Frequency Of Development Of Connective Tissue Disease In Statin-Users Versus Nonusers

Statins have pleiotropic properties that may affect the development of connective tissue diseases (CTD). The objective of this study was to compare the risk of CTD diagnoses in statin users and nonusers. This study was a propensity score-matched analysis of adult patients (30 to 85 years old) in the San Antonio military medical community. The study was divided into baseline (October 1, 2003 to September 30, 2005), and follow-up (October 1, 2005 to March 5, 2010) periods. Statin users received a statin prescription during fiscal year 2005. Nonusers did not receive a statin at any time during the study. The outcome measure was the occurrence of 3 diagnosis codes of the International Classification of Diseases, 9th Revision, Clinical Modification consistent with CTD. We described co-morbidities during the baseline period using the Charlson Comorbidity Index. We created a propensity score based on 41 variables. We then matched statin users and nonusers 1:1, using a caliper of 0.001. Of 46,488 patients who met study criteria (13,640 statin users and 32,848 nonusers), we matched 6,956 pairs of statin users and nonusers. Matched groups were similar in terms of patient age, gender, incidence of co-morbidities, total Charlson Comorbidity Index, health care use, and medication use. The odds ratio for CTD was lower in statin users than nonusers (odds ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.05). Secondary analysis and sensitivity analysis confirmed these results. In conclusion, statin use was associated with a lower risk of CTD. Published by Elsevier Inc.Pharmac

Trypanosomatid Aquaporins: Roles in Physiology and Drug Response

In the class Kinetoplastida, we find an order of parasitic protozoans classified as Trypanosomatids. Three major pathogens form part of this order, Trypanosoma cruzi, Trypanosoma brucei, and Leishmania, which are responsible for disease and fatalities in millions of humans worldwide, especially in non-industrialized countries in tropical and sub-tropical regions. In order to develop new drugs and treatments, the physiology of these pathogenic protozoans has been studied in detail, specifically the significance of membrane transporters in host parasites interactions. Aquaporins and Aquaglyceroporins (AQPs) are a part of the major intrinsic proteins (MIPs) super-family. AQPs are characterized for their ability to facilitate the diffusion of water (aquaporin), glycerol (aquaglyceroporin), and other small-uncharged solutes. Furthermore, AQPs have been shown to allow the ubiquitous passage of some metalloids, such as trivalent arsenic and antimony. These trivalent metalloids are the active ingredient of a number of chemotherapeutic agents used against certain cancers and protozoan parasitic infections. Recently, the importance of the AQPs not only in osmotic adaptations but also as a factor in drug resistance of the trypanosomatid parasites has been reported. In this review, we will describe the physiological functions of aquaporins and their effect in drug response across the different trypanosomatids

GTE. A new software for gravitational terrain effect computation: theory and performances

The computation of the vertical attraction due to the topographic masses, the so-called Terrain Correction, is a fundamental step in geodetic and geophysical applications: it is required in high-precision geoid estimation by means of the remove–restore technique and it is used to isolate the gravitational effect of anomalous masses in geophysical exploration. The increasing resolution of recently developed digital terrain models, the increasing number of observation points due to extensive use of airborne gravimetry in geophysical exploration and the increasing accuracy of gravity data represents nowadays major issues for the terrain correction computation. Classical methods such as prism or point masses approximations are indeed too slow while Fourier based techniques are usually too approximate for the required accuracy. In this work a new software, called Gravity Terrain Effects (GTE), developed to guarantee high accuracy and fast computation of terrain corrections is presented. GTE has been thought expressly for geophysical applications allowing the computation not only of the effect of topographic and bathymetric masses but also those due to sedimentary layers or to the Earth crust-mantle discontinuity (the so-called Moho). In the present contribution, after recalling the main classical algorithms for the computation of the terrain correction we summarize the basic theory of the software and its practical implementation. Some tests to prove its performances are also described showing GTE capability to compute high accurate terrain corrections in a very short time: results obtained for a real airborne survey with GTE ranges between few hours and few minutes, according to the GTE profile used, with differences with respect to both planar and spherical computations (performed by prism and tesseroid respectively) of the order of 0.02 mGal even when using fastest profiles

Torsion and the Gravity Dual of Parity Symmetry Breaking in AdS4/CFT3 Holography

We study four dimensional gravity with a negative cosmological constant deformed by the Nieh-Yan torsional topological invariant with a spacetime-dependent coefficient. We find an exact solution of the Euclidean system, which we call the torsion vortex, having two asymptotic AdS4 regimes supported by a pseudoscalar with a kink profile. We propose that the torsion vortex is the holographic dual of a three dimensional system that exhibits distinct parity breaking vacua. The torsion vortex represents a (holographic) transition between these distinct vacua. We expect that from the boundary point of view, the torsion vortex represents a `domain wall' between the two distinct vacua. From a bulk point of view, we point out an intriguing identification of the parameters of the torsion vortex with those of an Abrikosov vortex in a Type I superconductor. Following the analogy, we find that external Kalb-Ramond flux then appears to support bubbles of flat spacetime within an asymptotically AdS geometry.Comment: 26 pages, 4 figures; v2: minor improvements, references adde

Self-dual gravitational instantons and geometric flows of all Bianchi types

We investigate four-dimensional, self-dual gravitational instantons endowed with a product structure RxM_3, where M_3 is homogeneous of Bianchi type. We analyze the general conditions under which Euclidean-time evolution in the gravitational instanton can be identified with a geometric flow of a metric on M_3. This includes both unimodular and non-unimodular groups, and the corresponding geometric flow is a general Ricci plus Yang-Mills flow accompanied by a diffeomorphism.Comment: Latex, 12 pages; Final versio

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer.

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity