IMPORTANCE: Because of the severity of disease and additional surgery, Crohn disease (CD) may result in intestinal failure (IF) and dependency on home parenteral nutrition (HPN). Defining the ...indication and timing for intestinal transplantation (ITx) is challenging. OBJECTIVES: To determine the limitations of conventional surgery and to facilitate the decision making for transplantation. DESIGN, SETTING, AND PARTICIPANTS: Data were collected prospectively and obtained by retrospective review of medical records from all patients with CD who were assessed for ITx in Oxford, United Kingdom, and Berlin, Germany, from October 10, 2003, through July 31, 2013. Patients were considered suitable for ITx if a diagnosis of irreversible IF was established and life-threatening complications under HPN were unresolvable. Twenty patients with CD and IF, established on HPN, were evaluated for ITx. The mean (SD) age at CD onset was 17.8 (9.8) years. On first diagnosis, most patients had a stricturing CD. By the time of referral, most had a combination of stricturing and fistulizing disease. INTERVENTIONS: New scoring system: a modification of the American Gastroenterology Association guidelines for ITx. Modifications are related to CD-specific issues that potentially lead to a poorer outcome and are based on the findings of the study to determine the expected benefit from ITx. MAIN OUTCOMES AND MEASURES: A scoring system that would alert the physician to the severity of the patient’s CD and trigger early referral for ITx. This system may translate into better long-term outcomes for patients with CD. In addition, the Karnofsky performance status score was used to compare pretransplantation and posttransplantation outcomes. RESULTS: Ten patients underwent ITx, 4 were on the waiting list, and 4 were unavailable for follow-up. One patient was taken off the waiting list because of severe deterioration. One patient underwent conventional stricturoplasty and did not need transplantation. Among the transplant recipients, 17 (85%) had a stoma or enterocutaneous fistula, and the mean (SD) residual bowel length was 71.5 (38) cm. A total of 80% of transplant recipients had life-threatening catheter infections, and 13 (65%) had a significant decrease in the estimated glomerular filtration rate. At a mean (SD) follow-up of 27.6 (36.1) months for transplant recipients, the patient and graft survival is 80%, and their Karnofsky performance status score increased by a mean of 18.6%. CONCLUSIONS AND RELEVANCE: Intestinal transplantation is a suitable treatment option for patients with CD and IF. It should be considered before any additional attempts at conventional surgery, which may cause eligible patients to miss this opportunity through perioperative complications. The suggested scoring system enables the physician to identify patients who may benefit from transplantation before HPN-associated secondary organ failure.
The aorta is a major source of cerebral thromboembolism, but its role in stroke pathogenesis is not well understood due to its poor accessibility for non-invasive imaging. We examined whether ...thoracic aortic calcification (TAC), a marker of aortic plaque load, is associated with stroke in addition to established risk factors.
A total of 3930 subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for incident stroke events over 109.0 ± 23.3 months. Cox proportional hazards regressions were used to examine associations with stroke of TAC in addition to established risk factors (age, sex, systolic blood pressure, LDL, HDL, diabetes, and smoking) and coronary artery calcification (CAC). 101 incident strokes occurred during the follow-up period. Subjects suffering a stroke had significantly higher TAC values at baseline than the remaining subjects (median = 83.1 Q1;Q3 = 4.7;472.9 vs. 15.7 0.0;117.1; P < 0.001). In a multivariable Cox proportional hazards regression, log(TAC + 1) (hazards ratio HR = 1.09 95% confidence interval = 1.00-1.19; P = 0.044) was associated with stroke in addition to established risk factors. Further analyses revealed that log(DTAC + 1), i.e. calcification of the descending aorta (1.11 1.02-1.20; P = 0.016), but not log(ATAC + 1), i.e. calcification of the ascending aorta (1.02 0.93-1.11; P = 0.713), was associated with stroke. The HR for log(TAC + 1) decreased to 1.06 (0.97-1.16; P = 0.202), when log(CAC + 1) was also inserted into multivariable analyses.
Calcification of the thoracic aorta, more specifically its descending segment, is associated with incident stroke in addition to established risk factors. CAC outperforms aortic calcification as a stroke predictor.
Abstract
Background and study aims.
MRI-guided procedures combine high-quality imaging with lack of radiation. Percutaneous transhepatic cholangiodrainage under real-time MRI guidance (MRI-PTCD) ...seems promising, allowing targeted puncture and avoiding multiple blind passes and use of contrast, which are associated with standard PTCD's heaviest complications.
Patients and methods.
Aim of this study was to investigate the feasibility of MRI-PTCD in three outbred piglets. Obstructive cholestasis was induced by common bile duct ligation. Two days later, MRI-PTCD was performed (open MRI, 1.0 Tesla) with prototype MRI-compatible accessories. Visualization was achieved with a balanced steady-state free precession real-time sequence (bSSFP: 0.75 frames/s, TR/TE ms: 7.2/3.6; flip angle: 45°; 200 × 200 matrix size; resolution: 1.3 × 1.3 mm2, slice thickness: 7 mm). Cannulation of the bile ducts was followed by placement of Yamakawa drainages.
Results.
Twelve punctures were performed (four per animal, 10/12 successful); in 2/10 the bile ducts could not be cannulated. Animal survival was 100% and no significant complications occurred.
Conclusions.
Initial data show that MRI-PTCD can be successfully performed. This may lead to establishment of a new optimized PTCD technique compared to the standard approach under fluoroscopy.
ABSTRACTHoppe, MW, Baumgart, C, Sperlich, B, Ibrahim, H, Jansen, C, Willis, SJ, and Freiwald, J. Comparison between three different endurance tests in professional soccer players. J Strength Cond Res ...27(1)31–37, 2013—The aims of this study were (a) to assess and correlate interval shuttle run test (ISRT) performance, maximum oxygen uptake (VCombining Dot AboveO2max), running economy (RE), running velocity at the first rise in blood lactate concentrations above baseline (vLT) and running velocity at 4 mmol·L blood lactate concentration (v4) in professional soccer players and (b) to investigate whether a correlation exists between the respective results of time to exhaustion (Tlim) from continuous and intermittent endurance tests, respectively. Eleven male professional field soccer players (mean ± SDage 23.8 ± 3.0 years, VCombining Dot AboveO2max 58.2 ± 4.9 ml·kg·min) completed a continuous Incremental Test with lactate measurements to determine vLT and v4, a continuous Ramp Test with gas exchange analysis to determine VCombining Dot AboveO2max and RE, and an intermittent ISRT to determine intermittent endurance capacity during the first week of preseason preparation. There were significant correlations between ISRT performance and VCombining Dot AboveO2max (r = 0.70, p < 0.05), and between Tlim in both continuous endurance tests (r = 0.89, p < 0.01). Between all other variables no significant correlations were found overall (best r = 0.60, p > 0.05). The assessment of all values of VCombining Dot AboveO2max, RE, vLT, and v4 should be included when investigating aerobic endurance performance among groups or over time in professional soccer players. Although VCombining Dot AboveO2max, RE, vLT, and v4 have been regarded as important factors of aerobic performance in endurance related sports, the present data revealed that VCombining Dot AboveO2max was the only factor, which correlated with intermittent endurance capacity in professional soccer players. Hence, VCombining Dot AboveO2max should be increased through soccer-specific training interventions including universal agility components. The Tlim in continuous and intermittent endurance tests differs and is therefore an independent endurance performance factor in professional soccer players.
Corynebacterium glutamicum is an important industrial bacterium as well as a model organism for the order Corynebacteriales, whose citric acid cycle occupies a central position in energy and ...precursor supply. Expression of aconitase, which isomerizes citrate into isocitrate, is controlled by several transcriptional regulators, including the dimeric aconitase repressor AcnR, assigned by sequence identity to the TetR family. We report the structures of AcnR in two crystal forms together with ligand binding experiments and in vivo studies. First, there is a citrate-Mg2+ moiety bound in both forms, not in the canonical TetR ligand binding site but rather in a second pocket more distant from the DNA binding domain. Second, the citrate-Mg2+ binds with a KD of 6 mm, within the range of physiological significance. Third, citrate-Mg2+ lowers the affinity of AcnR for its target DNA in vitro. Fourth, analyses of several AcnR point mutations provide evidence for the possible involvement of the corresponding residues in ligand binding, DNA binding, and signal transfer. AcnR derivatives defective in citrate-Mg2+ binding severely inhibit growth of C. glutamicum on citrate. Finally, the structures do have a pocket corresponding to the canonical tetracycline site, and although we have not identified a ligand that binds there, comparison of the two crystal forms suggests differences in the region of the canonical pocket that may indicate a biological significance.
Background: AcnR is an aconitase repressor in the biotechnologically important bacterium Corynebacterium glutamicum.
Results: Citrate-Mg2+ occupies a non-canonical ligand site and lowers the DNA affinity of AcnR.
Conclusion: AcnR is regulated by citrate-Mg2+ through a non-canonical binding site.
Significance: AcnR is the first TetR member with potentially two independent ligand binding sites. Identification of citrate-Mg2+ as a ligand is crucial for understanding its physiological role.
. 1. Knowledge of global diversity patterns is important for research into the factors that shape them, and for systematic conservation planning. However, most species inventories are incomplete and ...biased towards conspicuous, charismatic, geographically widespread, and temperate species. These biases hamper attempts to gain a clear view of underlying diversity patterns, and compromise conservation plans that are based upon what is known.
2. Here we investigate this problem using two methods to estimate species diversity in the parasitic wasp family Braconidae. The first quantifies the effect of taxonomic revisions on species numbers within genera to estimate the present level of underdescription. The second additionally considers the numbers of specimens referred to in descriptions and revisions.
3. Modelling underdescription as a function of region and body size shows that research carried out thus far displays significant geographical and taxonomic biases.
4. Correcting for these biases affects the distribution of inferred undiscovered diversity among braconid subfamilies and among regions, as well as the total diversity estimates for the family.
5. The geographic distribution of levels of underdescription also has implications for latitudinal diversity gradients. Weak or non‐existent gradients in some taxa may be caused simply by differences in the number of undescribed species between tropical and temperate regions.
6. Such analyses can enlighten researchers as to where, taxonomically and geographically, research should be directed to economically improve species richness estimates. In the case of braconid wasps the greatest gains are to be made in Africa and southern America, and for the Braconinae and Microgastrinae.