical readout has been plagued by the need to achieve sufficiently high signal-to-noise ratio (SNR) for single fluorophore sensing, while still maintaining millisecond resolution. One of the main factors degrading the optical SNR in solid-state nanopores is the high photoluminescence (PL) background emanating from the silicon nitride (SiNx) membrane in which pores are commonly fabricated. Focusing on the optical properties of SiNx nanopores we show that the local membrane PL intensity is substantially reduced, and its spectrum is shifted toward shorter wavelengths with increasing e-beam dose. This phenomenon, which is correlated with a marked photocurrent enhancement in these nanopores, is utilized to perform for the first time single molecule fluorescence detection using both green and red laser excitations. Specifically, the reduction in PL and the concurrent measurement of the nanopore photocurrent enhancement allow us to maximize the background suppression and to detect a dual color, five-unit DNA barcode with high SNR levels.


Boron in disguise: the parent "fused" BN indole.
"Fused" BN indoles are an emerging class of boron-containing indole mimics, featuring geometric structure and electophilic aromatic substitution reactivity similar to those of indoles but exhibiting distinct electronic structure, leading to unique optoelectronic properties. Herein we report the synthesis of the parent N-H BN indole and provide a head-to-head comparison of the structural features, pK(a) values, and optoelectronic properties of this hybrid organic/inorganic indole with the classic natural indole.


Colonic polyps in children: frequently multiple and recurrent.
A retrospective chart review on 77 children and adolescents (45 males and 32 females) with colorectal polyps seen over a 15-year period (1980-1994) was undertaken. Their presenting symptoms, demographic data, methods of diagnosis, pathologic diagnosis, and outcome were assessed. The age at presentation varied from 6 months to 19 years (mean age 77 months), 66.2% presenting under 6 years of age. The presenting symptoms were rectal bleeding in 71 patients, mass per rectum in 12, abdominal pain in nine, diarrhea in nine, vomiting in two, and one patient was asymptomatic. Air contrast barium enema was confirmatory in 41/54 patients (76%). Polyps were palpable in 16 patients during the rectal examination. A single polyp was present in 50 patients, whereas two to five polyps were present in 20 patients, and more than five in seven patients. Successful endoscopic removal was accomplished in 71/73 patients (97.3%). In 83.1% of patients polyps were located in the rectosigmoid area and in 32.5% polyps occurred proximal to the sigmoid colon. However, multiple polyps in the same location or at other locations were also present simultaneously. Recurrence was observed in five of 63 patients (7.9%) with juvenile polyps, in one patient with infantile polyposis, and in one with solitary adenomatous polyp. We conclude that a full colonoscopic evaluation should be performed in all patients with suspected polyps if feasible, for multiple polyps occurred in 35% of children without polyposis syndromes in this series. Parents of patients with more than three polyps and/or a family history of juvenile polyposis should be warned regarding the possibility of an increased risk of malignancy in future if polyps continue to recur.


Tasks of infertile couples.
The author presents four psychological tasks that face infertile couples as they attempt to deal with the childlessness and restore stability to their lives. Each task is discussed with attention to how the nurse can assist couples in dealing with their infertility. Emphasis is placed on the role of the nurse as facilitator, with the couple being the ones who must work through the problem.


First Description of KPC-2-Producing Klebsiella oxytoca Isolated from a Pediatric Patient with Nosocomial Pneumonia in Venezuela.
During the last decade, carbapenem resistance has emerged among clinical isolates of the Enterobacteriaceae family. This has been increasingly attributed to the production of β-lactamases capable of hydrolyzing carbapenems. Among these enzymes, Klebsiella pneumoniae carbapenemases (KPCs) are the most frequently and clinically significant class-A carbapenemases. In this report, we describe the first nosocomial KPC-2-producing K. oxytoca isolated from a pediatric patient with pneumonia admitted to the intensive care unit at The Andes University Hospital, Mérida, Venezuela. This strain was resistant to several antibiotics including imipenem, ertapenem, and meropenem but remained susceptible to ciprofloxacin, colistin, and tigecycline. Conjugation assays demonstrated the transferability of all resistance determinants, except aminoglycosides. The isolate LMM-SA26 carried a ~21 kb conjugative plasmid that harbored the bla KPC-2, bla CTX-M-8, and bla TEM-15 genes. Although carbapenem resistance in the Enterobacteriaceae is still unusual in Venezuela, KPCs have a great potential to spread due to their localization on mobile genetic elements. Therefore, rapid detection of KPC-carrying bacteria with phenotypic and confirmatory molecular tests is essential to establish therapeutic options and effective control measures.


Test of an electronic program to query clinicians about nonspecific causes reported for pneumonia deaths, New York City, 2012.
We tested an electronic cause-of-death query system at a hospital in New York City to evaluate clinicians' reporting of cause of death. We used the system to query clinicians about all deaths assigned International Classification of Disease code J189 (pneumonia, unspecified) as the underlying cause of death. Of 29 death certificates that generated queries, 28 were updated with additional information, which led to revisions in the underlying cause of 27 deaths. The electronic system for querying reported cause of death was feasible and enabled quicker than usual responses; however, follow-up with clinicians to ensure timely, accurate, and complete responses was labor-intensive. Educating clinicians and enforcing reporting standards would reduce the time and effort required to ensure accurate and timely cause-of-death reporting.


[Avian Chlamydia psittaci phyla and their pathogenic significance for turkeys].
The present study demonstrates that Chlamydia psittaci is an important cause of respiratory disease in turkeys in Europe. The serotyping of isolates revealed that European turkeys frequently become infected with Chlamydia psittaci serovar D strains, but also can become infected with serovar A and B strains. In turkeys, differences in pathogenicity were observed not only between strains belonging to the serovars A (strain 84/55), serovar B (strain 89/1326) and serovar D (Texas Turkey strain and strain 92/1293), but also between two strains belonging to the same serovar D (Texas Turkey strain and strain 92/1293). In order to find an explanation for these differences in pathogenicity, the pathogenesis of the infection was studied in specific pathogen free turkeys. However, for all three serovars examined a similar pathogenetic sequence of events was deduced. In order to try and elucidate the observed differences in pathogenicity between different Chlamydia psittaci strains, the bacterium-host cell interaction was studied in BGM cell culture using transmission electron microscopy and immuno electron microscopy. Strains most pathogenic for turkeys, namely the serovar A strain and strain 92/1293 (serovar D) produced significantly larger inclusions with more numerous infectious organisms, produced the most severe degenerative changes in the host cell an also replicated freely in the cytoplasm of the host cell.


Formation and Properties of a Self-Assembled Nanoparticle-Supported Lipid Bilayer Probed through Molecular Dynamics Simulations.
We have carried out coarse-grained molecular dynamics (MD) simulations to study the self-assembly procedure of a system of randomly placed lipid molecules, water beads, and a nanoparticle (NP). The self-assembly results in the formation of the nanoparticle-supported lipid bilayer (NPSLBL), with the self-assembly mechanism being driven by events such as the formation of small lipid clusters, merging of the lipid clusters in the vicinity of the NP to form NP-embedded vesicle with a pore, and collapsing of that pore to eventually form the equilibrated NPSLBL system overcoming a large free-energy barrier. Subsequently, we quantify the properties and the configurations of this NPSLBL system. We reveal that unlike our proposition of an equal number of lipid molecules occupying the inner and outer leaflets in a recent report studying the properties of a preassembled lipid bilayer, the equilibrated self-assembled NPSLBL system demonstrates a much larger number of lipid molecules occupying the outer leaflet as compared to the inner leaflet. Second, the thickness of the water layer entrapped between the NP and the inner leaflet shows similar values as predicted by experiments and our previous study. Finally, we reveal that, similar to our previous study, the diffusivity of the lipid molecules in the outer leaflet is larger than that in the inner leaflet but, due to higher temperature employed during our simulations, are even larger than that predicted by our previous study.


Real-time regeneration of a working zeolite monitored via operando X-ray diffraction and crystallographic imaging: how coke flees the MFI framework.
We have monitored the regeneration of H-ZSM-5 via operando time-resolved powder X-Ray diffraction (PXRD) coupled with mass spectroscopy (MS). Parametric Rietveld refinements and calculation of the extra-framework electronic density by differential Fourier maps analysis provide details on the mode of coke removal combined with the corresponding sub-unit cell changes of the zeolite structure. It is clear that the coke removal is a complex process that occurs in at least two steps; a thermal decomposition followed by oxidation. In a coked zeolite, the straight 10-ring channel circumference is warped to an oval shape due to structural distortion induced by rigid aromatic coke species. The data presented explain why the difference in length between the a-vector and the b-vector of the MFI unit cell is a robust descriptor for bulky coke, as opposed to the unit cell volume, which is affected also by adsorbed species and thermal effects. Our approach holds the promise to quantify and identify coke removal (and formation) in structurally distinct locations within the zeolite framework.


Cancer stem cell associated eight gene-based signature predicts clinical outcomes of colorectal cancer.
Previous studies have suggested that cancer stem cells serve crucial functions in tumorigenesis, metastasis and therapy failure. Stem cell signaling transduction pathways are frequently dysregulated in cancer and associated with tumorigenesis, metastasis and the cell cycle, which are necessary for cancer proliferation. However, cancer stem cell-associated gene signatures have not been established for predicting patient outcomes in colorectal cancer. Using a gene-mining approach, the present study performed mRNA expression profiling in large colorectal cancer cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, including a TCGA colorectal cancer cohort (n=383) and three independent validation series GSE39582 (n=582), GSE17536 (n=177) and GSE17537 (n=55). The present study identified that an eight-gene signature in cancer stem cell signaling was associated with the overall survival and disease/recurrence-free survival of patients with colorectal. On the basis of this signature, patients in the TCGA training sets were divided into high-risk and low-risk subgroups with a significantly different overall survival rate (hazard ratio, 2.38; P=0.0005). The prognostic value of this signature was confirmed using three independent GEO colorectal cancer sets. Identifying this prognostic stem cell signaling signature may provide an efficient classification tool for clinical prognosis evaluation, and facilitate cancer stem cell-targeted therapy.


Characterization of 1-to 2-cm liver nodules detected on hcc surveillance ultrasound according to the criteria of the American Association for the Study of Liver Disease: is quadriphasic CT necessary?
The purpose of this study was to identify the essential number of phases from multiphasic CT for 1- to 2-cm hepatocellular carcinoma (HCC) on surveillance ultrasound and to compare the results with the American Association for the Study of Liver Disease (AASLD) standard (arterial phase hypervascularity and portal venous phase [PVP] or delayed phase hypovascularity). The study included 110 newly detected nodules (1-2 cm; 36 HCC, 74 benign) in 96 patients detected in an HCC surveillance program. Three radiologists prospectively evaluated the attenuation of each nodule relative to the liver on each phase of quadriphasic CT. Univariate and multivariate logistic regression analyses were used to identify parameters associated with HCC. Multiple combinations of phases were compared with the AASLD standard. Only arterial phase hypervascularity and delayed phase hypovascularity were significantly associated with HCC both on univariate (odds ratio, arterial phase 7.51 [95% CI, 2.79-20.20]; delayed phase, 2.80 [1.14-6.90]) and multivariate analyses (arterial phase, 11.30 [4.30-29.68]; delayed phase, 4.39 [1.20-16.13]). The combination of arterial phase and delayed phase yielded the highest specificity (99%) and sensitivity (57%). There was no significant difference between AASLD standard (sensitivity, 57%; specificity, 98%) versus biphasic (arterial phase hypervascularity and delayed phase hypovascularity: sensitivity, 57%; p = 1 and specificity, 99%; p = 0.32), triphasic (arterial phase hypervascularity and unenhanced or PVP hypovascularity: sensitivity, 53%; p = 0.325 and specificity, 97%; p = 0.32), or quadriphasic combination (arterial phase hypervascularity and unenhanced, PVP or delayed phase hypovascularity: sensitivity, 57%; specificity, 97%), whereas the sensitivity of biphasic arterial phase and PVP was significantly lower (39% vs 57%, p = 0.022). For diagnosing 1- to 2-cm HCC detected on surveillance ultrasound, arterial phase and delayed phase are two essential phases, providing higher sensitivity than the combination of arterial phase and PVP, and equal performance with triphasic and quadriphasic combinations. The biphasic combination of arterial phase and delayed phase may replace quadriphasic CT recommended by AASLD.


[Effects of prolonged administration of dapiprazole in rats].
In this paper we have studied the rat under chronic treatment with dapiprazole ip. (a drug with alpha-adrenergic blocking properties). For a 4 week period we have recorded, once a week, weight, rectal temperature, tail-flick, general activity and explorative behaviour on rotarod and one-arm radial maze. Surface (SEEG) and deep (DEEG) EEGrams were also recorded at the end of the experiments (4th week). SEEG and DEEG underwent the Fourier analysis (Fast Fourier Transform--see text). The findings were: 1) No change was observed in weight, rectal temperature and tail-flick time, glycemia and haematocrit. 2) Motor coordination on rotaroad dropped in 1st and 3rd week of treatment. 3) The treated rats, when in a one arm radial maze, showed signs of sedation (no grooming) from 2nd week of treatment. 4) SEEG and DEEG recordings showed a slowing activity; Fourier analysis confirmed these results. The slowing of activity (4) well agrees with the signs of sedation and behaviour (2, 3). It seems thus confirmed that alpha-adrenergic blockade is a feature of the drug together with the psychotropic effects previously described.


[Oversupercoiling and compactization of supercoiled DNA].
Supercoiled DNA pGEMEX with length of 3993 nucleotides was immobilized on the different substrates (freshly cleaved mica, standard aminomica and modified aminomica) and visualized by atomic force microscopy. Plectonomically supercoiled DNA molecules as well as molecules with extremely high level of compactization (i.e. molecules with considerably higher supercoiled density values in comparing with experimentally measured and theoretically investigated ones) were visualized on modified aminomica. At the further increasing of the compactization level an axis length of oversupercoiled molecules was decreased from approximately 390 nm to approximately 140 nm and formation of minitoroids of approximately 50 nm diameter and molecules in sphere conformation were observed. Model of possible conformational transitions of supercoiled DNA was proposed basing on the analysis of captured AFM images at the increasing of supercoiling density.


A Randomized Controlled Trial of Virtual Reality in Awake Minor Pediatric Plastic Surgery Procedures.
Virtual reality has been used to alleviate pain and anxiety in a variety of medical procedures. The authors sought to explore the effects of virtual reality in common awake minor plastic surgery procedures where children may experience discomfort. A randomized controlled trial compared virtual reality to standard-of-care distraction among children aged 6 to 16 years undergoing awake minor plastic surgery procedures at a quaternary children's hospital. Primary outcome was change in Faces Pain Scale-Revised pain score, and secondary outcomes included change in Venham Situational Anxiety Scale score, procedure duration, administration of local anesthetic, and pain/anxiety management satisfaction. Mean pain and anxiety scores were similar in both groups (p = 0.60 and p = 0.18, respectively), and procedure duration was shorter with virtual reality (22 minutes versus 29 minutes; p = 0.002). Duration remained shorter in a linear regression model accounting for procedure type (p = 0.01). Similar proportions of children received additional local anesthetic after the initial dose (virtual reality, n = 6; standard of care, n = 9; p = 0.19) and median pain management satisfaction was similar (virtual reality, 9 of 10; standard of care, 9 of 10; p = 0.41). Median anxiety management satisfaction was similar (virtual reality, 9 of 10; standard of care, 9 of 10; p = 0.05). Younger children reported more "fun" than older children with virtual reality (p = 0.02). Surgeons reported interest "using virtual reality again" in 83 percent of cases. The use of virtual reality for awake pediatric plastic surgery reduced procedure time but not pain or anxiety compared to standard of care in children aged 6 to 16 years. Virtual reality was safe and well-liked and should be considered as an additional tool. Increased efficiency may allow more cases to be performed. Therapeutic, II.


Dipolar Relaxation of Water Protons in the Vicinity of a Collagen-like Peptide.
Quantitative magnetic resonance imaging is one of the few available methods for noninvasive diagnosis of degenerative changes in articular cartilage. The clinical use of the imaging data is limited by the lack of a clear association between structural changes at the molecular level and the measured magnetic relaxation times. In anisotropic, collagen-containing tissues, such as articular cartilage, the orientation dependency of nuclear magnetic relaxation can obscure the content of the images. Conversely, if the molecular origin of the phenomenon would be better understood, it would provide opportunities for diagnostics as well as treatment planning of degenerative changes in these tissues. We study the magnitude and orientation dependence of the nuclear magnetic relaxation due to dipole-dipole coupling of water protons in anisotropic, collagenous structures. The water-collagen interactions are modeled with molecular dynamics simulations of a small collagen-like peptide dissolved in water. We find that in the vicinity of the collagen-like peptide, the dipolar relaxation of water hydrogen nuclei is anisotropic, which can result in orientation-dependent relaxation times if the water remains close to the peptide. However, the orientation-dependency of the relaxation is different from the commonly observed magic-angle phenomenon in articular cartilage MRI.


Lyapunov Exponent and Out-of-Time-Ordered Correlator's Growth Rate in a Chaotic System.
It was proposed recently that the out-of-time-ordered four-point correlator (OTOC) may serve as a useful characteristic of quantum-chaotic behavior, because, in the semiclassical limit ℏ→0, its rate of exponential growth resembles the classical Lyapunov exponent. Here, we calculate the four-point correlator C(t) for the classical and quantum kicked rotor-a textbook driven chaotic system-and compare its growth rate at initial times with the standard definition of the classical Lyapunov exponent. Using both quantum and classical arguments, we show that the OTOC's growth rate and the Lyapunov exponent are, in general, distinct quantities, corresponding to the logarithm of the phase-space averaged divergence rate of classical trajectories and to the phase-space average of the logarithm, respectively. The difference appears to be more pronounced in the regime of low kicking strength K, where no classical chaos exists globally. In this case, the Lyapunov exponent quickly decreases as K→0, while the OTOC's growth rate may decrease much slower, showing a higher sensitivity to small chaotic islands in the phase space. We also show that the quantum correlator as a function of time exhibits a clear singularity at the Ehrenfest time t_{E}: transitioning from a time-independent value of t^{-1}lnC(t) at t<t_{E} to its monotonic decrease with time at t>t_{E}. We note that the underlying physics here is the same as in the theory of weak (dynamical) localization [Aleiner and Larkin, Phys. Rev. B 54, 14423 (1996)PRBMDO0163-182910.1103/PhysRevB.54.14423; Tian, Kamenev, and Larkin, Phys. Rev. Lett. 93, 124101 (2004)PRLTAO0031-900710.1103/PhysRevLett.93.124101] and is due to a delay in the onset of quantum interference effects, which occur sharply at a time of the order of the Ehrenfest time.


Three one-dimensional coordination polymers based on 1,1'-bis(pyridin-4-ylmethyl)-2,2'-bi-1H-benzimidazole and HgX2 (X = Cl, Br and I).
A new 2,2'-bi-1H-benzimidazole bridging organic ligand, namely 1,1'-bis(pyridin-4-ylmethyl)-2,2'-bi-1H-benzimidazole, C26H20N6, L or (I), has been synthesized and used to create three new one-dimensional coordination polymers, viz. catena-poly[[dichloridomercury(II)]-μ-1,1'-bis(pyridin-4-ylmethyl)-2,2'-bi-1H-benzimidazole], [HgCl2(C26H20N6)]n, (II), and the bromido, [HgBr2(C26H20N6)]n, (III), and iodido, [HgI2(C26H20N6)]n, (IV), analogues. Free ligand L crystallizes with two symmetry-independent half-molecules in the asymmetric unit and each L molecule resides on a crytallographic inversion centre. In structures (II)-(IV), the L ligand is also positioned on a crystallographic inversion centre, whereas the Hg centre resides on a crystallographic twofold axis. Compound (I) adopts an anti conformation in the solid state and forms a two-dimensional network in the crystallographic bc plane via π-π and C-H...π interactions. The three Hg(II) coordination complexes, (II)-(IV), have one-dimensional zigzag chains composed of L and HgX2 (X = Cl, Br and I), and the Hg(II) centres are in a distorted tetrahedral [HgX2N2] coordination geometry. Complexes (III) and (IV) are isomorphous, whereas complex (II) displays an interesting conformational difference from the others, i.e. a twist in the flexible bridging ligand.


Cellular Redox Profiling Using High-content Microscopy.
Reactive oxygen species (ROS) regulate essential cellular processes including gene expression, migration, differentiation and proliferation. However, excessive ROS levels induce a state of oxidative stress, which is accompanied by irreversible oxidative damage to DNA, lipids and proteins. Thus, quantification of ROS provides a direct proxy for cellular health condition. Since mitochondria are among the major cellular sources and targets of ROS, joint analysis of mitochondrial function and ROS production in the same cells is crucial for better understanding the interconnection in pathophysiological conditions. Therefore, a high-content microscopy-based strategy was developed for simultaneous quantification of intracellular ROS levels, mitochondrial membrane potential (ΔΨm) and mitochondrial morphology. It is based on automated widefield fluorescence microscopy and image analysis of living adherent cells, grown in multi-well plates, and stained with the cell-permeable fluorescent reporter molecules CM-H2DCFDA (ROS) and TMRM (ΔΨm and mitochondrial morphology). In contrast with fluorimetry or flow-cytometry, this strategy allows quantification of subcellular parameters at the level of the individual cell with high spatiotemporal resolution, both before and after experimental stimulation. Importantly, the image-based nature of the method allows extracting morphological parameters in addition to signal intensities. The combined feature set is used for explorative and statistical multivariate data analysis to detect differences between subpopulations, cell types and/or treatments. Here, a detailed description of the assay is provided, along with an example experiment that proves its potential for unambiguous discrimination between cellular states after chemical perturbation.


Indoor Dust/Air Partitioning: Evidence for Kinetic Delay in Equilibration for Low-Volatility SVOCs.
Effective modeling of semivolatile organic chemical (SVOC) partitioning between air and indoor dust is investigated by calculating partition ratios for selected SVOCs between air and n-octanol as well as 8 other oligomers similar in chemical structure to common components of household dust. COSMO-RS solvation theory was used to calculate air-oligomer partition ratios, which were converted to estimates for KOA (octanol-air) and Kdust-air. The results are compared with reported monitored partition ratios with good agreement for the more volatile SVOCs of vapor pressure (VP) exceeding 10-5 Pa and corresponding calculated log Kdust-air (m3 g-1) of <5.5 or unitless log KOA of <11.5. For less volatile SVOCs, reported values of KDA are significantly lower than predicted, with the deviation increasing with decrease in VP. This effect is attributed to a kinetic delay in which characteristic times for equilibration exceed the dust-air contact time, and equilibrium is not achieved. It is hoped that the approach of computing partition ratios of SVOCs using oligomers selected on the basis of likely dust sources and compositions may improve the estimation of indoor human exposure to SVOCs present in air and dust and assist in exploiting dust samples to monitor and evaluate the fate and exposure of organic chemicals used indoors.


Modeling the morphology and mechanical properties of sheared ternary mixtures.
Through a combination of simulation techniques, we determine both the structural evolution and mechanical properties of blends formed from immiscible ternary mixtures. In this approach, we first use the lattice Boltzmann method to simulate the phase separation dynamics of A/B/C fluid mixtures for varying compositions within the spinodal region. We also investigate the effect of an imposed shear on the phase ordering of the mixture. We assume that the fluid is quenched sufficiently rapidly that the phase-separated structure is preserved in the resultant solid. Then, the output from our morphological studies serves as the input to the lattice spring model, which is used to simulate the elastic response of solids to an applied deformation. These simulations reveal how the local stress and strain fields and the global Young's modulus depend on the composition of the blend and the stiffness of the components. By comparing the results for the sheared and unsheared cases, we can isolate optimal processing conditions for enhancing the mechanical performance of the blends. Overall, the findings provide fundamental insight into the relationship between structure, processing, and properties for heterogeneous materials and can yield guidelines for formulating blends with the desired macroscopic mechanical behavior.


TURBINATES IN THERAPSIDS: EVIDENCE FOR LATE PERMIAN ORIGINS OF MAMMALIAN ENDOTHERMY.
The structure and function of the nasal conchae of extant reptiles, birds, and mammals are reviewed, and the relationships to endothermy of the mammalian elements are examined. Reptilian conchae are relatively simple, recurved structures, which bear primarily sensory (olfactory) epithelium. Conversely, the conchae, or turbinates, of birds and mammals are considerably more extensive and complex, and bear, in addition, nonsensory (respiratory) epithelium. Of the mammalian turbinates, only the exclusively respiratory maxilloturbinal has a clear functional relationship with endothermy, as it reduces desiccation associated with rapid and continuous pulmonary ventilation. The other mammalian turbinates principally retain the primitive, olfactory function of the nasal conchae. The maxilloturbinates are the first reliable morphological indicator of endothermy that can be used in the fossil record. In fossil mammals and mammallike reptiles, the presence and function of turbinates are most readily revealed by the ridges by which they attach to the walls of the nasal cavity. Ridges for olfactory turbinals are located posterodorsally, away from the main flow of respiratory air, whereas those of the respiratory maxilloturbinals are situated in the anterolateral portion of the nasal passage, directly in the path of respired air. The maxilloturbinal is also characterized by its proximity to the opening of the nasolacrimal canal. Posterodorsal ridges, for olfactory turbinals, have long been recognized in many mammallike reptiles, including early forms such as pelycosaurs. However, ridges for respiratory turbinals have not been identified previously in this group. In this paper, the presence of anterolateral ridges, which most likely supported respiratory turbinals, is reported in the primitive therocephalian Glanosuchus and in several cynodonts. The presence of respiratory turbinals in these advanced mammallike reptiles suggests that the evolution of "mammalian" oxygen consumption rates may have begun as early as the Late Permian and developed in parallel in therocephalians and cynodonts. Full mammalian endothermy may have taken as much as 40 to 50 million yr to develop.


Stages in the life cycle of community care planning.
Local and health authorities have been required to plan community care since 1992. Expectations of the purpose and utility of the process still differ widely. This article explores experience to date and explains the changes in practice identified.


Cerenkov imaging.
Cerenkov luminescence (CL) has been used recently in a plethora of medical applications like imaging and therapy with clinically relevant medical isotopes. The range of medical isotopes used is fairly large and expanding. The generation of in vivo light is useful since it circumvents depth limitations for excitation light. Cerenkov luminescence imaging (CLI) is much cheaper in terms of infrastructure than positron emission tomography (PET) and is particularly useful for imaging of superficial structures. Imaging can basically be done using a sensitive camera optimized for low-light conditions, and it has a better resolution than any other nuclear imaging modality. CLI has been shown to effectively diagnose disease with regularly used PET isotope ((18)F-FDG) in clinical setting. Cerenkov luminescence tomography, Cerenkov luminescence endoscopy, and intraoperative Cerenkov imaging have also been explored with positive conclusions expanding the current range of applications. Cerenkov has also been used to improve PET imaging resolution since the source of both is the radioisotope being used. Smart imaging agents have been designed based on modulation of the Cerenkov signal using small molecules and nanoparticles giving better insight of the tumor biology.


Comparison of vaporization using 120-W GreenLight laser versus 2-micrometer continuous laser for treating benign prostatic hyperplasia: A 24-month follow-up study of a single center.
To evaluate safety, efficacy, and long-term outcomes of photoselective vaporization of prostate using 120-W HPS GreenLight KTP laser and compare the results with those obtained with 2-micrometer continuous-wave (2 um CW) laser for treatment of patients with benign prostatic hyperplasia (BPH). One group of 216 patients diagnosed with BPH underwent 120-W KTP laser vaporization of the prostate, while another group of 198 BPH patients underwent 2 um CW laser vaporization. The relevant pre-, peri-, and post-operative parameters were compared between the two therapy groups. Functional results in terms of improvement of International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and post-void residual (PVR) urine were assessed at 3, 6, 12, and 24 months. BPH was successfully treated with 120-W HPS KTP laser and 2 um CW laser in all patients. There were no significant difference between two patient groups in the baseline characteristics (such as PSA, IPSS, QoL, and Qmax). No major complications occurred intraoperatively (capsule perforation and TUR syndrome) or postoperatively (electric unbalance), and no blood transfusions were required in both groups. Average catheterization time was 1.9±1.3 days for the 120-W PVP and 2.2±1.9 days for the 2 um CW laser treatment. In addition, the hospitalization times were 3.8±1.2days (120-W PVP) and 4.8±1.5 days (2 um CW laser), respectively. The incidence of dysuria and urge incontinence was higher in the 2 um CW laser group (35/198, 24/198) than in the 120 W PVP group (15/216, 10/216). Dramatic improvement was observed in Qmax, IPSS, Qol, and PVR as compared with the respective pre-operative values. The degree of improvement during the follow-up period was comparable in both groups. No significant differences were observed in terms of re-operation rates, bladder neck stricture, and urethral stricture. Both 120-W HPS laser and 2 um CW laser vaporization present effective treatment options in patients with BPH, but 120-W PVP provides safer therapy with less post-operative complications within the 2-year follow-up period.


Induction, purification, and properties of 2'5' oligoadenylate synthetase.
The results presented above relate to several aspects of the 2-5A system. A simple but insensitive radiochemical assay fro 2-5A and its synthetase is described. Progress towards the molecular characterization of the synthetase suggested that it is composed of a single 56,000 dalton polypeptide chain that is synthesized in response to IF treatment. Degradation of 2-5A occurs at the same rapid rate in extracts of IF-treated and untreated chick cells. However, this breakdown can be inhibited by its end-product, 5'AMP, or by the activated synthetase which can further elongate 2-5A and thereby protect it from degradation. The direction of elongation is from the 5' to the 2' terminus. Molecules other than 2-5A can act as substrates fro 2'-adenylation by the activated synthetase. These include some dinucleoside monophosphates, ADP-ribose and NAD+, and methylene-bridged analogues of ATP. The methylene-bridged analogues of 2-5A that are synthesized in the latter case retain some of the biological activity of authentic 2-5A, indicating that cleavage of the 5'-terminal phosphate group(s) is not involved in the mechanism of nuclease activation by 2-5A.


The role of mitochondrial and oxidative injury in BDE 47 toxicity to human fetal liver hematopoietic stem cells.
The polybrominated diphenyl ethers (PBDEs) are a group of flame retardants whose residues have markedly increased in the environment and in human tissues during the last decade. Of the various congeners, BDE 47 (2,2',4,4'-tetrabromodiphenyl ether) is typically the predominant congener observed in fish and wildlife samples, as well as in human tissues. Several studies indicate in utero transfer of PBDEs during pregnancy with residues accumulating in fetal tissues, and thus the potential for BDE 47-mediated injury in utero is of concern. In this study, we examined the mechanisms of BDE 47-mediated injury to primary human fetal liver hematopoietic stem cells (HSCs), which comprise a large proportion of fetal hepatic cells and play a key role in hematopoiesis during fetal development. Incubation of fetal liver HSCs with BDE 47 led to a loss of mitochondrial membrane potential and the onset of apoptosis. These effects were observed in the low micromolar range of BDE 47 exposures. At higher concentrations, BDE 47 elicited a loss of viability, which was accompanied by the generation of reactive oxygen species and peroxidation of HSC lipids. Preincubation of fetal liver HSCs with N-acetylcysteine, a glutathione (GSH) precursor, caused an increase in cellular GSH concentrations, restored mitochondrial redox status, and ameliorated the toxicity of BDE 47. BDE 47-mediated cytotoxicity or oxidative injury was not evident at the lower concentrations (< 1microM). Collectively, these data support a role for oxidative stress in the cytotoxicity of BDE 47 and indicate that oxidative stress-associated biomarkers may be useful in assessing the sublethal effects of BDE 47 toxicity in other models. However, the fact that BDE 47 undergoes a concentration-dependent accumulation in other primary cells in media that can underestimate cellular concentrations (W. R. Mundy et al., 2004, Toxicol. Sci. 82, 164-169) suggests that the HSC cell injury observed in our study may be of less relevance to human in utero PBDE exposures.


[Bioartificiality thresholds: oscillations of genetic patenting].
The legal interpretations that both patent offices and courts in the US and in Europe have applied to biotechnological inventions seem to go back an forth in defining to what extent DNA sequences can be patented. This process has given rise to the creation of different thresholds of bioartificiality, and to the blurring of boundaries between what can and cannot be patented. The different legal rules established in both systems during the last decade have been also oscillating between increased international harmonization and concern for the internal regulatory framework.


Effect of previous diet on feed intake and body weight gain of broiler and Leghorn chicks.
An experiment was conducted to examine the effect of previous diet on feed intake and weight gain, in the subsequent period, for broiler and Leghorn cockerels. Three dietary treatments, consisting of 20% protein and either 2400, 2800, or 3200 kcal Me/kg, were fed in combinations consisting of three, 2-week periods, with nine combinations in all. The experimental design was balanced for residual effects, and period weight gains and feed intake were determined. Analysis of the data by period indicated that treatments by residual interactions were confined to the final period. Therefore, it was concluded that diets fed in the previous two periods may be acting in combination to effect weight gain and feed intake in the final period. Examination of the pooled period data indicated that for optimum performance, broilers required a dietary regimen consisting of increased calorie-to-protein ratios with time while Leghorns required lower calorie-to-protein ratios. Type differences were also observed in the ability to adapt to high protein, low intakes: Leghorns grew optimally but body weight gain for broilers was reduced with such a feeding program.


The hydrophobic face orientation of apolipoprotein A-I amphipathic helix domain 143-164 regulates lecithin:cholesterol acyltransferase activation.
Apolipoprotein A-I (apoA-I) activates the plasma enzyme lecithin:cholesterol acyltransferase (LCAT), catalyzing the rapid conversion of lipoprotein cholesterol to cholesterol ester. Structural mutants of apoA-I have been used to study the details of apoA-I-LCAT-catalyzed cholesterol ester formation. Several studies have shown that the alpha-helical segments corresponding to amino acids 143-164 and 165-186 (repeats 6 and 7) are essential for LCAT activation. In the present studies, we examined how the orientation of the hydrophobic face, independent of an increase in overall hydrophobicity, affects LCAT activation. We designed, expressed, and characterized a mutant, reverse of 6 apoA-I (RO6 apoA-I), in which the primary amino acid sequence of repeat 6 (amino acids 143-164) was reversed from its normal orientation. This mutation rotates the hydrophobic face of repeat 6 approximately 80 degrees. Lipid-free RO6 apoA-I showed a marked stabilization when denatured by guanidine hydrochloride, but showed significant destabilization to guanidine hydrochloride denaturation in the lipid-bound state compared with wild-type apoA-I. Recombinant high density lipoprotein discs (rHDL) formed from RO6 apoA-I, sn-1-palmitoyl-sn-2-oleoyl phosphati-dylcholine, and cholesterol were approximately 12 A smaller than wild-type apoA-I rHDL. The reduced size suggests that one of the repeats did not effectively participate in phospholipid binding and organization. The sn-1-palmitoyl-sn-2-oleoyl phosphatidylcholine RO6 rHDL were a less effective substrate for LCAT. Mapping the entire lipid-free and lipid-bound RO6 apoA-I with a series of monoclonal antibodies revealed that both the lipid-free and lipid-bound RO6 apoA-I displayed altered or absent epitopes in domains within and adjacent to repeat 6. Together, these results suggest that the proper alignment and orientation of the hydrophobic face of repeat 6 is an important determinant for maintaining and stabilizing helix-bilayer and helix-helix interactions.


Functional Brain Activation in Response to a Clinical Vestibular Test Correlates with Balance.
The current study characterizes brain fMRI activation in response to two modes of vestibular stimulation: Skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either a vestibulo-spinal reflex [saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)], or an ocular muscle response [utricle-mediated ocular VEMP (oVEMP)]. Research suggests that the skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for subjects than the high decibel tones required to elicit VEMPs. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of brain activity. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that pneumatically powered skull taps would elicit a similar pattern of brain activity as shown in previous studies. Our results provide the first evidence of using pneumatically powered skull taps to elicit vestibular activity inside the MRI scanner. A conjunction analysis revealed that skull taps elicit overlapping activation with auditory tone bursts in the canonical vestibular cortical regions. Further, our postural control assessments revealed that greater amplitude of brain activation in response to vestibular stimulation was associated with better balance control for both techniques. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects, highlighting the utility of this approach for future clinical and basic science research.


Siccibacter turicensis from Kangaroo Scats: Possible Implication in Cellulose Digestion.
Microbiota in the kangaroo gut degrade cellulose, contributing to the kangaroo's energy and survival. In this preliminary study, to discover more about the gut microbes that contribute to the survival of kangaroos, cellulose-degrading bacteria were isolated from kangaroo scats by selection on solidified media containing carboxymethyl cellulose as the main carbon source. One frequently occurring aerobic bacterium was Siccibacter turicensis, a microbe previously isolated in fruit powder and from a patient with angular cheilitis. The whole genome sequence of the kangaroo isolate was obtained using the Illumina MiSeq platform. Its sequence shared 97.98% identity of the S. turicensis Type strain, and the ability of the Type strain to degrade cellulose was confirmed. Analysis of the genomic data focused on the cellulose operon. In addition to genes from the operon, we suggest that a gene following the operon may have an important role in regulating cellulose metabolism by signal transduction. This is the first report of S. turicensis found within microbiota of the animal gut. Because of its frequent presence in the kangaroo gut, we suggest that S. turicensis plays a role in cellulose digestion for kangaroos.


Detection of Memory B Activity Against a Therapeutic Protein in Treatment-Naïve Subjects.
Bridging immunoassays commonly used to detect and characterize immunogenicity during biologic development do not provide direct information on the presence or development of a memory anti-drug antibody (ADA) response. In this study, a B cell ELISPOT assay method was used to evaluate pre-existing ADA for anti-TNFR1 domain antibody, GSK1995057, an experimental biologic in treatment naive subjects. This assay utilized a 7-day activation of PBMCs by a combination of GSK1995057 (antigen) and polyclonal stimulator followed by GSK1995057-specific ELISPOT for the enumeration of memory B cells that have differentiated into antibody secreting cells (ASC) in vitro. We demonstrated that GSK1995057-specific ASC were detectable in treatment-naïve subjects with pre-existing ADA; the frequency of drug-specific ASC was low and ranged from 1 to 10 spot forming units (SFU) per million cells. Interestingly, the frequency of drug-specific ASC correlated with the ADA level measured using an in vitro ADA assay. We further confirmed that the ASC originated from CD27+ memory B cells, not from CD27--naïve B cells. Our data demonstrated the utility of the B cell ELISPOT method in therapeutic protein immunogenicity evaluation, providing a novel way to confirm and characterize the cell population producing pre-existing ADA. This novel application of a B cell ELISPOT assay informs and characterizes immune memory activity regarding incidence and magnitude associated with a pre-existing ADA response.


Utility of the Spanish version of the Everyday Cognition scale in the diagnosis of mild cognitive impairment and mild dementia in an older cohort from the Argentina-ADNI.
The performance of activities of daily living in elderly patients with memory disorders is directly related to living independently and to autonomy. Documenting and assessing functional capacity through detailed scales is important for both diagnostic and treatment recommendations. The Everyday Cognition (ECog) scale is a relatively new informant-rated measure of cognitive and functional abilities. In the present study, the discriminant validity of the ECog scale was evaluated in cognitively intact controls (CN) and in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) from the Argentina-ADNI cohort to establish diagnostic accuracy. In addition, we compared the sensitivity and specificity of ECog against Functional Assessment Questionnaire (FAQ) scale to discriminate among the three groups. We evaluated 15 CN, 28 MCI, and 13 mild AD subjects. External, convergent and divergent validity and internal consistency were examined. The average total score on the ECog was significantly different across the three diagnostic syndromes (p < .05). The ECog was more sensitive than FAQ in discriminating between CN and MCI patients and between MCI and AD subjects. The ECog showed a strong correlation with FAQ, and moderate correlations with neuropsychological tests. Cronbach's alpha was .98. The ECog scale is an efficient instrument for the differentiation of individuals with mild dementia or MCI from normal older adults, with good accuracy and good correlation with other tests measuring daily and cognitive functions. Comparing against FAQ, ECog was more useful in assessing changes in functionality in MCI patients.


Innervation of ectopic endometrium in a rat model of endometriosis.
Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimic those in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and A delta fibers), substance P (SP) (sensory C and A delta fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.


Survivals of D. galeata in sub-tropical reservoirs: harmful effects of toxic cyanobacteria in food source.
In the present study, we tested the hypothesis that massive occurrence of cyanobacteria as food source is one of the factors limiting the distribution of the zooplankton Daphnia galeata in the warm water reservoirs of South China. D. galeata was fed with Chlorella pyrenoidosa, 4 strains of cyanobacteria (three strains of Microcystis aeruginosa: MC1, MC2 and MC3, and one strain of Pseudoanabaena sp. :PA), a mixture of C. pyrenoidosa and cyanobacterial strains, and natural particles from the reservoir where the animal was initially collected. On medium and high food levels (1 and 1.5 mg C L(-1)) of C. pyrenoidosa, D. galeata showed a typical Type III of survivorship, and had a high intrinsic rate of population increase (0.37-0.41). On low food levels, the intrinsic rate of population increase declined but lifespan largely increased (84 days). When feeding with natural particles, the intrinsic rate of increase was evidently reduced (0.19), but the maximal body length (2 mm) was much longer than that of individuals observed in the fields implying that D. galeata was strongly preyed upon by size-selective predators. Applying a mixture of Chlorella and cyanobacteria, the strain and proportion of cyanobacteria significantly affected life history variables of the animal and its somatic growth. On the sole diet of each stain of cyanobacteria, D. galeata failed to reproduce. Microcystin and colonial morphology of Microcystis strains reduced clutch size and somatic growth rate. In comparison, the less negative effect of the strain MC3 indicates that the morphology was critical for actual ingestion of toxic cyanobacteria by the zooplanktons. Pseudoanabaena sp. had a short filament (15 μm), can be easily used as a food by D. galeata. Composition of phytoplankton community plays a significant role in survival and population sizes of D. galeata and massive occurrence of cyanobacterial blooms limits the distribution of D. galeata in the reservoirs of South China.