High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

Dual mobility cup reduces dislocation rate after arthroplasty for femoral neck fracture

<p>Abstract</p> <p>Background</p> <p>Hip dislocation after arthroplasty for femoral neck fractures remains a serious complication. The aim of our study was to investigate the dislocation rate in acute femoral neck fracture patients operated with a posterior approach with cemented conventional or dual articulation acetabular components.</p> <p>Methods</p> <p>We compared the dislocation rate in 56 consecutive patients operated with conventional (single mobility) cemented acetabular components to that in 42 consecutive patients operated with dual articulation acetabular components. All the patients were operated via posterior approach and were followed up to one year postoperatively.</p> <p>Results</p> <p>There were 8 dislocations in the 56 patients having conventional components as compared to no dislocations in those 42 having dual articulation components (p = 0.01). The groups were similar with respect to age and gender distribution.</p> <p>Conclusions</p> <p>We conclude that the use of a cemented dual articulation acetabular component significantly reduces the dislocation rates in femoral neck fracture patients operated via posterior approach.</p

Creating a medical dictionary using word alignment: The influence of sources and resources

<p>Abstract</p> <p>Background</p> <p>Automatic word alignment of parallel texts with the same content in different languages is among other things used to generate dictionaries for new translations. The quality of the generated word alignment depends on the quality of the input resources. In this paper we report on automatic word alignment of the English and Swedish versions of the medical terminology systems ICD-10, ICF, NCSP, KSH97-P and parts of MeSH and how the terminology systems and type of resources influence the quality.</p> <p>Methods</p> <p>We automatically word aligned the terminology systems using static resources, like dictionaries, statistical resources, like statistically derived dictionaries, and training resources, which were generated from manual word alignment. We varied which part of the terminology systems that we used to generate the resources, which parts that we word aligned and which types of resources we used in the alignment process to explore the influence the different terminology systems and resources have on the recall and precision. After the analysis, we used the best configuration of the automatic word alignment for generation of candidate term pairs. We then manually verified the candidate term pairs and included the correct pairs in an English-Swedish dictionary.</p> <p>Results</p> <p>The results indicate that more resources and resource types give better results but the size of the parts used to generate the resources only partly affects the quality. The most generally useful resources were generated from ICD-10 and resources generated from MeSH were not as general as other resources. Systematic inter-language differences in the structure of the terminology system rubrics make the rubrics harder to align. Manually created training resources give nearly as good results as a union of static resources, statistical resources and training resources and noticeably better results than a union of static resources and statistical resources. The verified English-Swedish dictionary contains 24,000 term pairs in base forms.</p> <p>Conclusion</p> <p>More resources give better results in the automatic word alignment, but some resources only give small improvements. The most important type of resource is training and the most general resources were generated from ICD-10.</p

A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle ≥ 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles ≥ 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle ≥ 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness

Biview learning for human posture segmentation from 3D points cloud

Posture segmentation plays an essential role in human motion analysis. The state-of-the-art method extracts sufficiently high-dimensional features from 3D depth images for each 3D point and learns an efficient body part classifier. However, high-dimensional features are memory-consuming and difficult to handle on large-scale training dataset. In this paper, we propose an efficient two-stage dimension reduction scheme, termed biview learning, to encode two independent views which are depth-difference features (DDF) and relative position features (RPF). Biview learning explores the complementary property of DDF and RPF, and uses two stages to learn a compact yet comprehensive low-dimensional feature space for posture segmentation. In the first stage, discriminative locality alignment (DLA) is applied to the high-dimensional DDF to learn a discriminative low-dimensional representation. In the second stage, canonical correlation analysis (CCA) is used to explore the complementary property of RPF and the dimensionality reduced DDF. Finally, we train a support vector machine (SVM) over the output of CCA. We carefully validate the effectiveness of DLA and CCA utilized in the two-stage scheme on our 3D human points cloud dataset. Experimental results show that the proposed biview learning scheme significantly outperforms the state-of-the-art method for human posture segmentation. © 2014 Qiao et al

Comparison of four mathematical models to analyze indicator-dilution curves in the coronary circulation

While several models have proven to result in accurate estimations when measuring cardiac output using indicator dilution, the mono-exponential model has primarily been chosen for deriving coronary blood/plasma volume. In this study, we compared four models to derive coronary plasma volume using indicator dilution; the mono-exponential, power-law, gamma-variate, and local density random walk (LDRW) model. In anesthetized goats (N = 14), we determined the distribution volume of high molecular weight (2,000 kDa) dextrans. A bolus injection (1.0 ml, 0.65 mg/ml) was given intracoronary and coronary venous blood samples were taken every 0.5–1.0 s; outflow curves were analyzed using the four aforementioned models. Measurements were done at baseline and during adenosine infusion. Absolute coronary plasma volume estimates varied by ~25% between models, while the relative volume increase during adenosine infusion was similar for all models. The gamma-variate, LDRW, and mono-exponential model resulted in volumes corresponding with literature, whereas the power-model seemed to overestimate the coronary plasma volume. The gamma-variate and LDRW model appear to be suitable alternative models to the mono-exponential model to analyze coronary indicator-dilution curves, particularly since these models are minimally influenced by outliers and do not depend on data of the descending slope of the curve only

Primary gastric non-Hodgkin's lymphoma in Chinese patients: clinical characteristics and prognostic factors

<p>Abstract</p> <p>Background</p> <p>Optimal management and outcome of primary gastric lymphoma (PGL) have not been well defined in the rituximab era. This study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in Chinese patients with PGL.</p> <p>Methods</p> <p>The clinicopathological features of 83 Chinese patients with PGL were retrospectively reviewed. Staging was performed according to the Lugano staging system for gastrointestinal non-Hodgkin's lymphoma.</p> <p>Results</p> <p>The predominant pathologic subtype among Chinese patients with PGL in our study was diffuse large B cell lymphoma (DLBCL), followed by mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 57 patients with gastric DLBCL, 20 patients (35.1%) were classified as the germinal center B cell-like (GCB) subtype and 37 patients (64.9%) as the non-GCB subtype. The 83 patients had a five-year overall survival (OS) and event-free survival (EFS) of 52% and 59%, respectively. Cox regression analysis showed that stage-modified international prognostic index (IPI) and performance status (PS) were independent predictors of survival. In the 67 B-cell lymphoma patients who received chemotherapy, 36 patients treated with rituximab (at least 3 cycles) had a mean OS of 72 months (95% CI 62-81) versus 62 months (95% CI 47-76) for patients without rituximab treatment (P = 0.021).</p> <p>Conclusion</p> <p>The proportion of Chinese gastric DLBCL cases with non-GCB subtype was higher than the GCB subtype. Stage-modified IPI and PS were effective prognostic factors in Chinese patients with PGL. Our data suggested that primary gastric B-cell lymphoma might have an improved outcome with rituximab in addition to chemotherapy. More studies are necessary, preferentially large prospective randomized clinical trials to obtain more information on the impact of the rituximab in the primary gastric B-cell lymphoma.</p

Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity

Background: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).Methods: Female patients (n = 15) and controls (n = 15) performed a cardiopulmonary exercise test (CPET) by cycling at a continuously increased work rate till maximal exertion. The CPET was repeated 24 h later. Before the tests, blood was taken for the isolation of peripheral blood mononuclear cells (PBMC), which were processed in a special way to preserve their oxidative phosphorylation, which was tested later in the presence of ADP and phosphate in permeabilized cells with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and succinate with rotenone plus or minus the complex II inhibitor malonate in order to measure the ATP production via Complex I and II, respectively. Plasma CK was determined as a surrogate measure of a decreased oxidative phosphorylation in muscle, since the previous finding that in a group of patients with external ophthalmoplegia the oxygen consumption by isolated muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after exercise.Results: At both exercise tests the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients. In the past this was also found in patients with defects in the mitochondrial oxidative phosphorylation. However the oxidative phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma creatine kinase levels before and 24 h after exercise were low in patients and controls, suggesting normality of the muscular mitochondrial oxidative phosphorylation.Conclusion: The decrease in mitochondrial ATP synthesis in the CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing oxidative phosphorylation, but in another factor

Gene Expression Profiling of Vasoregression in the Retina—Involvement of Microglial Cells

Vasoregression is a hallmark of vascular eye diseases but the mechanisms involved are still largely unknown. We have recently characterized a rat ciliopathy model which develops primary photoreceptor degeneration and secondary vasoregression. To improve the understanding of secondary vasoregression in retinal neurodegeneration, we used microarray techniques to compare gene expression profiles in this new model before and after retinal vasoregression. Differential gene expression was validated by quantitative RT-PCR, Western blot and immunofluorescence. Of the 157 genes regulated more than twofold, the MHC class II invariant chain CD74 yielded the strongest upregulation, and was allocated to activated microglial cells close to the vessels undergoing vasoregression. Pathway clustering identified genes of the immune system including inflammatory signaling, and components of the complement cascade upregulated during vasoregression. Together, our data suggest that microglial cells involved in retinal immune response participate in the initiation of vasoregression in the retina