Characterising the patient experience of diagnostic lumbar puncture in idiopathic intracranial hypertension: a cross-sectional online survey.
Patients with idiopathic intracranial hypertension (IIH) usually require multiple lumbar punctures (LPs) during the course of their disease, and often report significant morbidity associated with the procedure. The aim of this study was to assess the patient's experience of diagnostic LP in IIH. A cross-sectional study of patients with IIH was conducted using an anonymous online survey, with the questions designed in collaboration with IIH UK (the UK IIH charity). Responses were collated over a 2-month period from April to May 2015. Patients were asked to quantify responses using a Verbal Rating Score (VRS) 0-10 with 0 being the minimum and 10 the maximum score. 502 patients responded to the survey, of which 463 were analysed for this study. 40% of patients described severe pain during the LP (VRS ≥8), and the median pain score during the LP was 7 (VRS, IQR 5-7). The majority of patients felt they received insufficient pain relief (85%). Levels of anxiety about future LPs were high (median VRS 7, IQR 4-10), with 47% being extremely anxious (VRS ≥8). LPs performed as an emergency were associated with significantly greater pain scores compared with elective procedures (median 7, IQR 5-7 vs 6, IQR 4-8, p=0.012). 10.7% went on to have an X-ray-guided procedure due to failure of the initial LP, and the body mass index was significantly higher in this group (mean kg/m240.3 vs 35.5, p=0.001). Higher LP pain scores (VRS) were significantly associated with poorly informed patients (Spearman's correlation, r=-0.32, p<0.001). Patients felt more informed when the LP was performed by a specialist registrar compared with a junior doctor (median 7 vs 5, p=0.001) or a consultant compared with a junior doctor (median 8 vs 5, p<0.001). This study was commissioned by the IIH patient group and is the first to document the patient experience of diagnostic LPs in IIH. It shows that the majority of these patients are experiencing significant morbidity from pain and anxiety. Patient experience of LP may be improved through changing clinical practice to include universal detailed preprocedural information, and where possible, avoiding emergency LPs in favour of LPs booked on an elective day-case unit.


[Infection control and hand hygiene in nursing homes in Oslo].
Nosocomial infections and transmission can be substantially reduced by good infection control. The laws and regulations for infection control in heath care institutions emphasize establishment of infection control programs and improved hand hygiene. Our study reviews some factors that are important for practicing adequate hand hygiene (knowledge about infection control and hand-washing facilities). Health care workers (HCW) in nursing homes in Oslo participated in this study in 2006-2007. A questionnaire was made and SPSS was used to analyse the data . 70.7% of 324 HCW (in 42 nursing homes) answered the questionnaires. Nearly all of the respondents (95.6%) knew about the written procedures for hygiene and infection control; 88.5% knew that an infection control program was in place and about 50% had received information through internal education. Three of four had read the National guidelines for hand hygiene, 77.5% thought that hand disinfection was more effective than hand washing, and 97% reported hand hygiene after contact with a patient having an infection. Dispensers for hand disinfection were situated at central work places. At the same time, 17.9% informed that they worked in more than one place at the same time. This study confirms that most nursing homes in Oslo have an infection control program and training that improves the knowledge and awareness of hand hygiene among HCWs. However, the fact that nursing homes in Oslo have the resources, knowledge and education, is not the same as compliance.


Endoscopic resection (endoscopic submucosal dissection/endoscopic mucosal resection) for superficial Barrett's esophageal cancer.
Recently developed endoscopic resection (endoscopic submucosal dissection [ESD]/ endoscopic mucosal resection) has dramatically changed the therapeutic approach for Barrett's esophageal cancer. The rationale for endoscopic resection is that lesions confined to the mucosal layer have negligible risk for developing lymph node metastasis and can be successfully eradicated by endoscopic treatment as a curative treatment with minimal invasiveness. According to some reports that analyzed the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor infiltration, endoscopic resection is clearly indicated for intramucosal carcinoma and might be extended to lesions with invasion into the submucosa (<200 μm, sm1) because of the low risk for lymph node metastasis. Most Japanese experts recommend ESD for Barrett's esophageal cancer after accurate diagnosis of the margin of cancer using narrow band imaging with magnifying endoscopy because of its high curative rate. However, few studies have evaluated the long-term outcomes of endoscopic resection for Barrett's esophageal cancer in Japan. Further investigations should be conducted to establish endoscopic resection for Barrett's esophageal cancer.


Zn2+ Differentially Influences the Neutralisation of Heparins by HRG, Fibrinogen, and Fibronectin.
For coagulation to be initiated, anticoagulant glycosaminoglycans (GAGs) such as heparins need to be neutralised to allow fibrin clot formation. Platelet activation triggers the release of several proteins that bind GAGs, including histidine-rich glycoprotein (HRG), fibrinogen, and fibronectin. Zn2+ ions are also released and have been shown to enhance the binding of HRG to heparins of a high molecular weight (HMWH) but not to those of low molecular weight (LMWH). The effect of Zn2+ on fibrinogen and fibronectin binding to GAGs is unknown. Here, chromogenic assays were used to measure the anti-factor Xa and anti-thrombin activities of heparins of different molecular weights and to assess the effects of HRG, fibrinogen, fibronectin, and Zn2+. Surface plasmon resonance was also used to examine the influence of Zn2+ on the binding of fibrinogen to heparins of different molecular weights. Zn2+ had no effect on the neutralisation of anti-factor Xa (FXa) or anti-thrombin activities of heparin by fibronectin, whereas it enhanced the neutralisation of unfractionated heparin (UFH) and HMWH by both fibrinogen and HRG. Zn2+ also increased neutralisation of the anti-FXa activity of LMWH by fibrinogen but not HRG. SPR showed that Zn2+ increased fibrinogen binding to both UFH and LMWH in a concentration-dependent manner. The presented results reveal that an increase in Zn2+ concentration has differential effects upon anticoagulant GAG neutralisation by HRG and fibrinogen, with implications for modulating anti-coagulant activity in plasma.


Requirement of nuclear factor kappaB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts.
Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappaB) since proteasome inhibitors and antioxidants that abrogated NF-kappaB activity suppressed the induction of both genes. The time-dependent fall of the mRNA levels of NOS-2 and COX-2 paralleled the inhibition of NF-kappaB, determined by electrophoretic mobility shift assays, and the increase of the IkappaBalpha and IkappaBbeta inhibitory proteins. Isolated trophoblasts synthesized reactive oxygen intermediates (ROI), a process impaired after culturing the cells, and that might be involved in the NF-kappaB activation process. Moreover, treatment of recently isolated cells with ROI scavengers suppressed the expression of COX-2 and NOS-2. Challenge of trophoblasts with interleukin-1beta up-regulated the expression of both proteins, an effect that was potentiated by lipopolysaccharide. These results indicate that the physiological expression of NOS-2 and COX-2 in trophoblasts involves a sustained activation of NF-kappaB which inhibition abrogates the inducibility of both genes.


A method for the simultaneous isolation of factor X and prothrombin from bovine plasma.
1. A method is described for the simultaneous isolation of both Factor X and prothrombin from bovine plasma. The proteins are adsorbed on and eluted from barium sulphate and chromatographed on DEAE-Sephadex and are finally purified by rechromatography on DEAE-Sephadex. 2. The proteins can be purified in 48h from the collection of the blood and the method can be used to process large volumes of plasma. 3. The prothrombin has a molecular weight of 70300; the Factor X, on the other hand, is polydisperse, with most of the protein (86%) having a molecular weight of 56000.


Electronystagmography and audio potentials in space flight.
Beginning with the fourth flight of the Space Transport System (STS-4), objective measurements of inner ear function were conducted in near-zero G conditions in earth orbit. The problem of space motion sickness (SMS) was approached much like any disequilibrium problem encountered clinically. However, objective testing techniques had built-in limitations superimposed by the strict parameters inherent in each mission. An attempt was made to objectively characterize SMS, and to first ascertain whether the objective measurements indicated that this disorder was of peripheral or central origin. Electronystagmography and auditory brain stem response recordings were the primary investigative tools. One of the authors (W.E.T.) was a mission specialist on board the orbiter Challenger on the eight shuttle mission (STS-8) and had the opportunity to make direct and personal observations regarding SMS, an opportunity which has added immeasurably to our understanding of this disorder. Except for two abnormal ENG records, which remain to be explained, the remaining ENG records and all the ABR records made in the weightless environment of space were normal.


Extended clinical trial and evaluation of glucose determination with the Eastman Kodak Ektachem GLU/BUN Analyzer.
We followed the "abbreviated precision protocol" of the National Committee for Clinical Laboratory Standards for the evaluation of precision, accuracy, and carryover in analyses for glucose with the "Ektachem." We analyzed 760 clinical samples by this technique, by the FDA Proposed Class Standard glucose reference method, and with the Beckman System I GLU/BUN Analyzer. Precision and accuracy were estimated for 500, 1000, 1200, 1500, and 3000 mg/L glucose concentrations in 100, 30, or 20 microL of serum or plasma. Potential interference of 19 compounds was evaluated. Random error (1.965 X SD) was 22, 30, 34, 40, and 88 mg/L. Systematic error was 8, 1.5, -2, -5, and -27 mg/L. Total analytical error was 30, 32, 36, 46, and 110 mg/L for analysis of 100 microL of serum at the above-stated glucose concentrations. The greatest interference (-39 mg/L) in the glucose (at 1200 mg/L) determination was caused by L-ascorbate (40 mg/L). Glucose concentrations as determined with the Ektachem were found to be linearly related to the expected concentration up to at least 5660 mg/L. Carryover was not statistically significant.


Dopamine Modulation of Drosophila Ellipsoid Body Neurons, a Nod to the Mammalian Basal Ganglia.
The central complex (CX) is a neural structure located on the midline of the insect brain that has been widely studied in the last few years. Its role in navigation and goal-oriented behaviors resembles those played by the basal ganglia in mammals. However, the neural mechanisms and the neurotransmitters involved in these processes remain unclear. Here, we exploited an in vivo bioluminescence Ca2+ imaging technique to record the activity in targeted neurons of the ellipsoid body (EB). We used different drugs to evoke excitatory Ca2+-responses, depending on the putative neurotransmitter released by their presynaptic inputs, while concomitant dopamine administration was employed to modulate those excitations. By using a genetic approach to knockdown the dopamine 1-like receptors, we showed that different dopamine modulatory effects are likely due to specific receptors expressed by the targeted population of neurons. Altogether, these results provide new data concerning how dopamine modulates and shapes the response of the ellipsoid body neurons. Moreover, they provide important insights regarding the similitude with mammals as far as the role played by dopamine in increasing and stabilizing the response of goal-related information.


Atypical hypocortisolism.
To report a patient who had developed reversible hypocortisolism during the use of quetiapine. Early morning cortisol levels were measured on two separate days. In addition, the patient underwent testing with intravenous synthetic adrenocorticotropic hormone (1 mcg tetracosactide) before and after tapering of quetiapine. Pituitary function was assessed and magnetic resonance imaging (MRI) was performed. The patient had low early morning cortisol levels at presentation when using quetiapine. Tetracosactide testing indicated hypocortisolism. A MRI of the pituitary was unremarkable. The patient was treated temporarily with hydrocortisone and quetiapine was tapered. After quetiapine had been discontinued, the patient's cortisol production had returned to normal. Although lowering cortisol levels has been previously reported, this is the first report of hypocortisolism associated with the use of quetiapine. It is possible symptoms of malaise in patients who use quetiapine could be attributed to quetiapine-related hypocortisolism.


Dental anxiety and pain related to dental hygienist treatment.
To evaluate different groups of patients' self-reported assessments of dental anxiety and pain related to various routine dental hygienist treatment procedures, and to investigate the relationship between anxiety concerning dental and dental hygienist treatment. A consecutive sample of 393 patients participated in the study (59.7% F, age range 20 to 85 years, mean 47.6 years). Periodontology (PC), oral medicine (OM), student and general practice (GP) clinics were included. Each patient was asked to answer a questionnaire which included different demographic information, self-reported levels of dental anxiety, and experience of pain in relation to different dental hygienist treatments. Higher dental anxiety was found in relation to gender (women), dentist treatment, and PC and OM patients. Experiences of high or extreme pain were reported by between 7.1% and 9.7% of participants for all dental hygienist procedures except polishing (0.8%). There were significant correlations between dental hygienist fear levels and reported extreme pain experiences among all five treatment procedures. Patients treated at the PC clinic scored significantly higher on pain compared with patients at the other clinics, with the exception of the OM clinic. Patients reported higher dental anxiety levels for dentist treatment as compared with dental hygienist treatment. Moreover, dental anxiety was significantly associated with perceived pain related to different dental hygienist treatment procedures.


Genetic and functional modularity of Hox activities in the specification of limb-innervating motor neurons.
A critical step in the assembly of the neural circuits that control tetrapod locomotion is the specification of the lateral motor column (LMC), a diverse motor neuron population targeting limb musculature. Hox6 paralog group genes have been implicated as key determinants of LMC fate at forelimb levels of the spinal cord, through their ability to promote expression of the LMC-restricted genes Foxp1 and Raldh2 and to suppress thoracic fates through exclusion of Hoxc9. The specific roles and mechanisms of Hox6 gene function in LMC neurons, however, are not known. We show that Hox6 genes are critical for diverse facets of LMC identity and define motifs required for their in vivo specificities. Although Hox6 genes are necessary for generating the appropriate number of LMC neurons, they are not absolutely required for the induction of forelimb LMC molecular determinants. In the absence of Hox6 activity, LMC identity appears to be preserved through a diverse array of Hox5-Hox8 paralogs, which are sufficient to reprogram thoracic motor neurons to an LMC fate. In contrast to the apparently permissive Hox inputs to early LMC gene programs, individual Hox genes, such as Hoxc6, have specific roles in promoting motor neuron pool diversity within the LMC. Dissection of motifs required for Hox in vivo specificities reveals that either cross-repressive interactions or cooperativity with Pbx cofactors are sufficient to induce LMC identity, with the N-terminus capable of promoting columnar, but not pool, identity when transferred to a heterologous homeodomain. These results indicate that Hox proteins orchestrate diverse aspects of cell fate specification through both the convergent regulation of gene programs regulated by many paralogs and also more restricted actions encoded through specificity determinants in the N-terminus.


Determination of dichloroanilines in human urine by gas chromatography/mass spectrometry: validation protocol and establishment of Reference Values in a population group living in central Italy.
3,4- and 3,5-Dichloroanilines (DCAs) are common markers of some non-persistent pesticides, e.g. linuron, diuron, vinclozolin, and iprodione. The general population may be exposed to these DCAs and/or their precursors mainly through diet. Since adverse effects on human health, such as endocrine disruption, have been reported, biological monitoring is essential for exposure assessment both of occupationally exposed subjects and of the general population. A highly sensitive and selective gas chromatography/mass spectrometry (GC/MS) method has been developed for the determination of 3,4- and 3,5-DCAs in urine using 4-chloro-2-methylaniline as an internal standard. The selected ion monitoring (SIM) mode was employed for quantitation of the analytes. The sample treatment procedure is simple and fast and no derivatization is required. The overall method was validated including uncertainty measurement. The limit of detection (LOD) and the lower limit of quantitation (LLOQ) were determined to be 0.005 and 0.010 microg/L for both analytes. The method was then applied to the establishment of reference values for a population group living in a rural area of central Italy (Novafeltria, Marche). A total of 151 out of 153 samples were found to be positive for 3,5-DCA, and 81.7% were positive for 3,4-DCA. For this group, 3,4-DCA levels ranged from 0.01 to 6.19 microg/L, while 3,5-DCA urinary concentrations were between 0.02 and 6.71 microg/L.


Ophthalmic malpractice lawsuits with large monetary awards.
Malpractice claims against ophthalmologists that were closed with patient indemnification of at least $250,000(18% of all eye claims closed with payments to patients) were analyzed for risk prevention. The incident of alleged malpractice occurred within 1 month of the initial physician-patient encounter in 43% of claims and on the initial encounter in 17%. Cataract was the most frequent problem for which these patients sought treatment. Eighty-four percent of these patients sustained injuries resulting in legal blindness or worse. The most frequent complication of treatment (25%) was failure or delay in diagnosis of detached retina, or negligent treatment resulting in a retinal detachment. The most frequent factors influencing the decision to seek a settlement included altered records, poor documentation, informed consent problems, failure to see the patient promptly, and failure to obtain or follow the advice of a consultant.


Distinctive phenotype for HLA-E- versus HLA-A2-restricted memory CD8 αβT cells in the course of HCMV infection discloses features shared with NKG2C+CD57+NK and δ2-γδT cell subsets.
The human cytomegalovirus (HCMV) triggers both innate and adaptive immune responses, including protective CD8+ αβT cells (CD8T) that contributes to the control of the infection. In addition to CD8T restricted by classical HLA class Ia molecules, HCMV also triggers CD8T recognizing peptides from the HCMV UL40 leader peptide and restricted by HLA-E molecules (HLA-EUL40 CD8T). This study investigated the frequency, phenotype and functions of HLA-EUL40 CD8T in comparison to the immunodominant HLA-A2pp65 CD8T upon acute (primary or secondary infection) or chronic infection in kidney transplant recipients (KTR) and in seropositive (HCMV+) healthy volunteer (HV) hosts. The frequency of hosts with detected HLA-EUL40 CD8T was similar after a primary infection (24%) and during viral latency in HCMV+ HV (26%) and equal to the frequency of HLA-A2pp65 CD8T cells in both conditions (29%). Both CD8T subsets vary from 0.1% to >30% of total circulating CD8T according to the host. Both HLA-EUL40 and HLA-A2pp65 CD8T display a phenotype specific of CD8+ TEMRA (CD45RA+/CCR7-) but HLA-EUL40 CD8T express distinctive level for CD3, CD8 and CD45RA. Tim3, Lag-3, 4-1BB, and to a lesser extend 2B4 are hallmarks for T cell priming post-primary infection while KLRG1 and Tigit are markers for restimulated and long lived HCMV-specific CD8T responses. These cell markers are equally expressed on HLA-EUL40 and HLA-A2pp65 CD8T. In contrast, CD56 and PD-1 are cell markers discriminating memory HLA-E- from HLA-A2-restricted CD8T. Long lived HLA-EUL40 display higher proliferation rate compared to HLA-A2pp65 CD8T consistent with elevated CD57 expression. Finally, a comparative immunoprofiling indicated that HLA-EUL40 CD8T, divergent from HLA-A2pp65 CD8T, share the expression of CD56, CD57, NKG2C, CD158 and the lack of PD-1 with NKG2C+CD57+ NK and δ2-γδT cells induced in response to HCMV and thus defines a common immunopattern for these subsets.


Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts.
We determined the independent influence of coronary hyperperfusion on myocardial metabolism in isolated and intact hearts. In an isovolumic blood-perfused rat heart preparation working against a left ventricular (LV) balloon, the effect of increasing coronary perfusion pressure from 100 to 150 mmHg was assessed. In three groups of rat hearts LV volume was fixed to obtain LV peak pressures of 42 +/- 3, 101 +/- 5, and 130 +/- 6 mmHg. With coronary hyperperfusion, LV pressure increased 27, 18, and 16%, LV maximum time derivative of pressure (dP/dt) increased 39, 20, and 22%, and myocardial O2 consumption (VO2) increased 16, 17, and 33%, respectively. In a fourth group, LV peak pressure was held constant at 92 +/- 4 mmHg during coronary hyperperfusion by decreasing LV volume. In this group, despite an increase in coronary blood flow of 48%, there was no significant difference in LV maximum dP/dt or myocardial VO2. Thus, in isolated rat hearts, coronary hyperperfusion was not an independent stimulus to myocardial VO2. To further test this, the effect of coronary hyperperfusion on myocardial metabolism was studied in an intact working swine heart preparation where the cardiac output was fixed with a right heart bypass circuit. Fatty acid oxidation in the left anterior descending bed was assessed by production of 14CO2 from [14C(U)]palmitate. A comparison of coronary perfusion 106 +/- 5 vs. 197 +/- 5 mmHg resulted in no significant change in global LV function, including LV internal diameter. Despite a 70% increase in coronary blood flow, there was no significant change in myocardial VO2 or fatty acid utilization.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the Root End Sealing Ability of Four Different Retrograde Filling Materials in Teeth with Root Apices Resected at Different Angles - An Invitro Study.
Insufficient apical seal is the significant reason for surgical endodontic disappointment. The root-end filling material utilized should avoid egress of potential contaminants into periapical tissue. The aim of this study was to compare the sealing ability of four root-end filling materials MTA, Portland cement, IRM, RMGIC in teeth with root apices resected at 0 and 45 angle using dye penetration method under fluorescent microscope. Hundred extracted human maxillary anterior teeth were sectioned horizontally at the cement-enamel junction. After cleaning, shaping and obturation with gutta-percha and AH Plus sealer, the tooth samples were randomly divided in two groups (the root apices resected at 0° and 45° to the long axis of the root). The root resections were carried out by removing 2 mm and 1 mm in both the groups. Following which 3 mm deep root-end cavities were prepared at the apices and the root were coated with nail varnish except the tip. The teeth in both the group were randomly divided into four subgroups each (Pro root MTA, Portland cement, IRM and Light cure nano GIC Ketac N-100). All the retrofilled samples were stored in acrydine orange for 24 hours after which they were cleaned and vertically sectioned buccolingually. The sectioned root samples were observed under fluorescent microscope. The root apex sealing ability of Mineral Trioxide Aggregate (MTA) was superior to Portland cement, Intermediate Restorative Material (IRM) and LC GIC. IRM demonstrated the maximum apical leakage value among all the materials. Portland cement and LC GIC showed comparable sealing ability. The angulation whether 0° or 45° angle did not affect the sealing ability of all the four materials used, MTA proved to be one of the superior materials for root-end filling.


Genetic structure of populations of Rhizoctonia solani AG-3 on potato in eastern North Carolina.
A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to identify and differentiate genotypes of Rhizoctonia solani anastomosis group 3 subgroup PT (AG-3 PT), a fungal pathogen of potato. Polymorphic co-dominant single-locus PCR-RFLP markers were identified after sequencing of clones from a genomic library and digestion with restriction enzymes. Multilocus genotypes were determined by a combination of PCR product and digestion with a specific restriction enzyme for each of seven loci. A sample of 104 isolates from one commercial field in each of five counties in eastern North Carolina was analyzed, and evidence for high levels of gene flow between populations was revealed. When data were clone-corrected and samples pooled into one single North Carolina population, random associations of alleles were found for all loci or pairs of loci, indicating random mating. However, when all genotypes were analyzed, the observed genotypic diversity deviated from panmixia and alleles within and between loci were not randomly associated. These findings support a model of population structure for R. solani AG-3 PT on potato that includes both recombination and clonality.


Alcohol and other drug abuse. Current perspectives for occupational health nurses.
1. Trends in alcohol, drug, and tobacco use indicate that the upward surge of the 1960s and 1970s has subsided, but the amount of drug use in this country is still higher than in any other industrial nation. Risk factors associated with age, gender, culture, and family point to a significant increase in the number of individuals in the work force with a substance abuse problem. 2. The etiology of alcohol and other drug addictions is a subject of controversy. One position adheres to biological determinants of disease, another adheres to psychological disorders. 3. Implications for nurses involve effective teaching/learning strategies that range from didactic content emphasizing long term consequences of the disease to specific methods of employee instruction.


[Influencing factors on HRQOL of physically disabled persons].
The purpose of this study was to investigate the influencing factors on health-related quality of life of physically disabled persons. Data was collected from 96 persons with a physical disability in three cities in Korea from June to September, 2003. Social support and depression were measured by a Social Support Questionnaire 6 (SSQ6) and Center for Epidemiologic Studies Depression questionnaire (CES-D). The Rosenberg Self-esteem Scale was used to measure self-esteem. Health-related quality of life (HRQOL) was measured using Smith Kline Beecham Quality of Life Scale (SBQOL). The SPSS WIN 11.0 version program was used for data analysis. There were significant differences of HRQOL according to monthly income and economic status. All subjects had a high level of depression and low self-esteem. The findings of this study show that self-esteem and the size of the social support network are significant influencing variables on HRQOL in physically disabled persons. Nursing intervention and counseling programs which improve self-esteem and increase the size of a social support network are needed to promote HRQOL in physically disabled persons.


Epidemiology for and with a distrustful community.
The epidemiology of diseases associated with chemical waste disposal sites has often been delayed for years after the affected community became aware of the exposure. Frequently, this has resulted in an aroused neighborhood community that is distrustful of those public agencies and officials responsible for protecting their health. It is thus important that positive steps be taken to alleviate the antagonism and to involve the community in an active and constructive role in the epidemiology study. This paper presents a case history of such an incident and highlights some of the lessons learned. The first steps were to involve and inform the community. A citizen and industry advisory committee was formed to participate in the work, publish a newsletter, and conduct regular community meetings. The newsletter and the community meetings were used to identify problems and to explain them; to describe uncertainties of a scientific as well as of political or financial nature; to involve community leaders, including those distrustful; to conduct an epidemiologic census and a neighborhood environmental exposure survey. The end results were a defusing of the antagonism toward authorities, complete acceptance by the community of the merit of the report, a higher quality of report than might otherwise have been possible, and the freedom to move toward alleviating the problems of the disposal site.


Hypoventilation: a risk factor for milk alkali syndrome?
A 67-year-old woman was admitted to the hospital due to progressive mental changes, nausea and vomiting after a dose increase of an intrathecal morphine pump. We found severe hypercalcaemia due to milk alkali syndrome (MAS). Her symptoms resolved quickly after normalisation of hypercalcaemia. Similar to the original and the modern versions of the syndrome, ingested carbonate was the main source of bicarbonate in our case. The main trigger was a morphine overdose with volume contraction due to vomiting and a further aggravation of chronic compensatory elevation of bicarbonate due to hypoventilation leading to MAS; thus, suggesting hypoventilation as a risk factor for MAS.


Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT).
The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure. One hundred eighty-one patients in New York Heart Association class I to III, with ejection fraction <40% and 6-minute walk distance <500 meters, were recruited into a randomized, controlled, single-blind trial comparing 3 months of supervised training, then 9 months of home-based training with usual care. There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences. Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months (0.104 +/- 0.026 L/min vs 0.025 +/- 0.023 L/min; P =.026) and 12 months (0.154 +/- 0.074 L/min vs 0.024 +/- 0.027 L/min; P =.081). Compared with the control group, significant increases were observed in the exercise group for arm and leg strength. No significant changes were observed in cardiac function or quality of life. Adherence to exercise was good during supervised training but reduced during home-based training. Exercise training improves peak oxygen uptake and strength during supervised training. Over the final 9 months of the study, there was little further improvement, suggesting that some supervision is required for these patients. There were no adverse effects on cardiac function or clinical events.


Psychiatric nurses and undergraduate nursing students' perceptions of preceptorship in the mental health setting.
The importance of clinical education for nursing is widely acknowledged and considerable effort has been invested into identifying the most effective models. Psychiatric nursing has the additional imperative of increasing recruitment into the field. While clinical experience has been found to influence nursing students' attitudes towards psychiatric nursing and people experiencing a mental illness, little attention has been paid towards the factors that influence these outcomes. This study addresses the question, what is the experience of preceptorship for mental health nurses and undergraduate nursing students' in the mental health setting? An examination of the interactions within this model and the development of a substantive theory are facilitated by utilising the qualitative methodological approach, grounded theory. Findings indicate that psychiatric nurse preceptors seek to accomplish connectedness in the preceptorship relationship, through overcoming fear and other misconceptions. In addition, a number of factors emerged where commonality exists between the experiences of mental health nurse preceptors andthe nursing students. These included the need to manage the reconciling of difference between general acute health and mental health settings, the challenge for both groups to address student fear and preconceived ideas of mental illness and the need of preceptors to 'protect' the students.


Current evidence on the health-beneficial effects of berry fruits in the prevention and treatment of metabolic syndrome.
Berries belong to the best dietary sources of bioactive compounds, which exert a synergistic and cumulative effect on promotion of human health and prevention of diseases. The present review presents the most recent findings of animal and human studies regarding the health benefits of berries in terms of prevention and treatment of obesity, hypertension, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. In the last years, there was a growing number of evidence from human epidemiological and interventional studies, which emphasized the role of berries in the management of metabolic diseases. Based on the results from recent clinical trials, it can be established that a berry diet rich in antioxidants and bioactive phytochemicals has beneficial effects on hepatic function, increase of insulin sensitivity and high-density lipoprotein-cholesterol, decrease of serum glucose and low-density lipoprotein-cholesterol, and finally is inversely associated with the incidence of type 2 diabetes. Numerous recent studies have shown that berries provide great benefits in preventing or mitigating metabolic disorders. The results of this review indicate that regular long-term consumption of different berries could potentially delay the progression of metabolic syndrome and comorbidities.


Development of novel oxygen carriers by coupling hemoglobin to functionalized multiwall carbon nanotubes.
Preparation of stable and effective artificial oxygen carriers (AOCs) is a promising strategy to temporarily replace transfused blood and solve tissue hypoxia. Developing hemoglobin (Hb) loaded particles is one of the main ways to prepare suitable AOCs. Particles with a hierarchical micro/nanostructure can be loaded with plenty of proteins and have attracted great attention. Therefore, multiwall carbon nanotubes (MWCNTs) were chosen to fabricate AOCs. To improve the Hb-loading capacity of MWCNTs, functionalized MWCNTs, including carboxyl-functionalized MWCNTs (MWCNT-COOH), amino-functionalized MWCNTs (MWCNT-NH2), and heparin-conjugated MWCNTs (MWCNT-Hep), were prepared. Then, in this study, Hb was coupled to the functionalized MWCNTs to fabricate the AOCs. The functionalized MWCNTs and the AOCs were characterized by FTIR, SEM, TEM, and zeta potential analysis. The oxygen/Hb-loading capacity of the AOCs was also measured. The adverse effects of the AOCs on human umbilical vein endothelial cells (HUVECs) and human red blood cells (RBCs) were evaluated. The results showed that (1) the functional groups were grafted on the surface of the MWCNTs, and Hb was bound to the functionalized MWCNTs, thus the AOCs were successfully prepared; (2) MWCNT-Hep-Hb had the most stable dispersibility (i.e., the most negative zeta potential) in 0.9 wt% NaCl solution (MWCNT-Hep-Hb < MWCNT-COOH-Hb < MWCNT-Hb < MWCNT-NH2-Hb < 0); (3) MWCNT-Hep had the best Hb-loading capability, which was three times that of purified MWCNTs; (4) with concentrations increased up to 400 μg mL-1, MWCNT-Hep-Hb still had the highest cell viability (97.63% > 80%, ISO 10993-5:2009) and excellent blood biocompatibility. Therefore, MWCNT-Hep-Hb might be a satisfactory candidate as a blood substitute.


Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.
Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.


Accuracy of height loss during prospective monitoring for detection of incident vertebral fractures.
Vertebral fractures are the most common type of osteoporotic fracture, but more than two-thirds remain undetected. We have examined the relationship between height loss and the development of new vertebral fractures to determine whether there is a height loss threshold that has useful clinical accuracy to detect new fractures. We studied 985 postmenopausal women with osteoporosis in the placebo arms of the Vertebral Efficacy with Risedronate Therapy studies. Height was measured annually for 3 years using a wall-mounted stadiometer. New fractures were determined using quantitative and semi-quantitative radiographic morphometry. The relationship between height loss over three years and the number of new vertebral fractures was: height loss (cm) = 0.95 x number of new vertebral fractures-0.4 cm (r = 0.33). The odds ratio for the development of a new fracture increased up to 20.6 (95% confidence interval, 9.3, 45.8) when height loss was greater than 4.0 cm. At a threshold of > 2.0 cm height loss over 3 years, sensitivity was 35.5% for detecting new vertebral fractures and specificity was 93.6%. These findings show that there is a strong relationship between the amount of height loss and the risk of a new vertebral fracture. While there is no cut-off that can reliably rule in a new fracture, height loss of < or = 2.0 cm over 1-3 years has acceptable accuracy for ruling out an incident fracture.


Patients' experience with teledentistry compared to conventional follow-up visits in TMD clinic: A pilot study.
Teledentistry has been used in many dental specialties including temporomandibular joint disorders (TMD). Studies have measured patients' experience with teledentistry visits. Thus, this study aimed to assess the experience of patients seen using teledentistry compared to the traditional Orofacial Pain (OFP) and TMD visits. An interventional study was conducted on 25 patients following up at the TMD clinic. The first follow-up occurred in person at the hospital clinic, where patients were given a survey at the end of the visit. A questionnaire included the following sections: socio-demographic information, patient experience of the visit, preferred online platforms, and patients' familiarity with these platforms. Patients had teledentistry visits via ZOOM Premium. After the visit, patients were given a second survey highlighting their experience towards the virtual visit and sections from the first survey. The study compares patients' satisfaction between conventional and virtual follow-up visits and compares patient experience differences based on their demographics. Twenty-five patients completed both surveys. Over half of the participants were younger than 35 years old (64 %), and the majority were female (80 %). A total of 76 % had used virtual platforms prior to the study, and 74 % of them were convenient. Regarding patients' experience, only a borderline difference existed among the age groups of the study in effectively using teledentistry in the follow-ups compared to conventional visits (p = 0.05). Other results revealed no significant differences in patients' experience between virtual and conventional visits, indicating that high-quality dental care services can be provided remotely. Therefore, teledentistry could be integrated into the OFP and TMD Clinic flow without adversely affecting patient experience or quality of care. Virtual follow-up visits could save patients' time, effort, and travel costs compared to conventional visits. Waiting lists are increasing in almost all dental; thus, integrating virtual follow-up visits would shorten these lists.


Uncorrected versus demographically-corrected scores on the NIH Toolbox Cognition Battery in persons with traumatic brain injury and stroke.
The association between demographic characteristics and neurocognitive performance is well established; however, clinicians may have difficulty selecting when to use uncorrected versus demographically corrected scores. We compared these score types in individuals with traumatic brain injury (TBI) and stroke, on the National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB). Adults with TBI and stroke were demographically matched to controls, and completed the NIHTB-CB. Published "corrected scores" are adjusted for age, education, sex, and race/ethnicity; "uncorrected scores" were created using census data to represent the average adult in the U.S. Effect sizes for the TBI and stroke groups versus controls were larger using corrected scores compared with uncorrected scores for the fluid composite (uncorrected to corrected effect sizes: TBI: d = 0.66, p < .001 to 0.83, p < .001; stroke d = 0.97, p < .001 to 1.10, p < .001). For the crystallized composite, effect sizes for the TBI and stroke groups versus controls were smaller and nonsignificant using corrected scores (uncorrected to corrected effect sizes: TBI d = 0.23, p = .03 to 0.20, p = .06; stroke d = 0.40, p < .001 to 0.17, p = .09). In the injury groups, demographic characteristics accounted for up to 33% of variance in uncorrected scores (p < .001), but <5% of variance in corrected scores (p > .06). Corrected scores were more sensitive to neurocognitive impairments in the brain-injured groups. Corrected scores have the advantage of controlling for variance associated with premorbid factors rather than changes in neurological functioning; are more helpful in characterizing acquired neurocognitive changes; and can aid in the interpretation of test performance. (PsycINFO Database Record


Non-invasive assessment and clinical strategy of stable coronary artery disease by magnetic resonance imaging, multislice computed tomography and myocardial perfusion SPECT.
Coronary multislice computed tomography (MSCT) angiography and magnetic resonance angiography (MRA) have emerged as new diagnostic techniques that allow direct visualization of the coronary artery. These new modalities have both advantages and disadvantages concerning radiation exposure, the use of contrast medium, ability of visualizing heavily calcified artery lumens, and spatial and temporal resolution. However, these modalities only provide anatomical information of the coronary artery. Functional assessment of the severity of coronary artery disease (CAD) is essential for the management of patients with known or suspected CAD in practical clinical settings. Myocardial perfusion single-photon emission computed tomography is thought to be the most suitable diagnostic procedure for the determination of therapeutic strategy when coronary MSCT and MRA show significant and also insignificant coronary artery lesions. (Circ J 2010; 74: 34 - 40).


The impact of sampling and measurement on the prevalence of self-reported pain in Canada.
Pain is an important public health problem in Canada. International estimates of general population pain prevalence range from 2% to 46%. The purpose of this paper is to critically examine the potentially misleading use of overall prevalence estimates in the pain literature and to use two Canadian population-based surveys to assess the impact of sampling and measurement on prevalence. Two of the secondary data sets used were the 1996/97 National Population and Health Survey (NPHS) and the Canadian Multicentre Osteoporosis Study (CaMos). This paper is based on the assessment of chronic pain in the NPHS, and the assessment of short term pain using the Medical Outcomes Trust's 36-item health survey and the Health Utilities Index, both collected by CaMos. Data are presented as frequencies and percentages overall and stratified by age and sex. CaMos prevalence estimates were age- and sex-standardized to the NPHS population. The overall prevalence of pain was 39% for one-week pain, 66% for four-week pain and 15% for chronic pain. Women were more likely to report pain than men and the prevalence of pain increased with age. This study yields useful information about the self-reported responses to a variety of questions assessing pain in the general population. Responses to the different questions likely represent different categories of pain, such as short term versus chronic pain, which in turn may have different epidemiological risk factors and profiles. Longitudinal studies of the epidemiology, predictors and natural history of chronic pain are urgently needed in the Canadian population.


An analysis of the effectiveness of heat-killed lactic acid bacteria in alleviating allergic diseases.
Allergic diseases are reported to be caused by a skew in the balance between T helper type 1 and 2 cells. Because some lactic acid bacteria have been shown to stimulate IL-12 (p70) production, which in turn shifts the balance between the T helper type 1 and 2 cell response from the latter to the former, they have the potential to either prevent or ameliorate disease conditions or both. They have therefore been extensively studied in the recent past for their probiotic activities. Nevertheless, much less information is available concerning the microbial factors that determine the strain-dependent ability to affect the production of cytokines. The objectives of our study were first to select potentially probiotic lactobacilli that strongly stimulate cytokine production in vitro, and then to determine whether the selected Lactobacillus strains could suppress antigen-specific IgE production in vivo by using allergic model animals. Finally, our investigation was extended to analyze which bacterial components were responsible for the observed biological activity. Twenty strains of heat-killed lactobacilli isolated from humans were screened for their stimulatory activity for the production of IL-12 (p70) by murine splenocytes in vitro. The results showed that some strains of Lactobacillus plantarum and Lactobacillus gasseri had a higher stimulatory activity for IL-12 (p70) production than the other lactobacilli tested; however, this effect was strain dependent rather than species dependent. Oral administration of the heat-killed strains that showed higher stimulatory activity for IL-12 (p70) production tended to reduce the serum antigen-specific IgE levels in ovalbumin-sensitized BALB/c mice compared with the controls. Among the lactobacilli tested, L. gasseri OLL2809 showed the highest activity in reducing the level of antigen-specific IgE. Furthermore, the stimulatory activity for IL-12 (p70) production was found to be reduced after treating the lactobacilli with N-acetyl-muramidase and to be positively correlated with the amount of peptidoglycan in the cells. The present data suggest that L. gasseri OLL2809 is a good candidate for potential probiotics in terms of either the prevention or amelioration of allergic diseases or both. In addition, the strain-dependent stimulatory activity for IL-12 (p70) production was found to be due, at least in part, to the amount of peptidoglycan present in the cells.


The pain intensity at analgesic intake, and the efficacy of diflunisal in single doses and effervescent acetaminophen in single and repeated doses.
A double-blind, randomized analgesic trial was carried out in 150 patients undergoing surgical removal of their 2 impacted lower wisdom teeth. The analgesic efficacy of effervescent acetaminophen 500 or 1000 mg in a 2-dose regimen was compared with that of diflunisal 500 mg in a single dose. Each dose was taken when subjectively needed and the pain intensity was measured on a visual analog scale during the 10-hour period after first medication. The best pain reduction was achieved with diflunisal. The difference between diflunisal 500 mg and acetaminophen 1000 mg was significant, as was that between acetaminophen 1000 and 500 mg. The peak effect after the first dose occurred later but was greater with diflunisal than with acetaminophen. Patients needing analgesics at low pain intensities seemed to discriminate better between treatments, and the efficacy of acetaminophen was weakly dependent on the initial pain intensity. This intensity was difficult to predict, and only a poor correlation was found between the initial pain intensity and the patient's prior estimate of this.


[Isolated jejunal Crohn disease].
Crohn Disease (CD) is a chronic granulomatous inflammatory disorder of not well known etiology. It may affect the whole digestive tract, segmentally, from the mouth to the anus although the rectum is usually not involved. Digestive symptoms of CD depend on the location and extension of the disease, its fistulating or stenosing evolution as well as the presence of local or systemic complications. 40% of the patients affected with CD have simultaneous terminal ileal and colonic involvement, 30% have terminal ileitis and 25% have granulomatous colitis. Isolated esophageal, gastroduodenal and perianal affection reach no more than 5% of the patients. We describe a case of a patient affected with CD with isolated jejunal involvement who was admitted to the hospital because of iron deficiency anemia and bowel subocclusion as an atypical clinical manifestation of the disease. After surgical resection of the affected segment of the bowel, the patient became asymptomatic up to now.


Statin use and hip fractures in U.S. kidney transplant recipients.
Basic and translational research supports beneficial effects of statins on bone metabolism. Clinical studies suggest that statin use may reduce the risk of hip fractures in the general population. Whether statin use is associated with hip fracture risk in kidney transplant recipients, a particularly high-risk group for this outcome, is unknown. From the U.S. Renal Data System (2007-2011), we identified all hip fracture events recorded in Medicare billing claims of first-time kidney transplant recipients. We then matched all cases to an unlimited number of controls on age (±3 years), sex, race (black vs. non-black), and time since transplant. Cases and controls were required to have >1 year of Medicare Parts A + B + D coverage and be without a recorded history of hip fracture. We ascertained any statin use in the previous year and defined adherent statin use as those who had filled prescriptions for statins to cover >80% of days in that year (proportion of days covered, PDC). We ascertained several potential confounders (demographics, comorbidities, BMI, transplant-related factors) and applied conditional logistic regression with multiple imputation for missing data to estimate odds ratios (OR) and 95% confidence intervals (CI). We identified 231 hip fracture cases (mean age 51.8 years; 53% female; 11.3% black; 6.9 years from transplant, and 9.9 years from ESRD) and 15,575 matched controls. Any prior statin use was present in 64.1% of cases and 60.3% of controls with 37.2% of cases and 33.9% of controls being found adherent. Unadjusted conditional logistic regression showed an OR of 1.17 (0.89-1.54) for any statin use, and a fully-adjusted OR of 0.89 (0.67-1.19). Compared with statin non-users, the adjusted OR for patients with lesser adherence (PDC ≤80%) and those with greater adherence (PDC >80%) were 0.93 (0.66-1.31) and 0.87 (0.63-1.20), respectively. Statin use was not associated with hip fracture risk in first-time kidney transplant recipients.


High resolution processing techniques for ultrasound doppler velocimetry in the presence of colored noise. Part I: Nonstationary methods.
Real-time flow velocity measurement is a practical issue in industrial and biomedical applications. Because their good frequency resolution, parametric methods such as autoregressive (AR) modeling and time-frequency distributions (TFD) are generally preferred to Fourier analysis. However, these methods become highly inaccurate in the presence of colored noise. We review here the principal parametric and nonparametric techniques and show their limitations in the estimation of Doppler frequency in the presence of strong colored noise. Different solutions to overcome these limitations are then proposed and compared using synthetic Doppler signals with colored noise.


Gastrointestinal stromal tumor.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These form a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is used not only for diagnosis but also for targeted therapy of GISTs. Imatinib, a tyrosine kinase inhibitor, is widely used in the treatment of advanced and metastatic GISTs and has been recently employed in the neo adjuvant and adjuvant set-up with encouraging results. Certain specific mutations in an exon (such as in exon 9) of the KIT gene result in GISTs that are relatively unresponsive to the Imatinib treatment. New therapeutic agents like Sunitinib have now been approved for the treatment of Imatinib-resistant GIST. This review summarizes the salient features of GIST along with a detailed review of targeted multi-disciplinary approach to the treatment of these special tumors.


Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a validated radiolabeling technique.
A scintigraphic study was carried out to compare the lung deposition of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in healthy volunteers. Validation of Technetium-99m ((99m)Tc) radiolabeling of the budesonide/lactose blend used in the Clickhaler and excipient-free budesonide used in the Turbuhaler was carried out using a multistage liquid impinger, and compared with reference unlabeled devices. Budesonide was quantified using high-performance liquid chromatography and (99m)Tc by scintillation counting. The percentages (SD) of fine particles (<5.5 microm diameter) from radiolabeled and unlabeled devices were not significantly different (p > 0.05). Mean values for drug and radiolabel, respectively, were 34.6% (2.5) and 31.6% (3.8) for the Clickhaler, and 29.8% (5.5) and 31.4% (5 6) for the Turbuhaler. Fifteen healthy male volunteers received a single dose (2 x 200 microg actuations) from both devices in a double-blinded, double dummy, crossover study. During dosing, each inhalation maneuver was recorded using a computer-linked pressure transducer. To permit accurate determination of radiolabeled drug deposition, the lung margins of each volunteer were determined by Krypton-81m ((81m)Kr) gas imaging. Mean [SD] lung deposition for the Clickhaler (26.8% [6.8], RSD 25.2) was significantly greater (p < 0.001) than for the Turbuhaler (15.8% [6.6], RSD 42.2). Inspiratory flow rate parameters were similar for both devices with peak and mean values of 73 and 51 L/min for the Clickhaler, and 73 and 47 L/min for the Turbuhaler, respectively. These results indicate that, in healthy volunteers, budesonide lung deposition was higher and more consistent with the Clickhaler than with the Turbuhaler.


Talking about cancer: Patient responses to raising awareness of oral cancer in primary dental care.
Dentists and other members of the dental team could raise awareness by talking about oral cancer during routine dental check-ups. A communication guide has been developed to facilitate this. However, it has been suggested that discussions about oral cancer may raise patients' anxiety and this has been documented by dentists as a barrier to having these conversations. The current research aimed to investigate implementation of the communication guide and its impact on the dental patient. A consecutive-case sample of adult dental patients attending primary dental care for a routine NHS check-up at one dental practice were invited to take part in the study via letter prior to their appointment. Consultations of participating patients (n = 77) were audio-recorded. Before and after their appointment, patients were asked to rate their current anxiety via the six-item version of Spielberger's State-Trait Anxiety Inventory. Audio recordings of each consultation were reviewed by two raters to determine the extent to which the dentist covered the topics recommended in the communication guide. The dentist informed all patients that they were being checked for oral cancer, spoke about signs and symptoms, and discussed risk factors. However, they rarely recommended where help should be sought or addressed barriers to seeking help. Discussions took an average of 95 s. The extent to which oral cancer was discussed did not correlate with patients' post-appointment anxiety. Patients made positive or neutral responses to the discussions. The few questions that were asked were easily addressed. As findings are based on one dentist working at one practice, generalization of these results should be cautious. The study indicated that using an evidence-based guide to talk about oral cancer did not appear to raise patients' anxiety in this practice population. This could help to increase awareness of oral cancer in the endeavour to facilitate early cancer diagnosis.


Urinary catheter care in the intensive care unit.
Urinary catheters are associated with a number of complications, and nurses are ideally suited to minimize the associated risks by utilizing the available research in their practice. Urine tract infections caused by urine catheters are associated with increased mortality; however, urine catheter care is a nursing procedure, the importance of which is sometimes overlooked. This study reviews recommended guidelines on urine catheter care and current published literature on the subject. The aim of the study was to identify recommended practice and compare it with the current research and literature to conclude best practice. Conclusions made from this study are that existing guidelines correspond to the recommendations and findings in recent research and literature. However, more detailed guidelines and further research on how to prevent catheter-associated urine tract infections and other complications may be of benefit.


Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection.
Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.


[Novel pharmacologic form of ondansetron (Zofran)--lingual tablets in the prevention of cytostatic chemotherapy-induced loss of appetite, nausea and vomiting].
Ondanserton (zofran), 16-32 mg/24 hr, lingual tablets, 2 days, was administered in 40 patients with advanced tumors who received combination chemotherapy (ABVD) (9 patients with Hodgkin's disease), CHOP (16--non-Hodgkin's lymphoma), gemzar + cisplatin (6--ovarian and 5--breast cancer), CAF, AC and taxol + carboplatin) (4). Distinct prophylactic antiemetic effect, delayed effect (94%) included, was reported in the CHOP group: full control--64% and partial control in gemzar + cisplatin treatment (27%). Loss of appetite was prevented in most patients receiving CHOP and gemzar + cisplatin. Untoward side-effects of ondansetron were not registered.


The First Definition of Pulmonary Component of Hypereosinophilic Syndrome: Bronchial Casts.
Hypereosinophilic syndrome is a heterogeneous disease characterized by eosinophilic tissue inflammation and eosinophilia. Pulmonary involvement could be seen in up to 55% among children with hypereosinophilic syndrome. A 3-year-old boy with chronic hypereosinophilia and respiratory complaints was diagnosed with idiopathic hypereosinophilic syndrome. Atelectasis was detected in the radiological evaluation, and bronchial casts with eosinophilic structures were removed by bronchoscopy. Steroid, inhaled hypertonic saline, inhaled bronchodilator, inhaled corticosteroid, and leukotriene receptor antagonist were used for 1 year in the management of hypereosinophilic syndrome, and related eosinophilic casts and repetitive bronchoscopies were administered for removal of the casts. The patient was successfully managed with an inhaled N-acetyl cysteine treatment. In children, the long-term prognosis of hypereosinophilic syndrome is uncertain. Comprehensive diagnostic tests are required for the early diagnosis and management of pediatric hypereosinophilic syndrome. In the presented case, the rare occurrence of pulmonary involvement of hypereosinophilic syndrome in a 3 year-old-boy with recurrent hypereosinophilic casts and its management were discussed.


Safety of Novel Protein Sources (Insects, Microalgae, Seaweed, Duckweed, and Rapeseed) and Legislative Aspects for Their Application in Food and Feed Production.
Novel protein sources (like insects, algae, duckweed, and rapeseed) are expected to enter the European feed and food market as replacers for animal-derived proteins. However, food safety aspects of these novel protein sources are not well-known. The aim of this article is to review the state of the art on the safety of major novel protein sources for feed and food production, in particular insects, algae (microalgae and seaweed), duckweed, and rapeseed. Potential hazards for these protein sources are described and EU legislative requirements as regard to food and feed safety are explained. Potential hazards may include a range of contaminants, like heavy metals, mycotoxins, pesticide residues, as well as pathogens. Some safety aspects of novel protein sources are intrinsic to the product, but many potential hazards can also be due to production methods and processing conditions. These aspects should be considered in advance during product development. European law is unclear on several issues regarding the use of novel protein sources in food and feed products. For food product applications, the most important question for food producers is whether or not the product is considered a novel food. One of the major unclarities for feed applications is whether or not products with insects are considered animal-derived products or not. Due to the unclarities in European law, it is not always clear which Regulation and maximum levels for contaminants apply. For market introduction, European legislation should be adjusted and clarified.


miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer.
MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren's classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103's oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.


Positive predictive value of the AHRQ Patient Safety Indicator "postoperative wound dehiscence".
The Agency for Healthcare Research and Quality patient safety indicator (PSI) 14, or "postoperative wound dehiscence," is 1 of 4 PSIs recently adopted by the Centers for Medicare & Medicaid Services to compare quality and safety across hospitals. We determined how well it identifies true cases of postoperative wound dehiscence by examining its positive predictive value (PPV). A retrospective cross-sectional study of hospitalization records that met PSI 14 criteria was conducted within the Veterans Health Administration hospitals from fiscal years 2003 to 2007. Trained abstractors used standardized abstraction instruments to review electronic medical records. We determined the PPV of the indicator and performed descriptive analyses of cases. Of the 112 reviewed cases, 97 were true events of postoperative wound dehiscence, yielding a PPV of 87% (95% CI 79% to 92%). Sixty-one percent (n = 59) of true positive cases had at least 1 risk factor, such as low albumin level, COPD, or superficial wound infection. False positives were due to coding errors, such as cases in which the patient's abdomen was intentionally left open during the index procedure. PSI 14 has relatively good predictive ability to identify true cases of postoperative wound dehiscence. It has the highest PPV among all PSIs evaluated within the Veterans Health Administration system. Inaccurate coding was the reason for false positives. Providing additional training to medical coders could potentially improve the PPV of this indicator. At present, this PSI is a promising measure for both quality improvement and performance measurement; however, its use in pay-for-performance efforts seems premature.


The importance of intracytoplasmic DPAS positivity in fine needle aspirates of breast lesions.
For many years the presence of strong intracytoplasmic periodic acid Schiff (PAS) positive, diastase resistant (DPAS) staining within atypical cells has been used in this laboratory as a marker for carcinoma in fine needle aspirates from breast lesions. The aim of the current study was to document such DPAS positivity across the spectrum from benign to malignant breast disease and assess its value in the upgrading of cytology reports. Over a six month period, 315 aspirates were studied, each having sufficient cellular material for DPAS staining to be carried out on one whole slide. DPAS staining was recorded semiquantitatively as negative, equivocal, or positive (+, ++, or +++). The cytology results were correlated with any subsequent histology performed on these patients. DPAS positive material was seen in both intracellular and extracellular locations. Care was needed in its interpretation. Occasional cells with apparently genuine intracytoplasmic positivity (+) were found in both benign and malignant cases. Frequent or particularly strong intracellular DPAS positivity (++, +++) correlated best with malignancy. Two cases were reliably upgraded from immediate reports suspicious of malignancy to final reports diagnostic of malignancy on the basis of the intracytoplasmic DPAS staining. Strict criteria are required for the interpretation of intracytoplasmic DPAS positivity and routine cytological appearances should also be taken into account. Weak positivity in occasional cells, especially in flat epithelial sheets, may be seen in benign lesions and is not reliable as a marker of malignancy. DPAS positivity with internal structure and producing nuclear indentation, especially in dissociated or atypical cells, correlates well with malignant histology and can be reassuring in the cytological diagnosis of malignancy.


Binding specificity of the periplasmic oligopeptide-binding protein from Escherichia coli.
The structural properties required for the binding of peptide substrates to the Escherichia coli periplasmic protein involved in oligopeptide transport were surveyed by measuring the ability of different peptides to compete for binding in an equilibrium dialysis assay with the tripeptide Ala-Phe-[3H]Gly. The protein specifically bound oligopeptides and failed to bind amino acids or dipeptides. Acetylation of the peptide amino terminus of (Ala)3 severely impaired binding, whereas esterification of the carboxyl terminus significantly reduced but did not completely eliminate binding. Peptides composed of L-amino acids competed more effectively than did peptides containing D-residues or glycine. Experiments with a series of alanyl peptide homologs demonstrated a decrease in competitive ability with increasing chain length beyond tripeptide. Competition studies with tripeptide homologs indicated that a wide variety of amino acyl side chains were tolerated by the periplasmic protein, but side-chain composition did affect binding. Fluorescence emission data suggested that this periplasmic protein possesses more than one substrate-binding site capable of distinguishing peptides on the basis of amino acyl side chains.


Coincidence-anticipation timing and reaction time in youth tennis and table tennis players.
The purpose of this study was to compare the coincidence-anticipation timing and reaction times (RT) of 10- to 14-year-old tennis and table tennis players and examine possible sex differences. 107 (51.4%) tennis and 101 (48.6%) table tennis players participated in this study. Players were compared on coincidence-anticipation timing and reaction time. Tennis players performed with less error in the coincidence-anticipation timing task than table tennis players, whereas table tennis players had lower mean reaction time than tennis players. It was also found that male players made fewer errors in the coincidence-anticipation timing task than their female counterparts.


Latent membrane protein 1 of Epstein-Barr virus induces CD83 by the NF-kappaB signaling pathway.
Epstein-Barr virus (EBV) infects human resting B cells and transforms them in vitro into continuously growing lymphoblastoid cell lines (LCLs). EBV nuclear antigen 2 (EBNA2) is one of the first viral proteins expressed after infection. It is able to transactivate viral as well as cellular target genes by interaction with cellular transcription factors. EBNA2 target genes can be studied easily by using an LCL (ER/EB2-5) in which wild-type EBNA2 is replaced by an estrogen-inducible EBNA2. Since the cell surface molecule CD83, a member of the immunoglobulin superfamily and a marker for mature dendritic cells, appeared on the surface of ER/EB2-5 cells within 3 h after the addition of estrogen, we analyzed the regulation of CD83 induction by EBV in more detail. Despite its rapid induction, CD83 turned out to be an indirect target gene of EBNA2. We could show that the viral latent membrane protein 1 (LMP1) is responsible for the induction of CD83 by using an LCL expressing a ligand- or antibody-inducible recombinant nerve growth factor receptor-LMP1 fusion protein. The inducibility of the CD83 promoter by LMP1 was mediated by the activation of NF-kappaB, as seen by use of luciferase reporter assays using the CD83 promoter and LMP1 mutants. Additionally, fusion constructs of the transmembrane domain of LMP1 and the intracellular signaling domain of CD40, TNF-R1, and TNF-R2 likewise transactivated the CD83 promoter via NF-kappaB. Our studies show that CD83 is also a target of the NF-kappaB signaling pathway in B cells.


The effect of theophylline on sleep-disordered breathing in patients with stable chronic congestive heart failure.
To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients. Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment. Patients were divided into two groups. Group I (n = 21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AHI)] per hour or less; Group II (n = 15, 41.7%) individuals had an index of more than 15 episodes per hour. In group II, the AHI varied from 16.8 to 78.8 (42.6 +/- 15.5) in which the obstructive AHI was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in group I) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76.7% +/- 4.6% compared with 86.5% +/- 2.8%) and lower left ventricular ejection fraction (24.2% +/- 8.8% compared with 31.5% +/- 10.6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11.3 +/- 2.5) micro g/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20.8 +/- 13.2 vs. 42.6 +/- 15.5; P < 0.001) and the number of episodes of central apnea-hypopnea per hour (10.1 +/- 7.6 vs. 31.5 +/- 9.6; P < 0.001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO(2)) was less than 90 percent (8.8% +/- 8.6% vs. 23.4% +/- 24.1%; P < 0.05) and the arousals per hour (18.7 +/- 21.2 vs. 36.8 +/- 21.3; P < 0.05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment. The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.


Lepidopteran cell variants resistant to 5-bromodeoxyuridine and their use for transfection of the HSV-TK gene.
Following mutagenesis of cultured lepidopteran cells (Spodoptera frugiperda) by ethylmethanesulfonate, three variants resistant to 5-bromodeoxyuridine (BrdUrd) were isolated. These clones were 100- to 200-fold more resistant to BrdUrd than the parental cells and were shown to be deficient in thymidine kinase (TK). The drug-resistant phenotype was stable for up to three years of culture under nonselective conditions. It was also found that the S. frugiperda cell line was highly resistant to aminopterin. A selective medium was formulated and used to select herpes simplex virus thymidine kinase (HSV-TK) transfectants from the TK-deficient cells.


Soluble levels of CD27 and CD30 are associated with risk of non-Hodgkin lymphoma in three Chinese prospective cohorts.
Prospective studies conducted in Western populations have suggested that alterations in soluble CD27 (sCD27) and soluble CD30 (sCD30), two markers indicative of B-cell activation, are associated with risk of non-Hodgkin lymphoma (NHL). Given that the characteristics of NHL in East Asia differ from the West and mechanistic commonalities between these populations with respect to the role of intermediate endpoint biomarkers in lymphomagenesis have not been explored, we conducted a pooled nested case-control study from three prospective studies of Chinese men and women including 218 NHL cases and 218 individually matched controls. Compared with the lowest quartile, ORs (95% CIs) for the second, third and fourth quartiles of sCD27 were 1.60 (0.83-3.09), 1.94 (0.98-3.83) and 4.45 (2.25-8.81), respectively (p(trend) = 0.000005). The corresponding ORs for sCD30 were 1.74 (0.85-3.58), 1.86 (0.94-3.67) and 5.15 (2.62-10.12; p(trend) = 0.0000002). These associations remained statistically significant in individuals diagnosed with NHL 10 or more years after blood draw. Notably, the magnitude of the associations with NHL risk was very similar to those in Western populations in previous studies. These findings of the similar association between sCD27 or sCD30 and NHL risk across different populations support an important underlying mechanism of B-cell activation in lymphomagenesis.


An approach for cutting large and complex pedigrees for linkage analysis.
Utilizing large pedigrees in linkage analysis is a computationally challenging task. The pedigree size limits applicability of the Lander-Green-Kruglyak algorithm for linkage analysis. A common solution is to split large pedigrees into smaller computable subunits. We present a pedigree-splitting method that, within a user supplied bit-size limit, identifies subpedigrees having the maximal number of subjects of interest (eg patients) who share a common ancestor. We compare our method with the maximum clique partitioning method using a large and complex human pedigree consisting of 50 patients with Alzheimer's disease ascertained from genetically isolated Dutch population. We show that under a bit-size limit our method can assign more patients to subpedigrees than the clique partitioning method, particularly when splitting deep pedigrees where the subjects of interest are scattered in recent generations and are relatively distantly related via multiple genealogic connections. Our pedigree-splitting algorithm and associated software can facilitate genome-wide linkage scans searching for rare mutations in large pedigrees coming from genetically isolated populations. The software package PedCut implementing our approach is available at http://mga.bionet.nsc.ru/soft/index.html.


Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables.
Head-down bed rest changes the values of many cardiovascular and endocrine variables and also elicits significant hypovolemia. Because previous studies had not controlled for hypovolemia, it is unknown whether the reported changes were primary effects of bed rest or secondary effects of bed rest-induced hypovolemia. We hypothesized that restoring plasma volume with salt tablets and water after 12 days of head-down bed rest would result in an absence of hemodynamic and endocrine changes and a reduced incidence of orthostatic hypotension. In 10 men, we measured changes from pre-bed-rest to post-bed-rest in venous and arterial pressures; heart rate; stroke volume; cardiac output; vascular resistance; plasma norepinephrine, epinephrine, vasopressin, renin activity (PRA), and aldosterone responses to different tilt levels (0 degrees, -10 degrees, 20 degrees, 30 degrees, and 70 degrees); and plasma volume and platelet alpha2- and lymphocyte beta2-adrenoreceptor densities and affinities (0 degrees tilt only). Fluid loading at the end of bed rest restored plasma volume and resulted in the absence of post-bed-rest orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Fluid loading did not prevent post-bed-rest increases in beta2-adrenoreceptor density or decreases in the aldosterone-to-PRA ratio (P = 0.05 for each). Heart rate, epinephrine, and PRA responses to upright tilt after bed rest were increased (P < 0.05), despite the fluid load. These results suggest that incidents of orthostatic hypotension and many of the changes in supine hemodynamic and endocrine variables in volume-depleted bed-rested subjects occur secondarily to the hypovolemia. Despite normovolemia after bed rest, beta2-adrenoreceptors were upregulated, and heart rate, epinephrine, and PRA responses to tilt were augmented, indicating that these changes are independent of volume depletion.


Should mesenteric tumor deposits be included in staging of well-differentiated small intestine neuroendocrine tumors?
Well-differentiated small intestine neuroendocrine tumors can give rise to mesenteric tumor deposits, which are not included in the current American Joint Committee on Cancer staging system for small intestine neuroendocrine tumors, and their impact on patient prognosis is unknown. Seventy-two small intestine neuroendocrine tumors resections were identified in our files with slides, reports, and follow-up data available. Cases were assessed for T-category and for the presence of mesenteric tumor deposits, lymph node metastases, lymphovascular invasion, and liver metastases. Mesenteric tumor deposits were defined as discrete mesenteric tumor nodules ≥1 mm with an irregular growth profile. Similar lesions clearly resulting from extranodal extension or direct contiguous spread by the primary lesion were excluded. Forty-three of the 72 cases had mesenteric tumor deposits (60%). The deposits were significantly associated with lymphovascular invasion (P=0.001), pT3 or pT4 disease (P=0.001), nodal metastases (P=0.040), and liver metastases (P<0.001) at the time of surgery. In addition, four of six cases with tumor deposits and no nodal disease had liver disease. Tumor deposits were associated with an increased incidence of disease progression and death due to the disease (P=0.001). Finally, the presence of tumor deposits at the time of surgery was associated with an increase in hazard of progression or death due to disease (hazard ratio: 4.0; 95% confidence interval: 1.3, 12.5; P=0.016). Mesenteric tumor deposits are present in the majority of cases of small intestine neuroendocrine tumors and are indicators of poor prognosis for this disease. Therefore, they may have a place in staging of small intestine neuroendocrine tumors, perhaps as analogous to lymph node disease.


Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of prostaglandins.
We investigated the role of prostaglandins in the renal vascular response to exogenous and endogenous adenosine in control and streptozotocin (STZ) diabetic rats. Exogenous adenosine (0.01-100 nmol) injected into the abdominal aorta decreased renal blood flow (RBF) in a dose-dependent manner to a much greater extent in STZ rats than in control rats (P < 0.001). Inhibition of prostaglandin synthesis with indomethacin (Indo; 10 mg/kg iv) potentiated the adenosine-induced renal vasoconstriction in control rats but not in STZ rats. In control rats, Indo shifted the dose response curve of exogenous adenosine-induced RBF reductions to the left by a factor of 10 (ED(50): from 5.5 +/- 0.51 to 0.55 +/- 0.07 nmol adenosine, n = 6, P < 0.001) and in STZ rats only by a factor of two (ED(50): from 0.32 +/- 0.03 to 0.16 +/- 0.02 nmol adenosine, n = 6, P > 0.05). The renal response to endogenous adenosine was assessed by the magnitude of the postocclusive reduction of RBF (POR), an adenosine-mediated phenomenon. POR was greater in STZ rats (-65.3 +/- 5.2%, P < 0.001) compared with control rats (-36.2 +/- 3.5%). Indo markedly enhanced POR in control rats (-20.3 +/- 3.7%) but not in STZ rats (-4.5 +/- 2.7%). Renal cortical and medullary PGE(2) microdialysate concentrations and urinary PGE(2) excretions were clearly not lower in STZ (cortex: 169 +/- 61 pg/ml; medulla: 640 +/- 88 pg/ml, urine: 138 +/- 25 pg/min) compared with control rats (cortex: 99 +/- 12 pg/ml; medulla: 489 +/- 107 pg/ml; urine: 82 +/- 28 pg/min). Indo significantly decreased renal cortical, medullary, and urinary excretion of PGE(2) in STZ and control rats. These findings demonstrate that the adenosine-induced renal vasoconstriction is increased in the presence of Indo in control rats but not in STZ rats. The observations suggest that the diabetic renal vasculature may have a diminished vasodilatory capacity in response to prostaglandins to counteract adenosine-induced renal vasoconstriction.


Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.
ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only.


Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev.
Astrocytes infected with human immunodeficiency virus type 1 (HIV-1) produce only minimal quantities of virus. The molecular events that limit acute-phase HIV-1 infection of astrocytes were examined after inducing acute-phase replication by transfection with the pNL4-3 proviral plasmid. The levels of HIV-1 mRNA were similarly high in both astrocytes and HeLa cells, but astrocytes produced approximately 50-fold less supernatant p24 than HeLa cells. We found that diminished HIV-1 production in astrocytes resulted from inefficient translation of gag, env, and nef mRNAs that were efficiently transported to the cytoplasm. Tat- or Rev-dependent reporter constructs showed no defect in Tat or Rev function in astrocytes compared with HeLa cells. HIV-1 mRNAs were correctly spliced, but only Rev and Tat proteins were efficiently translated from their native mRNAs. Pulse-chase labelling and immunoblot experiments revealed no defect in protein processing, but levels of Gag, Env, or Nef protein expressed were dramatically reduced in astrocytes compared to HeLa cells. These results demonstrate that inefficient translation of HIV-1 structural proteins underlies the restricted infection of astrocytes. The efficient expression of functional Tat and Rev by astrocytes may contribute to HIV-1 neuropathogenesis.


S-adenosylmethionine decarboxylase from human prostate. Activation by putrescine.
1. The presence of S-adenosylmethionine decarboxylase in human prostate gland is reported. A satisfactory radiochemical enzymic assay was developed and the enzyme was partially characterized. 2. Putrescine stimulates the reaction rate by up to 6-fold at pH7.5: the apparent activation constant was estimated to be 0.13mm. The stimulation is pH-dependent and a maximal effect is observed at acid pH values. 3. Putrescine activation is rather specific: other polyamines, such as spermidine and spermine, did not show any appreciable effect. 4. The apparent K(m) for the substrate is 4x10(-5)m. The calculated S-adenosylmethionine content of human prostate (0.18mumol/g wet wt. of tissue) demonstrates that the cellular amounts of sulphonium compound are saturating with respect to the enzyme. 5. The enzyme is moderately stable at 0 degrees C and is rapidly inactivated at 40 degrees C. The optimum pH is about 7.5, with one-half of the maximal activity occurring at pH6.6. 6. Several carboxy-(14)C-labelled analogues and derivatives of S-adenosylmethionine were tested as substrates. The enzyme appears to be highly specific: the replacement of the 6'-amino group of the sulphonium compound alone results in a complete loss of activity. 7. Inhibition of the enzyme activity by several carbonyl reagents suggests an involvement of either pyridoxal phosphate or pyruvate in the catalytic process. 8. The inhibitory effect of thiol reagents indicates the presence of ;essential' thiol groups.


Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization.
the expression of ATP-binding cassette transporters on circulating tumor cells (CTCs) is predictive of response to chemotherapy in cancer patients. We tested the hypothesis that drug-resistant CTCs might have predictive value in metastatic breast cancer (MBC) and possibly retain stem-like properties. CTCs obtained from 42 MBC patients were evaluated for multidrug-resistance-related proteins (MRPs), aldehyde dehydrogenase 1 (ALDH1), estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2/neu). Primary objective was to evaluate the prognostic and predictive value of CTCs profile. Secondary end points were the level of concordance in ERα and HER2/neu status between primary tumors and CTCs and the correlation in CTCs between ALDH1, drug resistance profile and number of MRPs. A difference in progression-free survival (PFS) was found between CTCs-positive and CTCs-negative patients. PFS was shorter in patients with a 'drug resistance' CTCs profile and in patients whose CTCs expressed two or more MRPs. No correlation was found between tumor characteristics and ALDH1. ALDH1 correlated to negative ERα and positive HER2/neu status in CTCs. The correlation between the number of MRPs expressed in CTCs and ALDH1 was statistically significant. in MBC, the presence of CTCs expressing MRPs and ALDH1 is predictive of response to chemotherapy.


Root Exudation of Specialized Molecules for Plant-Environment Interaction.
It has been estimated that between 40 and 60 % of the assimilated carbon is diverted to the roots and released in the rhizosphere in form of root exudates. Root exudates thus define a complex mixture of low and high molecular weight compounds, including carbohydrates, amino acids, organic, and proteins, but also a broad spectrum of specialized molecules, such as flavonoids, glucosinolates, terpenoids, or alkaloids. Root exudates favour soil mineral nutrition, can bind to soil aggregate and in turn modify soil physico-chemical properties, but also mediate plant-plant, plant-microbe, and plant-animal interactions belowground. With this review, we aim to highlight how chemical ecologists have approached the study of root exudates-mediated interactions between plants and their biotic and abiotic surroundings. We do so by presenting a series of study cases for, on one hand, showcasing different methodologies that have been developed to test the activity of different root exudates, and, on the other hand, to show the broad array of interactions mediated by root exudates. Ultimately, we aim to spur further research and collaborations between chemists and ecologists studying belowground chemically-mediated interactions, so as to tackle essential challenges in terms of food security and climate change in the near future.


Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle.
Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α.