Rice blast infection of Brachypodium distachyon as a model system to study dynamic host/pathogen interactions.
Interactions between plants and compatible fungal pathogens are spatially and temporally dynamic, posing a major challenge for sampling and data analysis. A protocol is described for the infection of the model grass species Brachypodium distachyon with Magnaporthe grisea (rice blast), together with modifications to extend the use to rice and barley. We outline a method for the preparation of long-term stocks of virulent fungal pathogens and for the generation of fungal inoculants for challenge of host plants. Host plant growth, pathogen inoculation and plant sampling protocols are presented together with methods for assessing the efficiency of both infection and sampling procedures. Included in the anticipated results is a description of the use of metabolite fingerprinting and multivariate data analysis to assess disease synchrony and validate system reproducibility between experiments. The design concepts will have value in any studies using biological systems that contain dynamic variance associated with large compositional changes in sample matrix over time.


Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).
The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.


Inhibition of vection by grasping an object.
The present study investigated whether vection could be modified by an object grasping movement. Twenty-five university students were asked to do one of the following four types of left-hand movements while they were viewing a radial optic flow: (1) grasping the hand-gripper strongly; (2) holding the hand-gripper; (3) clenching fist strongly; and (4) open hand without having anything in their left hands (normal hand condition). The participants' tasks were to keep pressing a button with their right hands while they were perceiving vection. After each trial, they estimated the subjective strength of vection on a 101-point scale. The result showed that the vection was inhibited by strongly grasping the hand-gripper task more than by the other hand movements. Vection could be weakened by the object grasping movement. It might be suggested that vection could be inhibited by the presence of an object being grasped and also by the grasping movement itself. We speculated that the mechanism underlying this inhibition might be related to cognitive pressure, attentional load, power and muscle tonus, and multisensory and proprioception interactions.


The effects of lipoxin A and lipoxin B on functional responses of human granulocytes.
Lipoxin A and lipoxin B (LXA and LXB) are formed from arachidonic acid by leukocyte 5- and 15-lipoxygenases. We have assessed the effects of synthetic lipoxins on functional responses of human granulocytes. LXA stimulated migration at 1 nM. The effect was highly stereospecific, since e.g. 6S-LXA and LXB were less active than LXA. Neither synthetic LXA nor several of its stereoisomers provoked degranulation or aggregation. LXB and its isomers did not induce any of these functional responses. These results indicate that migratory granulocyte responses to LXA are highly stereospecific.


Modeling cellular processes with variational Bayesian cooperative vector quantizer.
Gene expression of a cell is controlled by sophisticated cellular processes. The capability of inferring the states of these cellular processes would provide insight into the mechanism of gene expression control system. In this paper, we propose and investigate the cooperative vector quantizer (CVQ) model for analysis of microarray data. The CVQ model could be capable of decomposing observed microarray data into many different regulatory subprocesses. To make the CVQ analysis tractable we develop and apply variational approximations. Bayesian model selection is employed in the model, so that the optimal number processes is determined purely from observed micro-array data. We test the model and algorithms on two datasets: (1) simulated gene-expression data and (2) real-world yeast cell-cycle microarray data. The results illustrate the ability of the CVQ approach to recover and characterize regulatory gene expression subprocesses, indicating a potential for advanced gene expression data analysis.


THREE-DIMENSIONAL MULTI-SEGMENTED SPINE JOINT REACTION FORCES DURING COMMON WORKPLACE PHYSICAL DEMANDS/ACTIVITIES OF DAILY LIVING.
The quantification of inter-segmental spine joint reaction forces during common workplace physical demands. Many spine reaction force models have focused on the L5/S1 or L4/L5 joints to quantify the vertebral joint reaction forces. However, the L5/S1 or L4/L5 approach neglects most of the intervertebral joints. The current study presents a clinically applicable and noninvasive model which calculates the spinal joint reaction forces at six different regions of the spine. Subjects completed four ambulatory activities of daily living: level walking, obstacle crossing, stair ascent, and stair descent. Peak joint spinal reaction forces were compared between tasks and spine regions. Differences existed in the bodyweight normalized vertical joint reaction forces where the walking (8.05±3.19N/kg) task had significantly smaller peak reaction forces than the stair descent (12.12±1.32N/kg) agreeing with lower extremity data comparing walking and stair descent tasks. This method appears to be effective in estimating the joint reaction forces using a segmental spine model. The results suggesting the main effect of peak reactions forces in the segmental spine can be influenced by task.


Different neuroligands and signal transduction pathways stimulate CREB phosphorylation at specific developmental stages along oligodendrocyte differentiation.
We have shown previously that the pattern of expression of the transcription factor CREB (cyclic AMP-response element binding protein) in developing oligodendrocytes (OLGs) suggests a role during a period that precedes the peak of myelination in rat brain. We have now investigated the signaling pathways that could be responsible for activating CREB by phosphorylation at different stages along OLG maturation. CREB phosphorylation was studied in short-term cultures of immature OLG precursor cells and young OLGs isolated from 4- and 11-day-old rat cerebrum, respectively. The results indicated that at both developmental stages, CREB phosphorylation could be stimulated by either increased concentrations of cyclic AMP and cyclic AMP-dependent protein kinase activation or increased Ca2+ levels and a protein kinase C activity. The results also showed that CREB phosphorylation in immature OLG precursor cells could be up-regulated by treatment with histamine, carbachol, glutamate, and ATP (neuroligands known to increase Ca2+ levels in these cells), by signaling cascade(s) that involve a protein kinase C activity, as well as the mitogen-activated protein kinase pathway. In contrast, in cells isolated from 11-day-old rats, at a developmental stage that immediately precedes the beginning of the active period of myelin synthesis, CREB phosphorylation was only stimulated by treatment with the beta-adrenergic agonist isoproterenol in a process that appears to be mediated by a cyclic AMP/cyclic AMP-dependent protein kinase-dependent pathway. These results support the idea that CREB could be a mediator of neuronal signals that, coupled to specific signal transduction cascades, may play different regulatory roles at specific stages along OLG differentiation.


Deregulation of cell-signaling pathways in HTLV-1 infection.
Human T-lymphotropic virus type 1 (HTLV-1) infection is associated with the clonal expansion and transformation of mature T lymphocytes. While the mechanisms involved are incompletely understood the viral regulatory protein Tax plays a central role in these processes. Recent studies employing genomic and proteomic approaches have demonstrated the marked complexity of gene deregulation associated with Tax expression and confirmed the remarkable pleiotropism of this protein as evidenced by the numerous Tax-cellular protein interactions in infected cells. In this review, we summarize the role of Tax in the deregulation of selected cellular-signaling pathways. Specifically, this has focused on the influence and interaction of Tax with the AP-1 and NF-AT transcription factors, PDZ domain-containing proteins, Rho-GTPases, and the Janus kinase/signal transducer and activator of transcription and transforming growth factor-beta-signaling pathways. In addition to identifying the deregulation of events within these pathways, attempts have been made to highlight differences between HTLV-1 and -2, which may relate to differences in their pathogenic properties.


Rhodococcus equi in fecal and environmental samples from Kansas horse farms.
Horse farms in Kansas were surveyed for the incidence of Rhodococcus equi. Fecal specimens and soil or cobweb samples were collected from each farm and cultured on selective media. One control farm (with no history of R. equi infection), one farm which had an outbreak 3 and 4 years previously and 2 farms which had R. equi-infected foals that season were surveyed. In addition, fecal samples from 21 horses hospitalized in the Kansas State University Veterinary Hospital were cultured. There was no significant difference in the incidence of R. equi in fecal samples from the 2 farms with recent disease problems. The farm with a history of disease had a significantly higher percentage of positive fecal cultures than the 2 farms with a more recent history of disease. Neither ration composition nor sex of the horses appeared to affect the fecal culture results. Fecal samples from 2 birds on 1 farm were positive for R. equi.


Age-Dependent Risk of Respiratory Syncytial Virus Infection: A Systematic Review and Hazard Modeling From Serological Data.
There is no immunization campaign that currently exist for respiratory syncytial virus (RSV). Seroprevalence studies are critical for assessing epidemiological dynamics before and during an immunization program. A systematic literature review was conducted to summarize the evidence from seroprevalence studies on RSV. A systematic search of age-dependent RSV seroprevalence was conducted using the PubMed database and EMBASE. Age-dependent force of infections (FoI) and the decay rate of immunity were estimated. A mixture finite model was used, estimating the age-dependent disease state and the antibody concentrations in susceptible and infected or recovered populations. Twenty-one studies were identified from 15 countries, with studies using enzyme-linked immunosorbent assay being the most represented. Using a catalytic model, the age-dependent force of infection was estimated to be the lowest in infants aged 6 months to 1 year and increased in older age groups. The proportion ever-infected/recovered was estimated to be above 90% by 3 years of age. The number of seroprevalence studies covering a broad range of ages are limited. The age-dependent FoI indicated that the risk of infection was greatest among those aged >5 years. Additional data using valid assays are required to describe the transmission dynamics of RSV infection.


Arabidopsis UBC22, an E2 able to catalyze lysine-11 specific ubiquitin linkage formation, has multiple functions in plant growth and immunity.
Protein ubiquitination is critical for various biological processes in eukaryotes. A ubiquitin (Ub) chain can be linked through one of the seven lysine (K) residues or the N-terminus methionine of the Ub, and the Ub-conjugating enzymes called E2s play a critical role in determining the linkage specificity of Ub chains. Further, while K48-linked polyubiquitin chain is important for protein degradation, much less is known about the functions of other types of polyubiquitin chains in plants. We showed previously that UBC22 is unique in its ability to catalyze K11-dependent Ub dimer formation in vitro and ubc22 knockout mutants had defects in megasporogenesis. In this study, further analyses of the Arabidopsis ubc22 mutants revealed four subtypes of plants based on the phenotypic changes in vegetative growth. These four subtypes appeared consistently in the plants of three independent ubc22 mutants. Transcriptomic analysis showed that transcript levels of genes related to several pathways were altered differently in different subtypes of mutant plants. In one subtype, the mutant plants had increased expression of genes related to plant defenses and showed enhanced resistance to a necrotrophic plant pathogen. These results suggest multiple functions of UBC22 during plant development and stress response.


Effects of the chlorination and pressure flushing of drippers fed by reclaimed wastewater on biofouling.
Milli-channel baffle labyrinths are widely used in drip irrigation systems. They induce a pressure drop enabling drip irrigation. However, with a section thickness that is measured in mm2, they are sensitive to clogging, which reduces the performance and service life of a drip irrigation system. The impact of chlorination (1.5 ppm of free chlorine during 1 h application) and pressure flushing (0.18 MPa) on the biofouling of non-pressure-compensating drippers, fed by real reclaimed wastewater, was studied at lab scale using optical coherence tomography. The effect of these treatments on microbial composition (bacteria and eukaryotes) was also investigated by High-throughput DNA sequencing. Biofouling was mainly observed in the inlet, outlet and return areas of the milli-labyrinth channel from drippers. Chlorination reduced biofilm development, particularly in the mainstream of the milli-labyrinth channel, and it was more efficient when combined with pressure flushing. Moreover, chlorination was more efficient in maintaining water distribution uniformity (CU < 95% compared to less than 85% for unchlorinated lines). It reduced more efficiently the bacterial concentration (≈1 log) and the diversity of the bacterial community in the dripper biofilms compared to the pressure flushing method. Chlorination significantly modified the microbial communities, promoting chlorine-resistant bacteria such as Comamonadaceae or Azospira. Inversely, several bacterial groups were identified as sensitive to chlorination such as Chloroflexi and Planctomycetes. Nevertheless, one month after stopping the treatments bacterial diversity recovered and the chlorine-sensitive bacteria such as Chloroflexi phylum and the Saprospiraceae, Spirochaetaceae, Christensenellaceae and Hydrogenophilaceae families re-emerged in conjunction with the growth of biofouling, highlighting the resilience of the bacteria originating from drippers. Based on PCoA analyses, the structure of the bacterial communities still clustered separately from non-chlorinated drippers, showing that the effect of chlorination was still detectable one month after stopping the treatment.


Influence of sucralose, acesulfame-k, and their mixture on brain's fish: A study of behavior, oxidative damage, and acetylcholinesterase activity in Daniorerio.
Sucralose (SUC) and acesulfame-k (ACE-K) are widely used artificial sweeteners worldwide; however, they are frequently detected in aquatic environments due to their low metabolism and inadequate removal during wastewater treatment. The harmful effects of these compounds on hydrobionts have yet to be fully understood, as data on their toxicity is limited and inconclusive. This research aimed to determine the impact of SUC (50, 75, 125 μg/L) and ACE-K (50, 75, 125 μg/L), individually and in combination, on fish's swimming behavior, acetylcholinesterase activity, and oxidative stress response after four months of exposure. Following exposure, adult Danio rerio displayed anxiety-like behavior, as evidenced by increased freezing time and decreased swimming activity. Additionally, analysis of fish brain tissue revealed a disruption of REDOX homeostasis, leading to oxidative stress, which may be responsible for the observed inhibition of AChE activity. The results indicated that ACE-K was more toxic than SUC, and the mixture of both compounds produced a more detrimental effect than when each compound was administered alone. These findings highlight the hazardous impacts of SUC and ACE-K on fish in environmentally relevant concentrations, suggesting that these compounds should be added to the priority pollutant list.


What's new in obstetric anesthesia: the 2011 Gerard W. Ostheimer lecture.
The Gerard W. Ostheimer lecture is delivered at the Society for Obstetric Anesthesia and Perinatology Annual Meeting. The lecture provides a comprehensive review of the previous year's literature in obstetric anesthesia, obstetrics, perinatology, and health services research relevant for obstetric anesthesiologists. This article covers several of the major themes that emerged from the 2010 literature.


The intrinsic vulnerability of networks to epidemics.
Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks' structural properties, so that the same pathogen can generate different epidemic dynamics on different networks. Here we ask whether there are general properties that make a contact network intrinsically vulnerable to epidemics (that is, regardless of specific epidemiological parameters). By conducting simulations on a large set of modelled networks, we show that, when a broad range of network topologies is taken into account, the effect of specific network properties on outbreak magnitude is stronger than that of fundamental pathogen features such as transmission rate, infection duration, and immunization ability. Then, by focusing on a large set of real world networks of the same type (potential contacts between field voles, Microtus agrestis), we showed how network structure can be used to accurately assess the relative, intrinsic vulnerability of networks towards a specific pathogen, even when those have limited topological variability. These results have profound implications for how we prevent disease outbreaks; in many real world situations, the topology of host contact networks can be described and used to infer intrinsic vulnerability. Such an approach can increase preparedness and inform preventive measures against emerging diseases for which limited epidemiological information is available, enabling the identification of priority targets before an epidemic event.


Glycoprotein A as a biomarker of pulmonary infection and inflammation in children with cystic fibrosis.
Serum Glycoprotein A (GlycA) levels are increased in a variety of inflammatory disease states. However, GlycA has not been previously evaluated in children with cystic fibrosis (CF). We assessed the relationship between GlycA and pulmonary infection, inflammation, bronchial wall thickening (BWT) and bronchiectasis in young children with CF. From 95 patients, we obtained 311 paired serum and bronchoalveolar lavage (BAL) samples at multiple timepoints, with concurrent chest computed tomography on 168 occasions. Quantitative GlycA was determined using high-throughput nuclear magnetic resonance metabolomic testing. Participants were considered to be infected if ≥1 significant proinflammatory organism was isolated from their BAL. The presence of free neutrophil elastase (NE) above the limit of detection was considered evidence of inflammation. The relationships between GlycA levels and infection state, inflammation, and bronchiectasis were examined using a generalized estimating equation approach. There was a positive relationship between GlycA (mean 1.01 mmol/L, range 0.68-1.92 mmol/L) and being infected with one or more proinflammatory organisms, even after adjusting for age and gender (odds ratio [OR], 1.2 per 0.1 mmol/L, 95% confidence interval [CI], 1.02, 1.4, P = .03). There was also a positive relationship between GlycA and NE (unadjusted OR, 1.2 95% CI, 1.01, 1.4, P = .04), not significant after adjustment. GlycA concentration was associated with BWT but not bronchiectasis. Although GlycA levels were higher on average in those who had an infection or neutrophilic inflammation, there was also considerable variability, limiting the clinical utility of this biomarker alone in determining early disease status in CF.


A New Score to Predict the Risk of Hearing Impairment After Microvascular Decompression for Hemifacial Spasm.
Intraoperative monitoring of brainstem auditory evoked potentials (BAEPs) has been implemented to reduce the risk of hearing impairment during microvascular decompression for hemifacial spasm. To evaluate intraoperative monitoring of BAEPs during microvascular decompression in patients with hemifacial spasm for predicting the risk of hearing impairment after surgery. This prospective study included 100 patients. BAEPs were recorded for all patients. We established a scoring system for the changes in wave I amplitude, I-III interpeak latency, and wave V amplitude and latency. For each change, total points were calculated, and a score out of 6 was assigned to every patient. We classified the patients based on the points scored into 3 risk groups: low-risk (0-3), medium-risk (4-5), and high-risk (6). Further, the correlation between the score and the hearing outcome was evaluated to detect the incidence and degree of hearing impairment. Eighty-seven patients scored 0 to 3, 10 scored 4 to 5, and 3 scored 6. The degree of hearing impairment was proportionate to the score recorded at the end of surgery, and patients in the low-risk group showed no impairment; medium-risk group, deterioration of maximum 2 grades according to World Health Organization classification of hearing impairment; and high-risk group, deterioration of 3 to 4 grades. Intraoperative monitoring of BAEPs evaluated through our scoring system was valuable in predicting hearing impairment after surgery.


[Optimization of the components of intensive care of heart and hemodynamic disorders in patients with acute amitriptyline poisoning].
Cardio- and hemodynamics were examined in 56 patients with acute suicidal poisonings with amitriptyline, a tricyclic antidepressant, in order to select and optimize the main agents for intensive care of disorders developing in the circulatory system. Adsorption detoxication in parallel with adequate correction of volemic disorders was found to be advisable. A possibility of hemodynamic stabilization in patients with normo- and tachycardia without sharp hypotonia by nonspecific antidotes proserine or obsidan was shown, and by inotropic support with dobutrex in patients with signs of exotoxic shock. The mechanisms underlying the efficacy of therapy are discussed.


Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience.
Intrahepatic cholangiocarcinoma (ICC) is an unusual tumour. The clinicopathological data of 67 patients with ICC and combined hepatocellular-cholangiocarcinoma (HCC-ICC) are presented. HCV-HBV infection was present in 37.3% and chronic liver disease in 38.7% of cases, a rate higher than in the normal population; in these patients the cancer was small, often asymptomatic and of combined type. Liver resection was performed in 51 patients; at 1, 3 and 5 years, overall survival was 87.9%, 59.0%, and disease-free survival was 47.7% and 78.8%, 51.4%, and 46.7%, respectively. The better results were in the group of cirrhotic patients in whom ICC was diagnosed by a screening program for HCC (5-year survival 76.6%). Nodal metastasis showed negative prognostic value for both overall and disease-free survival; in N+ patients mean survival was 14.7 months after liver resection and lymph node dissection. Viral infection and cirrhosis may be considered risk conditions for ICC and combined HCC-ICC; in resected patients survival was good. Nodal metastases must not be considered a contraindication for liver resection.


Body Mass Index and Adverse Outcomes in Elderly Patients With Atrial Fibrillation: The AMADEUS Trial.
Obesity has been associated with increased cardiovascular risk in atrial fibrillation, but little is known in elderly patients with atrial fibrillation. Post hoc analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. We studied 1588 elderly patients, who were categorized as normal body mass index (BMI, 18.5-25 kg/m(2); n=515 [32.4%]), overweight (BMI, 25-30 kg/m(2); n=711 [44.8%]), and obese (BMI≥30 kg/m(2); n=362 [22.8%]). There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category, being 5.0%, 3.2%, and 1.5% per 100 patient-years, respectively (P for trend=0.01). Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome (hazard ratio, 0.29; 95% confidence interval, 0.11-0.77; P=0.01). In the warfarin arm (n=814), multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60% (odds ratio, 1.84; 95% confidence interval, 1.21-2.80; P=0.004). Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients. Obesity was related to good quality anticoagulation control.


Artificial urinary sphincter infection: causative organisms in a contemporary series.
Traditionally Staphylococcus epidermidis has been the primary organism responsible for genitourinary prosthetic infection. However, the increasing prevalence of S. aureus infection poses a serious problem. We determined the organisms that produce artificial urinary sphincter infection in a contemporary series. A single-institution, retrospective study was performed examining men undergoing artificial urinary sphincter explantation surgery between January 1997 and January 2007. Patients with clinical signs of infection at surgery were selected for study. Infection was noted in 23 patients, including 5 implanted at other institutions. The median age was 72 years (IQR 70-76). The median interval from artificial urinary sphincter implantation or revision to explantation was 110 days (IQR 38-199). Culture of the periprosthetic fluid at the time of explantation was positive in 20 of 23 patients. Gram-positive cocci were cultured from 13 patients, including S. aureus in 7, S. epidermidis in 5 and Enterococcus in 1. Methicillin resistant S. aureus and S. epidermidis in 3 cases each represented a considerable proportion of isolated organisms (6 of 26 or 26%). Gram-negative bacilli were cultured from 6 patients and yeast was cultured from 1. In this contemporary series S. aureus was the most common organism producing artificial urinary sphincter infection. Methicillin resistant S. aureus and S. epidermidis are often cultured during artificial urinary sphincter explantation due to infection. Strategies to prevent artificial urinary sphincter infection should target methicillin resistant S. aureus and S. epidermidis as well as gram-negative pathogens.


Automated reaction mechanisms and kinetics with the nudged elastic band method-based AMK_Mountain and its description of the preliminary alkaline hydrolysis of nitrocellulose monomer.
To improve the transition state (TS) search capability in complex chemical environments, AMK_Mountain is constructed based on the automated reaction mechanisms and kinetics (AutoMeKin) package. AMK_Mountain does not distinguish the reaction type of the TSs, which is beneficial to obtaining a more comprehensive reaction mechanism. In this study, the first step of the alkaline hydrolysis process of nitrocellulose monomer was adopted as the research object, and 730 possible initial configurations are constructed and 22 TSs pass high-level calculations. Energy difference and interaction region indicator reveal that the first step of alkaline hydrolysis is mainly the combination of nitrogen-containing functional groups at the positions α and β with hydroxide anions, followed by the formation of nitric acid and the further loss of protons to form nitrate. Overall, in combination with GFN2 -xTB and ORCA, the AMK_Mountain technique provides a reliable method for the location of the TSs in complex environments.


["Progressive" hypothenar hammer syndrome Indication for operative treatment].
Hypothenar hammer syndrome (HHS) is ischemia of the distal ulnar artery caused by injury to the ulnar part of the palmar arch. This disease often involves workers who frequently use the hypothenar part of the hand as a hammer. The aneurysmatic form of HHS represents an indication for operative treatment; the thrombotic form is treated mainly conservatively. In our opinion, the symptomatic thrombotic form represents an indication for operation if symptoms persist during conservative therapy, particularly if symptoms progress. In fresh embolic occlusions, regional thrombolysis is usually successful. We present here the symptomatic treatment and course in two patients with complaints increasing during conservative therapy. The patients reported progressive Raynaud's phenomenon of the fingers. Angiography confirmed corkscrew-like aneurysmatic configuration of the distal ulnar artery and subsequent embolization of digital arteries. In both cases, we removed the source of the embolism with resection of the involved arterial segment and anastomosis with autologous vein grafts.


Accuracy and clinical outcomes of CT image integration with Carto-Sound compared to electro-anatomical mapping for atrial fibrillation ablation: a randomized controlled study.
Carto-Sound integrates 2D intra-cardiac ultrasound imaging into a 3D environment to allow left atrial mapping from the right atrium without fluoroscopic assistance. We conducted an open randomized controlled study to compare procedural, clinical and accuracy parameters between CT integrated Carto-Sound and electro-anatomic mapping (EAM) for AF ablation. Sixty index AF ablation patients were randomized equally to either the Carto-Sound or EAM mapping/navigation for their procedure performed at a single institution. Procedure and X-ray times, X-ray dose, navigational accuracy and clinical success were assessed. The study was powered to the primary outcome of fluoroscopy time. Total procedure (232 ± 60 vs 223 ± 48 min; p = 0.51), ablation (p = 0.84) and mapping times (p = 0.11) were similar in each group. In contrast, Carto-Sound reduced total X-ray time (65 ± 18 vs 51 ± 12 min; p = 0.001), via a reduction in both mapping (p<0.001) and remaining procedure X-ray time (p = 0.03). Left atrial access time (p = 0.03) was also reduced using Ultra-sound assisted 3D mapping compared to the EAM group. Carto-Sound maps demonstrated equivalent mean navigational accuracy (p>0.17) compared to EAM. Ultra-sound assisted 3D mapping did not improve single procedure drug free clinical success (EAM: 13/30 [43%] vs Carto-Sound: 15/30 [50%]) at a mean of 13 ± 5 months (p = 0.79). In the context of long left atrial procedures with high radiation doses, reduced X-ray and left atrial access times using CT integrated Carto-Sound mapping/navigation may have implications for patients and laboratory staff, albeit at an extra financial cost and the requirement of an additional access site for a right sided catheter. ACTRN12612000089831.


Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia.
A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.


The histopathology of fiberglass dermatitis in relation to von Hebra's concept of eczema.
A group of 36 normal control persons was patch-tested with glass fibers. The tested filaments had a length of about 3 to 5 mm and a diameter of 9 to 13 microns. The glass fibers were obtained from the normal production process. They were coated with cured epoxy resin. A group of 29 normal control persons was tested with the same type of fibers from which the epoxy finish had been burned off. Another group of 36 persons was patch-tested with ultrasmall glass globes with a diameter of 10 to 15 microns. Coated and uncoated glass globules were tested. On every person 5 patch tests with the same material were done. They were removed after 1, 5, 24, 48 and 72 h. On coated fiber, 12 of 36 tested people reacted with either a + or a ++ reaction. On the uncoated fibers a reaction could be noted in 10 out of 29 persons. The patch tests with coated as well as uncoated glass globules were all negative. A total of 60 biopsies was performed in those cases where + or ++ reactions were noted. The histological examination of the biopsies showed no differences between the reactions on coated and uncoated fibers. The skin reactions to glass fiber showed, besides microtraumatic changes, several histological characteristics of an eczematous reaction, like spongiosis and perivascular lymphocytic infiltration. The importance of these findings is discussed. It is emphasized that histological alterations are only one of the six points which must be taken into account when the diagnosis of eczema is considered.


Parkinson's disease, macular degeneration and cutaneous signs of mercury toxicity.
The objective of this study was to determined if there was a relationship between Grover's disease and Parkinson disease. Fourteen patients with Parkinson disease and 14 control patients were randomly selected and examined for cutaneous eruptions and blood mercury levels. Of the 14 patients with Parkinson's disease, 13 had Grover's disease and detectable blood mercury. None of the patients in the control group had a cutaneous eruption and only 2of the 14 had detectable blood mercury. Mercury may play a role in the etiology of Parkinson disease and Grover's disease.


Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations.
Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic support or on the surface of an activated glass capillary. The resulting chromatographic columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K(d) values) and non-linear chromatography can be used to assess the association (k(on)) and dissociation (k(off)) rate constants and the thermodynamics of the binding process. Membrane-based affinity columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein.


Cognitive and behavioural inhibition deficits in neurodegenerative dementias.
Disinhibition, mainly caused by damage in frontotemporal brain regions, is one of the major causes of caregiver distress in neurodegenerative dementias. Behavioural inhibition deficits are usually described as a loss of social conduct and impulsivity, whereas cognitive inhibition deficits refer to impairments in the suppression of prepotent verbal responses and resistance to distractor interference. In this review, we aim to discuss inhibition deficits in neurodegenerative dementias through behavioural, cognitive, neuroanatomical and neurophysiological exploration. We also discuss impulsivity and compulsivity behaviours as related to disinhibition. We will therefore describe different tests available to assess both behavioural and cognitive disinhibition and summarise different manifestations of disinhibition across several neurodegenerative diseases (behavioural variant of frontotemporal dementia, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, Huntington's disease). Finally, we will present the latest findings about structural, metabolic, functional, neurophysiological and also neuropathological correlates of inhibition impairments. We will briefly conclude by mentioning some of the latest pharmacological and non pharmacological treatment options available for disinhibition. Within this framework, we aim to highlight i) the current interests and limits of tests and questionnaires available to assess behavioural and cognitive inhibition in clinical practice and in clinical research; ii) the interpretation of impulsivity and compulsivity within the spectrum of inhibition deficits; and iii) the brain regions and networks involved in such behaviours.


The Swedish childhood diabetes study--results from a nine year case register and a one year case-referent study indicating that type 1 (insulin-dependent) diabetes mellitus is associated with both type 2 (non-insulin-dependent) diabetes mellitus and autoimmune disorders.
From July 1, 1977 to July 1, 1986, 3,503 incident cases of Type 1 (insulin-dependent) diabetes mellitus were registered in the Swedish childhood diabetes study. Using data from this register and from a case-referent study, including all incident Type 1 diabetic children in Sweden during one year and, for each patient, two referent children matched according to age, sex and county, we have studied the associations between Type 1 diabetes and familial Type 1 and Type 2 (non-insulin-dependent) diabetes, thyroid, adrenal, allergic, rheumatic, heart and bowel disease. The mean annual incidence per 100,000 during the nine year period was 25.1 for boys and 23.5 for girls. In 8.5% of the patients, one parent had Type 1 diabetes, 73% of whom were fathers. Fifty-six of the patients (1.7%) had a parent with Type 2 diabetes. The prevalence of parental Type 1 diabetes tended to be higher in patients with younger age at onset; whereas, the opposite was found for patients with parental Type 2 diabetes. In the case-referent study, the age-adjusted odds ratio for Type 1 diabetes when a first and/or second degree relative had Type 1 diabetes was 5.5 (95% confidence limits 4.0-7.7), and in accordance with the findings of the case register, the odds ratio tended to be highest in patients with the youngest age at onset. Season at onset of the patients was not associated with parental Type 1 diabetes. The odds ratio for Type 1 diabetes was significantly increased 3.3 (95% confidence limits: 2.3-4.6) when Type 2 diabetes was reported in relatives (three generations).(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on the interaction of phosphate anions with N-functionalised polyaza[n]paracyclophanes: the role of N-methylation.
The synthesis and interaction of N,N',N'',N'''-tetramethyl-2,6,9,13-tetraaza[14]paracyclophanes (B323Me(4)) with nucleotides and inorganic phosphates is described. An easy methodology is used to define thermodynamic selectivity. The interaction of B323Me4 and ATP has been monitored by (1)H, (31)P NMR and by molecular mechanics, ruling out the possibility of the participation of pi-stacking interactions. Results show that N-methylation is accompanied by a strong increase in the interaction of the resulting macrocycle with ATP.


Intrinsic differences between the superficial and deep layers of the Xenopus ectoderm control primary neuronal differentiation.
In Xenopus, primary neurons differentiate early, in the deep layer of the neuroectoderm. In contrast, the neural precursors of the superficial layer continue to proliferate. We report that superficial layer precursors differ from deep layer precursors in that they are refractory to the neuronal-promoting activity of bHLH genes, dominant-negative X-Delta-1, FGF-8, or signals from the organizer. In this system, neuronal differentiation is guided by an early established, intrinsic, cell-autonomous difference in the competence of the precursor cells to differentiate. This difference may be controlled in part by ESR6e, a bHLH gene of the Enhancer-of-split family, which is expressed in the superficial layer of the late blastula and when expressed ectopically suppresses primary neurogenesis in the deep layer.


Retrospective study for risk factors for febrile UTI in spinal cord injury patients with routine concomitant intermittent catheterization in outpatient settings.
Retrospective study. The objective of this study was to investigate the clinical risk factors for febrile urinary tract infection (UTI) in spinal cord injury-associated neurogenic bladder (NB) patients who perform routine clean intermittent catheterization (CIC). Rehabilitation Hospital, Kobe, Japan. Over a 3-year period, we retrospectively assessed the clinical risk factors for febrile UTI in 259 spinal cord injury patients diagnosed as NB and performing routine CIC with regard to the factors such as gender, the presence of pyuria and bacteriuria, and the categories of the American Spinal Injury Association (ASIA) impairment scale. A total of 67 patients had febrile UTI in the follow-up period, with 57 cases of pyelonephritis, 11 cases of epididymitis and 2 cases of prostatitis, including the patients with plural infectious diseases. The causative bacteria were ranked as follows: Escherichia coli (74 cases), Pseudomonas aeruginosa (17 cases), Enterococcus faecalis (14 cases) and Klebsiella pneumoniae (12 cases). Antibiotic-resistant E. coli were seen, with 10.5% instances of extended-spectrum β-lactamase (ESBL) production and 23.8% of fluoroquinolone resistance. Multivariate analyses of clinical risk factors for febrile UTI showed that gender (male, P=0.0431), and ASIA impairment scale C or more severe (P=0.0266) were significantly associated with febrile UTI occurrence in NB patients with routine CIC. Our data demonstrated gender (male) and ASIA impairment scale C or more severe were significantly associated with febrile UTI occurrence in NB patients using routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile UTI in these patients.


CO2 laser in decubitus ulcers: a comparative study.
This is a comparative study of conventional surgery (knife/electric knife) and CO2 laser surgery and their effect on the outcome of stage III (including muscle) and stage IV (including bone) decubitus ulcers with an average area of 400 cm2. It is a prospective clinical study done with two groups of patients of similar age, economic and social background, as well with similar types of decubitus ulcers. Thirty patients were studied in each group. The study demonstrated a statistically significant difference in favor of the patients treated with CO2 laser with regard to operative blood loss, 0.5 cc/cm2 or 20% (P less than .01), infection rate (chi 2 test, P less than .01), and difference (60%) in recovery time (P less than .01). This translated into an average saving of 23 hospitalization days per patient. It also showed a difference, though not statistically significant, favoring the group treated with laser with respect to survival and full recovery. This probably is attributable to the lowered blood loss and infection rate as well as improved operative time and analgesia.


Nutritional and social contribution of meat in diets: Interplays among young urban and rural men.
Considering the recent increase in the demand for meat and its subsequent implications for health and food security, there is an increasing need to explore its nutritional and social importance among young men in settings experiencing nutrition transition. A better understanding of meat in the diets of this group could contribute to the design of socio-culturally appropriate interventions to improve healthy eating, as these men are key decision makers in family food choices. This mixed-methods study aimed to assess the nutritional and social contribution of meat in the diet of young adult men in urban and rural Zambia. A food frequency questionnaire, multiple pass 24-h dietary recall, anthropometric measurements and a socio-demographic questionnaire were utilized while qualitative interviews explored the socio-cultural importance of meat consumption. Rural and urban participants had an isocaloric diet. All macronutrient intakes except carbohydrates were significantly higher in the urban population than the rural population (p < 0.01). Zinc intake was significantly greater in the urban than the rural sample (χ2 (39) = 40, p-value = 0.04). Except for vitamin A, calcium and folate, participants met the recommendations for all micronutrients. Regardless of being rural or urban, the higher the participant's level of education, the weaker the socio-cultural importance of meat. In both settings, increased consumption of meat was associated with prosperity, authority and respect within society. There are strong social and cultural beliefs among participants about meat consumption, reflecting the symbolic meaning in their customs. These findings could help improve the design and implementation of dietary interventions, incorporating specific cultural beliefs and socio-economic factors in the targeted population, to achieve healthy eating practices.


Use of a three-dimensional humanized liver model for the study of viral gene vectors.
Reconstituted three-dimensional (3D) liver models obtained by engrafting hepatic cells into an extracellular matrix (ECM) are valuable tools to study tissue regeneration, drug action and toxicology ex vivo. The aim of the present study was to establish a system for the functional investigation of a viral vector in a 3D liver model composed of human HepG2 cells on a rat ECM. An adeno-associated viral (AAV) vector expressing the Emerald green fluorescent protein (EmGFP) and a short hairpin RNA (shRNA) directed against human cyclophilin b (hCycB) was injected into the portal vein of 3D liver models. Application of the vector did not exert toxic effects, as shown by analysis of metabolic parameters. Six days after transduction, fluorescence microscopy analysis of EmGFP production revealed widespread distribution of the AAV vectors. After optimization of the recellularization and transduction conditions, averages of 55 and 90 internalized vector genomes per cell in two replicates of the liver model were achieved, as determined by quantitative PCR analysis. Functionality of the AAV vector was confirmed by efficient shRNA-mediated knockdown of hCycB by 70-90%. Our study provides a proof-of-concept that a recellularized biological ECM provides a valuable model to study viral vectors ex vivo.


Efficacy of mitomycin C against alveolar Echinococcus.
Mitomycin C was tested against the metacestode stage of Echinococcus multilocularis in jirds. The efficacy of 61-76% was achieved within 1 month of treatment with a total dose of 0.04, 0.08 or 0.3 mg.


Classification of clubfoot.
Clubfeet must be classified according to severity to obtain reference points, assess the efficacy of orthopaedic treatment, and analyze the operative results objectively. A scale of 0-20 was established on the basis of four essential parameters: equinus in the sagittal plane, varus deviation in the frontal plane and derotation around the talus of the calcaneo-forefoot (CFF) block and adduction of forefoot on hindfoot in the horizontal plane. Four grades of clubfeet can be individualized: (a) Benign feet so-called "soft-soft feet," grade I, similar to postural feet, with a score of 5 to 1 (these mild feet must be excluded from any statistics as they tend to increase good results); (b) moderate feet, so-called "soft > stiff feet," grade II (reducible but partly resistant, with a score of 5-10); (c) severe feet, so-called "stiff > soft feet," grade III (resistant but partly reducible, with a score of 10-15); and (d) very severe, pseudoarthrogryposic feet, so-called "stiff-stiff feet," grade IV (score of 15-20 points). To avoid risks of errors, our method is based on a very complete checklist and on diagrams. Our training material inculdes an audiovisual package.


A dyadic approach to depression, resilience and quality of life on marital adjustment among infertile couples in Karachi, Pakistan: A cross-sectional study.
Infertility is a major reproductive health problem in Pakistan. It has the potential to cause serious negative impact on a couple's marital life and psychological health. This study aimed to assess the factors associated with maladjustment among infertile couples. An analytical cross-sectional design was employed. Validated scales were used to assess marital adjustment, depression, resilience and quality of life among infertile couples. Purposive sampling was employed to enrol 334 infertile couples from a private infertility medical centre, of Karachi, Pakistan. Among couples, marital adjustment scores were comparable, but resilience and quality of life were significantly low among wives whereas depression was significantly high among wives compared with husbands. Wives' marital adjustment was positively correlated with husband's resilience and quality of life and negatively related with his depression. After employing adjusted actor-partner interdependence modelling, wives' own depression and resilience had significant effect on their marital adjustment and their partner's resilience, depression and quality of life did not have any impact on their outcome. On the contrary, wives' resilience had a significant effect in increasing the marital adjustment of their husband. This study highlights the need to promote psychological support (resilience building skills) or couples' therapy to all those couples undergoing infertility treatment.


Hydration of Closely Related Manganese and Magnesium Porphyrins in Aqueous Solutions: Ab Initio Quantum Mechanical Charge Field Molecular Dynamics Simulation Study.
To the best of our knowledge, the current study based on ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) is the first to explore the difference in the hydration behavior between Mn(II)- and Mg(II)-associated porphyrins (Mn(II)-POR and Mg(II)-POR) in aqueous solution. The simulation study highlights similar and dissimilar characteristics of the structural, dynamical, and thermodynamical properties of these closely related metals bound to porphyrins in aqueous solution. The structural analysis is based on radial and angular distribution functions, coordination number distributions, and angular-radial distributions. Both hydrated systems demonstrate similar pentacoordinated structures formed via the axial coordination of one water molecule to the metal ion in addition to the four nitrogen atoms of the porphyrin ring. However, in the case of Mn(II)-POR, the formation of a distorted square pyramidal geometry was observed. It was envisaged as a weak coordination of the water molecule to the Mn(II) atom and thus higher atomic fluctuation for all atoms in contrast to that for the hydrated Mg(II)-POR. The dynamical data in terms of the mean residence times, velocity autocorrelation function, free energy, and other parameters revealed the difference in the metal binding effect because the Mn(II) atom was observed to inhibit H-bond formation more than the presence of Mg(II) atoms in the core of the porphyrin. The current study thus highlights the significant differences in the structural and dynamical properties of Mn(II)- and Mg(II)-associated porphyrin systems.


Synthetic influenza viral double-stranded RNA induces an acute-phase response in rabbits.
Numerous studies have characterized the physiological effects of synthetic, high-molecular-weight, homopolymeric, double-stranded RNA (dsRNA), particularly polyriboinosinic.polyribocytidylic acid [Carter and De Clercq (1974): Science 186:1172-1178], but limited information exists regarding the physiological effects of dsRNA of viral composition and size. In this report, we determined sleep and fever responses of rabbits to intracerebroventricular injection of different doses of synthetic viral dsRNA (either 108 base pairs or 661 base pairs) derived from the N-terminal sequence of gene segment 3 of the A/PR/8/34-H1N1 (PR8) influenza virus. Both the108-mer and the 661-mer dsRNAs increased nonrapid eye movement sleep, suppressed rapid eye movement sleep, and induced fever. The 661-mer dsRNA had more potent somnogenic and pyrogenic effects than the 108-mer dsRNA on the basis of weight. Neither single-stranded RNA from the corresponding sequences had significant effects on sleep or brain temperature. These results demonstrate for the first time that low-molecular-weight, viral dsRNA has the stability in vivo that is required to induce the fever and sleep changes found in natural viral infections, and the hypothesis is supported that virus-associated dsRNA may be responsible for initiating the acute-phase response during viral infections.


A power-free, parallel loading microfluidic reactor array for biochemical screening.
This paper presents a power-free, self-contained microfluidic device in which a number of nanoliter-sized droplets can be parallelly and accurately metered and mixed for high-throughput analysis and/or portable systems. In this system, the absorption of air by pre-degassed PDMS and the change of capillary force due to sudden narrowing of the channel cross-section provide the mechanism for actuating, metering and mixing the flow of fluid in the microfluidic channels and chambers. With an array of channels and capillary valves combined with an array of pre-degassed PDMS pump chambers, the device can perform multiple liquid dispensing and mixing in parallel, and its performance and reproducibility are also evaluated. As a practical application, the proposed device is used to screen crystallization conditions of lysozyme. This device needs neither external power nor complex instruments for fluid handling. Thus, it offers an easy-to-use, inexpensive and power-free way to perform multiple nanoliter-volume distinct reactions in parallel format and should be ideally suitable for individual laboratories for various applications such as enzyme assay, protein crystallization, drug discovery, and combinatorial chemistry.


Impact of CCR2 and SDF1 polymorphisms on disease progression in HIV-infected subjects in Thailand.
The genotypic polymorphisms of CCR5, CCR2, and SDF1 were analyzed to determine their impact as potential confounders with regard to disease progression because of the role that host genetic factors appear to be involved in determining rates of disease progression. Genomic DNA was extracted from Ethylenediaminetetraacetate whole blood using Qiagen DNA extraction kit. The amplification of CCR5, CCR2, and SDF1 genes was performed by PCR. Two hundred and twenty-one samples were genotyped for the CCR5, CCR2, and SDF1 mutation. Among these, all (100%) were identified as wild type for CCR5. All were then investigated considering the impact on CD4+ T-cell counts. Samples were divided into two groups based on the CD4+ T-cell numbers. It revealed that in the group of CD4+ T-cell counts ≥200 cells/μl, 15 were found for the homozygous for SDF1 gene (3'A/3'A) whereas one was found in the group of CD4+ T-cell counts <200 cells/μl. Homozygosity for the CCR2 polymorphisms (64I/64I) were five in the group of CD4+ T-cell counts ≥200 cells/μl and none were found in the group of CD4+ T-cell counts <200 cells/μl. These results demonstrated that there was a significant association between CD4+ T-cell numbers and CCR2 and SDF1 polymorphisms (P < 0.001). The mutation of CCR2 and SDF1 genes showed a significant difference in the distribution of CD4+ T-cell numbers (P < 0.001) whereas mutation of chemokine coreceptor CCR5 was not appeared to be associated with the impact of CD4+ T-cell counts.


Comparison of lipid and lipoprotein values in men and women differing in training status.
The aim of this study was to compare plasma lipid and lipoprotein concentrations of male and female subjects in different training levels and to examine the risks of cardiovascular diseases. For this purpose, 20 male athletes from the National Turkish Wrestling Team (age 23.5 +/- 1.25 years) and 44 male and 51 female students (ages 21.7 +/- 1.72 and 20.20 +/- 1.68 years, respectively) from physical education and sports department and 40 sedentary females (ages 21.14 +/- 1.72 years) participated in this study. Trigliceride (TG), total cholesterol (TC), HDL-C and LDL-C levels were determined by a Hitachi 717 Autoanalyser. Apo A-l, Apo B, and Lp(a) levels were determined by Behringer Nephelometer 100. Maximum Oxygen Consumption (VO(2) max) values were determined by 12-min run test and the anaerobic power values were measured by Jump Meter Instrument. Energy consumption of basal metabolic rates were for males 1 kcal for an hour and 0.9 kcal for females. There were no significant differences in plasma TC, TG, and small lipoprotein a (Lp(a)) values between four groups (p > .05). No significant differences were found in HDL-C, LDL-C, apolipoprotein Al (Apo-Al), and apolipoprotein B100 (Apo-B) values between wrestlers and male students, and between female students and sedentary females (p > .05). HDL-C values of female students and sedentary females were significantly higher when compared with the same values of wrestlers and male students (41.52 and 40.93 mg/100 ml versus 51.92 and 50.10 mg/100 ml). However, LDL-C values were found to be lower in females than males (121.83 and 101.10 mg/100 ml as opposed to 97.7 and 98.4 mg/100 ml) but only significantly lower than in wrestlers (p < .05). Although the wrestlers' training levels were always higher than male students, the lipid and lipoprotein values were not different. These variables were not different between female groups either. But the lipid and lipoprotein profile of female subjects was found to be better than that of males. These results showed that medium and high level of exercises did not cause significant differences in lipid and lipoprotein levels, but the sex differences were very pronounced. Lipid and lipoprotein values of the four groups have indicated that the individuals in these groups would not be exposed to danger of cardiovascular diseases.


Loss of Endothelial Cell Matrix Metalloproteinase 14 Reduces Melanoma Growth and Metastasis by Increasing Tumor Vessel Stability.
Matrix metalloproteinase (MMP) 14 belongs to a large family of zinc-dependent endopeptidases and plays a critical role in skin physiological and pathological processes. Complete loss of the protease resulted in severe developmental defects leading to early death. However, because of the premature death of the mice, the functional significance for endothelial cell (EC) expression of MMP14 in skin physiology and pathology in vivo after birth is yet unknown. Using a mouse model with constitutive EC-specific deletion of Mmp14 (Mmp14EC‒/‒), we showed that mice developed and bred normal, but melanoma growth and metastasis were reduced. Although vascularity was unaltered, vessel permeability was decreased. Deletion of MMP14 in ECs led to increased vessel coverage by pericytes and vascular endothelial-cadherin expression in mice in vivo and in vitro but not in human ECs. Endothelial nitric oxide synthase expression and nitric oxide production were significantly reduced in Mmp14EC‒/‒ ECs and MMP14-silenced human umbilical vein ECs. A direct correlation between endothelial nitric oxide synthase and MMP14 expression was detected in intratumoral vessels of human malignant melanomas. Altogether, we show that endothelial MMP14 controls tumor vessel function during melanoma growth. These data suggest that EC-derived MMP14 direct targeting alone or with vascular stabilizing agents may be therapeutically crucial in inhibiting melanoma growth and metastasis.


Low CERVICAL-2 plane block, a proposed regional anesthetic technique for acute cholecystitis.
Acute cholecystitis is a painful inflammatory disease of the gallbladder. The Low Cervical-2 Plane Block is a retrolaminar block that targets the C3, C4, and C5 spinal nerves, which provide sensory innervation to the gallbladder, in order to potentially provide analgesia to patients with pain associated with acute cholecystitis. In this brief report, a softly embalmed cadaver was injected with a dye mixture bilaterally. Subsequent cadaveric dissection revealed spread of the injectate deep to the prevertebral fascia to the C4 lamina on the right side and the C5 lamina on the left side. Also, diffusion of the anesthetic over the ligamenta flava could spread inferiorly and laterally to the spinal nerve roots of C3-C5 and thus potentially target the direct sensory innervation of the gallbladder. The Low Cervical-2 Plane Block is a potentially effective modality for treating intractable pain from acute cholecystitis. However, further cadaveric injections are needed to confirm the exact extent of spread of anesthetic. Clinical application of the Low Cervical-2 Plane Block in patients with acute cholecystitis is needed to establish the efficacy of this theoretical technique.


Direct coronary motion extraction from a 2D fat image navigator for prospectively gated coronary MR angiography.
Direct 2D tracking of cardiac motion may provide superior respiratory navigator gating for coronary magnetic resonance angiography compared to conventional liver-diaphragm navigators. However, additional 2D processing for motion extraction is unsuitable for real-time prospective gating. In this work, a 2D fat-selective image navigator, which delineates the epicardial fat surrounding coronary arteries, is developed to directly monitor epicardial fat motion at every heartbeat in real-time for prospective gating. The proposed navigator is incorporated into a real-time interactive software that allows rapid setup and efficient motion extraction, and runs on standard clinical hardware without any additional dedicated components for processing. The proposed 2D cardiac fat image navigator was compared with the conventional 1D diaphragm navigator in free-breathing b-SSFP coronary MRAs in 12 healthy volunteers at 1.5T. Real-time motion extraction from 2D cardiac fat navigator images was feasible within 20 ms, enabling successful prospectively gated coronary magnetic resonance angiographies in all subjects. Compared to 1D diaphragmatic navigator, 2D fat image navigator reduced scan time by 38% (P < 0.0005), and significantly improved vessel sharpness, myocardial suppression, and image quality (P < 0.05). This demonstrates the feasibility of a 3D SSFP coronary magnetic resonance angiography sequence using a 2D epicardial fat image as a navigator for real-time prospective motion tracking.


[The induction of seizures in "Papio papio" following allylglycine alone or in combination with intermittent photic stimulation (author's transl)].
Allylglycine, an inhibitor of GABA synthesis, produces increased sensitivity to photic stimulation and in convulsant doses spontaneous seizures arising occipitally in the baboon (Horton and Meldrum, 1973). In this study, convulsant doses of allylglycine induced either sharp wave and polyspike frontorolandic discharges (FR) or critical posterior discharges which then reinforce the fronto-rolandic spikes. A seizure may then arise from the fronto-rolandic region and secondarily spread to the rest of the cerebral cortex. Intermittent photic stimulation produces a reinforcement of the fronto-rolandic sharp waves and can also induce self-maintaining mechanisms similar to those just described. In this situation, however, and with the animals paralysed with Flaxedil no seizures arising occipitally have been observed. The role of the occipital cortex as the sensory visual and somatic afferent in photosensitive epilepsy in the baboon is discussed in the light of these results.


α-Arrestins participate in cargo selection for both clathrin-independent and clathrin-mediated endocytosis.
Clathrin-mediated endocytosis (CME) is a well-studied mechanism to internalize plasma membrane proteins; however, to endocytose such cargo, most eukaryotic cells also use alternative clathrin-independent endocytic (CIE) pathways, which are less well characterized. The budding yeast Saccharomyces cerevisiae, a widely used model for studying CME, was recently shown to have a CIE pathway that requires the GTPase Rho1, the formin Bni1, and their regulators. Nevertheless, in both yeast and mammalian cells, the mechanisms underlying cargo selection in CME and CIE are only beginning to be understood. For CME in yeast, particular α-arrestins contribute to recognition of specific cargos and promote their ubiquitylation by recruiting the E3 ubiquitin protein ligase Rsp5. Here, we show that the same α-arrestin-cargo pairs promote internalization through the CIE pathway by interacting with CIE components. Notably, neither expression of Rsp5 nor its binding to α-arrestins is required for CIE. Thus, α-arrestins are important for cargo selection in both the CME and CIE pathways, but function by distinct mechanisms in each pathway.


Total glucosides of paeony alleviates scleroderma by inhibiting type I interferon responses.
Type I interferon (IFN) is believed to play a pathogenic role in systemic sclerosis (SSc, also called scleroderma), which is an autoimmune rheumatic disease. Our previous studies have found that Chinese medicine formula Si-Ni-San (SNS, composed of Glycyrrhiza uralensis Fisch., Bupleurum chinense DC., Paeonia lactiflora Pall., and Citrus aurantium L.) had inhibitory effects on type I IFN responses. Among these herbal products, Paeonia lactiflora Pall. has been traditionally used to treat inflammation-related diseases, yet its therapeutic effects against type I IFN-related diseases and potential bioactive ingredients are not characterized. We aim to identify bioactive ingredient with anti-type I IFN activity from herbal products in SNS and further elucidate its therapeutic effect against scleroderma and underlying mechanisms. We constructed a Gaussia-luciferase (Gluc) reporter assay system to identify ingredients with anti-type I IFN activities from SNS. In RAW264.7 cells, real-time PCR (RT-PCR) and western blotting were used to investigate the induction of type I IFN pathway. Additionally, in a bleomycin (BLM)-induced experimental scleroderma model, the expression of fibrotic genes, type I IFN-related genes, inflammatory cytokines, and cytotoxic granules were measured by RT-PCR, and the histopathological changes were determined by H&E staining, Masson's staining and immunohistochemistry analysis. Our data demonstrated that total glucosides of paeony (TGP) was the bioactive component of SNS that selectively inhibited TLR3-mediated type I IFN responses and blocked type I IFN-induced downstream JAK-STAT signaling pathways. In the BLM-induced scleroderma mouse model, TGP ameliorated skin fibrosis by inhibiting multiple targets in the upstream and downstream of type I IFN signaling. Further research found that TGP hindered polarization of M2 macrophages and their profibrotic effects and reduced cytotoxic T lymphocytes and their cytotoxic granules by suppressing Cxcl9 and Cxcl10 in the skin tissue of scleroderma mice. Our study not only sheds novel lights into the immunoregulative effects of TGP but also provides convincing evidence to develop TGP-based therapies in the treatment of scleroderma and other autoimmune diseases associated with type I IFN signatures. Skin.


Error analysis in titration microcalorimetry of biochemical systems.
A simplified method for titrations of biochemical systems is described as well as extensive error propagation through the data analysis. This work uses a Tronac Model 450 isoperibol titration calorimeter. Sample volumes of 2 ml are used and total heats of less than 5 mcal can be routinely measured. The binding of 3'-CMP to bovine pancreatic ribonuclease A is used to illustrate the methods. The binding enthalpy can be determined with a standard deviation of 1.5% and the free energy with a standard deviation of 2 to 3%.


Economics of the Management of Craniospinal Chordoma and Chondrosarcoma and the feasibility of the bundled payment model.
The Centers for Medicare and Medicaid Services (CMS) created a new reimbursement model "Bundled Payment for Care Improvement (BPCI)" which reimburses providers a predetermined payment in advance to cover all possible services rendered within a certain time window. Chordoma and Chondrosarcoma are locally aggressive malignant primary bony tumors. Treatment includes surgical resection and radiotherapy with substantial risk for recurrence which necessitates monitoring and further treatment. We assessed the feasibility of the BPCI model in these neurosurgical diseases. We selected patients with chordoma/chondrosarcoma from inpatient admission table using the International Classification of Disease, 9th (ICD-9), and 10th (ICD-10) revision codes. We collected the patients' demographics and insurance type at the index hospitalization. We recorded the following outcomes length of stay, total payment, discharge disposition, and complications for the index hospitalization. For post-discharge, we collected the 30 days and 3/6/12 months inpatient admission, outpatient service, and medication refills. Continuous variables were summarized by means with standard deviations, median with interquartile and full ranges (minimum-maximum); Continuous outcomes were compared by nonparametric Wilcoxson rank-sum test. All tests were 2-sided with a significance level of 0.05. Statistical data analysis was performed in SAS 9.4 (SAS Institute, Inc, Cary, NC). The population size was 2041 patients which included 1412 patients with cranial (group1), 343 patients with a mobile spine (group 2), and 286 patients with sacrococcygeal (group 3) chordoma and chondrosarcoma. For index hospitalization, the median length of stay (days) was 4, 6, and 7 for groups 1, 2, and 3 respectively (P<.001). The mean payments were ($58,130), ($84,854), and ($82,440), for groups 1, 2, and 3 respectively (P=.02). The complication rates were 30%, 35%, and 43% for groups 1, 2, and 3 respectively (P<.001). Twelve months post-discharge, the hospital readmission rates were 44%, 53%, and 65% for groups 1, 2, and 3, respectively (P<.001). The median payments for this period were ($72,294), ($76,827), and ($101,474), for groups 1, 2, and 3, respectively (P <.001). The management of craniospinal chordoma and chondrosarcoma is costly and may extend over a prolonged period. The success of BPCI requires a joint effort between insurers and hospitals. Also, it should consider patients' comorbidities, the complexity of the disease. Finally, the adoptionof quality improvement programs by hospitals can help with cost reduction.


Complex convolutions in neurons of the dorsal lateral geniculate nucleus of the normal albino rat.
The postnatal development of complex convolutions (CCs) of the dorsal lateral geniculate nucleus (LGNd) in normal rats has been studied quantitatively with light microscopy. We report that immature neurons do not contain these scarcely understood organelles, since they can be seen for the first time in very few, mature neurons of the 30 day rat; their number constantly increases during the following 4 months. These cytoplasmic inclusions can be equally seen in the aged rat. CCs are present in neurons of all sizes, except the smallest, which correspond to the interneuron population. Although, morphologically, CCs of the LGNd of the rat are similar, but not identical, to the cytoplasmic multilaminated bodies of the cat, intermediate forms are described.


The efficiency of energy utilization in growing cattle consuming fresh perennial ryegrass (Lolium perenne cv. Melle) or white clover (Trifolium repens cv. Blanca).
1. Twenty Friesian steers (225 kg live weight) were fed on mid- (M) (June-July) and late- (L) (August-September) season crops of either fresh perennial ryegrass (Lolium perenne cv. Melle) (G) or white clover (Trifolium repens cv. Blanca) (C). Each of the forage diets was offered at three restricted planes of nutrition above maintenance to compare the effect of forage species on the efficiency of energy utilization. All diets were harvested daily from swards of regrowth forage of intended equivalent digestibility. 2. Faecal and urine excretions were measured for 7 and 5 d respectively, followed by two consecutive 24 h measurements of methane, carbon dioxide and oxygen exchange in open-circuit respiration chambers. 3. The apparent digestibility of the energy in perennial ryegrass (0.759) was marginally higher (P less than 0.01) than that in white clover (0.748); the mid- and late-season forages were of similar (P greater than 0.05) digestibilities. Metabolizable energy (ME): digestible energy (DE) in diet G (0.837) was significantly (P less than 0.001) different from that in diet C (0.812). The partition of energy losses when expressed as MJ/GJ gross energy intake (GEI) indicated that energy lost as methane was not significantly different (P greater than 0.05) either between forages (G 62.8, C 63.4) or between seasons (M 63.2, L 63.1). Energy excretion in urine was higher for cattle fed on diet C (77.5) compared with diet G (60.5) (P less than 0.001). Heat production was similar (P greater than 0.05) between forages (G 480, C 478), but lower (P less than 0.01) for L (471) compared with M(486). Energy retention (by difference) was lower (P less than 0.001) for diet C (132) than G (156) and for M (138) than L (149) (P less than 0.05). 4. Parallel-line analysis of unscaled ME intake (MEI) in relation to retained energy (RE; MJ/d) indicated that the efficiency of utilization (kt) was similar (P greater than 0.05) between perennial ryegrass (0.42) and white clover (0.46). Linear extrapolation of the values to zero energy retention indicated that maintenance requirements of ME (Em; MJ/d) were 23.3 for diet G and 28.8 for diet C. The extrapolated Em when expressed in relation to a measured fasting heat production (FHP) of 22.8 (MJ/d) resulted in a derived efficiency of utilization of ME for maintenance (km) of 0.97 (G) and 0.79 (C), suggesting an underestimate of Em for diet G.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of the 3-hydroxyanthranilic acid analogue NCR-631 on anoxia-, IL-1 beta- and LPS-induced hippocampal pyramidal cell loss in vitro.
The kynurenine pathway intermediate 3-hydroxyanthranilic acid (3-HANA) is converted by 3-HANA 3,4-dioxygenase (3-HAO) to the putative neuropathogen quinolinic acid (QUIN). In the present study, the neuroprotective effects of the 3-HANA analogue and 3-HAO inhibitor NCR-631 was investigated using organotypic cultures of rat hippocampus. An anoxic lesion was induced by exposing the cultures to 100% N2 for 150 min, resulting in a pronounced loss of pyramidal neurons, as identified using NMDA-R1 receptor subunit immunohistochemistry. NCR-631 provided a concentration-dependent protective effect against the anoxia. NCR-631 was also found to counteract the loss of pyramidal neurons in two models of neuroinflammatory-related damage; incubation with either LPS (10 ng/ml) or IL-1 beta (10 IU/ml). The findings suggest that NCR-631 has neuroprotective properties and that it may be a useful tool to study the role of kynurenines in neurodegeneration.


BAT: Bisulfite Analysis Toolkit: BAT is a toolkit to analyze DNA methylation sequencing data accurately and reproducibly. It covers standard processing and analysis steps from raw read mapping up to annotation data integration and calculation of correlating DMRs.
Here, we present BAT, a modular bisulfite analysis toolkit, that facilitates the analysis of bisulfite sequencing data. It covers the essential analysis steps of read alignment, quality control, extraction of methylation information, and calling of differentially methylated regions, as well as biologically relevant downstream analyses, such as data integration with gene expression, histone modification data, or transcription factor binding site annotation.


Management of Osteoporotic and Neuropathic Ankle Fractures in the Elderly.
Treatment of osteoporotic and neuropathic ankle fractures in the elderly is challenging. The purpose of this paper is to review recent publications on this topic and to identify the optimal treatment for these fractures. Treatment consists of a variety of conservative or operative options all with advantages and disadvantages as described in this review. Little research has been published that specifically focuses on elderly patients with ankle fractures. Operative treatment has a high complication rate. Multiple comorbidities are predictors for complications. An optimal treatment could not be distilled but based on the available literature, a general treatment algorithm is proposed. Since the elderly typically are accompanied by multiple comorbidities as well as impaired mobility, the physician should focus not only on treating the fractured ankle but also on the patient as a whole. Further research on this specific topic is needed.


Complete Genome Sequence of Campylobacter jejuni RM1285, a Rod-Shaped Morphological Variant.
Campylobacter jejuni is a spiral shaped Gram-negative food-borne bacterial pathogen of humans found on poultry products. Strain RM1285 is a rod-shaped variant of this species. The genome of RM1285 was determined to be 1,635,803 bp, with a G+C content of 30.5%.


Undergraduate student nurses' lived experiences of anxiety during their first clinical practicum: A phenomenological study.
The Fundamental Nursing clinical practicum is an essential module for nursing students. Some feel stress or anxiety about attending this first placement; however, evidence demonstrates that it is rare to explore the feelings of anxiety felt by the nursing students concerning their first clinical practicum. This study was designed to explore student nurses' experiences of anxiety felt regarding their initial clinical practicum while studying for their University degree. A phenomenological approach was used. A university in Southern Taiwan. A purposive sampling of fifteen student nurses with anxiety reactions who had completed their first clinical practicum. Data were collected using a semi-structured guide and deep interview. Data were analyzed using Colaizzi's seven-step phenomenological method. Three themes surfaced in the findings. The first theme was anxiety around their first clinical practicum, which stirred up anxiety about: self-doubt, worry and fear; difficulty coping with the learning process; worry hampered establishing therapeutic relationships with patients; the progress of the patients' illness could not be predicted; and anxiety felt about lecturer-student interactions. The second theme was three phases of anxiety reactions, which included increasing anxiety before clinical practicum; exacerbated anxiety during clinical practicum, and relief of anxiety after clinical practicum. The third theme was coping behaviors. This comprised: self-reflection in preparation for clinical practicum; finding ways to release emotions; distractions from the anxiety; and, also facing their difficulties head-on. The findings could help raise the awareness of lecturers and students by understanding student nurses' anxiety experiences and facilitating a healthy preparation for their initial clinical practicum, consequently proactively helping reduce potential anxiety experiences.


Thin boundary layer model underestimates greenhouse gas diffusion from inland waterways.
Inland waters are significant sources of atmospheric greenhouse gas (GHG) emissions. The thin boundary layer (TBL) model is often employed as a means of estimating GHG diffusion in inland waters based on gas transfer velocity (k) at the air-water interface, with k being subject to regulation by near-surface turbulence that is primarily driven by wind speed in many cases. This wind speed-based estimation of k (wind-k), however, can introduce substantial uncertainty for turbulent waterways where wind speed does not accurately represent overall turbulence. In this study, GHG diffusion in the Beijing-Hangzhou Grand Canal (China), the first and longest man-made canal in the world, was estimated using the TBL model, revealing that this model substantially underestimated GHG diffusion when relying on wind-k. Strikingly, the carbon dioxide, methane, and nitrous oxide diffusions were respectively underestimated by 159%, 162%, and 124% when using this model. These findings are significant for developing more reliable approaches to evaluate GHG emissions from inland waterways.


Cerebrospinal fluid rhinorrhea complicating pregnancy.
Cerebrospinal fluid rhinorrhea is an uncommone occurrence, especially when a history of previous trauma is absent. This report describes a case of cerebrospinal fluid rhinorrhea occurring in a pregnant patient during the pushing portion of her Lamaze exercises, and discusses the management of labor and delivery.


Is Treating Motor Problems in DCD Just a Matter of Practice and More Practice?
Developmental coordination disorder (DCD) is often called a motor learning deficit. The question addressed in this paper is whether improvement of motor skills is just a matter of mere practice. Without any kind of intervention, children with DCD do not improve their motor skills generally, whereas they do improve after task-oriented intervention. Merely offering children the opportunity to practice motor skills, for instance by playing active video games, did lead to improved motor performance according to recent research findings, but to a lesser extent than task-oriented intervention. We argue that children with DCD lack the required motor problem-solving skills necessary to further improve their performance. Explicit motor teaching with an emphasis on developing these problem-solving skills is a necessary ingredient of intervention in DCD, leveraging the effectiveness of intervention above that of mere practicing.


Organic and nitrogen removal in a two-stage rotating biological contactor treating municipal wastewater.
A laboratory scale rotating biological contactor (RBC) predenitrification system incorporating anoxic and aerobic units was evaluated for the treatment of settled high-strength municipal wastewater. The system was operated under four recycle ratios (1, 2, 3 and 4) and loading rates of 38-182 gCOD/m(2)d and 0.22-14 gOxid-N/m(2)d on the anoxic unit and 3.4-18 gCOD/m(2)d and 0.24-1.8 gNH(4)-N/m(2)d on the aerobic. The average removal efficiency in terms of chemical oxygen demand (COD), biochemical oxygen demand (BOD(5)), total suspended solids (TSS) and total nitrogen (Total-N) was 82%, 86%, 63% and 54%; settling of the RBC effluent increased COD and TSS removal to 94% and 97%. An increase in hydraulic loading resulting from higher recirculation, had limited negative effect on organic removal but improved nitrogen removal, and in terms of Total-N removal efficiency increased up to a ratio of 3 and then decreased.


Changes in the role of general practitioners in child health surveillance.
Changes in their Contract in 1990 gave general practitioners the opportunity to become more involved in child health surveillance. This study aimed to describe and compare child health surveillance services provided by general practitioners before and after the changes of the 1990 GP contract. A questionnaire was sent to all general practices within the Nottingham Health Authority area in 1990, and this process was repeated in 1994, ascertaining the services provided for child health surveillance. Outcome measures were: the reported provision of services, keeping of records and facilities for following up non-attenders. Also recorded were the training and qualifications of general practitioners and their attitudes towards child health surveillance. Response rates were 62% in 1990 and 80% in 1994. More practices were involved in the provision of child health surveillance services in 1994, more held a baby clinic and more reported having a recall system for non-attenders. There was little change in the training or qualifications of GPs in child health between 1990 and 1994. In 1994, there was evidence of GPs meeting regularly with Health Visitors. There remained a small number of practices who were not interested in child health surveillance. The 1990 GP contract appears to have increased the provision of child health surveillance services by GPs and improved liaison with Health Visitors in general practice.


Transient attention does not alter the eccentricity effect in estimation of duration.
Previous research investigating the influence of stimulus eccentricity on perceived duration showed an increasing duration underestimation with increasing eccentricity. Based on studies showing that precueing the stimulus location prolongs perceived duration, one might assume that this eccentricity effect is influenced by spatial attention. In the present study, we assessed the influence of transient covert attention on the eccentricity effect in duration estimation in two experiments, one online and one in a laboratory setting. In a duration estimation task, participants judged whether a comparison stimulus presented near or far from fixation with a varying duration was shorter or longer than a standard stimulus presented foveally with a constant duration. To manipulate transient covert attention, either a transient luminance cue was used (valid cue) to direct attention to the position of the subsequent peripheral comparison stimulus or all positions were marked by luminance (neutral cue). Results of both experiments yielded a greater underestimation of duration for the far than for the near stimulus, replicating the eccentricity effect. Although cueing was effective (i.e., shorter response latencies for validly cued stimuli), cueing did not alter the eccentricity effect on estimation of duration. This indicates that cueing leads to covert attentional shifts but does not account for the eccentricity effect in perceived duration.


Preventing surgical-site infections after colorectal surgery.
Surgical-site infection (SSI) is a major contributor to patient mortality rates and health care costs. Due to the high risk of bacterial contamination, colorectal surgery is associated with a particularly high risk of postoperative infection. The surveillance reported here was conducted at Aichi Medical University Hospital on 304 patients who underwent elective colorectal resection--total or partial--from June 2006 to May 2009. To determine risk factors for SSI, multivariate analysis was used. Forty-six (15.1%) patients were diagnosed with SSI. Patients who received cefotiam for prophylaxis showed the highest incidence of SSI (26.6%), and patients who were administered flomoxef showed the lowest incidence (8.1%). Patients who developed SSI were more likely to intraoperative blood loss (308.1 ± 29.8 vs. 153.9 ± 12.2; p < 0.05), longer postoperative antimicrobial administration (5.3 ± 2.2 vs. 4.5 ± 1.5; p < 0.05), and longer operative time (3.3 ± 1.6 vs. 2.7 ± 1.2; p < 0.05). Intraoperative bleeding, antimicrobial choices to cover both anaerobic and aerobic bacteria, and length of antimicrobial administration were independently predictive of SSI development according to multivariate logistic regression analysis. These results suggest that the degree of operative invasion and anaerobic bacteria contribute to SSI following colorectal surgery.


Validation of an indirect ELISA employing a chimeric recombinant gag and env peptide for the serological diagnosis of equine infectious anemia.
The National Reference Center for equine infectious anemia (EIA) validated a commercial ELISA (Eradikit® EIAV Indirect ELISA, In3diagnostic®, Turin, Italy) employing a chimeric recombinant gag and env peptide for the detection of EIA virus antibodies, following the guidelines of the World Organization for Animal Health. The validation parameters evaluated were: analytical sensitivity (Se) and specificity (Sp); diagnostic Se and Sp; precision, based on repeatability and reproducibility through the estimation of the standard deviation (SD) and the coefficient of variation (CV); accuracy, estimated from a multiple K and relative Sp and Se with respect to those of the agar gel immunodiffusion test (AGIDT). Positive and negative predictive values were also defined. The assay showed a high specificity and a limit of detection of 1.43 log10 major than AGIDT. Diagnostic Se was 100% and Sp was 99.3%, while SD values ranged from 1.58 to 5.01 with a CV between 2.8% and 28.8%. Multiple K was 0.98 and relative Se and Sp were respectively 99.1% and 100%. The assay proved to be robust and to possess a high sensitivity in detecting first antibodies produced at onset of infection as well as high analytic and diagnostic Se and Sp values, confirming it as a serological assay fit for purpose within EIA surveillance programs.


Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and predicts survival after anthracycline chemotherapy treatment.
Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 % CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent prognostic factor. High eIF4E expression was associated with worse outcome also after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060). In the subgroup analysis the survival effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.


Surface IR immunosensors for label-free detection of benzo[a]pyrene.
Polycyclic aromatic hydrocarbons (PAHs) are a family of contaminants originating from the incomplete combustion of organic compounds, present in the urban air, water, soil and also foodstuff. Due to their recognised carcinogenicity, their concentration in urban air is routinely monitored and governmental instances have set rules as regards their maximum allowable concentration. Benzo[a]pyrene (BaP) is one of the PAHs, highly toxic, whose concentration correlates well with the total PAHs contents in environmental samples; its detection by immunosensors has been rarely described because of its low molecular weight and poor solubility in water. In this paper, we report the design and testing of optical and piezoelectric immunosensors for the determination of BaP by using Polarisation-Modulation Infrared Reflection-Absorption Spectroscopy (PM-IRRAS) or Quartz Crystal Microbalance with dissipation measurements (QCM-D) as transduction techniques, and a comparison of their analytical performances. We found relevant to set up immunosensors based on a direct or indirect competitive format. BaP was detected by PM-IRRAS with both immunosensor formats with similar sensitivity, ca. 5 μM. Flow-injection piezoelectric transduction in the indirect competitive format set up led to a slightly better sensitivity than that reached by PM-IRRAS. No general conclusion about the most efficient set up could be drawn from comparing the sensitivities, but the reported data illustrate the potential of PM-IRRAS as well as flow-injection QCM-D as efficient label-free transduction techniques.


Increased proportion of high-affinity dopamine D2 receptors in rats with excitotoxic damage of the entorhinal cortex, an animal model of schizophrenia.
Excitotoxic lesions of the left entorhinal cortex (EC) cause dopamine supersensitivity. In order to determine if these lesions selectively alter the high-affinity state of dopamine D2 receptors (D2(High)), these high-affinity states were measured by competition between dopamine and [3H]domperidone in striata from lesioned rats and sham-operated animals. The proportion of D2(High) sites was significantly elevated by 200% in the EC-lesioned rats while that of the D1(High) sites, measured by dopamine/[3H]SCH23390 competition, was unaltered. These results provide a biochemical basis for behavioral supersensitivity in rats with EC lesions.


Effect of oral and inhalation exposure to cadmium on the oestrous cycle in rats.
Female rats were administered by gavage an aqueous solution of CdCl2 for 14 weeks, 5 days per week, at doses of 0.04, 0.4, 4 and 40 mg Cd/kg/day or exposed by inhalation to CdO for 20 weeks (5 h per days, 5 days per week) at concentrations of 0.02, 0.16 and 1 mg Cd/m3. A pronounced increase in the mean duration of the oestrous cycle mainly due to lengthening of dioestrus was noted already 6 weeks after treatment of females given per os 40 mg Cd/kg or exposed to a concentration of 1 mg Cd/m3. No changes in the mean duration of the oestrous cycle were found in other experimental groups, although in the 0.16 mg Cd/m3 group an increased percentage of females with oestrous cycles lasting over 6 days was shown 18 weeks after exposure. Since Cd-induced lethality and decrease in body weight gain were observed in females given by gavage 40 mg Cd/kg or exposed by inhalation to a concentration of 1 mg Cd/m3, it is concluded that exposure to cadmium does not affect the sexual cycle unless other overt signs of Cd-toxicity are induced.


[Modern aortic surgery in Marfan syndrome--2011].
Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.