KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P 0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

Networked statehood: an institutionalised self-contradiction in the process of globalisation?

World economy and world science have not yet found a counterpart in a world state and probably never will. However, the contours of a political system have emerged, which fulfil the functions of statehood at the global level. Such a system does not take the form of a uniform corporative-hierarchical collectivity but of networked statehood, ie a network of individual states, international organisations, and transnational regimes. Relying on social science and legal constructions, this article offers a positive and negative definition of this concept and an analysis of its intrinsically self-contradictory character traits. Despite these unavoidable contradictions, this article argues that networked statehood still provides considerable advantages and outlines general principles of a future law of networked statehood. These outlines are founded on the belief that networked statehood must be seen as a new and distinct legal form of action but likewise facing the problem of democratic legitimacy

Common Scaling Patterns in Intertrade Times of U. S. Stocks

We analyze the sequence of time intervals between consecutive stock trades of thirty companies representing eight sectors of the U. S. economy over a period of four years. For all companies we find that: (i) the probability density function of intertrade times may be fit by a Weibull distribution; (ii) when appropriately rescaled the probability densities of all companies collapse onto a single curve implying a universal functional form; (iii) the intertrade times exhibit power-law correlated behavior within a trading day and a consistently greater degree of correlation over larger time scales, in agreement with the correlation behavior of the absolute price returns for the corresponding company, and (iv) the magnitude series of intertrade time increments is characterized by long-range power-law correlations suggesting the presence of nonlinear features in the trading dynamics, while the sign series is anti-correlated at small scales. Our results suggest that independent of industry sector, market capitalization and average level of trading activity, the series of intertrade times exhibit possibly universal scaling patterns, which may relate to a common mechanism underlying the trading dynamics of diverse companies. Further, our observation of long-range power-law correlations and a parallel with the crossover in the scaling of absolute price returns for each individual stock, support the hypothesis that the dynamics of transaction times may play a role in the process of price formation.Comment: 8 pages, 5 figures. Presented at The Second Nikkei Econophysics Workshop, Tokyo, 11-14 Nov. 2002. A subset appears in "The Application of Econophysics: Proceedings of the Second Nikkei Econophysics Symposium", editor H. Takayasu (Springer-Verlag, Tokyo, 2003) pp.51-57. Submitted to Phys. Rev. E on 25 June 200

Imaging assessment and clinical significance of pneumatosis in adult patients.

Gas detection in the bowel wall and in portomesenteric venous vessels in adults has long been related to intestinal infarction and poor outcome; many case reports have shown that pneumatosis may be associated with a large variety of pathological situations, ranging from absolutely benign and asymptomatic forms to abdominal catastrophes. Several studies have been conducted on this topic with different conclusions, probably due to differences in population so that the clinical value of these signs is still questioned. Intestinal pneumatosis, especially if presenting with a band-like pattern and if associated with portomesenteric vein gas, when observed in an acute abdominal setting should raise the suspicion of mesenteric infarct and prompt a careful search for other signs of intestinal involvement, so as not to miss cases of life-threatening intestinal infarct or allow them to further evolve into extensive necrosis with worse prognosis. In this review we illustrate the most relevant aspects of these debated but significant radiological signs

Developments in unsteady pipe flow friction modelling

This paper reviews a number of unsteady friction models for transient pipe flow. Two distinct unsteady friction models, the Zielke and the Brunone models, are investigated in detail. The Zielke model, originally developed for transient laminar flow, has been selected to verify its effectiveness for "low Reynolds number" transient turbulent flow. The Brunone model combines local inertia and wall friction unsteadiness. This model is verified using the Vardy's analytically deduced shear decay coefficient C* to predict the Brunone's friction coefficient k rather than use the traditional trial and error method for estimating k. The two unsteady friction models have been incorporated into the method of characteristics water hammer algorithm. Numerical results from the quasi-steady friction model and the Zielke and the Brunone unsteady friction models are compared with results of laboratory measurements for water hammer cases with laminar and low Reynolds number turbulent flows. Conclusions about the range of validity for the three friction models are drawn. In addition, the convergence and stability of these models are addressed.Anton Bergant, Angus Ross Simpson, John Vìtkovsk

Executive function abnormalities in pathological gamblers

Background: Pathological gambling (PG) is an impulse control disorder characterized by persistent and maladaptive gambling behaviors with disruptive consequences for familial, occupational and social functions. The pathophysiology of PG is still unclear, but it is hypothesized that it might include environmental factors coupled with a genetic vulnerability and dysfunctions of different neurotransmitters and selected brain areas. Our study aimed to evaluate a group of patients suffering from PG by means of some neuropsychological tests in order to explore the brain areas related to the disorder. Methods: Twenty outpatients (15 men, 5 women), with a diagnosis of PG according to DSM-IV criteria, were included in the study and evaluated with a battery of neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Wechsler Memory Scale revised (WMS-R) and the Verbal Associative Fluency Test (FAS). The results obtained in the patients were compared with normative values of matched healthy control subjects. Results: The PG patients showed alterations at the WCST only, in particular they had a great difficulty in finding alternative methods of problem-solving and showed a decrease, rather than an increase, in efficiency, as they progressed through the consecutive phases of the test. The mean scores of the other tests were within the normal range. Conclusion: Our findings showed that patients affected by PG, in spite of normal intellectual, linguistic and visual-spatial abilities, had abnormalities emerging from the WCST, in particular they could not learn from their mistakes and look for alternative solutions. Our results would seem to confirm an altered functioning of the prefrontal areas which might provoke a sort of cognitive "rigidity" that might predispose to the development of impulsive and/or compulsive behaviors, such as those typical of PG. © 2008 Marazziti et al; licensee BioMed Central Ltd

The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial

Objective: To evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. Study design: Multicenter, prospective, randomized controlled trial. Setting: University hospitals. Participants: 80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. Methods: Subjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. Results: On the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician's assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. Conclusion: Treatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman's compliance. Trial registration: ClinicalTrials.gov NCT06316219

Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis

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