Understanding the adsorption mechanism of noble gases Kr and Xe in CPO-27-Ni, CPO-27-Mg, and ZIF-8.

An experimental study of Xe and Kr adsorption in metal-organic frameworks CPO-27-Ni, CPO-27-Mg, and ZIF-8 was carried out. In situ synchrotron X-ray powder diffraction experiments allowed precise determination of the adsorption sites and sequence of their filling with increasing of gas pressure at different temperatures. Structural investigations were used for interpretation of gas adsorption measurements.

Genetic deletion of caspase-2 accelerates MMTV/c-neu-driven mammary carcinogenesis in mice.

Despite being the most evolutionarily conserved of the mammalian caspases, little is understood about the cellular function of caspase-2 in normal tissues or what role caspase-2 may have in the progression of human disease. It has been reported that deletion of the caspase-2 gene (Casp2), accelerates Eµ-myc lymphomagenesis in mice, and thus caspase-2 may act as a tumor suppressor in hematological malignancies. Here, we sought to extend these findings to epithelial cancers by examining the potential role of caspase-2 as a tumor suppressor in the mouse mammary carcinogenesis model; MMTV/c-neu. The rate of tumor acquisition was significantly higher in multiparous Casp2(-/-)/MMTV mice compared with Casp2(+/+)/MMTV and Casp2(+/-)/MMTV mice. Cells from Casp2(-/-)/MMTV tumors were often multinucleated and displayed bizarre mitoses and karyomegaly, while cells from Casp2(+/+)/MMTV and Casp2(+/-)/MMTV tumors never displayed this phenotype. Tumors from Casp2(-/-)/MMTV animals had a significantly higher mitotic index than tumors from Casp2(+/+)/MMTV and Casp2(+/-)/MMTV animals. Cell cycle analysis of Casp2(-/-) E1A/Ras-transformed mouse embryonic fibroblasts (MEF) also indicated a higher proliferative rate in the absence of caspase-2. In vitro assays further illustrated that MEF had increased genomic instability in the absence of caspase-2. This appears to be due to disruption of the p53 pathway because we observed a concomitant decrease in the induction of the p53 target genes, Pidd, p21 and Mdm2. Thus caspase-2 may function as a tumor suppressor, in part, through regulation of cell division and genomic stability.

Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.

ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region.

A pilot study of personality pathology in patients with anorexia nervosa: modifiable factors related to outcome after hospitalization.

OBJECTIVE: To assess improvement in aspects of personality in patients hospitalized with anorexia nervosa (AN) and its relationship to improved depression, body mass index (BMI), and eating disorder outcome after treatment. METHOD: Twenty females hospitalized with AN completed intake and discharge assessments of BMI, depression and eating disorder severity, as well as personality pathology with the Minnesota Multiphasic Personality Inventory (MMPI-2) and the Revised NEO Personality Inventory (NEO PI-R). Clinical outcome for a subset of patients at 1-year post-hospitalization was determined. RESULTS: The only factor that predicted better versus worse outcome at 1-year post-hospitalization was change in Low Self-Esteem (LSE) from the MMPI-2. Improved LSE from admission to discharge predicted remission at 1-year post-hospitalization, while worsening LSE predicted relapse. Regardless of outcome, NEO PI-R Neuroticism remained pathologically elevated in AN patients during hospitalization. DISCUSSION: Pathological levels of neuroticism may represent a vulnerability factor for AN. In contrast, self-esteem appears to be a modifiable factor that predicts outcome following hospitalization, and may be an important target for treatment.

Paramedic-led prehospital thrombolysis is safe and effective: the East Anglian experience.

INTRODUCTION: Prehospital thrombolysis has been shown to improve patient outcomes in clinical trials and this has been confirmed in the ongoing large national myocardial infarction registry (Myocardial Infarction National Audit Project; MINAP) reports. This paper describes a system to improve the delivery of prehospital thrombolysis and the associated governance requirements to gain maximum patient benefit. METHODS: Demographic data were prospectively collected on all patients treated by the East Anglian Ambulance Trust with bolus thrombolytics for a presumed diagnosis of ST elevation myocardial infarction between November 2003 and February 2007. Survival status was determined from the NHS strategic tracing service. RESULTS: 1062 patients (mean age 64.0 years (SD 10.6), 795 men) were treated in this time period. There were 71 deaths in this group, with actuarial survival of 93.9% (SE 0.9%) at 30 days, 91.7% (SE 1.0%) at 6 months and 90.8% (SE 1.1%) at 12 months after treatment. Age and cardiac arrest were most strongly associated with mortality (both p<0.001). Twelve (1.2%) patients received thrombolysis that on review was considered inappropriate. There were no deaths in this subgroup. CONCLUSIONS: Prehospital thrombolysis can be administered safely by ambulance staff supported by a Trust clinical support system with excellent clinical outcomes.

The value of contrast administration in the MRI evaluation of scoliosis in the pediatric population.

The aim of this study was to analyze the added utility of contrast administration for spine MRI in children with scoliosis. A retrospective review of 663 consecutive contrast-enhanced spine MRI performed in 319 patients as part of the work up of scoliosis in children 2-18 years with clinically suspected or known scoliosis over a seven year period. Those patients with known tumors (13 patients) being evaluated for scoliosis were excluded from the study. In 306 patients with scoliosis and no history of tumor pathologic contrast enhancement was seen in seven (2%) patients. Lack of enhancement helped to characterize benign lesions in 31 (10%) of the patients. Although MRI is often recommended to exclude intraspinal pathology in pediatric patients with scoliosis, the need for contrast enhanced imaging is very limited and contrast medium should not be administered unless questionable pathology is detected on noncontrast MR spine imaging.

MRI findings in spinal MRI of 306 children with scoliosis.

The aim of this study was to analyze the MRI findings and assess the prevalence of different associated structural abnormalities in children with scoliosis and to determine if the age of onset is a possible indicator of intraspinal pathology. This is a retrospective analysis of 663 consecutive MR examinations (319 patients). Thirteen patients with known intraspinal tumors were excluded and a total of 306 patients aged 2-18 years with scoliosis were subjected for analysis. The scoliosis was regarded as idiopathic in 62% of patients. Among the remaining 38% the most commonly seen abnormality was syrinx and Chiari malformations. There was no statistically significant difference in the occurrence of syrinx only or syrinx associated with Chiari I malformation in patients younger than ten years and those older than ten years. MRI examination is an essential part of the work up of scoliosis in the pediatric population especially before any corrective surgery. This study and a review of the current literature suggest there is no clinical marker that would definitely serve as an indicator of the presence of intraspinal pathology in these patients.

Organizing emergency preparedness within United States public health departments.

OBJECTIVES: We examined the manner in which state public health agencies have organized their operations to accomplish the goals associated with emergency preparedness (EP) funds. We also examined the leadership challenges associated with the effective utilization of preparedness funds. METHODS: The websites of all 50 state public health organizations in the USA were examined in order to determine the different approaches that states have used to organize for preparedness. Thirty-eight states provided sufficient information to allow for classification of their organizational approach to EP. Telephone interviews were conducted with representatives in three model states to obtain deeper insights into the organizational approach. RESULTS: Three predominant organizational models were identified as a means to address the challenge of organizing for preparedness. The results confirmed the equifinality principle of organization (there may be more than one equally effective way to organize) and demonstrated that, contrary to the prescription of early management thought, there is no 'one best way' to organize. Leadership rather than formal management emerged as the primary contributor to perceived EP. Specifically, interviews with preparedness professionals indicated that they believed expert power was more important than position power and the ability to negotiate and influence through persuasion was more important than formal authority. CONCLUSIONS: All three models contained, to a greater or lesser degree, elements of matrix management with the associated leadership challenges for emergency preparedness (EP) directors. Recommendations were provided for successful leadership in the context of EP directors in state departments of public health.

Rofecoxib administration to paediatric patients undergoing adenotonsillectomy.

BACKGROUND: Rofecoxib is a selective COX-2 inhibitor that does not interfere with platelet function and is associated with fewer bleeding complications than other nonsteroidal anti-inflammatory agents (NSAIDs). Our aims were to evaluate the safety and the efficacy of rofecoxib administration to paediatric patients undergoing adenotonsillectomy (T&A). METHODS: We conducted a double-blind, randomized, placebo-controlled study of rofecoxib in 45 ASA 1-2 patients > or = 4 years of age undergoing outpatient T&A. All patients received midazolam 0.5 mg x kg(-1) (max 15 mg) p.o. and either rofecoxib 1 mg x .kg(-1) (max 25 mg) or placebo p.o. 30 min preoperatively. All patients had a standardized anaesthetic and were extubated awake in the operating room at the conclusion of surgery. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores were obtained on arrival in the postanaesthetic care unit (PACU). Morphine 25 microg x kg(-1) i.v. were administered up to six times for pain in the PACU. Wong-Baker FACES Scales were obtained at discharge from the PACU and the day surgery unit (DSU). Outcome measures included intraoperative estimated blood loss (EBL), pain scores, PACU morphine requirements and discharge times. RESULTS: There were 23 patients in the rofecoxib group and 22 patients in the placebo group. There were no differences between the rofecoxib and placebo groups in terms of bleeding, pain scores, PACU morphine requirements, PACU times or DSU times. CONCLUSION: Rofecoxib administration to paediatric patients undergoing T&A did not result in increased bleeding. Rofecoxib, however, was not found to decrease morphine use or improve pain scores prior to hospital discharge in T&A patients who received intraoperative morphine and acetaminophen.

[Mild cognitive impairments in the elderly: a critical review]. / Les troubles cognitifs légers de la personne âgée: revue critique.

The aging of the population leads to increased awareness of problems associated with age-related degenerative dementias. Given that these dementias are progressive in onset, many clinicians and researchers have proposed criteria that allow for the identification of older subjects manifesting cognitive impairment, but not responding to the criteria for dementia. Our knowledge of subjects with mild cognitive impairment is limited; it is, however, established that they present a high risk of developing dementia in the future. Although it is essential to increase our comprehension of their cognitive and functional decline, the study of subjects presenting mild cognitive impairment is compromised due to the existence of numerous non-converging classifications. The goal of the present article is to conduct a critical review of the different classifications of mild cognitive impairment in the elderly in order to attempt to identify the optimal criteria, allowing for a distinction to be made between subjects with mild cognitive impairment, who remain in a stable state and those whose condition evolves to a dementia. These criteria may enable us to describe a homogenuous group of individuals presenting with different rates of dementia risk factors. We present the classifications most frequently used in clinical and research settings. After listing them according to categorial, clinical or dimensional approaches, we performed a critical analysis for each one. Depending on the diagnostic criteria applied, major variations are revealed for the prevalence of cognitive impairment and the incidence of dementia. They are explained by methodological and theoretical shortcomings that we point out and discuss (e.g., reference group, lack of diagnostic criteria or exclusion criteria, high level of subjectivity). Beyond these criticisms, we discuss the challenges to be met in order to reach the optimal identification criteria. Notably, the impact of mild cognitive impairment on daily living activities should be tested with the use of more specific questionnaires/tasks. The goal of the objective definition of cognitive impairment should be to minimize subjectivity in the diagnosis. It is also suggested that sensitive cognitive measures would be used on all aspects of cognition, while recognizing and taking into account all confounding factors (e.g., age, education level). Given the nature and consequences of mild cognitive impairment, an inter-disciplinary approach is suggested (e.g., neurobiological, psychiatric, and genetic cues). A consensus on optimal diagnostic criteria is essential to propose cognitive and pharmacological treatments for the effective prevention of ementia.

A cross sectional study of water quality from dental unit water lines in dental practices in the West of Scotland.

OBJECTIVE: To determine the microbiological quality of water from dental units in a general practice setting and current practice for disinfection of units. DESIGN: A cross-sectional study of the water quality from 40 dental units in 39 general practices and a questionnaire of the disinfection protocols used in those practices. SETTING: NHS practices in primarydental care. SUBJECTS: Thirty-nine general practices from the West of Scotland. METHODS: Water samples were collected on two separate occasions from dental units and analysed for microbiological quality by the total viable count (TVC) method. Water specimens were collected from the triple syringe, high speed outlet, cup filler and surgery tap. Each participating practitioner was asked to complete a questionnaire. Results Microbial contamination was highest from the high speed outlet followed by the triple syringe and cup filler. On average, the TVC counts from the high speed water lines at 37 degrees C and for the high speed lines, triple syringe and cup filler at 22 degrees C were significantly higher than that from the control tap water specimens. The study included units from 11 different manufacturers with ages ranging from under one year to over eight years. The age of the dental unit analysed did not appear to influence the level of microbial contamination. Five of the practices surveyed used disinfectants to clean the dental units but these had no significant effect on the microbiological quality of the water. The majority of dental units (25 out of 40) were never flushed with water between patients. A number of different non-sterile irrigants were used for surgical procedures. CONCLUSION: The microbiological quality of water from dental units in general dental practice is poor compared with that from drinking water sources. Suitable sterile irrigants should be used for surgical procedures in dental practice. Further work is required for pragmatic decontamination regimens of dental unit water lines in a general dental practice setting

Mechanisms underlying the sensitivity of neurons in the lateral superior olive to interaural intensity differences.

The initial processing of interaural intensity differences (IIDs), the major cue to the azimuthal location of high-frequency sounds in mammals, is carried out by neurons in the lateral superior olivary nucleus (LSO) that receive excitatory input from the ipsilateral ear and inhibitory input from the contralateral ear (IE neurons). The "latency" hypothesis asserts that it is the effects of intensity differences on the latency, and hence the relative timing, of the synaptic inputs to these neurons that is the basis of their sensitivity to IIDs, while other models assign the major role to changes in the relative amplitude of the inputs. To test the latency hypothesis and to determine the contributions of changes in the relative timing and amplitude of synaptic inputs to the IID sensitivity of LSO neurons, a method was developed of generating sets of stimuli that produced either the same changes in the relative timing of inputs without any change in their amplitude (equivalent interaural time difference stimuli) or the same differences in amplitude without any difference in timing (delay-cancelled IID stimuli) as a given range of IIDs. Data were obtained from a sample of IE neurons in the LSO of anesthetized rats using these stimulus paradigms and click and tone-burst stimuli. For click stimuli, the IID sensitivity of a small proportion of neurons was explained entirely by sensitivity to differences in input timing, but the sensitivity of most neurons reflected either sensitivity to the relative amplitude of inputs or to the joint operation of both factors. In neurons whose sensitivity was tested at a number of different absolute sound pressure levels (SPLs), the relative contributions of the two factors tended to differ at different SPLs. The IID sensitivity of onset responses to tone stimuli could be classified into the same three categories but was explained for a larger proportion of neurons by sensitivity to differences in input timing. The IID sensitivity of the late response component of neurons with sustained responses to tones in all cases reflected sensitivity to the relative amplitude of the inputs. The results confirm the contribution of changes in latency produced by intensity changes to the IID sensitivity of the onset responses of many IE neurons in LSO but require rejection of the strong form of the latency hypothesis, which asserts that this factor alone accounts for such sensitivity.

Diffusion coefficient of DNA molecules during free solution electrophoresis.

The free-draining properties of DNA normally make it impossible to separate nucleic acids by free-flow electrophoresis. However, little is known, either theoretically or experimentally, about the diffusion coefficient of DNA molecules during free-flow electrophoresis. In fact, many authors simply assume that the Nernst-Einstein relation between the mobility and the diffusion coefficient still holds under such conditions. In this paper, we present an experimental study of the diffusion coefficient of both ssDNA and dsDNA molecules during free-flow electrophoresis. Our results unequivocally show that a simplistic use of Nernst-Einstein's relation fails, and that the electric field actually has no effect on the thermal diffusion process. Finally, we compare the dependence of the diffusion coefficient upon DNA molecular size to results obtained previously by other groups and to Zimm's theory.

Capillary electrophoretic separation of uncharged polymers using polyelectrolyte engines. Theoretical model.

We recently demonstrated that the molecular mass distribution of an uncharged polymer sample can be analyzed using free-solution capillary electrophoresis of DNA-polymer conjugates. In these conjugates, the DNA is providing the electromotive force while the uncharged polydisperse polymer chains of the sample retard the DNA engine with different amounts of hydrodynamic drag. Here we present a theoretical model of this new analytical method. We show that for the most favourable, diffusion-limited electrophoresis conditions, there is actually an optimal DNA size to achieve the separation of a given polymer sample. Moreover, we demonstrate that the effective friction coefficient of the polymer chains is related to the stiffness of the two polymers of the conjugate, thus offering a method to estimate the persistence length of the uncharged polymer through mobility measurements. Finally, we compare some of our predictions with available experimental results.

Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.

This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia. This was a multicenter, randomized, open-label, parallel-design study of patients with total cholesterol >200 mg/dl, triglycerides between 200 and 800 mg/dl, and apolipoprotein B >110 mg/dl. Patients were randomly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein (VLDL) particles (-31% and -29%, respectively) and small low-density lipoprotein (LDL) particles (-44% and -35%, respectively). Niacin increased the concentration of large LDL (+75%). Atrovastatin reduced the number of LDL particles more than niacin (31% vs 14%). In patients with atherogenic dyslipidemia, both drugs had important effects on lipoprotein subfractions, which contributed to a reduction in coronary heart disease risk. The drugs equally reduced VLDL subclass levels. Niacin shifted the LDL subclass distribution toward the larger particles, more effectively converted patients from LDL phenotype B to phenotype A, and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles. In contrast, atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL, and more effectively, reduced LDL particle numbers. Atorvastatin had a preferred LDL effect, whereas niacin had a preferred high-density lipoprotein effect.

The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein.

The low density lipoprotein receptor-related protein-deleted in tumor (LRP1B, initially referred to as LRP-DIT) was cloned and characterized as a candidate tumor suppressor. It is a new member of the low density lipoprotein receptor gene family. Its overall domain structure and large size (approximately 600 kDa) are similar to LRP and suggest that it is a multifunctional cell surface receptor. Herein, we characterize a series of ligands for the receptor using cell lines that stably express it as a domain IV minireceptor (mLRP1B4). Ligands of LRP including receptor-associated protein, urokinase plasminogen activator, tissue-type plasminogen activator, and plasminogen activator inhibitor type-1 each demonstrate binding, internalization, and degradation via mLRP1B4. Interestingly, the kinetics of ligand endocytosis is distinctly different from that of LRP, with LRP1B exhibiting a markedly diminished internalization rate. In addition, tissue expression analysis reveals that the LRP1B gene is expressed in brain, thyroid, and salivary gland. These studies thus extend the physiological roles of members of the LDL receptor family.

Dissection of receptor folding and ligand-binding property with functional minireceptors of LDL receptor-related protein.

The LDL receptor-related protein (LRP) is a large, multifunctional endocytic receptor that binds and endocytoses a variety of structurally and functionally distinct ligands. LRP contains four putative ligand-binding domains. However, only domains II, III and IV, but not domain I, bind the receptor-associated protein (RAP), a molecular chaperone and universal antagonist for LRP. In order to dissect the function of RAP in LRP folding and to examine the ligand-binding properties of LRP, we generated LRP minireceptors that represent each of the four putative ligand-binding domains (termed mLRP1, mLRP2, mLRP3 and mLRP4, respectively). We found that proper folding and trafficking of mLRP2, mLRP3, mLRP4, but not mLRP1, is facilitated by coexpression of RAP. When these mLRPs were stably expressed in Chinese Hamster Ovary cells that lack the endogenous LRP, we found that each of these receptors was processed and traffics through the secretory pathway. Cell surface expression of these minireceptors was quantitatively examined by flow cytometric analyses. Using these minireceptor cell lines to map the ligand-binding domains, we found that although the majority of LRP ligands bind to both domain II and domain IV, Pseudomonas exotoxin A utilizes only domain IV for its binding to LRP. We conclude that while domains II and IV of LRP share many ligand-binding properties, each of the putative ligand-binding domains of LRP is unique in its contribution to ligand binding.

Sleep in right hemispherectomized patients: evidence of electrophysiological compensation.

OBJECTIVES: The goal of this study is to provide a better understanding of the role of the cortex in sleep's macro- and microstructure modulation. METHODS: Sleep architecture and phasic events were investigated in 4 patients having undergone right functional or anatomical hemispherectomy and 8 control subjects. Between-groups differences were assessed using the Wilcoxon-Mann-Whitney test. RESULTS: Findings provide evidence for overall similarity between patients' and control subjects' left hemispheric sleep architecture. In addition, results clearly indicate that it is possible to detect electrical activity over the operated side of a hemispherectomized patient's brain, even when resection of the hemi-cortex has been complete. Finally, findings provide evidence for similar left and right hemispheric relative spectral activities and for an increase in fast activity bands over the intact hemisphere in anatomical hemispherectomized patients. CONCLUSIONS: This study provides evidence that right hemispherectomy does not produce significant sleep architecture alterations as recorded over the intact hemisphere. In addition, residual activity detected over the operated side in anatomical hemispherectomized patients is interpreted as resulting from volume conduction originating from generators located in the intact hemisphere. Finally, there is strong evidence for electrophysiological compensation in the intact hemisphere following complete resection of the contralateral hemi-cortex.