第7章 平成22～24年度特別研究「地域歴史遺産保全活用教育研究を基軸とした地域歴史文化育成支援拠点の整備」事業を定着・普及させる活動

Purpose: Intra-abdominal hypertension (IAH) and Abdominal compartment syndrome (ACS) are relatively rare, but severe complications. Although many advances were made in recent years, the recognition and management remain subject of debate. The aim of this study was to determine the current state of awareness, knowledge and use of evidence-based medicine regarding IAH and ACS among Dutch surgeons. Methods: A literature-based and expert consensus survey was developed. One surgeon in every hospital in The Netherlands was asked to complete the online questionnaire. Results: Sixty of 87 (69 %) invited surgeons completed the questionnaire. Intra-abdominal pressure (IAP) was measured using intra-vesical methods by 55 (98 %) respondents. Diuretics (N = 38; 63 %) and laparotomy (N = 33; 55 %) were considered useful treatments for IAH or prevention of ACS by a majority. Only 16 (27 %) respondents used these guidelines in daily practice, and 37 (62 %) respondents are willing to do so. Although 35 (58 %) surgeons agreed that IAH is only a symptom, not requiring treatment. Forty-one percent of experienced respondents suggested that prevalence of ACS remained unchanged. Nearly all respondents (N = 59; 98 %) believed that open abdomen management improves patient outcomes, many (N = 46; 77 %) confirm the high complications rate of this treatment. Conclusion: The definitions of IAH and ACS and the related diagnostic and therapeutic challenges are relatively well known by Dutch surgeons. Despite limited use of the evidence-based gui

Structural study of the membrane protein MscL using cell-free expression and solid-state

a b s t r a c t High-resolution structures of membrane proteins have so far been obtained mostly by X-ray crystallography, on samples where the protein is surrounded by detergent. Recent developments of solid-state NMR have opened the way to a new approach for the study of integral membrane proteins inside a membrane. At the same time, the extension of cell-free expression to the production of membrane proteins allows for the production of proteins tailor made for NMR. We present here an in situ solid-state NMR study of a membrane protein selectively labeled through the use of cell-free expression. The sample consists of MscL (mechano-sensitive channel of large conductance), a 75 kDa pentameric a-helical ion channel from Escherichia coli, reconstituted in a hydrated lipid bilayer. Compared to a uniformly labeled protein sample, the spectral crowding is greatly reduced in the cell-free expressed protein sample. This approach may be a decisive step required for spectral assignment and structure determination of membrane proteins by solid-state NMR

Visually guided inspiration breath-hold facilitated with nasal high flow therapy in locally advanced lung cancer

Background and purpose Reducing breathing motion in radiotherapy (RT) is an attractive strategy to reduce margins and better spare normal tissues. The objective of this prospective study (NCT03729661) was to investigate the feasibility of irradiation of non-small cell lung cancer (NSCLC) with visually guided moderate deep inspiration breath-hold (IBH) using nasal high-flow therapy (NHFT). Material and methods Locally advanced NSCLC patients undergoing photon RT were given NHFT with heated humidified air (flow: 40 L/min with 80% oxygen) through a nasal cannula. IBH was monitored by optical surface tracking (OST) with visual feedback. At a training session, patients had to hold their breath as long as possible, without and with NHFT. For the daily cone beam CT (CBCT) and RT treatment in IBH, patients were instructed to keep their BH as long as it felt comfortable. OST was used to analyze stability and reproducibility of the BH, and CBCT to analyze daily tumor position. Subjective tolerance was measured with a questionnaire at 3 time points. Results Of 10 included patients, 9 were treated with RT. Seven (78%) completed the treatment with NHFT as planned. At the training session, the mean BH length without NHFT was 39 s (range 15-86 s), and with NHFT 78 s (range 29-223 s) (p = .005). NHFT prolonged the BH duration by a mean factor of 2.1 (range 1.1-3.9s). The mean overall stability and reproducibility were within 1 mm. Subjective tolerance was very good with the majority of patients having no or minor discomfort caused by the devices. The mean inter-fraction tumor position variability was 1.8 mm (-1.1-8.1 mm;SD 2.4 mm). Conclusion NHFT for RT treatment of NSCLC in BH is feasible, well tolerated and significantly increases the breath-hold duration. Visually guided BH with OST is stable and reproducible. We therefore consider this an attractive patient-friendly approach to treat lung cancer patients with RT in BH

The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation

Polycomb group (PcG) proteins form transcriptional repressor complexes with well-established functions during cell-fate determination. Yet, the mechanisms underlying their regulation remain poorly understood. Here, we extend the role of Polycomb complexes in the temporal control of neural progenitor cell (NPC) commitment by demonstrating that the PcG protein Ezh2 is necessary to prevent the premature onset of gliogenesis. In addition, we identify the chromodomain helicase DNA-binding protein 4 (Chd4) as a critical interaction partner of Ezh2 required specifically for PcG-mediated suppression of the key astrogenic marker gene GFAP. Accordingly, in vivo depletion of Chd4 in the developing neocortex promotes astrogenesis. Collectively, these results demonstrate that PcG proteins operate in a highly dynamic, developmental stage-dependent fashion during neural differentiation and suggest that target gene-specific mechanisms regulate Polycomb function during sequential cell-fate decisions

Validity of the Patient Experiences and Satisfaction with Medications (PESaM) Questionnaire

Background: This study assessed the validity and reliability of the generic module of the recently developed Patient Experiences and Satisfaction with Medications (PESaM) questionnaire in a sample of patients in the Netherlands. Methods: The generic module of the PESaM questionnaire consists of 18 items related to the domains effectiveness, side effects and ease of use of medications. It assesses patients’ experiences regarding the impact of the medication on daily life, health and satisfaction. In 2017, the PESaM questionnaire was sent out to idiopathic pulmonary fibrosis patients using pirfenidone or nintedanib, atypical haemolytic uraemic syndrome patients receiving eculizumab and patients using tacrolimus after kidney transplantation. Mean scores for each domain were calculated applying a scoring algorithm. Construct validity and reliability were assessed using recommended methods. Results: 188 participants completed the generic module, of whom 48% used pirfenidone, 36% nintedanib, 11% tacrolimus and 5% eculizumab. The generic module has good structural properties. Internal consistency values of the domains were satisfactory (i.e. Cronbach’s coefficient alpha above 0.7). Confirmatory factor analysis provided further evidence for construct validity, with good convergent and discriminant validity. The PESaM questionnaire also showed different scores for patients using different medications, in line with expectations, and was therefore able to differentiate between patient groups. Test–retest reliability of the items and domains were rated as moderate to fair (i.e. intraclass coefficients ranged between 0.18 and 0.76). Conclusions: The PESaM questionnaire is a unique patient-reported outcome measure evaluating patient experiences and satisfaction with medications. It has been developed in conjunction with patients, ensuring coverage of domains and issues relevant from the patient’s perspective. This study has shown promising validity of the generic module of the PESaM questionnaire. Further research is recommended to assess reliability in greater detail as well as the responsiveness of the measure. Trial registration: The study

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Cell-free expression and labeling strategies for a new decade in solid-state NMR

International audienc

Relationship between self-reported disability and functional capacity in patients with Whiplash Associated Disorder

Purpose Patients with chronic Whiplash Associated Disorders (WAD) report symptoms and disability. Neither the relationship between self-reported disability and functional capacity, nor its predictors have been investigated in patients with WAD. This was the purpose of this study. Method This was a cross-sectional study. Participants were patients with WAD on sick leave. Self-reported disability was assessed with the Neck Disability Index (NDI). Functional capacity was assessed with a six-item neck functional capacity evaluation (FCE). Correlation coefficients were used to express the relationship between NDI (total and items) and FCE. Multivariate linear regression analyses were performed to identify independent predictors of NDI and FCE. Results Forty patients were measured, of whom 18 (45 %) were male. Mean age was 33 years, median duration of complaints was 12 months, and 75 % had a pending insurance claim. Correlations between NDI and FCE tests varied from −0.39 to −0.70. Independent predictors of NDI were pain intensity and a pending claim, explaining 43 % of the variance. Independent predictors of FCE were NDI, gender, and pain intensity, explaining 20–55 % of the variance. Conclusions Self-reported disability and functional capacity are related but different. Both can part be predicted by pain intensity. A pending claim can predict higher self-reported disability. Both constructs are complementary and are recommended to determine disability in patients with WAD comprehensively