Interdependencies of acquisition, detection, and reconstruction techniques on the accuracy of iodine quantification in varying patient sizes employing dual-energy CT.
To assess the impact of patient habitus, acquisition parameters, detector efficiencies, and reconstruction techniques on the accuracy of iodine quantification using dual-source dual-energy CT (DECT). Two phantoms simulating small and large patients contained 20 iodine solutions mimicking vascular and parenchymal enhancement from saline isodensity to 400 HU and 30 iodine solutions simulating enhancement of the urinary collecting system from 400 to 2,000 HU. DECT acquisition (80/140 kVp and 100/140 kVp) was performed using two DECT systems equipped with standard and integrated electronics detector technologies. DECT raw datasets were reconstructed using filtered backprojection (FBP), and iterative reconstruction (SAFIRE I/V). Accuracy for iodine quantification was significantly higher for the small compared to the large phantoms (9.2 % ± 7.5 vs. 24.3 % ± 26.1, P = 0.0001), the integrated compared to the conventional detectors (14.8 % ± 20.6 vs. 18.8 % ± 20.4, respectively; P = 0.006), and SAFIRE V compared to SAFIRE I and FBP reconstructions (15.2 % ± 18.1 vs. 16.1 % ± 17.6 and 18.9 % ± 20.4, respectively; P ≤ 0.003). A significant synergism was observed when the most effective detector and reconstruction techniques were combined with habitus-adapted dual-energy pairs. In a second-generation dual-source DECT system, the accuracy of iodine quantification can be substantially improved by an optimal choice and combination of acquisition parameters, detector, and reconstruction techniques.


Influenza and bacterial pneumonia--constant companions.
Sequential or concomitant influenza and bacterial pneumonia are two common syndromes seen in community-acquired pneumonia. Inadequacies of diagnostic testing make separating simple pneumonia with either bacteria or influenza from concomitant or sequential influenza with both microorganisms difficult, although the novel 2009 H1N1 epidemic may improve the availability of molecular testing for viruses. Given the frequency of viral pneumonia and diagnostic limitations, empirical antivirals may be underutilized in community-acquired pneumonia. Thankfully, increasingly effective vaccines appear to disrupt this synergistic relationship.


Targets for pollutants in rat and human pancreatic beta-cells: The effect of prolonged exposure to sub-lethal concentrations of hexachlorocyclohexane isomers on the expression of function- and survival-related proteins.
Decades after most countries banned hexachlorocyclohexane, HCH isomers still pollute the environment. Many studies described HCH as a pro-diabetic factor; nevertheless, the effect of HCH isomers on pancreatic beta-cells remains unexplored. This study investigated the effects of a one-month exposure to α-HCH, β-HCH, and γ-HCH on protein expression in human (NES2Y) and rat (INS1E) pancreatic beta-cell lines. α-HCH and γ-HCH increased proinsulin and insulin levels in INS1E cells, while β-HCH showed the opposite trend. α-HCH altered the expression of PKA, ATF3, and PLIN2. β-HCH affected the expression of GLUT1, GLUT2, PKA, ATF3, p-eIF2α, ATP-CL, and PLIN2. γ-HCH altered the expression of PKA, ATF3, PLIN2, PLIN5, and IDH1. From the tested proteins, PKA, ATF3, and PLIN-2 were the most sensitive to HCH exposure and have the potential to be used as biomarkers.


The Thermal and Mechanical Behaviour of Wood-PLA Composites Processed by Additive Manufacturing for Building Insulation.
This study was aimed at considering the potential of wood-based composites processed using additive manufacturing as insulators in the building sector. A polylactic acid blend with 30% wood particles was used as a feedstock material in fused filament technology. Its thermal and mechanical properties were determined for various processing conditions, including printing temperature and infill rate. The results showed a minor contraction in its tensile performance as a result of the printing process. The printing temperature had a negligible effect on its stiffness and a limited influence on the other engineering constants, such as the tensile strength and ultimate stress. The thermal properties of printed structures have been found to significantly depend on the infill rate. Although the tested 3D printed wood-PLA material exhibited good thermal properties, which were tuneable using the printing conditions, its performance was still 38% to 57% lower compared to insulators such as the glass wool of the synthetic foams used in the building sector.


Identification of quantitative trait loci for haloperidol-induced catalepsy on mouse chromosome 14.
Previous studies have established that neuroleptic-induced catalepsy in mice is a highly heritable trait. The current study focuses on the detection of quantitative trait loci (QTL) for haloperidol-induced catalepsy in a BALB/cJ x LP/J F(2) intercross. One thousand thirty-seven F(2) animals were phenotyped and divided into four categories: very responsive (RR), responsive, nonresponsive, and very nonresponsive (NN). The RR and NN phenotypes comprised approximately 18% each of the total and differed in their haloperidol sensitivity by >10-fold. Sex differed significantly between the NN and RR groups (chi(2) = 14.0; p <.0002); females comprised 58% of the RR individuals but only 38% of the NN individuals. The difference between the extreme phenotypes in the number of piebald animals was highly significant (chi(2) = 30, p <. 00001). Eight percent of the RR individuals were piebald compared with 30% of the NN individuals. A genome wide scan confirmed the presence of a QTL (peak LOD = 6.4) on chromosome 14 near the piebald (Ednrb) and 5-hydroxytryptamine(2A) (Htr2a) loci. Although the parental BALB/cJ and LP/J strains differed significantly in striatal 5-hydroxytryptamine(2A) receptor binding, no marked differences were detected between the phenotypic extremes. A second QTL was detected on chromosome 14 (peak LOD = 6.9), which was located more proximally and included the Chat locus. No QTLs were detected on chromosomes 1 and 9, thus differentiating this cross from previous results obtained for a C57BL/6J x DBA/2J intercross.


Pseudomonas abyssi sp. nov., isolated from the abyssopelagic water of the Mariana Trench.
A novel heterotrophic, Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain MT5T, was isolated from deep seawater in the Mariana Trench and characterized phylogenetically and phenotypically. Bacterial optimal growth occurred at 28 °C (range, 4-45 °C), pH 5-7 (pH 4-11) and with 3-7 % (w/v) NaCl (0-18 %). Phylogenetic analysis based on 16S rRNA gene sequence showed that strain MT5T was related to members of the genus Pseudomonas and shared the highest sequence identities with Pseudomonas pachastrellae CCUG 46540T (99.6 %), Pseudomonas aestusnigri VGXO14T (98.5 %) and Pseudomonas oceani KX 20T (98.4 %). The 16S rRNA gene sequence identities between strain MT5T and other members of the genus Pseudomonas were below 96.7 %. The digital DNA-DNA hybridization values between strain MT5T and the two type strains, P. pachastrellae and P. aestusnigri, were 38.9±2.5 and 25.8±2.4 %, respectively. The average nucleotide identity values between strain MT5T and the two type strains were 90.3 and 87.0 %, respectively. Strain MT5T and the two type strains shared 94.98 and 86.2 % average amino acid identity, and 30 and 33 Karlin genomic signature, respectively. The sole respiratory menaquinone was Q-9. The major polar lipids were phosphatidylethanolamine, diphosphatidyglycerol and phosphatidylglycerol. The predominant cellular fatty acids of strain MT5T were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) (35.3 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (24.1 %), C16 : 0 (15.9 %) and C12 : 0 (7.2 %). The G+C content of the genomic DNA was 61.2 mol%. The combined genotypic and phenotypic data indicated that strain MT5T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas abyssi sp. nov. is proposed, with the type strain MT5T (=KCTC 62295T=MCCC 1K03351T).


A daily diary examination of caffeine mixed with alcohol among college students.
Caffeinated alcoholic beverage (CAB) use is associated with a range of substance-related problems. The majority of prior research on CABs is based on cross-sectional and retrospective reports, which do not account for intraindividual differences in use and may be subject to recall biases. The current research used a daily diary, within-subjects design to compare days where individuals simultaneously mixed alcohol with caffeine (CAB days) and days where individuals drank other types of alcohol (non-CAB days) on alcohol use outcomes. These relationships were tested further by examining the impact of the type of mixer (i.e., energy drink or cola-caffeinated). Participants were 122 (73.8% women) heavy drinking, college student CAB users. Mean age was 20.39 (SD = 2.08) years. Students completed a baseline questionnaire and up to 14 consecutive daily surveys about the previous night's drinking behavior. Multilevel modeling results indicated that CAB days were associated with heavier alcohol use, regardless of mixer type. In addition, beyond amount of alcohol consumed the previous night and trait impulsivity, CAB days were linked with more alcohol-related problems, but only when the mixer was an energy drink. CAB days did not differ from non-CAB days on driving or sex after drinking. This study was the first to demonstrate the unique risks posed by simultaneously consuming caffeine and alcohol in a within-subjects, daily diary design. Future research investigating use patterns may benefit from the use of fine-grained approaches in order to provide information relevant for CAB prevention and intervention efforts. (PsycINFO Database Record


Sexual partner age preferences of homosexual and heterosexual men and women.
The sexual age preferences of 192 adults (equal groups of heterosexual men, heterosexual women, homosexual men, and homosexual women) were examined. Participants rated the sexual attractiveness of pictures of 15 male and 15 female faces arranged into five apparent average age categories ranging from 18 to 60 years. It was predicted that homosexual and heterosexual men would prefer younger partners of their preferred sex than would homosexual and heterosexual women and that age preference would not vary with participant age. Both predictions were supported, although homosexual women preferred older partners than expected. Results suggest that age and sex preferences develop independently.


Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome.
Glucocorticoid (GC) resistance complicates the treatment of ~10-20% of children with nephrotic syndrome (NS), yet the molecular basis for resistance remains unclear. We used RNAseq analysis and in silico algorithm-based approaches on peripheral blood leukocytes from 12 children both at initial NS presentation and after ~7 weeks of GC therapy to identify a 12-gene panel able to differentiate steroid resistant NS (SRNS) from steroid-sensitive NS (SSNS). Among this panel, subsequent validation and analyses of one biologically relevant candidate, sulfatase 2 (SULF2), in up to a total of 66 children, revealed that both SULF2 leukocyte expression and plasma arylsulfatase activity Post/Pre therapy ratios were greater in SSNS vs. SRNS. However, neither plasma SULF2 endosulfatase activity (measured by VEGF binding activity) nor plasma VEGF levels, distinguished SSNS from SRNS, despite VEGF's reported role as a downstream mediator of SULF2's effects in glomeruli. Experimental studies of NS-related injury in both rat glomeruli and cultured podocytes also revealed decreased SULF2 expression, which were partially reversible by GC treatment of podocytes. These findings together suggest that SULF2 levels and activity are associated with GC resistance in NS, and that SULF2 may play a protective role in NS via the modulation of downstream mediators distinct from VEGF.


Development of functional extruded snacks by utilizing paste shrimp (Acetes spp.): process optimization and quality evaluation.
Functional extruded snacks were prepared using paste shrimp powder (Acetes spp.), which is rich in protein. The process variables required for the preparation of extruded snacks was optimized using response surface methodology. Extrusion temperature (130-144 °C), level of Acetes powder (100-200 g kg-1 ) and feed moisture (140-200 g kg-1 ) were selected as design variables, and expansion ratio, porosity, hardness, crispness and thiobarbituric acid reactive substance value were taken as the response variables. Extrusion temperature significantly influenced all the response variables, while Acetes inclusion influenced all variables except porosity. Feed moisture content showed a significant quadratic effect on all responses and an interactive effect on expansion ratio and hardness. Shrimp powder incorporation increased the protein and mineral content of the final product. The extruded snack made with the combination of extrusion temperature 144.59 °C, feed moisture 178.5 g kg-1 and Acetes inclusion level 146.7 g kg-1 was found to be the best one based on sensory evaluation. The study suggests that use of Acetes species for the development of extruded snacks will serve as a means of utilization of Acetes as well as being a rich source of proteins for human consumption, which would otherwise remain unexploited as a by-catch. © 2017 Society of Chemical Industry.


The magnitude of decrease in hepatic very low density lipoprotein apolipoprotein B secretion is determined by the extent of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition in miniature pigs.
It has been postulated that the rate of hepatic very low density lipoprotein (VLDL) apolipoprotein (apo) B secretion is dependent upon the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. To test this hypothesis in vivo, apoB kinetic studies were carried out in miniature pigs before and after 21 days treatment with high-dose (10 mg/kg/day), atorvastatin (A) or simvastatin (S) (n = 5). Pigs were fed a diet containing fat (34% of calories) and cholesterol (400 mg/day; 0.1%). Statin treatment decreased plasma total cholesterol [31 (A) vs. 20% (S)] and low density lipoprotein (LDL) cholesterol concentrations [42 (A) vs. 24% (S)]. Significant reductions in plasma total triglyceride (46%) and VLDL triglyceride (50%) concentrations were only observed with (A). Autologous [131I]VLDL, [125I]LDL, and [3H]leucine were injected simultaneously, and apoB kinetic parameters were determined by triple-isotope multicompartmental analysis using SAAM II. Statin treatment decreased the VLDL apoB pool size [49 (A) vs. 24% (S)] and the hepatic VLDL apoB secretion rate [50 (A) vs. 33% (S)], with no change in the fractional catabolic rate (FCR). LDL apoB pool size decreased [39 (A) vs. 26% (S)], due to reductions in both the total LDL apoB production rate [30 (A) vs. 21% (S)] and LDL direct synthesis [32 (A) vs. 23% (S)]. A significant increase in the LDL apoB FCR (15%) was only seen with (A). Neither plasma VLDL nor LDL lipoprotein compositions were significantly altered. Hepatic HMG-CoA reductase was inhibited to a greater extent with (A), when compared with (S), as evidenced by 1) a greater induction in hepatic mRNA abundances for HMG-CoA reductase (105%) and the LDL receptor (40%) (both P < 0.05); and 2) a greater decrease in hepatic free (9%) and esterified cholesterol (25%) (both P < 0.05). We conclude that both (A) and (S) decrease hepatic VLDL apoB secretion, in vivo, but that the magnitude is determined by the extent of HMG-CoA reductase inhibition.


Distinct genetic profiles of Leishmania (Viannia) braziliensis associate with clinical variations in cutaneous-leishmaniasis patients from an endemic area in Brazil.
American tegumentary leishmaniasis (ATL) samples obtained from the lesions of patients with typical (n = 25, 29%), atypical (n = 60, 69%) or both (n = 2%) clinical manifestations were analysed by multilocus enzyme electrophoresis, hsp70 restriction-fragment length polymorphism (PCR-RFLP), hsp70 sequencing and phylogenetics methods. The hsp70 PCR-RFLP analysis revealed two different profiles whose the most samples differed from those expected for Leishmania braziliensis and the other Leishmania species tested: of 39 samples evaluated, two (5%) had a restriction profile corresponding to L. braziliensis, and 37 (95%) had a restriction profile corresponding to a variant pattern. A 1300-bp hsp70 gene fragment was sequenced to aid in parasite identification and a phylogenetic analysis was performed including 26 consensus sequences from the ATL patient's samples and comparing to other Leishmania and trypanosomatids species. The dendrogram allowed to observe a potential population structure of L. braziliensis complex in the studied region, emphasizing that the majority of clinical samples presented a variant genetic profile. Of interest, the L. braziliensis diversity was associated with different clinical manifestations whose parasites with hsp70 variant profile were associated with atypical lesions. The results may be helpful to improve the diagnosis, treatment and control measures of the ATL in endemic areas.


Molecular cloning and characterization of the glucosyltransferase C gene (gtfC) from Streptococcus mutans LM7.
A glucosyltransferase (GTF) gene, designated gtfC, was cloned from Streptococcus mutans LM7. Its gene product was detected by screening a bacteriophage lambda library with rabbit antiserum raised against S. mutans LM7 extracellular proteins. DNA isolated from the immunopositive recombinant phage revealed two S. mutans chromosomal EcoRI fragment inserts, 8.1 and 4.7 kilobase pairs in size. Escherichia coli minicell analyses revealed the approximate position and direction of transcription of the gtfC gene. The gene product was determined to be a polypeptide of about 150 kilodaltons which synthesized a water-soluble glucan. Restriction endonuclease mapping and DNA hybridization indicated a repeated region of DNA corresponding to a portion of the coding region of gtfC immediately downstream from the intact gtfC locus on the chromosome. A 300-base-pair gtfC-specific probe showed that the gene and the putative duplicated sequence were present in S. mutans serotypes c, e, and f, but not in other related oral streptococci which had GTF activity. In addition, the gtfC determinant displayed homology to sequences corresponding to the carboxy-terminal coding region of a gene (gtfB) encoding a GTF activity that synthesized water-insoluble glucans. These data suggest that at least one class of GTF genes may be present in multiple copies in S. mutans and, further, that GTF genes may contain conserved sequences internal to their coding regions.


[Recurrent theca cell tumor].
Thecomas are considered to be benign ovarian tumours. Whether there are malignant thecomas, is a subject of controversy in literature. This contribution describes a case of recurrent thecoma with a clinically malignant course and histological signs of malignant dedifferentiation. The particular diagnostic and therapeutic consequences of this rare disease are discussed with emphasis on the need for radical surgical intervention.


An integrated multi-omics approach to identify regulatory mechanisms in cancer metastatic processes.
Metastatic progress is the primary cause of death in most cancers, yet the regulatory dynamics driving the cellular changes necessary for metastasis remain poorly understood. Multi-omics approaches hold great promise for addressing this challenge; however, current analysis tools have limited capabilities to systematically integrate transcriptomic, epigenomic, and cistromic information to accurately define the regulatory networks critical for metastasis. To address this limitation, we use a purposefully generated cellular model of colon cancer invasiveness to generate multi-omics data, including expression, accessibility, and selected histone modification profiles, for increasing levels of invasiveness. We then adopt a rigorous probabilistic framework for joint inference from the resulting heterogeneous data, along with transcription factor binding profiles. Our approach uses probabilistic graphical models to leverage the functional information provided by specific epigenomic changes, models the influence of multiple transcription factors simultaneously, and automatically learns the activating or repressive roles of cis-regulatory events. Global analysis of these relationships reveals key transcription factors driving invasiveness, as well as their likely target genes. Disrupting the expression of one of the highly ranked transcription factors JunD, an AP-1 complex protein, confirms functional relevance to colon cancer cell migration and invasion. Transcriptomic profiling confirms key regulatory targets of JunD, and a gene signature derived from the model demonstrates strong prognostic potential in TCGA colorectal cancer data. Our work sheds new light into the complex molecular processes driving colon cancer metastasis and presents a statistically sound integrative approach to analyze multi-omics profiles of a dynamic biological process.


Quantum control using quantum memory.
We propose a new quantum numerical scheme to control the dynamics of a quantum walker in a two dimensional space-time grid. More specifically, we show how, introducing a quantum memory for each of the spatial grid, this result can be achieved simply by acting on the initial state of the whole system, and therefore can be exactly controlled once for all. As example we prove analytically how to encode in the initial state any arbitrary walker's mean trajectory and variance. This brings significantly closer the possibility of implementing dynamically interesting physics models on medium term quantum devices, and introduces a new direction in simulating aspects of quantum field theories (QFTs), notably on curved manifold.


Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals.
Amphotericin B (AmB) is one of the few drugs able to prolong survival times in experimental scrapie and delays the accumulation of PrPres, a specific marker of this disease in the brain in vivo. Previous reports showed that the AmB effect is observed only if the drug is administered around the time of infection. In the present study, intracerebrally infected mice were treated with AmB or one of its derivatives, MS-8209, between 80 and 140 days postinoculation. We observed an increased incubation time and a delay in PrPres accumulation and glial fibrillary acidic protein gene expression. Treatment starting at 80 days postinoculation was as efficient as long-term treatment starting the day of inoculation. Our results indicate that polyene antibiotics may interfere, throughout the course of the experimental disease, with the propagation of the scrapie agent.


Breivik--the Norwegian terrorist case.
On July 22, 2011, there were two murderous attacks in Norway. Both assaults - the bombing of governmental buildings in Oslo City center and the lethal shooting down of young members of the Labour Party on an island - were planned and accomplished by a lone perpetrator. These episodes give rise to several interesting questions. What happened really, and how could it happen? Was the perpetrator sane or insane? What was the ideological background for the attacks? It is unnecessary to discuss in any detail whether or not these acts should be categorized as terrorism. However, there is good reason to consider what these terror attacks imply for Norwegian society at large. What significance did the attacks have for Norwegian democracy, and did they have any impact on the 2013 parliamentary elections? What will be the future for the offender, both in the short term and in years to come? What will happen to the Norwegian insanity defense? These questions are addressed in this article.


Prospective, Single-center, Open-label, Pilot Study Using Cryopreserved Umbilical Tissue Containing Viable Cells in the Treatment of Complex Acute and Chronic Wounds.
Complex wounds with exposed bone, muscle, tendon, or hardware continue to be a therapeutic challenge for wound care providers. Wounds with exposed structures are more susceptible to infection, necrosis, and amputation. As such, rapid granulation to cover exposed deep tissue structures is essential for patient recovery. In this prospective, pilot study, the authors evaluate the clinical outcomes of a cryopreserved umbilical tissue graft containing viable cells (vCUT) in the treatment of complex wounds. Ten patients with 12 wounds each received 1 application of vCUT. Two patients did not complete the study and were removed from the per-protocol population. Data analyses were performed on the remaining 8 patients with 10 wounds. The average wound area was 16.5 cm2 with an average duration of 10 months. Post-application, patients were followed for an additional 4 weeks for granulation, closure, and safety outcomes. By the end of the study, 8 of 10 (80.0%) vCUT-treated wounds achieved 100% granulation, and 3 wounds (30.0%) went on to achieve complete closure. The median area reduction was 40.5% and the median volume reduction was 59.4%. The results of this study suggest vCUT in conjunction with standard of care can be a viable treatment option for acute and chronic lower extremity complex wounds.


Photocatalytic degradation of toluene by platinized titanium dioxide photocatalysts.
A photoreactor has been set up to study the photodegradation of volatile organic compound (VOC) in situ. In the reactor, TiO2 and Pt/TiO2 photocatalysts were immobilized on to UV-transparent quartz support. Scanning electron microscope (SEM) studies and Brunauer-Emmett-Teller (BET) surface area measurements revealed that the quartz fiber support was mostly coated with catalyst with a total surface area of 4.0 +/- 0.3 m2/g. The photocatalytic activity of the photocatalysts was evaluated for the photodegradation of 160 ppm toluene-laden air. It was found that 50-70% of toluene was degraded within the first 5 min of UV illumination. Both TiO2 and Pt/TiO2 photocatalysts suffered from deactivation after 18 hours of continuous operation, and the photocatalysts' activity was significantly reduced. However, platinization doubled the photocatalyst life and delayed the onset of de-activation. The presence of moisture was found to shift the onset of catalyst de-activation to an earlier time. It is concluded that the de-activation of the photocatalyst was due to the accumulation of intermediates on the photocatalysts surface preventing the toluene being adsorbed on the photocatalyst surface for degradation.


The Impact of Comorbid Chronic Pain on Pharmacotherapy for Veterans with Post-Traumatic Stress Disorder.
Chronic pain can worsen PTSD symptomatology and may increase the risk of the prescription of multiple central nervous system (CNS)-active medications. The objective is to determine the impact of chronic pain on the number of CNS medications, including psychiatric medications, as well as the amount of medication changes. Veterans Affairs (VA) administrative data were used to identify VA-served Veterans with PTSD (N = 637,428) who had chronic pain (50.3%) and did not have chronic pain (49.7%) in 2020. The outcomes included the number of changes in psychiatric medications and the number of currently prescribed CNS-active mediations during a one-year observation period. The number of changes in psychiatric medications was significantly higher for those with chronic pain (mean (M) = 1.8) versus those without chronic pain (M = 1.6) (Z = 38.4, p < 0.001). The mean number of concurrent CNS-active medications were significantly higher for those with chronic pain (M = 2.7) versus those without chronic pain (M = 2.0) (Z = 179.7, p < 0.001). These differences persisted after adjustment for confounding factors using negative binomial regression. Veterans with comorbid chronic pain and PTSD are at increased risk for a higher number of medication changes and for receiving CNS-active polytherapy.


"All in the Day's Work": Cold War Doctoring and Its Discontents in William Burroughs's Naked Lunch.
In Naked Lunch, the institutions and practices of science and medicine, specifically with regard to psychiatry/psychology, are symptoms of a bureaucratic system of control that shapes, constructs, defines, and makes procrustean alterations to both the mind and body of human subjects. Using sickness and junk (or heroin) as convenient metaphors for both a Cold War binary mentality and the mandatory consumption of twentieth-century capitalism, Burroughs presents modern man as fundamentally alienated from any sense of a personal self. Through policing the health of citizens, the doctors are some of the novel's most overt "Senders," or agents of capital-C Control, commodifying and exploiting the individual's humanity (mind and body) as a raw material in the generation of a knowledge that functions only in the legitimation and reinforcement of itself as authoritative.


Visual skills essential for rugby.
Keen vision is one of the most important qualities required of athletes. It enables players to perform sports-related drills and apply decision-making skills. To accurately measure the visual ability of athletes, it is important to first identify the variety of visual skills involved in the particular sport. The objectives of this novel review are to identify the most important visual skills required for rugby, and to create a reference point for further studies to include visual skills essential to rugby players. We conducted an electronic search with various combinations of relevant keywords using the following databases: Sport Discuss, Ovid's Evidence-Based Medicine Reviews, PubMed/MEDLINE, Current Contents, Science Direct, the National Research Council's Canada Institute for Scientific and Technical Information, Cochrane Database of Systematic Reviews, Google Scholar, and international electronic catalogues to assess the scientific literature related to the visual skills required for rugby. Only the records published in English were included. We extracted data on the relationship between vision and match performance, the defined problem or purpose of the study, and the inclusion of theoretical definitions of tactical behaviors. Our search yielded 80 records, 51 of which fulfilled the inclusion criteria. The most important visual skills in rugby are classified based on whether they meet the requirements for visual hardware or visual software skills. Visual hardware skills include visual acuity, depth perception, fusion flexibility, and contrast sensitivity; visual software skills include eye tracking, hand-eye coordination, eye focusing, peripheral vision, speed and span of recognition, visual response time, and visual memory. Rugby players must use both visual hardware and software skills to reliably observe their teammates' positions, understand their opponents' actions and tactics, handle the ball, analyze the immediate circumstances, and anticipate what will occur. Further studies are needed to verify the significance of each visual skill in actual competition to determine a relationship between vision and the results of a championship.


Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Presenting in Adulthood: a French Nationwide Retrospective Study.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart disease usually diagnosed during the first months of life. Without surgical treatment, ALCAPA carries a high mortality risk, and disease presentation in adulthood is rare. We describe the diagnosis and management of patients presenting with ALCAPA in adulthood. This multicenter French nationwide retrospective study included adult patients diagnosed from 1980 to 2014. Eleven adult patients (mean age: 38 ± 17 years) were analyzed. All patients were symptomatic, presenting with chest pain, palpitations, heart failure, or syncope. Electrocardiogram was abnormal in 8 (73%) patients. Echocardiogram showed a mildly depressed left ventricular ejection fraction of 50 ± 13%, kinetic abnormalities in 5 (45%) patients, and significant mitral regurgitation in 8 (73%) patients. Coronary angiography was performed in 10 (91%) patients and confirmed the diagnosis. Computerized tomography scan, magnetic resonance imaging, and myocardial scintigraphy were performed when deemed necessary. Ten patients underwent reconstructive surgery, but 1 patient was not operated because of age. Four patients experienced postoperative complications including cardiogenic shock, heart failure, renal failure, or additional surgery. After a median follow-up of 2.5 years, all 10 operated patients were alive and asymptomatic, and the nonoperated patient had died at the age of 70 from syncope related to ventricular tachycardia. ALCAPA may be diagnosed in adults. Although complications may occur postoperatively, long-term outcome is favorable in adult patients undergoing surgical correction. Surgery should be discussed as first-line therapy in adults with ALCAPA.


Indolent lymphoplasmacytic and marginal zone B-cell lymphomas: absence of both IRF4 and Ki67 expression identifies a better prognosis subgroup.
Small B-cell indolent lymphomas postulated to be of a post-germinal center origin include marginal zone lymphomas of the spleen (S-MZL) or lymph nodes (N-MZL) and mucosa-associated lymphoid tissue (MALT) lymphomas and lymphoplasmacytic lymphomas (LPL). The existence of rather aggressive cases stresses the need for new biological prognostic markers. We analyzed 90 tumors (20 LPL, 41 MALT lymphomas, 12 N-MZL, 17 S-MZL), investigating the expression of CD5, CD10, CD20, CD23, CD27, CD38, CD79a, CD138, Bcl6, cyclin D1, IRF4 and Ki67 antigens by immunohistochemistry. Results were compared to the histology, the standard clinical and biological parameters, and the global survival. Tumors were all positive for CD20 and CD79a, occasionally positive for CD5, CD23, CD138 and cyclin D1, and all negative for Bcl-6 and CD10. CD38, CD27 and IRF4 expression was heterogeneous. IRF4 expression was correlated with plasma-cell differentiation (p=0.0017). Ki67 expression was increased mainly in N-MZL (66%) and LPL (45%). In terms of overall survival, Ki67, IRF4 and C-reactive protein levels were found to be the 3 independent parameters associated with a worse outcome. Lack of both Ki67 and IRF4 expression was associated with a longer survival (median overall survival 9.8+/-1.1 years versus 3.6+/-1.3 years in the other group) (p=0.0011). Absence of expression of both Ki67 and IRF4 is likely to define a group of memory B-cell lymphomas with a better prognosis. This may have an important impact in the staging of patients since expression of these markers is easily assessed in routine diagnosis.


[Important cardiovascular studies and results in the elderly].
Along with the medical technology that has developed in recent years, the elderly population has started to increase all over the world due to the extension of human life. Chronic diseases have been commonly diagnosed with the increasing population of elderly people. Cardiovascular diseases are the most common cause of death in men and women over 65 years of age. High morbidity and mortality due to cardiovascular disease in elderly patients requires effective prevention and treatment in patients. The incidence of cardiovascular diseases is in direct proportion to age; therefore, hypertension, coronary artery disease, carotid artery disease, stroke, heart failure, arrhythmia and valvular diseases can be identified as common cardiovascular diseases in the elderly population.


Laser-induced thermal lens effect: a new theoretical model.
A theoretical model for the laser-induced thermal lens effect in weakly absorbing media is derived. The model predicts the intensity variation in the far field of the laser beam in the presence of the lensing medium and takes into account the aberrant nature of the thermal lens. Some experimental results which support the validity of this approach are presented.


The omnivorous Tyrolean Iceman: colon contents (meat, cereals, pollen, moss and whipworm) and stable isotope analyses.
The contents of the colon of the Tyrolean Iceman who lived ca. 5300 years ago include muscle fibres, cereal remains, a diversity of pollen, and most notably that of the hop hornbeam (Ostrya carpinifolia) retaining cellular contents, as well as a moss leaf (Neckera complanata) and eggs of the parasitic whipworm (Trichuris trichiura). Based almost solely on stable isotope analyses and ignoring the work on the colon contents, two recently published papers on the Iceman's diet draw ill-founded conclusions about vegetarianism and even veganism. Neither the pollen nor the moss is likely to have been deliberately consumed as food by the Iceman. All the available evidence concerning the Iceman's broad-based diet is reviewed and the significance of the colon contents for matters other than assessment of food intake is outlined.


Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry.
89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2 ± 1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6 ± 3.6% (n = 3) with an equivalent RCP > 90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus and optimisation of the method are required before the flow process is competitive with manual reactions.


[Changes in the rate of surface blood microcirculation studied by photon-correlation spectroscopy in the practical treatment and diagnosis of diabetes mellitus].
The paper is concerned with the results of studies on the basal blood flow and responses of the microcirculatory channel to physiological and pharmacological loads in health and diabetes mellitus using the method of photon-correlation spectroscopy in the light fiber variant. The rate of the basal blood flow in patients with diabetes mellitus (irrespective of the diabetes type) as compared to that in health was significantly lower in the finger tip and tended toward reduction in the inner side of the forearm, lobule of the auricle and in the conjunctiva. The presence of retinopathies in patients with diabetes mellitus resulted in a significant decrease in the rate of the blood flow in the conjunctiva as compared to those in health and diabetes mellitus without retinopathy. The response of the blood flow to physiological (orthostatic and ischemic) and pharmacological (nitroglycerin and pentoxifyllin) tests in patients with diabetes mellitus was also low; the presence of angiopathies caused a more acute reduction of the reactive power of the microcirculatory channel to the orthostatic test. The nature of the nitroglycerin effect in health and diabetes mellitus was different: in the first case noticeable vascular reactions were observed, in the second case a persistent vasodilative effect was observed. The pentoxifyllin effect was characterized by an elevated rate of the blood flow in health and diabetes mellitus.


Gray and color image contrast enhancement by the curvelet transform.
We present in this paper a new method for contrast enhancement based on the curvelet transform. The curvelet transform represents edges better than wavelets, and is therefore well-suited for multiscale edge enhancement. We compare this approach with enhancement based on the wavelet transform, and the Multiscale Retinex. In a range of examples, we use edge detection and segmentation, among other processing applications, to provide for quantitative comparative evaluation. Our findings are that curvelet based enhancement out-performs other enhancement methods on noisy images, but on noiseless or near noiseless images curvelet based enhancement is not remarkably better than wavelet based enhancement.


Neurogenic tumours of the mediastinum: a report of 60 cases.
To analyze retrospectively 60 patients (13 infants and children, 47 adults--21 men and 39 women) with mediastinal neurogenic tumours admitted to Atatürk Centre for Chest Disease and Chest Surgery, Ankara, Turkey between 1988 and 1999. This comprised 21.2% of 283 patients who had surgical operations for all mediastinal masses during the same period. The patients ranged from four to 67 years of age. Thirteen patients were younger than 15 years and 47 were 15 years of age or older. Medical records were reviewed for demographic data, clinical presentation, diagnostic investigations, operative procedures, and tumour location and invasion. Postoperative morbidity and mortality were noted as well as long term follow-up. The clinical investigations included chest x-ray and computed tomography of the thorax in all patients, and spinal magnetic resonance imaging and bronchoscopical examination in some. Clinical variables were compared. The tumours had the following characteristics: 42 (70%) were nerve sheath tumours; 15 (25%) were autonomic ganglion tumours; two (3.6%) were paragangliomas; and one (1.4%) was a malignant peripheral neuroectodermal tumour (Askin's tumour). Nerve cell tumours comprised the majority of tumours in infants and children (nine of 13, 69%), whereas the nerve sheath tumours were most frequent in adults (39 of 47, 83%). There were 48 benign and 12 (20%) malignant tumours when all age groups were considered; the malignancy rate was 61.5% (eight of 13) in children and 8.5% (four of 47, P<0.05) in adults. All patients were operated via a posterolateral thoracotomy. Surgical resection of the tumour was complete in 56 of 60 patients (93.3%). Resection of malignant tumours was grossly incomplete in four cases (four of 12, 33.3%). All benign tumours were totally excised. There were two major complications (respiratory failure and pulmonary emboli) and 14 minor complications in the perioperative period. The mean follow-up period was five years and seven months. Tumours recurred in 5.3% (three of 56) of patients who had a complete resection initially. There were no late deaths related to benign tumours. Complete resection of tumours can be performed safely by a thoracotomy approach and is important for achieving satisfactory long term survival in most mediastinal neurogenic tumours.


The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain.
HIV-1 Vpr is a highly conserved accessory protein that is involved in many functions of the virus life cycle. Vpr facilitates the entry of the HIV pre-integration complex through the nuclear pore, induces G2 cell cycle arrest, regulates cell apoptosis, increases transcription from the long terminal repeat and enhances viral replication. Vpr contains a Leu/Ile-rich domain (amino acids 60-81) in its C-terminal part, which is critical for dimerization. The sequence comprising residues 52-96 is implicated in properties of the protein such as DNA interaction and apoptosis via interaction with the adenine nucleotide translocator. To understand the specific interactions of Vpr-(52-96), the ability of this peptide to dimerize via a leucine-zipper mechanism has been investigated, by NMR and fluorescence spectroscopy. In contrast with results from a study performed in the presence of trifluoroethanol, our results, obtained in 30% (v/v) [2H]acetonitrile, show that Vpr-(52-96) in solution still forms an a-helix spanning residues 53-75, but dimerizes in an antiparallel orientation, through hydrophobic interactions between leucine and isoleucine residues and stacking between His71 and Trp54. Moreover, to demonstrate the physiological relevance of the dimer structure, fluorescence spectroscopy experiments have been performed in a Mes buffer, which confirmed the formation of the dimer in aqueous solution and highlighted the spatial proximity between Trp54 and His71. Surprisingly, the leucine-zipper structure shown in the present work for Vpr-(52-96) mimics the structure of full-length Vpr-(1-96), and this could explain why some of the properties of Vpr-(52-96) and Vpr-(1-96) are identical, while some are even enhanced for Vpr-(52-96), particularly in the case of DNA transfection experiments.


Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis.
To evaluate the efficacy of a biodegradable polymeric scleral plug containing the immunosuppressive agent, FK506, in a rabbit model for experimental uveitis. The scleral plugs were prepared by dissolving poly(DL-lactide-co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high performance liquid chromatography 2 and 4 weeks after intravitreous plug implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, the right eyes of all rabbits were challenged with an intravitreal injection of 50 micro g of antigen. After the first challenge, the 16 eyes of 16 pigmented rabbits were divided into two groups. Scleral plugs were implanted into the vitreous of the right eye of eight rabbits. Eight control rabbits received a sham device. The aqueous protein concentrations and cell counts were determined on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 14 and were observed for 1 month. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG) and histologic examination. Clinical scores (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes had significantly less inflammation than untreated eyes (P<0.001). Quantitative analysis of inflammatory cells (P<0.001) and protein concentrations (P<0.0001) in the anterior chamber showed significant decreases in treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated eyes. No retinal toxicity was detected, histopathologically and electroretinographically. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. Intravitreal sustained-release of FK506 from a biodegradable polymeric scleral plug was highly effective in suppressing the inflammation of experimental uveitis in a rabbit model for at least 6 weeks. This device may be useful in the management of patients with severe chronic uveitis.


Penumbral cooling in ischemic stroke with intraarterial, intravenous or active conductive head cooling: A thermal modeling study.
In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.


The ground state of (CS)4 is different from that of (CO)4: an experimental test of a computational prediction by negative ion photoelectron spectroscopy.
Cyclobutane-1,2,3,4-tetrathione, (CS)4, has recently been calculated to have a singlet ground state, (1)A1g, in which the highest b2g σ MO is doubly occupied and the lowest a2u π MO is empty. Thus, (CS)4 is predicted to have a different ground state than its lighter congener, (CO)4, which has a triplet ground state, (3)B1u, in which these two MOs are each singly occupied. Here, we report the results of a negative ion photoelectron spectroscopy (NIPES) study of the radical anion (CS)4(•-), designed to test the prediction that (CS)4 has a singlet ground state. The NIPE spectrum reveals that (CS)4 does, indeed, have a singlet ground state with electron affinity (EA) = 3.75 eV. The lowest triplet state is found to lie 0.31 eV higher in energy than the ground state, and the open-shell singlet is 0.14 eV higher in energy than the triplet state. Calculations at the (U)CCSD(T)/aug-cc-pVTZ//(U)B3LYP/6-311+G(2df) level support the spectral assignments, giving EA = 3.71 eV and ΔEST = 0.44 eV. These calculated values are, respectively, 0.04 eV (0.9 kcal/mol) smaller and 0.13 eV (3.0 kcal/mol) larger than the corresponding experimental values. In addition, RASPT2 calculations with various active spaces and basis sets converge on a (1)B1u-(3)B1u energy gap of 0.137 eV, in excellent agreement with the 0.14 eV energy difference obtained from the NIPE spectrum. Finally, calculations of the Franck-Condon factors for transitions from the ground state of (CS)4(•-) to the ground ((1)A1g) and two excited states ((3)B1u, (1)B1u) of (CS)4 account for all of the major spectral peaks and nicely reproduce the vibrational structure observed in each electronic transition. The close correspondence between the calculated and the observed features in the NIPE spectrum of (CS)4(•-) provides unequivocal proof that (CS)4, unlike (CO)4, has a singlet ground state.


Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.
Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in patients with chronic heart failure (CHF), and it may be associated with sympathetic activation. The aim of the present study was to evaluate whether CSR could affect prognosis in patients with CHF. Sixty-two CHF patients with left ventricular ejection fraction </=35%, in NYHA class II to III, underwent clinical evaluation, Doppler echocardiography, ergospirometry, phenylephrine test, Holter recording, and a sleep study to evaluate the occurrence of CSR, expressed as percentage of periodic breathing, and apnea/hypopnea index (AHI) (ie, the number of apneas and hypopneas per hour of recording). During a mean follow-up of 28+/-13 months, 15 patients died of cardiac causes. Nonsurvivors were in a higher NYHA functional class than survivors (P<0.001) and had a more depressed left ventricular ejection fraction (P<0.03), a shorter deceleration time of early filling (P<0. 05), larger left and right atria (P<0.05 and P<0.02, respectively) and a lower peak V(O2) (P<0.05). Nonsurvivors also spent a greater percentage of the night in periodic breathing (P<0.01) with a greater AHI (P<0.03) and showed lower values of diurnal baroreflex sensitivity (P<0.05) and of heart rate variability (sdNN: P<0.01). Multivariate analysis revealed the AHI (chi2, 10.4; P<0.01), followed by left atrial area (chi2, 5.7; P<0.01), as the only independent and additional predictors of subsequent cardiac death. Patients at very high risk for fatal outcome could be identified by an AHI >/=30/h and left atria >/=25 cm2. The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI >/=30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.


Andrographolide Protects PC12 Cells Against β-Amyloid-Induced Autophagy-Associated Cell Death Through Activation of the Nrf2-Mediated p62 Signaling Pathway.
Recent studies mentioned that Andrographolide (Andro), the main bioactive component of traditional Chinese medicine Andrographis paniculata, may be a potential natural product for treating Alzheimer's disease, but the underlining mechanism remains to be discovered. In this study, we investigated whether Andro regulates the nuclear factor E2-related factor 2 (Nrf2)/Sequestosome 1 (p62) signaling pathway and activates autophagy to protect neuronal PC12 cells from the toxicity of the β-amyloid (Aβ) peptide. Our results revealed that Andro protected and rescued PC12 cells from Aβ1⁻42-induced cell death and restored abnormal changes in nuclear morphology, lactate dehydrogenase, malondialdehyde, intracellular reactive oxygen species, and mitochondrial membrane potential. RT-PCR and Western blotting analysis demonstrated that Andro activated autophagy-related genes and proteins (Beclin-1 and LC3); meanwhile, it also augmented the Nrf2 and p62 expression in mRNA and protein levels, and reduced p-tau and p21 protein expression in Aβ1⁻42-stimulated cells. Then, further study showed that the pre-transfection of cells with Nrf2 small interfering RNA (siRNA) resulted in the downregulation of p62, Beclin-1, and LC3 proteins expression, as well as the upregulation of p21. Furthermore, the pre-transfection of cells with p62 siRNA didn't block the Nrf2 protein expression, accompanying with an elevated p21. Taken together, these results showed that Andro significantly ameliorated cell death due to Aβ1⁻42 insult through the activation of autophagy and the Nrf2-mediated p62 signaling pathway.


Obesity before age 30 years and risk of advanced prostate cancer.
Adult obesity has shown little association with prostate cancer risk, but obesity at younger ages may be associated with reduced risk. In 1997-2000, the relation between obesity before age 30 years and incident advanced prostate cancer was investigated in a population-based case-control study of African-American and White men (568 cases, 544 controls) in California. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusted for age, race, family history of prostate cancer, and saturated fat intake. Measures of obesity for age 10 years tended to be inversely associated with prostate cancer (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.46, 1.38 for selecting the "obese" pictogram and OR = 0.76, 95% CI: 0.52, 1.11 for reporting being heavier than peers). The decreased risk was more pronounced at ages 20-29 years (OR = 0.53, 95% CI: 0.28, 1.00 for the "obese" drawing, OR = 0.59, 95% CI: 0.40, 0.88 for being heavier than peers, and OR = 0.40, 95% CI: 0.20, 0.81 for body mass index > or =30 kg/m(2)). In addition, both "obese" and small waist size at ages 20-29 years showed inverse trends. This research implicating early-life body size in prostate cancer development helps to elucidate causal mechanisms, such as altered sex hormone profiles during critical developmental periods, potentially involved in development of the disease.


Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma.
Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133(+) cancer stem cells. The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed in colony formation assays, cell invasion assays, chemotherapy resistance studies, and analyzed for the expression of the drug resistance gene ABCG2. About 1% - 2% of Hep-2 cells were CD133(+) cells, and the CD133(+) proportion was enriched by chemotherapy. CD133(+) cancer stem cells exhibited higher potential for clonogenicity and invasion, and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2. This study suggested that CD133(+) cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133(+) cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.


Leber's hereditary optic neuropathy misdiagnosed as optic neuritis and Lyme disease in a patient with multiple sclerosis.
A 28-year-old Caucasian man developed sudden painless vision loss in the right eye. He was diagnosed with optic neuritis. MRI showed white matter lesions consistent with multiple sclerosis (MS), but no optic nerve enhancement. Eight months later, the left eye was affected in the same manner. Examination showed right optic atrophy and apparent left optic disc swelling. Workup revealed positive Lyme IgG. Differential diagnosis included optic neuritis and Lyme optic neuropathy, and he was treated with intravenous steroids, intravenous immunoglobulin, plasmapheresis and intravenous ceftriaxone without improvement. Neuro-ophthalmology consultation led to identification of pseudo-optic disc oedema, and Leber's hereditary optic neuropathy (LHON) was suspected and confirmed by genetic testing. LHON may occur in association with MS, and should be considered in patients with MS with vision loss atypical for optic neuritis. This is especially important as new treatments for LHON (including gene therapy) are currently undergoing clinical trials.


Interventions encouraging the use of systematic reviews by health policymakers and managers: a systematic review.
Systematic reviews have the potential to inform decisions made by health policymakers and managers, yet little is known about the impact of interventions to increase the use of systematic reviews by these groups in decision making. We systematically reviewed the evidence on the impact of interventions for seeking, appraising, and applying evidence from systematic reviews in decision making by health policymakers or managers. Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment Database, and LISA were searched from the earliest date available until April 2010. Two independent reviewers selected studies for inclusion if the intervention intended to increase seeking, appraising, or applying evidence from systematic reviews by a health policymaker or manager. Minimum inclusion criteria were a description of the study population and availability of extractable data. 11,297 titles and abstracts were reviewed, leading to retrieval of 37 full-text articles for assessment; four of these articles met all inclusion criteria. Three articles described one study where five systematic reviews were mailed to public health officials and followed up with surveys at three months and two years. The articles reported from 23% to 63% of respondents declaring they had used systematic reviews in policymaking decisions. One randomised trial indicated that tailored messages combined with access to a registry of systematic reviews had a significant effect on policies made in the area of healthy body weight promotion in health departments. The limited empirical data renders the strength of evidence weak for the effectiveness and the types of interventions that encourage health policymakers and managers to use systematic reviews in decision making.


Beta-endorphin elevations in the ventral tegmental area regulate the discriminative effects of Delta-9-tetrahydrocannabinol.
beta-Endorphin is an endogenous opioid that produces behavioral effects similar to heroin and morphine and is released in the nucleus accumbens by cocaine, amphetamine and ethanol, suggesting a general involvement in the reinforcing effects of abused drugs. Here we show that, in rats, Delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, produces large increases in extracellular levels of beta-endorphin in the ventral tegmental area and lesser increases in the shell of the nucleus accumbens. We then used a two-lever choice THC-discrimination procedure to investigate whether THC-induced changes in endogenous levels of beta-endorphin regulate the discriminative effects of THC. In rats that had learned to discriminate injections of THC from injections of vehicle, the opioid agonist morphine did not produce THC-like discriminative effects but markedly potentiated discrimination of THC. Conversely, the opioid antagonist naloxone reduced the discriminative effects of THC. Bilateral microinjections of beta-endorphin directly into the ventral tegmental area, but not into the shell of the nucleus accumbens, markedly potentiated the discriminative effects of ineffective threshold doses of THC but had no effect when given alone. This potentiation was blocked by naloxone. Together these results indicate that certain psychotropic effects of THC related to drug abuse liability are regulated by THC-induced elevations in extracellular beta-endorphin levels in brain areas involved in opiate reward and reinforcement processes.


Dg93, a nodule-abundant mRNA of Datisca glomerata with homology to a soybean early nodulin gene.
We have isolated a 590-bp full-length cDNA clone designated Dg93, an mRNA that is highly expressed in symbiotic root nodules of the actinorhizal host Datisca glomerata. Dg93 mRNA encodes a deduced polypeptide of 105 amino acids with significant identity (74%) to the soybean (Glycine max) early nodulin (ENOD) gene GmENOD93 (Kouchi and Hata, 1993). Dg93 mRNA is abundant in nodules at 4 weeks post inoculation, the earliest time assayed, and steady-state mRNA levels remain elevated 11 weeks after inoculation. Spatial patterns of Dg93 mRNA expression are complex, with transcript accumulation in the nodule lobe meristem, early infection zone, periderm, and cells of the vascular cylinder, but not in the surrounding uninfected cortical cells. Dg93 is encoded by a small gene family in D. glomerata. To our knowledge, this is the first report of a gene from an actinorhizal host that is expressed in the nodule meristem and that shares sequence homology with an early nodulin gene from a legume.


Frequency of thrombophilia-related genetic variations in patients with idiopathic pulmonary embolism in an urban emergency department.
The frequency of the thrombophilic genetic variants factor V Leiden (FVL) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic pulmonary embolism (PE) has not been measured. This prospective case-control study included patients presenting to urban emergency departments (EDs) with chest pain or shortness of breath. Cases were classified as idiopathic PE (49 patients with PE, but without overt risk factors for thrombosis). Control groups included (a) patients with nonidiopathic PE (152 patients with PE and risk factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out with a structured protocol, including follow-up); and (c) patients in whom PE was not suspected (193 patients without a workup for PE, who were free of PE on follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence variations. Either the FVL or prothrombin variant was found in 10% (95% confidence interval, 3%-22%) of patients with idiopathic PE compared with 13% (8%-20%) of nonidiopathic PE, 2% (5%-14%) of PE excluded, and 9% (5%-14%) of PE not suspected patients. Patients with idiopathic PE tended to have a higher frequency of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine concentrations were not increased [15.6 (5.4) micromol/L vs 12.8 (4.6) micromol/L for homozygous, and wild-type, respectively; P = 0.40]. The frequency of either the FVL or prothrombin sequence variant was not increased in idiopathic PE patients compared with nonidiopathic PE patients or patients who had PE excluded. These data suggest that genotyping to detect idiopathic PE would have limited clinical utility in the urban ED setting.


Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia.
The counterregulatory response to hypoglycemia (CRR), which ensures a sufficient glucose supply to the brain, is an essential survival function. It is orchestrated by incompletely characterized glucose-sensing neurons, which trigger a coordinated autonomous and hormonal response that restores normoglycemia. Here, we investigate the role of hypothalamic Tmem117, identified in a genetic screen as a regulator of CRR. We show that Tmem117 is expressed in vasopressin magnocellular neurons of the hypothalamus. Tmem117 inactivation in these neurons increases hypoglycemia-induced vasopressin secretion leading to higher glucagon secretion in male mice, and this effect is estrus cycle phase dependent in female mice. Ex vivo electrophysiological analysis, in situ hybridization, and in vivo calcium imaging reveal that Tmem117 inactivation does not affect the glucose-sensing properties of vasopressin neurons but increases ER stress, ROS production, and intracellular calcium levels accompanied by increased vasopressin production and secretion. Thus, Tmem117 in vasopressin neurons is a physiological regulator of glucagon secretion, which highlights the role of these neurons in the coordinated response to hypoglycemia.


A consideration of patterns of virulence arising from host-parasite coevolution.
In this article we explore how host survival and fecundity are affected by host-parasite coevolution. We examine a situation in which hosts upon being infected can mount a defensive response to clear the infection, but in which there is a fecundity cost to such immunological up-regulation. We also suppose that the parasite exploits the host and thereby causes an elevated host mortality rate. We determine the coevolutionary stable strategies of the parasite's level of exploitation and the host's level of up-regulation, and illustrate the patterns of reduced host fitness (i.e., virulence) that these produce. We find that counterintuitive patterns of virulence are often expected to arise as a result of the interaction between coevolved host and parasite strategies. In particular, despite the fact that the parasite imposes only a mortality cost on the host, coevolution by the host results in a pattern whereby infected hosts always have the same probability of death from infection, but they vary in the extent to which their fecundity is reduced. This contrasts with previous results and arises from our inclusion of two important factors absent from previous theory: costs of immunological up-regulation and a more suitable measure of parasite-induced mortality.


Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Male Reproductive Functions in Mice.
This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on male reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 males. Prenatal exposure to BPA, BPE, and BPS decreased sperm counts and/or motility and disrupted the progression of germ cell development as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F3 males. Dysregulated serum levels of estradiol-17β and testosterone, as well as expression of steroidogenic enzymes in F3 adult testis were also observed. In the neonatal testis, although apoptosis and DNA damage were not affected, mRNA levels of DNA methyltransferases, histone methyltransferases, and their associated factors were increased by BP exposure. Furthermore, BP exposure induced immunoreactive expression of DNMT3A in Sertoli cells, strengthened DNMT3B, and weakened H3K9me2 and H3K9me3 in germ cells of the neonatal testis, whereas DNMT1, H3K4me3, and H3K27ac were not affected. In adult testis, stage-specific DNMT3B was altered by BP exposure, although DNMT3A, H3K9me2, and H3K9me3 expression remained stable. These results suggest that prenatal exposure to BPA, BPE, and BPS induces transgenerational effects on male reproductive functions probably due to altered epigenetic modification following disruption of DNMTs and histone marks in the neonatal and/or adult testis.


Screening tests for Chlamydia trachomatis or Neisseria gonorrhoeae using the cobas 4800 PCR system do not require a second test to confirm: an audit of patients issued with equivocal results at a sexual health clinic in the Northwest of England, U.K.
To assess the clinical utility of supplementary PCRs following a positive cobas 4800 CT/NG PCR screening test result. Laboratory reports, for Chlamydia trachomatis or Neisseria gonorrhoeae, issued to genitourinary medicine patients between April 2010 and April 2011 were reviewed retrospectively. Positive reports were routinely confirmed by supplementary PCRs and N gonorrhoeae culture. Clinical records of patients with unconfirmed positive (equivocal) reports were retrieved to determine if the infection was confirmed by a second sample obtained at patient recall and the impact of this process on antibiotic management. Over 15 000 patients were tested during the study period. The prevalence of chlamydia and gonorrhoea was 972 (5.75%) and 76 (0.50%), respectively. A further 78 chlamydia and 2 gonorrhoea equivocal reports were issued. Only 56 (72%) patients with an equivocal chlamydia report returned to the clinic, and of these, only 41 (73%) gave a second sample to retest. Positive predictive value (PPV) of the PCR screening test was calculated at 98.0% and 97.5% for detection of chlamydia infection from urine and rectal swabs, respectively. Most patients accepted antibiotic treatment before their infection status had been confirmed. Prevalence of gonorrhoea infection was low but the PPV of the screening PCR in urine specimens remained high (98.75%). Equivocal reports introduce delays to patient management, while the risk of unnecessary antibiotic therapy appears acceptable to most patients. The cobas 4800 CT/NG PCR screening assay can achieve UK testing standards (PPV >90%) for chlamydia, and low prevalence gonorrhoea in urine without supplementary tests. A patient-led confirmation algorithm is proposed.


[Electron transfer in hemoproteins. VI. The dependence of the reduction rate of ferricytochrome c by oxymyoglobin on ionic strength].
The rate of the redox-reaction between MbO2 and ferri-Cyt c has been investigated in the pH range 5-8 under different ionic strength of the solution. The influence of various anions-phosphate, chloride, sulfate and acetat on the rate of the reaction were also studied. It has been shown that under the low ionic strength, I less than 0.1, all pH-dependence curves have pronounced maximum near pH 6.0. While the ionic strength values increase in this interval the reaction rate falls markedly, the profile of lg k versus square root of I/1 + square root of I is linear. Under high ionic strength values, I greater than 0.1, the reaction rate in MbO2-Cyt c system is only slightly influenced by increasing salt concentrations and by pH changing. The results obtained support the idea that the local interactions of charged groups in " active sites" of MbO2 and Cyt c play the most important role in the mechanism of electron transfer. On the contrary net charges of the molecules have a negligible effect on the rate of the reaction. Compared to anions Cl-, SO42- and CH3COO- which influence the reaction rate in an analogous way, phosphate ions have essential inhibiting effect. This is most likely explained by the specific bonding of the phosphate ions to Cty c in the immediate vicinity from the site of the "active contact" with Mb molecule.


Axillary versus Forearm Crutches: A Prospective Cohort Comparing which is Superior for 3-Point Crutch Gait.
Two common crutches utilised for orthopaedic rehabilitation include the axillary crutch and forearm crutch, with either crutch providing weight transfer through different mechanisms. This study aims to determine which crutch is best for patients, with specific reference to crutch gait and stability. This is a level 2 prospective cohort study, recruiting 20 volunteers between 40 to 80 years old. Participants underwent 3 stations in 3 point crutch gait: straight line ambulation of 20m, timed-up-and-go-test, and computerised dynamic posturography. Participants also answered a subjective questionnaire on their crutch preferences. Axillary crutches demonstrated a faster speed of ambulation compared to forearm crutches (Axillary crutch v=0.5m/s, Forearm crutch v=0.44m/s, p=0.002). There was a lower increase in heart rate post activity for axillary crutches. For the timed-up-and-go test, completing the circuit with Axillary crutches was faster (t=63.06, p<0.001) versus the forearm crutch (t=75.36, p<0.001). For computerised dynamic posturography, participants recorded lower effort scores for backward tilts when using axillary crutches (39.13, p=0.0497) versus forearm crutches (42.03, p=0.0497). Subjectively, majority of participants felt that axillary crutches had an easier learning curve and were superior in the areas of ambulation, balance and stability. Our study demonstrated that axillary crutches were superior to forearm crutches for 3-point crutch gait; axillary crutches had a faster ambulation speed, required less effort during use, provided superior stability and were the preferred choice subjectively. This study would be helpful for clinicians and therapists when prescribing mobility aids to individuals with impaired gait.


Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events.
We sought to assess prospectively whether patients with normal coronary angiograms but with impaired myocardial blood flow (MBF) increases to cold pressor testing (CPT) are at increased risk for cardiovascular events. Invasive angiographic assessments of coronary vasomotor function have demonstrated an impairment of endothelium-related coronary flow increases to independently predict future cardiovascular events. It is unknown whether noninvasive positron emission tomography (PET)-measured MBF alterations to sympathetic stimulation with CPT are associated with the risk of developing cardiovascular events. A total of 72 patients (44 men, 28 women, age 58 +/- 8 years) referred for diagnostic cardiac catheterization were studied. Myocardial blood flow was measured in absolute units with (13)N-ammonia using PET, at baseline and during CPT in each patient. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 66 +/- 8 months. Patients were assigned to three groups: group 1, patients with >/=40% increase in MBF (%DeltaMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32; and group 3, patients with decreases in MBF (</=0%), n = 18. During follow-up, one of the group 1 patients developed a cerebral stroke. In group 2, 15 cardiovascular events occurred in 9 patients and in group 3, 7 patients experienced 9 cardiovascular events (p </= 0.0001, univariate by log-rank test). Impaired MBF increases in group 2 and group 3 were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis (p = 0.033, log-rank test). After adjusting for known coronary risk factors, MBF responses to CPT revealed a nonsignificant trend to be independently associated with a higher incidence for cardiovascular events (p = 0.065, multivariate by Cox regression model). Noninvasive PET-measured impaired MBF increases to sympathetic stimulation are associated with the risk of developing cardiovascular events.


The impact of environmental interventions among mouse siblings on the heritability and malleability of general cognitive ability.
General cognitive ability can be highly heritable in some species, but at the same time, is very malleable. This apparent paradox could potentially be explained by gene-environment interactions and correlations that remain hidden due to experimental limitations on human research and blind spots in animal research. Here, we shed light on this issue by combining the design of a sibling study with an environmental intervention administered to laboratory mice. The analysis included 58 litters of four full-sibling genetically heterogeneous CD-1 male mice, for a total of 232 mice. We separated the mice into two subsets of siblings: a control group (maintained in standard laboratory conditions) and an environmental-enrichment group (which had access to continuous physical exercise and daily exposure to novel environments). We found that general cognitive ability in mice has substantial heritability (24% for all mice) and is also malleable. The mice that experienced the enriched environment had a mean intelligence score that was 0.44 standard deviations higher than their siblings in the control group (equivalent to gains of 6.6 IQ points in humans). We also found that the estimate of heritability changed between groups (55% in the control group compared with non-significant 15% in the enrichment group), analogous to findings in humans across socio-economic status. Unexpectedly, no evidence of gene-environment interaction was detected, and so the change in heritability might be best explained by higher environmental variance in the enrichment group. Our findings, as well as the 'sibling intervention procedure' for mice, may be valuable to future research on the heritability, mechanisms and evolution of cognition.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.


Exercise using tongue-holding swallow does not improve swallowing function in normal subjects.
We evaluated the effects of repetitive tongue-holding swallow (THS) as an exercise for improving swallowing function. Twenty healthy subjects were randomly divided into two groups. One group [THS group (THSG)] performed the tongue-holding manoeuvre every 5s for 20min. The other group (normal swallow group) swallowed without tongue-holding for the same length of time as a control. Twenty sessions of training were performed for 4weeks. All participants also had a videofluoroscopic swallowing study for analysing the biomechanical parameters of swallowing (hyolaryngeal movement, posterior pharyngeal wall movement and the pharyngeal constriction ratio). After 4weeks of training, none of the biomechanical parameters changed in either group. Exercise using THS did not affect swallowing function in normal subjects.


Metal-containing peptide nucleic acid conjugates.
Peptide Nucleic Acids (PNAs) are non-natural DNA/RNA analogues with favourable physico-chemical properties and promising applications. Discovered nearly 20 years ago, PNAs have recently re-gained quite a lot of attention. In this Perspective article, we discuss the latest advances on the preparation and utilisation of PNA monomers and oligomers containing metal complexes. These metal- conjugates have found applications in various research fields such as in the sequence-specific detection of nucleic acids, in the hydrolysis of nucleic acids and peptides, as radioactive probes or as modulators of PNA·DNA hybrid stability, and last but not least as probes for molecular and cell biology.


Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation.
Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.


Acute Mitral Regurgitation due to Spontaneous Chordal Rupture in a Patient With Obstructive Hypertrophic Cardiomyopathy.
A 69-year-old male presented with obstructive hypertrophic cardiomyopathy, mitral valve regurgitation, and myxomatous mitral valve prolapse. A spontaneous chordal rupture and acute severe mitral regurgitation resulted in abrupt clinical deterioration despite complete relief of severe left ventricular outflow tract obstruction and systolic anterior motion of the anterior mitral leaflet. The patient underwent extensive cardiac surgery due to intractable heart failure. Surgical procedures included a mitral valve replacement, a septal myectomy, and the Maze procedure.


[Transient elastography (FibroScan): a new tool in hepatology].
Liver stiffness, measured by transient elastography (FibroScan), reflects not only fibrosis of the liver but also intrahepatic inflammation and portal hypertension. The diagnostic performance of FibroScan depends on the care and quality of the procedures used to measure liver stiffness. An experienced physician must interpret the liver stiffness measurement as a function of the clinical situation and other imaging and test results. Liver stiffness is strongly correlated with fibrosis of the liver during hepatitis, with co-infection by HCV (hepatitis C virus) and HIV (human immunodeficiency virus), with recurrence of HCV infection after liver transplantation, and with chronic cholestatic diseases. Liver stiffness is strongly correlated with the severity of portal hypertension and of cirrhosis.


Neural Circuit Transitions Supporting Developmentally Specific Social Behavior.
Environmentally appropriate social behavior is critical for survival across the lifespan. To support this flexible behavior, the brain must rapidly perform numerous computations taking into account sensation, memory, motor-control, and many other systems. Further complicating this process, individuals must perform distinct social behaviors adapted to the unique demands of each developmental stage; indeed, the social behaviors of the newborn would not be appropriate in adulthood and vice versa. However, our understanding of the neural circuit transitions supporting these behavioral transitions has been limited. Recent advances in neural circuit dissection tools, as well as adaptation of these tools for use at early time points, has helped uncover several novel mechanisms supporting developmentally appropriate social behavior. This review, and associated Minisymposium, bring together social neuroscience research across numerous model organisms and ages. Together, this work highlights developmentally regulated neural mechanisms and functional transitions in the roles of the sensory cortex, prefrontal cortex, amygdala, habenula, and the thalamus to support social interaction from infancy to adulthood. These studies underscore the need for synthesis across varied model organisms and across ages to advance our understanding of flexible social behavior.


Serotonin Syndrome in a Patient on Trazodone and Duloxetine Who Received Fentanyl following a Percutaneous Liver Biopsy.
Serotonin syndrome is a rare but potentially life-threatening adverse drug reaction resulting from the use or overuse of serotonergic medications alone or in combination. Mild symptoms, overlapping features with similar conditions and clinician lack of awareness are the major reasons for an often missed diagnosis. Not surprisingly, this condition is significantly underreported as a potential complication of endoscopy if serotonergic medications are used periprocedurally for sedation and analgesia. Here we report the case of a patient with relapsed chronic hepatitis C on antidepressant medications who developed signs and symptoms of serotonin syndrome after a percutaneous liver biopsy. Review of the patient's medication list suggested a possible interaction between her home antidepressants and the post-procedure use of fentanyl for abdominal pain. The patient required monitoring in the medical intensive care unit and stabilized after the administration of benzodiazepines and temporary discontinuation of her home medications. We propose that clinicians need to be aware of the increased risk of serotonin syndrome in the outpatient endoscopy setting, particularly with the wider use of serotonergic antidepressants now available and the repeated number of liver biopsies being performed for management of patients with chronic liver disease.


[What information do patients with schizophrenia have about their illness and treatment?].
Improved compliance with antipsychotic medication is a major issue in schizophrenic management. For this purpose educational programs have been used, but up to now, little or no information has been gathered or published in France concerning schizophrenic patients' opinion on information they have about their disease and their treatment. Thus we conducted a survey in concert with 78 psychiatrists from the French psychiatric health service. From this cross sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4 years) with schizophrenia according to the DSM IV (paranoid sub type: 57%, disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed a questionnaire which assessed their level of information on mental illness and treatment. The diagnosis of schizophrenia has been told to their patients by 39% of the psychiatrists, and treatment has been explained to the patients by 96% of the practitioners. Results indicate less than half of the patients (45%) felt ill, only 46% thought they knew their illness well or very well (nevertheless only 31% of them named spontaneously the diagnosis of schizophrenia or psychosis), and 61% considered that they had been given sufficient information. Most of the patients (79%) were persuaded that their treatment was useful, and 75% of patient were completely satisfied with their treatment. Surprisingly 92% reported taking their medication regularly. Most patients think that a high level of information about their illness (74%) and treatment (79%) help them to cope better with their schizophrenia. Analysis performed according to patients characteristics indicated that paranoid patients felt more ill (p = 0.035) than others, thought to know less about their illness (p = 0.0065), and were less satisfied with their treatment (p = 0.04) and their level of information (p = 0.03). Patients with a duration of their illness longer than 10 years were more convinced of the utility of their treatment (p = 0.02) and had debated more on the choice of their treatment with their psychiatrist (p = 0.047). Patients older than 35 years were more satisfied with their information (p = 0.002). More patients with atypical antipsychotics accepted to take their treatment on a regular basis (p = 0.035) compared to patients under classical neuroleptics. This survey underlines that mental health consumers' opinions can be obtained even in the field of schizophrenia, and argues in favour of further such investigations. It also highlights the need for educational programs on schizophrenia and antipsychotic medications.


Neutral endopeptidase inhibits neuropeptide-mediated transactivation of the insulin-like growth factor receptor-Akt cell survival pathway.
G-protein coupled receptor (GPCR) agonists such as neuropeptides activate the insulin-like growth factor-1 receptor (IGF-IR) or the serine-threonine protein kinase Akt, suggesting that neuropeptides-GPCR signaling can cross-communicate with IGF-IR-Akt signaling pathways. Neutral endopeptidase 24.11 (NEP) is a cell-surface peptidase that cleaves and inactivates the neuropeptides endothelin-1 (ET-1) and bombesin, which are implicated in progression to androgen-independent prostate cancer (PC). We investigated the mechanisms of NEP regulation of neuropeptide-mediated cell survival in PC cells, including whether neuropeptide substrates of NEP induce phosphorylations of IGF-IR and Akt in PC cells. Western analyses revealed ET-1 and bombesin treatment induced phosphorylation of IGF-IRbeta and Akt independent of IGF-I in TSU-Pr1, DU145, and PC-3 PC cells, which lack NEP expression, but not in NEP-expressing LNCaP cells. Recombinant NEP and induced NEP expression in TSU-Pr1 cells using a tetracycline-repressive expression system inhibited ET-1-mediated phosphorylation of IGF-IRbeta and Akt, and blocked the protective effects of ET-1 against apoptosis induced by serum starvation. Incubation of TSU-Pr1 cells with specific kinase inhibitors together with ET-1 or bombesin showed that IGF-IR activation is required for neuropeptide-induced Akt phosphorylation, and that neuropeptide-induced Akt activation is predominantly mediated by Src and phosphatidylinositol 3-kinase but not by mitogen-activated protein kinase or protein kinase C. These data show that the neuropeptides ET-1 and bombesin stimulate ligand-independent activation of the IGF-IR, which results in Akt activation, and that this cross-communication between GPCR and IGF-IR signaling is inhibited by NEP.


Presupervised and post-supervised prototype classifier design.
We extend the nearest prototype classifier to a generalized nearest prototype classifier (GNPC). The GNPC uses "soft" labeling of the prototypes in the classes, thereby encompassing a variety of classifiers. Based on how the prototypes are found we distinguish between presupervised and postsupervised GNPC designs. We derive the conditions for optimality (relative to the standard Bayes error rate) of two designs where prototypes represent: 1) the components of class-conditional mixture densities (presupervised design) or 2) the components of the unconditional mixture density (postsupervised design). An artificial data set and the "satimage" data set from the database ELENA are used to experimentally study the two approaches. A radial basis function (RBF) network is used as a representative of each GNPC type. Neither the theoretical nor the experimental results indicate clear reasons to prefer one of the approaches. The postsupervised GNPC design tends to be more robust and less accurate than the presupervised one.


Effects of correction of Class II malocclusion on the kinesiographic pattern of young adolescents: a case- control study.
The aim of this study was to assess the dynamic activity of the mandible by means of a computerised kinesiograph in Class II patients treated with orthodontic therapy and to compare the results of this group with those of a sample of untreated Class II patients. Twenty young adolescents who had undergone orthodontic treatment for correction of Class II malocclusion and twenty age and sex-matched adolescents exhibiting Class II malocclusion, whose parents refused the orthodontic treatment, were enrolled. Maximum vertical opening (MVO), maximum anterior-posterior movement (MAPM), maximum right deviation (MRD), maximum left deviation (MLD), MVO/ MAPM ratio, maximum velocity in opening (MVIO), maximum velocity in closure (MVIC), verticality (ID-V), anterior-posteriority (ID-AP) and laterality (ID-L) were recorded during the kinesiographic evaluations. Differences in the kinesiographic data were analysed using the Wilcoxon sum rank test; data are expressed as means and standard deviations (SD). Differences between groups in age were analysed using unpaired t-test, while differences in gender distribution were assessed using the Fisher's exact test. The level of significance was set at p < 0.05. No differences were detected in the distribution of sex and age between the two groups. Significant differences between the two groups were observed for MVO, MAPM, that were higher in the control group, and MLD, which was higher in the case group; no other significant differences were detected for MRD, MVO/ MAPM, MVIO, MVIC, ID-V, ID-AP, ID-L. Orthodontic treatment of young patients with Class II malocclusion may reduce the maximum vertical opening as well as the maximum anterior-posterior movement and enhance the lateral displacement; however, further studies are needed to assess the relationship between impaired mandible kinetics of orthodontic treatment in patients with Class II malocclusion and craniomandibular disorders.


A sub-process view of working memory capacity: evidence from effects of speech on prose memory.
In this article we outline a "sub-process view" of working memory capacity (WMC). This view suggests that any relationship between WMC and another construct (e.g., reading comprehension) is actually a relationship with a specific part of the WMC construct. The parts, called sub-processes, are functionally distinct and can be measured by intrusion errors in WMC tasks. Since the sub-processes are functionally distinct, some sub-process may be related to a certain phenomenon, whereas another sub-process is related to other phenomena. In two experiments we show that a sub-process (measured by immediate/current-list intrusions) is related to the effects of speech on prose memory (semantic auditory distraction), whereas another sub-process (measured by delayed/prior-list intrusions), known for its contribution to reading comprehension, is not. In Experiment 2 we developed a new WMC task called "size-comparison span" and found that the relationship between WMC and semantic auditory distraction is actually a relationship with a sub-process measured by current-list intrusions in our new task.


Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial.
The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.