Electrophysiological measures and dual-task performance in Tourette syndrome indicate deficient divided attention mechanisms

Tourette syndrome has been associated with impairments of attentional functions such as distractability, even in subjects without co-morbid attention deficit hyperactivity disorder. Based on the results of earlier research we hypothesized that Tourette syndrome patients might employ altered control mechanisms of attentional processes and have concurrent difficulties in allocating their attentional resources among competing tasks. Event-related brain potentials (ERPs) were recorded in a group of Tourette syndrome patients and in a matched control group during a dual task experiment. This experiment required the simultaneous detection of visual and auditory target stimuli which were manipulated to yield two different difficulty levels each of which were varied orthogonally. The behavioural parameters confirmed the intended performance differences between difficult-to-detect targets and easy-to-detect targets. This was paralleled by lower amplitudes and longer latencies of the corresponding P3b-ERP subcomponents. Although Tourette syndrome patients were unimpaired in overall performance they showed an increased interference of visual task demands with auditory target perception. In parallel they also exhibited a reduced amplitude of the P3b component to auditory targets. The findings show that Tourette syndrome patients are not generally impaired in their dual task performance. The allocation of attentional resources to competing tasks however, is altered. We speculate that this may be related to deficient inhibitory functions.     

Inactivation of Apoe and Apoc1 by two consecutive rounds of gene targeting: effects on mRNA expression levels of gene cluster members

The genes encoding apolipoprotein (apo) E and apoC1 are, togetherwith the gene for apoC2, located in a conserved gene clusteron human chromosome 19q12-13.2 and mouse chromosome 7. Althoughthe significance of apoE as a ligand for receptor-mediated uptakeof lipoprotein remnant particles is undisputed, the in vivofunction of apoC1 and the possible interaction between apoEand apoC1 in the modulation of plasma cholesterol and triglyceridelevels is far from understood. Our strategy to unravel the metabolicrelationship between apoE and apoC1 in vivo is to first generatemice deficient in both apolipoproteins, enabling future productionof transgenic mice with variable ratios of normal and mutantapoE and apoC1 on a null background. Here we report the creationand characterization of mice deficient in both apoE and apoC1.As these genes are tightly genetically linked, double-deficientmice were obtained by two consecutive rounds of gene targetingin mouse embryonic stem cells. Surprisingly, double in activationof the Apoe and Apoc1 gene loci as well as single inactivationsat either one of these loci were found to affect also the RNAexpression levels of the other gene members in the Apoe-c1-c2cluster. This indicates that targeted insertions are not necessarilyneutral for the expression of nearby gene members in a givengene cluster. Homozygous Apoe-c1 knockout mice are hypercholesterolemic,with serum cholesterol levels of 12.5 ± 4.3 mM comparedwith 2.9 ± 0.5 mM in control mice, resembling mice solelydeficient in apoE.     

Role of cytokines in the progression of renal damage in IgA nephropathy

Summary: IgA nephropathy, or Berger's disease (IgAN), is a worldwide disease which is characterized by a slowly progressive loss of renal function accompanied by decreasing kidney size with the development of glomerulosclerosis and interstitial fibrosis. Immunologic and non-immunologic factors are implicated in the progression of renal damage, since they are potent inducers in stimulating glomerular, tubular and interstitial cells and non-resident cells to produce free oxygen radicals, cytokines, growth factors, chemokines, etc. Recent data from our laboratory and other groups, synthesized in this review, have demonstrated the remarkable involvement of these humoral factors in the progression of renal damage in IgAN patients. Therefore, prospective therapeutic approaches have been suggested in blocking the inflammatory mediators during the pathophysiologic sequelae of immune and non-immune mechanisms which may intervene in the outcome of the disease.     

KGF-transfected cells can stimulate growth and proliferation of human cultured keratinocytes in vitro

Objective: To establish two stably KGF-transfected, immortalized cell lines. Methods: HaCaT-keratinocytes and KMST-6-fibroblasts were transfected by liposome mediated gene transfer. Transfection effectivity, gene integration and configuration of the transgenic protein were investigated by ELISA, DANN-PCR and β-Gal-staining. Results: Most effective GF producing clones were tested by a colorimetric XTT-test. Conclusion: This is a significant acceleration of cell proliferation and mitosis of human keratinocytes in an Air Liquid Interface (ALI) test system.     

A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals

Background Despite the potential of clinical practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before–after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain management, antithrombotics, fluid and electrolyte management, prescribing in case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophylaxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consultations, combining medication review of patients who are at risk for drug related problems with visits to ward physicians. Main outcome measure The outcome measure was the proportion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49–0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.     

Low pH and ketoacids induce insulin receptor binding and postbinding alterations in cultured 3T3 adipocytes

The etiology of insulin resistance during diabetic ketoacidosis is still poorly understood. Changes in insulin receptor binding and the existence of postreceptor alterations have been proposed. In an attempt to clarify the role of low pH and ketone bodies in the insulin resistance, we examined the effectiveness of insulin during and after 48 h of exposure of cultured 3T3-L1 adipocytes to low pH and ketoacids. In the "acute" stage, lowering of physiologic pH (pH 7.4) to pH 6.9 induced a decrease in insulin binding (50%), which was due to a decrease in the rate of association. Concomitantly, the insulin sensitivity was decreased (ninefold). The basal hexose uptake and insulin responsiveness were only slightly decreased at low pH. Beta-hydroxybutyrate partially counteracted the effect of low pH on insulin binding and sensitivity in a dose-dependent fashion (ED50: 10 mM). The binding-enhancing effect of ketoacids was more pronounced at low pH than at physiologic pH and absent at optimum pH (pH 8.0). After 48 h of exposure of the cells to pH 6.9, insulin binding and insulin sensitivity (measured at physiologic pH) were similar as in cells cultured at pH 7.4. The insulin response, however, was substantially impaired (40%), due to an increase in basal hexose uptake as well as a decrease in maximal insulin-stimulated uptake. These postbinding alterations induced by low pH could be reversed by culturing the cells at physiologic pH for another 48 h. Prolonged exposure to ketoacids did not affect the insulin effectiveness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Communism and women's same-sex practises in post-Suharto Indonesia

The Indonesian Communist Organization Gerwani was banned in 1966. It had been associated with sexual perversions during the 1 October 1965 putsch in which senior figures within the Indonesian army were killed. These accusations helped fuel the massacre of over a million people and brought General Suharto to power. Yet in many ways Gerwani's ideology was puritanical and geared towards strengthening the monogamous family unit. It breached traditional gender ideology only in its insistence that women should be political actors and militant mothers. More recently, the organization has been accused of 'promoting lesbianism', when it in fact has never discussed the issue. This paper analyses Gerwani's ideology to explore the link between political activism and sexuality. The women's organization can be regarded as one of the forces of 'modernity' which stimulated homophobia. It is suggested that Gerwani's political activism was considered such a breach of traditional gender ideologies that it triggered a fear of social disorder in which women would be free from male heterosexual control - either as loose, perverted women who were seen as liable to castrate generals, or as lesbians.     

Positioning functional foods in an ecological approach to the prevention of overweight and obesity

To contribute to the social debate about the role of functional foods in the prevention of overweight and obesity using an ecological model to study the positioning of functional foods and their social implications. Positioning was conceptualized as the relative attention given to functional foods within the range of preventive strategies, and the way in which they address specific causes of overweight. A systematic review was conducted to identify (A) preventive strategies aiming at the individual; (B) technological approaches; and (C) environmental strategies. All strategies were further classified according to the nature of causes they refer to – either individual or environmental. In the prevention of overweight/obesity, an emphasis on strategies designed to change the quality of food products and supplies has developed. Technological strategies particularly relate to functional foods; however, while providing a new dimension to food products, they do not challenge the underlying lifestyles causing overweight. Furthermore, they also stress individual responsibility for overweight/obesity and technological solutions to it. From a societal perspective, the characteristics of functional foods indicate that they can only be expected to play a limited role in overweight/obesity prevention. The ecological approach suggests that other strategies targeting individual and social causes need to be developed and marketed equally well.