[Analyses of answers presented by children with and without specific language impairment].
children start to differentiate questions from non-questions and also start to adjust their answers at the age of two. This participation in verbal exchanges requires basic conversational abilities such as the competence to initiate interact and reply appropriately, and to maintain the interaction. to analyze and correlate the pragmatic aspects of language, related to the type of answers, during an adult/child interaction in children with normal language development and in those diagnosed with Specific Language Impairment (SLI). 16 children with SLI (GP) and ages between three and six years, and 60 children with normal language development (GC) and ages between three to five years - 20 for each age group, 10 of each gender. Data gathering occurred in two different days, with the adult/child interaction being facilitated by toys. Data (speech of child and adult) were transcribed and analyzed, obtaining a Reliability Index of 93.75%, and later were submitted to statistical analyses. answers were classified in categories and grouped according to the following: Adequate Answers (RA) and Inadequate Answers (RI), always in accordance to the established communicative context. GC presented a significantly higher average of RA when compared to GP, and GP presented a significantly higher average of RI when compared to GC. GC presented a decrease in the use of RI at the increase of age. GP maintained the use of RI at the increase of age, including the age group of six. it was observed that the increase in age emphasized differences between GP and GC. GP presented a less effective communication maintaining unintelligible speech, whereas GC presented more elaborate communication abilities. More studies with older children are necessary for the better understanding of the observed trends.


[Correlation between diffusion anisotropy of the white matter fibers and cognitive function in patients with leukoaraiosis].
To investigate the correlation between the diffusion anisotropy of the white matter fibers and the cognitive function in patients with leukoaraiosis (LA). Thirty-one LA patients were enrolled in this study, including 13 with grade LA-1 (mild), 12 with grade LA-2 (moderate) and 6 with grade LA-3 (severe) condition. The control group consisted of 18 subjects who were free of obvious clinical symptoms or had only mild dizziness and headache but with negative history for neural system diseases and in the absence of cognitive dysfunction, brain trauma, positive signs in neurological examinations, or abnormities in MRI examination. The Mini-mental State Examination (MMSE) was applied to evaluate the patients' cognitive function. The LA patients underwent examination with diffusion tensor MR imaging (DTI), and the FA and MD values in the normal-appearing white matter (NAWM) were measured. The cognitive function of the LA patients tended to decline with the decrease of the MMSE scores, and their scores for time orientation, place orientation and calculation were significantly lower than those of the control group (P<0.05). No significant difference was found in memory, language and comprehensive abilities between the LA and control groups. In LA-1, LA-2 and total LA cases, the FA value in the NAWM was positively, and the MD value inversely, correlated to the cognitive function with correlation coefficients ranging from 0.5 to 0.8 (P<0.05). The DTI parameters of NAWM region are correlated to the cognitive function of LA patients. DTI is far more sensitive than MRI in evaluating cognitive dysfunction in LA patients.


Facial palsy after neck arteriovenous fistula embolization.
Facial palsy after embolization of neck arteriovenous fistula is an extremely rare complication. In our case, complete facial palsy occurred after embolization and was successfully treated with superficial parotidectomy, vessel ligation, and plug removal. We report the first case of unusual facial palsy that developed 13 days after neck arteriovenous fistula embolization. As a result of our findings, we recommend, when a patient suffers from acute ipsilateral facial palsy after arteriovenous fistula embolization, the clinician should consider the possibility of complications of embolization, and immediate and appropriate management should be performed.


A comparative study between the effects of 4% endotracheal tube cuff lignocaine and 1.5 mg/kg intravenous lignocaine on coughing and hemodynamics during extubation in neurosurgical patients: a randomized controlled double-blind trial.
A prospective, randomized double-blind trial was performed to compare the effects of 4% endotracheal tube cuff lignocaine and 1.5 mg/kg intravenous (IV) lignocaine on coughing and hemodynamics during extubation in patients undergoing elective craniotomies in supine position. Forty-one patients received 4% lignocaine into the endotracheal tube cuff after intubation (ETT group) and 41 patients received IV lignocaine at 1.5 mg/kg before extubation (IV group). Coughing was assessed by a scale of 3 at the time of extubation. Hemodynamic parameters recorded at 1-minute interval after extubation for 5 minutes were compared with the baseline values recorded before skin closure. Results showed that there was no significant difference between the groups in terms of coughing or the hemodynamic response to tracheal extubation. In conclusion, 4% endotracheal tube cuff lignocaine was not superior to 1.5 mg/kg IV lignocaine in attenuating coughing and hemodynamic changes during extubation.


Risk factors of severe ischemic biliary complications after liver transplantation.
Ischemia-related biliary tract complications remain high after orthotopic liver transplantation. Severe ischemic biliary complications often involve the hepatic duct bifurcation and left hepatic duct, resulting finally in obstructive jaundice. Prevention and management of such complications remain a challenge for transplant surgeons. All 160 patients were followed up for at least 180 days after transplantation. One-way analysis of variance (ANOVA) and comparative univariate analysis were made using 3 groups (no complications; mild complications; severe complications), to analyze risk factors associated with biliary complications. Multiple logistic regression and linear regression analysis were used to analyze independent risk factors for severe ischemic biliary complications, after excluding other confounding factors. By ANOVA and comparative univariate analysis, the risk factors associated with biliary complications were preoperative bilirubin level (P=0.007) and T-tube stenting of the anastomosis (P=0.016). Multiple logistic regression analysis showed that the use of T-tube and preoperative serum bilirubin were not independent risk factors for severe ischemic biliary complications after orthotopic liver transplantation. Chi-square analysis indicated that in the incidence of severe ischemic biliary lesions, bile duct second warm ischemic time longer than 60 minutes was a significant risk factor. Linear regression demonstrated a negative correlation between cold preservation time and warm ischemia time. Preoperative serum bilirubin level and the use of T-tube stenting of the anastomosis were independent risk factors for biliary complications after liver transplantation, but not for severe ischemic biliary complications. The second warm ischemia time of bile duct longer than 60 minutes and prolonged bile duct second warm ischemia time combined with cold preservation time were significant risk factors for severe ischemic biliary complications after liver transplantation with grafts from non-heart-beating donors.


A Population-Based Study on Nighttime Road Traffic Noise and Insomnia.
The aims of the present study were to investigate how nighttime road traffic noise relates to self-reported symptoms of insomnia and sleep medication use. We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-2010; n = 13019). The insomnia symptoms difficulties falling asleep, awakenings during the night, and waking up too early in the morning as well as self-reported sleep medication use were included as outcomes. Modeled noise levels (Lnight) were assigned to each participant's home address. For selecting covariates to the statistical model, we used a directed acyclic graph. The associations between noise and sleep were analyzed using logistic regression models. After adjustment for potential confounders, we found an odds ratio (OR) of 1.05 (95% confidence interval [CI]: 1.01-1.09) for the association between traffic noise and difficulties falling asleep, in the total study population. For the association between traffic noise and awakenings during the night, the OR was 1.04 (95% CI: 1.00-1.08) and for waking up too early, the OR was 1.06 (95% CI: 1.02-1.11). The effect estimates are given per 5-dB increase in traffic noise level (Lnight). Self-reported sleep medication use was not statistically significantly associated with traffic noise exposure. In an adult population from Oslo, traffic noise was associated with difficulties falling asleep and waking up too early. These findings indicate that sleep quantity may be compromised for individuals living in areas highly exposed to nighttime traffic noise.


Patient-generated health data: a pathway to enhanced long-term cancer survivorship.
The growing ability to collect and transmit patient-generated health data, also referred to as people-generated health data and patient-reported outcomes, is creating an opportunity to greatly improve how cancer survivors and their providers manage survivors' health in the months and years following cancer treatment. Although cancer survivors are at higher risk of chronic health problems and early death as a result of cancer treatment, some experience difficulty identifying and receiving the care they need to optimize their health post-treatment. This article describes the challenges that cancer survivors and their providers face in managing survivors' care and identifies several ways that using patient-generated health data can improve survivors' and providers' ability to manage survivorship care at the individual and population levels.


The contribution of chicken embryology to the understanding of vertebrate limb development.
The chicken is an excellent model organism for studying vertebrate limb development, mainly because of the ease of manipulating the developing limb in vivo. Classical chicken embryology has provided fate maps and elucidated the cell-cell interactions that specify limb pattern. The first defined chemical that can mimic one of these interactions was discovered by experiments on developing chick limbs and, over the last 15 years or so, the role of an increasing number of developmentally important genes has been uncovered. The principles that underlie limb development in chickens are applicable to other vertebrates and there are growing links with clinical genetics. The sequence of the chicken genome, together with other recently assembled chicken genomic resources, will present new opportunities for exploiting the ease of manipulating the limb.


Imitation in autism. A preliminary research note.
Previous studies have claimed that children with autism are poor imitators and a lack of imitative capacity has been included by some investigators as one early sign of autism. Presented here are results from a pilot study focusing on observed imitation after presenting 15 tasks to five children with autism (mental age 25-51 months). Imitation tasks involving simple object manipulation, vocal responses, facial and manual gestures, and object substitution were presented to each child. The performance of the children with autism is compared with (1) three normal 4-year-old children (for all 15 tasks), and (2) observations from 28 healthy 1-year-olds (for 10 of the tasks used). The findings indicate that the autistic group displayed the highest level of imitation on object manipulation and vocal tasks while object substitution, facial, and motor imitation acts seemed to be difficult for children with autism. However, the small number of children included as well as the individual variation observed among the autistic subjects precludes any definite conclusions from these pilot observations. It is hypothesized that imitation in children with autism has to be studied separately for different domains and probably also for different subgroups within the autistic population.


Sonographic characteristics of the facial nerve in healthy volunteers.
Peripheral nerve ultrasound has become an effective imaging technique. However, imaging of cranial nerves, especially in healthy volunteers, has received minimal attention. The objectives of this study were to describe the sonographic characteristics of the facial nerve and to establish average values of its diameter. The extra-cranial part of the facial nerve was scanned bilaterally along its longitudinal axis inside the parotid gland using a 13-MHz probe in 50 healthy adults. The diameter was measured at the nerve's thickest region. The facial nerve appeared as a thin, tubular, hypoechoic structure inside the parotid gland. The mean facial nerve diameter was 0.5 ± 0.1 mm, and the mean side-to-side difference in diameter was 0.1 ± 0.1 mm. The average facial nerve diameter values may provide help with identification of nerve abnormalities using ultrasound.


The co-administration of CpG-ODN influenced protective activity of influenza M2e vaccine.
In this report, we investigated the adjuvant effect of CpG-ODN on the immunogenicity and protective efficacy of influenza M2e peptide vaccine. We found that the addition of CpG-ODN 1826 into aluminum-adjuvant M2e peptide vaccine increased M2e-specific Th1 immune response, indicated by higher titers of M2e-specific IgG2a and more IFN-gamma-secreting lymphocytes. However, according to the result from virus challenge, enhancement of M2e-specific Th1 immune response failed to increase the protection against influenza virus. Moreover, when challenged with high dose of influenza virus, the addition of CpG-ODN even weakened the protective activity. These results suggested that the intensity of immune responses was not simply correlated with protective activity of influenza M2e vaccine and more comprehensive criterion should be built up for the evaluation of M2e-based vaccine.


Non-A, non-B hepatitis and anti-HCV antibodies in dialysis patients.
To define the prevalence of non-A, non-B hepatitis, antibodies to HCV were detected in 193 patients on renal replacement therapy (52 transplant and 141 hemodialysis patients) and in 50 staff members of a Nephrology Department. Unequivocal seroconversion was documented in 5 transplant (9.6%) and in 26 dialysis patients (18.4%). In the dialysis population, the prevalence of anti-HCV antibodies was evaluated in patients grouped according to the number of blood transfusions and to the different sections of dialytic treatment. The most striking findings were the marked differences in the prevalence of anti-HCV antibodies among patients treated in different sections (from 0% to 70%), and the presence of a significant increase in alanine-amino-transferase (ALT) concentrations in 14 anti-HCV negative patients. The results suggest that the diffusion of non-A, non-B hepatitis is mainly transfusion-related, with the possibility of significant environmental diffusion related to the violation of infection-control measures. The current immunoassay is probably unable to detect the actual frequency of the infection.


Nitric oxide donors stimulate bile flow and glutathione disulfide excretion independent of guanosine 3',5'-cyclic [corrected] monophosphate in the isolated perfused rat liver.
Nitric oxide (NO) modulates several metabolic functions in hepatocytes, but the role of NO in bile secretion has not been clearly defined. In the present study, we examined the effects of NO on bile flow and biliary HC03- and glutathione excretion in the isolated perfused rat liver and assessed the role of guanosine 3',5'-cyclic monophosphate (cGMP) in mediating these effects. The NO donors sodium nitroprusside (SNP) and S-nitroso-acetyl-penicillamine stimulated bile flow and increased both HCO3- and glutathione excretion. Increases in bile flow were linearly related to increases in biliary glutathione concentration and output (P < .0001), which were almost entirely caused by glutathione disulfide, whereas the excretion of reduced glutathione remained unchanged. NO donors increased cGMP concentrations in bile and perfusate, and the membrane-permeant cGMP analogue dibutyryl cGMP was also found to stimulate bile flow and HCO3- excretion. However, in contrast to the NO donors, dibutyryl cGMP did not increase glutathione excretion. Furthermore, the NO donors failed to stimulate bile flow in mutant TR- rats in which the canalicular transport of glutathione and glutathione conjugates is deficient, although dibutyryl cGMP increased bile flow and HCO3- excretion in the mutant rats as in normals. These findings indicate that exogenous sources of NO increase bile acid-independent bile flow by stimulating glutathione disulfide excretion, effects that are independent of cGMP.


Malignant melanoma in multiple endocrine neoplasia.
Because of its neurocrest APUD origin, malignant melanoma has been postulated to be a component of the multiple endocrine neoplasia (MEN) syndromes; however, such a case has not been previously described. Prior associations of melanocytes with the MEN syndromes have been confined to hyperplasia. This report describes the first case of malignant melanoma occurring in a patient with the MEN IIA syndrome (bilateral pheochromocytomas and medullary thyroid carcinoma). The role of melanocytic hyperplasia and neoplasia within the MEN syndromes is discussed.


[Study on prediction of compound-target-disease network of chuanxiong rhizoma based on random forest algorithm].
To collect small molecule drugs and their drug target data such as enzymes, ion channels, G-protein-coupled receptors and nuclear receptors from KEGG database as the training sets, in order to establish drug-target interaction models based on the random forest algorithm. The accuracies of the models were evaluated by the 10-fold cross-validation test, showing that the predicted success rates of the four drug target models were 71.34%, 67.08%, 73.17% and 67.83%, respectively. The models were adopted to predict the targets of 26 chemical components and establish the compound-target-disease network. The results were well verified by literatures. The models established in this paper are highly accurate, and can be used to discover potential targets in other traditional Chinese medicine ingredients.


The incidence of Escherichia coli on beef carcasses and its association with aerobic mesophilic plate count categories during the slaughter process.
An analysis of 535 prefabricated beef carcass samples taken in three processing plants demonstrated an association between the mesophilic aerobic plate count (APC) class and the incidence of obtaining an Escherichia coli-positive sample. Beef carcasses were sampled from three separate plants; one was a fed-beef processing plant and the other two were cow/bull plants. Samples were obtained by sponging and were analyzed for APC and E. coli. When samples were classified into four APC levels or classes (class 1: < 2, class 2: > or = 2 and < 3, class 3: > or = 3 and < 4, and class 4: > or = 4 log CFU/cm2), a trend indicating that samples from higher APC classes were more likely to be positive for E. coli biotype 1 was observed. Of the APC class 4 samples (> or = 4 log CFU/cm2), 88% were positive for the presence of E. coli, as opposed to 21% in APC class 1 (< 2 log CFU/cm2). Univariate chi-square analysis of the resulting contingency tables from reclassified data (class 1: < 2, class 2: > or = 2 and < 3, and class 3: > or = 3 log CFU/cm2) indicated a strong association between APC class and the incidence (presence or absence) of an E. coli-positive sample. Using multivariate analysis to account for influences of plant and within plant processing site, the data indicated a strong positive linear trend between the presence of E. coli and the APC class.


Perinephric Fat Stranding Is Associated with Elevated Creatinine Among Patients with Acutely Obstructing Ureterolithiasis.
Pyelovenous/pyelolymphatic backflow from acute ureteral obstruction, manifesting radiologically as perinephric fat stranding (PFS), may result in elevated serum creatinine. Among patients with acutely obstructing ureterolithiasis, we evaluated the relationship between degree of PFS and changes in serum creatinine from baseline. Our tertiary care center's radiology dictation system (Fluency Discovery, M Modal) was queried for noncontrast abdominopelvic CT studies obtained in the Emergency Department for patients with obstructing ureteral calculi from 7/2015 to 4/2016. A single radiologist blinded to clinical data reviewed all CT scans and coded stone size, location, severity of hydronephrosis, and degree of PFS (none, mild, moderate, severe). For patients who met imaging criteria, a retrospective chart review was performed. We evaluated 148 patients with mean age of 46 years (SD 14.6), 56.0% (n = 83) were male. On univariate analysis, moderate-severe perinephric stranding was associated with elevated creatinine from baseline (OR 2.93, p = 0.03). Mean creatinine increased as the severity of stranding increased (none Cr = 0.978 mg/dL, mild Cr = 0.983 mg/dL, moderate Cr = 1.165 mg/dL, severe Cr = 1.370 mg/dL; p < 0.01). An increase in creatinine from baseline was not associated with greater severity of hydronephrosis (OR 0.504, p = 0.189). There was no association between degree of PFS and severity of hydronephrosis, positive urine culture, stone location, or symptom duration (p > 0.05). On regression analysis controlling for positive urine culture and degree of hydronephrosis, there remained an association between elevated serum creatinine from baseline and moderate-severe PFS (OR 9.0, p = 0.01). Among patients with acute obstructive ureterolithiasis, moderate-severe PFS was associated with elevated serum creatinine from baseline. This elevated creatinine was not explained by the obstructed kidney alone, as there was no association between the severity of hydronephrosis and increased creatinine. Pyelovenous/pyelolymphatic backflow resulting in PFS may be a contributing factor to elevated serum creatinine in this setting.


Hippocampal neurogenesis and ageing.
Although significant inconsistencies remain to be clarified, a role for neurogenesis in hippocampal functions, such as cognition, has been suggested by several reports. Yet, investigation in various species of mammals, including humans, revealed that rates of hippocampal neurogenesis are steadily declining with age. The very low levels of hippocampal neurogenesis persisting in the aged brain have been suspected to underlie the cognitive deficits observed in elderly. However, current evidence fails to support the hypothesis that decrease of neurogenesis along normal ageing leads to hippocampal dysfunction. Nevertheless, current studies are suggestive for a distinct role of hippocampal neurogenesis in young versus adult and old brain.


Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma.
We investigated the alterations of natural killer (NK) cells in pregnancy, which led to decreased killing from the first trimester to the puerperium. We show that this phenomenon cannot be ascribed to a defective number of NK cells since the amounts of HNK-1+, CD16+ (Leu 11), and CD11b+ (OKM1) cells were within normal ranges. Recombinant interleukin 2 (rIL-2) corrects the functional defect in a dose and time-dependent manner, without modification in the surface phenotype of the population. Analysis of the pattern of target cell susceptibility to lysis, together with the similar ability of recombinant interferon gamma (rIFN-gamma) to correct the deficiency, and CD16+, CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. Inhibitors in pregnancy sera block IL-2 production by specific T cells, but we show that they do not influence either NK activity or its reconstitution by rIL-2. These findings place the deficiency at the level of NK cell maturation into cytotoxic effector lymphocytes. Thus, homeostasis of the NK activity of pregnant women may provide a biological model for clarifying the internal mechanisms regulating NK-cell activation in vivo. Present studies in vitro suggest that modulation of lymphokine production may play a role in the adaptive response of NK cells in pregnancy.


Expanding the substrate repertoire of a DNA polymerase by directed evolution.
Nucleic acid polymerases are the most important reagents in biotechnology. Unfortunately, their high substrate specificity severely limits their applications. Polymerases with tailored substrate repertoires would significantly expand their potential and allow enzymatic synthesis of unnatural polymers for in vivo and in vitro applications. For example, the ability to synthesize 2'-O-methyl-modified polymers would provide access to materials possessing properties that make them attractive for biotechnology and therapeutic applications, but unfortunately, no known polymerases are capable of efficiently accepting these modified substrates. To evolve such enzymes, we have developed an activity-based selection method which isolates polymerase mutants with the desired property from libraries of the enzyme displayed on phage. In this report, mutants that could efficiently synthesize an unnatural polymer from 2'-O-methyl ribonucleoside triphosphates were immobilized and isolated by means of their activity-dependent modification of a DNA oligonucleotide primer attached to the same phage particle. In each case, directed evolution resulted in relocating a critical side chain to a different position in the polypeptide, thus re-engineering the overall active site while preserving critical protein-DNA interactions. Remarkably, one evolved polymerase is shown to incorporate the modified substrates with an efficiency and fidelity equivalent to that of the wild-type enzyme with natural substrates.


Inhibition of Xenopus oocyte adenylate cyclase by progesterone and 2',5'-dideoxyadenosine is associated with slowing of guanine nucleotide exchange.
Adenylate cyclase activity in Xenopus oocyte membranes measured in the presence of guanyl-5'-yl imidodiphosphate and 1.5 mM Mn2+ was maximally inhibited to 57% of control by progesterone and to 89% by the P site agonists, 2',5'-dideoxyadenosine and 9-beta-d-arabinofuranosyladenine. Inhibition by saturating concentrations of 2',5'-dideoxyadenosine and progesterone was not additive, suggesting that inhibition of oocyte adenylate cyclase by progesterone may share a common mechanism with P site inhibition. Kinetic analysis of the effect of progesterone and 2',5'-dideoxyadenosine on the hysteretic activation of adenylate cyclase by guanyl-5'-yl imidodiphosphate indicates that both hormones exert their effects, at least in part, by lengthening the lag in cAMP formation, and this hysteretic effect is inversely proportional to the concentration of guanine nucleotide in the incubation mixture. Direct measurement of [3H] guanine nucleotide release from oocyte membranes preloaded with [3H] GTP demonstrated that treatment with either progesterone or 2',5'-dideoxyadenosine slows the rate of nucleotide exchange. Inhibition of oocyte adenylate cyclase by 2',5'-dideoxyadenosine was potentiated by millimolar concentrations of Mn2+, but inhibition by progesterone was abolished. The results indicate that inhibition of Xenopus oocyte adenylate cyclase by progesterone has features in common with both P site and receptor-mediated inhibitory mechanisms.


Comparison of peptide and nonpeptide receptor-mediated responses in rat tail artery.
Chronic uremia and metabolic acidosis impair vascular responses to norepinephrine (NE) and also cause multiple metabolic defects in skeletal muscle. These studies were conducted to determine whether decreased vascular responsiveness resulted from putative second messenger metabolism. Tail arteries were used from rats with metabolic acidosis or nonacidotic uremia and from normal controls. In normal arteries, the maximal responses were the same for arginine vasopressin (AVP), NE, and mixtures of the two agonists, suggesting that the two receptor types use the same transduction mechanism. Nonetheless, qualitative differences exist between AVP- and NE-induced responses: (a) Concentration-response curves are steeper for AVP than for NE, (b) EC50 values are similar for AVP between inositol phosphates (IP assays) and contraction, but not for NE, and (c) arteries from rats with metabolic acidosis or uremia show selective blunting of biochemical and contractile responses to NE but not to AVP. We conclude that these metabolic derangements selectively affect alpha-adrenergic receptors, but not AVP receptors or the transduction mechanism leading to contraction.


Simplification of the representation of the organic component of atmospheric particulates.
We present an analysis of recent field data to investigate the variation in the organic component of atmospheric aerosol and its behaviour in the moist environment. In all locations the degree of oxygenation of the organic material increases with photochemical age, as does the particulate hygroscopicity. These changes will generally occur in spatial scales comparable to a single cell in global models at representative boundary layer wind speeds. Using ADDEM, a new model of the equilibrium state of multicomponent aerosol, we show that inorganic component changes must be responsible for the increase in particulate hygroscopicity with photochemical age. It is suggested that a common representation of nearfield and background organic aerosol composition is sufficient to describe the behaviour of organic components in a variety of field experiments; nearfield small mode organics being dominated by a combustion-derived unoxidised signature, whilst the background accumulation mode is more oxygenated and dominates in air masses with a photochemical age of more than a couple of days. This representation may be used within the sub-saturated regime to predict the behaviour of ambient particulates in the moist atmosphere. Whether a similar common representation can be used for cloud activation prediction in supersaturated environments, or for investigation of gas-to-particle partitioning, should be investigated.


The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals, in the early stages of the drug discovery process.
There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.


[The tidal volume, arterial blood gas and functional residual capacity changes during negative extra-thoracic pressure ventilation and positive airway pressure ventilation].
Eight patients, of ASA physical status I or II soon after total knee replacement under general anesthesia, were studied to compare negative extra-thoracic pressure ventilation (NETPV) with positive airway pressure ventilation (PAPV). The measured parameters during the two ventilatory modes were tidal volume, arterial blood gas and functional residual capacity change (delta FRC). Tidal volume obtained during NETPV was 60 to 80% of that during PAPV at the same absolute values of peak pressure. delta FRC obtained during NETPV was 30 to 40% of that during PAPV at the same absolute values of end-expiratory pressure. A decrease in the esophageal pressure was 4 to 11cmH2O at an end-expiratory negative extra-thoracic pressure of -10 to -20 cmH2O. When the patients were ventilated with the same values of minute ventilation on NETPV and PAPV, there was no significant difference in blood gas values. These findings suggest that efficiency of NETPV is less than that of PAPV at the same absolute working pressure but pulmonary gas exchange of NETPV is almost equal to that of PAPV at the same minute ventilation in the normal lung.


Patients with pyoderma gangrenosum - analyses of the German DRG data from 2012.
Pyoderma gangrenosum (PG) is a rarely diagnosed non-infectious neutrophil ulcerative dermatosis with only limited knowledge on the underlying auto-inflammatory process. To unravel common cofactors and comorbidities in patients with PG we analysed Diagnosis Related Groups (DRG) cases of all inpatients diagnosed with PG in German hospitals in 2012. We received data of 1227 inpatient cases having PG as primary diagnosis and 985 inpatient cases with PG as secondary diagnosis. The ratio of women to men was 2:1, and the most often registered age was 75-79 years. Common comorbidities were arterial hypertension (50·3%), non-insulin-dependent diabetes mellitus (25·1%) and dysfunction of lipid metabolism (10·8%). In sum, 94·8% of the patients suffered from aspects of metabolic syndrome. Other comorbidities were Crohn's disease (4·5%), ulcerative colitis (4·2%), chronic polyarthritis (5·2%), monoclonal gammopathy or myelodysplastic syndrome (2·5%), leukaemia (1·1%) and lymphoma (0·4%). DRG data do not reflect individual patients, but rather patient cases. We described the worldwide largest PG population and confirmed a wide range of potentially relevant and partly not yet described cofactors and comorbidities such as metabolic syndrome.


Good laboratory practice in pharmaceutical quality control.
Experience in establishing a system of 'Good Laboratory Practice' (GLP) in the pharmaceutical industry is discussed with respect to the historical development and specific aspects of the system: training, safety, documentation, equipment and personnel management in the laboratory.


[The double-cup carpus: a demonstration of the variable geometry of the carpus].
The variable frontal geometry of the carpus has been known for many years, however there is no unanimity as to whether to describe the dynamic model of the carpus as comprising row or columnar functional units. The place of the scaphoid is also discussed. This study attempts to understand the organization and the composition of the functional units of the carpus. We took radiographs of 40 normal right wrists in radial and ulnar deviation and measured the displacement in the coronal plane of each carpal bone except the pisiform. We measured the angular movements of each carpal bone compared to a vertical axis passing through the geometric centre of the carpus. This axis is parallel to the radial axis which is defined as the line joining the midpoints of the radius at 2 and 5 cm proximal to the radial articular surface. We studied the movement of each row and each column. Recorded angular movements were the followings: scaphoid 26 degrees, lunate 28 degrees, triquetrum 29 degrees, trapezium 44 degrees, trapezoid 50 degrees, capitate 50 degrees, hamate 56 degrees. Average angular movement within the first row is 27 degrees, within the second row is 50 degrees. Average angular movement within the radial column is 38 degrees, middle column is 39 degrees, ulnar column is 42 degrees. The amplitude of movement are similar for the bones of each row, and different for the bones of each column. The bones of each row tend to move together and can alone account for all movements of the wrist. The movements measured between each column are torsional intrarow movements, allowing congruence between the two rows and the glenoid surface of the radius. The scaphoid movements are superposable with those of lunate and triquetrum. Scaphoid kinematics joins the first row. Radio-ulnar deviation of the wrist is shared equally between the radiocarpal and midcarpal joints. This sharing of wrist movement between the two rows constitutes for us a double cup carpal model.


Structural analysis of the 6 kb cryptic plasmid pFAJ2600 from Rhodococcus erythropolis NI86/21 and construction of Escherichia coli-Rhodococcus shuttle vectors.
The complete nucleotide sequence of the 5936 bp cryptic plasmid pFAJ2600 from Rhodococcus erythropolis NI86/21 was determined. Based on the characteristics of its putative replication genes, repA and repB, pFAJ2600 was assigned to the family of pAL5000-related small replicons identified in Mycobacterium (pAL5000), Corynebacterium (pXZ10142), Brevibacterium (pRBL1), Bifidobacterium (pMB1) and Neisseria (pJD1). The replication systems of these plasmids show striking similarities to the ones used by the ColE2 family of plasmids from Enterobacteria with respect to both trans-acting factors and ori sequences. Two possible plasmid stabilization systems are encoded on pFAJ2600: a site-specific recombinase (PmrA) related to the Escherichia coli Xer proteins for plasmid multimer resolution and an ATPase (ParA) related to the A-type of proteins in sop/par partitioning systems. The proposed replication termination region of pFAJ2600 has features in common with the Ter loci of Bacillus subtilis. Chimeras composed of a pUC18-Cmr derivative inserted in the parA-repA intergenic region of vector pFAJ2600 produced vectors that could be shuttled between Escherichia coli and several Rhodococcus species (R. erythropolis, R. fascians, R. rhodochrous, R. ruber). The pFAJ2600-based shuttle vector pFAJ2574 was stably maintained in R. erythropolis and R. fascians growing under non-selective conditions.


Computed tomography scan assessment of lung volume and recruitment during high-frequency oscillatory ventilation.
This review describes how computed tomography has increased our understanding of the pathophysiology of acute respiratory distress syndrome. It summarizes current knowledge about lung volume changes and alveolar recruitment during high-frequency oscillatory ventilation (HFOV) assessed by computed tomography (CT), outlines potential problems when comparing HFOV with conventional ventilation (CV) as a result of the different pressure-time profiles, and describes future research directions. CT allows accurate assessment of total lung volumes and differentiation between overinflated, normally aerated, poorly aerated, and nonaerated lung regions. It allows for classification of different patterns of consolidation and may be predictive for the potential for recruitment. Experimental data suggest that HFOV at mean airway pressures (mPaw) set according to a static PV curve leads to effective lung recruitment but results in overall lung volumes that are considerably higher than those predicted from the PV relationship. In saline-lavaged sheep, similar changes in total lung volumes and subvolumes were observed during HFOV and CV. One single study specifically assessed lung volume recruitment during HFOV as compared with CV in eight patients with acute respiratory distress syndrome from pneumonia or sepsis. After 48 hrs on HFOV, total ventilated lung volume was significantly increased, whereas only a minor increase in overinflated lung volume was observed. These changes correlated with a significant improvement in gas exchange. CT is a valuable tool to quantify recruitment and overinflation during HFOV. Additional studies are needed to better characterize the specific effects of HFOV on lung volume and morphology.


Reaction of a (Salen)ruthenium(VI) nitrido complex with thiols. C-H bond activation by (Salen)ruthenium(IV) sulfilamido species.
The reaction of [Ru(VI)(N)(L)(MeOH)](PF(6)) [1; L = N,N'-bis(salicylidene)-o-cyclohexyldiamine dianion] with a stoichiometric amount of RSH in CH(3)CN gives the corresponding (salen)ruthenium(IV) sulfilamido species [Ru(IV){N(H)SR}(L)(NCCH(3))](PF(6)) (2a, R = (t)Bu; 2b, R = Ph). Metathesis of 2a with NaN(3) in methanol affords [Ru(IV){N(H)S(t)Bu}(L)(N(3))] (2c). 2a undergoes further reaction with 1 equiv of RSH to afford a (salen)ruthenium(III) sulfilamine species, [Ru(III){N(H)(2)S(t)Bu}(L)(NCCH(3))](PF(6)) (3). On the other hand, 2b reacts with 2 equiv of PhSH to give a (salen)ruthenium(III) ammine species [Ru(III)(NH(3))(L)(NCCH(3))](PF(6)) (4); this species can also be prepared by treatment of 1 with 3 equiv of PhSH. The X-ray structures of 2c and 4 have been determined. Kinetic studies of the reaction of 1 with excess RSH indicate the following schemes: 1 --> 2a --> 3 (R = (t)Bu), 1 --> 2b --> 4 (R = Ph). The conversion of 1 to 2 probably involves nucleophilic attack of RSH at the nitrido ligand, followed by a proton shift. The conversions of 2a to 3 and 2b to 4 are proposed to involve rate-limiting H-atom abstraction from RSH by 2a or 2b. 2a and 2b are also able to abstract H atoms from hydrocarbons with weak C-H bonds. These reactions occur with large deuterium isotope effects; the kinetic isotope effect values for the oxidation of 9,10-dihydroanthracene, 1,4-cyclohexadiene, and fluorene by 2a are 51, 56, and 11, respectively.


[Molecular mechanisms of progression in human hepatocarcinogenesis].
Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide with poor prognosis. Based on high-throughput screening technology, we and others have identified factors and pathways that are pivotal for tumor progression including transcription factors and microtubule-interacting proteins. In addition, aberrant activation of the IGF signalling pathway is frequently observed in HCCs which is predominantly based on high level expression of its ligand IGF-II. Because protumorigenic effects of IGF-II such as proliferation, anti-apoptosis, and migration are transmitted through its receptor IGF-1R, selective inhibition of this tyrosine kinase by small molecule compounds might reduce IGF-II-driven tumor growth. Indeed, administration of IGF-1R-selective inhibitors reduces IGF-II-induced effects and was associated with a significant reduction of tumor growth in a xenograft transplantation model. In conclusion, the IGF-II/IGF-1R signalling pathway is critically involved in the regulation of tumor growth and tumor cell dissemination, representing a promising therapeutic target structure in the treatment of HCC.


Conductance volumetric model of an eccentrically positioned catheter within a three-compartment ellipsoidal ventricle.
This paper presents a mathematical model of the electric field generated and resistance measured by a conductance catheter within a three-compartment ellipsoidal approximation of a cardiac ventricle. The model is based on a novel combination of analytical and numerical techniques. The numerical component of the model predicts displacement of the catheter along the central longitudinal ventricular axis, as well as eccentric positions off that axis. The analytical component of the model enables interactive definition of model parameters during simulation. This versatile combination enables performance of validation studies that include simulations of various catheter movements within a ventricle of changing geometry. The results of our simulation studies agree with the results of previous investigators studying ex-vivo systems.


Genomic insights into the metabolism of 'Candidatus Defluviicoccus seviourii', a member of Defluviicoccus cluster III abundant in industrial activated sludge.
Filamentous cluster III Defluviicoccus (DF3) are known to proliferate and cause bulking issues in industrial wastewater treatment plants. Members of the genus Defluviicoccus are also known to exhibit the glycogen accumulating organism (GAO) phenotype, which is suggested to be detrimental to enhanced biological phosphorus removal (EBPR). Despite the reported negative impact members of the DF3 have on activated sludge wastewater treatment systems, limited research has focused on understanding the physiological traits that allow them to compete in these environments. In this study, a near complete genome of an abundant filamentous DF3 named 'Candidatus Defluviicoccus seviourii' was obtained from a full-scale sequencing batch reactor (SBR) treating winery wastewater. Annotation of the 'Ca. D. seviourii' genome revealed interesting metabolic features that help to understand the abundance of this microorganism in industrial wastewater treatment plants. Their potential for the storage of polyhydroxyalkanoates (PHA) is suggested to favour these organisms with the intermittent availability of carbon in these systems. An ability to fix nitrogen and take up urea may provide them with an additional advantage with the characteristically high carbon to nitrogen content of industrial waste. The genome and preliminary findings of this study provide a foundation for further research into these biotechnologically relevant organisms.


Adhesion molecules in lymphoma metastasis.
Recently, many surface proteins of lymphoid cells that mediate adhesion to other cells and extracellular matrix have been identified. Several of these cellular adhesion molecules (CAM) are also expressed by metastatic lymphoma cells and may mediate adhesion to tissue components during the metastatic process. Correlations observed between expression of certain CAM, like MEL-14 and CD44, and particular patterns of spread, support this notion, but conclusive evidence is scarce. We have used T-cell hybridomas to study the mechanisms of wide-spread lymphoid metastasis. The results obtained with this model are reviewed here. The advantages are that a large number of genetically similar cell lines can be generated, which can be grouped in large panels of highly invasive and non-invasive cells. Invasiveness of these cells in hepatocyte and fibroblast monolayers correlates with experimental metastasis. Lymphoid CAM that are potentially involved in metastasis are reviewed. Several of these CAM are not, or not consistently, expressed by the invasive T-cell hybridomas, indicating that they are not indispensable. Notably, some of the CAM involved in the onset of an immune response or in migration into inflamed tissues, like ICAM-1 and VLA-4, and the 'homing receptors' MEL-14 and LPAM-1 do not seem to be involved. CAM that are consistently expressed by the T-cell hybrids include LFA-1, the beta-1 integrin subunit CD29, CD31 (PECAM-1) and CD44 ('Hermes homing receptor'). We have generated considerable evidence that LFA-1 is required for efficient metastasis of T-cell hybrids, based on the behavior of LFA-1-deficient mutants and revertants. High levels of LFA-1 are required. The relevant counterstructure is probably ICAM-2 rather than ICAM-1. Preliminary results suggest that also a beta-1 integrin, possibly VLA-5, plays a role. Finally, we summarize evidence indicating that CD31 and CD44 are primary candidates for involvement in metastatic spread of T-cell hybridomas.


Efficacy of cobalt-60 radiation therapy for the treatment of nasal cavity nonkeratinizing squamous cell carcinoma in the dog.
The purposes of this study were to evaluate the efficacy of cobalt-60 radiotherapy in the treatment of nonkeratinizing squamous cell carcinoma of the nasal cavity in dogs and to compare this treatment group to historical controls. Six dogs with histopathologically confirmed nasal cavity nonkeratinizing squamous cell carcinoma were treated with cobalt-60 radiotherapy to a total dose of either 63 Gy or 54 Gy. Overall survival times ranged from 30 days to 330 days, with a median survival time of 165 days. Nasal cavity nonkeratinizing squamous cell carcinoma in the dog is an aggressive tumor that responds poorly to radiotherapy.


Multiple myeloma vs. breast cancer patients with bisphosphonates-related osteonecrosis of the jaws: a comparative analysis of response to treatment and predictors of outcome.
Multiple myeloma (MM) and breast cancer (BC) are the two most common diseases associated with bisphosphonates-related osteonecrosis of the jaws (BRONJ), for which different therapeutical approaches have been proposed. The aim of this study was to compare the clinical behaviour of BRONJ in patients with MM vs. BC and the time of healing in terms of clinical and symptomatological remission, following a standardized therapeutic protocol. Twenty-six BRONJ patients (13 men with MM and 13 women with BC) were prospectively enroled and treated with a specific systemic and topical antibiotic therapy. Several predictors of outcome were also evaluated. Nine patients (69.2%) with BC and 10 patients (76.9%) with MM progressed towards a complete clinical remission (CR) in a mean healing time of 183.3 days [SD: 113.7; 95% confidence interval (CI): 95.95-207.7] and 372.0 days (SD: 308.0; 95% CI: 151.7-592.3) (P = 0.776), respectively. The clinical improvement was statistically significant (P = 0.0013 and P = 0.0014), as well as the assessment of pain (P = 0.0015 and P = 0.0015), in MM and BC group, respectively. Cox regression analysis revealed that just triggering events (P = 0.036) were found to be significant predictors of outcome of BRONJ healing. Both groups of cancer patients experienced clinical and symptomatological remission regardless their malignancy, but BC patients earlier than MM patients.


Pulse oximetry: what the nurse needs to know.
Rationale and key points Measurement of peripheral oxygen saturation (SpO2) is used to identify early hypoxia in patients and evaluate the effectiveness of oxygen therapy. Nurses should be aware of the procedure for using a pulse oximeter to measure SpO2 levels and the normal range for SpO2 readings. » A pulse oximeter is used to measure SpO2 levels, and involves placing a probe on the patient's finger, toe or ear lobe. » A SpO2 level of less than 90% is a clinical emergency. If the SpO2 level is below 94%, the nurse should assume the patient is hypoxic until proven otherwise, and therefore they may require supplemental oxygen administration. » Nurses should be aware of the factors that might affect SpO2 readings, including anaemia, peripheral vasoconstriction, dark skin tone and skin discolouration.


Role of ventriculoperitoneal shunt valve design in the treatment of pediatric hydrocephalus--a single center study of valve performance in the clinical setting.
Previous studies have established risk factors for ventriculoperitoneal shunt failure in children. However, the role of valve type as a determinant of complications and outcome remains unclear. The aim of this study was to compare the fixed-pressure paediGAV and the programmable Codman Hakim valves in the clinical setting. We conducted a retrospective review of patients younger than 16 years who underwent primary implantation of a ventriculoperitoneal shunt with either valve type at our institution between January 2005 and December 2010. Shunt survival analyses were performed to identify variables associated with risk of shunt failure. Of the 44 patients in the paediGAV cohort, 50% reached the endpoint of shunt failure with a mean time to shunt failure of 7 months. The Codman Hakim cohort comprised 29 patients, of which 55% experienced shunt failure with a mean time to shunt failure of 8 months. Stratified analyses identified young age at implantation and posthemorrhagic hydrocephalus as risk factors for shunt failure. Shunt survival analysis revealed no significant difference with regard to valve type. This study confirmed important risk factors for shunt failure in children. Despite certain limitations and biases, similar findings for both valves examined in the clinical setting were obtained. Thus, valve type does not seem to influence risk of shunt failure. Prospective, randomized, and controlled trials are required to validate these results.


LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy.
Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation and abnormalities in myocyte contractile function. The improved LV pump function with early recovery from tachycardia-induced DCM was mediated by LV hypertrophy and a subsequent reduction in LV wall stress rather than a normalization of LV geometry and myocyte contractile function.


Biotransformation of halogenated nonylphenols with sphingobium xenophagum bayram and a nonylphenol-degrading soil-enrichment culture.
When discharged in chlorinated wastewater, alkylphenol ethoxylate metabolites (APEMs) are often discharged in halogenated form (XAPEMs, X = Cl, or Br). The potential environmental impact of XAPEM release was assessed by studying the biotransformation of halogenated nonylphenol by Sphingobium xenophagum Bayram and a soil-enrichment culture. S. xenophagum Bayram transformed chlorinated nonylphenol (ClNP) slowly and nearly completely to form nonyl alcohol; the monobrominated nonylphenol (BrNP) and dibrominated nonylphenol were transformed cometabolically with nonylphenol (NP) as the primary substrate. The presence of either ClNP or BrNP in the S. xenophagum Bayram cultures retarded the transformation of nonhalogenated NP. NP-degrading soil cultures transformed nonhalogenated NP to a mixture of nonyl alcohols but were not capable of transforming either ClNP or BrNP. The presence of either ClNP or BrNP retarded the transformation of nonhalogenated NP in the soil cultures, as was observed in S. xenophagum Bayram cultures. Predicting the environmental fate of alkylphenol ethoxylate residues requires considering APEM halogenation during effluent chlorination and inhibitory effects as well as the refractory nature of halogenated metabolites.


Administrating incompatible drugs by a retrograde intravenous infusion system.
Use of a retrograde infusion system for concurrent intravenous administration of two incompatible drugs separated by a barrier fluid was studied. Four different barrier fluids (5% dextrose injection, 10% dextrose injection, 0.9% sodium chloride injection, and sterile water for injection) were used to separate sodium bicarbonate and calcium chloride. The primary infusion was 5% dextrose injection. The delivery system was visually inspected for formation of precipitate (calcium carbonate) upon addition of the two drug solutions and 2 ml of the barrier fluid. If precipitation occurred, the procedure was repeated, increasing the volume of barrier fluid incrementally until no precipitate could be seen. If no precipitate was seen with the initial 2 ml of barrier fluid, the volume of barrier fluid was decreased until precipitation occurred. These procedures were repeated for each barrier fluid at flow rates of 5-20 ml/hr for 90 minutes. The minimum volume of barrier fluid needed to prevent precipitate formation was determined in triplicate at each flow rate. The minimum volume of barrier fluid that prevented precipitate formation was approximately 2.0 ml. This volume did not differ significantly by barrier solution type or by flow rate. Sodium bicarbonate and calcium chloride can be administered concurrently by the retrograde intravenous method without visual incompatibility when separated by greater than or equal to 2 ml of barrier fluid, and this method can probably be used for administration of other potentially incompatible drugs.


Mode of action of delta-9-tetrahydrocannabinol on hypothalamo-pituitary function in adult female rats.
Administration of delta-9-tetrahydrocannabinol (delta 9-THC) to pro-oestrous rats (5 mg/kg and 10 mg/kg, i.p. for 10 days) decreased the hypothalamic LH-RH content. Serum prolactin levels were reduced but serum LH and FSH and pituitary hormone content were similar to values in dioestrous rats. It is suggested that delta 9-THC acts primarily on the hypothalamus.


High prevalence of fibromyalgia among Israeli school teachers.
Fibromyalgia syndrome (FM), characterised by widespread pain and fatigue, has frequently been associated with stress in various models, including workplace related stress. In the current study we have evaluated the prevalence of FM symptoms among Israeli school teachers and have attempted to correlate such symptoms with work-related stress. Individuals, all currently employed as school teachers in Israel, were recruited to the study. Participants were asked to answer a questionnaire evaluating symptoms of FM, based on the current diagnostic criteria, which include the widespread pain index (WPI) and the symptom severity scale (SSS). Participants were further questioned regarding stressful experiences during their work and about post-traumatic symptoms as well as regarding work performance and motivation. 321 participants were recruited (79.4% female, 20.6 male). 30 individuals (9.3%) of the sample fulfilled current criteria for a diagnosis of FM, with a rate of 11.4% among females and 1.5% among males. While specific symptoms such as fatigue and irritable bowel symptoms were negatively correlated with work performance, no significant difference was found between teachers with or without fibromyalgia regarding work attendance and performance. FM symptoms were strongly correlated with work-related stress and were strongly correlated with post-traumatic stress disorder (PTSD) related symptoms. Motivation to work was significantly lower among teachers fulfilling FM criteria, but other performance-related parameters did not differ between teachers fulfilling or not fulfilling FM criteria. Fibromyalgia symptoms are highly prevalent among Israeli school teachers, and may be related to stress encountered in the classroom. These results are relevant both for physicians treating individuals involved in educational careers as well as for educators and decision-makers involved in planning and managing educational strategies.


Evaluation of butorphanol-azaperone-medetomidine in captive cheetah (Acinonyx jubatus) immobilization.
The butorphanol-azaperone-medetomidine fixed-dose combination (BAM, respectively, 30-12-12 mg mL-1) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive cheetahs (Acinonyx jubatus). Prospective, clinical trial. Twelve cheetahs (six males and six females, weighing 37-57 kg) housed in enclosures, were immobilized at Hoedspruit Endangered Species Centre in the Republic of South Africa. BAM volume dose rate was 0.009-0.014 mL kg-1 (mean ± standard deviation 0.010 ± 0.001 mL kg-1). Total dose in all animals was 0.5 mL. The actual doses were as follows: butorphanol (0.29 ± 0.04 mg kg-1), azaperone (0.12 ± 0.01 mg kg-1) and medetomidine (0.12 ± 0.01 mg kg-1). Physiologic variables and quality of immobilization were recorded every 5 minutes beginning at 15-20 minutes after darting. Arterial blood samples were collected three times at 20, 30 and 40 minutes after darting from all animals for analysis of blood oxygenation and acid-base status. The inductions were calm and smooth and mean induction time was 4.0 ± 1.1 minutes. Heart rate (50 ± 9 beats minute-1) and respiratory frequency (20 ± 3 breaths minute-1) were stable throughout immobilization. The recovery time after reversing with naltrexone and atipamezole was 9.1 ± 3.6 minutes. and clinical relevance BAM proved to be a reliable and cardiovascular stable drug combination for immobilization of cheetahs.


Skeletal muscle and hepatic insulin signaling is maintained in heat-stressed lactating Holstein cows.
Multiparous cows (n=12; parity=2; 136±8 d in milk, 560±32kg of body weight) housed in climate-controlled chambers were fed a total mixed ration (TMR) consisting primarily of alfalfa hay and steam-flaked corn. During the first experimental period (P1), all 12 cows were housed in thermoneutral conditions (18°C, 20% humidity) with ad libitum intake for 9 d. During the second experimental period (P2), half of the cows were fed for ad libitum intake and subjected to heat-stress conditions [WFHS, n=6; cyclical temperature 31.1 to 38.9°C, 20% humidity: minimum temperature humidity index (THI)=73, maximum THI=80.5], and half of the cows were pair-fed to match the intake of WFHS cows in thermal neutral conditions (TNPF, n=6) for 9 d. Rectal temperature and respiration rate were measured thrice daily at 0430, 1200, and 1630 h. To evaluate muscle and liver insulin responsiveness, biopsies were obtained immediately before and after an insulin tolerance test on the last day of each period. Insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT/protein kinase B (AKT), and phosphorylated AKT (p-AKT) were measured by Western blot analyses for both tissues. During P2, WFHS increased rectal temperature and respiration rate by 1.48°C and 2.4-fold, respectively. Heat stress reduced dry matter intake by 8kg/d and, by design, TNPF cows had similar intake reductions. Milk yield was decreased similarly (30%) in WFHS and TNPF cows, and both groups entered into a similar (-4.5 Mcal/d) calculated negative energy balance during P2. Insulin infusion caused a less rapid glucose disposal in P2 compared with P1, but glucose clearance did not differ between environments in P2. In liver, insulin increased p-AKT protein content in each period. Phosphorylation ratio of AKT increased 120% in each period after insulin infusion. In skeletal muscle, protein abundance of the IR, IRS, and AKT remained stable between periods and environment. Insulin increased skeletal muscle p-AKT in each period, but the phosphorylation ratio (abundance of phosphorylated protein:abundance of total protein) of AKT was decreased in P2 for TNPF animals, but not during WFHS. These results indicate that mild systemic insulin resistance during HS may be related to reduced nutrient intake but skeletal muscle and liver insulin signaling remains unchanged.


Perception of emotion and neurocognitive functioning in schizophrenia: what's the link?
In schizophrenia, relatively little is known about the association between deficits in emotion perception and basic neurocognitive functioning. The present study examined perception of emotion and a discrete set of neurocognitive functions in 28 treatment-resistant schizophrenic patients. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception test (brief interpersonal vignettes presented on videotape). Measures of neurocognitive functioning were selected based on hypothesized relationships to perception of emotion. These measures included: (a) Span of Apprehension task, a measure of early visual processing, visual scanning, and iconic read-out; (b) Degraded-Stimulus Continuous Performance Test, a measure of visual vigilance; and (c) Digit Span Distractibility Test, a measure of immediate or working memory. Among these measures, performance on the Span of Apprehension strongly correlated with performance on all three emotion perception tasks. The associations between perception of emotion and the other two measures were in the same direction, but were significantly smaller than those of the Span of Apprehension. These findings implicate the importance of early perceptual processing (i.e. visual scanning) in the ability of schizophrenic individuals to perceive emotion.


Clinical evaluation of a peptide-ELISA based upon N-terminal B-cell epitope of the VapA protein for diagnosis of Rhodococcus equi pneumonia in foals.
A total of 227 field samples from naturally exposed foals aged between 3 weeks and 6 months were used in an evaluation of a peptide-based enzyme-linked immunosorbent assay (ELISA) for diagnosis of Rhodococcus equi infection. A biotinylated peptide derived from the virulence-associated protein A (VapA) of R. equi, a horse pathogen, was synthesized and designated as PN11-14. The peptide corresponds to the N-terminal B-cell epitope TSLNLQKDEPNGRASDTAGQ of the VapA protein. Based upon a serum immunoglobulin (Ig)G titre of 512 as a positive cut-off value for the R. equi infection, the ELISA provided the overall sensitivity of 47.62%, specificity of 69.67% and an accuracy of 59.47% with a positive predictive value of 57.47% for true R. equi pneumonia. The assay was improved by detecting VapA-specific IgGb antibodies against N-terminal B-cell epitope of the VapA protein rather than IgG antibodies. The VapA-IgGb ELISA showed the overall sensitivity of 70.47%, specificity of 72.13% and accuracy of 71.36% with a positive predictive value of 68.52%. Diagnosis of R. equi disease in 6-week-old foals showed that the VapA-IgGb ELISA provided an increasing trend (P=0.0572) in sensitivity of 82.4% in comparison with the VapA-IgG ELISA which showed the sensitivity of 58.8%. However, differences in specificity of both tests were statistically insignificant (P=0.357) as analysed by the McNemar test. These results indicated that detection of VapA-specific IgGb antibodies may be a better predictor of R. equi disease in foals.


Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China.
To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.


Prognostic factors, morbidity and mortality in pancreatic trauma: a critical appraisal of 432 consecutive patients treated at a Level 1 Trauma Centre.
This large retrospective observational cohort study evaluated prognostic factors, 30-day morbidity and mortality and complications related to the pancreas in patients who had sustained pancreatic injuries. The records of 432 consecutive patients treated for pancreatic injuries at an urban Level 1 Trauma Centre in Cape Town between January 1982 and December 2012 were reviewed. Primary endpoints were postoperative morbidity and death. Bivariate and multivariate logistic regression analyses were used to assess significant predictors of morbidity and mortality. Overall mortality in 432 patients [394 men, median age 26, median RTS 7.8] was 15.7% and morbidity 66%. Bivariate logistic regression analysis showed that nine factors, age, RTS, presence of shock, need for a transfusion, volume of blood transfused, damage control surgery, AAST grade of pancreatic injury, an associated vascular injury and a repeat laparotomy were significant predictors of morbidity. In the final multivariate logistic regression analysis model however only two variables, AAST grade of pancreatic injury and a repeat laparotomy were significant predictors of morbidity. When factors associated with mortality were considered, logistic regression analysis found that 11 variables, age, RTS, the presence of shock, patients who required a major blood transfusion, the median number of units transfused, the need for a damage control laparotomy, AAST grade 3, 4, 5 pancreatic injuries, associated vascular injuries, the number of associated injuries, postoperative complications and days in ICU were significant. However in the final stepwise multivariate logistic regression analysis model only five variables, age, shock, median number of units transfused and the presence of associated complications were significant factors associated with mortality. Morbidity was 64% and AAST grade of pancreatic injury and a repeat laparotomy were significant predictors of morbidity. Overall mortality was 15.7%. Most deaths were due to associated injuries and were unrelated to the pancreatic injury. Five variables, age, shock, median number of units transfused and the presence of associated complications were significant factors associated with mortality. These data indicate that the magnitude of blood loss and haemorrhagic shock are primary determinants for survival and that urgent reversal of shock and control of bleeding are essential to reduce mortality in this cohort of patients.


Factors associated with continued participation in mammography screening.
Relatively little is known about factors that predict ongoing participation in mammography screening at regular intervals. Members of managed care plans have access to this preventive service; yet, many still do not receive it routinely. Using administrative data from HIP Health Plan of New York, a group model HMO, 24,215 women ages 50-80 years identified as having a screening mammogram during the baseline period were followed for 2 years to determine demographic and utilization factors that might be related to having a subsequent mammogram within the recommended time interval. Of the 24,215 women with an index mammogram, 71.8;pc had a subsequent screening mammogram within 2 years. Women ages 65-74 years and those with Medicare coverage had the highest mammogram rates among the age and coverage categories. Number of primary care and gynecology physician visits was strongly related to having a subsequent mammogram. The average (mean) time between index and subsequent mammogram was 14.4 months. The significance of health plan visits in subsequent mammography underscores the importance of physician-patient communication in a managed care plan and the integration of health plan members into the HMO delivery system. Even in this environment with equal access for all types of coverage, Medicaid members were less likely to receive this preventive service.


Nanoemulsion-templated polylelectrolyte multifunctional nanocapsules for DNA entrapment and bioimaging.
The emerging field of bionanotechnology aims at advancing colloidal and biomedical research via introduction of multifunctional nanoparticle-based containers intended for both gene therapy and bioimaging. In the present contribution we entrapped the model genetic material (herring testes DNA) in the newly-designed non-viral vectors, i.e., multifunctional nanocapsules obtained by layer-by-layer (LbL) adsorption of DNA and oppositely charged polysaccharide-based chitosan (CHIT) on the nanoemulsion core, loaded by IR-780 indocyanine (used as the fluorescent marker) and stabilized by gemini-type ammonium salts: N,N,N',N'-tetramethyl-N,N'-di(dodecyl)-ethylenediammonium bromide, d(DDA)PBr and N,N,N',N'-tetramethyl-N,N'-di(dodecyl)-butylenediammonium d(DDA)BBr. Ternary phase diagrams of the surfactant-oil-water systems were determined by titration method. Then, the stability of the nanoemulsions obtained with IR-780 solubilized in the oleic acid (OA) or isopropyl myristate (IPM) phase was evaluated by backscattering (BS) profiles and ζ-potential measurements. In the next step, CHIT and DNA layers were subsequently deposited on the kinetically stable nanoemulsion cores. The IR-780-loaded nanocarriers covered by (DNA/CHIT)4 bilayers shown the high ζ-potential value (about +43mV provided by Doppler electrophoresis), the size <120nm and the spherical shape as analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). Finally, the long-lasting nanosystems were subjected to in vitro biological studies on human cancer cell lines - doxorubicin-sensitive breast (MCF-7/WT), epithelial lung adenocarcinoma (A549) and skin melanoma (MEWO). Biological response of the cell culture was expressed as cytotoxic activity evaluated by MTT-based proliferation assay as well as bioimaging of intracellular localization of IR-780 molecules loaded in the multilayer DNA-deposited nanocontainers - provided by confocal laser scanning microscopy (CLSM) and total internal reflection fluorescence microscopy (TIRFM). Our results demonstrate that the fabricated oil-core CHIT-coated nanocapsules stabilized by both d(DDA)PBr and d(DDA)BBr surfactants are promising as multifunctional nanocarriers for DNA delivery and cancer diagnostics.


Serum miR-20a and miR-486 are potential biomarkers for discriminating colorectal neoplasia: A pilot study.
Recent advances in circulating microRNAs (miRNAs) as noninvasive biomarkers have provided promising prospect in detecting colorectal cancer (CRC). However, the capability of miRNAs for detecting colorectal neoplasia (CRN, including precancerous lesions and curable stage CRCs) remains unclear. This study aimed to identify the potential of serum miRNAs (miR-20a, miR-486, miR-92a, and miR-135b) selected from the literature for discriminating CRN patients. The serum samples from 46 CRN patients and 33 healthy controls were analyzed with quantitative reverse transcription-polymerase chain reaction. Serum miR-20a and miR-486 were significantly downregulated in CRN patients compared to that of in healthy controls (fold change = 0.697 and 0.696, P = 0.01 and 0.05, respectively). The serum level of miR-92a was not significantly different between two groups, while miR-135b level in serum was too low to be accurately quantified. In addition, serum miR-486 level was much more downregulated in tubulovillous adenoma and high-grade intraepithelial neoplasia patients than that of in healthy controls. For miR-20a and miR-486, the area under the receiver operating characteristic curve for discriminating CRN patients were 0.676 and 0.629, respectively, while their combined value was 0.698. No significant correlation was observed between miR-20a and miR-486 serum levels with age, gender, location, or lesion size. The results suggested that serum miR-20a and miR-486 could be potential noninvasive biomarkers for identifying CRN patients.


Isolation of plasma membranes and Golgi apparatus from a single chicken liver homogenate.
Chicken liver plasma membranes, minimally contaminated with Golgi apparatus-derived vesicles, were prepared from a low-speed (400 g) pellet by means of flotation in isotonic Percoll solution, followed by a hypotonic wash and flotation in a discontinuous sucrose gradient. Based on the analysis of suitable marker enzymes, alkaline phosphatase and alkaline phosphodiesterase, two plasma membrane fractions were isolated with enrichments, depending on the equilibrium density and marker of 28-97 and with a total yield of 4-5%. Golgi apparatus fractions were prepared by flotation of microsomes, obtained from the same homogenate as the low-speed pellet, in a discontinuous sucrose gradient. The trans-Golgi marker galactosyltransferase was 27-fold enriched in a fraction of intermediate density (d=1.077-1.116 g/ml). Approximately 12% of galactosyltransferase was recovered in the membranes equilibrating d=1.031-1.148 g/ml. Contamination with plasma membrane fragments was low in the light (d=1.031-1.077 g/ml) and intermediate density Golgi vesicles. The isolation of purified plasma membranes and Golgi vesicles from one liver homogenate will enable future studies on receptor cycling between these cell organelles.


Videogame Mechanics in Games for Health.
Game mechanics have been identified as "methods invoked by agents for interacting with the game world."(1) They are elements of game play that provide a primary source of interactivity and structure how videogames proceed. Many kinds of game mechanics have been generated. Some provide fun or enjoyment, others may provide excitement or even suspense (i.e., emotional aspects of game play), whereas some are guided by principles of behavior change theory. Game mechanics that succeed in off-the-shelf entertainment videogames, however, may not work in serious games, such as games for health (G4H). Although game mechanics are key to a serious videogame's success, maintaining a balance between the serious intent of the game while keeping it fun, there has been little attention to game mechanics in the academic G4H literature. Several eminent games for health developers (academics and nonacademics) were asked to share their experiences in regard to game mechanics in the serious videogames they have developed.


Dimer-to-tetramer assembly of Lac repressor involves a leucine heptad repeat.
The C-terminus of Lac repressor is responsible for the formation of repressor tetramers from active dimers. If properly grafted, the C-terminus of Lac repressor (amino acids 331 to 360) converts Gal repressor dimers into tetramers. Amino acids 342 to 356 of Lac repressor contain a 4-3 hydrophobic repeat of four leucines and one valine. Systematic amino acid replacements of all residues in this region show that the protein-protein interaction between repressor dimers depends mainly on the hydrophobic residues of the 4-3 repeat, which is constitutive for coiled coils. Thus the tetramerization site of Lac repressor resembles the leucine zipper motif found in a family of eukaryotic transcription factors.


Evidence of short-term adaptation to microgravity of neuromuscular synergy during a whole body movement.
Human, like any other animal systems, moves in the terrestrial gravity field and must learn gravity-related motor strategies during his ontogenetic development. Considering continuous gravity action upon body segments, movement involves particular muscle activation patterns depending on body orientation to gravity. Gravitational-altered environments provided by parabolic flight or orbital space mission offer a great opportunity to investigate how gravity is taken into account in posture and movement planning. Indeed, in a context where the mechanical constraints are modified, movement execution involves that new muscular activity have to be produced. Almost, only few studies in microgravity environment are included electromyographic analysis and this parameter is generally used only to confirm modification of the muscular activation patterns. This study is focused to analyse the adaptation capacity of the brain to a modified gravitational environment. In this aim, EMG activity have been recorded during a whole body movement execution in both normo- and microgravity environment during parabolic flight. This procedure allowed us to analyse the EMG patterns recorded during the very first moments of weightlessness. In this study are reported the results of this analyse.


Median Arcuate Ligament Syndrome - Literature Review and Case Report.
Median arcuate ligament syndrome (MALS) or Dunbar syndrome is a rare clinical entity characterized by celiac trunk compression by median arcuate ligament and variable gastrointestinal symptoms (postprandial epigastric pain, nausea, weight loss, anorexia and diarrhea). However, some degree of radiographic compression is observed in 10%-24% of asymptomatic patients. Besides the extrinsic vascular compression, MALS has a multifactorial etiology and it has been suggested as a neurogenic disease resulting in altered sensation and pain from the somatic nerves in the splanchnic plexus. MALS is a diagnosis of exclusion, so other causes must be excluded. Treatment options include release of median arcuate ligament (open, laparoscopic or robot-assisted) and open vascular reconstruction. Endovascular treatment is currently used only as adjuvant procedure after surgical approach, in refractory cases with residual stenosis of celiac trunk. To report a case of MALS and to review current literature. The authors report a clinical case and present a literature review using PubMed with the terms "median arcuate ligament", "Dunbar syndrome" and "MALS treatment" as major topics. The bibliography of relevant articles has been checked to identify other significant papers. A 34-year-old woman, previously healthy, recurred to a General Practitioner with a recurrent epigastric pain, exacerbated by ingestion, without relieving factors, in the previous 6 months. Patient also reported anorexia and unprovoked weight loss of 8Kg over 3 months. Physical examination was normal. Other gastrointestinal pathologies were ruled out. Computed Tomography Angiography (CTA) abdomen revealed a focal 80% stenosis of the celiac trunk, located 8mm from its origin in aorta and a post- -stenotic enlargement of 9mm. An open decompression of the celiac trunk was performed. Through an 8cm median supraumbilical laparotomy, supraceliac abdominal aorta was approached. The compressive band across the celiac trunk was identified and cut. Further dissection was performed until the celiac artery became completely exposed and its branches identified. The postoperative period was uneventful and the patient was discharged 5 days later, with normal gastrointestinal transit and without recurrence of the abdominal pain. 1 month later, the patient remained asymptomatic. A long-term follow-up with annual duplex scan and clinical evaluation must be done, in order to evaluate the need of a revascularization due to persistent stenosis or aneurysmal degeneration. MALS diagnostic and therapeutic approach must be patient focused, bearing in mind the multiple clinical presentation and treatment options. Open surgical decompression of median arcuate ligament is the base of therapy.


Deletion of alloantigen-activated cells by aminolevulinic acid-based photodynamic therapy.
Protoporphyrin IX (PpIX), an endogenously synthesized photosensitizer, can transiently accumulate in activated lymphocytes following administration of the heme precursor 5-aminolevulinic acid (ALA). One possible mechanism of this in lymphocyte accumulation is that actively dividing cells use intracellular iron stores for cytochrome and DNA synthesis and thus do not inactivate PpIX, the photoactive precursor of heme, by iron incorporation. This selective accumulation in activated cells should allow targeting by photodynamic therapy (PDT). To determine the effect of this accumulation, we studied PDT effects on the in vitro correlate of transplantation rejection: the one-way mixed lymphocyte reaction (MLR). Selective phototoxicity was determined by photoirradiating ALA-treated, MLR-activated cells and measuring subsequent stimulation either in a secondary MLR or with phytohemagglutinin (PHA). We found that proliferation of MLR-activated lymphocytes incubated with ALA and treated with light was only 12-20% of controls (ALA+, no light) after rechallenge with the stimulator cells (P < 0.05), although their response to nonspecific PHA stimulation was similar to controls. Thus alloantigen-specific depletion was shown. The data suggest a role for ALA-PDT in the treatment of diseases that require the selective elimination of activated lymphocytes and possibly as an immunomodulator.


The marital system of the hysterical individual.
The purpose of the present article is to supplement the considerable body of clinical literature that focuses on hysterical behavior from an individual perspective. Based on findings from a total sample of 16 couples, this paper accomplishes this task in a threefold manner. First, the characteristic type of individual who selects and is selected by the hysterical individual as a life partner is described. Second, the type of relationship these two individuals typically develop, which promotes and reinforces severely maladaptive behavior on the part of both is delineated. Third, a number of specific recommendations regarding psychotherapy for this type of relationship are proffered.


Carbon-14 in patagonian tree rings.
The radiocarbon activity found in tree rings from southern Argentina shows secular fluctuations which are synchronous with and of the same amplitude as those known for the Northern Hemisphere. Comparable measurements indicate that the activity in Patagonian trees is about five per mil lower than in European trees.


Factors associated with weight change among clients of a residential weight control program indicating binge and nonbinge traits.
The long-term effects of a 12- and 26-day residential weight control program on weight change were determined in 187 men and women, 1 to 5 years after treatment. Subjects completed a paper/pencil questionnaire assessing current diet, weight control techniques, exercise behaviors, behavior modification techniques, binge eating, and dieting behavior. General linear modeling was used to investigate the association between behaviors maintained posttreatment and current weight among subjects who demonstrated behaviors indicative of binge traits (BT) and nonbinge traits (NBT). Results indicate that dissimilar variables are predictive of weight change in the BT and NBT groups. Engaging in exercise behaviors and reduced attempts at dieting lead to greater weight loss in NBT individuals. The use of preplaning techniques was found to be indicative of greater weight loss in BT individuals. These findings suggest the importance of identifying individuals who indulge in binge-eating behaviors prior to intervention in order to deliver the appropriate treatment methods.


A breast cancer screening program in a community hospital.
Breast cancer screening continues to be underutilized in the United States. The National Cancer Institute has set a goal of increasing screening by the year 2000. The American Cancer Society wants to identify programs that target asymptomatic women and economically disadvantaged women. The purpose of this study was to develop, implement and evaluate a comprehensive breast cancer screening program for women in a community setting. One case of infiltrating ductal carcinoma was detected from the 144 women who participated in the study. Following the educational component, the post test demonstrated a significant increase (p less than 0.01) in the women's awareness of breast cancer. Additionally, 100% of the women were able to demonstrate breast self examination to an oncology nurse after the educational component of the study. The majority of the women who participated were not economically disadvantaged which sheds new light on the scope of the problem of taking care of the unmet cancer needs of the disadvantaged through outreach programs. However 27% of the women had a household income less than $10,000 with 19% of the women having no insurance and 7% having Medicare/Medicaid. The results of this study could help future programs in bringing breast cancer screening to women in the community setting.


Inhibition of glucose trimming by castanospermine results in rapid degradation of unassembled major histocompatibility complex class I molecules.
The CMT-cKd1 cell line provides a system for studying the initial processing steps of N-linked oligosaccharides as these cells have been shown to produce major histocompatibility complex (MHC) class I molecules which, due to a defect in assembly, recycle between the endoplasmic reticulum and a pre-Golgi compartment, failing to reach the cell surface (Hsu, V.W., Yuan, L. C., Nuchtern, J. G., Lippincott-Schwartz, J., Hämmerling, G. J., and Klausner, R. D. (1991) Nature 352, 441-444). In the present study we observed that when the MHC class I heavy chain of these CMT cells was pulse-radiolabeled with [35S]methionine in the presence of the glucosidase inhibitor, castanospermine (CST), it underwent a rapid degradation during a 60-min chase, in contrast to control cells in which it remained stable during that period. The CST-promoted instability of the MHC molecule appeared to be specific, as it did not occur when 1-deoxymannojirimycin, an inhibitor of mannosidase, was added to the cells. Although endomannosidase was found to be present in the CMT cells, the electrophoretic mobility of the MHC heavy chain produced in the presence of CST indicated that deglucosylation through the alternate route provided by this enzyme did not occur. Furthermore, gamma-interferon did not prevent the rapid disappearance of the MHC molecule, although it brought about entry of this glycoprotein into the secretory pathway in cells incubated without CST. The results of our studies suggest that retention of glucose on N-linked oligosaccharides may under certain circumstances provide a signal for pre-Golgi protein degradation.


Residual stumps associated with inguinal varicose vein recurrences: a multicenter study.
It is unclear whether a residual sapheno-femoral stump left in place after stripping of the great saphenous vein can contribute to the formation of late inguinal varicose vein recurrence. In order to obtain information about the time course of recurrence development, patients with histologically proven residual stumps were recruited and asked about the interval between the initial operation and the first clinical signs of varicose vein recurrence. A multi-centre study involving 7 centres was conducted amongst patients undergoing redo-surgery for inguinal varicose vein recurrences. The sapheno-femoral stumps resected during the redo-surgery were classified histologically. Patients with a proven long residual sapheno-femoral stump were asked to describe the first signs of varicose vein recurrence with the help of a standardised questionnaire. From these data the symptom-free interval, consisting of the time frame between the initial operation and the first signs of recurrence, was determined. In 279 legs of 251 patients a long residual sapheno-femoral stump was present. Most patients had experienced a symptom-free interval after the initial operation with a mean duration of 7.4 S.D. 5.5 years. Recurrent varicose veins became apparent after a mean time interval of 6.3 S.D. 5.3 years and congestion symptoms occurred after a mean interval of 8.5 S.D. 5.7 years. In patients with symptomatic groin recurrences, a long residual sapheno-femoral stump was found in about two thirds of cases. The first clinical signs of varicose vein recurrence can be expected 7-8 years after the initial treatment at the earliest. Long term follow up is required reliably to asses the outcome of treatment for varicose veins.


[Sleep-wake complaints in Parkinson's disease].
We analyzed the questionnaires concerning sleep-wake complaints in 1,575 Parkinsonian patients and 2,509 controls of 945 office workers and 1564 seniors living at home. The questionnaire included 20 contents. The Parkinsonian patients complained of sleep-wake disturbances more frequently than the controls in initiation disturbance, frequent awakenings in night, early morning awakening, day time sleepiness, usage of sleep pills, parasomnias, restless legs symptoms, nocturnal myoclonus, snoring, apnea episodes and dyspnea in night (chi-square method). The incidences of restless legs symptoms and nocturnal myoclonus increased significantly with worsening of physical symptoms in the Parkinsonian patients (p less than 0.01).


Phase relations between rhythmical movements and breathing in wind instrument players.
In 18 healthy age- and sex- matched controls and 13 patients with Wilsons disease (18-50 years) under continuous copper chelating therapy sinusoidal forearm movements of a given target rates (target rates: 0.2, 0.3, 0.4, 0.5, 0.6 Hz) as well as breathing movements were recorded by means of a goniometer and a breathing girdle in parallel. Additionally, controls and patients had to perform spontaneous forearm movements at their most comfortable rate. The percentage of time during which forearm and breathing movements were coupled was significantly reduced in the patients. With increasing target rate the mean breathing rate significantly increased in the controls but not in the patients. Furthermore, the variability of breathing rate significantly increased in the patients but not in the controls. These two factors probably caused that the coupling of breathing and extremity movements was significantly reduced in the patients.


Mechanisms of oncogene-mediated alterations in metastatic ability.
Transfected ras oncogenes have been shown to induce metastatic properties in some cells. This altered behavior is likely due to changes in ras-mediated signal transduction pathways, resulting in altered expression of genes important to metastasis. Clarification of the mechanisms by which ras is able to induce metastatic ability in model systems will improve our understanding of tumor progression, even in those cells in which ras activation has not been implicated. Many of the consequences of ras expression also have been detected in cells that have become metastatic in the absence of altered ras, suggesting that there is a set of common changes that can lead to metastasis, with multiple signals capable of eliciting these changes. We have identified several changes in metastatic, ras-transformed NIH 3T3 cells that may contribute to their increased malignancy, including expression of proteolytic enzymes and their inhibitors, and adhesive and calcium-binding proteins. Not all cells, however, respond in this way to expression of oncogenic ras. We have found that murine LTA cells, which are tumorigenic but nonmetastatic, are ras resistant and remain nonmetastatic when expressing high levels of transfected ras, in contrast to NIH 3T3 cells, which are ras sensitive and become both tumorigenic and metastatic in response to comparable levels of ras. LTA cells differ in their patterns of gene expression in response to ras when compared with NIH 3T3 cells, suggesting that the two cell lines process the ras signal differently. Here we review our results with ras-transfected NIH 3T3 and LTA cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute appendicitis: a clinical pattern in Port Harcourt Nigeria.
A retrospective study of 201 patients, 152 with simple and 49 with complicated, appendicitis is presented. Diagnosis of simple acute appendicitis was made on symptoms of abdominal pain, anorexia, nausea and vomiting, together with rebound abdominal tenderness and not on white blood cell count. Normal white blood cell count was found in 80.3% cases of simple acute appendicitis while elevated white cell count was associated with 85.7% of complicated appendicitis. There was no mortality in 152 patients who had appendectomies for uncomplicated acute appendicitis, but the mortality rate in the 49 patients with complications was 12.2%. This was responsible for the overall mortality rate of 3% for all appendectomies in this report. Complicated appendicitis in this review was largely due to pre-admission delays and the ingestion of strong cathartics, both of which could not be influenced by surgeons.


The efficacy of gamma knife radiosurgery alone as a primary treatment for intracranial dural arteriovenous fistulas.
The application of gamma knife radiosurgery (GKRS) alone has been expanded for dural arteriovenous fistulas (DAVFs). However, a standardized protocol delineating the appropriate circumstances for GKRS alone in cases of DAVF has yet to be determined. The purpose of this study was to report a single center's treatment algorithm for GKRS alone as a primary treatment for intracranial DAVFs and assess related clinical and radiological data. Among 31 DAVF patients treated according to our institute's treatment algorithm between February 2009 and November 2014, 20 patients underwent GKRS alone. DAVF patients treated with GKRS alone fell in two main subgroups: DAVF patients without cortical venous reflux (CVR) but with symptoms (n = 8) and DAVF patients with CVR but without a high bleeding risk (defined as CVR with aggressive symptoms including hemorrhage or non-hemorrhagic neurological deficit, n = 11). One DAVF patient with a high bleeding risk had GKRS alone because of difficult endovascular access. Mean radiation volume was 4.8 cc (range, 0.7-14.2 cc), and mean maximal dose was 33.5 Gy (range, 28-38 Gy). At mean follow-up of 29.1 months (range, 8-69 months), radiological findings demonstrated complete cures in 18 patients (90 %) and subtotal cures in 2 patients (10 %). One patient had a transient complication, but no neurologic sign. All symptomatic patients showed complete resolution. Our treatment algorithm showed GKRS alone may serve as a primary treatment for patients with DAVFs regardless of location and presence of CVR, unless there is a high bleeding risk. However, a multicenter, prospective study is necessary to generalize our treatment algorithm.