Postoperative urinary retention:Risk factors, bladder filling rate and time to catheterization: an observational study as part of a randomized controlled trial

Background: Knowledge of risk factors for postoperative urinary retention may guide appropriate and timely urinary catheterization. We aimed to determine independent risk factors for postoperative urinary catheterization in general surgical patients. In addition, we calculated bladder filling rate and assessed the time to spontaneous voiding or catheterization. We used the patients previously determined individual maximum bladder capacity as threshold for urinary catheterization.Methods: Risk factors for urinary catheterization were prospectively determined in 936 general surgical patients. Patients were at least 18 years of age and operated under general or spinal anesthesia without the need for an indwelling urinary catheter. Patients measured their maximum bladder capacity preoperatively at home, by voiding in a calibrated bowl after a strong urge that could no longer be ignored. Postoperatively, bladder volumes were assessed hourly with ultrasound. When patients reached their maximum bladder capacity and were unable to void, they were catheterized by the nursing staff. Bladder filling rate and time to catheterization were determined.Results: Spinal anesthesia was the main independent modifiable risk factor for urinary catheterization (hyperbaric bupivacaine, relative risk 8.1, articaine RR 3.1). Unmodifiable risk factors were a maximum bladder capacity &lt;500 mL (RR 6.7), duration of surgery &gt;= 60 min (RR 5.5), first scanned bladder volume at the Post Anesthesia Care Unit &gt;= 250mL (RR 2.1), and age &gt;= 60 years (RR 2.0). Urine production varied from 100 to 200 mL/h. Catheterization or spontaneous voiding took place approximately 4 h postoperatively.Conclusion: Spinal anesthesia, longer surgery time, and older age are the main risk factors for urinary retention catheterization. Awareness of these risk factors, regularly bladder volume scanning (at least every 3 h) and using the individual maximum bladder capacity as volume threshold for urinary catheterization may avoid unnecessary urinary catheterization and will prevent bladder overdistention with the attendant risk of lower urinary tract injury.</p

From failure to meet the clinical endpoint to US Food and Drug Administration approval: 15th antisense oligonucleotide therapy approved Qalsody (tofersen) for treatment of SOD1 mutated amyotrophic lateral sclerosis

Functional Genomics of Muscle, Nerve and Brain Disorder

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy:One-year follow-up

Objective: Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS). Methods: Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and number and duration of RP attacks were reported over a 2-week period. Perfusion was assessed with a cooling and recovery procedure at baseline and one year after SPTS. Furthermore, laser speckle contrast analysis, pulse wave velocity, heart rate variability and nailfold capillary microscopy were performed. Results: One year after SPTS the duration of the attacks of was reduced with 1.9 h in the left hand versus 0.3 h in the right hand. Furthermore, three aspects of the questionnaire showed a significant improvement (role limitations due to physical health (p = 0.017), pain (p = 0.027) and physical functioning (p = 0.025)). The total area under the curve of the total cooling and recovery procedure of the left hand was larger one year after surgery (101 (75–140) at baseline versus 118 (95–190) one year post-operatively, p = 0.012), implying a better perfusion in the fingers. This was mainly due to the improvement during the recovery phase (21 (1–41) at baseline versus 38 (24–43) one year post-operatively, p = 0.028). Conclusion: One year after unilateral R3 SPTS the benefit with regard to the majority of outcome variables persisted, though some effects seem to attenuate. Long-term effects and long-term follow-up results will be investigated in an on-going study. Clinical trial registration number: NCT02680509

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy:a novel minimally invasive endoscopic technique

OBJECTIVE: To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. METHODS: Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. RESULTS: Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. CONCLUSION: Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. CLINICAL TRIAL REGISTRATION NUMBER: NCT02680509

In patients with primary Sjögren’s syndrome innate-like MAIT cells display upregulated IL-7R, IFN-γ, and IL-21 expression and have increased proportions of CCR9 and CXCR5-expressing cells

Introduction: Mucosal-associated invariant T (MAIT) cells might play a role in B cell hyperactivity and local inflammation in primary Sjögren’s syndrome (pSS), just like previously studied mucosa-associated CCR9+ and CXCR5+ T helper cells. Here, we investigated expression of CCR9, CXCR5, IL-18R and IL-7R on MAIT cells in pSS, and assessed the capacity of DMARDs to inhibit the activity of MAIT cells. Methods: Circulating CD161+ and IL-18Rα+ TCRVα7.2+ MAIT cells from pSS patients and healthy controls (HC) were assessed using flow cytometry, and expression of CCR9, CXCR5, and IL-7R on MAIT cells was studied. Production of IFN-γ and IL-21 by MAIT cells was measured upon IL-7 stimulation in the presence of leflunomide (LEF) and hydroxychloroquine (HCQ). Results: The numbers of CD161+ and IL-18Rα+ MAIT cells were decreased in pSS patients compared to HC. Relative increased percentages of CD4 MAIT cells in pSS patients caused significantly higher CD4/CD8 ratios in MAIT cells. The numbers of CCR9 and CXCR5-expressing MAIT cells were significantly higher in pSS patients. IL-7R expression was higher in CD8 MAIT cells as compared to all CD8 T cells, and changes in IL-7R expression correlated to several clinical parameters. The elevated production of IL-21 by MAIT cells was significantly inhibited by LEF/HCQ treatment. Conclusion: Circulating CD161+ and IL-18Rα+ MAIT cell numbers are decreased in pSS patients. Given their enriched CCR9/CXCR5 expression this may facilitate migration to inflamed salivary glands known to overexpress CCL25/CXCL13. Given the pivotal role of IL-7 and IL-21 in inflammation in pSS this indicates a potential role for MAIT cells in driving pSS immunopathology

Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease

<p>Abstract</p> <p>Background</p> <p>Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.</p> <p>Results</p> <p>Before aggregation, up-regulation of gene expression predominated, while after aggregates became visible, down-regulation and up-regulation occurred to the same extent. After aggregates became visible there was a down-regulation of dopamine biosynthesis genes accompanied by down-regulation of dopamine levels in culture, indicating the utility of this model to identify functionally relevant pathways. Furthermore, genes of the anti-oxidant Nrf2-ARE pathway were up-regulated, possibly as a protective mechanism. In parallel, we discovered alterations in genes which may result in increased oxidative stress and damage.</p> <p>Conclusion</p> <p>Up-regulation of gene expression may be more important in HD pathology than previously appreciated. In addition, given the pathogenic impact of oxidative stress and neuroinflammation, the Nrf2-ARE signaling pathway constitutes a new attractive therapeutic target for HD.</p

Deregulated splicing is a major mechanism of RNA-induced toxicity in Huntington's disease

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant HTT RNA belong to the spliceosome pathway, (II) expression of mutant CAG repeat RNA induces mis-splicing in a HD cell model, (III) overexpression of one of the splice factors trapped by mutant HTT ameliorates the HD phenotype in a fly model and (VI) deregulated splicing occurs in human HD brain. Our data suggest that deregulated splicing is a prominent mechanism of RNA-induced toxicity in HD

On the lease rate, convenience yield and speculative effects in the gold futures market

By examining data on the gold forward offered rate (GOFO) and lease rates over the period 1996- 2009, we conclude that the convenience yield of gold is better approximated by the lease rate than the interest-adjusted spread of Fama & French (1983). Using the latter quantity, we study the relationship between gold leasing and the level of COMEX discretionary inventory and exhibit that lease rates are negatively related to inventories. We also show that Futures prices have increasingly exceeded forward prices over the period, and this effect increases with the speculative pressure and the maturity of the contracts

РАЗРАБОТКА НОВОГО РЕАГЕНТНОГО РЕЖИМА ФЛОТАЦИИ УГЛЕЙ ПАО "ДТЭК ДОБРОПОЛЬСКАЯ ЦОФ"

Совершенст- вование процесса флотации углей, поиск эффективных реагентов и оптималь- ных технологических режимов – один из главных факторов, от которых зависит технологическая и экономическая результативность флотационного обогаще- ния

Comparison of the confidence in freedom from infection based on different control programmes between EU member states: STOC free

The STOC free project constructed a generic framework that allows a standardised and harmonised description of different control programmes (CP) for cattle diseases. The STOC free model can be used to determine the confidence of freedom from infection that has been achieved in disease CPs, in support of an ongoing assessment of progress towards output-based standards as outlined in the EU Animal Health Law. With this information, and as required, further CP actions can be taken to mitigate the risks of persistence and (re-)introduction on the probability of freedom from infection. Bovine viral diarrhoea virus (BVDV) was chosen as the case disease because of the diversity in CPs in the six participating countries. A Bayesian hidden Markov model was considered the best modelling method. Detailed BVDVCP information was collected in the participating countries and the key aspects for inclusion in the STOCfree model were identified. A first version of STOC free model was developed and tested on simulated data. The risk factors for BVDV infection that needed to be included in the model were defined and default values for these risk factors were quantified. A data collection tool was finalised with which the data for the STOC free model was collected. Subsequently, the developed model was tested and validated using real BVDV CP data from partner countries. Based on the feedback, the model was finalised and the report and corresponding computer code were made publicly available. There were roughly three different BVDV situations that occurred in the partner countries: 1. Endemic situation with a CP operating at herd level, 2. Endemic situation with a CP operating at animal level and 3. BVD free situation. The STOC free model is able to include herd level data only and animal level data has to be aggregated to herd level before the model can be applied. The STOC free model is not applicable for a country that is completely BVDV free given that it needs some infections to estimate its parameters and converge. In the latter situation, a scenario tree model could be a better suited tool, and this was evaluated in the Swedish case study. Further work is needed for generalisation of the method to other diseases and expansion of the method to include socioeconomic aspects of CPs <br/